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Hypoglycemia is the most frequent metabolic abnormality in the newborn, and although it is the most common biochemical disorder in this age group [30], it is still a source of clinical concern and controversy, as no consensus exists on what level of blood glucose is able to protect the brain and influence the child’s neural development [6, 22, 53] and which is the best course of management in cases labeled as hypoglycemia. Early diagnosis, urgent treatment, and prevention of future episodes of hypoglycemia are the cornerstones of management, now supported by recent advances in molecular genetics [48] and in our understanding of the pathophysiology of neonatal hypoglycemia, particularly the pathogenesis of congenital hyperinsulinemic hypoglycemia [12].
Hypoglycemia occurs in 1.3–4.4 per 1000 full-term newborns and 15–55 per 1000 preterm newborns. This suggests that gestational age has enormous influence on its onset; in certain groups, adaptive mechanisms are not adequately developed, which predisposes them to increased risk of hypoglycemia. According to current evidence, the prevalence of hypoglycemia is approximately 10% in full-term neonates [45]; 6.5% in appropriate for gestational age (AGA), 8% in large for gestational age (LGA), and 15% in small for gestational age (SGA) newborns; and 15.5% in late-preterm infants [7].
The maintenance of physiological concentrations of glucose in newborns plays important roles, including protecting the brain from damage caused by insufficient glucose intake and preventing the consequences of hyperosmolarity caused by high glucose concentrations. Although glucose is the preferred energy source of neurons, other sources, such as lactate and ketone bodies [23], seem to exert a neuroprotective effect. However, in hypoketotic states, such as hyperinsulinism or fatty acid oxidation disorders, ketone and lactate concentrations are not high enough to replace glucose, and the risk of a cerebral energy deficit is greater [60, 61].
It is known that, during fasting, several metabolic systems are activated to prevent hypoglycemia, which may be seen as a failure in one of these systems or as an abnormality affecting one or more of the hormones that control these systems [24].
As the brain mass of newborn infants in relation to body size is larger than that of adults, the rate of glucose utilization per kg body weight in newborns is two- to threefold than that of adults (4–6 mg/kg/min) [61].
The first half of pregnancy is characterized by marked anabolism. In early pregnancy, increased caloric intake not only supports fetal development but also facilitates fat deposition in the mother in preparation for the second half of pregnancy, a period of accelerated fetal growth in which maternal stores are mobilized to meet the needs of the fetus. To this end, increased insulin secretion also occurs in early pregnancy, as a way to store energy.
From the midpoint of pregnancy onward, high levels of circulating maternal insulin are also observed, but high levels of anti-insulin factors override this effect, ensuring the provision of nutrients to the fetus during the postprandial period. Thus, in pregnant women with preexisting diabetes, the effects of these anti-insulin factors are potentiated, causing excess provision of glucose and other energy sources to the fetus and thus triggering the abnormalities observed in infants born to diabetic mothers.
In the expectant mother, glucose is found at levels 25–30% higher than in the fetus, and it is transported to the fetus by concentration gradients and simple diffusion and through the action of transporters. In the fetus, the predominant transporter is GLUT-1, which has a high affinity for glucose and facilitates its passage through tissues [28].
Most glucose in the fetus undergoes oxidation to supply its energy needs, while another part contributes significantly to a buildup of glycogen, protein, and fat in triglyceride form. Glucose is the most important source of energy for the fetus and the major substrate for brain metabolism.
At birth, the fetus becomes dependent on itself to obtain energy and meet the metabolic needs of its vital organs, particularly the central nervous system (CNS). Each mole of oxidized glucose provides 38 moles of adenosine triphosphate (ATP) [54].
Cerebral glucose transport takes place through a facilitated diffusion process, which is dependent on glycemia and is not regulated by insulin. Protection against hypoglycemia is coordinated by the autonomic nervous system by means of hormones that stimulate the production of glucose (through glycogenolysis and gluconeogenesis) and limit peripheral glucose utilization [54].
Glycogen is the only glucose storage medium in the body. Its deposits are found in the liver, striated muscle tissue (including cardiac muscle), kidneys, bowel, brain, and placenta.
The fetal liver contains a complete enzyme system for the synthesis and breakdown of glycogen, levels of which are low in early pregnancy but rise slowly and steadily from gestational weeks 15–20, before peaking in the third trimester. At this time, fat deposition also increases. Thus, part of the energy and substrates used for fetal growth is redirected for storage, which will play an important role in the peripartum and postpartum periods.
Hepatic glycogenolysis is the major mechanism of glucose release in the immediate neonatal period, which leads to depletion of glycogen stores. It is induced by an increase in glucagon and catecholamines and a reduction in insulin. This exhaustion of glycogen stores promotes activation of gluconeogenesis, which occurs largely as a result of free fatty acid oxidation in the liver.
Glucose homeostasis will thus depend on glucose intake; gluconeogenesis; glycogen, protein, and fat stores; and hormonal and neural factors.
Glucose produced from the breakdown of dietary lactose into galactose and glucose, for instance, is not taken up by the liver in the neonatal period; the newborn is thus dependent on hepatic gluconeogenesis to sustain glucose production.
Once glycogen stores are low, gluconeogenesis induced by glucagon, catecholamines, cortisol, and growth hormone mobilizes fat and protein substrates. Insulin, thyroid hormone, cortisol, and glucagon systematically promote induction of specific enzymes, thus adapting the neonate to the abrupt cessation of the supply glucose that was provided continuously before birth.
Upon clamping the umbilical cord, the maternal glucose supply, which was 54 mg/dL during pregnancy, ceases abruptly, and the neonate’s blood glucose levels decline rapidly and precipitously—from a concentration similar to that of the mother to approximately 41 mg/dL within the first 6 h of life. Physiologically, glucose concentration decreases to approximately 30 mg/dL in the first 2 h after birth, subsequently rises, and plateaus at approximately 45 mg/dL 12 h after birth.
Current evidence is still unable to define a specific glucose concentration that is safe to prevent acute neurological damage or chronic, irreversible neurological injury in the neonate. Weight and gestational age, as well as the age at onset, severity, duration, and number of episodes of hypoglycemia, are all determinants of the blood glucose level most appropriate for protection of the neonatal brain [54]; thus, doubts persist as to whether any single level may represent a red flag for neurological safety.
A plasma glucose level below 30 mg/dL (1.65 mmol/L) in the first 2 h of life or below 45 mg/dL (2.5 mmol/L) after these first 2 h has been considered diagnostic of hypoglycemia [54].
Various situations can influence the appropriateness of a blood glucose level for use as a cutoff point for treatment initiation, including nutritional timing and the presence and absence of symptoms [64]. Thus, in 2011, the American Academy of Pediatrics proposed that neonatal hypoglycemia be defined as a blood glucose level of 2.5 mmol/L before routine feeding [1, 20]. Other studies suggest a limit of 2 mmol/L in asymptomatic newborns and 2.5 mmol/L in symptomatic neonates [42]. Although cutoff values below 2.6 mmol/L have been cited in various studies as defining of neonatal hypoglycemia, there is no guarantee that such a concentration is the most appropriate choice for establishing a diagnosis of this disorder and prompting initiation of treatment. An important finding reported by McKinlay et al. [34] has encouraged neonatologists to consider a glucose concentration >47 mg/dL as the level at which no impairment of appropriate neurological development was observed at age 2 years.
These proposed levels serve to provide a margin of safety until additional data are available to support a more accurate definition. However, the potential risk of neurologic sequelae has led many authors to consider blood glucose values <50 mg/dL in infants as the limit beyond which treatment should be instituted [61].
In practice, blood glucose levels below 50 mg/dL as measured by a glucometer should warrant careful monitoring, and plasma glucose levels below 45 mg/dL should prompt initiation of diagnostic measures and immediate treatment.
Overall, neonatal hypoglycemia is caused by one of the three main mechanisms: situations associated with hyperinsulinemia, situations associated with low or depleted glycogen stores, and situations associated with excessive glucose consumption. These mechanisms may also be compounded by the effects of certain drugs used in pregnancy.
Offspring of diabetic mothers may be abnormally large at birth (LGA), even when the mother was able to keep blood glucose within normal or near-normal range throughout pregnancy. The risk of birth defects is two to four times higher in fetuses of pregnant women with diabetes, particularly when the disorder is poorly controlled during the period of fetal organ development (i.e., gestational weeks 6–7), and the neonatal mortality rate is fivefold than that of infants born to women without diabetes.
Intermittent maternal hyperglycemia causes fetal hyperglycemia, which, in turn, stimulates excess insulin production by the fetal pancreas. On the one hand, this increased fetal insulin synthesis stimulates excess organ growth (except of the brain and liver, which are not dependent on insulin supply for growth), thus causing fetal macrosomia. On the other hand, it is associated with a high incidence of neonatal hypoglycemia and marked lipolysis during the first few hours after birth. Hyperinsulinism and hyperglycemia may also cause fetal acidosis, which results in an increased rate of stillbirths. Although hyperinsulinemia is probably the leading cause of hypoglycemia, reduced epinephrine and glucagon responses can also be contributing factors. Levels of cortisol and growth hormone are normal [11].
Increased levels of glycated hemoglobin in fetal blood appear to precipitate tissue hypoxia, as this form of hemoglobin has high affinity for oxygen molecules.
Furthermore, chronic fetal hyperinsulinemia increases metabolic rates, thus increasing oxygen consumption and inducing relative hypoxemia; this, in turn, boosts red blood cell production, causing polycythemia and, consequently, hemolysis and neonatal hyperbilirubinemia. Severe hypoxemia can ultimately lead to fetal death.
After birth, the supply of glucose to the fetus is cut off, but hyperinsulinemia persists, speeding both exogenous glucose utilization and endogenous glucose production; this phenomenon may last approximately 3 days, until normal insulin secretion is established. Hypoglycemia may manifest in the intervening period.
LGA neonates may also develop hypoglycemia [44], through the same mechanism observed in infants born to diabetic mothers; however, in these infants, blood glucose reaches normal levels within the first few hours of life [32].
Hypoglycemia associated with congenital hyperinsulinism (CHH), also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is the result of inappropriate insulin secretion or hyperinsulinism. In infants with this disease, hypoglycemia is triggered by fasting and is always accompanied by an increase in plasma insulin concentrations, which are usually inappropriately high for the concomitant low blood glucose concentration. The disease appears to be more closely related to an increase in global endocrine functional activity of the pancreas rather than an increase in the number of pancreatic beta cells.
CHH is an important etiology that should be considered in cases of persistent and difficult-to-control hypoglycemia. It is a medical emergency that requires precise etiological diagnosis and represents a serious therapeutic challenge. The term PHHI was first proposed by Glaser in 1989 [19] and has since come to replace the now-outdated terms nesidioblastosis and islet-cell dysmaturity syndrome to describe pancreatic abnormalities associated with hypoglycemia and hyperinsulinism.
Most cases of CHH are sporadic (1:40,000–50,000 live births), but a higher prevalence has been described in communities with a high degree of consanguinity. This familial form associated with inbreeding may occur in up to 1:2500 live births. Thus, an autosomal recessive inheritance pattern has been posited to explain it. There is no evidence of sex predominance, and the maternal history is generally negative; however, a careful history may reveal prior neonatal deaths or unexplained seizures or mental retardation in other siblings.
Patients with CHH are mostly LGA, as a consequence of hyperinsulinism, but without significant hepatomegaly. They exhibit persistent symptoms of hypoglycemia, including hypotonia, cyanosis, apnea, and difficult-to-control seizures, as early as the neonatal period. Sudden infant death is also seen in patients with CHH. Although the condition is rare, the high frequency of brain damage and developmental delay as a result of severe, treatment-refractory hypoglycemia in these patients justifies the need for early etiologic diagnosis and immediate treatment.
Currently, the most accepted etiogenic hypothesis for the dysfunction of CHH is inappropriate insulin secretion by pancreatic beta cells. The molecular basis of congenital hyperinsulinism involves defects in key genes that regulate the complex mechanism of insulin secretion control [12]. Nine genes have been identified and classified within the potassium channelopathies (ABCC8, KCNJ11) and metabolic disorders (GLUD1, GCK, HNF4A, HNF1A, SLC16A1, UCP2, HADH) [47, 52]. Genetic defect mutations involving the ABCC8/KCNJ11 genes, which encode the SUR1/Kir 6.2 components of the ATP-sensitive potassium channels (KATP) in pancreatic beta cells, are the most common [13, 27]. In normal cells, the KATP channels remain open or closed in response to variation in blood glucose levels, which leads to changes in the action potential of the cell membrane. An increase in blood glucose raises the rate of glucose metabolism in beta cells, resulting in increased adenosine triphosphate (ATP) and decreased adenosine diphosphate (ADP) within the cell, triggering closure of KATP channels and subsequent depolarization of the beta-cell membrane. This change in potential opens voltage-dependent calcium channels and leads to calcium influx. The subsequent increase in the cytosolic calcium concentration stimulates exostosis of insulin secretory granules; thus, insulin is released continuously.
The potassium channel is a complex of two proteins: SUR1, a receptor with high affinity for sulfonylureas, and Kir 6.2, which forms the inner pore of the channel and maintains its alignment [39, 58, 59]. The regulatory genes of the sulfonylurea receptor and potassium channels were recently mapped to region 11p15.1 of chromosome 11. Individually; none of these proteins has the ability to act as a potassium channel. Depending on the type of mutation affecting the genes that regulate these proteins, CHH may manifest with three distinct phenotypes. The first represents the familial form, with truncation of SUR1 and the absence of KATP. These patients have the most severe form of CHH and, in most cases, respond poorly or not at all to clinical treatment. In the second type, which accounts for sporadic cases, there is loss of KATP function but partial response to clinical treatment, due to formation of new potassium ion channels. In the third type, onset is delayed and severity is mild, as these patients have functional KATPs and respond to clinical treatment.
A diagnosis of CHH is usually considered when hypoglycemia develops shortly after birth and requires glucose infusion at high rates, usually exceeding 10 mg/kg/min and occasionally up to 15–20 mg/kg/min. Typically, these infants have high blood levels of insulin, sometimes exceeding 10 μU/mL, and the insulin (μU/mL)-to-glucose (mg/dL) ratio is 1:4 or higher.
Beta-cell adenomas are characterized by marked, early onset hyperinsulinemia. These tumors require surgical removal or partial pancreatectomy. They are uncommon in the neonatal period. Definitive diagnosis can only be established through histopathology, and immunohistochemical study may be required.
Beckwith-Wiedemann syndrome is one of the most common overgrowth disorders and can be identified in more than 75% of neonates above the 90th percentile for weight and length. It is estimated to occur in 1 in 13,700 births, but mild cases may lead to underestimation of its true frequency [31]. There is no gender predominance. The syndrome is characterized by gigantism, omphalocele, and macroglossia, a triad that occurs in over 80% of cases. Other abnormalities that occur less frequently include earlobe creases and posterior helical ear pits, microcephaly, wide fontanels, a prominent occipital protuberance, facial nevus flammeus, nonspecific cardiac defects, abdominal wall defects (umbilical hernia, diastasis recti), visceromegaly, and hyperplasia of the kidneys, pancreas, adrenal cortices, gonadal interstitial cells, and pituitary [50].
Neonatal hypoglycemia occurs in at least 50% of cases of Beckwith-Wiedemann syndrome. It is generally serious and may be associated with future mental retardation. Thus, early diagnosis is important for proper treatment of low serum glucose levels, to prevent neurological damage. It is believed that hypoglycemia in this syndrome is secondary to hyperinsulinism caused by beta-cell hyperplasia and hypertrophy, but glucagon deficiency and a reduction in somatostatin-producing delta cells have also been documented.
There is a clear evidence of genomic influence in the development of Beckwith-Wiedemann syndrome. A mutation in 11p15.5, a region that encompasses multiple gene loci, has been implicated [37].
Prematurity and intrauterine growth restriction are among the situations that can influence neonatal blood glucose levels [35].
As very low-birth-weight preterm infants have limited glycogen stores, gluconeogenesis is their main source of glucose production. Gluconeogenesis is induced by decreased glucose intake, as well as by high cortisol, catecholamine, and glucagon levels.
Increased neurologic morbidity is particularly common in children with severe, recurrent hypoglycemia. Experimental observations have stressed the resistance of the immature brain to damage caused by hypoglycemia. This resistance is a consequence of compensatory increase in blood flow to the brain, reduced energy needs, increased endogenous carbohydrate stores, and ability to take up and consume alternative organic substrates while saving glucose for energy production [36].
As a result of intrauterine growth restriction, SGA neonates may exhibit several abnormalities shortly after birth, including increased susceptibility to infections, pulmonary hemorrhage, hyperbilirubinemia, and hypoglycemia. The widely varying incidence of the latter may reflect the different etiologies of intrauterine growth restriction (e.g., poor maternal nutrition, mothers with advanced age, uteroplacental insufficiency, derangements in maternal metabolism, or fetal infection). Furthermore, polycythemia and fetal and neonatal hypoxemia, which are often seen in SGA infants, can themselves contribute to development of hypoglycemia [49].
SGA infants are most at risk of hypoglycemia. Of those who do develop it, 65% are premature and 25% are post-term. Hypoglycemia can be asymptomatic or symptomatic and is generally observed in the first 24 h of life.
The factors contributing to low blood glucose levels include inadequate hepatic glycogen stores due to the high brain-to-body-mass ratio of SGA infants, the glucose-dependent nature of cerebral oxidative metabolism, and high overall metabolic rates. Furthermore, a reduction in rates of gluconeogenesis is probably responsible for 1% of episodes of prolonged hypoglycemia in SGA infants, as these infants exhibit high concentrations of gluconeogenesis precursors (such as alanine); this suggests an inability to convert these exogenous precursors into glucose.
Hypoglycemia combined with asphyxia is more damaging to the immature brain than either condition alone.
Various situations can increase glucose consumption in the neonate. These include severe birth asphyxia [9], severe respiratory distress, and sepsis.
Perinatal asphyxia may initially feature hyperglycemia secondary to cortisol and catecholamine release; this is followed by hypoglycemia secondary to depletion of hepatic glycogen stores, mobilized in response to this excess glucose consumption. The association of hypoglycemia with transient hyperinsulinism has been described [18].
The association of severe respiratory distress, from various causes, and hypoglycemia caused by increased glucose consumption has often been described.
Neonatal sepsis is defined as a clinical syndrome characterized by systemic signs of infection and bacteremia (detected by positive blood cultures) during the first month of life. It is becoming increasingly important due to the reduction of neonatal mortality among the most premature newborns and to the prolonged care of these infants in neonatal units.
Decreased glycogen stores, impaired gluconeogenesis, and increased peripheral glucose utilization appear to be the factors responsible for hypoglycemia associated with sepsis, although the usual response to sepsis observed in animal models has been an increase in the rates of glucose
Drugs such as beta-adrenergic agonists [57], corticosteroids, thiazide diuretics, oral antidiabetics, propranolol, labetalol [3], valproic acid [10], antidepressants (SSRIs) [40], phenytoin, and terbutaline [55], among others, can cause hypoglycemia in infants.
B. Zhu et al. (2016) [67] reported an association between metformin use by diabetic patients during pregnancy and a reduction in incidence of neonatal hypoglycemia when compared to mothers who used insulin. Metformin has proven an effective alternative for use in this patient population, although it can cross the placenta.
In most cases, infants—even those at risk—are asymptomatic. Nevertheless, an infant who is apathetic and refusing feeds and has a feeble cry should heighten suspicion of hypoglycemia. In high-risk infants, major findings include fine tremors, acrocyanosis, seizures, and apnea; if left untreated, coma and death may follow.
After birth, neonates born to mothers with diabetes develop complications related to their hyperinsulinemic state. In the first 3 days of life, these infants may exhibit episodes of irritability, tremor, and hyperexcitability or may present with hypotonia, lethargy, and weak suckling—manifestations consistent with early development of hypoglycemia and late onset of hypocalcemia. However, one must bear in mind that these infants are sometimes asymptomatic and the absence of symptoms should not delay testing for hypoglycemia.
The presence of tachypnea in the first days of life may be a transient manifestation of hypoglycemia, hypothermia, polycythemia, heart failure, cerebral edema secondary to traumatic delivery (particularly in macrosomic infants), or asphyxiation. The incidence of respiratory distress syndrome is high in these infants, since hyperinsulinemia may alter fetal lung maturation, inhibiting the development of enzymes required for the synthesis of pulmonary surfactant.
Glucometry is the method of choice for initial screening of glucose levels, due to its use and minimal blood sample required; however, levels should be confirmed through laboratory measurement in plasma, especially when the glucometer reading is very low, as this method is rather imprecise at the lower limit of detection. Several factors can affect the values obtained by glucometry, such as the expiration date of the test strip, ambient temperature and humidity in the storage environment, the presence of sugars other than glucose, metabolic acidosis, high PO2, hyperbilirubinemia, high hematocrit, and edema, among others [25, 66]. Several devices have been tested with the aim of demonstrating that their results may be unreliable and influence the management indicated by a reading [14].
A particular vulnerability of the occipital lobe to hypoglycemia has been observed on MRI [16], with no plausible explanation. Other authors have raised the possibility that variant anatomy of the circle of Willis and occipital lobe infarct may be implicated in these cases [2].
As mentioned previously, there are still no clearly set values to define hypoglycemia in the first 2 h of life. It is known that, in the healthy, full-term neonate, blood glucose levels are lowest between 30 and 60 min of life and rise thereafter to normal baseline values of 60–90 mg/dL between 90 and 180 min of life. This threshold should be considered the physiological goal or therapeutic target at which blood glucose levels should be maintained.
Although one may consider a diagnosis of hypoglycemia when plasma glucose levels are below 45 mg/dL, this is not an absolute cutoff. Depending on the etiology of hypoglycemia and, consequently, on the availability of alternative pathways for gluconeogenesis, patients may be symptomatic in the 45–60 mg/dL range, as in cases of fatty acid oxidation defects.
SGA and late-preterm infants should be fed every 2–3 h and screened before each feeding in the first 24 h. After 24 h, screening needs only be continued in those whose glucose levels remain below 50 mg/dL.
The need for treatment in these children has been called into question, as hypoglycemia may be transient and may resolve spontaneously through stimulant counter-regulatory mechanisms. In general, if the infant is asymptomatic, to start early breastfeeding without the need to draw blood for glucose measurement, formula feeding, or other special care.
However, in some newborns, this physiological process may fail, which may facilitate the development of hypoglycemia; therefore, the American Academy of Pediatrics suggests that in the first hour of life, asymptomatic at-risk infants should have a glucose check 30 min after feeding; if the blood glucose level remains below 25 mg/dL and the infant is asymptomatic, it should be fed again and blood glucose reassessed 1 h after the first check [67].
Late-preterm, LGA, SGA, and intrauterine growth restriction (IUGR) infants, as well as those born to diabetic mothers, are at particular risk of hypoglycemia. However, they are often asymptomatic. Breastfeeding followed by repeated glucose measurement has been the standard of care. However, if hypoglycemia persists despite frequent feedings, continuous intravenous infusion of glucose may be indicated.
A dextrose infusion rate of 3–5 mg/kg/min may be used in infants born to diabetic mothers, both to prevent overstimulation of glucose secretion and because of the greater fat mass of these infants. A dextrose infusion rate of 4–7 mg/kg/min may be used in most full-term and late-preterm neonates. In IUGR neonates, a glucose infusion rate of 6–8 mg/kg/min is often necessary. A study in an animal model of IUGR revealed increased peripheral insulin sensitivity, which may be associated with increased glucose infusion requirements. However, some children with IUGR should be followed closely, especially preterm infants, who may develop hyperglycemia due to reduced insulin secretion and less muscle mass for glucose utilization. Continuous intravenous glucose infusion, usually preceded by an IV bolus of dextrose (200 mg/kg over 5 min), is also indicated if these newborns develop symptomatic hypoglycemia. However, the need for such massive glucose administration is hotly contested due to the risk of undesirable effects, particularly in very-low-birth-weight preterm infants. Complete or partial resolution of symptoms once glucose concentration is corrected is considered definitive proof that symptoms were caused by hypoglycemia. Nevertheless, IV dextrose infusions are not an entirely appropriate treatment; they cause discomfort to the infant, which is made worse by the need for placement of a deep IV catheter, the need for NICU admission, and physical separation of the newborn from the mother, which hinders timely initiation of breastfeeding. However, when administered safely so as to prevent these complications, IV infusion of dextrose at low concentrations can be beneficial even in asymptomatic high-risk neonates.
Oral administration of glucose in gel form has been considered appropriate and should be part of any protocol to prevent episodes of hypoglycemia in asymptomatic newborns [41]. Current studies have shown that oral administration of 40% dextrose gel may reduce the occurrence of neonatal hypoglycemia by up to 70% [5] and should thus be considered as the first-line treatment in these patients [65].
Symptomatic neonates should be treated with glucose intravenously, not orally. A 200 mg/kg bolus of glucose should be administered over 1 min (10% dextrose at 2 mL/kg). This should be followed by IV infusion at 6–8 mg/kg/min. Glucose levels should be monitored after 30–60 min, with a therapeutic target of >45 mg/dL. Control measurements should be obtained every 1–2 h. Once levels are stable, they can be reassessed every 4–6 h. If values do not reach a normal range, the rate of glucose infusion is increased by 1–2 mg/kg/min every 3–4 h. In cases of hyperinsulinism, a rate of 15–30 mg/kg/min may be necessary. Oral feedings should only resume once blood glucose levels have been stable for 6 h.
High glucose concentrations (20–25%) may be necessary to maintain a rate of infusion of 15–30 mg/kg/min; concentrations above 12.5% will require a central venous catheter [56].
Physiologically, glucocorticoids promote increased resistance to insulin action, reduce the secretion of insulin, and activate enzymes involved in gluconeogenesis, mobilizing amino acids for this purpose. Thus, although such effects should theoretically induce an increase in blood glucose, there is no evidence to support glucocorticoid therapy in the treatment of hypoglycemia other than that caused by primary or secondary adrenal insufficiency.
Except in cases of hypoglycemia of self-limiting etiology (e.g., infants born to diabetic mothers), blood and urine samples should be drawn at the time of hypoglycemia for investigation of possible changes in energy and hormone metabolism (lactate, free fatty acids, ketones, insulin, cortisol, growth hormone, urinary organic acids) before any specific medications are administered.
Endogenous glucagon is the counter-regulatory hormone of insulin, secreted by pancreatic beta cells. Physiologically, hypoglycemia induces glucagon secretion to raise glucose levels [43]. The administration of glucagon has proven to be quite effective in full-term and preterm neonates without hyperinsulinism. Serum sodium levels should be monitored during glucagon infusion. Hyponatremia, thrombocytopenia, and a rare paraneoplastic phenomenon, called necrolytic migratory erythema, have been associated with continuous infusion of glucagon. Hypertonic saline solution (3% sodium chloride) may be indicated to treat glucagon-associated hyponatremia.
A dose of 0.02 mg/kg/dose has been recommended [43]. A 24-h continuous infusion has been used at doses of 20–40 μg/kg/h up to a maximum of 1 mg/day. A 50% rise in blood glucose is expected in normal infants. The effect is transient. Long-acting preparations are employed in patients with glucagon deficiency and, in combination with somatostatin, in the treatment of congenital hyperinsulinism. When the expected rise in blood glucose does not occur, the diagnosis of hepatic glycogen storage disease should be suspected.
This agent is indicated in cases of hypoglycemia associated with hyperinsulinism.
Diazoxide is a benzothiazine derivative that acts by opening ATP-sensitive potassium channels, causing inhibition of insulin secretion by pancreatic beta cells. Therefore, patients with genetic defects that affect SUR1 and Kir 6.2, the constituent proteins that form the ATP-sensitive potassium channel, may not benefit from administration of this drug. The recommended dose ranges from 10 to 15 mg/kg/day, divided in two or three oral doses, up to a maximum dose of 30 mg/kg/day. It promotes an increase in hepatic glucose production and decreases peripheral glucose utilization. Most of the drug is eliminated by glomerular filtration, and 90% of diazoxide is bound to albumin. Sodium and water retention, plasma volume expansion, edema, thrombocytopenia, anorexia, vomiting, ketoacidosis, and hyperuricemia are possible complications of the use of this drug [17].
When the drug is effective, blood glucose levels will return to normal range within 2–4 days. Any trial of diazoxide therapy should last at least 1 week before the possibility of treatment failure is considered. Onset of action occurs within 1 h of administration, and the duration of action is approximately 8 h, as long as renal function is normal.
Failure of diazoxide therapy suggests an abnormality in ATP-sensitive potassium channels. In these cases, a course of octreotide therapy, which acts further downstream on the insulin secretion pathway, is advised.
Octreotide was the first somatostatin analogue approved for clinical use, due to its more prolonged effect. This substance inhibits the secretion of glucagon, insulin, growth hormone, and thyrotropin, as well as the exocrine secretions of the bowel. Due to its ability to inhibit hormones, this drug can be used in infants with congenital hyperinsulinemic hypoglycemia [19]. A dose of 5–35 mcg/kg/day via subcutaneous injection has been recommended.
The management of diffuse hyperinsulinemic hypoglycemia, which does not respond to diazoxide, is a major therapeutic challenge. The successful use of sirolimus, both alone and as adjunctive therapy with octreotide, appears to be a potential alternative to subtotal pancreatectomy. Sirolimus is an immunosuppressant that inhibits the activation and proliferation of T lymphocytes, with effects
In a study involving four patients with diffuse hyperinsulinemic hypoglycemia [46], therapy with sirolimus allowed discontinuation of intravenous infusions of dextrose and glucagon in all for patients and maintenance treatment with octreotide alone. At the end of the first year of life, the four patients continued to receive sirolimus and were normoglycemic, without any apparent major adverse events. Sevim Ünal et al. [63] reported the use of sirolimus in a neonate with CHH due to a KCNJ11 gene mutation who had already failed treatment with continuous infusions of glucose (14 mg/kg/min) and prednisone (2 mg/kg/day). Addition of intensive therapy with multiple medications (diazoxide, chlorothiazide, octreotide, glucagon, and nifedipine) also failed to produce an adequate response. However, before partial pancreatectomy was attempted, at age 30 days, sirolimus therapy was instituted at a dose of 0.5 mg/m2/day. Improvements in glycemic control were achieved, enabling progressive dosage reduction of the other drugs. At the time of publication, at age 5 months, the infant was on minimal doses of hyperglycemic agents and continued to receive twice-daily sirolimus at a dose of 0.3 mg/m2/day, without any complications.
Recently, exendin-(9-39), a GLP-1 receptor antagonist that raises blood glucose levels in adults, has been introduced as a possible novel therapy for management of hypoglycemia in patients with CHH. However, further studies on its effectiveness and safety are needed [8].
Growth hormone is used in cases of hypoglycemia associated with deficiency of this hormone or with hypopituitarism.
In cases of hypoglycemia due to persistent hyperinsulinemic hypoglycemia that does not respond to treatment with diazoxide, glucose, and sirolimus, partial pancreatectomy may be indicated.
Recurrent or sustained hypoglycemia can cause neurological damage, mental retardation, epilepsy, and personality disorders [54]. Transient episodes of hypoglycemia are also associated with deficits in math learning around age 10 years [26].
Severe hypoglycemia can lead to impairment of cardiovascular function and is associated with high rates of neonatal mortality in very low-birth-weight infants [15].
Permanent brain damage is found in 25–50% of patients with recurrent severe symptomatic hypoglycemia under age 6 months. Furthermore, hypoxemia and ischemia may potentiate the permanent damage caused by hypoglycemia. The pathological changes described include gyral atrophy, reduced white-matter myelination, and cerebral cortical atrophy. It bears noting that the cerebral infarctions characteristic of hypoxic-ischemic processes are absent in hypoglycemia-associated brain injury [51].
Newborns with risk factors for neonatal hypoglycemia or those which, although not considered at risk, exhibit poor suckling or inadequate breast milk intake should receive follow-up monitoring and care after hospital discharge, so as to prevent possible undetected hypoglycemia.
Sponges are very primitive pluricellular aquatic organisms that belong to
Close to 9000 sponge species are estimated to exist in the world, but only do a few ones belong to the order
The demand of natural sponges has been growing because of the market preference for natural products and the increase of their use in man’s life, such as domestic, cosmetic, biomedicine, pharmaceutical, pottery, art industry, filter, cleaning and industrial purposes, among other uses. The commonly called ‘bath sponges’ of the family
Natural populations in sponge zones in the world, such as the Antillean region (Cuba, Bahamas and Florida), guarantee more than 50% of the world production. In Mexico, the Caribbean reefs (Isla Mujeres, QR) and the Gulf of Mexico have great species richness that includes the three classes that integrate
The species from the Mediterranean are considered as those with the best quality and commercial value, of which those that stand out are the species
In the Antillean region, the best commercial sponges have come from Cuba and the Bahamas Islands. Although several species have been reported in Cuba, four species have been the target for capture because of their abundance [1, 11, 12, 13]. Of the four species, three of them correspond to those commonly called ‘machos’ [males] from the genus
The presence of commercial sponges, as well as their fishing or recollection, has been reported in Cuba since the nineteenth century. During colony times, fishing boats from the Bahamas would reach the coasts of the Caribbean and Nuevitas (northeast of Cuba) to fish sponges with licence from Spanish authorities where more than 150 thousand dozen were fished by Cubans in 1867 [14]. Years later, sponge fishing was developed in southwestern Cuba with fishermen from Batabanó port, and because of their abundance, the two fishing zones in Cuba were established: (1) the northeast zone exploited by boats and fishermen from Caibarién where the Sabana-Camagüey Archipelago is located and (2) the Gulf of Batabanó, in southwest Cuba, exploited by boats from Batabanó fishing port. By 1886 offices in London and Paris were established to commercialise this product [15]. In 1930, the production went beyond 1 million dozen until 1939 and up to 1943 when a disease known as ‘tizón’ (blight), caused by the fungus
This chapter discusses the principal studies and criteria related to commercial sponge fishery and aquaculture advances in Cuba, the main impacting factors that limit their abundance, and the challenges to increase aquaculture production of this important resource sustainably in the long term and with an ecosystem approach.
Sponge fishery in Cuba has shown two extraction procedures, in accordance with the characteristics of the extraction zone, fishermen’s age and regional traditions [17, 18, 19]: (1) by means of hooking implements for sponge recollection from auxiliary (small) boats that are towed by a sponsor, so fisherman immersion is not needed, or (2) by diving in apnoea for detaching or cutting the sponges from the closest part to the fixation substrate. Practically, no evolution in the fishing form has taken place throughout the years. The shallowness of the area where sponges inhabit has determined the fishing system that has followed the traditional method, using a glass bottom bucket and a stick with a double hook or trident to detach the sponge from the substrate (Figure 1).
Traditional technique for sponge capture or recollection in Cuba, sponge boat, auxiliary boat and glass bottom bucket. Photography: La Empresa Pesquera Industrial de Caibarien (EPICAI).
Cuba reached an important commercial sponge production with an average of 166 t in the period from 1910 to 1919; 505 t for 1920–1929 and 391 t for 1930–1939 [20]. From 1939 to 1943, the fungus (blight) disease decimated the populations jointly with the hurricane at the end of 1944, generating lower production levels until 1947 [16, 21]. During the period after 1960, fishery activity was reorganised in Cuba; the fleet was modernised, which decreased the number of sponge boats and fishermen; fishing areas were divided into zones by territories, establishing two fishing regions (Figure 2) in terms of abundance [22, 23]. Currently, commercial sponge fishery in Cuba is regulated by catch quota, and minimum legal sizes have been established for perimetric length: 35.6 cm for
Distribution of the fishing areas according to zones of major commercial sponge abundance: northeast zone (Sabana-Camagüey Archipelago) and southwest zone (Gulf of Batabanó) Cuba.
Although current statistics have shown a tendency to increase sponge extractive activities since 1960, Cuba has not been able to reach the production levels previous to 1940. This tendency could have been due to a greater fishing effort. Almost all the fleets of Batabanó and Caibarién ports dedicated themselves to the capture of this resource and utilised boats type ‘Balandro’ and ‘Goleta’ with a crew from 14 to 16 fishermen. Before 1944 the fleets operated around 350 boats in the Gulf of Batabanó, which belonged to the Cuban ports of Batabanó, Coloma and Gerona [13, 14]. Production increased from 1960 with the proper fluctuations of a fishery that depended on different natural and human factors. Nonetheless, the average annual capture (40.15 ± 12.8 t) from 1960 to 2017 (58 years) did not go beyond 50 t (Figure 3).
Interannual variability of commercial sponge annual average extraction for the 1960–2017 period, in Cuba.
Sponge fishery production decreased in southwest Cuba (Gulf of Batabanó) by fishing region from the beginning of the 2000 decade. Production reported by the enterprise PESCAHABANA (Batabanó) fell from 28.2 ± 3.1 t (2000–2004) to 19.6 ± 1.6 t (2013–2017). A similar pattern was registered for the northeast region (Sabana-Camagüey Archipelago). Production from the industrial fishery (EPICAI) decreased from 25.4 ± 1.6 t (2000–2004) to 14.1 ± 3.0 t (2013–2017). In the case of Caibarién, a greater stability was observed in sponge production during the period 1990–2009 (23 ± 3.8 t). Nevertheless, average capture from the period 2010–2017 was 19.1 ± 9.0 t with a maximum capture (>33 t) in 2010 and 2011, much higher than the historic average (23.5 t) from the period 1972–2017 (47 years). All these data suggested that overfishing occurred during 2010 and 2011 whose consequence was observed several years later with a lower extraction of 15 t, which affected national sponge production. The situation of this region got worse in 2017 (10.4 t) due to the impact of Hurricane ‘Irma’.
Population density studies developed in the 2000 decade [13] showed a greater sample density in the region of the Sabana-Camagüey Archipelago (Caibarién) with respect to sample data for the region of the Gulf of Batabanó (Figure 4).
Sponge density according to southwest (Batabanó) and northeast (Caibarién) regions in Cuba. Different letters indicate significant differences
In both Cuban regions, northeast (Caibarién) and southwest (Batabanó), commercial extraction of the sponges locally known as ‘Machos’, which belong to the genus
Commercial sponge density by species on the natural banks of northeast Cuba (Sabana-Camagüey Archipelago). Different letters indicate significant differences
Commercial sponge density by species found on natural banks of southwestern Cuba (Gulf of Batabanó). Different letters indicate significant differences
In subsequent studies developed in a protected northeast zone of the Sabana-Camagüey Archipelago during 2013 [25], which is under the Special Regime of Use and Protection and in which commercial sponge extraction has not been performed, an average density of 0.457 ind/m2 was recorded (4570/ind/ha), estimating a potential precautionary capture of 1300 specimens (30% of the total) per hectare per year [25].
Density data obtained were by far superior to those reported by Blanco and Formoso [13] for the extraction zones of the Sabana-Camagüey Archipelago. Furthermore, they were superior to those reported by these same authors for the Gulf of Batabanó in the 2000 decade, which evidenced, among other causes, that fishery was also an impact factor.
What is more transcendental data from recent studies is that the ‘Hembra’ sponge
As previously mentioned, one of the main causes of abrupt decrease in sponge populations in Cuba was related to the disease known locally as ‘Tizón’ (smut or blight) caused by the fungus
Solar radiation, illumination and temperature are factors that regulate sponge distribution, colonisation and success in their natural reproductive processes. Although they can withstand extreme temperature (10–36°C) values in short periods, the optimum values for their sexual proliferation is from 23 to 29°C [27, 28]. In Cuba the southern sponge zones of the Gulf of Batabanó showed water temperature average of 28.03°C, while in the northern zone of Sabana-Camagüey Archipelago, average temperature was 27.33°C in Sabana and 28.32°C in Camagüey [29].
Even though these values are permissible for commercial sponges in Cuba, high temperatures (>30°C) can also favour the proliferation of bacteria and fungi. In coastal water bodies and bays in the inner part of the Camagüey Archipelago, extreme maximum temperatures up to 35°C could occur due to shallowness and limited water renovation [29]. Because of the shallowness from 3 to 7 m in the Gulf of Batabanó and from 2 to 8 m in the Sabana-Camagüey Archipelago, in which the greatest abundance of Cuban commercial sponges inhabit, they are very vulnerable to natural physical impacts.
Blanco [23] pointed out hurricanes as a cause of impact on sponge populations, above all on those that inhabited the Gulf of Batabanó due to a greater frequency and intensity of cyclonic disturbances after 1996. Hurricanes generate strong currents and surge of great height and intensity that provoke sediment in suspension besides the fracture and dragging of fragments or complete organisms. It occurs to sponges themselves due to their sessile condition that makes it impossible for them to escape from the energetic movement that occurs in waters, which makes the effect greater on the genera
The increase of anthropogenic activities, such as tourism development in keys and islands, above all in the Sabana-Camagüey Archipelago, adds contamination and increase in water turbidity; dragging and landfill for construction and repairing roads that link the coast of Cuba to these keys have led to periodical turbidity events that have affected seawater quality [33]. The excess of small particle solids suspended in the water column has caused clogging of the inhaling pores in commercial and noncommercial species, more so in those that have fine pores, causing them inadequate development, including death [1, 26]. The increase of siltation due to coastal erosion has been another impact additional to hurricanes, which has been derived from logging bordering mangroves, maritime construction and increase of average seawater level, as it has occurred in several coastal segments in the southwest region of the Gulf of Batabanó.
On the contrary, organic contamination at intermediate degrees seemed to have caused certain stimulation to sponge development and diversification, but it also reduced species diversity in reefs dramatically and, in extreme cases, has a greater decrease of their biomass [34]. Contamination has also brought as a consequence the disappearance of marine grass rich in commercial sponges and its substitution for muddy bottoms with turbid water loaded with sediments that do not favour
Finally, fishing activity itself could constitute an additional impact when resource exploitation goes beyond its recovery capacity since uncontrolled extraction levels lead to overfishing patterns. Blanco [23] points out a tendency of sponges to decrease, above all, the species
The development of sustainable and economically viable fishery production alternatives, such as sponge culture, constitutes an additional contribution to environment sustainability. It is a working alternative for fishermen to create new community employment sources and generate income of foreign currency besides the need of moving from a predatory recollection activity to a productive aquaculture work, as a step in economic and cultural fishery development in the country [8].
Sponge culture offers a safe and predictable production of a superior quality product to that offered by natural capture besides its elevated price according to the market, quality and species. Besides the easiness of their collection in their natural environment because they are sessile organisms that are generally found in shallow waters, they do not need additional food to that filtered from their environment. This is the reason why its culture requires low investment cost and availability to schedule a tiered harvest. Moreover, its culture reduces fishing pressure on sponges in their natural medium, constituting a sustainable repopulation alternative to increase natural banks surrounding the aquaculture farms because of their larval contribution to the environment [35].
Initial sponge culture in Cuba goes back to several decades. A variance of sponge culture suspended in vertical lines was tested in Cuba in 1965 and described by García del Barco [36, 37] in a sponge culture handbook. The method of vertical suspended lines allowed using a greater area vertically taking advantage of the zone in a greater depth and avoiding being affected by surge as it occurs in lower zones where they traditionally inhabit.
Complete experimental cycles included sponge collection from their natural environment, seeding, harvesting and reseeding from seeds obtained from the same culture, cleaning process and commercialisation. Aquaculture procedures were performed with the assessment of scientific institutions, such as Centro de Investigaciones Pesqueras de Cuba [38, 39].
Although sponge culture was not consolidated to a commercial level, important conclusions were obtained from these studies:
Cultured sponges showed less osculation density and diameter, increasing solid surface and weight per volume unit.
They showed less mechanical damage during recollection.
Cultured sponges were harvested in total absence of foreign materials.
They showed spherical shapes which reduced process expenses and wastes.
Cultured sponges reached a similar or greater size to those in their natural environment, in equal period, but with better and more rounded shape.
‘Seeds’ for a nondependant aquaculture could be obtained from their natural environment if not harvesting a part of the cultured sponges and allowing them to naturally grow for about 3 years to get a ‘mother sponge’.
The technical and scientific knowledge and field experiences derived from these experiments allowed editing a handbook of work procedures and operations for small sponge farms attended by the same extractive fishery crew [40]. Research and development has continued, and two culture methods have been tested during the last decade, which are briefly described below.
An experimental farm was projected by the Centro de Estudios y Servicios Ambientales (CESAM, its abbreviation in Spanish for Centre for Environmental Studies and Services) of Villa Clara, Cuba. It was sponsored by funding partners of the United Nations Development Programme for Global Environmental Finance (Small Donations GEF-PNUD). The sponge farm was located in a marine zone in the surroundings of the town Carahatas (Sabana-Camagüey Archipelago) northcentral coast of Cuba. One-hectare culture fences were built and installed in the sea. Metallic poles were buried in the seabed as basic support and plastic mesh cove to restrict access to predators. The ‘free’ sponge method was used in those subdivided 1-ha lots, planting a density of 1 sponge/4 m2 (Figure 7).
Experimental sponge farm in Carahatas, Sabana-Camagüey Archipelago, Cuba. Free sponge culture in lots. Graphic art and photography: [
Starting from the contribution of the project GEF/PNUD/’Protección de la biodiversidad en tres sectores productivos del Archipiélago Sabana-Camagüey’ [Biodiversity protection in three productive sectors of the Sabana-Camagüey Archipelago], fishermen from the Caibarien Basic Enterprise Unit (EPICAI) built a farm in a northeast shallow marine zone with the advice from Centro de Investigaciones Pesqueras.
Recollected sponges were cut in 4–5 cm3pieces named as ‘propagules’ that were used for ‘seeding’ and deposited in the substrate (approximately 2500 seeds/ha), at the mercy of currents and other natural water dynamics, until they reached a commercial size. A total of 12 ha seeded were obtained, which should provide 1 t of sponge in a year at a quote of more than $15,000 USD in the world market [41].
This method uses rope ‘tendales’ in a horizontal pattern, which is commonly identified in aquaculture as ‘suspended long-line’ method. Briefly, metallic poles are buried in the seabed as support for nylon-braided rope (long lines 1/4″), elevated 20–30 cm off-bottom. Two long lines support horizontal several tendales of nylon monofilament (150 lb) for sponge suspended aquaculture. Mother sponges are cut in propagues (5 to 8 cm3) to obtain sponges seeds. Propagues are tied to tendales in a collar-shape pattern using monofilament nylon lines (50 lb). In this way, sponge ‘seeds’ hang vertically to horizontal tendales with a separation of 30 cm between each one, during all the grow-out period (Figure 8A). Alternatively, sponge seeds can be put directly in the nylon tendales (Figure 8B).
Suspended line culture. System designed for the experimental farm in Caibarién, Sabana-Camagüey Archipelago, Cuba. Graphic art: M.A. Avilés-Quevedo. Photography: Empresa Pesquera Industrial de Caibarien (EPICAI).
After a grow-out from 15 to 18 months, 80% of planted sponges were obtained with acceptable commercial size (18–23 cm in diameter). Part of the recollection of this farm was used as ‘mother sponge’ to obtain new lots of ‘seeds’ for a second project with 130 suspended lines (trails), each one with 33 sponges for a total of 4290 cultured sponges [42].
All these projects, efforts and intentions to boost sponge cultivation in Cuba have remained at the stage of demonstrative experiments without scaling up to allow expansion to a systematic and eco-sustainable production level with an economic profitable income. The causes of this limited development have been related rather than beyond the indisputable potential of marine waters to human factors related to the will of introducing, developing and consolidating sponge culture, which could promote a regional socioeconomic progress.
Gradual reduction of natural sponge banks at national and global levels has been evident, and that risk situation could get worse due to the problems deriving from climate change. Sponge culture, besides being a sustainable production, constitutes an alternative in foreign currency with commercialisation prices according to Cuban commercial species from $4 to $74 USD/kg, depending on their quality classification.
The main challenges to develop and generalise sponge culture in Cuba are:
Link and implicate fishery enterprises and coastal communities to develop sponge culture projects.
Assess and select ideal sites for priority species, according to value and abundance of the natural resources, to implement a viable economical and eco-sustainable aquaculture.
Apply a differential price and payment policy to fishermen, according to natural and cultured sponges. It is essential although clearly established policies exist for the development of marine aquaculture in Cuba.
In other terms, cultured sponges should have more attractive prices to motivate their introduction and boost technologic development and generalisation or the activity.
The economical-environmental feasibility that fishermen themselves combine natural sponge extraction with aquaculture production may not be viable in practice due to their extractive tradition, timing annual fishery operations and compliance demand for official production plans or goals, among other subjective factors.
Facing the decrease in sponge capture and abundance, it shall be essential to reduce fishing effort on natural populations, diverting fleet and fishermen that are currently dedicated to sponge extraction towards aquaculture production.
Those challenges will imply economic and logistic support from state institutions until the first results have been reached, and after that first goal, a second step of continuity will be necessary to improve and continuously enhance this productive activity.
This study was financed by Public Sectorial Research Fund for Education of México, Basic Science project Conacyt No. 258282 and R&D project Proinnova Conacyt No. 241777, under the academic responsibility of JMMS. Authors are grateful to Centro de Investigaciones Pesqueras (CIP, Cuba), Centro de Investigaciones Biológicas del Noroeste, S.C. (CIBNOR, México), Antonio Grovas Hernández of Grupo Empresarial de la Industria Alimentaria (GEIA, Cuba) who provided updated sponge extraction data, and Diana Fisher for English edition.
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",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
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\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
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The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
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\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. 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Several treatments including antidepressants and hormonal restitution with estrogens have been suggested to ameliorate the symptoms. Also, in this period of life is frequent the use of other drugs to treat is also frequent the use of other drugs to treat comorbid pathologies that might even increase the risk of drug-drug interactions. Literature reports that some phytochemicals with estrogenic activity have beneficial effects during menopausal transition without collateral events. This chapter shows evidence about the use of phytoestrogens as an alternative therapy for the treatment of some psychiatric symptoms associated with the menopausal transition. Data derived from preclinical research related to the use of classical phytoestrogens (isoflavones), considering the beneficial effects, as well as adverse events, are discussed. Also, the use of polyphenols and organosulfurate compounds as an alternative for the treatment of anxiety- and depressive-like behavior as well as fibromyalgia is included. A narrative review was conducted using bibliography reporting the use of isoflavones (genistein, daidzein, equol), coumestans or lignans for the reduction of depressive-like or anxiety-like behavior. Furthermore, it is described if the use of this compounds impact in other signs of menopause, i.e. vasomotor and osteoporosis. In addition, due to the high frequency of comorbid pathologies as diabetes mellitus, dyslipidemia or metabolic syndrome with psychiatric disorders, the use of these phytochemicals is discussed.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"Erika Estrada-Camarena, Carolina López-Rubalcava, Brenda Valdés-\nSustaita, Gabriel Sinhue Azpilcueta-Morales and Eva María\nGonzález-Trujano",authors:[{id:"114710",title:"Dr.",name:"Erika",middleName:null,surname:"Estrada-Camarena",slug:"erika-estrada-camarena",fullName:"Erika Estrada-Camarena"},{id:"200969",title:"Prof.",name:"Carolina",middleName:null,surname:"López Rubalcava",slug:"carolina-lopez-rubalcava",fullName:"Carolina López Rubalcava"},{id:"200970",title:"MSc.",name:"Brenda",middleName:null,surname:"Valdés Sustaita",slug:"brenda-valdes-sustaita",fullName:"Brenda Valdés Sustaita"},{id:"200971",title:"BSc.",name:"Gabriel",middleName:null,surname:"Azpilcueta",slug:"gabriel-azpilcueta",fullName:"Gabriel Azpilcueta"},{id:"207957",title:"Prof.",name:"Eva",middleName:null,surname:"Gonzalez-Trujano",slug:"eva-gonzalez-trujano",fullName:"Eva Gonzalez-Trujano"}]},{id:"56195",doi:"10.5772/intechopen.69786",title:"Depression and Serotonergic Changes during the Climacteric and Postmenopausal Stages: Hormonal Influences",slug:"depression-and-serotonergic-changes-during-the-climacteric-and-postmenopausal-stages-hormonal-influe",totalDownloads:1503,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Depression is a psychiatric disorder that affects a high percentage of women. Most of the depression disorders turn up during the premenopause and perimenopause stages when the hormonal oscillations make an impact in the brain function principally on the serotonergic system, which is related to neurobiology of depression. 5-HT1A and 5-HT2A receptors change on functionality and density in afferent areas related to emotional modulation and increased serotonin clearance, and the binding potential of serotonin transport has been related to the underlying mechanism of the depression during the climacteric or postmenopausal stage. Some findings have been proven on preclinical studies. These studies on animals have recognized how estrogen treatment activates intracellular signaling pathways as mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK), tyrosine kinase brain-derived neurotrophic factor receptor (TrKB), insulin-like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3)/serine/threonine-specific protein kinase (Akt), and metabotropic glutamate receptor 1 (mGluR1) which interact with the serotonergic system to allow establishment of the estradiol effects on mood regulation. Thus, the interaction between the woman’s reproductive status and the serotonin changes could be useful to create prevention strategies, early diagnosis, and medical treatment of climacteric and postmenopausal women with depression, in order to improve their quality of life.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"Rosa Isela García-Ríos, Armando Mora-Pérez and Cesar Soria-\nFregozo",authors:[{id:"174653",title:"Dr.",name:"Rosa Isela",middleName:null,surname:"García-Ríos",slug:"rosa-isela-garcia-rios",fullName:"Rosa Isela García-Ríos"},{id:"174654",title:"Dr.",name:"Cesar",middleName:null,surname:"Soria-Fregozo",slug:"cesar-soria-fregozo",fullName:"Cesar Soria-Fregozo"},{id:"198327",title:"Dr.",name:"Armando",middleName:null,surname:"Mora-Perez",slug:"armando-mora-perez",fullName:"Armando Mora-Perez"}]},{id:"56181",doi:"10.5772/intechopen.69078",title:"Psychological and Social Aspects of Menopause",slug:"psychological-and-social-aspects-of-menopause",totalDownloads:2534,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Menopause is one of the age-related phases of physiological transition of females. There is robust research and information regarding its biological aspects specially its endocrine base, yet the psychosocial aspect is quite interesting and debatable due to its variability among different cultures and climates. There are certain subthreshold response in form fear and loss of reproductive life to no more ability to reproduce and a feeling of loss of femininity. The period of menstruation simulated to reproductive age or fertility is around half of their lives; therefore, loss of fertility or reproductive life may be a source of stress specially among tribes where long reproductive age period is desired on the cultural belief that this will lead to a large family size that is considered as a symbol of success. Psychological factors such personal or inter-psychic (personality, self-esteem, and coping skills) and intra-psychic (relationship issues and social support) may contribute in the onset, course, and repose to perimenopausal period. There are certain psychiatric conditions such as anxiety, depressive disorder, and premenstrual dysphoric syndrome related to premenopausal period that must be screened. Before embarking on pharmacological treatment, psychosocial intervention especially lifestyle modifications must be offered to avoid complications.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"Iqbal Afridi",authors:[{id:"203383",title:"Prof.",name:"Iqbal",middleName:null,surname:"Afridi",slug:"iqbal-afridi",fullName:"Iqbal Afridi"}]},{id:"33797",doi:"10.5772/28644",title:"Operative Vaginal Deliveries in Contemporary Obstetric Practice",slug:"operative-vaginal-deliveries-in-contemporary-obstetric-practise",totalDownloads:9027,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"1751",slug:"from-preconception-to-postpartum",title:"From Preconception to Postpartum",fullTitle:"From Preconception to Postpartum"},signatures:"Sunday E. Adaji and Charles A. Ameh",authors:[{id:"74801",title:"Dr.",name:"Sunday",middleName:null,surname:"Adaji",slug:"sunday-adaji",fullName:"Sunday Adaji"},{id:"86877",title:"Dr.",name:"Charles",middleName:"Anawo",surname:"Ameh",slug:"charles-ameh",fullName:"Charles Ameh"}]},{id:"56061",doi:"10.5772/intechopen.69657",title:"Menopause in Nonhuman Primates: A Comparative Study with Humans",slug:"menopause-in-nonhuman-primates-a-comparative-study-with-humans",totalDownloads:1662,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Although menopause is a phenomenon predominantly studied in humans or laboratory animals, this chapter discussed the case of nonhuman primates (NHPs), not only with the objective of employing them as study models but also to better understand phylogenetic divergence among species. Those taxonomic differences are reflected in reproductive processes that may be similar to those of human beings, with the presence of a defined cycle or periods of estrus, but perhaps at different ages as well, where menopause plays a crucial role. First, it is important to delimit the concept of menopause by considering its anatomical, physiological, and biochemical parameters, including the cessation of menstrual bleeding or perineal swelling—when present—or follicular depletion and hormonal changes. Thus, the aim of this chapter is to discuss some of the similarities between NHPs and human females, during the menopause period. Studying these phenomena should help us achieve a better understanding of the social, physiological, and environmental factors without adopting any particular cultural view of menopause.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"María de Jesús Rovirosa-Hernández, Marisela Hernández González,\nMiguel Ángel Guevara-Pérez, Francisco García-Orduña, Abril de los\nÁngeles Aguilar-Tirado, Abraham Puga-Olguín and Brisa Patricia\nVásquez-Domínguez",authors:[{id:"174651",title:"Dr.",name:"Abraham",middleName:null,surname:"Puga-Olguín",slug:"abraham-puga-olguin",fullName:"Abraham Puga-Olguín"},{id:"203584",title:"Dr.",name:"Ma De Jesus",middleName:null,surname:"Rovirosa Hernandez",slug:"ma-de-jesus-rovirosa-hernandez",fullName:"Ma De Jesus Rovirosa Hernandez"},{id:"203585",title:"MSc.",name:"Francisco",middleName:null,surname:"García-Orduña",slug:"francisco-garcia-orduna",fullName:"Francisco García-Orduña"},{id:"203586",title:"Dr.",name:"Marisela",middleName:null,surname:"Hernández-González",slug:"marisela-hernandez-gonzalez",fullName:"Marisela Hernández-González"},{id:"203587",title:"Dr.",name:"Abril De Los Ángeles",middleName:null,surname:"Aguilar-Tirado",slug:"abril-de-los-angeles-aguilar-tirado",fullName:"Abril De Los Ángeles Aguilar-Tirado"},{id:"206508",title:"Dr.",name:"Miguel Angel",middleName:null,surname:"Guevara-Pérez",slug:"miguel-angel-guevara-perez",fullName:"Miguel Angel Guevara-Pérez"},{id:"206510",title:"Dr.",name:"Brisa",middleName:null,surname:"Vásquez-Domínguez",slug:"brisa-vasquez-dominguez",fullName:"Brisa Vásquez-Domínguez"}]}],mostDownloadedChaptersLast30Days:[{id:"56181",title:"Psychological and Social Aspects of Menopause",slug:"psychological-and-social-aspects-of-menopause",totalDownloads:2529,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Menopause is one of the age-related phases of physiological transition of females. There is robust research and information regarding its biological aspects specially its endocrine base, yet the psychosocial aspect is quite interesting and debatable due to its variability among different cultures and climates. There are certain subthreshold response in form fear and loss of reproductive life to no more ability to reproduce and a feeling of loss of femininity. The period of menstruation simulated to reproductive age or fertility is around half of their lives; therefore, loss of fertility or reproductive life may be a source of stress specially among tribes where long reproductive age period is desired on the cultural belief that this will lead to a large family size that is considered as a symbol of success. Psychological factors such personal or inter-psychic (personality, self-esteem, and coping skills) and intra-psychic (relationship issues and social support) may contribute in the onset, course, and repose to perimenopausal period. There are certain psychiatric conditions such as anxiety, depressive disorder, and premenstrual dysphoric syndrome related to premenopausal period that must be screened. Before embarking on pharmacological treatment, psychosocial intervention especially lifestyle modifications must be offered to avoid complications.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"Iqbal Afridi",authors:[{id:"203383",title:"Prof.",name:"Iqbal",middleName:null,surname:"Afridi",slug:"iqbal-afridi",fullName:"Iqbal Afridi"}]},{id:"56195",title:"Depression and Serotonergic Changes during the Climacteric and Postmenopausal Stages: Hormonal Influences",slug:"depression-and-serotonergic-changes-during-the-climacteric-and-postmenopausal-stages-hormonal-influe",totalDownloads:1503,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Depression is a psychiatric disorder that affects a high percentage of women. Most of the depression disorders turn up during the premenopause and perimenopause stages when the hormonal oscillations make an impact in the brain function principally on the serotonergic system, which is related to neurobiology of depression. 5-HT1A and 5-HT2A receptors change on functionality and density in afferent areas related to emotional modulation and increased serotonin clearance, and the binding potential of serotonin transport has been related to the underlying mechanism of the depression during the climacteric or postmenopausal stage. Some findings have been proven on preclinical studies. These studies on animals have recognized how estrogen treatment activates intracellular signaling pathways as mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK), tyrosine kinase brain-derived neurotrophic factor receptor (TrKB), insulin-like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3)/serine/threonine-specific protein kinase (Akt), and metabotropic glutamate receptor 1 (mGluR1) which interact with the serotonergic system to allow establishment of the estradiol effects on mood regulation. Thus, the interaction between the woman’s reproductive status and the serotonin changes could be useful to create prevention strategies, early diagnosis, and medical treatment of climacteric and postmenopausal women with depression, in order to improve their quality of life.",book:{id:"5984",slug:"a-multidisciplinary-look-at-menopause",title:"Menopause",fullTitle:"A Multidisciplinary Look at Menopause"},signatures:"Rosa Isela García-Ríos, Armando Mora-Pérez and Cesar Soria-\nFregozo",authors:[{id:"174653",title:"Dr.",name:"Rosa Isela",middleName:null,surname:"García-Ríos",slug:"rosa-isela-garcia-rios",fullName:"Rosa Isela García-Ríos"},{id:"174654",title:"Dr.",name:"Cesar",middleName:null,surname:"Soria-Fregozo",slug:"cesar-soria-fregozo",fullName:"Cesar Soria-Fregozo"},{id:"198327",title:"Dr.",name:"Armando",middleName:null,surname:"Mora-Perez",slug:"armando-mora-perez",fullName:"Armando Mora-Perez"}]},{id:"65889",title:"Progesterone Resistance and Adult Stem Cells’ Genomic and Epigenetic Changes in the Puzzle of Endometriosis",slug:"progesterone-resistance-and-adult-stem-cells-genomic-and-epigenetic-changes-in-the-puzzle-of-endomet",totalDownloads:1064,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Endometriosis is a chronic inflammatory disease under hormonal/non-hormonal regulation, and microenvironment influences, originating in adult stem cells (mainly of bone marrow/endometrial progenitor mesenchymal type), and their exosomes, with special migratory and adhesion capacities. The postmenstrual repair with regeneration of eutopic and ectopic endometrium has similar genetic and epigenetic changes versus disease-free women. The competition between ectopic and eutopic endometrium for a limited supply of stem cells, and the depletion of normal stem cells flux to the uterus is considered the novel mechanism through which endometriosis interferes with endometrial functions and fertility. The gene expression DNA/RNA or microRNA changes/dysregulation of estrogen and progesterone receptors represent a possible explanation of progesterone resistance or loss of progesterone signalling in ectopic, and eutopic endometrium versus normal. The genes’ changes involved in hormonal/non-hormonal pathways control of eutopic/ectopic endometrial cells, and of invaded tissues/organs may explain the disease persistency, progression and severity. Deficient DNA methylation of ERβ, the initial genomic event is followed by pathologic over-expressed ERβ in ectopic stromal cells, and it dictates the decline of PR isoforms, PRB being significantly lower in ectopic and eutopic endometrium. Altered expression of ERα, ERβ, and PRs accompanies the conversion of resident normal endometrial cells to ectopic lesions.",book:{id:"8584",slug:"molecular-bases-of-endometriosis-the-integration-between-research-and-clinical-practice",title:"Molecular Bases of Endometriosis",fullTitle:"Molecular Bases of Endometriosis - The Integration Between Research and Clinical Practice"},signatures:"Manuela Cristina Russu",authors:[{id:"219629",title:"Distinguished Prof.",name:"Manuela Cristina",middleName:null,surname:"Russu",slug:"manuela-cristina-russu",fullName:"Manuela Cristina Russu"}]},{id:"33797",title:"Operative Vaginal Deliveries in Contemporary Obstetric Practice",slug:"operative-vaginal-deliveries-in-contemporary-obstetric-practise",totalDownloads:9021,totalCrossrefCites:0,totalDimensionsCites:3,abstract:null,book:{id:"1751",slug:"from-preconception-to-postpartum",title:"From Preconception to Postpartum",fullTitle:"From Preconception to Postpartum"},signatures:"Sunday E. Adaji and Charles A. Ameh",authors:[{id:"74801",title:"Dr.",name:"Sunday",middleName:null,surname:"Adaji",slug:"sunday-adaji",fullName:"Sunday Adaji"},{id:"86877",title:"Dr.",name:"Charles",middleName:"Anawo",surname:"Ameh",slug:"charles-ameh",fullName:"Charles Ameh"}]},{id:"56061",title:"Menopause in Nonhuman Primates: A Comparative Study with Humans",slug:"menopause-in-nonhuman-primates-a-comparative-study-with-humans",totalDownloads:1659,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Although menopause is a phenomenon predominantly studied in humans or laboratory animals, this chapter discussed the case of nonhuman primates (NHPs), not only with the objective of employing them as study models but also to better understand phylogenetic divergence among species. Those taxonomic differences are reflected in reproductive processes that may be similar to those of human beings, with the presence of a defined cycle or periods of estrus, but perhaps at different ages as well, where menopause plays a crucial role. First, it is important to delimit the concept of menopause by considering its anatomical, physiological, and biochemical parameters, including the cessation of menstrual bleeding or perineal swelling—when present—or follicular depletion and hormonal changes. Thus, the aim of this chapter is to discuss some of the similarities between NHPs and human females, during the menopause period. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). 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Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression"},{id:"15",title:"Chemical Biology",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors"},{id:"17",title:"Metabolism",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation"},{id:"18",title:"Proteomics",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/22935",hash:"",query:{},params:{id:"22935"},fullPath:"/profiles/22935",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()