\r\n\tHealth and mental health issues of both children and adults and evidence-based treatments will be included. The types of sexual violence that occur and prevention efforts that have – or have not – been made to address the occurrence of these types of violence will be covered.
\r\n\r\n\tCultural and governmental policies, as well as legal and jurisdiction issues to address victims of these crimes, will also be incorporated in the book. For instance, Meagan’s Law and its worthiness in protecting children will be incorporated as well as the Federal program to reimburse victims of online child pornography and the legal entanglements and ramifications of that program.
\r\n\r\n\tThe typology of offenders and the effectiveness of treatment will also be addressed.
\r\n\tFinally, the direction of prevention strategies, treatment needs for both victims and offenders, and policy issues to move the field forward, particularly in terms of research, will be presented. The field of sexual violence has made significant strides in the past 45 years in terms of understanding sexually deviant behavior, the impact on children who then experience the symptoms of that trauma in adulthood, how to effectively interview sexually victimized children, and finally, treatment and social mores that make disclosure possible and recovery hopeful.
The era of microfluidics started in 1980s with the development of silicon etching procedures which were made for microelectronics industry. This paved way for manufacturing of first of its kind devices called Micro Electro Mechanical Systems (MEMS). In these devices mechanical microelements were integrated together on a silicon wafer. In the 1990s, researchers explored applications of these devices in the field of biology, chemistry and biomedical. They used these devices for controlling liquid’s movement in micro channels which paved way for microfluidics. Laboratories on chip were developed for incorporating all the major procedures of biology, chemistry or biomedical on single platform. But, this use to come with huge cost and infrastructure for microelectronics industry. In 2000s a new era of microfluidics was started with the development of molding micro channels in polymers. This lead to decrease in cost as well as manufacturing time that caused the boom in the area of microfluidics and motivated researchers of all fields to work using them [1]. In the era of fast pacing science, microfluidic are devices to enhance pace of research and decrease the experimental cost. They run on principle of various types of taxis, majorly chemotaxis. Taxis is the movement of particles according to some external guiding agent. This agent can be heat, oxygen, pressure, electric field or chemical, etc. Various types of taxis, their applications and microfluidics are discussed in this chapter. Microfluidic is the technology where movement of the particles is on the basis of microenvironment consisting of viscosity, surface tension and pressure. In microfluidics, micro channels are molded or etched over the silicon, glass or various polymer materials such as PolyDimethylSiloxane. These types of devices are vastly being used in all the fields of research, diagnostics and therapeutics. In microfluidics, the micro channels are formed to attain the desired result which can consist of: mixing, sorting, pumping or controlling the biochemical microenvironment. They have the advantage of decreasing the response time and experimental consumables and overall cost. They have the potential to perform large scale experimentation in small scale. Important factors to be considered for fabrication of microfluidic devices are temperature resistance, superior optical transparency of the material, high hardness, excellent electrical isolation, thermal stability, chemical inertness to many fluids, biocompatibility, and surface wettability. The performance of microfluidic device depends majorly upon etched or molded micro channel’s surface properties. Therefore surface modification is an important factor to improve overall performance of microfluidic devices. Surface roughness, surface heterogeneity and solution impurity are the key parameter which affects the wettability of microfluidic device.
Molecules are always in motion irrespective of their state. Molecules in solid state have least freedom while in gaseous state have maximum freedom. Freedom of movement of molecules in liquid phase lies between molecules in solid and gaseous phases. Heat and temperature are factors that affect the movement of molecules. Enhance temperature increases the translational movement of molecules. Movement of molecules can be random or directed towards certain stimuli. Random movement is termed as “kinesis” while directed movement towards certain stimuli is termed is “taxis”. For taxis, there is sensory component to detect the attractant and motor component to enable the movement towards the stimuli [2]. Taxis are classified on the basis of the stimulus into various categories.
Aerotaxis is the movement of molecules where oxygen acts as stimulant [3]. It has been observed in bacteria and other microorganisms. Active movement of cells is observed along the gradient of oxygen. Aerotaxis plays role in cell survival as optimal concentration of oxygen is required for cell metabolism and growth [4].
Anemotaxis is the movement towards wind. It is observed in drosophila and some terrestrial mammals such as rats which tend to follow the wind. Drosophilla has been observed to move against the air current [5]. Rats were also observed to follow anemotaxis as air current carries information regarding location and odor content [6].
Barotaxis is the movement towards stimulus that is pressure. Movement due to hydraulic resistance (resistance to flow as a result of liquid) is also termed as barotaxis. This type of movement is observed in the neutrophils, a type of immune cell. Neutrophils follows path of least hydraulic resistance.
Chemotaxis can be defined as the movement of cells towards the higher chemical concentration gradient [7]. It is directional locomotion of cells and was first described in the bracken fern spermatozoa in 1884 by Pfeffer. Later in 1888, this phenomenon was described by Leber in mammalian leukocytes in response to an injury. Chemotaxis is an important process required for the growth and development of multicellular organism, immune response and cancer metastasis [8].
Durotaxis is the movement of cells towards more rigid gradient which is a result of variation in the structural property of the extracellular matrix. This type of motion implies movement towards more stiffness [9]. This type of motion has been observed in various cell types such as human fibroblast cells, mesenchymal cells and cancer cells. Substrate rigidity is the stimulus that initiates the movement in durotaxis [10].
Electrotaxis is also termed as galvanotaxis and implies movement guided through electric field or current [11]. Living cells have the tendency to sense and follow direct current electric field. This type of movement is observed in both
Gravitaxis is characterized by directional movement in response to gravity [13]. This type of movement is observed in the motile microorganisms such as euglena where gravity acts as stimulus to select their niche in environment. It can be both positive and negative. Positive gravitaxis implies movement towards water while negative gravitaxis implies movements towards the surface [14]. This type of motion is observed in
Moisture acts as stimulus in hydrotaxis. Movement of cells, animals or plants towards more moisture is termed as positive hydrotaxis and towards less moisture is termed as negative hydrotaxis. Hydrotaxis is observed in the
Magnetotaxis is the movement due to magnetic field. This type of movement is a character of diverse group of gram-negative bacteria that perform their orientation and coordination movements according to earth’s magnetic field [19]. They are majorly aquatic and swim along the geomagnetic field lines. These types of bacteria are also termed as magnetotactic bacteria [20]. Supramolecular adaptive nanomoters have been developed that exhibit magnetotactic behavior and their guided motion is observed in the tissue model [21].
Phototaxis is the movement towards or away from the light source. This type of movement is characteristic of phototrophic organisms and is also observed in plants. Prokaryotes use type-I sensory rhodopsin photoreceptors for phototaxis and it allows them movement towards steep light gradient. Cyanobacteria can also perform phototaxis but they also can perform it in two-dimension only through gliding on the surface. Eukaryotes have the ability to navigate through light vector in three-dimension in open water [22].
Rheotaxis is the movement in response to water or air current. This type of motion is observed in aquatic animals where their movement occurs in response to water current [23]. When movement is towards oncoming water current, it is termed as positive rheotaxis while movement opposite of oncoming water current is termed negative rheotaxis [24]. This type of motion is observed in zebrafish, Crustaceans and American lobsters [25].
Thermotaxis is the movement towards or away from temperature gradient. In this motion, organism move towards temperature source. Slime molds and nematodes are known to move along shallow temperature gradient [26, 27]. Mammalian sperm is also observed to perform theromtaxis to reach towards the oviduct in the female body [28].
Microfluidics is the technology based upon behavior of fluids in the microenvironment. Fluids tend to behave very differently in micrometric scale as compared to macro scale. These characteristics of fluids are now been used for various studies based upon taxis. In macroscopic system, pressure, volume and temperature are the key players whereas viscosity, surface tension, high shear rate and geometric effects (high surface to volume ratios, constriction, and bifurcation) are the key drivers of the microfluidic system [29]. Microfluidics is the integration of fluids physically restricted to sub-millimeter dimensions with micro/nanostructures and devices [30]. Microfluidics is an emerging interdisciplinary field consisting of engineering, physics, chemistry, microtechnology, biotechnology and material sciences [31]. The reason for its emergence is miniaturization of operational unit in the microfluidic devices. Miniaturization is preferred as all operations can be packed in small form that can be automated and is portable [32]. Low amount of materials and chemicals are required for development and samples required is also less. Automation enables widespread use of the system without any special training requirements. Easy disposals, low cost, reduction of cross-contamination and fast response time are other benefits of the microfluidic system [33].
The global size of microfluidic devices was USD 13.5 billion in 2019 and is supposed to have a compound annual growth rate of 11.3%. The large market size is due to its multi-application and ease of usability. Basic layout of microfluidic devices consist of incorporated fluid channels in at least one direction. These channels provide high surface to volume ratio which is useful in applications such as biochemical analysis, antimicrobial susceptibility test and heat exchange modules. This field started with applications in chromatography and electrophoresis [34]. With time it has evolve and currently it has vast applications due to development of new fabrication materials and technologies [31]. Its applications include environmental sensing, biomedical applications, drug discovery, drug delivery, micro scale energy systems, artificial organs, micro scale chemical testing and production, micro propulsion, combinatorial synthesis and assays. These applications have been classified under broad categories for discussion in this chapter.
Microfluidics can be used in biomedical field as analytical arrays, gradients, separators, microdiluters, gel structures, droplets, painting cells and devices [35]. In arrays, a set of multiple microchannels is used to study the relationship between different cells with proteins or chemicals within a combinatorial system. This type of system can be used for detection of specific proteins in large number of samples, antibiotic resistance testing, etc. Microfluidics can be used for generation of very steep gradients that cannot be created using other macro techniques [35]. These gradients are useful in the study of macromolecules and cells in response to their varying environment. Biochemical gradients are useful in dictating physiological processes such as proliferation, differentiation and migration. These gradients play an important role in tissue generation as well. They are used for organ on chip techniques also. Phil et al. used drug gradients for activity measurement over CHO cells [36]. Migration and behavior of neutrophils according to protein gradient has also been studied [37]. Chung et al. used growth factor gradient to study the differentiation of human neural stem cells [38].
Microfluidics can be used as diluters where solution is passed through series of controlled dilutions to be used in a specific assay. Ainla et al. have shown use of pulse width flow modulation based designing of microdiluter [39]. They used this microfluidic diluter for analyzing the effect of Ca(2+) concentration over phospholipid bilayer spread onto a SiO2 surface. Microdiluters can also be used as immunoassays for detection of multiple antigens at a same time [40]. Microfluidics can be used in conjunction with gels or microchannels can be made in gels using soft lithography technique. Various types of gels in which microfluidic can be fabricated are agarose, agar and calcium alginate. These types of systems can be used to study complex microenvironment of cells. Takeuchi et al. used microchannels fabricated in agarose to grow
Point of care devices are diagnostic measures that are directly used by patients and without requirement of medical staff. A simple paper based microfluidic that can be used as point of care device are known as lateral flow test (LFT). Porous material such as glass fiber, nitrocellulose and cellulose paper can be used for fabrication of LFT. The components on microfluidic LFT device are sample collection pad, a dried conjugate pad followed by a reaction area and an absorbent wicking pad. This is incorporated within a plastic housing and plastic barriers throughout to maintain one dimensional flow. The best example of LFT is dipstick pregnancy test kit. This test works on the principle of an immunoassay. Sample which is urine is applied to the sample pad and rehydrates the goldnanoparticles conjugated detection antibodies [43]. These rehydrates antibodies bind to the target antigen present in the sample. Together they flow to the capture region which consists of control and test line. At the test line, non-labeled antibodies specific for the detection antigen are immobilized. When rehydrated labeled antibodies conjugated with the sample antigen reaches test line, it binds to the non-labeled antibodies specific for that same antigen. This interaction gives visual color change thereby making test line visible in case of positive results. This process is depicted through Figure 1a and b. The wicking pad in the device performs function of attracting the sample through LFT. After reaction membrane is completely wetted, the capture region functions through capillary action.
(a) Non-wetting phenomenon, (b) wetting phenomenon, (c) larger contact angle (non wetting), (d) wetting, (e) angle close to zero complete (wetting).
Paper microfluidics has also been used to provide point of care diagnostics for non-communicable diseases such as cardiovascular disease and cancer. In this work, synthetic urinary biomarker is used which is detected through paper microfluidics [44]. These types of devices are also being used for saliva based detection of oral diseases. In the research work by Amy et al. point of care diagnostic device for oral diseased was developed using monolithic disposable cartridge. It was designed in a compact analytical device. This device combined sample pre-treatment procedure of filtering, enrichment and mixing of sample with electrophoretic immunoassays. It can efficiently and quickly measure analyte concentration in the minimally treated and very low volume (20 μl) of saliva sample [45]. Microfluidic devices are also used for digital polymerase chain reaction (PCR) which is a very powerful gene expression analytical tool. Christina et al. showed use of microfluidic based digital PCR for prenatal detection of fetal aneuploidy. Fetal Aneuploidy is the presence of an abnormal number of chromosomes (structures that contain genetic information) in the fetus [46].
Organ on chip is the new class of laboratory models that have advantages of both
The development in the field of integrated microfluidics was successfully laid by its incorporation with the optical elements such as plasmonic surfaces [51] and waveguides [52]. In 2000s, the development of liquid-crystal switchable gratings, microfluidically tunable photonic crystal fibers and bubble switch laid the foundation of using microfluidics as an essential part of the photonic devices. During mid-2000s a new field of “optofluidics” was evolved from the existing technologies in the field of photonics and microfluidics. Using microchannels and photonic elements, optofluidics has the strength of having precise control over light and fluidics at small scale [53]. Microfluidic systems are being used for development of photocatalytic microreactor. A planar microfluidic reactor was developed by Lei et al. It consisted of the small planar chamber where two TiO2 coated slides were used as top cover and bottom substrate. Microstructured UV-cured NOA81 layer was used as the sealant and flow input/output. This reactor has advantages of microfluidics such as easy control of flow, rapid fabrication and large surface/volume ratio. It is the key to more efficient photocatalytic water treatment [54]. TiO2 based microreactor has been developed by Matic et al. for photocatalytic applications. This system was fabricated on metal-titanium foil. Titania nanotubes were mechanically engraved in the substrate foil. Using anodization & hydrothermal treatment TiO2 anatase film was immobilized over the inner layer of these tubules. An additional TiO2 anatase layer was added on top of the film to provide larger photocatalytic area. This microreactor depicted enhanced durability and efficiency [55]. Meng et al. also developed microfluidic based photocatalytic microreactor. They used nanofibrous TiO2 through electrospun to develop this photocatalytic microreactor. It depicted enhance efficiency as compared to TiO2 film based microreactor [56].
Recently, applications of microfluidics have been developed in the form of microfluidic fuel cells. In these cells, all the systems such as fluid delivery, removal, etc. is confined to the microfluidic channel only. These cells do not require a physical barrier for separation of fuel and oxidant species and therefore they operate in co-laminar flow mode. Whereas, in conventional fuel cell a physical barrier such as proton exchange membrane is required. They can be used to power microsystems, generate on-chip power and in consume electronics as well [31]. Microfluidic fuel cells have attracted huge researchers as they are portable power sources with short startup time and environment friendly nature. Microfluidic fuel cell using laminar air flow had been developed by Eric et al. (Figure 2a). It was made through a Y-shaped microchannel consisting of two catalyst covered electrodes on opposite walls. Through these channels, fuel and oxidant merge and flow laminarly parallel between these two electrodes without turbulent mixing. They showed that this type of system can be effectively used to generate microscopic power source for room temperature [57]. There is patented microfluidic fuel cell system for portable energy applications. In this system, microfluidic container, substrate for catalytic composition, a liquid/gas separator, a fuel cell consisting of anode and cathode and electrical connections were all assembled to form this portable energy system [58]. The design of the system and fuel cell components is depicted through Figure 2b and c, respectively [58]. Luke et al. also developed these microfluidic cells based on microbial fuel that can be used to provide power supply to integrated biosensors. This system was developed in polydimethylsiloxane. Here, two carbon cloth electrodes and proton exchange membrane was used.
(a) The reaction of antibiotic dish with bacteria, (b) glass microchannel without bacterial coating, (c) reaction of antibiotic with bacteria in microchannel, and (d) the spreading of chemical reaction in microchannel with different antibodies.
Recent growth in the field of microfluidics has been observed in the field of environmental assessment. Microfluidics is advantageous as multiple processes such as pre-treatment, pre-concentration, separation and detection are incorporated at the same platform. It is used for trace analysis of materials as less risk of contamination is there due to preclusion of sample transportation process. Microfluidics play role in the development of subsurface energy based technologies in the future. Mark et al. developed a microfluidic system based upon high temperature and pressure. Within geo-material micromodels such as rock, cement, clay, etc., direct observations for flow and transport can be made using this system and that too in reservoir conditions. In this micromodel fabrication method, 3D tomography images of real fractures were used as micromodel template. This provided better representation of the pore space and fracture geometries in subsurface formations [61]. Several microfluidic devices can be used for detection and analysis based upon electrochemistry, surface enhanced Raman spectroscopy, chemiluminescence, absorbance and laser-induced fluorescence. These electrochemical and optical based systems can be conjugated on a single micro platform to perform environmental monitoring. These labs on chip systems can be used for real time tracking of pollutants in the environment. Major advantages of these systems are portable compact size, better process control, low-cost production, real-time analysis, low sample consumption and fast response. LOC is used for real-time analysis of pollutants in wastewater. Combining it with the wireless communication, make it a strong tool for modifying data acquisition parameters and data transfer [62].
Microfluidic systems are being used for detection of formaldehyde as well. Formaldehyde is the organic volatile compound found in many household products. It is associated with health risk factors and is also a cause of sick building syndrome. Therefore its detection at real-time in the surroundings is essential for a healthy living. Liu et al. developed a paper based microfluidic system for detection of formaldehyde. Acetoacetanilide reagent is used to implant paper-based chip at reaction site. Concentration of formaldehyde is detected using UV light which induces fluorescence intensity in the dihydropyridine. Dihydropyridine is the complex of formaldehyde with acetoacetanilide. This method was used to detect formaldehyde in the commercial food samples and proved to be an efficient method for detection of formaldehyde concentration [63]. Similarly, Czugala et al. developed a fully integrated microfluidic device to provide wireless and portable analytical platform. This system can be used for detection of nitrite anions in the water. Nitrite anions are one of the water contaminants along with lead, cadmium and nitrate. In this system detection is done through analysis of color intensity of complex formed between nitrite anions and Griess reagent. This color intensity was assessed using low cost Paired Emitter Detector Diode. Biomimetic photoresponsive ionogel microvalve controlled by LED was used for manipulation of on-chip fluid. This system was one of its type that conjugated fully functional microfluidics with photobased valving and photo detection [64]. Microfluidic devices along with porous plugs have also been developed. This device can be used for size based separation of particles including microorganisms and therefore have implications as miniature filter for analysis of water samples. Living radical photo-polymerization technique using wide range of polymers was used for fabrication of these devices. Salt-leaching technique was used for placement of porous plug in the microfluidic channels. Pore size of the porous plug in this device was determined using flow field-flow fractionation. It is a new and cost efficient simple tool for water assessment [65]. Research is moving at a fast pace for development and commercialization of such paper based microfluidic devices that can be conjugated with other existing techniques.
Surface wettability or wetting is the ability of the liquid to maintain contact and interact with the solid surface over which it is flowing. It results from the interaction of intermolecular forces between the molecules of liquid and molecules over the surface of the solid. Surface wettability measurement is a very critical technique to measure the flow of micro fluid in microfluidic applications. In microfluidic devices the detection of small volume change with change in fluid properties is very small because of the micrometer range. In order to detect this small change in micrometer range
In microfluidic devices the motion of chemical reaction governed by chemo taxis gradient and this gradient is responsible for the motion of droplet. The motion of droplet generally measured with the help of wettability and wettability of droplet depends upon the surface. Wettability has a dynamic impact on the displacement of fluid inside micro fluidic device. The change in displacement of any fluid inside any microfluidic device measured in term of spreading of fluid. The spreading behavior of any flowing liquid measured with its wetting behavior and it is generally measured in term of contact angle. The magnitude of contact angle formed by micro fluid with micro-channel wall has great importance to study the characteristics of micro fluidic device.
Example: Suppose a static fluid is placed at the center of any plate and we apply taxis gradient at the two end of plate. The taxis gradient (magnetic, chemotaxis) is responsible for the displacement of fluid inside. The fluid try to spread both in linear (parallel to gradient axis) and lateral (perpendicular to direction of applied gradient) direction. The two directional spreading of liquid makes difficulty in the quantitative measurement in displaced liquid. In order to overcome this issue microfluidic devices play the important role in various scientific testing applications.
The contact angle measurement is carried out using young’s equation is given in Eq. (1). The equation is derived by balancing different interfacial energy in all direction.
where θ = contact angle
σsv = solid/vapor interfacial energy
σsl = solid/liquid interfacial energy
σlv = liquid/vapor interfacial energy.
Wettability of fluid over the solid surface is measured in terms of contact angle (θ). The higher value of contact angle leads to lower wettability (low spreading area of displaced fluid) as shown in Figure 1c. The contact angle close to 0°, as droplet turns into flat puddle shows complete wetting (highest spreading area) as shown in Figure 1e, if angle exceeds zero but is less than 90° as shown in Figure 1d shows wetting [66].
In microfluidic devices the fluid displacement takes place only in linear direction because of micro channel cavity. The quantitative measurement of displaced fluid inside micro channel can be made by measuring the dimension of micro channel and displace length of fluid. The measurement of displace volume with little change in taxis gradient improves the overall sensitivity of device. Sensitivity of device is defined as the measurement of small change in the system by varying input parameter.
The existing process of antibiotic susceptibility measurement uses Petri dish coated with bacteria and divides the Petri dish into required number of segment using marker. An antibiotic dish (different concentrations) is then placed over the bacterial coated Petri dish. The petri dish is then placed over incubator for 24–48 hours. The reaction of bacteria with antibiotic takes place in petri dish and reaction takes place in radial outward direction as shown in Figure 1a. The measurement of reaction in radial direction is difficult to quantify in required scale. To overcome this issue a microfluidic device can be used as antibiotic susceptibility testing device. In this type of device, glass slide micro channel is coated with bacterial coating like petri dish as shown in Figure 1b. Different antibodies are then placed over bacterial coated micro channel for measuring the spreading of reaction due to chemo taxis in one direction and chemo taxis spreading phenomenon can be quantify using microfluidic chip time lapse microscopy as shown in Figure 1d. The spreading of reaction is then measured by the dimension of micro channel as shown in Figure 1c.
In this study, microfluidic device for mixing three liquid is used. In this device, three different liquid A, B and C is used to mix in different concentration and their mixing reaction is measured with the range of output mixing micro channel as shown in Figure 3. In this type of device the change in output parameter can be detect significantly my using small volume of liquid droplet. These devices are very useful to measure mixing behavior of two or more liquid for various chemical mixing applications.
Microfluidic device for mixing different liquid.
The wettability is generally are properties of displaced liquid measured in term of contact angle. The surface morphology, material impurity and porosity are the properties which affect the wettability.
Effect of surface roughness: All smother surfaces look rough in microscopic level. The rough surface of solid specimen affects the wettability of liquid over the solid surface. The contact angle formed with flat surface is called apparent contact angle θa and it is consider by considering ideal surface condition. The actual contact angle θA is generally higher than that of apparent contact angle θa as shown in Figure 4a,b. To calculate real surface free energies of liquid actual contact angle is used. Generally hydrophilic surface is considered to be the best surface where lower value of contact angle is obtain. The wettability of liquid surface generally increases as we decrease the surface roughness of solid surfaces. The relation between roughness and wettability was explained by Wenzel and stated that if the surface is chemically hydrophobic it will become more hydrophobic when surface roughness is added. According to Wenzel,
Effect of surface roughness on the wettability of fluid.
R is the surface ratio between actual and projected area of solid surface over which fluid is flowing. For smother surface R = 1 and apparent contact angle becomes equal to actual contact angle. Other than surface roughness, impurity and porosity in solid surface effect wettability.
In microfluidic device, the displacement of fluid takes place continuously, and it is very difficult to measure wettability (contact angle formed by moving fluid with the wall of micro channel). The Sessile drop method and image analysis techniques are the method used only for measuring the static contact angle of liquid in micro channel device. For biomedical and clinical application the chemotaxis reaction takes place continuously and required continuous monitoring of contact angle
In situ image capturing system for measuring wettability of microfluid devices.
In this system a microscope is just place at the top of microfluidic device and it captures the motion of chemical reaction change in micro channel. A light source is applied from the side to capture the video with more celerity with the help of high speed camera and store video into computer. The video is than sliced into image in required time interval as shown in lower left corner of figure. The Enlarge version of captured screen is shown in lower right corner of Figure 5 which shows the measurement of contact angle variation at different time interval.
The selection of microfluidic fabrication process is dependent on type of material selection for different microfluidic application. The special grade stainless steel, borosilicate glass, PDMS (polydimethylsiloxane), PMMA(Poly methyl metacrylate) copper, aluminum and Acrylic have been used as solid material for microfluidic device fabrication. Chemical etching, 3D printing, Additive manufacturing, micromachining are the common manufacturing practices for the development of different microfluidic devices [68, 69, 70].
Microfluidic devices are one of the most widely used devices of twenty-first century. They are being used in almost all the fields including biomedical, energy, chemical, environmental, etc. Microfluidics is the technology based upon various types of taxis, specifically chemotaxis. Surface wettability is an essential factor in the development of microfluidics. Elucidating mechanisms to improve surface wettability will help in the betterment of microfluidic devices. There are still unexplored applications of microfluidics such as in paint industry: to study the mixing and spreading of paints. Initially, microfluidics developed due to advancement in the field of silicon etching and molding of micro channels technique. The further advancement in the fabrication techniques will pave way for development of high-leveled microfluidic devices that will open a new era of research in all the fields.
We would like to acknowledge DARVUN India for providing us the opportunity of working for them.
The authors declare no conflict of interest.
The clinical manifestations of varicella-zoster virus (VZV) infections of the central nervous system (CNS) include aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and multiple cranial neuropathies (Figure 1) [1, 2, 3, 4]. In these patients, viral antigens or DNA are often detected in the cerebrospinal fluid (CSF) or the sites of pathology. Thus, those neurological disorders reflect reactivation of latent VZV in the trigeminal ganglia and dorsal root ganglion, with subsequent spread of the infection into the CNS [1]. In addition, the incidence of CNS complications caused by VZV is more likely higher in elderly individuals; those with underlying diseases, such as malignant tumors and HIV; and those who are immunosuppressed due to the use of steroids or immunosuppressive drugs [5, 6, 7, 8]. However, it can also affect healthy individuals; therefore, these CNS VZV infections may be suspected even in patients without underlying diseases. Among CNS infections caused by VZV, diseases other than meningitis are rare; however, clinicians should be aware of the various clinical features of CNS infections caused by VZV to start early and accurate antivirus drugs for treatment.
Neurological complications associated with VZV reactivation.
If neurological symptoms occur simultaneously or around the same time as the onset of herpes zoster infection, they can be considered complications of VZV infections. However, if lesions such as rashes, shingles, or blisters are not observed, VZV as a causative agent is likely to be missed. In fact, because VZV can cause CNS complications in the absence of skin lesions, such cases are referred to as zoster sine herpete [9]; clinicians have to consider the possibility of VZV as a causative virus in patients with neurological infections, such as meningitis or encephalitis (Figure 1).
Meningitis is inflammation of the pia mater and the arachnoid that cover the surface of the brain. Its clinical signs include fever, headache, nausea, vomiting, and meningeal irritation symptoms, such as nuchal rigidity and Kernig’s sign. Furthermore, jolt accentuation and neck flexion tests are often positive. However, these are common symptoms and findings of meningitis regardless of the cause. The CSF examination shows monocyte-dominant pleocytosis and elevated protein levels with normal glucose levels. Patients with meningitis wherein bacteria are not detected via the CSF test are generally diagnosed as having aseptic meningitis. Most cases of aseptic meningitis involve viral meningitis. The most common virus that causes viral meningitis is enterovirus. In adults, enterovirus is followed by herpes simplex virus type 2 (HSV-2) and VZV [10], and VZV infection accounts for 8% of the total meningitis cases [11].
VZV meningitis can sometimes cause cranial polyneuropathy or dysuria due to sacral radiculopathy, and dysuria due to sacral radiculopathy is known as Elsberg syndrome. Meningitis caused by VZV is also frequently observed among healthy young individuals. Such a condition generally has a good prognosis and rarely causes any sequelae.
Elsberg syndrome is caused by bilateral sacral radiculopathy, which is characterized by urinary retention, sensory disturbance, and neuralgia of the perineum and lower limbs. Although Elsberg syndrome was originally characterized by urinary retention due to sacral radiculopathy associated with genital herpes, it is now defined as aseptic meningitis-associated sacral radiculopathy. As the causative virus, HSV, particularly HSV-2, is the most common cause, followed by VZV [12, 13]. When urinary retention occurs, urethral catheterization is required. However, this condition resolves as meningitis improves.
A 32-year-old man was admitted to our hospital because of high fever, headache, nausea, acute urinary retention, and dysesthesia in a lumbosacral dermatome distribution. There were no motor symptoms and no rash. CSF analysis showed 249 leukocytes/mm3, 70 mg/dl protein, and positive of VZV DNA by PCR. Gadolinium-enhanced MRI revealed the meningeal lesions of the conus medullaris and the swollen radicular fibers in the upper lumbar spinal canal. Treatment of acyclovir and dexamethasone for 2 weeks led to complete resolution of meningitis and urinary retention.
The symptoms of encephalitis include acute disturbance of consciousness, headache, fever, and convulsions. Neurological findings of encephalitis include meningeal irritation symptoms, such as nuchal rigidity; however, patients with encephalitis sometimes present with motor paralysis and sensory disturbance due to parenchymal brain damage.
Among the pathogens that cause viral encephalitis, VZV is the second most common cause following HSV, accounting for 5% of the total encephalitis cases [14]. According to a recent analysis that used PCR, though, the risk of VZV encephalitis increases in elderly individuals, those with herpes zoster ophthalmicus, and those with disseminated herpes zoster, and this result indicates that the incidence of VZV encephalitis might have increased [15].
The clinical manifestations of VZV encephalitis include meningoencephalitis and vasculopathy [16]. The meningoencephalitis form shows no detectable lesions on MRI. In contrast, the vasculopathy form is characterized by non-specific ischemia, hemorrhagic lesions, and multiple white matter lesions on MRI [16]. Pathological studies suggested that VZV encephalitis develops based on vasculopathy in the large and small vessels. Therefore, MRI typically demonstrates ischemic or hemorrhagic infarction in both gray and white matter and particularly at gray-white matter junctions as characteristic imaging findings of VZV encephalitis [16]. In VZV encephalitis, lesions in the temporal lobe and limbic system, which are often observed in patients with herpes simplex encephalitis, are rare. Moreover, hemorrhagic lesions and necrosis, which are characteristics of herpes simplex encephalitis, are not commonly observed. Because VZV DNA is generally detected in the CSF of adult patients with VZV encephalitis, direct viral invasion to the CNS is believed to be the pathology of VZV encephalitis. In contrast, in varicella encephalitis in children who develop acute cerebellar ataxia associated with varicella infection, VZV is not detected in the CSF. Therefore, a secondary immunological allergic mechanism is considered as the pathology of varicella encephalitis.
Cerebral infarction caused by granulomatous vasculitis is a complication of herpes zoster infection [1, 17]. A typical patient presents with herpes zoster ophthalmicus, followed by postherpetic contralateral hemiplegia, and develops cerebral infarction between the eighth day and sixth month after herpes zoster infection (average of 7 weeks) [18, 19]. Patients with cerebral infarction often present with stenosis or obstruction in the anterior cerebral artery or middle cerebral artery. Because VZV DNA and antigens are detected in the walls of cerebral arteries, this evidence should provide an anatomic pathway for transaxonal spread of VZV after reactivation from trigeminal ganglia as a mechanism of intracerebral VZV vasculopathy [20, 21, 22]. The incidence of stroke increases 6 months after the onset of herpes zoster infection [23], and VZV vaccine and antiviral drug therapy may help reduce the risk of stroke after herpes zoster infection [24]. Cerebral infarction can also develop after varicella infection in children [25]. Although it is rare, it occurs within 6 months after varicella infection, and a similar mechanism as cerebral infarction after varicella zoster infection is considered [25]. In these conditions, VZV, which causes latent infection in the trigeminal ganglion after varicella infection, reactivates and directly invades the vessels in the CNS.
The patient was a 77-year-old woman who was admitted to our hospital due to convulsions and impaired consciousness. She presented with a Glasgow Coma Scale score of E1V1M4, and positive nuchal rigidity was observed. The convulsions were treated with the intravenous injection (IV) of diazepam and intramuscular injection of phenobarbital. However, the patient had high fever after admission at the hospital. CSF examination showed increased cell count (125.0 mg/dl), elevated protein level (125.0 mg/dl), and positivity for VZV DNA, and she was then diagnosed with VZV infection. The patient was treated with acyclovir and dexamethasone, and she regained consciousness and was able to talk on the second day of hospitalization. On the seventh day, she recovered with lucid consciousness without sequelae (Figure 2). Her MRI showed no abnormal lesions in the brain parenchyma, and she was diagnosed with meningoencephalitis.
Clinical course (Case 1).
The patient was a 76-year-old man who developed infarction in the right medial hypothalamus 34 days after the onset of right ophthalmic herpes zoster. He further developed an infarction in the right occipital lobe 73 days after the onset of herpes zoster infection. Although the MRI obtained while the patient presented with herpes zoster rash did not show any abnormal findings, the MRI performed 73 days later showed severe stenosis of the posterior communicating artery.
The patient was a 52-year-old woman with systemic lupus erythematosus (SLE) who exhibited altered levels of consciousness during immunotherapy for SLE. The CSF test showed pleocytosis, an elevated protein level, and positivity for VZV DNA, and the patient was then diagnosed with VZV meningoencephalitis. Brain MRI showed cerebral infarction in the left cerebral white matter, and MR angiogram showed stenosis of the left middle cerebral artery.
Cranial nerve palsy can sometimes develop in patients with herpes zoster of face or neck regions. Facial nerve palsy accompanying herpes zoster infection is known as Ramsay Hunt syndrome, and those patients often exhibit cranial polyneuropathy [26, 27]. Lower cranial polyneuropathy causes dysphagia, dysarthria, and hoarseness. Furthermore, there was no elevation or constriction in the unilateral soft palate, and tongue deviation and muscular weakness of the sternocleidomastoid and trapezius muscles were observed due to unilateral glossopharyngeal, vagus, accessary, and hypoglossal nerve paralyzes. Cranial polyneuropathy is often accompanied by meningitis, and CSF examination showed pleocytosis and elevated protein levels. In most cases, brain MRI shows no abnormalities. However, contrast MRI sometimes shows enhancement in the affected cranial nerves. As a mechanism of this condition, reactivation of VZV from the geniculate ganglion could result inflammatory process, circulatory disturbance, or edema to involve cranial nerves [28].
A 64-year-old woman developed acute paralysis of the IX, X, XI, and XII nerves on the left side after experiencing pain in the left ear and throat. CSF examination revealed lymphocytic pleocytosis and elevated protein levels. VZV DNA was detected with PCR using CSF. She was diagnosed with cranial polyneuropathy due to VZV reactivation. After the oral administration of antiviral agent and steroid, all signs and symptoms dramatically improved. Notably, there was no evidence of cutaneous or mucosal rash during the entire course of the disease. VZV reactivation should be included in the differential diagnosis of multiple cranial nerve palsies, particularly with pain and even without rash.
The patient was a 66-year-old man who presented with dysphagia and hoarseness 2 days after the onset of pain in the left occipital region to the shoulder. At an otorhinolaryngology clinic, recurrent nerve paralysis was observed, and lesions of herpes zoster were noted in the left side of the neck. Left glossopharyngeal, vagal, accessory, and hypoglossal nerve paralyzes were observed during neurological examination. CSF examination showed increased cell count and positivity for VZV DNA, and the patient was diagnosed with multiple lower cranial polyneuropathy.
VZV myelitis is a rare clinical manifestation. However, Brown-Séquard syndrome and transverse myelopathy may occur as a complication of herpes zoster infection [6, 7, 29, 30, 31]. Previous reports revealed that myelitis occurred in elderly or immunocompromised patients, such as those with HIV infection, and this condition often had severe sequelae such as motor paralysis [6, 7]. MRI shows low to equal signal intensity on T1-weighted images and high signal intensity on T2-weighted images, and sometimes, contrast enhancement can be observed as spinal cord lesions. In addition, MRI enhancement may be observed not only in the lesions in the spinal cord but also in the meninges around the spinal cord as well as in the dorsal root nerve, and these findings indicate myeloradiculitis.
Myelitis is often characterized by myelopathy at a level consistent with the spinal segment affected by herpes zoster. As a pathogenesis of this condition, reactivated VZV in the dorsal root ganglion of the spinal cord directly invades the spinal cord from the dorsal root nerve, resulting in myelitis [6, 7]. Moreover, spinal cord lesions are caused by vasculopathy, such as damage to the anterior spinal artery due to vasculitis, similar to cerebral infarction after herpes zoster infection, and this may be considered another mechanism.
The patient was a 60-year-old man with right lower extremity paralysis and sensory disturbance of the right trunk and lower extremity who was diagnosed with VZV myelitis based on CSF examination. MRI of the spinal cord showed a high-signal lesion in the right posterior funiculus at the thoracic vertebral level of Th6 and Th7, which should indicate that VZV directly invaded the spinal cord from the dorsal root.
An 87-year-old woman developed weakness of the right lower limb 2 days after developing herpes zoster lesions in the right side of the chest. Neurological examination revealed a spastic palsy in the right lower limb and loss of pain and temperature sensation in the left side to T6. However, vibration and position senses were not impaired in both sides. Thus, the patient presented with incomplete Brown-Séquard syndrome. Spinal T2-weighted MRI images showed a high-intensity lesion in the right side of the spinal cord except at the posterior funiculus at the Th2 level. CSF analysis showed the following results: leukocyte count, 109/mm3, and protein level, 79 mg/dl, as well as negativity for VZV PCR, elevated titer levels for anti-VZV IgM and IgG, and increased IgG index. Although she was treated with a combination of acyclovir and steroid pulse therapy, her weakness in the right lower limb did not improve. In this case, because the posterior funiculus circulating from the posterior spinal artery was not involved, the incomplete Brown-Séquard syndrome may have been caused by spinal cord infarction due to VZV vasculitis of the anterior spinal artery.
Although most cases of acute herpes zoster are self-limited, about 10–15% of patients with herpes zoster will develop postherpetic neuralgia (PHN) [32], particularly in older adults [33]. Immunosuppressed patients have a higher incidence of PHN. PHN refers to pain persisting for months to years after the resolution of the rash. Sensory symptoms can include pain, numbness, dysesthesias, and allodynia (pain precipitated by movement) in the affected dermatome. And these symptoms may be severe enough to restrict sleep, appetite, or daily activities. The diagnosis of PHN is clear-cut and could be made if those sensory symptoms including pain persist beyond 4 months in the same distribution as a preceding episode of acute herpes zoster [34]. Gabapentin, pregabalin, tricyclic antidepressants, and opioids are generally the first-line drugs for the treatment of PHN [35, 36, 37]. Vaccines are also available for prevention of acute zoster and PHN [38, 39].
For the diagnosis of CNS infection caused by VZV, the detection of VZV DNA with PCR using CSF is necessary [40, 41, 42]. However, a negative VZV DNA result does not rule out VZV infection, and particularly, PCR examination after the initiation of antiviral treatment will likely turn out negative. Thus, testing should be conducted using CSF before the antiviral treatment. When measuring anti-VZV antibodies, a significant increase of the anti-VZV antibody titer in CSF over the course of the illness or findings suggesting the production of intrathecal antibody [serum/CSF antibody ratio ≤ 20 or antibody titer index = (CSF antibody/serum antibody)/(CSF albumin/serum albumin ≥ 2)] should be confirmed.
Antiviral therapy with intravenous acyclovir (10 mg/kg intravenous every 8 hours) should be initiated as soon as the diagnosis is considered [43]. Although the prognosis of meningitis is good, encephalitis and myelitis often result in sequelae, and a delay in the initiation of acyclovir treatment leads to poor prognosis. Therefore, if CNS infection caused by VZV is suspected based on clinical symptoms as well as CSF examination and imaging findings, the administration of acyclovir must be immediately initiated. According to a recent study from the UK, some causative pathogens were identified in 42% of acute encephalitis cases, of which HSV or VZV was identified in one-fourth of the cases. Thus, the administration of acyclovir should be immediately initiated if encephalitis is clinically suspected, and then, acyclovir should be administered for 2 weeks in an immunocompetent host and for 3 weeks in an immunosuppressive host if encephalitis caused by HSV or VZV is confirmed [5]. In CNS infection caused by VZV, the standard administration period is similar. There is no evidence showing the therapeutic effect of adjunctive corticosteroid use. However, corticosteroids suppress the inflammatory response accompanied by cytotoxicity due to the host immune response to viral infection, and in cases of encephalitis/vasculitis, myelitis, and cranial polyneuropathy, the adjunctive administration of dexamethasone or steroid pulse therapy with acyclovir is recommended.
VZV causes the diverse spectrum of neurologic complications: aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and cranial polyneuropathy. Clinicians should be aware of the neurologic complications of VZV, because early acyclovir therapy is necessary for these disorders.
The authors would like to express their gratitude to Dr. Mitsuru Matsuki (Radiology, Kindai University), Dr. Takafumi Hosokawa (Neurology, Osaka Medical College), Dr. Shinichi Haginomori (Otorhinolaryngology, Osaka Medical College), Dr. Hiroshi Ymamamoto (Radiology, Sumitomo Hospital), and Dr. Mitsuyosi Ayabe and Dr. Kazuhito Noda (Neurology, Kurume University) for providing the information of the cases.
This work was supported by JSPS KAKENHI, Grant Number 16 K09704, from the Ministry of Education, Culture, Sports, Science and Technology, Japan.
The authors declare no conflicts of interest.
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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. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Overall, optical methods can support traditional periodontal diagnosis and improve treatment planning and clinical periodontal care.",book:{id:"7244",slug:"periodontology-and-dental-implantology",title:"Periodontology and Dental Implantology",fullTitle:"Periodontology and Dental Implantology"},signatures:"Fardad Shakibaie and Laurence Walsh",authors:[{id:"179467",title:"Prof.",name:"Laurence",middleName:null,surname:"Walsh",slug:"laurence-walsh",fullName:"Laurence Walsh"},{id:"235443",title:"Dr.",name:"Fardad",middleName:null,surname:"Shakibaie",slug:"fardad-shakibaie",fullName:"Fardad Shakibaie"}]},{id:"24363",title:"Biomechanics of Tooth-Movement: Current Look at Orthodontic Fundamental",slug:"biomechanics-of-tooth-movement-current-look-at-orthodontic-fundamental",totalDownloads:26685,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"277",slug:"principles-in-contemporary-orthodontics",title:"Principles in Contemporary Orthodontics",fullTitle:"Principles in Contemporary Orthodontics"},signatures:"Joanna Antoszewska and Nazan Küçükkeles",authors:[{id:"50158",title:"Prof.",name:"Joanna",middleName:null,surname:"Antoszewska",slug:"joanna-antoszewska",fullName:"Joanna Antoszewska"}]},{id:"71271",title:"Flap Techniques in Dentoalveolar Surgery",slug:"flap-techniques-in-dentoalveolar-surgery",totalDownloads:2524,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Most dentoalveolar procedures involve the reflection of mucosal flaps. This step is crucial for exposure or removal of impacted teeth, implant bed preparation, exposure of the alveolar bone for augmentation, periodontal surgeries, and repair of mucosal soft tissue defects, such as oroantral fistula. Because of the rich vascularity of the oral mucosa, great freedom is allowed for flap design, but it tends to result in carelessness and lack of thoughtful planning, which may lead to uneventful outcomes or/and complications. In this chapter, we review oral anatomy, classification, indications, and complications of common oral flap techniques; common flap designs are illustrated, and their fundamental principles are highlighted. The review has covered various flap designs based on their indications. Yet the common flap’s principles are fundamental for all types of flaps regardless of their application, namely, it should provide wide exposure, clear vision, good access, and assure rich vascularity and good final aesthetic outcome.",book:{id:"9387",slug:"oral-diseases",title:"Oral Diseases",fullTitle:"Oral Diseases"},signatures:"Randa Abdulmoein AlFotawi",authors:[{id:"308701",title:"Dr.",name:"Randa",middleName:"Abdulmoein",surname:"Alfotawi",slug:"randa-alfotawi",fullName:"Randa Alfotawi"}]},{id:"65088",title:"Evaluation and Management of Mandibular Fracture",slug:"evaluation-and-management-of-mandibular-fracture",totalDownloads:2862,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The mandibular bone is an important component of the facial bone, which has a unique role in digestive system, speech, and facial esthetics. For these important functions of mandibular bone, it is vital that surgeons should not only treat function but also consider the esthetics together. Mandibular fractures are among the most common traumatic injuries of the maxillofacial region. Even though treatment modalities are well established and being practiced for a long time, untreated and postoperative complications still decrease the patient’s quality of life. This chapter aims to describe the cause, clinical presentations, diagnoses, and current treatment methods on the basis of resent literature.",book:{id:"7572",slug:"trauma-in-dentistry",title:"Trauma in Dentistry",fullTitle:"Trauma in Dentistry"},signatures:"Guhan Dergin, Yusuf Emes and Buket Aybar",authors:[{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin"},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes"},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar"}]},{id:"56461",title:"Permanent Maxillary and Mandibular Incisors",slug:"permanent-maxillary-and-mandibular-incisors",totalDownloads:2611,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The permanent incisors are the front teeth that erupt between 6 and 8 years of age. They are eight in number, four upper and four lower, two centrals and two laterals. They have sharp biting surfaces designed for shearing and cutting of food materials into small chewable pieces. They are the teeth most visible to the others during eating, smiling and talking, and thus, they have high aesthetic value for the individuals. The unique characteristics, arch position, function, development and chronological age of each tooth will be highlighted. In addition, the different aspects with their geometric outlines, outlines and surface anatomy of these teeth will be described. A brief explanation about the pulp cavity, tooth socket and normal occlusion for each tooth will be included.",book:{id:"5814",slug:"dental-anatomy",title:"Dental Anatomy",fullTitle:"Dental Anatomy"},signatures:"Mohammed E. Grawish, Lamyaa M. Grawish and Hala M. Grawish",authors:[{id:"82989",title:"Prof.",name:"Mohammed",middleName:"E",surname:"Grawish",slug:"mohammed-grawish",fullName:"Mohammed Grawish"}]}],onlineFirstChaptersFilter:{topicId:"174",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:22,totalDimensionsCites:0,doi:"10.5772/intechopen.104725",abstract:"This chapter will address evidence-based prosthetic concepts in dental implantology as well as clinical evidence with focus on appropriate logic and technical skills. Those prosthetic factors are as just important as surgical factors, and long-term success can only be achieved if both of those factors are considered, respected, and strictly followed from planning to prosthetic phase of treatment. This chapter will deal with materials selection for prosthetic part, shape, size, and design of supracrestal parts of abutments and their influence on soft tissue and bone stability around dental implants. Furthermore, one of most important decisions is about choosing the proper way of retention: screw- vs. cement-retained restorations, and it will be discussed in detail. Additionally, emergence profile and its function in soft tissues adaptation and adhesion to different prosthetic materials also have important role in long-term success of dental implant restorations.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Ivica Pelivan"},{id:"80964",title:"Upper Airway Expansion in Disabled Children",slug:"upper-airway-expansion-in-disabled-children",totalDownloads:35,totalDimensionsCites:0,doi:"10.5772/intechopen.102830",abstract:"Breathing is essential for life in all of its stages. Cellular, mitochondrial respiration requires an adequate supply of oxygen, provided by the air we breathe, after airway conduction, treatment by the lungs, and transport to tissues. At different stages of life, pediatric dentists and orthodontists can intervene in the upper airway, expanding it, which helps with ventilation. The greater airway space, if used, contributes in different ways to the child’s development and the recovery of respiratory problems and should always be present as a weapon that physicians and the population should know. The value of the techniques becomes even more important when applied to children and young people with disabilities who can significantly improve their development and performance. Rapid Maxillary Expansion and Extraoral Traction Appliances are two important pediatric resources to treat these children. Clinical practice of the authors, is discussed, emphasizing the importance of early intervention and the need for multi and interdisciplinary collaboration in the follow-up of disabled people.",book:{id:"10827",title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg"},signatures:"David Andrade, Joana Andrade, Maria-João Palha, Cristina Areias, Paula Macedo, Ana Norton, Miguel Palha, Lurdes Morais, Dóris Rocha Ruiz and Sônia Groisman"},{id:"80963",title:"Pain Perception in Patients Treated with Ligating/Self-Ligating Brackets versus Patients Treated with Aligners",slug:"pain-perception-in-patients-treated-with-ligating-self-ligating-brackets-versus-patients-treated-wit",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.102796",abstract:"This study compared the perception of pain experienced by patients undergoing orthodontic treatment with conventional, self-ligating brackets and aligners, and investigated the impact that pain had on their daily lives. 346 consecutive patients were included in the study: 115 patients treated with conventional brackets, 112 Patients treated with self-ligating brackets, and 119 patients treated with aligners. The quantitative aspect of pain was assessed using the Visual Analogue Scale, while the qualitative aspect of pain was evaluated using the Moroccan Short Form of McGILL Pain questionnaire. In all three groups experienced pain after activation tended to decrease in the following week. This pain was greater in patients with conventional braces and less in patients with aligners. Using the M-SF-MPQ to describe the qualitative aspect of the pain revealed that the “cramping مزير,” “aching تيألم ” aspect was most accentuated in the 3 groups. Medication intake was correlated with the intensity of pain experienced in all 3 systems. As for the impact of pain on daily activities, patients in groups of conventional and self-ligating braces showed more pain than those in the aligners group. Overall, aligners were less painful than conventional and self-ligating appliances. Patients did not suffer from an alteration in their quality of life due to orthodontic treatment.",book:{id:"10780",title:"Current Trends in Orthodontics",coverURL:"https://cdn.intechopen.com/books/images_new/10780.jpg"},signatures:"Farid Bourzgui, Rania Fastani, Salwa Khairat, Samir Diouny, Mohamed El Had, Zineb Serhier and Mohamed Bennani Othmani"},{id:"80839",title:"Herbs and Oral Health",slug:"herbs-and-oral-health",totalDownloads:55,totalDimensionsCites:0,doi:"10.5772/intechopen.103715",abstract:"Herbal medicine has long been used to prevent and control disease, and it can minimize the potential side effects of chemical products. However, side effects from herbs do exist. Most of the challenges with herbal medicine revolves around inadequate information about the effect of herbs in the oral cavity, the mechanism of action, and potential side effects. There are several herbs described in this chapter have anti-inflammatory, anti-bacterial, anti-viral, anti-fungal in oral micro-organisms. It includes aloe vera, ginger, clove, cinnamon, garlic, neem, miswak, turmeric, tulsi, green tea, chamomile, fenugreek, anise plant, peppermint, bloodroot, caraway, eucalyptus, phyllanthus emblica, black seed, myrrh, rosemary, sage, and thyme; some may act as an alternative management option to current treatments for oral conditions such as caries prevention, gingivitis, periodontitis, oral burn, ulcers and inflammation, after extraction, dry mouth, pain reduction, anesthesia, intracanal medications, ill-fitting dentures, peri-implant mucositis and peri-implantitis. It can be used in several forms such as mouthwashes, toothpastes, topical agents or local drug delivery devices. However, more research is needed to understand their mechanisms and potential side effects.",book:{id:"10827",title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg"},signatures:"Zuhair S. Natto"},{id:"80500",title:"Novel Dental Implants with Herbal Composites: A Review",slug:"novel-dental-implants-with-herbal-composites-a-review",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.101489",abstract:"Missing a permanent tooth is a miserable condition faced by a common man. A tooth decay, periodontitis, mechanical trauma, or any systemic complications lead to such a complication. These bone defects when left untreated lead to severe resorption of the alveolar bone. A proper dental filling with an appropriate bone substitute material could prevent such resorption and paves a way for subsequent implant placement. Dental implants are considered as the prime option by dentists to replace a single tooth or prevent bone resorption. A variety of bone substitutes are available differ in origin, consistency, particle size, porosity, and resorption characteristics. Herbal composites in dentistry fabricated using biphospho-calcium phosphate, casein, chitosan, and certain herbal extracts of Cassia occidentalis, Terminalia arjuna bark, Myristica fragans also were reported to possess a higher ossification property, osteogenic property and were able to repair bone defects. C. occidentalis was reported to stimulate mineralization of the bone and osteoblastic differentiation through the activation of the PI3K-Akt/MAPKs pathway in MC3T3-E1 cells of mice. This implant proved better osteoconductivity and bioactivity compared to pure HAP and other BCP ratios. Terminalia Arjuna was also worked in the incorporation in the graft to enhance the osteogenic property of the implant and gave good results. Another implant bone graft was synthesized containing BCP, biocompatible casein, and the extracts of Myristica fragans and subjected to in vitro investigations and the results revealed the deposition of apatite on the graft after immersing in SBF and also the ALP activity was high when treated with MG-63 cells, NIH-3 T3, and Saos 2 cell lines. This study indicates that the inclusion of plant extract enhances the osteogenic property of the graft. Thus, these novel dental implants incorporated with herbal composites evaluated by researchers revealed an enhanced bone healing, accelerates osseointegration, inhibits osteopenia, and inhibits inflammation. This application of herbal composite inclusion in dentistry and its applications has a greater potential to improve the success rate of dental implants and allows the implications of biotechnology in implant dentistry.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Gopathy Sridevi and Seshadri Srividya"},{id:"78320",title:"Implant-Retained Maxillary and Mandibular Overdentures - A Solution for Completely Edentulous Patients",slug:"implant-retained-maxillary-and-mandibular-overdentures-a-solution-for-completely-edentulous-patients",totalDownloads:63,totalDimensionsCites:0,doi:"10.5772/intechopen.99575",abstract:"The main goal of modern removable prosthodontics is to restore the normal appearance, function, esthetics and speech in each completely edentulous patient. However, if all teeth are missing in a patient, it becomes very complicated to achieve it using traditional protocols. Therefore, implants were introduced into removable prosthodontics to ensure better retention and stability of the conventional dentures. In case of a large amount of bone missing in the jaw it is necessary to ensure the functioning of the dentures constructing various additional stabilizing and retentive prosthodontic solutions on the osseointegrated implants. Numerous types of attachment systems have been used recently for relating implant-retained overdentures to underlying implants: basically splinting (various bar shape designs) and non-splinting attachments (various ball type attachment, magnet attachment, telescopic coping systems). Indications for their use depend on the surgical and prosthodontic factors such as the number and position of the implants, the amount of free intermaxillary space and the type and size of the overdentures. Different indications, types of the overdentures and the attachment systems will be discussed in this chapter.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Dubravka Knezović Zlatarić, Robert Ćelić and Hrvoje Pezo"}],onlineFirstChaptersTotal:53},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:16,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:4,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/22.jpg",latestPublicationDate:"June 23rd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"356540",title:"Prof.",name:"Taufiq",middleName:null,surname:"Choudhry",slug:"taufiq-choudhry",fullName:"Taufiq Choudhry",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000036X2hvQAC/Profile_Picture_2022-03-14T08:58:03.jpg",biography:"Prof. Choudhry holds a BSc degree in Economics from the University of Iowa, as well as a Masters and Ph.D. in Applied Economics from Clemson University, USA. In January 2006, he became a Professor of Finance at the University of Southampton Business School. He was previously a Professor of Finance at the University of Bradford Management School. He has over 80 articles published in international finance and economics journals. His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. Dr. Bobek is a member of the editorial boards of six international journals and a member of the Strategic Council of the Minister of Foreign Affairs of the Republic of Slovenia. He has a long history in academia, consulting, and entrepreneurship. His own consulting firm, Palemid, has managed twenty significant projects, such as Cooperation Program Interreg V-A (Slovenia-Austria) and Capacity Building for the Serbian Chamber of Enforcement Agents. He has also participated in many international projects in Italy, Germany, Great Britain, the United States, Spain, Turkey, France, Romania, Croatia, Montenegro, Malaysia, and China. Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:null},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. 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