Oral biology, oral pathology, and oral treatments are interesting fields in dentistry. The rapid evolution of technologies and the continuous apparition of new materials and products available for practitioners oblige searchers to evaluate their impact on oral tissues and teeth. The evaluation of the biocompatibility of new products is essential to avoid any tissues damage caused by an eventual toxicity or side effects of therapeutic products or materials.This special issue is a compendium of different studies and fundamental and clinical researches. Some papers are focused on the microbiological evaluation of the effect of low level laser therapy (LLLT) in peri-implantitis treatment, a new diagnostic approach using microRNAs as salivary markers for periodontal diseases, evaluation of safety irradiation parameters of Nd:YAP laser beam during an in vitro endodontic treatments, a literature overview about the effects of Nd:YAG 1064 nm and diode 810 nm and 980 nm in infected root canals, efficacy of ultrasonic and Er:YAG laser in removing bacteria from the root canal system, a comparative study of microleakage on dental surfaces bonded with three self-etch adhesive systems treated with the Er:YAG laser and bur, and the study of laser Doppler measurement of flow variability in the microcirculation of the palatal mucosa.We hope that the content of this special issue allows readers to understand the interaction of materials with oral tissues and provides to practitioners new therapeutic methods for their daily practices.Samir NammourToni ZeinounKenji YoshidaAldo Brugnera Junior


The adult pumping heart is formed by distinct tissue layers. From inside to outside, the heart is composed by an internal endothelial layer, dubbed the endocardium, a thick myocardial component which supports the pumping capacity of the heart and exteriorly covered by a thin mesothelial layer named the epicardium. Cardiac insults such as coronary artery obstruction lead to ischemia and thus to an irreversible damage of the myocardial layer, provoking in many cases heart failure and death. Thus, searching for new pathways to regenerate the myocardium is an urgent biomedical need. Interestingly, the capacity of heart regeneration is present in other species, ranging from fishes to neonatal mammals. In this context, several lines of evidences demonstrated a key regulatory role for the epicardial layer. In this manuscript, we provide a state-of-the-art review on the developmental process leading to the formation of the epicardium, the distinct pathways controlling epicardial precursor cell specification and determination and current evidences on the regenerative potential of the epicardium to heal the injured heart. The development of the heart is a complex process. The primitive heart tube is formed from cardiogenic mesoderm of the cardiac crescents, i.e., first heart field (FHF), while anterior and venous poles are derived from a subsequent subset of cardiogenic cells located medial to the cardiac crescents, dubbed second heart field  is a small protuberance that progressively develops within limiting boundaries between the hepatic and cardiac primordia. It is composed of an external epithelial lining configured as a cauliflower structure and an internal mesenchymal component , detaching from the epithelial epicardial layer and migrating first into the subepicardial space. These cells subsequently invade the myocardial walls, giving rise to the epicardial derived cells (EPDCs)  and small non-coding RNAs. Our current understanding of lncRNAs is still in its infancy with just a limited number of reports in the developing heart  of the Spanish Government and the Consejeria de IEconomia y Conocimiento (CTS-446) of the Junta de Andalucia Regional Council.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The assessment of medical outcomes is important in the effort to contain costs, streamline patient management, and codify medical practices. As such, it is necessary to develop predictive models that will make accurate predictions of these outcomes. The neural network methodology has often been shown to perform as well, if not better, than the logistic regression methodology in terms of sample predictive performance. However, the logistic regression method is capable of providing an explanation regarding the relationship(s) between variables. This explanation is often crucial to understanding the clinical underpinnings of the disease process. Given the respective strengths of the methodologies in question, the combined use of a statistical  and machine learning  technology in the classification of medical outcomes is warranted under appropriate conditions. The study discusses these conditions and describes an approach for combining the strengths of the models.


Perineuronal nets (PNNs) are mesh-like structures, composed of a hierarchical assembly of extracellular matrix molecules in the central nervous system (CNS), ensheathing neurons and regulating plasticity. The mechanism of interactions between PNNs and neurons remain uncharacterized. In this review, we pose the question: how do PNNs regulate communication to and from neurons? We provide an overview of the current knowledge on PNNs with a focus on the cellular interactions. PNNs ensheath a subset of the neuronal population with distinct molecular aspects in different areas of the CNS. PNNs control neuronal communication through molecular interactions involving specific components of the PNNs. This review proposes that the PNNs are an integral part of neurons, crucial for the regulation of plasticity in the CNS. Perineuronal nets (PNNs) were first described by Camillo Golgi as a reticular structure that enveloped nerve cells  Table  and subsIn the cortex, PNN neurons occur in high density in the motor and sensory cortex, as well as in the prefrontal and the temporal cortex. They are mostly found in layers 2–5 of the cortex   in the amygdala ensheath parvalbumin and calbindin positive neurons  influence neurons through different mechanisms: it acts as 1) a physical barrier between the neuron and the soluble extracellular matrix; (2) a binding partner for molecules that interact with neurons; and (3) a barrier to prevent lateral mobility of molecules on the neuronal membrane  which is enriched in PNNs compared to the soluble extracellular matrix (ECM) , needs to be captured by PNNs to be internalized by the neuron  was identified in the glial scar  limit the mobility of membrane bound proteins on the neuronal surface. When the PNNs are removed from the neuronal surface using hyaluronidase in neuronal cultures, lateral diffusion of AMPA receptor subunits increases  binds the PNNs and potentiates the inhibition of PNNs to the growth of axons  are an integral part of a neuron and regulate communication between neurons. The PNNs are found in most brain regions and in each region, the PNNs envelope a limited group of neurons. In general, the PNNs are mostly formed around subpopulations of inhibitory neurons but also around some excitatory neurons. The PNN interneurons are mostly fast spiking neurons. It is likely these neurons have evolved to produce PNNs because they are in need of a tool to handle this high level of synaptic activity. PNNs allow the neuron to react to the stress of a high amount of inhibitory and excitatory stimuli.3+ and thus protect the neuron from oxidative stress. The negative charge also regulates ion sorting, which is crucial for fast spiking neurons that have a high utilization of ions. The PNNs have binding capacities for specific molecules, such as Otx2 and Sema3A. They also specifically bind several synaptic receptors and ion channels to regulate the synapse. Furthermore, the PNNs limit lateral mobility of membrane bound proteins. The limitation of lateral mobility affects synaptic proteins such as AMPA receptors. The localization of synaptic proteins is crucial for the efficiency of the synapse, which can in turn lead to plasticity. The three molecular mechanisms described here are mechanisms by which PNNs regulate plasticity.The PNNs regulate plasticity through a variety of molecular interactions. They function as a physical barrier to block the entrance of toxic substances such as amyloid β. The components of PNNs bear a highly negative charge, which allows the PNNs to buffer FeThe molecular interactions in which the PNNs are involved allow the PNNs to regulate communication between neurons. The PNNs regulate which molecules produced by other neurons reach the neuron through its selective binding properties. The PNNs also present signaling molecules to other neurons. Lastly, the PNNs are directly involved in the cell signaling taking place at the synapse. The different communication methods are essential for highly active interneurons to adapt to their surroundings. Interneurons process high amounts of input and fire at a high rate, which leads to high metabolic activity and the risk of oxidative stress. The interneurons produce PNNs to manage this high amount of activity. It is possible that PNNs enable neurons to synchronize their activity. Removal of PNNs with ChABC increases high frequency oscillations in the anterior angulate cortex (Steullet et al., Further investigations into function of the PNNs need to focus on the PNNs as a tool which neurons actively apply to regulate communication. The PNNs form at the outermost surface of the neuron and can serve as an easily accessible target for plasticity treatment to be applied. This would facilitate the modification of neuronal communication. Currently, the enzymatic removal of PNNs by ChABC and hyaluronidase is widely applied as tools for PNN regulation but these are very harsh and non-specific treatments since they remove PNNs and the loose ECM completely. More subtle manipulations of the PNNs by changing the ratio of the different proteoglycans would potentially allow for fine modifications of neuronal plasticity without harming the neuron. In diseases which present with a loss of PNNs, stimulation of PNN formation by providing of PNN components could help to protect neurons. Application of binding partners of PNNs might be another approach to modulate PNN functions without damaging it. Treatment designed to alter the PNNs would not have to enter cells, which makes the PNNs an accessible molecular structure for treatments. Since the PNNs are involved in a variety of diseases, such as schizophrenia (Pantazopoulos et al., Both HvS and JK contributed equally to the idea and the writing of the review.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Manual therapy has been an approach in the management of patients with various disorders dating back to ancient times and continues to play a significant role in current health care. The future role of manual therapy in health care is an important area of research. This paper reviews the history of manual therapy, examines the current literature related to the use of manual techniques , and discusses future research topics. The literature related to manual therapy has historically been anecdotal and theoretical, and current research tends to have a generic approach with broad definitions of manual therapy and inconsistencies in the classification of specific disorders. Systematic reviews of various types of manual therapy have differed on their conclusions regarding the effectiveness of this treatment modality. The current demand in health care for evidence-based practice necessitates a movement towards more specificity in the research of the effectiveness of manual therapy, with emphasis on specific patient signs and symptoms and specific manual techniques that result in effective care.


This paper describes a novel technique for joining similar and dissimilar metal foils, namely micro clinching with cutting by laser shock forming. A series of experiments were conducted to study the deformation behavior of single layer material, during which many important process parameters were determined. The process window of the 1060 pure aluminum foils and annealed copper foils produced by micro clinching with cutting was analyzed. Moreover, similar material combination  and dissimilar material combination  were successfully achieved. The effect of laser energy on the interlock and minimum thickness of upper foils was investigated. In addition, the mechanical strength of different material combinations joined by micro clinching with cutting was measured in single lap shearing tests. According to the achieved results, this novel technique is more suitable for material combinations where the upper foil is thicker than lower foil. With the increase of laser energy, the interlock increased while the minimum thickness of upper foil decreased gradually. The shear strength of 1060 pure aluminum foils and 304 stainless steel foils combination was three times as large as that of 1060 pure aluminum foils and annealed copper foils combination. With the rapid development of the automobile industry, the lightweight design of the automobile has been a wide concern. In order to reduce the weight of the automobile body, lightweight materials such as aluminum alloy has been widely used, which has set a higher standard for the joining technology of similar and dissimilar metal plates . In mostHowever, there are two main problems while joining similar and dissimilar materials by mechanical clinching process. Firstly, the poor formability of materials limits the application scope of mechanical clinching. To this end, two possible solutions are available: increasing the material formability by pre-heating and improving the material flow by optimizing the geometry of the clinching tools . Based oThe miniaturization of products is an important growing trend in precision mechanics and the electronic industry, which brings increased demands on joining processes in micro scale . NeverthThe purpose of the current study was to experimentally verify the feasibility of a novel micro clinching with cutting process for joining similar and dissimilar metal foils. Many important process parameters were determined by studying the deformation behavior of single layer metal foil in the mold. The process window of the 1060 pure aluminum foils and annealed copper foils (Al/Cu) was given through a series of experiments. The effect of laser energy on the interlock and the minimum thickness of upper foils were studied. Moreover, the connection strength of different joints was measured by the single lap shearing tests.The basic schematic diagram of micro clinching with cutting by laser shock forming is shown in The necessary condition for the process of micro clinching with cutting by laser shock forming is the generation of interlock without fracture of upper foils . The intIn this research, a Spitlight 2000 Nd-YAG laser  with Gaussian distribution beam was employed, and its main parameters are listed in h) can be adjusted by changing the thickness of the spacer. As the depth of the mold (h) gradually increases, the width of the chute (w) on both sides of the mold also increases. The combined mold used in the experiments was made of SKH-51 high speed steel. This kind of high speed steel is suitable for processing the mold with high hardness, high stiffness, and good impact resistance. As shown in 2 and the lower foils are cut into square pieces of 15 × 15 mm2. The upper and lower foils were stacked on the combined mold. The combined mold was fixed on a three-dimensional mobile platform. By adjusting the distance between the metal foils and the focusing lens, the spot diameter was controlled so that it was larger than the mold diameter. In this experiment, a spot diameter of 3 mm was used. The detailed experimental parameters are listed as follows in There were three kinds of metal foils used in the experiments: 1060 pure aluminum foils, pure copper foils annealed at 450 °C, and 304 stainless steel foils. Different kinds of metal foils with different thicknesses were combined together to verify the feasibility of joining similar and dissimilar materials by the micro clinching with cutting process. The upper foils were cut into square pieces of 10 × 10 mmIn this experiment, single lap shearing tests were carried out to measure the mechanical strength of the clinched joints under different material combinations. For each processing condition, three samples were tested. Micro clinching with cutting by laser shock forming is a very complicated process which involves many process parameters such as the number of laser pulses, the depth of the combined mold, laser energy, and the combination of different materials with different thicknesses. In order to study the influence of various process parameters on different material combinations, the deformation behavior of single layer metal foil under different experimental conditions was studied first. During this study, some important process parameters were determined. Subsequently, the experiments of different material combinations were carried out according to the laws derived from the study of single layer metal foil.The study of the deformation behavior of single layer metal foil under different laser energy and the different number of laser pulses is essential for better understanding the micro clinching with cutting process. The deformation behavior of single layer 1060 pure aluminum foil with the thickness of 100 μm produced under different laser energy is shown in Veenaas et al.  producedThe total thickness of materials and the die depth are two important parameters in the process of micro clinching with cutting. It was important for this experimental research to study the matching relationship between the two process parameters. Firstly, the matching relationship between the thickness of single layer 1060 pure aluminum foil and the die depth was investigated. The deformation behaviors of single layer 1060 pure aluminum foil differ when produced under differing mold depths, as can be observed in On the basis of the above research, the matching relationship between the total thickness of two layers of metal foils and die depth was identified. After additional experiments, the matching relationship between the total thickness of the materials and die depth was determined and is illustrated in In the conventional mechanical clinching, the main failure modes of clinched joints are button separation, neck fracture, or a combination of both mechanisms . The sepIn contrast, the main failure modes of micro clinching with cutting by laser shock forming differ from the conventional mechanical clinching. To obtain optimum joining conditions of the metal foils, a series of experiments were conducted. As shown in The joinability for the 1060 pure aluminum foils and annealed copper foils combination of different thickness by micro clinching with cutting process is shown in The cross sections of the clinched joints with different material combinations are shown in The interlock and the minimum thickness of upper foil were the main quality criteria of the clinched joints. It is very important to study the variation tendency of the interlock and minimum thickness of upper foil under different laser energy. As shown in For each processing condition, three samples were tested. In the conventional mechanical clinching, the main failure modes on clinched joints can be categorized into full shear, partial shear, and unbuttoning with crack as well as the full unbuttoning. The failure mode of the clinched joints depends on the size of interlock and α-angle . Moreove(1)Under the single laser pulse, the large interlock could not simply be formed by the increase of laser energy. The use of moderate energy and multiple laser pulses can solve this problem. After a series of experiments, the number of laser pulses was determined to be three pulses.(2)There is a certain matching relationship between the total thickness of the materials to be connected and the die depth. With the increase of the total thickness of materials, the corresponding die depth that can form a large interlock increases. In addition, the change of the die depth has less influence on the joining of thicker materials. When the total thickness of the materials was in the range of 60–100 μm, the optimum die depth was about two-thirds of the total thickness.(3)The similar and dissimilar materials could be joined by the micro clinching with cutting process. Seen from the process window of 1060 pure aluminum foils and annealed copper foils, micro clinching with cutting process is more suitable for the material combinations where the upper foil is thicker than the lower foil.(4)The optimal laser energy for joining the 1060 pure aluminum foils and annealed copper foils (Al/Cu) was in the range of 1200–380 mJ. With the increase of laser energy, the interlock between the metal foils increased while the minimum thickness of the upper foil gradually decreased.(5)According to the load-displacement curves, it was observed that the maximum load force of Al/Ss combination is about 13.12 N, which is three times larger than that of the Al/Cu combination. The Al/Ss combination with higher shear strength may be due to higher tensile strength of the lower foil or larger interlock and neck thickness of the upper foil. Furthermore, different material combinations had different failure modes.In this paper, a novel micro clinching with cutting by laser shock forming technology is described. Many important process parameters were determined by studying the deformation behavior of single layer 1060 pure aluminum foil under different experimental conditions. The feasibility of this novel technology was verified by joining similar and dissimilar materials in micro scale. The effect of laser energy on the interlock and minimum thickness of upper foil was investigated. In addition, the mechanical strength of different material combinations joined by micro clinching with cutting process was measured. The main results are summarized as follows:


The new epicenter of the tularemia outbreak was 300 km west of the epicenter of the previous outbreak in Eastern Bulgaria. The authors undertook to track the source of the outbreak using molecular methods .Their study is remarkable for, among other things, the relative lack of the application of traditional epidemiological methods in tandem with the molecular methods. They made no definite conclusion.Myrtannas et al.  studied Francisella tularensis (FT) from the old to the new foci of outbreaks. However, the high BMR may not necessarily be a physical barrier to the aerosolized transmission of FT.[The authors of the study referred to above did not mention the total number of cases detected during in new outbreaks, making one wonder how the authors defined an outbreak. Also, iton of FT.The authors  suspecteThe study presented by Myrtannas et al.  shows th


A large self-report population study in Denmark found twofold increased prevalence of infantile autism in offspring of mothers that suffered influenza infection during pregnancy, and a threefold increased prevalence of ASD in children of mothers who experienced prolonged period of fever  employing 257 postmortem samples from ASD and matched control brains that were subjected to H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq)  that are small non-coding regulatory RNAs which mediate mRNA destabilization and/or translational repression Hammond,  has alsoAlthough the above-mentioned studies demonstrate the role of epigenetics in predisposition to ASD, some investigations does not support a role for epigenetics in autism. A study reported no difference in the proportion of global methylation between control and autistic brain  or brain samples from a larger sample size to determine the role of epigenetics in ASD and confirm the validity of results. Nevertheless, the well-controlled studies can provide critical insights into the role of epigenetics in the pathophysiology of ASD. With the emergence of new state-of-the-art cutting edge technologies such as whole genome sequencing (WGS), it is possible to comprehend the complex role of epigenetics in ASD. The new genomic techniques allow more coverage of the genome, can provide better knowledge about ASD specific histone markers as well as can help in determining the contribution of non-coding regions such as intergenic regions and noncoding RNAs.Autism researchers and individuals with ASD themselves have plenty to benefit from in learning through the fundamentals of epigenetics, as there exists a sense of robustness in the search for new epigenetic biomarkers that can be used for future interventions. Efforts in research of the epigenetics of autism are still uncertain and at times unrewarded, yet the prospective payoff of alleviating ASD-symptoms is too great a reward to not delve even further. A better knowledge about the role of epigenetics in autism will help in developing novel diagnostic biomarkers and treatment modalities leading to improved quality of life of many ASD patients and their families.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study was a landmark investigation whose positive results led to increased funding and support to build first episode psychosis programs across the US. Every state in the country received dedicated funding to implement a coordinated specialty care (CSC) program designed to identify and treat persons with first episode psychosis within the context of the nation’s multi-payer health system. Since the funding began in 2014, numerous CSC programs have been developed but little is known about which models of treatment providers are implementing and the success of these programs. The research here presents data from a survey focusing on providing feedback from the first episode psychosis programs in the US implementing NAVIGATE, the CSC program utilized in RAISE-ETP. The survey targets the program directors in the NAVIGATE programs; the aims of the survey include 1) to describe the program characteristics of NAVIGATE teams in the US and 2) to better understand how NAVIGATE programs are identifying and enrolling people into their services. Capturing local data on CSC team composition and case identification strategies is particularly critical in multi-payer systems lacking guidance and oversight from a national health system.An online survey is being conducted to assess the implementation of NAVIGATE programs in the US and evaluate the procedures that the program director utilizes to identify and enroll NAVIGATE participants in services. Program directors from NAVIGATE programs are being identified and contacted to participate by national trainers to join a national database of first episode programs. Program data collected includes information about the location of the program, staff in the different NAVIGATE team roles , program enrollment criteria, number of participants screened and enrolled, and rates of planned and unplanned discharge. In addition, program directors are asked questions to report community based strategies to identify participants and screening procedures to enroll participants. Data analysis will focus on presenting the demographic and clinical characteristics of the programs. Common themes will be ascertained, including barriers and facilitators to identifying and enrolling participants with first episode psychosis. Helpful recommendations provided by the project directors on identifying and screening participants will be synthesized and reported.There are approximately 30 NAVIGATE programs in 14 states in the US. Results will highlight the dissemination of NAVIGATE in the US and implementation of these programs across a wide range of different communities. We will describe the dissemination of NAVIGATE across the US and similarities and differences across NAVIGATE programs. Results also will provide feedback on the challenges and helpful strategies that program directors have used to engage people in treatment.The findings from this survey will be the first to provide an overview of the implementation of the NAVIGATE program in the US. The results will provide an overview of the dissemination of the NAVIGATE program, the only CSC program evaluated in a national US trial. Recommendations could help inform the ongoing development and dissemination of coordinated specialty care programs.


Pain is an integrative phenomenon that results from dynamic interactions between sensory and contextual  processes. In the brain the experience of pain is associated with neuronal oscillations and synchrony at different frequencies. However, an overarching framework for the significance of oscillations for pain remains lacking. Recent concepts relate oscillations at different frequencies to the routing of information flow in the brain and the signaling of predictions and prediction errors. The application of these concepts to pain promises insights into how flexible routing of information flow coordinates diverse processes that merge into the experience of pain. Such insights might have implications for the understanding and treatment of chronic pain. Pain is a vital phenomenon that depends on the dynamic integration of sensory and contextual processes. In chronic pain the adaptive integration of sensory and contextual processes is severely disturbed.Neuronal oscillations and synchrony at different frequencies provide evidence on information flow across brain areas. The flexible relationship between oscillations at different frequencies and pain indicates flexible routing of information flow in the cerebral processing of pain.The systematic assessment of oscillations and synchrony in the processing of pain provides insights into how sensory and contextual processes are flexibly integrated into a coherent percept and into abnormalities of these processes in chronic pain. Predictive coding frameworks might help us understand these integration processes. Pain results from dynamic interactions between sensory and contextual  processes Here we review recent evidence on the role of neuronal oscillations and synchrony in the processing of pain. We begin with a brief discussion of the peculiarities of pain and its processing in the brain. We then summarize recent insights into the significance of neuronal oscillations and synchrony for the routing of information flow in the brain. On this basis we review evidence on the role of oscillations in the processing of pain. We specifically discuss how oscillations and synchrony serve the flexible routing of information flow in the integration of sensory and contextual factors into a coherent percept. Moreover, we review and discuss the role of these processes in pathological abnormalities of the pain experience in chronic pain. Finally, we consider perspectives and future directions for the study of the role of neuronal oscillations in the cerebral processing of pain.nociception , electroencephalography (EEG), or magnetoencephalography (MEG) supragranular layers and terminate in layer IV. Feedback projections predominantly start in infragranular layers and terminate in layers other than layer IV. Second, the non-homogeneous distribution of feedforward and feedback connections is complemented by a non-homogeneous distribution of brain oscillations across cortical layers. Several studies demonstrate that oscillations at alpha and beta frequencies (8–29 Hz) are stronger in infragranular layers than in supragranular layers. By contrast, oscillations in the gamma frequency band (∼30–100 Hz) are stronger in supra- than in infragranular layers of the cortex Granger causality) indicated stronger connectivity in the gamma band from lower towards higher hierarchical areas  whereas directed connectivity in the opposite direction (from higher to lower areas) is stronger in alpha/beta frequencies.This framework is based on a convergence of anatomical and functional findings in animals and humans. First, in the visual system anatomical connections have been differentiated into feedforward (bottom-up) and feedback (top-down) connections Taken together these findings indicate that neuronal oscillations and synchrony in distinct frequency bands serve the dynamic routing of information flow in the brain. Previously seemingly independent strands of research converged on the notion that alpha/beta oscillations mediate feedback signals whereas gamma oscillations mediate feedforward signals. In predictive coding frameworks of brain function, this might correspond to the signaling of predictions and prediction errors, respectively . The invMost studies on the cerebral processing of pain have investigated responses to phasic pain stimuli in the range of milliseconds to seconds. These results are likely to apply to acute pain events that signal threat and promote protective behavior. Fewer studies have investigated the brain mechanisms of longer-lasting pain of months and years as a key feature of pathological chronic pain conditions. Furthermore, experimental studies on longer-lasting pain in the range of minutes (tonic pain) have investigated pain at timescales between those of phasic and chronic pain and are intended to represent an experimental approach towards chronic pain.EEG and MEG studies showed that brief noxious stimuli induce a complex spectral–temporal–spatial pattern of neuronal responses with at least three different components. First, pain stimuli evoke increased neural activity at frequencies below 10 Hz. These increases occur between 150 and 400 ms after stimulus application. They originate from the sensorimotor cortex and the frontoparietal operculum including the insula and secondary somatosensory cortex as well as from the mid-/anterior cingulate cortex. They correspond to the well-investigated pain-related evoked potentials The functional significance of the different components of pain-related brain activity is not yet fully understood. So far the evidence indicates that the components are differentially sensitive to different modulations of pain. Bottom-up modulations of pain by varying stimulus intensity  influences all three components The findings, however, indicate that brain activity at different frequencies provides different and complementary information about pain. Moreover, they indicate that there is no one-to-one correspondence between any frequency component of brain activity and pain, which extends the lack of specificity of brain activity for pain The assessment of brain responses to phasic painful stimuli shows the impact of contextual modulations on stimulus processing but not the mechanisms of the modulations. A straightforward approach to the disentangling of contextual processes from stimulus processing is the assessment of prestimulus activity, which cannot be contaminated by any stimulus-related processes. The few studies on this topic with respect to pain intracranial recordings in a few patients with epilepsy investigated the significance not only of prestimulus oscillations but also of prestimulus connectivity between brain areas for pain. The results indicate that attention to pain changes the connectivity between pain-relevant brain areas at alpha and beta frequencies Studies using The above-reviewed evidence relates to the processing of brief experimental pain stimuli. It is, however, unclear how these findings relate to the brain mechanisms of longer-lasting pain of months and years, which is the key feature of chronic pain. Experimental studies using longer-lasting tonic experimental pain stimuli in the range of minutes represent a step further in that direction. These studies have shown that tonic pain is associated with suppression of oscillations at alpha frequencies Thus, during a few minutes of painful stimulation the encoding of pain shifts from gamma oscillations over brain areas encoding sensory processes to gamma oscillations over brain areas encoding emotional–motivational phenomena. These findings indicate that pain-related information flow might change not only with the behavioral context but also with the duration of pain. In the current framework of flexible routing of information flow , these fThe analysis of oscillations and synchrony is conceptually promising and methodologically well suited for the investigation of ongoing processes such as chronic pain. However, remarkably few studies have addressed this topic and the results are not fully consistent see , 35. ThiA less-noticed finding is an increase of oscillations at alpha and beta frequencies In summary, the data show mostly changes of theta and beta oscillations in chronic pain, the latter particularly in frontal brain areas. Considering disturbed integration of nociceptive and contextual processes in chronic pain, an abnormal balance of feedforward and feedback signaling and thereby an abnormal balance of oscillations at different frequencies might play an important role in chronic pain. However, the role of neuronal oscillations and synchrony in chronic pain is a largely unexplored field and the emerging concepts await further empirical testing.Recent evidence has shown that oscillations and synchrony play a crucial role in the flexible routing of information flow in the brain. In particular, oscillations at gamma and alpha/beta frequencies have been shown to serve feedforward and feedback processing, respectively. The flexible routing of information flow might be particularly relevant in the processing of pain where the dynamic integration of sensory and contextual processes plays a crucial role . The resChronic pain appears to be associated with abnormal oscillations at theta and beta frequencies. Although the specificity of these findings has remained unclear, at least part of them would be compatible with abnormal contextual feedback processes playing a central role in the pathology of chronic pain. More standardized approaches, larger patient samples, data-sharing initiatives, and more sophisticated and timely analysis strategies such as graph theory-based network analyses Furthermore, considering the preeminent role of the integration of contextual and sensory information in the processing of pain, an application of predictive coding frameworks  to the pOutstanding QuestionsRecent studies discuss the significance of interactions of oscillations at different frequencies . What is the role of cross-frequency coupling in pain? In particular, how do infraslow fluctuations observed by fMRI relate to oscillations at higher frequencies in the processing of pain?Pain modulations can be harnessed for pain therapy. However, a systematic understanding of pain modulations is so far lacking. Can the assessment of oscillations and patterns of cerebral information flow help to establish a brain-based taxonomy of pain modulations?It is tempting to relate the interaction between sensory input, contextual information, and pain to predictive coding frameworks of brain function. How can this relationship be specified and experimentally tested? What are the consequences for the understanding of pain and chronic pain?The analysis of oscillations is conceptually and methodologically well suited for the investigation of the brain mechanisms of chronic pain. However, evidence on the role of oscillations and synchrony in chronic pain is remarkably limited. Can timely network analyses of EEG, MEG, and fMRI data specify abnormalities of oscillations and synchrony underlying chronic pain?Subcortical areas including the ventral striatum, amygdala, and hippocampus play an important role in chronic pain. Although neuronal oscillations from these areas are well known they have not so far been investigated during pain. How can subcortical oscillations be recorded and how do they integrate in patterns of cerebral information flow?Recent studies discuss the use of patterns of brain activity as markers of pain. Can patterns of neuronal oscillations and synchrony serve as diagnostic and/or prognostic markers of pain? Can we target neuronal oscillations and synchrony for pain therapy using pharmacological, behavioral, neuromodulatory, or neurofeedback approaches?Thus, based on recent progress in our understanding of neuronal oscillations, their systematic assessment might provide a unique window onto the dynamics of cerebral information flow and related predictive coding processes underlying the experience of pain in health and disease.


Rheological techniques and methods have been employed for many decades in the characterization of polymers. Originally developed and used on synthetic polymers, rheology has then found much interest in the field of natural (bio) polymers. This review concentrates on introducing the fundamentals of rheology and on discussing the rheological aspects and properties of the two major classes of biopolymers: polysaccharides and proteins. An overview of both their solution properties (dilute to semi-dilute) and gel properties is described.


In connection with the sustainable development of scenic spots, this paper, with consideration of resource conditions, economic benefits, auxiliary industry scale and ecological environment, establishes a comprehensive measurement model of the sustainable capacity of scenic spots; optimizes the index system by principal components analysis to extract principal components; assigns the weight of principal components by entropy method; analyzes the sustainable capacity of scenic spots in each province of China comprehensively in combination with TOPSIS method and finally puts forward suggestions aid decision-making. According to the study, this method provides an effective reference for the study of the sustainable development of scenic spots and is very significant for considering the sustainable development of scenic spots and auxiliary industries to establish specific and scientific countermeasures for improvement. The sustainable development of tourism occupies a dominant position in Sustainable Development Goals (SDGs) of the whole world at present. In the opinion of the World Tourism Organization (WTO), sustainable development of tourism should not only meet existing demands from scenic spots and tourists but also meet future ones . A sceniIn order to promote the sustainable development of scenic spots, scholars have undertaken extensive and in-depth exploration from various perspectives, mainly including those described below.The first is to discuss about the influence of a certain factor or driving mechanism on the sustainable development of scenic spots. Jin and Hu start from the crowding of scenic spots to study the influence of crowding as perceived by tourists on the development of scenic spots, focus on analyzing the psychological influence and provide suggestions to the management of scenic spots . Yao andThe second is to discuss about the influence of coordinated development of stakeholders on the sustainable development of scenic spots. Mónica et al. evaluated the sustainable tourism strategy of stakeholders of National Park by analytic network analysis and Delphi-type judgment-ensuring process . Carlos-The third is to organize the multiple-objective study and evaluation of the development of scenic spots to facilitate the sustainable development of scenic spots. Early in 1998, Garrod and Fyall pointed out that the focus should be shifted from the definition to the practice of sustainable development of tourism, and established a frame to measure the sustainable tourism . EvaluatSignificant achievements have been made with respect to the study of sustainable development of scenic spots and many scholars have made great contributions resulting from their own understanding of the nature of sustainable scenic spots. However, there are few quantitative studies on the sustainable development of scenic spots. Existing ones often focus on a certain aspect of the scenic spot development, such as natural resource , ecologiFollowing the logic shown in R represents principal component score matrix after extraction and rotation of factors.In n measured objects and each object possesses p index data to constitute the initial measurement matrix of p indexes, so it is able to obtain m aggregate indexes from p indexes (p indexes by such m indexes with little information lost [(1)Data standardization. This paper relies on the raw data of measurement index of each province and city to establish the initial measurement matrix (2)Computing related coefficient matrix (3)According to the characteristic equation (4)Computing principal component contribution rate Principal Components Analysis (PCA) reduces the dimensionality of a higher dimensional variable space and replaces existing multi-dimensional variables with a few aggregate variables by linear transformation and abandoning some information while minimizing the loss of raw data . Its basion lost . This pai principal components has reached 80–95%, the first i principal components should be set as new variables.(5)Computing principal component loading (6)Computing the score of each principal component:If the accumulated contribution rate of the first The entropy method is an objective method for constructing the judgment matrix based on the value of evaluation index and determining the weight by the degree of variation of each index. Determining the weight of each principal component by entropy method may eliminate the influence brought by subjective factors to the largest extent to obtain a more practical result. Steps of determining the entropy weight are listed below:(1) Standardization of principal component indexesAssuming there are n measured objects (province and city) and m principal component factors, the standardization matrix established according to the score of each principal component of the measured object is (2) Determination of entropy and entropy weight of principal component factorsjth principal component factor are:In accordance with the definition of entropy, the entropy value In the equation, the original expression of ningless , so the Technique for Order Preference by Similarity to an Ideal Solution (“TOPSIS” for short), which is the one of group of MCDM methods, was first proposed by Hwang and Yoon in 1981 . TOPSIS (1) Establishing weighted standardized matrix jth principal component factor and ijy is the score of the jth principal component of the ith measured object:In the equation: jth index and jth inverse index.In the equation: (2) Computing the distance of each province and city to the positive ideal point A larger Development of scenic spots more and more involves challenges from society, economy and the ecological environment to complement the urgently needed sustainable development. The sustainability of scenic spots is affected by many factors, commonly comprising economic, resource and environmental aspects. The essence of sustainable development of scenic spots is to ensure the long-term reasonable economic development and fair distribution of social and economic benefits to stakeholders (auxiliary industries in relation to the sustainable development of scenic spots); and resources and environment should be utilized to the optimal extent as critical elements for the development of scenic spots. In the establishment of measurement indexes of sustainable development of scenic spots, indexes should not only reflect the authentic situation of sustainable tourism but also keep sufficient comparability and applicability for a certain period. Therefore, based on the existing relevant literature ,35,36,37Such an index system of the sustainable development of scenic spots divides two types of sustainable development into five aspects, including resource condition, economic benefits, ecological environment, auxiliary industry scale and benefit (primary index), and establishes measurement indexes under such five aspects (secondary index). The logic of index selection is as follows.Resource condition of scenic spot, including natural resource, human resource and market resource, is fundamental for the sustainable development. Natural resource is the foundation and precondition of tourism activity. Difference and relative advantage of natural resource are critical for the tourism activity and directly influence the selection and flow of tourists. Natural resource indicators include B11 and B12. Moreover, management of the scenic spot is only effective under the support from human resource, the situation of human resources in scenic spots is reflected by B13, and the market resources are measured by B14 and B15.Economy of scenic spots, which is the economic benefit generated by tourism activities on the basis of resource condition, offers a physical guarantee of the sustainable development of the scenic spot. It comprises of economic benefits (reflected by B21–B24) from food & beverage, amusement and sightseeing, and also experience of tourists brought by tourism activities (measured by B25).Ecological environment of scenic spot is the radical guarantee of the sustainable development. Ecological environment should be concerned at all times while tourism resources are being developed reasonably. Ecological environment is especially important when the green, low-carbon and cyclic economic development is advocated. Therefore, ecological environment indexes should cover the greening of scenic spot and ecological environment improvement. B31 and B34 quantitatively reveal the amount of atmospheric pollutant emissions and the number of treatment facilities caused by the development of tourism economy; B32 and B33 can demonstrate the situation of green cover of green space and forest around the scenic spot; B35 and B36 outline the status of pollutants and waste disposal.Auxiliary industry refers to surrounding auxiliary industries and transportation industry, which are important parts of stakeholders of the development of scenic spot. While integrating its own resource advantages in the sustainable development, the scenic spot should give consideration to the development demand of stakeholders (auxiliary industry). On the other hand, coordination and cooperation of the auxiliary industry facilitates the sustainable development of the scenic spot greatly. Therefore, measurement of the sustainable capacity of the scenic spot should also include measurement indexes of the development of auxiliary industry. B41 and B43 measure the size of the scenic area auxiliary industry; B42 and B44 can better reflect the human resources situation of auxiliary industry in scenic spots; B45 and B46 reveal the training status of tourism professionals; B47 and B48 reflect the accessibility of scenic spots; B51–B56 are mainly used for the economic benefits of scenic auxiliary industry (including tourism enterprises and transportation).It should be noted that these indexes are correlated and mutually promoted to drive the sustainable development of scenic spots. As a result, study on the sustainable capacity of scenic spots should consider each index comprehensively and conduct the analysis one by one. The relation among indexes and evaluation objectives of the sustainable capacity of scenic spots is shown in As required by the index system, the data in this study mainly comes from The Yearbook of China Tourism 2016 , China SThis paper adopts SPSS 22.0  to standardize the measurement index data and adopts principal components analysis to optimize the sustainable capacity measurement index system. Specific steps are listed below.As per the principle of keeping accumulated variance contribution rate above 80%, 5 principal components are extracted from 16 indexes of self-sustainability of the scenic spot and 3 principal components are extracted from 14 indexes of sustainable capacity of auxiliary industry. Containing 80.231% and 88.118% of information respectively in the measurement of sustainable capacity of scenic spot, they are able to interpret and express the raw index  and (13). Assigning the weight of each principal component Z and further obtain the positive ideal solution Z+ and negative ideal solution Z−  , areas wFrom the perspective of scale and benefit of auxiliary industry , areas wFrom the overall sustainability of scenic spots , the topThe average value of sustainable capacity of scenic spots in 30 Chinese provinces and cities is 0.444, generally in the intermediate level. The development of Chinese tourism industry differs significantly that it is stronger in East China, intermediate in Middle China and weaker in Northeast and West China. According to the score form, East China is much advantageous to other areas in the scale and benefit of auxiliary industry but is only slightly better than Middle China in the resource condition and ecological environment, so it can be concluded that the sustainable development of scenic spots in East China focuses on the expansion of industrial scale and elevation of economic benefit while concerning the protection and improvement of resources and ecological environment, thus possessing the strong sustainable capacity; moreover, East China covers much coastal areas with obvious geographical advantage and sufficient tourist source. Middle China is full of natural tourism resources and great potentiality in the tourism market  but behaves ordinary in the scale and benefit of auxiliary industry, and due to the low economic strengthen of tourism and poor geographic condition, its sustainability is quite week. Although Northeast China and West China possess featured landscapes like glacier, snowfield, forest and wetland, the low traffic accessibility, far distance from major tourist sources and weak availability lead to insufficient potentiality in domestic and international tourism market; the extensive development and operation mode restrict the substantial expansion of the scale and benefit of tourism industry; moreover, these areas lack excellent development concepts with respect to the management of scenic spots and improvement of ecological environment; with serious weakness in the service system and tourism infrastructure of scenic spots, the sustainability of Northeast China and West China (0.253 and 0.366) is lower than the average level of China (as shown in (1)Local governments need to increase financial support, improve the scenic area software support to the scenic area function of scientific planning and positioning, give full play to the advantages of scenic resources, create a distinctive tourism brand, improve the attraction and competitiveness of scenic areas, promote the development of the scenic area economy from the policy and technological innovation, and then lead the development of auxiliary industries around the scenic area;(2)Developing scenic resources reasonably and paying attention to the protection and management of ecological environment for protecting the future tourism development depends on the existence of environmental quality, improving the scenic area management mode for getting rid of extensive development and management mode of scenic area;(3)Improving the basic public facilities and entertainment services around the scenic area, reasonably planning the network of scenic traffic, better the quality of life in the tourist reception area for providing tourists with high quality tourism experience.For the western and northeastern regions where the sustainable development levels of all aspects of scenic areas are relatively low, the following two measures are proposed:For the central region where the scale and benefit of the auxiliary industry of scenic spots are not outstanding, it is necessary to excavate the characteristics of its own tourism resources, differentiate and accurately locate the market, and provide high-quality tourism services; Strengthening the cooperation of regional tourism and the comprehensive integration of tourism resources, commonly designing and developing the routes of cross regional tourism, the construction of tourism fine lines and the establishment of barrier-free tourism mechanism, promoting the free flow of industrial factors for accelerating the integration process of regional tourism development.For the eastern region with good scenic resources and ecological management, it is necessary to promote the optimization and upgrading of tourism industrial structure and the accelerated development of tourism economy on the premise of protecting the existing ecological environment. Deepening the reform and innovation of the management system and related policies, constructing a number of tourist pioneer areas and demonstration areas for promoting the development of the central, western and northeastern regions in China, cultivating new growth point of tourism economy innovatively.In view of the differentiated extensity of sustainable development of Chinese scenic spots and the low sustainable development in West China and Northeast China, following countermeasures are proposed in this paper:(1)After giving comprehensive consideration to the resource condition, economic benefit, auxiliary industrial scale, auxiliary industry benefit and ecological environment in relation to the sustainable capacity of scenic spots, this model establishes a relatively comprehensive sustainable capacity evaluation index system to provide relatively reliable reference to the objective multiple-objective measurement;(2)Utilizing the principal component analysis and entropy TOPSIS method, this model establishes the sustainable capacity measurement model of scenic spots. Firstly, while decreasing the computation quantity effectively by principal components analysis, this model reduces the multi-dimensional index influencing the sustainable development of scenic spots to the lower dimensional index; secondly, through assigning the objective weight to the lower dimensional index by entropy method, this model avoids the subjective influence brought by the personal preference to make the result more objective and scientific; finally, this model further lowers the weighted low dimensional index to one dimensional index by TOPSIS method to analyze the sustainable development of scenic spots of each province and city in an easier manner. Therefore, this measurement model is better adapted to the sustainable development of scenic spots that it may ensure the scientific and reasonable result while decreasing the workload;(3)Study on the measurement of the sustainable development of scenic spots is very significant for understanding the sustainable development of scenic spots and their auxiliary industries to establish specific and scientific countermeasures;Based on the statistics information of tourism of each province in 2015, this paper establishes the comprehensive measurement index system of the sustainable capacity of scenic spots, further determines the weight of each index by the entropy method, analyzes by TOPSIS method to obtain the comprehensive value of sustainable capacity of scenic spots of each province, and finally conducts the comprehensive analysis of the sustainable capacity of scenic spots of each provinces. Conclusion of this paper is listed below:Although the measurement index system established in this paper gives comprehensive consideration to indexes in relation to the measurement of sustainable capacity of scenic spots, it does not cover all indexes influencing the sustainable development of scenic spots; therefore, this index system is still restrictive to a certain extent. Besides, principal components analysis may decrease the workload of the large-volume data computation but the converted data volume is still relatively large and the computation is quite complicated. As a result, it is still to be studied as how to better improve the measurement index system and analyze the sustainable development of scenic spots by a faster and more effective measurement method.


Congenital chordee and penile torsion are commonly observed in the presence of hypospadias, but can also be seen in boys with the meatus in its orthotopic position. Varying degrees of penile curvature are observed in 4–10% of males in the absence of hypospadias. Penile torsion can be observed at birth or in older boys who were circumcised at birth. Surgical management of congenital curvature without hypospadias can present a challenge to the pediatric urologist. The most widely used surgical techniques include penile degloving and dorsal plication. This paper will review the current theories for the etiology of penile curvature, discuss the spectrum of severity of congenital chordee and penile torsion, and present varying surgical techniques for the correction of penile curvature in the absence of hypospadias.


To find the prevalence as well as to identify the predictors as protective and risk factors of Non-Suicidal Self-Injury (NSSI) among children with autism spectrum disorder (ASD).In this analytical cross sectional survey 83 children with ASD age range from 8 to 18 years were selected through convenient sampling technique from five special schools of Lahore city. The Urdu form of a standardized tool was used to assess NSSI.Statistical analysis indicated overall point prevalence of NSSI was 33%. Moreover banging/self-beating (47%), scratching (38), pinching (35%), picking scabs (33%), self-biting (32%), pulling hair (30%) and rubbing skin (19%) emerged as common forms of challenging behavior. Further regression analysis showed that age B, gender B and severity level of ASD B as risk factors/positive predictors of NSSI. However early intervention  and involvement of parents in counselling  emerged as protective factors/negative predictors of NSSI among children with ASD.Non-suicidal self-injury is a serious challenge among children with ASD. Early intervention, counselling and parental involvement in managing the children with ASD will not only prevent but reduce the challenging behaviors. Autism Spectrum Disorder (ASD) is a neuro-developmental disorder. The individuals with ASD show deficits in social functioning, language, communication skills and ability to maintain relationships. It is a spectrum disorder which means that its symptom patterns range of abilities and characteristics are expressed in many different combinations and in any degree of severity. They are also found to exhibit unusual interest and stereotype behaviors.1Self-injurious behaviors (SIB) are self-inflicted behaviors that are harmful for the child’s own body and these include head banging, hand or arm biting, excessive scratching and rubbing, self-choking, hair pulling and many others.7There are some studies which showed the prevalence of SIB 30% or higher in the population with ASD.3Though prevalence of self-injury without the intentions of suicide is common in ASD but it is not considered the symptom of ASD because self-injury has been recorded in the individuals’ with other disabilities as well as in the normal population. Self injurious behaviors is assumed to be a repetitive behavior at the same time it can be episodic as it either occurs under highly specific stimulus contexts, or in bursts after long periods without problematic behavior.11There is a dearth of published studies on NSSI of individuals with ASD in Pakistan in spite of the fact that SIB is highly associated with ASD. Self-injury is a source of frustration to parents, caregivers, teachers and other professionals working with these children. The present study examined the point prevalence of NSSI among children with ASD and can be a source of awareness to the parents, teachers and other stakeholders. The results also identify the role of demographics and other environmental factors contributing as risk as well as the protecting factors of developing NSSI. This study can be helpful to design preventive measures to control the NSSI among children with ASD by indicating the protective and risk factors.13The main objectives of this study were to:Find prevalence of Non suicidal self-injury among children with ASD across forms of NSSI and across the personal characteristics of the participants.Explore the common forms of self-harm behaviors and identify the risk as well as protective factors of NSSI among the children with ASD.Total 95 children with ASD were conveniently selected from the five institutions located in Lahore city. Their mean age was 11.77 . Of them 60 were male and gender mean was 1.36 . The detail of the personal characteristics of the participants are given in The assessment process was carried out at two phases. At first phase the management of the schools pointed 132 children with ASD. At the second phase the childhood autism rating scale (CARS)The study was approved by departmental review board. Informed consent was taken from the heads of the institutions and the parents of the participants. The participants were told that they can quit from the study at any stage.In order to find the prevalence and forms of self-injurious behavior among children with ASD frequency program was run and percentages were calculated. The detail is given in The prevalence of forms of self-injurious behaviors in percentages among children with ASD is shown in Overall prevalence of NSSI among the participants and the prevalence of NSSI among children with ASD according to associated characteristics is shown in It is further supported by the results of multiple regressions 2 (0.88) and F ratio  show the goodness of fit of the model. It means that the independent variables are explaining 88% of the variance in dependant variables. In the result age, gender, severity level of ASD, parental involvement in counselling and early intervention emerge as significant predictors of NSSI. However Age and severity level of ASD are the positive and turned out as risk factors. On the other hand early intervention and parental involvement in the management plans of the children emerged as protective factors and negative predictors of NSSI.In order to identify the predictors of NSSI among the participants with ASD standard multiple regression was run on the data. The values of ∆RThe scarcity of research on prevalence of NSSI among children with ASD in Pakistan was the motive to conduct present study. Although a fair number of studies investigated the prevalence of SIB among the population with intellectual disabilities but there is a limited published data describing challenging behaviors of ASD. The previous studies highlighted the need of identifying the associated factors of self-injury among ASD so that the challenging behaviors may be stopped.1The exact reasons of these stereotype self-stimulatory injurious behaviors are not known. However ASD limits the functioning of many parts of the brain which further affects every aspect of social interactions with others and weakens the abilities like social responsiveness, communication and feelings for other people.The results of frequencies in the form of percentages in this study indicates that majority of the participants showed head banging or self-beating, scratching, pinching, picking scabs, biting, pulling hair and rubbing skin against rough surface as self-injurious behaviors. These findings are consistent with the results of previous studies.3Results of present study indicate 30% overall prevalence of NSSI among the participants. The findings of the researches conducted in west indicates up to 50% prevalence of SIB among individuals with ASD.17Further the comparison across personal characteristics indicated that females appeared to be scored higher on non-suicidal self injurious behaviors as compared to their male counterparts. A reason of these gender differences can be that girls with ASD were found to show more cognitive developmental delays and behavioral problems as compare to the boys with similar disorder.3Present study also found the highest prevalence of NSSI among the participants who had severe level of ASD. It means the severe the level of symptoms of ASD the more frequent and severe SIB among the individuals. Similarly researcher24The findings of regression analysis supported the above mentioned statements hence parental involvement in the process of counseling and provision of early intervention as protective factors as well as the severity of ASD is a major risk factor of NSSI among the children with ASD.21The main limitations of the study was small sample size selected from the Lahore city due to time and financial constraints. The more generalizable results would have been generated in case of recruiting the sample from other regions also.The present study found some associated factors as predictors of Non-suicidal Injury among children with ASD which further may help to tailor preventive and intervention programs to reduce the life threatening challenging behaviors. Early interventions, the focus counselling in adolescence and involvement of parents/caregivers in the treatment or management plans of the individuals with ASD will reduce the severity of symptoms which will further help in minimizing the challenging behaviors.BA conceived, designed and editing of manuscript.MB, ZR, AA, did data collection, statistical analysis and manuscript writing.BA takes the responsibility and is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


We present a case of spontaneous rupture of the diaphragm, characterized by nonspecific symptoms. The rapid diagnosis and appropriate surgical approach led to a positive resolution of the pathology.


The Moon-based Extreme Ultraviolet Camera (EUVC) of the Chang’e 3 mission provides a global and instantaneous meridian view (side view) of the Earth’s plasmasphere. The plasmasphere is one inner component of the whole magnetosphere, and the configuration of the plasmasphere is sensitive to magnetospheric activity (storms and substorms). However, the response of the plasmaspheric configuration to substorms is only partially understood, and the EUVC observations provide a good opportunity to investigate this issue. By reconstructing the global plasmaspheric configuration based on the EUVC images observed during 20–22 April 2014, we show that in the observing period, the plasmasphere had three bulges which were located at different geomagnetic longitudes. The inferred midnight transit times of the three bulges, using the rotation rate of the Earth, coincide with the expansion phase of three substorms, which implies a causal relationship between the substorms and the formation of the three bulges on the plasmasphere. Instead of leading to plasmaspheric erosion as geomagnetic storms do, substorms initiated on the nightside of the Earth cause local inflation of the plasmasphere in the midnight region. Kp index2RE) for relatively quiet geomagnetic condition1151112141516The plasmasphere contains dense and cold thermal plasmas that surround and corotate with the Earth234567841in situ measurement of plasma density via spacecraft, the configuration of the plasmasphere can be observed by remote imaging+ ions in the plasmasphere)192123252627RE away from the Earth. Thus it can provide a global and instantaneous meridian view (side view)31in situ data from various space missions have demonstrated the reliability of the EUVC data for identifying plasmapause locations3334In addition to Here we use the EUVC data obtained on 20–22 April 2014 to analyze the shape of the plasmaspheric configuration and its relationship with substorms (see Methods for the EUVC data reduction procedure). The cadence of the EUVC images is about 10 minutesIn When discussing configurations of the plasmasphere, we are more interested in the magnetic coordinate systems  direction and the magnetic dipole axis. The plasmapause boundary in the image for field line fitting is identified via visual inspection, in which we use a threshold of intensity  to get a rough dayside plasmapause position for reference. L-values. The curve of the L-values with observing times is plotted in L-value curve can be identified in L-value curve in L-values determined from the profile fitting process are consistent with the variation of plasmapause locations illustrated in the time-distance diagram.After performing the dayside plasmapause profile fitting for the 153 EUVC images, we have the coordinates of 153 field lines. The radial distances of the field lines at the magnetic equatorial plane are quantified by their L-value curve in We employ the geomagnetic (MAG) coordinate system (see Methods for the definition of the MAG coordinate system) to reconstruct the global plasmaspheric configuration based on the 153 field lines. It is widely accepted that the plasmaspheric plasmas are confined in the field lines and corotate with the Earthin situ electron density data of the Electric Field and Waves (EFW)in situ density data and those determined from the reconstructed plasmaspheric configuration along the orbits of VAP. The plasmapause locations obtained from the VAP in situ data  are indicated by the vertical dashed lines. The intersection locations of the satellites’ orbit to the plasmapause surface of the reconstructed configuration are indicated by the vertical dotted lines. It is interesting that most of the dashed and dotted lines are close even if the observational times of them are different, which means that the reconstructed plasmaspheric configuration is almost preserved during the observing period. This result verifies the reliability of the reconstructed plasmaspheric configuration based on the EUVC images.In order to verify the reconstructed plasmaspheric configuration based on the EUVC images, we use the L-value curve of the fitting field lines using the midday transit times overlying the AE index curve, and L-value curve shifting back 12 hours (midnight transit time) overlying the AE index curve. It can be seen in The three bulges of the plasmasphere are identified from the dayside shape profiles of the plasmapause, while an examination of the observed EUVC images see  shows thWe also compared the midnight transit times of the three bulges with the AL and AU indices40From the time series of EUVC images observed during 20–22 April 2014, we identified three bulges which successively appeared at the dayside of the plasmasphere along with the rotation of the Earth. The inferred midnight transit times of the three bulges coincide with the contemporary expansion phases of three substorms. These observations demonstrate that the expansion phases of the three substorms cause the three bulges in the plasmasphere. Different from the concept that geomagnetic storms lead to erosion of the plasmasphere, a substorm can cause plasmaspheric inflation in a local magnetic longitude range around midnight.A possible mechanism for this inflation process is a rapid filling of the upper magnetic field lines (or flux tubes) at the midnight region during the expansion phase of substorm, which affects the size of the flux tubes. Then these flux tubes rotate to the dayside and are recorded by the EUVC observations. Since the substorms happened successively, the three bulges deduced from EUVC images were also formed successively and thus are distributed at different geomagnetic longitudes. Besides, the newly formed bulge can overlap the previous plasmapause, which leads to a mismatch between the plasmaspheric reconstructions (see the overlapping region in The hypothesis of flux tube rapid filling is inspired by the direct observation of the substorm dynamic process on the nightside of the plasmasphere in the EUVC images around the time period from 8:00 UT to 12:00 UT on 21 April 2014 see . We perf3 counts per pixel), which reflects the He+ column density of the plasmasphere along LOS293132The EUVC uses a reflective optical system, which includes a spherical multilayer film mirror, a thin film filter, and a spherical photon-counting imaging detector29RE , then the size of Earth radius will be the same (10 pixels/RE) in all the processed EUVC images  Rescale the image and let the FOV be 15 × 15 The noise in the EUVC images shown in The definitions of the geophysical coordinate systems45The orbit positions of the Moon in the whole month of April 2014 shown in We use the dipole field model to calculate the geomagnetic field lines. The dipole axis is defined by the International Geomagnetic Reference Field (IGRF) model48L-values of the plasmapause locations studied in this paper are less than 4.2 RE (see 50The 2 RE see  and we oin situ electron density measurements. One instrument is the Electric and Magnetic Field Instrument Suite and Integrated Science (EMFISIS)37Two instruments aboard the VAP satellites can provide in situ electron density values (as well as the timing and orbit data of VAP satellites) are taken from the Level 3 data files (in CDF format) of the EFW. Although the EFW data is not as accurate as the EMFISIS data, they are sufficient for determining the plasmapause positions via visual inspection , only the EFW electron density data are available. So we adopt the EFW electron density measurements in this paper  web site (http://s-cubed.info). The SuperMAG auroral electrojet index data are supplied by the SuperMAG project (http://supermag.jhuapl.edu/indices).The AE indices (including AL and AU indices) data are supplied by World Data Center for Geomagnetism, Kyoto. The ground-based magnetometer data are provided by NASA’s Coordinated Data Analysis Web (CDAWeb). The Wp index data are supplied by the Substorm Swift Search (SKp ~ 4) and then the corotation of the plasmasphere is less disturbed; (2) The bulges are large-scale plasmaspheric structure, thus they are relatively stable and are less affected by local convection .


Variations of the testicular veins are relevant in clinical cases of varicocele and in other therapeutic and diagnostic procedures. We report herein on a unique variation of the left testicular vein observed in an adult male cadaver. The left testicular vein bifurcated to give rise to left and right branches which terminated by joining the left renal vein. There was also an oblique communication between the two branches of the left testicular vein. A slender communicating vein arose from the left branch of the left testicular vein and ascended upwards in front of the left renal vein and terminated into the left suprarenal vein. The right branch of the testicular vein received an unnamed adipose tributary from the side of the abdominal aorta. Awareness of these venous anomalies can help surgeons accurately ligate abnormal venous communications and avoid iatrogenic injuries and it is important for proper surgical management. Venous blood from the testis is drained through the pampiniform plexus of veins. This plexus condenses to form four veins at the superficial inguinal ring; two veins at the deep inguinal ring and one testicular vein at varying levels. The right testicular vein terminates into the inferior vena cava and the left testicular vein terminates into the left renal vein.During dissection classes for medical undergraduates, we observed a unique variation of the left testicular vein in an adult male cadaver aged approximately 70 years. The left testicular vein was formed by the union of the pampiniform plexus of veins, as described in anatomy textbooks. Its course in the lower part of the abdomen was also normal. It ascended retroperitoneally towards the left renal vein. Approximately 3 cm below the left renal vein, it bifurcated to give rise to left and right branches . The lefThe importance of anatomical variants of the testicular veins has greatly increased in recent times because of the development of advanced operative procedures within the abdominal cavity for varicocele and undescended testes.Testicular vein variations have been extensively studied by Asala et al.,Varicocele is a well-recognized cause of decreased testicular function and is said to be present in about 40% of infertile males.The variations we report here are surgically very important because they could go unnoticed until discovered during surgery. The communicating vein could suffer iatrogenic injuries during suprarenal surgery, leading to bleeding. The terminal bifurcation of the testicular vein could also lead to increased chances of its damage during upper abdominal retroperitoneal surgeries. One of the segments of the bifurcated vein could be used as a graft during surgeries. Left-sided varicocele is more common than right. The variant bifurcated termination of the left testicular vein and its communication with the left suprarenal vein could further increase the possibility of a left-sided varicocele. It could also result in post-surgical recurrence of varicocele. In view of the practical importance of such variations to renal transplantation, renal and gonadal surgeries, and other therapeutic and diagnostic procedures, the present report is of significant importance to surgeons, radiologists and andrologists.


To evaluate integrated learning program of neurosciences for continuation of integrated learning in the forthcoming teaching and learning modules of undergraduate medical curriculum at Bahria University Medical & Dental College (BUMDC).A mixed method design was conducted from August 2016to February2017 after ethical approval from BUMDC. The quantitative aspect was evaluated retrospectively by desk records ofmarks obtained in integrated module and nonintegrated module. Focused group discussionwere conducted with primary intended users to share their expectations and concerns and get responses on key evaluation questions for implementationand outcome evaluation of integrated learning program.The desk record revealed a positive perception of students and faculty at the time of implementation with improvement in results after integration in subjects of basic sciences. The discussions highlighted reasons which resulted in failure of its continuation and affirmedreadiness for re-induction and continuation of integration with clinicalsciences.Evaluators considered approval and re-application of integrated curriculum at BUMDC after utilization focused evaluation. The conventional non-integrated approach of MBBS curriculum disseminates knowledge by afragmented approach which fails to build learning skills of case investigations and analysis. As a result of which students fail to acquire conceptual understanding of the topic and hence its application in treatment and prevention of disease.3In Bahria University Medical & Dental College (BUMDC) teaching of basic science subjects is accomplished by modular and hybrid system with a mixture of traditional teaching and problem based learning (PBL). Integrated Learning Program (ILP) was implemented in 2010 to integrate the subjects of Anatomy, Physiology, Biochemistry, and Community Medicine disciplines in module of Neurosciences.1Although, ILP was executed with favorable results, yet integration was not followed in the succeeding modules. With this the stake holders taught about its evaluation by external evaluators with the aim to ascertain its usefulness and efficacy in real time environment. They wanted to identify any gaps, deficiencies and weakness for implementation and improvement in the forthcoming modules. In order to acquire this objective, utilization focused evaluation (UFE) with its 17 steps frameworkThe study was conducted from August 2016 to February 2017 after ethical approval from BUMDC. A mixed method design was adopted with the qualitative aspect acquired by Focused group discussion (FGD) and quantitative data was assessed retrospectively by the available desk records from January 2012 to December 2015. The evaluator team comprised of external and internal evaluators selected on the basis of their command on professional practical knowledge, systemic enquiry skills, project management skills, reflective practice competence and interpersonal competence from inside and outside the institution. To assess and enhance readiness for evaluation, evaluators shared their expectations and concerns with the primary intended users (PIU); chair integration committee, students, teachers from basic and clinical sciences. Evaluation of ILP was done by all the steps of UFE as shown in 6Three focus group discussions (FGD) with; chair of integration committee, faculty members and students were conducted by KEQ developed by the researchers from an iterative literature process. All the faculty members of Basic Sciences especially those who took part in integration of Neuroscience Module (2010) were invited. Medical students of first and second year MBBS were invited and informed about the purpose of FGD. They were later short listed on the basis of their academic performance (scores in the previous modules). The evaluators took consent from the participants and confirmed about anonymity and confidentiality of data. Each FGD lasted for approximately 60to 90 minutes in a private place free from noise and disturbance and were audio taped after obtaining the consent. The data obtained after debriefing from FGD answered all KEQs in terms of difficulties faced during implementation of the program, perception of usefulness of program by students and teachers. The quantitative data of results of nonintegrated (NI) and integrated module after ILP, guide book for students, schedule of both modules, feedback forms filled by students and faculty members was also acquired and analyzed. The comparative analysis of modules done in SPSS-15 with comparison by Student’s t -test was taken into account.On the basis of retrieved desk records, comparison of module results after intervention of ILP declared better performance of medical students after integration. The upgrading of results attained by ILP in disciplines of Anatomy, Physiology and Biochemistry in neuroscience module. In discipline of Anatomy interactive sessions and model study facilitated in understanding of structural and functional association of nervous system in 86% students through reinforcement, interpretation and description of structured objectives in pleasant manner. Assimilation of knowledge in 80.25% of students was the result of interactive lectures of biochemistry linked with molecular and functional aspects. Elucidation of physiological mechanisms that construct basis of disease assisted 84% of students to grasp pertinent pathologies. Implementation of ILP apprehended students greater expertise and interest on subject and effectiveness of integrated teaching for better scoring in assessments and clinical postings. The feedback response from students and faculty suggested that problem solving skills, through provision of structured integrated model of neurosciences was made possible.Qualitative Results of qualitative analysis was provided after thematic analysis from responses to all the KEQ, sorted out in the form of usefulness of ILP and steps required for outcome and implementation evaluation. One of the faculty members responded; “Brain Storming, Self learning, Connections among all subjects and a sense of accomplishment was acquired by the students during ILP”. “Framing of time table” was the most important impediment to its continuation, mentioned by few participants. A senior faculty member mentioned; “Interpersonal skills in terms of listening, and receiving criticism developed positive attitude, when we implemented ILP way back in 2010”. One of the student said; “we lack integration of basic sciences in clinical practice that needs to be catered by implementation of case based session”. Majority of students in FGD recommended that understanding and application of Basic Sciences in clinical scenarios can be improved by integration of modules. The chair said; “we were not able to take forward integrated learning due to the reason that all the schedules were not made after intra and interdepartmental discussions among “Basis Science Departments”  with contribution from clinical faculty”. Furthermore, he said “Objectives were not aligned with the learning outcome and mode of information transfer hence integration could not be achieved “Faculty criticized that the time table of whole module was not finalized before the start of the module rather was constructed after it had started which resulted in serious flaws. In the FGD with chair of integration committee, it was concluded that since all the political powers are in favor of implementation of integration, all efforts should be made to make it possible. The discussions with stake holders on the basis of KEQ  thus shoProgram evaluation is recognition, purification and implementation of secure benchmarks to govern the objectives of evaluation meaningfully. The goal of evaluation was focused on organization of central themes or concepts that combined several subjects using multiple learning strategies in ILP.9The two imperative hypothesis of UFE are that no evaluation should progressunless there are managers who will essentially be working on proofs that the evaluation will engender and dynamically participated in the course of overall assessment.12The evaluation model used at BUMDC connected all stakeholders in planning of evaluation, given responses and understanding of findings.15UFE determines practical agenda for conducting evaluations with progress of its utility.4The application of UFE actively involved PIU in the decision making process with the guidance for improvement of program. The most important limitation was time interval in application of program and its evaluation however the approach of UFE can look up for the causes of failure of its continuation. It would further give emphasis to solve the problems with well-defined goals and strategic directions acquired by feedback from all PIU.Evaluators considered approval and application of transformation from nonintegrated to integrated curriculum at BUMDC in view of recommendations from chair integration committee, faculty members and students and desk record of an integrated module. The evaluators also highlighted the benefits of integration in undergraduate curriculum and informed them that any insufficiencies at the end of evaluation will help in further modification in the forthcoming modules.Organizations should employ UFERehana Rehman: Principal Investigator took part in conception and study design & compilation of write up, drafting the article & revising it critically for important intellectual content.Rabiya Ali: Took part in study design, acquisition, analysis and interpretation of data, compilation of write up drafting the article.Hina Moazzam: Took part in compilation of write up and formulation of tables.Saifullah Shaikh: Took part in data analysis.Rabiya Ali: Takes the responsibility and is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.


Recent discovery of hair follicle keratin 75 (KRT75) in enamel raises questions about the function of this protein in enamel and the mechanisms of its secretion. It is also not clear how this protein with a very specific and narrow expression pattern, limited to the inner root sheath of the hair follicle, became associated with enamel. We propose a hypothesis that KRT75 was co-opted by ameloblasts during the evolution of Tomes' process and the prismatic enamel in synapsids. Since early days of enamel research the question regarding the presence of keratins in this epithelial tissue intrigued scientists , which are hairless, lost a number of hair and hair follicle keratin genes (Nery et al., The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CR and handling Editor declared their shared affiliation.


This is a patient aged 35 years old, farmer, who consults for chronic fistula of the soles lasting for three months without any notion of trauma. The review found a swelling of the outer edge of the foot of inflammatory appearance with pus coming through a fistula at the top. Plain radiography shows a well limited round osteolysis recalling the appearance of an abscess of Broca. The scanner confirms the osteolysis and highlights intra-osseous foreign body. The patient underwent surgical treatment by trimming, removal of a piece of wood and curettage of the bone cavity. The outcome was favorable with disappearance of infectious signs and filling the bone cavity.


Mycoplasma gallisepticum S6. Atomic force microscopy studies show that the above-mentioned forms of the mycoplasma have different values of DNA parameters . We suppose that the observed phenomenon may be connected with the process of adaptation of these bacteria to severe environments.Recent studies show that mycoplasmas have various programs of life. This means that changes in morphology and genome expression may occur once the environment of these microorganisms becomes extremely altered. In this article, we report on changes in the DNA molecule obtained from the vegetative forms and the viable but nonculturable (VBNC) forms of


The peak particle velocity datasets recorded during quarry blasts in the neighborhood villages and towns in Ibadan and Abeokuta were processed and analyzed in order to recommend a safe blast design for each of the quarries. The minimum peak particle velocity of 48.27 mm/s was recorded near the foundation of the nearest residence at the shot to monitored distance of 500 m. The tendency of ground vibration emanating from the quarry sites to cause damage to the structures in the nearby dwelling areas is very high. The peak particle velocity datasets recorded were not within the safe limit. Therefore the peak particle velocity that will not exceed 35 mm/s is recommended for a safe blast design. Specifications TableValue of the data•The data could be used as a source of information for quarry blasters to determine the relationship between the peak particle velocity and ground vibration.•The data could be used to monitor the level of damage on structures in the neighborhood of the quarry sites.•The data revealed Shot - Monitored distances , shot-monitored distance, charge weight and scaled distance. Of all the parameters in the datasets, the peak particle velocity dataset is the blast induced earthquake predictor. Blair Pal Roy The components of these datasets were considered to minimize the complaints of the residents in the neighborhood of the quarry sites. In recent years, one of the problems encountered by technical personnel who are responsible for excavation with blasting is the rightful or unjustifiable complaints of people or organizations in the neighborhood of quarry sites 2The data were generated during the survey of residential buildings in the neighborhood of the quarry sites. A Global Positioning System (GPS) was used to measure Shot-Monitored distances (the distance between the shot points at the quarry sites and Building Monitored Station Points (BMSP) in the neighbourhood of quarry sites). Shot-Monitored distances (D) were recorded from GPS. 3-component blast Seismographs were positioned at twenty BMSP in the dwelling areas surrounding each site. Longitudinal, vertical and transverse PPV datasets associated with the blast-induced earthquakes were recorded from the Seismograph.Twenty PPV datasets were obtained for each site  was used as explosive. The explosives were detonated using magnadet detonator. Scaled distance (SD) data were obtained for each BMSP  that can be detonated safely was determined using Eqs. The maximum quantity of explosives  at 55% of BMSP. The PPV data revealed that the vibration intensities were not bearable at most of the monitored stations. The analysis of data signifies that there is a correlation between the exceeded or large PPV recorded and the cracked walls of buildings in the vicinity of quarry sites.A combination of scaled distance and geological constants, k and β parameters obtained from the regression lines in