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Predation exerts a strong selective force on prey, and hence prey species have evolved a multitude of ways to escape predation. One strategy by which many mobile species escape predation is by fleeing when approached by predators. However, fleeing too early can have fitness costs. Thus, optimal escape theory suggests that escape behaviour in prey depends on the risk of being eaten and the fleeing costs. Several studies on mammals, birds and lizards lend support to this hypothesis. However, few studies have explored escape behaviour in snakes. Here, using radio telemetry to track snakes in the field, we study the escape behaviour in Russell’s vipers, a highly venomous and cryptic snake, responsible for the highest number of snakebite deaths in India. We show that escape response, i.e., the decision to stay or flee, was influenced by intrinsic factors such as the snake’s behaviour and body temperature. We also show that the flight initiation distance, the distance at which the snake flees, was mostly determined by habitat selection, i.e., the visibility of the snake and the distance to the nearest cover. Overall, we show that different factors could determine the decision to flee and when to flee. We also highlight how understanding escape response in such highly venomous, medically important yet secretive snakes could potentially help reduce human-snake encounters and mitigate the snakebite crisis.

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as inducible nitric oxide synthase, nitric oxide, reactive oxygen species, transforming growth factor-β, and arginase-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation. Mechanistically, MDSCs-induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened cross-talk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data about the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process.

Green pit vipers, a name that can refer to several unrelated species, comprise a large group of venomous snakes found across the humid areas of tropical and sub-tropical Asia, and are responsible for most of the bite cases across this region. In India, green pit vipers belonging to several genera are prevalent in the northern and north-eastern hilly region, unrelated to species present in the peninsular region. In the present study, crude venom of representative species of green pit vipers present in the north and north-eastern hilly region of India (Trimeresurus erythrurus, T. septentrionalis, Viridovipera medoensis, and Popiea popieorum) were characterized to elucidate venom composition and venom variation. Profiling of crude venoms using SDS-PAGE and RP-HPLC methods revealed quantitative differences among the species. Further, in vitro biochemical assays reveal variable levels of phospholipase activity, coagulation activity, thrombin-like activity, fibrinogenolytic and haemolytic activity. This correlates with the pseudo-procoagulant effects on the haemostatic system of victims, which causes consumptive coagulopathy, frequently observed in patients bitten by green pit vipers. The immunoreactivity of Indian polyvalent antivenom and Thai green pit viper antivenom towards crude venoms were also evaluated by western blotting and inhibition of biochemical activities. The results exhibited poor efficacy of Indian polyvalent antivenom in neutralizing the venom toxins of crude venoms; however, Thai green pit viper antivenin (raised against the venom of Trimeresurus allbolabris, not present in India) showed higher immunoreactivity towards congeneric venoms tested. Analysis of green pit viper bite patients records from a community health centre in Assam, India, further revealed the inability of Indian polyvalent antivenom to reverse the extended coagulopathy featured.

Introduction Intracranial volume (ICV) is an important tool in the management of patients undergoing decompressive craniectomy (DC) surgery. The aim of this study was to validate ICV measurement applying the shape-based interpolation (SBI) method using open source software on computed tomography (CT) images. Methods The pre- and post-operative CT images of 55 patients undergoing DC surgery were analyzed. The ICV was measured by segmenting every slice of the CT images, and compared with estimated ICV calculated using the 1-in-10 sampling strategy and processed using the SBI method. An independent t test was conducted to compare the ICV measurements between the two different methods. The calculation using this method was repeated three times for reliability analysis using the intraclass correlations coefficient (ICC). The Bland–Altman plot was used to measure agreement between the methods for both pre- and post-operative ICV measurements. Results The mean ICV (±SD) were 1341.1 ± 122.1 ml (manual) and 1344.11 ± 122.6 ml (SBI) for the preoperative CT data. The mean ICV (±SD) were 1396.4 ± 132.4 ml (manual) and 1400.53 ± 132.1 ml (SBI) for the post-operative CT data. No significant difference was found in ICV measurements using the manual and the SBI methods (p = .983 for pre-op, and p = .960 for post-op). The intrarater ICC showed a significant correlation; ICC = 1.00. The Bland–Altman plot showed good agreement between the manual and the SBI method. Conclusion The shape-based interpolation method with 1-in-10 sampling strategy gave comparable results in estimating ICV compared to manual segmentation. Thus, this method could be used in clinical settings for rapid, reliable and repeatable ICV estimations.

Context: Postconcussion syndrome (PCS) is a set of symptoms occurred after a mild traumatic brain injury (MTBI). Aims: This study aims to determine the prevalence of PCS in a young adult population from a single Neurological Centre in Malaysia's East Coast and to evaluate the factors associated with PCS in MTBI patients. Settings and Design: This was a cross-sectional study conducted in a Neurological Centre at Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia, from January 2016 to December 2016. Subjects and Methods: A total of 209 patients; 133 males and 76 females, in the age range of 16–84 years, were randomly recruited for this study. All the selected patients were subjected to the checklist for diagnosis of PCS as per International Statistical Classification of Diseases and Related Health Problems 10th edition classification at a 2-week interval. Statistical Analysis Used: Descriptive statistic and Multivariable Logistic Regression Model were used for frequency and percentage analyses of categorical variables, using SPSS version 23.0. Results: Only 20 patients were identified with PCS. There were more female (70%) patients with PCS than the male (30%) patients. The prevalence of PCS for 2 weeks, 3 and 6 months since injuries were 9.6%, 8.1%, and 8.1% respectively. Majority (80%) of the patients were found to have PCS due to road traffic accidents, while the remaining were attributed to assault (15%), and falls (5%). Among the sample population, 25% were smokers, while 10% of them had either skull fracture or premorbidity. Conclusion: Less than 10% of patients with MTBI had PCS after 6 months' following trauma. None of the variables tested were significant factors for the development of PCS symptoms.

A novel series of EP4 agonists and antagonists have been identified, and then used to validate their potential in the treatment of inflammatory pain. This paper describes these novel ligands and their activity within a number of pre-clinical models of pain, ultimately leading to the identification of the EP4 partial agonist GSK726701A.

This paper explores the connection between paclitaxel, a chemotherapeutic agent, and gastric cancer cells. In this experiment, it is demonstrated that paclitaxel triggers autophagy and inhibits proliferation of gastric cancer cells. An 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to detect cell viability and the IC50 of paclitaxel. Western blot was used to detect the expression levels of P62, and to measure the protein expression of autophagy. Immunofluorescence was used to reveal the appearance of punctate structures in the cytoplasm-this ultrastructure associated with autophagy was observed by microscopy. Electron microscopy revealed the formation of double-membrane autophagosomes, a typical structure of autophagy. In conclusion, our research indicates that paclitaxel may influence gastric cancer BGC823 cells by way of inducing autophagy.

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as inducible nitric oxide synthase, nitric oxide, reactive oxygen species, transforming growth factor-β, and arginase-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation. Mechanistically, MDSCs-induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened cross-talk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data about the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process.

Resumen Este ensayo reflexiona sobre la oportunidad y las posibles maneras de ampliar el trabajo de memoria histórica de las víctimas del conflicto armado en Medellín, con investigaciones sobre las víctimas de otras violencias en la ciudad, en particular las del crimen organizado y mafioso, fuertemente relacionado con el tráfico de cocaína. El autor argumenta que sin incluir aquellas otras víctimas en los trabajos de memoria histórica es imposible comprehender la tragedia de Medellín en su totalidad. El autor sugiere varias maneras de abordar esta tarea de visibilización de aquellas otras víctimas. Abstract This essay reflects on the opportunity and potential ways to enlarge historic memory studies of the victims of the armed conflict in Medellin, through research about victims of other forms of violence, in particular of cocaine trafficking based organized crime and its mafia-like networks. The author argues that without including these other victims in historic memory research, it will be imposible to comprehend Medellin's tragedy in a comprehensive way. The author suggests various approaches to further the task of visualizing the voices of these other victims. Resumo Este ensaio reflete sobre a oportunidade e possíveis formas de expandir o trabalho de memória histórica das vítimas do conflito armado em Medellín, com investigações sobre as vítimas de outras violências na cidade, em particular as do crime organizado e suas redes de máfia, fortemente relacionadas ao tráfico de cocaína. O autor argumenta que, sem incluir essas outras vítimas nas obras da memória histórica, é impossível compreender a tragédia de Medellín como um todo. O autor sugere várias maneiras possíveis de abordar essa tarefa de visibilização dessas outras vítimas.

The Common Krait (Bungarus caeruleus) shares a distribution range with many other &lsquo, phenotypically-similar&rsquo, kraits across the Indian subcontinent. Despite several reports of fatal envenomings by other Bungarus species, commercial Indian antivenoms are only manufactured against B. caeruleus. It is, therefore, imperative to understand the distribution of genetically distinct lineages of kraits, the compositional differences in their venoms, and the consequent impact of venom variation on the (pre)clinical effectiveness of antivenom therapy. To address this knowledge gap, we conducted phylogenetic and comparative venomics investigations of kraits in Southern and Western India. Phylogenetic reconstructions using mitochondrial markers revealed a new species of krait, Romulus&rsquo, krait (Bungarus romulusi sp. nov.), in Southern India. Additionally, we found that kraits with 17 mid-body dorsal scale rows in Western India do not represent a subspecies of the Sind Krait (B. sindanus walli) as previously believed, but are genetically very similar to B. sindanus in Pakistan. Furthermore, venom proteomics and comparative transcriptomics revealed completely contrasting venom profiles. While the venom gland transcriptomes of all three species were highly similar, venom proteomes and toxicity profiles differed significantly, suggesting the prominent role of post-genomic regulatory mechanisms in shaping the venoms of these cryptic kraits. In vitro venom recognition and in vivo neutralisation experiments revealed a strong negative impact of venom variability on the preclinical performance of commercial antivenoms. While the venom of B. caeruleus was neutralised as per the manufacturer&rsquo, s claim, performance against the venoms of B. sindanus and B. romulusi was poor, highlighting the need for regionally-effective antivenoms in India.

In January 2012, the National Athletic Trainers' Association, along with the National Strength and Conditioning Association, convened a meeting in Colorado Springs, Colorado. Its purpose was to hold an interdisciplinary forum and gather input to address sudden death in collegiate conditioning sessions. Based on these discussions, a writing group drafted the following recommendations. To date, these best practices have been endorsed by the American College of Emergency Physicians, American College of Sports Medicine, American Medical Society for Sports Medicine, American Osteopathic Academy of Sports Medicine, Canadian Athletic Therapists' Association, Collegiate Strength and Conditioning Coaches association, Gatorade Sports Science Institute, Korey Stringer Institute, National Academy of Sports Medicine, National Athletic Trainers' Association, and National Strength and Conditioning Association. Other reviewers and meeting participants are listed with the professional organizations they represent at the end of this article. Maximizing strength and conditioning sessions has become fundamental to sport. The right combination of strength, speed, cardiorespiratory fitness, and other components of athletic capacity can complement skill and enhance performance for all athletes. A sound and effective training program that relies on scientific principles of exercise physiology and biomechanics intended to produce outcomes that are sensitive and specific to the sport should be the goals. Unfortunately, the athlete's development, health, and safety are sometimes overshadowed by a culture that values making athletes tough, instilling discipline, and focusing on success at all costs. This ill-conceived philosophy has been a contributor to the alarming increase in collegiate athlete deaths and serious injuries during conditioning sessions. A total of 21 National Collegiate Athletic Association (NCAA) football players have died during conditioning workouts since 2000.1 The 3 most common causes of the fatalities were (in order) exercise-related sudden death associated with sickle cell trait (SCT), exertional heat stroke, and cardiac conditions.1 Seventy-five percent of the fatalities (n = 16) were Division I football players. Also, the incidence of exertional rhabdomyolysis in collegiate athletes appears to be increasing. Excesses in strength training and conditioning—workouts that are too novel, too much, too soon, or too intense (or a combination of these)—have a strong connection to exertional rhabdomyolysis. Introducing full-intensity workouts too quickly is especially high risk: 11 of the 21 deaths occurred during day 1 or day 2 workouts. Rule changes enacted in 2003 related to heat acclimatization procedures during August football practices have been extremely effective. In the NCAA Division I Football Bowl Subdivision, no player died from practicing or playing in a game between 2000 and 2011. However, conditioning workouts continue to be a catalyst for catastrophic outcomes. It is imperative that similar guidelines be implemented to improve the safety of conditioning sessions. This consensus statement provides specific conditioning recommendations with the intent of ending conditioning-related morbidity and deaths of collegiate athletes.

An electrochemical (EC) gas sensor is a 3+ terminal electrochemical device which, when biased correctly with a potentiostat circuit, behaves as a current source whose output is proportional to the target gas concentration. The short lifetime of these sensors has become a key functional safety issue for hazardous gas detection modules. In order to predict the failure of EC gas sensors, a high precision and wide bandwidth EC impedance measurement is required [1]. For example, an electrochemical impedance spectroscopy (EIS) instrument is often used in the laboratory for failure rate analysis and there is a trend towards integration of the EIS at the chip level. However, it is extremely challenging to integrate the precision high-speed/high-power EIS with the precision low-power EC potentiostat system. For instance, [2] demonstrated a very low-power integration of the EIS and bio-potentiostat; however the EIS bandwidth is only 80Hz and the EIS dynamic range (DR) is limited at 77dB. [3] and [4] presented good EIS performance because there were no trade-off limitations between the low-power module and the high speed EIS. Furthermore, two additional challenges, not met by [2, 3, 4], are to apply an AC stimulus without disturbing the large DC potentiostat and to improve the DR for stimulus-sensitive sensors. This paper demonstrates a highly integrated SoC to support EIS applications for diverse sensors. Figure 17.4.1 shows the implemented architecture. The analog front end (AFE) and digital back end (DBE) are implemented on a 0.18μσι die and a 90nm die respectively and stacked in a 5×6×1mm3 LGA package. A Cortex-M3, featuring UART/SPI/I2C interfaces, is integrated in the top DBE die. The bottom AFE die has two EC potentiostat channels, with sensor readout, as well as a chip scale 0.1Hz∼200kHz EIS solution, which is realized by a transmitter (Tx), receiver (Rx) and DSP. A sequencer can flexibly control all these modules through a programmable 6KB SRAM, which is shared by command memory and data FIFO.

Decompressive craniectomy (DC) is a surgical option in managing uncontrolled raised intracranial pressure refractory to medical therapy. The authors evaluate the addition of zygomatic arch (ZA) resection with standard DC and analyze the resulting increase in brain volume using three-dimensional volumetric CT scans. Measurements of brain expansion dimension morphometrics from CT images were also analyzed. Eighteen patients were selected and underwent DC with ZA resection. The pre- and post-operative CT images were analyzed for volume and dimensional changes. CT images of 29 patients previously operated on at the same center were retrieved from the picture archiving and communication system (PACS) and were similarly studied. The findings obtained from the two groups were compared and analyzed. Analysis from three-dimensional CT volumetric techniques revealed an significant increase of 27.97ml (95% confidence interval [CI]: 39.98-180.36; p=0.048) when compared with standard DC. Brain expansion analysis of maximum hemicraniectomy diameter revealed a mean difference of 0.82cm (95% CI: 0.25-1.38; p=0.006). Analysis of the ratio of maximum hemicraniectomy diameter to maximum anteroposterior diameter gave a mean difference of 0.04 (95% CI: 0.05-0.07; p=0.026). The addition of ZA resection to standard DC may prove valuable in terms of absolute brain volume gain. This technique is comparable to other maneuvers used to provide maximum brain expansion in the immediate post-operative period.

The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P1 receptors, while a variety of side effects have been ascribed to its S1P3 receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P1 receptor agonism. Here we describe a study of the tolerance of the S1P1 and S1P3 receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P1 receptor agonists with good selectivity vs S1P3 receptors, efficacy at

Tuberous sclerosis is a known phakomatosis and the associated finding of a subependymal giant cell astrocytoma is common with this disorder. A case of tuberous sclerosis with a finding not previously reported, i.e. that of a pleomorphic xanthoastrocytoma, is presented here.

This Letter details the SAR of a novel series of piperidine-derived gamma-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Abeta42, increase Abeta38 and have no effect on Abeta40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse.