Cannibalism Research Articles

Higher susceptibility of males to bleomycin-induced pulmonary inflammation is associated with sex-specific transcriptomic differences in myeloid cells

Idiopathic pulmonary fibrosis, a condition with likely genetic and environmental etiology, is relatively more prevalent with poor prognosis in human males. However, the underlying mechanisms for these gender-associated differences in the severity of fibrosis remain unknown. Here, we tested the hypothesis that the transcriptomic repertoire of myeloid cells determines the higher susceptibility of male mice to bleomycin (BLM)-induced lung fibrosis. Adult mice were oropharyngeally challenged with saline or BLM. Lung injury, inflammation, and fibrosis outcomes were assessed, and airspace myeloid-cells were subjected to RNA-sequencing. As compared with the female mice, the male mice manifested significantly increased lung injury, inflammation, proinflammatory cytokines (IL-6, IL-1β, IL-7, and IP-10), and fibrosis in response to BLM challenge. Interestingly, several pro-inflammatory and extracellular matrix-associated genes were significantly up-regulated in male myeloid-cells compared to female myeloid-cells in the saline-control group. Similarly, BLM challenge resulted in greater pro-inflammatory and pro-fibrotic transcriptomic changes in male compared to female myeloid cells. On the other hand, anti-inflammatory and regulatory cytokine, Il10 and Ifng respectively, were uniquely upregulated in BLM-challenged female but not in male myeloid cells when compared to their respective saline-control groups. Further, cross-sex bone marrow transplantation experiments revealed that male hematopoietic progenitor cells (HPCs) increased the granulocytic infiltration in female mice while female HPCs decreased the granulocytic infiltration in male mice post-BLM challenge. These findings suggest that there are inherent transcriptomic differences between the male and female lung myeloid cells and that the pro-inflammatory nature of male myeloid cells is sufficient to increase the susceptibility of female mice to BLM-induced inflammation.

Blood pressure and the kidney cortex transcriptome response to high-sodium diet challenge in female nonhuman primates.

Blood pressure (BP) is influenced by genetic variation and sodium intake with sex-specific differences; however, studies to identify renal molecular mechanisms underlying the influence of sodium intake on BP in nonhuman primates (NHP) have focused on males. To address the gap in our understanding of molecular mechanisms regulating BP in female primates, we studied sodium-naïve female baboons (n = 7) fed a high-sodium (HS) diet for 6 wk. We hypothesized that in female baboons variation in renal transcriptional networks correlates with variation in BP response to a high-sodium diet. BP was continuously measured for 64-h periods throughout the study by implantable telemetry devices. Sodium intake, blood samples for clinical chemistries, and ultrasound-guided kidney biopsies were collected before and after the HS diet for RNA-Seq and bioinformatic analyses. We found that on the LS diet but not the HS diet, sodium intake and serum 17 β-estradiol concentration correlated with BP. Furthermore, kidney transcriptomes differed by diet-unbiased weighted gene coexpression network analysis revealed modules of genes correlated with BP on the HS diet but not the LS diet. Our results showed variation in BP on the HS diet correlated with variation in novel kidney gene networks regulated by ESR1 and MYC; i.e., these regulators have not been associated with BP regulation in male humans or rodents. Validation of the mechanisms underlying regulation of BP-associated gene networks in female NHP will inform better therapies toward greater precision medicine for women.

The impact of sexual orientation on how men experience disordered eating and drive for muscularity

Introduction : Research into disordered eating in men paints a mixed picture regarding the relationship to sexual orientation and muscularity. Method : Participants completed the Eating Disorder Examination Questionnaire 6.0 and Drive for Muscularity scale via Qualtrics. Results : Gay men experience more symptoms related to body attitudes and shape and weight concerns. Heterosexual men experience more muscularity and restricting related symptoms. Bisexual men generally score lower than the other groups, so should be considered independently. Conclusion : Sexual orientation relates to both rates of eating disorders in men and also the kind of symptoms they experience. This should be taken into account in treatment and diagnostic approaches.

P04-03 Does physical activity improve an interaction between motor control and cognitive functions in elderly?

BackgroundNormal aging is associated with progressive functional loss in many cognitive domains, including working memory, attention (van Raalten et al., 2008) and executive functions (Nyberg et al., 2008), responsible for the control of behavioral activities (Miller & Cohen, 2001). Research aim was to evaluate postural control and executive function during dual tasking in physically active and inactive old adults.MethodsParticipants were 42 older healthy human males and females (Mean age: 70.17±6.08 years). Posturography method with a single piezoelectric force plate was used to measure postural sway activity. For the evaluation of cognitive functions, we used Word Memory task with ten audio-recorded words (Lithuanian nouns) in each trial, and the Mathematical Processing Task, where negative or positive one-digit integer-numbers (10 in total) were presented in each trial at 2-second intervals. Physical activity of participants was evaluated according to WHO recommendations.ResultsThe study showed that there was a strong correlation between physically active time spent and balance behavior. The balance of physically active older people was statistically significantly more stable when they performed cognitive tasks than that of those who were physically inactive. Dual-task interferences on postural sway were evident in both Word Memory task and the Mathematical Processing Task conditions. Dual-task effect on Mathematical Processing Task and Word Memory task was not statistically different.DiscussionTaken together, we suggest that physical activity improves proprioceptive control which also improves balance control. In dual tasking, more attention is required in cognitive tasking, so better proprioception allows for better balance control with fewer attention resources. However, it is also evident that participants can reduce sway activity and increase balance stability by increasing attentional control.

Data-Driven Clustering of Functional Signals Reveals Gradients in Processing Both within the Anterior Hippocampus and across Its Long Axis.

A particularly elusive puzzle concerning the hippocampus is how the structural differences along its long anteroposterior axis might beget meaningful functional differences, particularly in terms of the granularity of information processing. One measure posits to quantify this granularity by calculating the average statistical independence of the BOLD signal across neighboring voxels, or intervoxel similarity (IVS), and has shown the anterior hippocampus to process coarser-grained information than the posterior hippocampus. This measure, however, has yielded opposing results in studies of developmental and healthy aging samples, which also varied in fMRI acquisition parameters and hippocampal parcellation methods. To reconcile these findings, we measured IVS across two separate resting-state fMRI acquisitions and compared the results across many of the most widely used parcellation methods in a large young-adult sample of male and female humans (Acquisition 1, N = 233; Acquisition 2, N = 176). Finding conflicting results across acquisitions and parcellations, we reasoned that a data-driven approach to hippocampal parcellation is necessary. To this end, we implemented a group masked independent components analysis to identify functional subunits of the hippocampus, most notably separating the anterior hippocampus into separate anterior-medial, anterior-lateral, and posteroanterior-lateral components. Measuring IVS across these components revealed a decrease in IVS along the medial-lateral axis of the anterior hippocampus but an increase from anterior to posterior. We conclude that intervoxel similarity is deeply affected by parcellation and that grounding one's parcellation in a functionally informed approach might allow for a more complex and reliable characterization of the hippocampus.SIGNIFICANCE STATEMENT Processing information along hierarchical scales of granularity is critical for many of the feats of cognition considered most human. Recently, the changes in structure, cortical connectivity, and apparent functional properties across parcels of the hippocampal long axis have been hypothesized to underlie this hierarchical gradient in information processing. We show here, however, that the choice of parcellation method itself drastically affects one particular measure of granularity across the hippocampus and that a functionally informed approach to parcellation reveals gradients both within the anterior hippocampus and in nonlinear form across the long axis. These results point to the issue of parcellation as a critical one in the study of the hippocampus and reorient interpretation of existing results.

Objective evaluation of mechanical expressiveness in android and human faces

ABSTRACT Extensive research has been conducted to realize highly expressive android faces. In contrast, not much is being discussed which android faces are mechanically better and how advanced each android is because a fair and meaningful standard index of expressiveness does not exist. Therefore, in this study, we propose a numerical index and three types of visualization methods for facial deformation expressiveness to investigate the mechanical performance of android faces compared to humans. We used a data set of three-dimensional displacement vectors of over 100 facial points on the faces of two androids and three human males to calculate the expressiveness that reflects how diversely each facial point could move. As a result, we found that the expressiveness of the androids was significantly lower than humans, especially in the lower faces. The expressiveness of the androids was approximately only 20 that of humans even in the most expressive axis and two orders of magnitude lower than humans in three-dimensional evaluation. Thus, our method revealed the lackness of mechanical performance in recently developed androids to move facial skin widely. This method enabled us to reasonably discuss future directions to realize next generation androids with expressiveness similar to that in humans.

Mapping of pituitary stress-induced gene regulation connects Nrcam to negative emotions

SummaryEnvironmental stressors such as repeated social defeat may initiate powerful activation of subconscious parts of the brain. Here, we examine the consequences of such stress (induced by resident-intruder paradigm) on the pituitary gland. In male stressed vs. control rats, by RNA- and bisulfite DNA sequencing, we found regulation of genes involved in neuron morphogenesis and communication. Among these, Neuronal cell adhesion molecule (Nrcam) showed reduced transcription and reduced DNA methylation in a region corresponding to intron 1 in human NRCAM. Also, genetic variability in this area was associated with altered stress response in male humans exposed to repeated social defeat in the form of abusive supervision. Thus, our data show that the pituitary gene expression may be affected by social stress and that genetic variability in NRCAM intron 1 region influences stress-induced negative emotions. We hope our shared datasets will facilitate further exploration of the motions triggered by social stressors.

Has Canada's 21st‐Century Grand Gender Convergence Stalled? Male and Female Income and Human Resource Stock Distributions Viewed Through an Equal Opportunity Lens

AbstractThe increasing similarity of male and female labor market roles in advanced economies over the past 50 years, dubbed the “Grand Gender Convergence” by Goldin (2014), appears to have stalled. Given commonality of preferences for work and human resource acquisition across the gender divide, women and men with similar human resources and efforts should have similar income distributions in a non‐discriminatory equal opportunity equilibrium. However, income convergence is a necessary but not sufficient condition for a “Grand Gender Convergence” as similarities in incomes could be achieved with differences in human resources and efforts given discriminatory rewards. In this study, using new tools for examining distributional convergence processes, the progress of Canada's 21‐st Century “Grand Gender Convergence” is examined in the context of an equal opportunity paradigm. While income convergence is almost universally apparent, human resource stock distributions appear to be diverging, with women having increasingly superior resources to men, evidence that the grand convergence is not progressing.

Charisma: Closing the Venture Funding Gender Gap

. This paper examines how changing verbal and nonverbal behavior in female entrepreneurs can alter their prospects of being invited to meetings with investors, raising funds, potentially reducing the venture funding gap. In a field study we examine how the use of charismatic tactics in the pitch influences the likelihood of succeeding in a startup competition. In an experimental study, we investigate how the implementation of verbal and nonverbal charismatic tactics (a distinct type of verbal and nonverbal behavior), influences the funding success of female and male entrepreneurs. We investigate the impact of verbal and nonverbal charisma, separately and jointly, on the raised investment pitches using virtual humans acting as entrepreneurs. The verbal content and nonverbal aspects (e.g., gestures, tone of voice) are identical for the female and male virtual humans. This enables us to examine pure gender perception effects while controlling for effects stemming from existing gender differences in verbal and nonverbal behavior. Our results show that charisma matters as the number of charismatic tactics corresponds to a higher likelihood of succeeding into the next round of an entrepreneurial competition. Furthermore, nonverbal charisma has a strong positive effect on funding for female and male entrepreneurs, nevertheless the lack of nonverbal charisma penalizes female entrepreneurs to a greater extent than male entrepreneurs.

Association between muscle dysmorphia psychopathology and binge eating in a large at-risk cohort of men and women

BackgroundCurrent research on muscle dysmorphia (MD) has focused on restrained eating behaviors and has adopted a primarily male perspective. Despite initial evidence, the role of possible binge eating associated with MD has only been scarcely investigated. To extend the transdiagnostic and cross-gender approaches and address the dearth in research related to MD, this study investigated the association between MD psychopathology and binge eating in men and women.MethodsThis study investigated the association between MD psychopathology and binge eating in both men and women. Participants were a sample of 5905 men (n = 422) and women (n = 5483) social media users aged 18–72 years. They completed an online survey that included self-report measures assessing demographics, binge eating, MD psychopathology, and drive for thinness and leanness. Binge eating was assessed using the diagnostic questions of the validated German version of the Eating Disorder Examination-Questionnaire. The Muscle Dysmorphic Disorder Inventory (MDDI) was used to assess MD psychopathology. A total score of > 39 was set as a cutoff to define an “MD at-risk” state for both men and women. Hierarchical logistic regression analysis was used to analyze the association between MD psychopathology and binge eating.ResultsMD psychopathology was significantly positively associated with binge eating in both men and women. Among the three MDDI subscales, only appearance intolerance was significantly associated with MD, and drive for size and functional impairment were not associated. MD at-risk status yielded a predicted probability of binge eating of 25% for men and 66.9% for women. The increased probability of binge eating associated with MD at-risk status was mainly accounted for by appearance intolerance in men and drive for thinness in women.ConclusionMD psychopathology is positively associated with binge eating in both men and women. Binge eating episodes should therefore form part of the clinical assessment of MD.

Metabolic transitions define spermatogonial stem cell maturation.

Do spermatogonia, including spermatogonial stem cells (SSCs), undergo metabolic changes during prepubertal development? Here, we show that the metabolic phenotype of prepubertal human spermatogonia is distinct from that of adult spermatogonia and that SSC development is characterized by distinct metabolic transitions from oxidative phosphorylation (OXPHOS) to anaerobic metabolism. Maintenance of both mouse and human adult SSCs relies on glycolysis, while embryonic SSC precursors, primordial germ cells (PGCs), exhibit an elevated dependence on OXPHOS. Neonatal porcine SSC precursors reportedly initiate a transition to an adult SSC metabolic phenotype at 2 months of development. However, when and if such a metabolic transition occurs in humans is ambiguous. To address our research questions: (i) we performed a meta-analysis of publicly available and newly generated (current study) single-cell RNA sequencing (scRNA-Seq) datasets in order to establish a roadmap of SSC metabolic development from embryonic stages (embryonic week 6) to adulthood in humans (25 years of age) with a total of ten groups; (ii) in parallel, we analyzed single-cell RNA sequencing datasets of isolated pup (n = 3) and adult (n = 2) murine spermatogonia to determine whether a similar metabolic switch occurs; and (iii) we characterized the mechanisms that regulate these metabolic transitions during SSC maturation by conducting quantitative proteomic analysis using two different ages of prepubertal pig spermatogonia as a model, each with four independently collected cell populations. Single testicular cells collected from 1-year, 2-year and 7-year-old human males and sorted spermatogonia isolated from 6- to 8-day (n = 3) and 4-month (n = 2) old mice were subjected to scRNA-Seq. The human sequences were individually processed and then merged with the publicly available datasets for a meta-analysis using Seurat V4 package. We then performed a pairwise differential gene expression analysis between groups of age, followed by pathways enrichment analysis using gene set enrichment analysis (cutoff of false discovery rate < 0.05). The sequences from mice were subjected to a similar workflow as described for humans. Early (1-week-old) and late (8-week-old) prepubertal pig spermatogonia were analyzed to reveal underlying cellular mechanisms of the metabolic shift using immunohistochemistry, western blot, qRT-PCR, quantitative proteomics, and culture experiments. Human PGCs and prepubertal human spermatogonia show an enrichment of OXPHOS-associated genes, which is downregulated at the onset of puberty (P < 0.0001). Furthermore, we demonstrate that similar metabolic changes between pup and adult spermatogonia are detectable in the mouse (P < 0.0001). In humans, the metabolic transition at puberty is also preceded by a drastic change in SSC shape at 11 years of age (P < 0.0001). Using a pig model, we reveal that this metabolic shift could be regulated by an insulin growth factor-1 dependent signaling pathway via mammalian target of rapamycin and proteasome inhibition. New single-cell RNA sequencing datasets obtained from this study are freely available through NCBI GEO with accession number GSE196819. Human prepubertal tissue samples are scarce, which led to the investigation of a low number of samples per age. Gene enrichment analysis gives only an indication about the functional state of the cells. Due to limited numbers of prepubertal human spermatogonia, porcine spermatogonia were used for further proteomic and in vitro analyses. We show that prepubertal human spermatogonia exhibit high OXHPOS and switch to an adult-like metabolism only after 11 years of age. Prepubescent cancer survivors often suffer from infertility in adulthood. SSC transplantation could provide a powerful tool for the treatment of infertility; however, it requires high cell numbers. This work provides key insight into the dynamic metabolic requirements of human SSCs across development that would be critical in establishing ex vivo systems to support expansion and sustained function of SSCs toward clinical use. This work was funded by the NIH/NICHD R01 HD091068 and NIH/ORIP R01 OD016575 to I.D. K.E.O. was supported by R01 HD100197. S.K.M. was supported by T32 HD087194 and F31 HD101323. The authors declare no conflict of interest.

Food-seeking behavior is triggered by skin ultraviolet exposure in males

Sexual dimorphisms are responsible for profound metabolic differences in health and behavior. Whether males and females react differently to environmental cues, such as solar ultraviolet (UV) exposure, is unknown. Here we show that solar exposure induces food-seeking behavior, food intake, and food-seeking behavior and food intake in men, but not in women, through epidemiological evidence of approximately 3,000 individuals throughout the year. In mice, UVB exposure leads to increased food-seeking behavior, food intake and weight gain, with a sexual dimorphism towards males. In both mice and human males, increased appetite is correlated with elevated levels of circulating ghrelin. Specifically, UVB irradiation leads to p53 transcriptional activation of ghrelin in skin adipocytes, while a conditional p53-knockout in mice abolishes UVB-induced ghrelin expression and food-seeking behavior. In females, estrogen interferes with the p53–chromatin interaction on the ghrelin promoter, thus blocking ghrelin and food-seeking behavior in response to UVB exposure. These results identify the skin as a major mediator of energy homeostasis and may lead to therapeutic opportunities for sex-based treatments of endocrine-related diseases.

Swelling of kappa carrageenan hydrogels in simulated body fluid for hypothetical vessel occlusion applications.

The swelling ability of kappa-carrageenan (KC) hydrogels was investigated in simulated body fluid (SBF). The SBF mimics the ionic concentrations in the vasa deferentia of human males. The study clarifies if these hydrogels can be adjusted to occlude the vasa deferentia by swelling. For this purpose, swelling to twice the initial volume is desirable. In this study, hydrogels of different primary potassium concentrations, biopolymer concentrations and ethanol-exchanged gels, were immersed in SBF either directly or after drying (pre-dried). We measured the absolute and relative swelling degree, and the swelling rates of the gels. Extensive pre-drying leads to irreversible gel densification and absolute swelling magnitudes decrease. We found that immersion into the SBF also leads to potassium ion accumulation, and network restructuring in the hydrogels. This markedly increases the storage moduli of the gel networks. The ion content in the gel structures also directly affects the swelling speed, the fastest swelling occurred in ethanol-exchanged and pre-dried gels. We found that by pre-drying and potassium content adjustment, swelling of the hydrogels is sufficient to render KC hydrogels as a possible candidate for the occlusion of the vasa deferentia.

Fertility Preservation and Restoration Options for Pre-Pubertal Male Cancer Patients: Current Approaches.

Fertility preservation for prepubertal male patients undergoing gonadotoxic therapies, potentially depleting spermatogonial cells, is an expanding necessity, yet most of the feasible options are still in the experimental phase. We present our experience and a summary of current and novel possibilities regarding the different strategies to protect or restore fertility in young male patients, before proceeding with chemotherapy or radiotherapy for malignances or other diseases. Adult oncological patients should always be counselled to cryopreserve the semen before starting treatment, however this approach is not suitable for prepubertal boys, who aren’t capable to produce sperm yet. Fortunately, since the survival rate of pediatric cancer patients has skyrocketed in the last decade and it’s over 84%, safeguarding their future fertility is becoming a major concern for reproductive medicine. Surgical and medical approaches to personalize treatment or protect the gonads could be a valid first step to take. Testicular tissue autologous grafting or xenografting, and spermatogonial stem cells (SSCs) transplantation, are the main experimental options available, but spermatogenesis in vitro is becoming an intriguing alternative. All of these methods feature both strong and weak prospects. There is also relevant controversy regarding the type of testicular material to preserve and the cryopreservation methods. Since transplanted cells are bound to survive based on SSCs number, many ways to enrich their population in cultures have been proposed, as well as different sites of injection inside the testis. Testicular tissue graft has been experimented on mice, rabbits, rhesus macaques and porcine, allowing the birth of live offspring after performing intracytoplasmic sperm injection (ICSI), however it has never been performed on human males yet. In vitro spermatogenesis remains a mirage, although many steps in the right direction have been performed. The manufacturing of 3D scaffolds and artificial spermatogenetic niche, providing support to stem cells in cultures, seems like the best way to further advance in this field.

HapCon: estimating contamination of ancient genomes by copying from reference haplotypes.

MotivationHuman ancient DNA (aDNA) studies have surged in recent years, revolutionizing the study of the human past. Typically, aDNA is preserved poorly, making such data prone to contamination from other human DNA. Therefore, it is important to rule out substantial contamination before proceeding to downstream analysis. As most aDNA samples can only be sequenced to low coverages (<1× average depth), computational methods that can robustly estimate contamination in the low coverage regime are needed. However, the ultra low-coverage regime (0.1× and below) remains a challenging task for existing approaches.ResultsWe present a new method to estimate contamination in aDNA for male modern humans. It utilizes a Li&Stephens haplotype copying model for haploid X chromosomes, with mismatches modeled as errors or contamination. We assessed this new approach, hapCon, on simulated and down-sampled empirical aDNA data. Our experiments demonstrate that hapCon outperforms a commonly used tool for estimating male X contamination (ANGSD), with substantially lower variance and narrower confidence intervals, especially in the low coverage regime. We found that hapCon provides useful contamination estimates for coverages as low as 0.1× for SNP capture data (1240k) and 0.02× for whole genome sequencing data, substantially extending the coverage limit of previous male X chromosome-based contamination estimation methods. Our experiments demonstrate that hapCon has little bias for contamination up to 25–30% as long as the contaminating source is specified within continental genetic variation, and that its application range extends to human aDNA as old as ∼45 000 and various global ancestries.Availability and implementationWe make hapCon available as part of a python package (hapROH), which is available at the Python Package Index (https://pypi.org/project/hapROH) and can be installed via pip. The documentation provides example use cases as blueprints for custom applications (https://haproh.readthedocs.io/en/latest/hapCon.html). The program can analyze either BAM files or pileup files produced with samtools. An implementation of our software (hapCon) using Python and C is deposited at https://github.com/hyl317/hapROH.Supplementary information Supplementary data are available at Bioinformatics online.

Prostate cancer screening awareness among expatriates’ adults living in Saudi Arabia

Background: Cancer is the second major cause of death worldwide. Early detection of cancer is a cornerstone of cancer survival. Cancer of the prostate is a major cause of concern for all men, as it offers a serious health risk, particularly to human males over 40 years. The main aim of the current study was to determine the level of awareness of prostate cancer screening among expatriates’ adults living in Saudi Arabia. Methods: A prospective cross-sectional study was used during March 2020 and January 2021; 337 expatriates' men were selected using a convenient sampling from shopping centers and coffee shops. A structured questionnaire designed included 16 questions, the first 4 questions designed to know the demographic features, while the other 12 questions concerned with the level of knowledge about PC and the level of awareness regarding PC screening. Results: Collected data revealed that 259 (77%) of the study participants did not have any information in regards to prostate cancer and prostate cancer screening methods. Conclusion: More than half of expatriates’ adults’ men have poor knowledge in regard of prostate cancer and screening. Therefore, Special attention should be paid for raising awareness about male prostate cancer and prostate cancer screening.

Sex differences in the detection of motor unit action potentials identified using high-density surface electromyography

Sex-related disparities in force production of humans have been widely observed. Previous literature has attributed differences in peripheral traits, such as muscle size, to explain these disparities. However, less is known about potential sex-related differences in central neuromuscular traits and many comparable studies, not exploring sex-related differences, exhibit a selection-bias in the recruitment of subjects making the generalization of their findings difficult. Utilizing high-density electromyography arrays and motor unit (MU) decomposition, the aim of the current study is to compare MU yield and discharge properties of the tibialis anterior between male and female humans. Twenty-four subjects (10 females) performed two submaximal (20%) isometric dorsiflexion contractions. On average, males yielded nearly twice the amount of MUs as females. Further, females had significantly higher MU discharge rate, lower MU action potential amplitude, and lower MU action potential frequency content than males despite similar levels of torque and MU discharge variability. These findings suggest differences in central neuromuscular control of force production between sexes; however, it is unclear how lower yield counts affect the accuracy of these results.

Method Development and Validation of a Novel UHPLC Coupled with MS/MS System for the Estimation of Brivaracetam in Human (K2EDTA) Plasma Samples and its Application to Pharmacokinetic Study

Background: Brivaracetam is a novel antiepileptic drug clinically approved for the treatment of partial onset seizures in adults and adolescents. It has some abuse potential and assigns to Schedule V category under the Controlled Substance Act by the Drug Enforcement Administration. It is essential to develop a faster, simple, and highly sensitive method for the quantification of Brivaracetam in human plasma by employing simple liquid-liquid extraction. Objective: The objective of this study is to develop and validate a novel UHPLC-MS/MS method for the estimation of brivaracetam in human plasma samples and application to pharmacokinetic study. Methods: An ultra-high-pressure liquid chromatography-tandem mass spectrometry method was developed and validated according to current regulatory guidelines for bioanalytical methods. Sample processing (50 μL) involved only a simple liquid-liquid extraction by ethyl acetate as extraction solvent. Brivaracetam-d7 was used as an internal standard. The chromatographic analysis was performed by a Unisol C18 (4.6 X 100 mm, 5μm) column using 0.1% formic acid in water/acetonitrile (20/80 V/V) as an isocratic mobile phase, at a flow rate of 1.0 mL/min with a run time of 2.2 min. Brivaracetam and its internal standard Brivaracetam D7 were detected and quantified in positive ion mode using multiple reaction monitoring transitions at m/z 213.100→168.100 and m/z 220.000→175.100, respectively. The developed method was applied to assess pharmacokinetic parameters like Cmax, Tmax, t1/2 and AUC for Brivaracetam in healthy, male, and adult humans. Results: The method was validated over a concentration range of 20.000 ng/mL to 4000. 000 ng/mL. Both intra- and inter-assay precision and accuracy were &lt;15% for all quality control samples. No matrix effect was observed. Pharmacokinetic results showed that test formulation is bioequivalent with reference formulation. Conclusion: The present assay is faster, highly sensitive and simpler than previously published analytical reports for brivaracetam in human plasma samples and is suitable for pharmacokinetic evaluation of any marketed formulation.

Acquisition of threat responses are associated with elevated plasma concentration of endocannabinoids in male humans

Endocannabinoids (eCBs) are involved in buffering threat and stress responses. Elevation of circulating eCBs in humans was reported to strengthen inhibition (i.e., extinction) of threat responses and to reduce effects of stressors. However, it remains unclear whether the acquisition of threat responses involves a physiological change in circulating eCBs. Here, we demonstrate in male human volunteers that the plasma concentration of the eCB N-arachidonoylethanolamine (AEA) and its metabolite arachidonic acid (AA) are increased during acquisition of threat responses. Furthermore, elevated responses to a learned threat cue (e.g., rating of fear) were associated with individual increases in plasma concentration of the eCB 2-arachidonoylglycerol (2-AG). In complementing these observations, we found individual increases in AEA associated with elevated neural responses during threat learning in the amygdala. Our results thereby suggest that physiological increases in circulating eCB levels are part of a response mechanism to learned threats.

Exploring Nature in the Selected Poems of Derek Walcott and Kaiser Haq: An Ecocritical Approach

The main goal of this article is to look into the relationship between nature and man as it is portrayed in the poetry of Derek Walcott and Kaiser Haq, two renowned poets from two distinct realms, namely St. Lucia and Bangladesh, respectively. Taking into consideration the rising level of environmental awareness, both poets have attempted to produce poetry that integrates man with nature. The poetry, particularly nature poetry, of these poets is explored in order to undertake study from an individual viewpoint, but there has yet to be a major examination into a comparative technique by adopting an ecocritical approach. In this study, the researchers attempt to uncover the nature of poetry disguised inside the chosen poems of the legendary poets by examining the creative and aesthetic characteristics of their works. This study examines the interaction between man and the environment via the lens of an ecocritical approach in a comparative manner. In this research, one poem by Kaiser Haq, "Poor Man Eating," and one poem by Derek Walcott, "Map of the New World," are examined from the perspective of environmental awareness. By concentrating on these poems and using an ecocritical perspective, this study attempts to demonstrate how the poet is sensitive to nature and how people are concerned about the environment.