Variation of terpene alkaloids in Daphniphyllum macropodum across plants and tissues.

Daphniphyllum macropodum produces alkaloids that are structurally complex with polycyclic, stereochemically rich carbon skeletons. Understanding how these compounds are formed by the plant may enable exploration of their biological function and bioactivities. We employed multiple metabolomics techniques, including a workflow to annotate compounds in the absence of standards, to compare alkaloid content across plants and tissues. Different alkaloid structural types were found to have distinct distributions between genotypes, between tissues and within tissues. Alkaloid structural types also showed different isotope labelling enrichments that matched their biosynthetic relationships. The work suggests that mevalonate derived 30-carbon alkaloids are formed in the phloem region before their conversion to 22-carbon alkaloids which accumulate in the epidermis. This sets the stage for further investigation into the biosynthetic pathway.

The influence of self-focused attention on emotional picture processing: An ERP study.

Research has documented neurophysiological indicators of anticipation (Stimulus Preceding Negativity [SPN]) and perception (Late Positive Potential [LPP]) of threat, yet little is known as to how self-focused attention manipulations influence emotion processing within the context of cued picture viewing. With self-referent attention moderating attention to external stimuli, it is necessary to document how self-focused attention impacts attention and the ability to emotionally process external threat. The goal of the present study was to evaluate the impact of self-focused attention on the anticipation and perceptual processing of unpleasant pictures within a cued-picture viewing paradigm among 33 participants. Overall, the results suggest that the self-focused attention manipulations disrupted anticipation but not processing of pictures, as indexed by the SPN and LPP respectively. Self-focused attention appears to disrupt the preparatory attention for upcoming unpleasant stimuli, potentially through loading cognitive resources or activation of associative defensive responding. Collectively, these findings demonstrate the impact of self-focused attention within the context of emotional picture processing and suggest further areas of investigation.

Providing multimedia information to children and young people increases recruitment to trials: pre-planned meta-analysis of SWATs.

BACKGROUND: Randomised controlled trials are often beset by problems with poor recruitment and retention. Information to support decisions on trial participation is usually provided as printed participant information sheets (PIS), which are often long, technical, and unappealing. Multimedia information (MMI), including animations and videos, may be a valuable alternative or complement to a PIS. The Trials Engagement in Children and Adolescents (TRECA) study compared MMI to PIS to investigate the effects on participant recruitment, retention, and quality of decision-making. METHODS: We undertook six SWATs (Study Within A Trial) within a series of host trials recruiting children and young people. Potential participants in the host trials were randomly allocated to receive MMI-only, PIS-only, or combined MMI + PIS. We recorded the rates of recruitment and retention (varying between 6 and 26 weeks post-randomisation) in each host trial. Potential participants approached about each host trial were asked to complete a nine-item Decision-Making Questionnaire (DMQ) to indicate their evaluation of the information and their reasons for participation/non-participation. Odds ratios were calculated and combined in a meta-analysis. RESULTS: Data from 3/6 SWATs for which it was possible were combined in a meta-analysis (n = 1758). Potential participants allocated to MMI-only were more likely to be recruited to the host trial than those allocated to PIS-only (OR 1.54; 95% CI 1.05, 2.28; p = 0.03). Those allocated to combined MMI + PIS compared to PIS-only were no more likely to be recruited to the host trial (OR = 0.89; 95% CI 0.53, 1.50; p = 0.67). Providing MMI rather than PIS did not impact on DMQ scores. Once children and young people had been recruited to host trials, their trial retention rates did not differ according to intervention allocation. CONCLUSIONS: Providing MMI-only increased the trial recruitment rate compared to PIS-only but did not affect DMQ scores. Combined MMI + PIS instead of PIS had no effect on recruitment or retention. MMIs are a useful tool for trial recruitment in children and young people, and they could reduce trial recruitment periods.

Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (taVNS) may be useful in treating disorders characterized by chronic parasympathetic disinhibition. Acute taVNS decreases resting heart rate in healthy individuals, but little is known regarding the effects of taVNS on the cardiac response to an acute stressor. To investigate effects on the acute stress response, we investigated how taVNS affected heart rate changes during a cold pressor test (CPT), a validated stress induction technique that reliably elicits a sympathetic stress response with marked increases in heart rate, anxiety, stress, and pain. MATERIALS AND METHODS: We recruited 24 healthy adults (ten women, mean age = 29 years) to participate in this randomized, crossover, exploratory trial. Each subject completed two taVNS treatments (one active, one sham) paired with CPTs in the same session. Order of active versus sham stimulation was randomized. Heart rate, along with ratings of anxiety, stress, and pain, was collected before, during, and after each round of taVNS/sham + CPT. RESULTS: In both stimulation conditions, heart rate was elevated from baseline in response to the CPT. Analyses also revealed a difference between active and sham taVNS during the first 40 seconds of the CPT (Δ heart rate [HR] = 12.75 ± 7.85 in the active condition; Δ HR = 16.09 ± 11.43 in the sham condition, p = 0.044). There were no significant differences in subjective ratings between active and sham taVNS. CONCLUSIONS: In this randomized, sham-controlled study, taVNS attenuated initial increases in HR in response to the CPT. Future studies are needed to investigate the effects of various taVNS doses and parameters on the CPT, in addition to other forms of stress induction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT00113453.

Psychometric Properties of the Iranian Version of Contrast Avoidance Questionnaires: Could Contrast Avoidance Be a New Transdiagnostic Construct?

The contrast avoidance model (CAM) hypothesizes that individuals with chronic worry recruit worry to create and maintain a negative emotional state to avoid sudden increases in negative emotions. Preliminary evidence using the contrast avoidance questionnaires (CAQs) suggests that there might be a similar mechanism across mood and other anxiety disorders. To continue to assess the CAQs, they should be adapted for other languages and evaluated across multiple symptom domains. The present study aimed to develop the Persian versions of the CAQs and examine the transdiagnostic nature of CAM across two studies. A large Persian-speaking college student sample (Total n = 1438) was used to evaluate the factor structure of the CAQs (Study 1) and the psychometric properties of CAQs (Study 2). Results supported the two-factor structure of the CAQ-W (worry) and CAQ-GE (general emotion). Results showed that CAQ-W was a significant predictor of anxiety-related measures. However, CAQ-GE and IUS-12 significantly predicted depressive and other symptoms over the CAQ-W. Results demonstrated excellent psychometric properties. They indicate that contrast avoidance, measured via CAQ-GE, could be a transdiagnostic construct, and CAQ-W may be more sensitive to anxiety-specific contrast avoidance among Persian speaking and/or Iranian individuals.

A vulnerable residential environment is associated with higher risk of mortality and early transition to permanent residential aged care for community dwelling older South Australians.

OBJECTIVES: This study examined the impact of the residential environment, measured by the Healthy Ageing/Vulnerable ENvironment (HAVEN) Index, on risk of mortality or entry into Permanent Residential Aged Care (PRAC). DESIGN: A retrospective cohort study using data from the Registry of Senior Australians (ROSA) was conducted. HAVEN Index values were matched to the ROSA by residential postcode. STUDY SETTING AND PARTICIPANTS: Older individuals living in metropolitan Adelaide and receiving their first eligibility assessment for aged care services between 2014 and 2016 (N = 16,944). MAIN OUTCOME MEASURE: Time to death and entry into PRAC were the main outcomes. RESULTS: A higher HAVEN Index value, which represents a favourable residential environment, was associated with a lower risk of mortality and delayed entry to PRAC. For every 0.1 unit increase in HAVEN Index value, the risk of mortality is 3% lower (adjusted hazard ratio [HR], 95% confidence interval [CI] = 0.97, 0.96-0.99) and the risk of entry to PRAC is 5% lower (adjusted subdistribution HR, 95%CI = 0.95, 0.94-0.97) in the first 2 years following aged care assessment. After 2 years, the HAVEN Index was not associated with the risk of transition to PRAC. CONCLUSION: Place-based health inequalities were identified in Australians seeking aged care services, demonstrating that a better understanding of local neighbourhoods may provide insight into addressing ageing inequalities. Spatial indexes, such as the HAVEN Index, are useful tools to identify areas where populations are more vulnerable to adverse health outcomes, informing responses to prioritise local improvements and health interventions to enable healthy ageing.

Independent Psychometric Evaluation and Predictive Utility of The Social Anxiety Questionnaire.

The Social Anxiety Questionnaire (SAQ) is a 10-item measure of social anxiety developed to comprehensively and concisely target the mechanisms described in Clark and Wells' model of social anxiety and address the breadth of social anxiety symptoms which may not all be encompassed in existing questionnaires. The aim of the current studies is to independently investigate the factor structure of the SAQ (i.e., Study 1 and 2) and determine its predictive validity and utility (i.e., Study 3 and 4). Data were collected across 4 studies to evaluate the factor structure and utility. Overall, the results suggest that a total summed score of the SAQ appeared to capture unique aspects of social anxiety that may not be captured using a single measure and appears to provide utility in experimental manipulations of theoretical maintenance factors. The current study was limited by a convenience sample and future research should continue to document the psychometric properties and clinical utility of this novel measure of social anxiety. The SAQ may show promise in both correlational and experimental research but future research should consider further evaluation of its utility.

Topically delivered 22 nt siRNAs enhance RNAi silencing of endogenous genes in two species.

MAIN CONCLUSION: 22 nt siRNAs applied to leaves induce production of transitive sRNAs for targeted genes and can enhance local silencing. Systemic silencing was only observed for a GFP transgene. RNA interference (RNAi) is a gene silencing mechanism important in regulating gene expression during plant development, response to the environment and defense. Better understanding of the molecular mechanisms of this pathway may lead to future strategies to improve crop traits of value. An abrasion method to deliver siRNAs into leaf cells of intact plants was used to investigate the activities of 21 and 22 nt siRNAs in silencing genes in Nicotiana benthamiana and Amaranthus cruentus. We confirmed that both 21 and 22 nt siRNAs were able to silence a green fluorescent protein (GFP) transgene in treated leaves of N. benthamiana, but systemic silencing of GFP occurred only when the guide strand contained 22 nt. Silencing in the treated leaves of N. benthamiana was demonstrated for three endogenous genes: magnesium cheletase subunit I (CHL-I), magnesium cheletase subunit H (CHL-H), and GENOMES UNCOUPLED4 (GUN4). However, systemic silencing of these endogenous genes was not observed. Very high levels of transitive siRNAs were produced for GFP in response to treatment with 22 nt siRNAs but only low levels were produced in response to a 21 nt siRNA. The endogenous genes tested also produced transitive siRNAs in response to 22 nt siRNAs. 22 nt siRNAs produced greater local silencing phenotypes than 21 nt siRNAs for three of the genes. These special properties of 22 nt siRNAs were also observed for the CHL-H gene in A. cruentus. These experiments suggest a functional role for transitive siRNAs in amplifying the RNAi response.

A global approach to long-term follow-up of targeted and immune-based therapy in childhood and adolescence.

While considerable efforts and progress in our understanding of the long-term toxicities of surgery, radiation and chemotherapy in children with cancer have been made over the last 5 decades, there continues to be a wide gap in our knowledge of the long-term health impact of most novel targeted and immunotherapy agents. To address this gap, ACCELERATE, a multi-stakeholder collaboration of clinical and translational academics, regulators from the EMA and FDA, patient/family advocates and members spanning small biotechnology through to large pharmaceutical companies have initiated the development of an international long-term follow-up data registry to collect this important information prospectively. Providing critical safety data on the long-term use of these approved and investigational therapies in children will support the regulatory requirements and labeling information. It will also provide the necessary insight to help guide physicians and families on the appropriateness of a targeted or immune therapy for their child and inform survivorship planning.

The association between sarcopenia and quality of life in patients undergoing colorectal cancer surgery: an exploratory study.

OBJECTIVE: To describe changes in health-related quality of life (QoL) from before colorectal cancer (CRC) surgery to 1 and 3-month post-surgery in patients diagnosed pre-operatively as sarcopenic or non-sarcopenic by computed tomography (CT) analysis. METHODS: Secondary analysis of a prospective observational cohort study with one pre-operative and two post-operative assessments. Patient-reported outcome measures (PROMs) were collected at each timepoint using Functional Assessment of Cancer Therapy-Colorectal and the EuroQol-5D (EQ-5D) questionnaires. Pre-operative staging CT scans of the third lumbar vertebra (axial slice) were analysed using Slice-O-Matic Software to determine if patients had CT defined sarcopenia by employing sex-specific threshold values for skeletal muscle index. Patient-reported outcome measure scores were compared with minimal clinical important difference estimates to determine if changes were clinically significant. RESULTS: Twenty-five of 40 patients were found to be sarcopenic. The difference between sarcopenic groups on the EQ-5D was medium-sized and clinically significant, with the sarcopenic group reporting lower health status. The non-sarcopenic group displayed a clinically significant reduction in physical wellbeing post-operatively. The sarcopenic group did not demonstrate a clinically important reduction in physical wellbeing. For functional wellbeing, the sarcopenic group recorded a clinically significant reduction at the 1-month timepoint, trending back towards baseline by the 3-month timepoint. The non-sarcopenic group recorded almost no change in functional scores. CONCLUSION: This study explored the novel concept of the effect of sarcopenia on QoL in the CRC surgical setting. Clinically significant changes were identified at both post-operative timepoints. This highlights an important proof of concept that PROMs can detect meaningful clinical change in CRC patients in the context of sarcopenia and should be further explored.

Neural indices of orienting, discrimination, and conflict monitoring after contextual fear and safety learning.

Investigations of fear conditioning have recently begun to evaluate contextual factors that affect attention-related processes. However, much of the extant literature does not evaluate how contextual fear learning influences neural indicators of attentional processes during goal-directed activity. The current study evaluated how early attention for task-relevant stimuli and conflict monitoring were affected when presented within task-irrelevant safety and threat contexts after fear learning. Participants (N = 72) completed a Flanker task with modified context before and after context-dependent fear learning. Flanker stimuli were presented in the same threat and safety contexts utilized in the fear learning task while EEG was collected. Results indicated increased early attention (N1) to flankers appearing in threat contexts and later increased neural indicators (P2) of attention to flankers appearing in safety contexts. Results of this study indicate that contextual fear learning modulates early attentional processes for task-relevant stimuli that appear in the context of safety and threat. Theoretical and clinical implications are discussed.

'Home is where the health is': Housing quality and adult health outcomes in the Survey of Income and Program Participation.

Nearly a quarter of the homes in the United States were considered unhealthy or inadequate, but whether these housing characteristics have direct effects on health or whether they are driven by other contextual housing and neighborhood characteristics remains unclear. The purpose of this study was to quantify the independent associations between poor housing quality and adult health outcomes, adjusting for socioeconomic factors (e.g. income to poverty ratio, food insecurity) and other contextual housing characteristics (e.g. rental status, number of people per household, unsafe neighborhood). Using in-person household interview data from wave 1 of the 2014 Survey of Income and Program Participation (SIPP), a secondary analysis was performed using a series of logistic regression models. The 2014 SIPP sample is a multistage stratified sample of 53,070 housing units designed to represent the civilian, noninstitutionalized population of the United States (N = 55,281 adults ages 18 and older). Our results indicate that each additional poor housing characteristic was associated with poorer health status (OR: 1.17, CI [1.11, 1.23]), higher medical utilization (OR: 1.11 CI: [1.06, 1.16]), and a higher likelihood of hospitalization (OR: 1.07, CI [1.02, 1.12]). Non-housing-related government assistance, food security, and safe neighborhoods only partially explained associations between housing quality and health outcomes. Evaluating current local, state, and federal policy on housing quality standards may help determine if these standards decrease the number of Americans residing in inadequate homes or result in improvements in health and reductions in healthcare costs. Simply put, the home is where [we suggest] the health is.

Assessing the psychometric properties of the Attentional Style Questionnaire.

Attentional control has grown in importance within theoretical and predictive models of psychopathology over past decades. The Attentional Style Questionnaire (ASQ) is a novel measure of internal and external attentional control. However, no study has independently validated this questionnaire. Two studies assessed the factor structure for the ASQ within an English-speaking population (Study 1), evaluated the construct and content validity, and assessed incremental predictability (Study 2). Results of Study 1 observed two factors that could be characterised as distractibility/cognitive avoidance and focusing, whereas the original study had observed factors defined as internal and external. Results of Study 2 confirmed the factor structure of Study 1, in addition to providing evidence for the ASQ's predictability for anxiety, depression and worry behaviours above established measures of attentional control. Overall, these results indicated that the ASQ measures factors of attentional control which provides incremental utility for predicting psychopathology. Implications on psychopathology and discrepancies to previous findings are discussed.

Next steps for drowning prevention in rural and remote Australia: A systematic review of the literature.

OBJECTIVE: To examine unintentional drowning by remoteness in Australia. DESIGN: A systematic review of both peer-reviewed and grey literature published between January 1990 and December 2019 (inclusive). METHOD: Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, MEDLINE (Ovid), PubMed, EMBASE, Scopus, PsycINFO (ProQuest), SPORTDiscus and Google Scholar were searched for studies exploring fatal and non-fatal unintentional drowning by remoteness. Epidemiological data, common factors and prevention strategies were extracted and mapped to Australian standard geographical classifications (major cities, inner regional, outer regional, remote and very remote). Level of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation and prevention strategies aligned to the hierarchy of control. RESULT: Thirty-two studies satisfied inclusion criteria (66% reporting epidemiology; 59% risk factors; and 44% prevention strategies). All (100%) included studies were assessed very low against Grading of Recommendations Assessment, Development and Evaluation. Findings indicate rural populations (ie, excluding major cities) have higher rates of drowning positively correlated with increasing remoteness. Common factors included age (child), natural water bodies, undertaking boating and watercraft activities and alcohol consumption. While a range of prevention strategies has been proposed, only one study outlined a rural drowning prevention strategy which had been implemented and evaluated. Strategies were generally low on the hierarchy of control. CONCLUSION: Rural populations are proportionately overrepresented in drowning statistics. Proposed prevention strategies have unknown efficacy. Greater research into rural drowning of Australians is needed especially exploring behavioural motivations, program delivery, cost-effectiveness and evaluation. Development and use of a standard definition for remoteness are recommended. Rural populations use water extensively; therefore, there is an urgent need to keep them safe.

Genetic association analysis of N-methyl-D-aspartate receptor subunit gene GRIN2B and clinical response to clozapine.

OBJECTIVE: Approximately 30% of patients with schizophrenia fail to respond to antipsychotic therapy and are classified as having treatment-resistant schizophrenia. Clozapine is the most efficacious drug for treatment-resistant schizophrenia and may deliver superior therapeutic effects partly by modulating glutamate neurotransmission. Response to clozapine is highly variable and may depend on genetic factors as indicated by twin studies. We investigated eight polymorphisms in the N-methyl-D-aspartate glutamate receptor subunit gene GRIN2B with response to clozapine. METHODS: GRIN2B variants were genotyped using standard TaqMan procedures in 175 European patients with schizophrenia deemed resistant or intolerant to treatment. Response was assessed using change in Brief Psychiatric Rating Scale scores following six months of clozapine therapy. Categorical and continuous response was assessed using chi-squared test and analysis of covariance, respectively. RESULTS: No associations were observed between the variants and response to clozapine. A-allele carriers of rs1072388 responded marginally better to clozapine therapy than GG-homozygotes; however, the difference was not statistically significant (p = 0.067, uncorrected). CONCLUSIONS: Our findings do not support a role for these GRIN2B variants in altering response to clozapine in our sample. Investigation of additional glutamate variants in clozapine response is warranted.

Real-time monitoring of peptide grafting onto chitosan films using capillary electrophoresis.

Chitosan, being antimicrobial and biocompatible, is attractive as a cell growth substrate. To improve cell attachment, arginine-glycine-aspartic acid-serine (RGDS) peptides were covalently grafted to chitosan films, through the widely used coupling agents 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC-HCl) and N-hydroxysuccinimide (NHS), via the carboxylic acid function of the RGDS molecule. The grafting reaction was monitored, for the first time, in real time using free-solution capillary electrophoresis (CE). This enabled fast separation and determination of the peptide and all other reactants in one separation with no sample preparation. Covalent RGDS peptide grafting onto the chitosan film surface was demonstrated using solid-state NMR of swollen films. CE indicated that oligomers of RGDS, not simply RGDS, were grafted on the film, with a likely hyperbranched structure. To assess the functional properties of the grafted films, cell growth was compared on control and peptide-grafted chitosan films. Light microscopy and polymerase chain reaction (PCR) analysis demonstrated greatly improved cell attachment to RGDS-grafted chitosan films.

Vac14 protein multimerization is a prerequisite step for Fab1 protein complex assembly and function.

Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) helps control various endolysosome functions including organelle morphology, membrane recycling, and ion transport. Further highlighting its importance, PtdIns(3,5)P2 misregulation leads to the development of neurodegenerative diseases like Charcot-Marie-Tooth disease. The Fab1/PIKfyve lipid kinase phosphorylates PtdIns(3)P into PtdIns(3,5)P2 whereas the Fig4/Sac3 lipid phosphatase antagonizes this reaction. Interestingly, Fab1 and Fig4 form a common protein complex that coordinates synthesis and degradation of PtdIns(3,5)P2 by a poorly understood process. Assembly of the Fab1 complex requires Vac14/ArPIKfyve, a multimeric scaffolding adaptor protein that coordinates synthesis and turnover of PtdIns(3,5)P2. However, the properties and function of Vac14 multimerization remain mostly uncharacterized. Here we identify several conserved C-terminal motifs on Vac14 required for self-interaction and provide evidence that Vac14 likely forms a dimer. We also show that monomeric Vac14 mutants do not support interaction with Fab1 or Fig4, suggesting that Vac14 multimerization is likely the first molecular event in the assembly of the Fab1 complex. Finally, we show that cells expressing monomeric Vac14 mutants have enlarged vacuoles that do not fragment after hyperosmotic shock, which indicates that PtdIns(3,5)P2 levels are greatly abated. Therefore, our observations support an essential role for the Vac14 homocomplex in controlling PtdIns(3,5)P2 levels.

Understanding the important characteristics of neighbourhoods to facilitate ageing in place and longevity.

OBJECTIVES: This study investigates which local area characteristics, included in the Healthy Ageing/Vulnerable ENvironment (HAVEN) Index, are the strongest factors predicting transition into permanent residential aged care (PRAC) and mortality, and the geographic distribution of these factors. METHODS: A retrospective cohort study of older individuals living in the community in Adelaide who received their first eligibility assessment for age care services between 2013 and 2015 (n = 16,939) was conducted. The study cohort, from the Registry of Senior Australians (ROSA), was linked by postcode to HAVEN Index items, selected following item response theory (IRT) analysis to determine the strongest local area factors associated with PRAC and mortality. Geospatial mapping of the factors determined the geographic distribution of these significant factors. RESULTS: Fourteen HAVEN Index items were associated with entry into PRAC and mortality. Three area-level items, lower educational attainment, financial housing stress and low levels of volunteering by older people, were risk factors for entry into PRAC and mortality while the remainder of the items identified were different for each outcome. The mapped local area risk factors for each outcome highlighted similar geographical areas of vulnerability. CONCLUSIONS: Local area characteristics are associated with entering PRAC and mortality. Our findings can inform area-level responses to make neighbourhoods more age-friendly, potentially allowing more people to age longer in place. Similar analyses, conducted for other areas, could provide evidence to support the widespread development of age-friendly neighbourhoods reducing area-level inequalities in ageing.

Amyand's hernia with concurrent appendicitis: A case of interval laparoscopic herniorrhaphy and literature review.

INTRODUCTION AND IMPORTANCE: Amyand's hernia with concurrent appendicitis is rare, with a reported incidence of 0.13 % of all inguinal hernias. This condition is challenging to diagnose and manage and no optimal treatment has been established. CASE PRESENTATION: A 71-year-old man presented with an acutely painful, tender, and irreducible right inguinal hernia. He had a history of a right inguinal hernia for several months and had undergone open left inguinal hernia repair. The patient had no other medical comorbidities. Blood test results were nonspecific, with a C-reactive protein of 90 mg/L. Ultrasound scan suggested a strangulated right inguinal hernia. Laparoscopy revealed an Amyand's hernia with concurrent appendicitis and a pus-filled right inguinal hernia sac. The patient underwent laparoscopic appendicectomy, followed by staged laparoscopic transabdominal preperitoneal right inguinal hernia repair with mesh after eight weeks to reduce mesh infection. Histopathological examination confirmed acute uncomplicated appendicitis without perforation or malignancy. The patient had an unremarkable post-operative recovery. DISCUSSION: This case highlights the diagnostic challenges associated with Amyand's hernia and concurrent appendicitis. Laparoscopy provides both diagnostic and therapeutic opportunities. In this case, laparoscopic mesh herniorrhaphy was delayed and staged until local hernia sac inflammation resolved following appendicectomy. CONCLUSION: Surgeons should have an index of suspicion for Amyand's hernia given the heterogeneity of presentations. A case-by-case approach is required to prevent post-operative complications and determine the safe timing of definitive hernia repair when the inguinal hernial sac is inflamed. Further research is required to provide surgeons with evidence-based approaches for this unique condition.

Electrophysiological Phenotypes of Hippocampal Synaptic and Network Functions in Cannabinoid Receptor 2 Knockout Mice.

Background: The cannabinoid receptor 2 (CB2R), a cannabinoid receptor primarily expressed in immune cells, has been found in the brain, particularly in the hippocampus, where it plays crucial roles in modulating various neural functions, including synaptic plasticity, neuroprotection, neurogenesis, anxiety and stress responses, and neuroinflammation. Despite this growing understanding, the intricate electrophysiological characteristics of hippocampal neurons in CB2R knockout (CB2R KO) mice remain elusive. Aim and Methods: This study aimed to comprehensively assess the electrophysiological traits of hippocampal synaptic and network functions in CB2R KO mice. The focus was on aspects such as synaptic transmission, short- and long-term synaptic plasticity, and neural network synchrony (theta oscillations). Results: Our findings unveiled multiple functional traits in these CB2R KO mice, notably elevated synaptic transmission in hippocampal CA1 neurons, decreased both synaptic short-term plasticity (paired-pulse facilitation) and long-term potentiation (LTP), and impaired neural network synchronization. Conclusion: In essence, this study yields insightful revelations about the influence of CB2Rs on hippocampal neural functions. By illuminating the electrophysiological modifications in CB2R KO mice, our research enriches the comprehension of CB2R involvement in hippocampal function. Such insights could hold implications for advancing our understanding of the neural mechanisms under the influence of CB2Rs within the brain.