Activation of androgen receptor-expressing neurons in the posterior medial amygdala is associated with stress resistance in dominant male hamsters.

Social stress is a negative emotional experience that can increase fear and anxiety. Dominance status can alter the way individuals react to and cope with stressful events. The underlying neurobiology of how social dominance produces stress resistance remains elusive, although experience-dependent changes in androgen receptor (AR) expression is thought to play an essential role. Using a Syrian hamster (Mesocricetus auratus) model, we investigated whether dominant individuals activate more AR-expressing neurons in the posterior dorsal and posterior ventral regions of the medial amygdala (MePD, MePV), and display less social anxiety-like behavior following social defeat stress compared to subordinate counterparts. We allowed male hamsters to form and maintain a dyadic dominance relationship for 12 days, exposed them to social defeat stress, and then tested their approach-avoidance behavior using a social avoidance test. During social defeat stress, dominant subjects showed a longer latency to submit and greater c-Fos expression in AR+ cells in the MePD/MePV compared to subordinates. We found that social defeat exposure reduced the amount of time animals spent interacting with a novel conspecific 24 h later, although there was no effect of dominance status. The amount of social vigilance shown by dominants during social avoidance testing was positively correlated with c-Fos expression in AR+ cells in the MePV. These findings indicate that dominant hamsters show greater neural activity in AR+ cells in the MePV during social defeat compared to their subordinate counterparts, and this pattern of neural activity correlates with their proactive coping response. Consistent with the central role of androgens in experience-dependent changes in aggression, activation of AR+ cells in the MePD/MePV contributes to experience-dependent changes in stress-related behavior.

Sleep in people with and without intellectual disabilities: a systematic review and meta-analysis.

BACKGROUND: Sleep problems are regularly reported in people with intellectual disabilities. Recent years have seen a substantial increase in studies comparing sleep in people with intellectual disabilities to control participants, with an increase in the use of validated, objective measures. Emerging patterns of differences in sleep time and sleep quality warrant pooled investigation. METHODS: A systematic search was conducted across three databases (Ovid Embase, PsycInfo and Medline) and returned all papers comparing sleep in people with intellectual disabilities to a control group, published since the last meta-analysis on the topic. A quality framework was employed to rate the risk of bias across studies. Separate meta-analyses of sleep duration and sleep quality were conducted. Subgrouping compared findings for those studies with participants with genetic syndromes or neurodevelopmental conditions and those with heterogeneous intellectual disability. RESULTS: Thirteen new papers were identified and combined with those from the previous meta-analysis to provide 34 papers in total. Quality of studies was generally rated highly, though sampling provided risk of bias and adaptive functioning was rarely measured. People with intellectual disability associated with genetic syndromes or neurodevelopmental conditions sleep for shorter time periods (standardised mean difference = .26) and experience worse sleep quality (standardised mean difference = .68) than their peers. People with intellectual disability of heterogeneous origin show no difference in sleep time but have poorer sleep quality. There was some evidence that age moderated these effects. CONCLUSIONS: People with intellectual disability have poorer sleep than those without. Subtle patterns suggest that aetiology of intellectual disability moderates the topography of these difficulties, with further work needed to differentiate common and distinct mechanisms across groups.

Losing a part of life: experiences of cancer survivors accessing treatment and sheltering in place during the COVID-19 pandemic.

PURPOSE: To explore experiences of sheltering in place and accessing treatment during the initial stages of the COVID-19 pandemic among survivors with cancer receiving tyrosine kinase inhibitor (TKI) therapy. METHODS: Participants from two pilot studies evaluating TKI therapy use in the Southeastern United States during the start of the COVID-19 pandemic (March 2020) were interviewed. Identical interview guides were used across both studies to assess participants' experiences accessing cancer treatment, sheltering in place, and coping during the COVID-19 pandemic. Digitally recorded sessions were transcribed professionally and checked for accuracy. Descriptive statistics were used to summarize participant sociodemographics, and a six-step thematic approach was used to analyze interview data and identify salient themes. Dedoose qualitative research software was used to manage and organize qualitative codes, themes, and memos. RESULTS: Participants (n = 15) ranged from 43 to 84 years of age, and were mostly female (53.3%), married (60%), and survivors with hematologic malignancies (86.7%). The research team identified five salient themes: Participants followed pandemic guidelines, Variable impact on well-being, Common feelings of fear, anxiety and anger, No barriers to accessing therapy and medical care, and Faith and God as powerful forces for coping. CONCLUSIONS: The conclusions of the study provide several implications for survivorship programs or clinics for supporting survivors who are taking chronic TKI therapy during COVID-19, including enhancement of current psychosocial support efforts for cancer survivors or development of new programs tailored to the unique needs of a survivor during a pandemic, such as focused coping strategies, modified physical activity programs, family/professional role changes, and access to safe public spaces.

CFTR modulator therapies - Effect on life expectancy in people with cystic fibrosis.

CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.

Telemedicine and cystic fibrosis: Do we still need face-to-face clinics?

There has been growing interest in telemedicine for cystic fibrosis over recent years based largely on convenience for patients and/or increasing the frequency of surveillance and early detection which, it is assumed, could improve treatment outcomes. During 2020, the covid-19 pandemic catalysed the pace of development of this field, as CF patients were presumed to be at high risk of infection. Most clinics adapted to digital platforms with provision of lung function monitoring and sample collection systems. Here, we present the views of multidisciplinary team members at a large paediatric CF centre on what has worked well and what requires further optimisation in the future. In response to the question posed, 'Do we still need face to face clinics?' our answer is 'Yes, but not every time, and not for everyone'.

Mode of delivery following obstetric anal sphincter injury: a 7-year retrospective review and follow-up cohort survey.

INTRODUCTION AND HYPOTHESIS: Limited evidence exists regarding long-term outcomes following birth after prior obstetric anal sphincter injury (OASI). This article set out to describe outcomes following birth after OASI by reviewing the grades of tear, endoanal ultrasound (EAUS) findings, subsequent delivery outcomes and long-term symptoms. METHODS: This study was conducted in two parts. The first involved a retrospective review of all OASI at a tertiary hospital in Australia over 7 years (2013-2019 inclusive) where the patient underwent a subsequent delivery. Following this, a retrospective cohort survey of this group was performed. RESULTS: There were 27,284 vaginal births and 828 OASIs (3.03%); 247 (29.8%) had at least one subsequent birth by January 2021. Vaginal delivery occurred in 68%; recurrence of OASI was 5.4%. There were 90 responses (36.4%) to the follow-up survey. EAUS had been performed in 87.5%; none demonstrated a defect. Vaginal birth was the preferred mode for 77.8%; this occurred in 64%. The majority had high levels of satisfaction, this related to communication rather than the mode of delivery itself. Ongoing faecal or flatal incontinence was reported by 12%. There was no statistically significant difference in St Mark's incontinence scores between modes of birth. CONCLUSIONS: In our unit most women who sustain OASI will have a subsequent vaginal delivery in future pregnancies. The majority remain asymptomatic at long-term follow-up with no statistically significant difference in incontinence scores regardless of mode of delivery. The rate of recurrent OASI was 5.4%.

Managing flood flow connectivity to landscapes to build buffering capacity to disturbances: An ecohydrologic modeling framework for drylands.

Increased flooding, droughts, and sediment transport are watershed-scale problems negatively impacting agriculture and ecosystems in drylands worldwide. Vegetation loss in upland watersheds is leading to scouring floods, which in turn decreases infiltration, soil moisture levels, and downstream groundwater recharge. Management to confront these intractable problems has been hindered by a lack of accessible decision support tools for both land and water managers that synthesize the watershed processes that buffer against dryland disturbances. Flood flow connectivities across the landscape create buffer zones through replenishing soil moisture and reducing flood energy, which in turn support multiple functions. This study developed a decision support tool, the Flood Flow Connectivity to the Landscape (FlowCon) framework that quantifies the most efficient management efforts to increase the key watershed buffering functions of increasing infiltration and reducing flow energy. FlowCon links three spatially explicit, process-based, and predictive models to answer two critical management questions: what key processes acting in what optimal areas are drivers of infiltration dynamics and what roles do peak flows of differing scales of energy play. The spatial models delineated the buffer zone to characterize the heterogeneous and optimal infiltration dynamics across the landscape. The hydrologic process model, using a curve number technique, identified the key ecohydrologic processes that affect infiltration and characterized peak flows and flow regime variability. The predictive flood routing model quantified the potential management benefits. We calibrated the models with measured runoff and the corresponding rainfall events for a six-year period, which included thirty-six flow events. The synthesized ecohydrologic indicators provided critical calibrations, improving the relationship between the hydrologic modeling results and observed data by 12% for the linear regression R2 and 69% for the root mean square error (RMSE). Implementation of prioritized management is estimated to reduce peak flow by half, with interventions focused on 24% of floodplains that infiltrate three times the flow volume per area than the floodplain average. FlowCon provides an efficient assessment framework that integrates watershed process understanding in an accessible decision support tool to achieve tangible improvements in dryland watershed management.

The endocranium and trophic ecology of Velociraptor mongoliensis.

Neuroanatomical reconstructions of extinct animals have long been recognized as powerful proxies for palaeoecology, yet our understanding of the endocranial anatomy of dromaeosaur theropod dinosaurs is still incomplete. Here, we used X-ray computed microtomography (µCT) to reconstruct and describe the endocranial anatomy, including the endosseous labyrinth of the inner ear, of the small-bodied dromaeosaur, Velociraptor mongoliensis. The anatomy of the cranial endocast and ear were compared with non-avian theropods, modern birds, and other extant archosaurs to establish trends in agility, balance, and hearing thresholds in order to reconstruct the trophic ecology of the taxon. Our results indicate that V. mongoliensis could detect a wide and high range of sound frequencies (2,368-3,965 Hz), was agile, and could likely track prey items with ease. When viewed in conjunction with fossils that suggest scavenging-like behaviours in V. mongoliensis, a complex trophic ecology that mirrors modern predators becomes apparent. These data suggest that V. mongoliensis was an active predator that would likely scavenge depending on the age and health of the individual or during prolonged climatic events such as droughts.

Comparative Greenhouse Gas Footprinting of Online versus Traditional Shopping for Fast-Moving Consumer Goods: A Stochastic Approach.

Variability in consumer practices and choices is typically not addressed in comparisons of environmental impacts of traditional shopping and e-commerce. Here, we developed a stochastic model to quantify the variability in the greenhouse gas (GHG) footprints of product distribution and purchase of fast-moving consumer goods (FMCGs) via three prevalent retail channels in the United Kingdom (U.K.). We found that shopping via bricks and clicks (click and fulfillment via physical store delivery) most likely decreases the GHG footprints when substituting traditional shopping, while FMCGs purchased through pure players with parcel delivery often have higher GHG footprints compared to those purchased via traditional retail. The number of items purchased and the last-mile travel distance are the dominant contributors to the variability in the GHG footprints of all three retail channels. We further showed that substituting delivery vans with electric cargo bikes can lead to a GHG emission reduction of 26% via parcel delivery. Finally, we showed the differences in the "last mile" GHG footprint of traditional shopping in the U.K. compared to three other countries (China, Netherlands, and the United States), which are primarily caused by the different shares of modes of transport (walking and by car, bus, and bike).

Estrogen receptor-alpha knockouts and maternal memory in nulliparous rats.

The current study investigated the role of estrogen receptor alpha (Esr1) in maternal memory in rats, comparing the induction and retention responses of Esr1 knockout (KO) and wild type (WT) nulliparous rats towards foster pups. Thirty days after completion of induction testing, subjects were tested for the retention of maternal care in their home cage and then for maternal behaviors in a novel cage. Both WT and Esr1 KO females displayed similar latencies to respond to foster young during the initial induction testing. Likewise, reinduction latencies to display full maternal responsiveness were similar in the Esr1 KO and WT groups during maternal memory testing in the home cage. However, in the novel cage testing WT subjects displayed modest modifications in maternal care. WT females had shorter latencies to first retrieve and mouth a test pup. These findings suggest that while Esr1 does not appear to affect the establishment of maternal care or the display of maternal memory, it may modulate aspects of pup-directed behaviors associated with the reinduction of maternal care in female rats.

Identifying patients' support needs following critical illness: a scoping review of the qualitative literature.

BACKGROUND: Intensive care survivors suffer chronic and potentially life-changing physical, psychosocial and cognitive sequelae, and supporting recovery is an international priority. As survivors' transition from the intensive care unit to home, their support needs develop and change. METHODS: In this scoping review, we categorised patients' support needs using House's Social Support Needs framework (informational, emotional, instrumental, appraisal) and mapped these against the Timing it Right framework reflecting the patient's transition from intensive care (event/diagnosis) to ward (stabilisation/preparation) and discharge home (implementation/adaptation). We searched electronic databases from 2000 to 2017 for qualitative research studies reporting adult critical care survivors' experiences of care. Two reviewers independently screened, extracted and coded data. Data were analysed using a thematic framework approach. RESULTS: From 3035 references, we included 32 studies involving 702 patients. Studies were conducted in UK and Europe (n = 17, 53%), Canada and the USA (n = 6, 19%), Australasia (n = 6, 19%), Hong Kong (n = 1, 3%), Jordan (n = 1, 3%) and multi-country (n = 1, 3%). Across the recovery trajectory, informational, emotional, instrumental, appraisal and spiritual support needs were evident, and the nature and intensity of need differed when mapped against the Timing it Right framework. Informational needs changed from needing basic facts about admission, to detail about progress and treatments and coping with long-term sequelae. The nature of emotional needs changed from needing to cope with confusion, anxiety and comfort, to a need for security and family presence, coping with flashbacks, and needing counselling and community support. Early instrumental needs ranged from managing sleep, fatigue, pain and needing nursing care and transitioned to needing physical and cognitive ability support, strength training and personal hygiene; and at home, regaining independence, strength and return to work. Appraisal needs related to obtaining feedback on progress, and after discharge, needing reassurance from others who had been through the ICU experience. CONCLUSIONS: This review is the first to identify the change in social support needs among intensive care survivors as they transition from intensive care to the home environment. An understanding of needs at different transition periods would help inform health service provision and support for survivors.

Mathematical modelling of contact dermatitis from nickel and chromium.

Dermal exposure to metal allergens can lead to irritant and allergic contact dermatitis (ACD). In this paper we present a mathematical model of the absorption of metal ions, hexavalent chromium and nickel, into the viable epidermis and compare the localised irritant and T-lymphocyte (T-cell) mediated immune responses. The model accounts for the spatial-temporal variation of skin health, extra and intracellular allergen concentrations, innate immune cells, T-cells, cytokine signalling and lymph node activity up to about 6 days after contact with these metals; repair processes associated with withdrawal of exposure to both metals is not considered in the current model, being assumed secondary during the initial phases of exposure. Simulations of the resulting system of PDEs are studied in one-dimension, i.e. across skin depth, and three-dimensional scenarios with the aim of comparing the responses to the two ions in the cases of first contact (no T-cells initially present) and second contact (T-cells initially present). The results show that on continuous contact, chromium ions elicit stronger skin inflammation, but for nickel, subsequent re-exposure stimulates stronger responses due to an accumulation of cytotoxic T-cell mediated responses which characterise ACD. Furthermore, the surface area of contact to these metals has little effect on the speed of response, whilst sensitivity is predicted to increase with the thickness of skin. The modelling approach is generic and should be applicable to describe contact dermatitis from a wide range of allergens.

Experiences of coeliac disease in a changing gluten-free landscape.

BACKGROUND: Coeliac disease is an autoimmune disorder triggered by the ingestion of gluten. In recent years, there has been considerable increase in the availability of gluten-free products in North America. The present study investigated how the recent proliferation of the gluten-free industry has affected individuals living with coeliac disease, with a primary focus on their social lives and relationships. METHODS: Interpretive phenomenology was utilised for study design and analysis. Semi-structured interviews were conducted with 17 adults diagnosed with coeliac disease in Calgary, Alberta. Interviews were audio recorded and then transcribed for analysis. RESULTS: People living with coeliac disease experience the growth of the gluten-free industry as a 'double-edged sword'. Although they are grateful for more palatable gluten-free options, they are increasingly faced with misunderstandings about the severity of coeliac disease as a result of many noncoeliac disease individuals subscribing to the gluten-free diet. This 'double-edged sword' made certain types of social situations more easily manageable (e.g. more gluten-free options available at restaurants), whereas others produced distress (e.g. increased risk of inadvertently consuming gluten). Participants also felt they may be perceived or even perceived themselves differently (e.g. felt high maintenance). To help mitigate these social ramifications of following the gluten-free diet, participants utilised various strategies. CONCLUSIONS: The sole medical recommendation of a gluten-free diet fails to acknowledge the ongoing difficulties those with coeliac disease can endure in the current gluten-free landscape. Recommendations beyond the gluten-free diet are advisable to alleviate many of the indirect burdens revealed in the present study.

Mercury-induced aggregation of human lens γ-crystallins reveals a potential role in cataract disease.

Cataract disease results from non-amyloid aggregation of eye lens proteins and is the leading cause of blindness in the world. A variety of studies have implicated both essential and xenobiotic metals as potential etiological agents in cataract disease. Essential metal ions, such as copper and zinc, are known to induce the aggregation in vitro of human γD crystallin, one of the more abundant γ-crystallins in the core of the lens. In this study, we expand the investigation of metal-crystallin interactions to heavy metal ions, such as divalent lead, cadmium and mercury. The impact of these metal ions in the non-amyloid aggregation, protein folding and thermal stability of three homologous human lens γ-crystallins has been evaluated using turbidity assays, electron microscopy, electronic absorption and circular dichroism spectroscopies. Our results show that Hg(II) ions can induce the non-amyloid aggregation of human γC and γS crystallins, but not γD crystallin. The mechanism of Hg-induced aggregation involves direct metal-protein interactions, loss of thermal stability, partial unfolding of the N-terminal domain of these proteins, and formation of disulfide-bridged dimers. Putative Hg(II) binding sites in γ-crystallins involved in metal-induced aggregation are discussed. This study reveals that mercury ions can induce the aggregation of human lens proteins, uncovering a potential role of this heavy metal ion in the bioinorganic chemistry of cataract disease.

Subliminal and supraliminal processing of reward-related stimuli in anorexia nervosa.

BACKGROUND: Previous studies have highlighted the role of the brain reward and cognitive control systems in the etiology of anorexia nervosa (AN). In an attempt to disentangle the relative contribution of these systems to the disorder, we used functional magnetic resonance imaging (fMRI) to investigate hemodynamic responses to reward-related stimuli presented both subliminally and supraliminally in acutely underweight AN patients and age-matched healthy controls (HC). METHODS: fMRI data were collected from a total of 35 AN patients and 35 HC, while they passively viewed subliminally and supraliminally presented streams of food, positive social, and neutral stimuli. Activation patterns of the group × stimulation condition × stimulus type interaction were interrogated to investigate potential group differences in processing different stimulus types under the two stimulation conditions. Moreover, changes in functional connectivity were investigated using generalized psychophysiological interaction analysis. RESULTS: AN patients showed a generally increased response to supraliminally presented stimuli in the inferior frontal junction (IFJ), but no alterations within the reward system. Increased activation during supraliminal stimulation with food stimuli was observed in the AN group in visual regions including superior occipital gyrus and the fusiform gyrus/parahippocampal gyrus. No group difference was found with respect to the subliminal stimulation condition and functional connectivity. CONCLUSION: Increased IFJ activation in AN during supraliminal stimulation may indicate hyperactive cognitive control, which resonates with clinical presentation of excessive self-control in AN patients. Increased activation to food stimuli in visual regions may be interpreted in light of an attentional food bias in AN.

Evaluation of InnoTyper® 21 in a sample of Rio de Janeiro population as an alternative forensic panel.

The use of bi-allelic markers such as retrotransposable element insertion polymorphisms or Innuls (for insertion/null) can overcome some limitations of short tandem repeat (STR) loci in typing forensic biological evidence. This study investigated the efficiency of the InnoTyper® 21 Innul markers in an urban admixed population sample in Rio de Janeiro (n = 40) and one highly compromised sample collected as evidence by the Rio de Janeiro police. No significant departures from Hardy-Weinberg equilibrium were detected after the Bonferroni correction (α' ≈ 0.05/20, p < 0.0025), and no significant linkage disequilibrium was observed between markers. Assuming loci independence, the cumulative random match probability (RMP) was 2.3 × 10-8. A lower mean Fis value was obtained for this sample population compared with those of three North American populations (African-American, Southwest Hispanic, US Caucasian). Principal component analysis with the three North American populations and one from 21 East Asian population showed that African Americans segregated as an independent group while US Caucasian, Southwest Hispanic, East Asian, and Rio de Janeiro populations are in a single large heterogeneous group. Also, a full Innuls profile was produced from an evidence sample, despite the DNA being highly degraded. In conclusion, this system is a useful complement to standard STR kits.

Variability of Greenhouse Gas Footprints of Field Tomatoes Grown for Processing: Interyear and Intercountry Assessment.

Our study provides an integrated analysis of the variability of greenhouse gas (GHG) footprints of field-grown tomatoes for processing. The global farm-specific data set of 890 observations across 14 countries over a three-year period (2013-2015) was obtained from farms grown under Unilever's sustainable agricultural code. It represents on average 3% of the annual global production of processing tomatoes: insights can be used to help inform corporate sourcing strategies and certification schemes. The median GHG footprint ranged from 18 in Chile to 61 kg CO2-equiv per tonne of tomatoes in India, lower than results reported in other studies. We found that footprints are more consistent within countries than between them. Using linear mixed effect models, we quantified the relative influence of environmental conditions and farm management factors. Key variables were area of production and the method of fertilizer application. GHG footprints decreased with increasing area of production to a threshold of 17.4 ha. Farms using single fertilizer application methods in general had a larger GHG footprint than those using a combination of methods. We conclude that farm management factors should be prioritized for future data collection, and more stringent guidance on acceptable practices is required if greater comparability of outcomes is needed either within a scheme, such as the Unilever's sustainable agriculture code, or between schemes.

Effect of benazepril and pimobendan on serum angiotensin-converting enzyme activity in dogs.

To support their combined use, the objective of the study was to evaluate the effects of benazepril and pimobendan on serum angiotensin-converting enzyme (ACE) activity in dogs. A total of 48 healthy beagle dogs were randomized into four groups (n = 12 per group) in a parallel-group design study: A (control, placebo twice daily (BID)); B (0.5-1.0 mg/kg benazepril once daily (SID) in the morning, placebo in the evening); C (0.25-0.5 mg/kg benazepril BID); D (0.25-0.5 mg/kg benazepril and 0.125-0.25 mg/kg pimobendan, both BID). The test items were administered orally for 15 days. Serum ACE activity was measured on days 1 and 15. Groups B, C and D had significantly lower average serum ACE activity compared to baseline and to the control group, on both days 1 and 15. There were no significant differences in average ACE activity between groups B, C and D. Noninferiority of group C to B was demonstrated. In conclusion, 0.25-0.5 mg/kg benazepril administered BID produced noninferior inhibition of serum ACE activity compared to 0.5-1.0 mg/kg benazepril dosed SID. Pimobendan had no significant effect on benazepril's action on serum ACE activity. The results support the use of benazepril BID in dogs and in combination with pimobendan.

Safety of a benazepril and pimobendan combination tablet in adult healthy dogs.

The objective of the study was to investigate the safety of a combination tablet of benazepril and pimobendan, Fortekor PLUS® , in a randomized, blinded, parallel-group design study in healthy adult beagle dogs. The test article, Fortekor PLUS® tablets, was administered orally twice daily for 6 months at one, two, and four times the highest recommended dosage of 0.5 mg/kg benazepril hydrochloride/0.25 mg/kg pimobendan (four males and four females per group). An additional control group was sham-dosed. Fortekor PLUS® did not induce any treatment-related effects on body weight, food consumption, neurological, ophthalmologic or physical assessments over the 6-month treatment period. The test article was possibly associated with an increased frequency of occasional vomiting. Fortekor PLUS® was associated with small, but significant, increases in heart rate and reductions in PR and QT intervals, which were assessed by electrocardiography. These effects were most probably related to reflex tachycardia secondary to reduced systemic blood pressure. Statistically significant changes in some clinical pathology variables were noted after test article administration, but were considered to be of no clinical relevance as values remained within reference ranges and/or were not dose-dependent. No treatment-related macroscopic or microscopic findings were observed. In conclusion, Fortekor PLUS® tablets were well tolerated in healthy adult dogs when administered at one, two, and four times the highest recommended dosage for 6 months.