Environmental factors shaping the gut microbiome in a Dutch population.

The gut microbiome is associated with diverse diseases1-3, but a universal signature of a healthy or unhealthy microbiome has not been identified, and there is a need to understand how genetics, exposome, lifestyle and diet shape the microbiome in health and disease. Here we profiled bacterial composition, function, antibiotic resistance and virulence factors in the gut microbiomes of 8,208 Dutch individuals from a three-generational cohort comprising 2,756 families. We correlated these to 241 host and environmental factors, including physical and mental health, use of medication, diet, socioeconomic factors and childhood and current exposome. We identify that the microbiome is shaped primarily by the environment and cohabitation. Only around 6.6% of taxa are heritable, whereas the variance of around 48.6% of taxa is significantly explained by cohabitation. By identifying 2,856 associations between the microbiome and health, we find that seemingly unrelated diseases share a common microbiome signature that is independent of comorbidities. Furthermore, we identify 7,519 associations between microbiome features and diet, socioeconomics and early life and current exposome, with numerous early-life and current factors being significantly associated with microbiome function and composition. Overall, this study provides a comprehensive overview of gut microbiome and the underlying impact of heritability and exposures that will facilitate future development of microbiome-targeted therapies.

Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice.

Protein Kinase RNA-activated (PKR) is an enzyme that plays a role in many systemic processes, including modulation of inflammation, and is implicated in neurodegenerative diseases, such as Alzheimer's disease (AD). PKR phosphorylation results in the production of several cytokines involved in the regulation / modulation of sleep, including interleukin-1ß, tumor necrosis factor-α and interferon-γ. We hypothesized targeting PKR would alter spontaneous sleep of mice, attenuate responses to sleep deprivation, and inhibit responses to immune challenge. To test these hypotheses, we determined the sleep-wake phenotype of mice lacking PKR (knockout; PKR-/-) during undisturbed baseline conditions; in responses to six hours of sleep deprivation; and after immune challenge with lipopolysaccharide (LPS). Adult male mice (C57BL/6J, n = 7; PKR-/-, n = 7) were surgically instrumented with EEG recording electrodes and an intraperitoneal microchip to record core body temperature. During undisturbed baseline conditions, PKR -/- mice spent more time in non-rapid eye movement sleep (NREMS) and rapid-eye movement sleep (REMS), and less time awake at the beginning of the dark period of the light:dark cycle. Delta power during NREMS, a measure of sleep depth, was less in PKR-/- mice during the dark period, and core body temperatures were lower during the light period. Both mouse strains responded to sleep deprivation with increased NREMS and REMS, although these changes did not differ substantively between strains. The initial increase in delta power during NREMS after sleep deprivation was greater in PKR-/- mice, suggesting a faster buildup of sleep pressure with prolonged waking. Immune challenge with LPS increased NREMS and inhibited REMS to the same extent in both mouse strains, whereas the initial LPS-induced suppression of delta power during NREMS was greater in PKR-/- mice. Because sleep regulatory and immune responsive systems in brain are redundant and overlapping, other mediators and signaling pathways in addition to PKR are involved in the responses to acute sleep deprivation and LPS immune challenge.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Onyx®, A New Tool for Intraoperative Localization of Liver Lesions.

BACKGROUND: Precise preoperative localization of liver tumors facilitates successful surgical procedures, Intraoperative ultrasonography is a sensitive imaging modality. However, the presence of small non-palpable isoechoic intraparenchymal lesions may be challenging intraoperatively. METHODOLOGY AND MATERIAL DESCRIPTION: Onyx® is a non-adhesive liquid agent comprised of ethylene-vinyl alcohol usually used dissolved in dimethyl-sulfoxide and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy and ultrasonography and a macroscopic black shape. This embolization material has been increasingly used for the embolization of intracranial arteriovenous malformations. We present the novel application of Onyx® on liver surgery. CURRENT STATUS: We present the case of a female, 55 years-old, whose medical history revealed an elective sigmoidectomy (pT3N1a). After 17 months of follow up, by PET-CT scan, the patient was diagnosed of a small intraparenchymal hypo-attenuated 13 mm tumor located at segment V consistent with metachronous colorectal liver metastasis. Open metastasectomy was performed, ultrasonography-guided Onyx® infusion was delivered the day after, intraoperative ultrasonography showed a palpable hyperechoic material with a posterior acoustic shadowing artifact around the lesion. Onyx® is a promising new tool, without any previous application on liver surgery, feasible with advantages in small not palpable intraparenchymal liver lesions.

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

Expert opinion on the treatment of vulvovaginal atrophy with ospemifene based on new evidence.

Vulvovaginal atrophy (VVA) is an underdiagnosed and undertreated chronic condition resulting in physiological and histological changes in the genitourinary tract of postmenopausal women. Treatment of moderate to severe VVA includes local estrogens, dehydroepiandrosterone (DHEA) and oral ospemifene, a third-generation selective estrogen receptor modulator (SERM). Due to venous thromboembolism (VTE) safety concerns classically associated with the SERM class, and as part of its original marketing authorization approval (MAA), the European Medicines Agency (EMA) requested the performance of a 5-year post-authorization safety study (PASS) to study the incidence rate of VTE among women receiving ospemifene. The results have led to important regulatory changes to ospemifene's labeling, extending its indication and eliminating concerted risk management measures. A panel of experts discussed and reached consensus on the impact of these regulatory changes on clinical practice, reflecting on the reassurance of ospemifene's benefit-risk balance and recommending its positioning as a first-line pharmacological treatment option for moderate to severe VVA together with local therapies. In a scenario where different treatments present similar efficacy and safety profiles, a shared decision between clinician and patient, according to her needs and preferences over time, is fundamental to improve adherence and persistence with sequential treatment, contributing to the achievement of health outcomes.

Population-based survey on menopausal symptoms and treatment use.

OBJECTIVE: This article aimed to study the use of menopausal hormone therapy (MHT) among Spanish perimenopausal and postmenopausal women, the presence of menopausal symptoms and the sources of information. METHODS: The epidemiological study using a survey included Spanish perimenopausal or postmenopausal women aged between 40 and 70 years in August 2021. RESULTS: A total of 1254 women were included. In the postmenopausal group, 86% reported one or more menopausal symptoms; the most frequent was vulvovaginal dryness (57%). Among the symptomatic women, 15.2% used some treatment. Vasomotor symptoms (p = 0.001), vulvovaginal atrophy (p < 0.001) and symptoms related to sexuality (p < 0.001) were associated with greater use of treatments; 2.5% of postmenopausal women used MHT. In the perimenopausal group, 75.1% were symptomatic, hot flashes being the most frequent. Only insomnia was related to greater use of some treatment (p = 0.021); 1.6% of perimenopausal women used MHT. The most common reason for women's rejection of MHT was the fear of side effects, especially cancer. The gynecologist was the most frequently used source of information. CONCLUSIONS: Although there is a high prevalence of symptoms, the use of MHT in Spanish perimenopausal and postmenopausal women is very low.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 µM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 µM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, µm) and curvilinear velocity (VCL, µm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 µM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

Genomic Epidemiology of Salmonella enterica Circulating in Surface Waters Used in Agriculture and Aquaculture in Central Mexico.

Salmonella enterica can survive in surface waters (SuWa), and the role of nonhost environments in its transmission has acquired increasing relevance. In this study, we conducted comparative genomic analyses of 172 S. enterica isolates collected from SuWa across 3 months in six states of central Mexico during 2019. S. enterica transmission dynamics were assessed using 87 experimental and 112 public isolates from Mexico collected during 2002 through 2019. We also studied genetic relatedness between SuWa isolates and human clinical strains collected in North America during 2005 through 2020. Among experimental isolates, we identified 41 S. enterica serovars and 56 multilocus sequence types (STs). Predominant serovars were Senftenberg (n = 13), Meleagridis, Agona, and Newport (n = 12 each), Give (n = 10), Anatum (n = 8), Adelaide (n = 7), and Infantis, Mbandaka, Ohio, and Typhimurium (n = 6 each). We observed a high genetic diversity in the sample under study, as well as clonal dissemination of strains across distant regions. Some of these strains are epidemiologically important (ST14, ST45, ST118, ST132, ST198, and ST213) and were genotypically close to those involved in clinical cases in North America. Transmission network analysis suggests that SuWa are a relevant source of S. enterica (0.7 source/hub ratio) and contribute to its dissemination as isolates from varied sources and clinical cases have SuWa isolates as common ancestors. Overall, the study shows that SuWa act as reservoirs of various S. enterica serovars of public health significance. Further research is needed to better understand the mechanisms involved in SuWa contamination by S. enterica, as well as to develop interventions to contain its dissemination in food production settings. IMPORTANCE Surface waters are heavily used in food production worldwide. Several human pathogens can survive in these waters for long periods and disseminate to food production environments, contaminating our food supply. One of these pathogens is Salmonella enterica, a leading cause of foodborne infections, hospitalizations, and deaths in many countries. This research demonstrates the role of surface waters as a vehicle for the transmission of Salmonella along food production chains. It also shows that some strains circulating in surface waters are very similar to those implicated in human infections and harbor genes that confer resistance to multiple antibiotics, posing a risk to public health. This study contributes to expand our current knowledge on the ecology and epidemiology of Salmonella in surface waters.

Lytic to temperate switching of viral communities.

Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.

Emerging alternatives against Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is a significant worry within healthcare institutions and the community. It is one of the leading agents causing severe diarrhea worldwide. Effective management is critical since the morbidity and mortality attributed to CDI have increased exponentially over the past 20 years. Currently, antibiotics are the standard treatment for primary C. difficile infection, but at the same time, they are associated with disease relapse and increased drug resistance. CDI's high recurrence rates, spore generation, and antimicrobial resistance are currently significant challenges that urge the development of new options to combat this infection. This review describes up-and-coming alternatives and how they can mitigate the challenges associated with CDI. Here we have discussed the advantages and challenges of current and experimental alternatives against CDI.

Food industrial biowaste-based magnetic activated carbons as sustainable adsorbents for anthropogenic mercury emissions.

Bio-derived magnetic activated carbons from industrial chestnut shell waste have been obtained through a novel, optimized and sustainable methodology where impregnation, pyrolysis, acid washing or other intermediate steps commonly used in the activation process were eliminated saving time, energy and costs. The resulting materials (MACs) were obtained at 220-800 °C showed interesting properties: textural (SBET up to 568 m2 g-1) and magnetic (different iron species developed), depending on the activation temperature employed. Data showed outstanding results when MACs were tested for Hg removal in pollution emissions at 150 °C in lab-scale device. In MACs obtained at 500-600 °C, where the highest concentration of magnetite was found, the best Hg adsorption capacity was achieved, while it decreased when metallic iron or iron carbides were present (MACs obtained at 800 °C). Moreover, the difference of Hg0 removal/adsorption in N2+O2 and Simulated Flue Gas atmosphere between MACs obtained at 500 and 600 °C pointed out the influence on Hg removal of additional parameters, as surface chemistry and the existence of sulfur or chloride. The determination of Hg species in post-retention solids confirmed the mercury oxidation by high-valence iron ions (Fe3+) and the involvement of physisorption and chemisorption processes for the gas-solid interaction mechanism.

Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.

BACKGROUND: COVID-19 pandemic causes high global morbidity and mortality and better medical treatments to reduce mortality are needed. OBJECTIVE: To determine the added benefit of cyclosporine A (CsA), to low-dose steroid treatment, in patients with COVID-19. METHODS: Open-label, non randomized pilot study of patients with confirmed infection of SARS-CoV-2 hospitalized from April to May 2020 at a single centre in Puebla, Mexico. Patients were assigned to receive either steroids or CsA plus steroids. Pneumonia severity was assessed by clinical, laboratory, and lung tomography. The death rate was evaluated at 28 days. RESULTS: A total of 209 adult patients were studied, 105 received CsA plus steroids (age 55.3 ± 13.3; 69% men), and 104 steroids alone (age 54.06 ± 13.8; 61% men). All patients received clarithromycin, enoxaparin and methylprednisolone or prednisone up to 10 days. Patient's death was associated with hypertension (RR = 3.5) and diabetes (RR = 2.3). Mortality was 22 and 35% for CsA and control groups (P = 0.02), respectively, for all patients, and 24 and 48.5% for patients with moderate to severe disease (P = 0.001). Higher cumulative clinical improvement was seen for the CsA group (Nelson Aalen curve, P = 0.001, log-rank test) in moderate to severe patients. The Cox proportional hazard analysis showed the highest HR improvement value of 2.15 (1.39-3.34, 95%CI, P = 0.0005) for CsA treatment in moderate to severe patients, and HR = 1.95 (1.35-2.83, 95%CI, P = 0.0003) for all patients. CONCLUSION: CsA used as an adjuvant to steroid treatment for COVID-19 patients showed to improve outcomes and reduce mortality, mainly in those with moderate to severe disease. Further investigation through controlled clinical trials is warranted.

Spatial control of gene expression in flies using bacterially derived binary transactivation systems.

Controlling gene expression is an instrumental tool for biotechnology, as it enables the dissection of gene function, affording precise spatial-temporal resolution. To generate this control, binary transactivational systems have been used employing a modular activator consisting of a DNA binding domain(s) fused to activation domain(s). For fly genetics, many binary transactivational systems have been exploited in vivo; however, as the study of complex problems often requires multiple systems that can be used in parallel, there is a need to identify additional bipartite genetic systems. To expand this molecular genetic toolbox, we tested multiple bacterially derived binary transactivational systems in Drosophila melanogaster including the p-CymR operon from Pseudomonas putida, PipR operon from Streptomyces coelicolor, TtgR operon from Pseudomonas putida and the VanR operon from Caulobacter crescentus. Our work provides the first characterization of these systems in an animal model in vivo. For each system, we demonstrate robust tissue-specific spatial transactivation of reporter gene expression, enabling future studies to exploit these transactivational systems for molecular genetic studies.

Animal and human RNA viruses: genetic variability and ability to overcome vaccines.

RNA viruses, in general, exhibit high mutation rates; this is mainly due to the low fidelity displayed by the RNA-dependent polymerases required for their replication that lack the proofreading machinery to correct misincorporated nucleotides and produce high mutation rates. This lack of replication fidelity, together with the fact that RNA viruses can undergo spontaneous mutations, results in genetic variants displaying different viral morphogenesis, as well as variation on their surface glycoproteins that affect viral antigenicity. This diverse viral population, routinely containing a variety of mutants, is known as a viral 'quasispecies'. The mutability of their virions allows for fast evolution of RNA viruses that develop antiviral resistance and overcome vaccines much more rapidly than DNA viruses. This also translates into the fact that pathogenic RNA viruses, that cause many diseases and deaths in humans, represent the major viral group involved in zoonotic disease transmission, and are responsible for worldwide pandemics.

B-type natriuretic peptide over N-terminal pro-brain natriuretic peptide to predict incident atrial fibrillation after cryptogenic stroke.

BACKGROUND AND PURPOSE: B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients. METHODS: Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers. RESULTS: From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model. CONCLUSIONS: Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Population health management in France: specifying population groups through the DRG system.

BACKGROUND: Population health management (PHM) by hospital groups is not yet defined nor implemented in France. However, in 2019, the French Hospitals Federation launched a pilot program to experiment PHM in five territories around five Territorial Hospital Groups (GHT's). In order to implement PHM, it is necessary to firstly define the population which healthcare facilities (hospitals) have responsibility for. In the French healthcare system, mapping of health territories however relies mainly on administrative data criteria which do not fit with the actual implementation of GHT's. Mapping for the creation of territorial hospital groups (GHTs) also did not include medical criteria nor all healthcare offers particularly in private hospitals and primary care services, who are not legally part of GHT's but are major healthcare providers. The objective of this study was to define the French population groups for PHM per hospital group. METHODS: A database study based on DRG (acute care, post-acute and rehabilitation, psychiatry and home care) from the French National Hospitals Database was conducted. Data included all hospital stays from 1 January 2016 to 31 December 2017. The main outcome of this study was to create mutually exclusive territories that would reflect an accurate national healthcare service consumption. A six-step method was implemented using automated analysis reviewed manually by national experts. RESULTS: In total, 2840 healthcare facilities, 5571 geographical zones and 31,441,506 hospital stays were identified and collated from the database. In total, 132 GHTs were included and there were 72 zones (1.3%) allocated to a different GHTs. Furthermore, 200 zones were manually reviewed with 33 zones allocated to another GHT. Only one area did not have a population superior to 50,000 inhabitants. Three were shown to have a population superior to 2 million. CONCLUSIONS: Our study demonstrated a feasible methodology to define the French population under the responsibility of 132 hospital groups validated by a national group of experts.

Synergistic activation of AMPK prevents from polyglutamine-induced toxicity in Caenorhabditis elegans.

Expression of abnormally long polyglutamine (polyQ) tracks is the source of a range of dominant neurodegenerative diseases, such as Huntington disease. Currently, there is no treatment for this devastating disease, although some chemicals, e.g., metformin, have been proposed as therapeutic solutions. In this work, we show that metformin, together with salicylate, can synergistically reduce the number of aggregates produced after polyQ expression in Caenorhabditis elegans. Moreover, we demonstrate that incubation polyQ-stressed worms with low doses of both chemicals restores neuronal functionality. Both substances are pleitotropic and may activate a range of different targets. However, we demonstrate in this report that the beneficial effect induced by the combination of these drugs depends entirely on the catalytic action of AMPK, since loss of function mutants of aak-2/AMPKα2 do not respond to the treatment. To further investigate the mechanism of the synergetic activity of metformin/salicylate, we used CRISPR to generate mutant alleles of the scaffolding subunit of AMPK, aakb-1/AMPKß1. In addition, we used an RNAi strategy to silence the expression of the second AMPKß subunit in worms, namely aakb-2/AMPKß2. In this work, we demonstrated that both regulatory subunits of AMPK are modulators of protein homeostasis. Interestingly, only aakb-2/AMPKß2 is required for the synergistic action of metformin/salicylate to reduce polyQ aggregation. Finally, we showed that autophagy acts downstream of metformin/salicylate-related AMPK activation to promote healthy protein homeostasis in worms.

Pathologic findings and causes of death in bottlenose dolphins Tursiops truncatus stranded along the Georgia coast, USA (2007-2013).

Between 2007 and 2013, before the 2013 cetacean morbillivirus outbreak, 26 fresh bottlenose dolphin carcasses were necropsied on the coast of Georgia, USA. Here, we present the pathological and microbiological findings associated with their most likely causes of death. The primary cause of death was determined in 25 individuals and included systemic bacterial infection (n = 7), verminous and bacterial bronchopneumonia (n = 5), drowning/entanglement (n = 5), disseminated histoplasmosis (n = 1), intestinal intussusception (n = 1), vegetative endocarditis (n = 1), meningitis (n = 1), necrotizing dermatitis (n = 1), disseminated angiomatosis (n = 1), emaciation (n = 1) and stingray spine trauma (n = 1). Histiocytic and eosinophilic bronchopneumonia associated with Halocerchus sp. infection was observed in 69% of the animals (18/26) and eosinophilic gastritis due to Anisakidae nematodes was found in 36% of the examined stomachs (8/22). Moderate to severe eosinophilic pancreatitis with fibrosis was observed in 4 animals infected with Brachycladiidae trematodes. Proliferative and ulcerative lymphoplasmacytic dermatitis was found in 5 animals and was considered to contribute to deteriorated health status in 2 calves. Pulmonary and lymph node angiomatosis were observed in 15 and 10 animals, respectively. In at least 2 animals, the concentration of polychlorinated biphenyls (PCBs) in the blubber exceeded 1500 µg g-1 of lipid. Bottlenose dolphins stranded on the Georgia coast have a wide range of inflammatory lesions associated with a variety of helminth, bacterial, and fungal pathogens. Some resident animals have also been exposed to high levels of PCB contamination, which could reduce host immunocompetence. Higher exposure to these or other pathogens could result in further decline in the health of resident and migrant dolphin populations in this region.

[Representation of Female speakers at French psychiatry conferences]. / Sous-représentation des femmes intervenant dans les congrès de psychiatrie en France.

OBJECTIVES: First, the main objective was to describe the evolution of the representation of women at the two main conferences of psychiatry in France-Encephale and French Congress of Psychiatry-from 2009 to 2018, and to compare it to the evolution of the representation of women among French psychiatrists. Second, we aimed to describe this evolution within the themes of general psychiatry, child psychiatry and addictology and compare it to the evolution of the number of adult psychiatrists, child psychiatrists and addictologists in France, and likewise to describe this evolution within the organizing and scientific committees, chairpersons and symposia of pharmaceutical companies at these conferences. We hypothesized that women are underrepresented at French speaking psychiatry conferences and sought to quantify this. METHODS: Programs from the 2009-2018 meetings of the Encephale and the French Congress of Psychiatry were included in analysis. We collected for each intervention information about the sex of the participant, the type of the intervention (i.e., speaker, moderator, chairperson) and its main theme (i.e., general psychiatry, child psychiatry, addictology, pharmaceutical company symposium). We also collected from the National Council of the French Medical Association the number of male and female psychiatrists active in France from 2009 to 2018, and the number of male and female psychiatrists who have validated a specific competence in child psychiatry and addictology. The average proportion of women at the two conferences per year was obtained by weighting the average by the different numbers of speakers at the two conferences. À Chi-squared test was used to compare the evolution of the proportion gap over time. RESULTS: The proportion of women speaking at these conferences ranged from 25 % in 2009 to 32 % in 2018. Among French psychiatrists, the proportion of female psychiatrists increased from 46 % to 51 %, with a higher proportion of women since 2016. In that ten year span, the difference between the proportion of females amongst the French psychiatrists and the speakers at these French conferences varied between 21 % in 2009 and 17 % in 2016, with a higher proportion of female psychiatrists registered at the National Council of the French Medical Association than female speakers at these conferences. The proportion of female speakers at these conferences tends to increase more quickly than the proportion of active female psychiatrists. The proportion of women speaking on child psychiatry topics (41-59 %) is much higher for each year than those of women speaking on general psychiatry topics (24-33 %) or on addictology topics (10-39 %). Also, the proportion of women speaking on child psychiatry and addictology topics tends to increase more quickly than the proportion of active female child psychiatrists and addictologists in France, while the proportion of women speaking on general psychiatry topics tends to increase more slowly than the proportion of active female psychiatrists for adults in France. The proportion of female speakers is very low in symposia of pharmaceutical companies (7-24 %), members of organizing and scientific committees (13-33 %) and chairpersons (19-28 %), although it increases sfrom 2009 to 2018. PERSPECTIVES: This observation of the underrepresentation of women at French psychiatry conferences could make it possible to achieve greater equity. This count could be continued in the next few years and could raise the question of the inclusion of parity in the policy of psychiatric conferences, both among the speakers and among the scientific and organizational committees. Higher exposure of women to conferences would reduce the Matilda effect, defined by minimizing women's contribution to research.