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During 2009, pandemic influenza A(H1N1)pdm09 virus affected humans on Réunion Island. Since then, the virus has sustained circulation among local swine herds, raising concerns about the potential for genetic evolution of the virus and possible retransmission back to humans of variants with increased virulence. Continuous surveillance of A(H1N1)pdm09 infection in pigs is recommended.

We report a cluster of infections with genetically related toxigenic Corynebacterium diphtheriae linked to an outbreak among asylum seekers in Switzerland that subsequently affected patients without known exposure. This discovery highlights the importance of rapid, interdisciplinary outbreak investigations and regular vaccination status assessment, especially in elderly populations with waning immunity.

Abstract Pigment particles used in tattooing may exert long terms effect by releasing diffusible degradation products. In the present work, aqueous suspensions of the organic orange diazo pigment PO13 were aged by exposure to simulated sunlight at 40 °C. The morphology and the surface charge of PO13 particles were barely modified upon aging, but primary particles were released by de-agglomeration. Soluble photoproducts were detected in the liquid fractions. One of this photoproduct (DCBP) was produced in large amount in suspension in isopropanol and purified. The toxicological profiles of aged suspensions, their soluble fractions and DCBP were then determined on the keratinocyte cell line HaCaT. Impact of suspensions of PO13 on viability was hardly affected by aging. In contrast, the soluble fractions were more toxic after photo-aging. Suspensions and filtrates induced neither release of reactive oxygen species nor formation of DNA strand breaks. The samples exhibited only limited effects on the proteome of HaCaT cells. Conversely, DCBP was cytotoxic and induced the production of ROS, but was not genotoxic. DCBP was found to activate CYP450 monooxygenases known to be involved in the metabolism of xenobiotics. Altogether, our results show that aging of PO13 leads to the release of toxic soluble compounds.

Abstract Central venous catheter (CVC) cannulation can be accompanied by serious complications. The appearance of catheter-related infections is associated with high morbimortality. The aim of this study is to evaluate the incidences of colonization and central line-associated bloodstream infections (CLABSI) in short-term CVCs in the elective surgery setting, as well as to analyze the related risk factors. Prospective observational study including patients undergoing elective surgery with a CVC inserted perioperatively. Patients with current infection, taking preoperative antibiotics, those planning to have CVC for longer than 14 days, those under 18 years old, and those refusing to participate were excluded. Patients without cultures at the moment of CVC retrieval were not included. 200 patients were included, with a mean catheter duration of 6.8 ± 3.1 days, and a total duration of 1,358 days. Incidence of colonized catheters was 6% (8.84/1000 catheter-days), and 3.5% had CLABSI (5.15/1000 catheter-days). Catheter duration was longer in patients whose CVCs had been removed due to suspected infection (p

Abstract In human neuroscience, machine learning can help reveal lower-dimensional neural representations relevant to subjects’ behavior. However, state-of-the-art models typically require large datasets to train, and so are prone to overfitting on human neuroimaging data that often possess few samples but many input dimensions. Here, we capitalized on the fact that the features we seek in human neuroscience are precisely those relevant to subjects’ behavior rather than noise or other irrelevant factors. We thus developed a Task-Relevant Autoencoder via Classifier Enhancement (TRACE) designed to identify behaviorally-relevant target neural patterns. We benchmarked TRACE against a standard autoencoder and other models for two severely truncated machine learning datasets (to match the data typically available in functional magnetic resonance imaging [fMRI] data for an individual subject), then evaluated all models on fMRI data from 59 subjects who observed animals and objects. TRACE outperformed alternative models nearly unilaterally, showing up to 12% increased classification accuracy and up to 56% improvement in discovering “cleaner”, task-relevant representations. These results showcase TRACE’s potential for a wide variety of data related to human behavior.

Abstract Background Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to the formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive the development of many tumours, limited data exist on ES. This work therefore aimed to study the transcriptional regulation of KCNA2 and define the involvement of the Kv1.2 channel encoded by KCNA2 in a key function of ES development, cell proliferation. Methods KCNA2 expression in patients and cell lines was measured via bioinformatic analysis (RNA-Seq). The presence of a functional Kv1.2 channel was shown using patch-clamp experiments. Molecular biology approaches were used after EWS::FLI1 silencing to study the transcriptional regulation of KCNA2. Proliferation and cell count assessment were performed using cell biology approaches. KCNA2 silencing (siRNA) and RNA-Seq were performed to identify the signalling pathways involved in the ability of KCNA2 to drive cell proliferation. The regulation of the Hippo signalling pathway by KCNA2 was studied by measuring Hippo/YAP target genes expression, while YAP protein expression was studied with Western-Blot and immunofluorescence approaches. Results This research identified KCNA2 (encoding for a functional Kv1.2 channel) as highly expressed in ES biopsies and cell lines. The results indicated a correlation between KCNA2 expression and patient survival. The data also demonstrated that KCNA2/Kv1.2 is a direct target of EWS::FLI1, and identified the molecular mechanisms by which this chimeric protein regulates KCNA2 gene expression at the transcriptional level. Furthermore, the results indicated that KCNA2 expression and Kv1.2 activity regulate ES cell proliferation and that KCNA2 expression drives the Hippo/YAP signalling pathway. Using the specific Kv1.2 channel inhibitor (κ-Conotoxin), the results suggested that two complementary mechanisms are involved in this process, both dependently and independently of Kv1.2 functional channels at the plasma membrane. Conclusion This study is the first to describe the involvement of KCNA2 expression and Kv1.2 channel in cancer development. The study also unveiled the involvement of KCNA2 in the regulation of the Hippo/YAP signalling cascade. Thus, this work suggests that KCNA2/Kv1.2 could be a potential therapeutic target in ES.

Abstract An automatic system for pathology classification in chest X-ray scans needs more than predictive performance, since providing explanations is deemed essential for fostering end-user trust, improving decision-making, and regulatory compliance. CLARE-XR is a novel methodology that, when presented with an X-ray image, identifies the associated pathologies and provides explanations based on the presentation of similar cases. The diagnosis is achieved using a regression model that maps an image into a 2D latent space containing the reference coordinates of all findings. The references are generated once through label embedding, before the regression step, by converting the original binary ground-truth annotations to 2D coordinates. The classification is inferred minding the distance from the coordinates of an inference image to the reference coordinates. Furthermore, as the regressor is trained on a known set of images, the distance from the coordinates of an inference image to the coordinates of the training set images also allows retrieving similar instances, mimicking the common clinical practice of comparing scans to confirm diagnoses. This inherently interpretable framework discloses specific classification rules and visual explanations through automatic image retrieval methods, outperforming the multi-label ResNet50 classification baseline across multiple evaluation settings on the NIH ChestX-ray14 dataset.

Abstract Background Hemorrhagic shock (HS) corresponds to absolute hypovolemia creating an imbalance between oxygen supply and consumption. This causes an impaired hemostasis, a systemic inflammatory response, and microvascular permeability which can lead to multiple organ failure (MOF). There is no specific treatment for the endothelial dysfunction that plays a major role in the evolution towards MOF. Mesenchymal stromal cells (MSC) have been used in clinical trials for their immunomodulation and tissue repair capabilities for many years. Moreover, we previously showed that IL-1β-primed-MSC (MSCp) attenuated HS-induced organ injuries. The objective of the study was to determine whether MSCp could prevent the onset of MOF after HS by preventing endothelial dysfunction. Methods We established a rat model of HS, inducing 90 min of HS at a fixed mean arterial pressure of 35 mmHg, followed by resuscitation and transfusion. MSCp treatment was administered intravenously at the onset of resuscitation. After 6 h, we assessed plasma levels of endothelial markers, vascular permeability using Evans Blue (EB) dye, and renal and hepatic water content by measuring the wet-to-dry weight difference. Additionally, we investigated the ability of MSCp to inhibit leukocyte adhesion to activated endothelium in vitro. Results Our results indicate that early administration of MSCp significantly reduced the percentage of water content and EB dye in the liver but not in the kidney. These results were associated with a trend toward decreased plasma levels of Syndecan-1, ICAM-1, vWF, and VCAM-1. In vitro, MSCp reduced leukocyte-endothelial cell adhesion. Together, our results suggest that MSCp help to prevent endothelial dysfunction and vascular leakage, which, in turn, could protect the liver from injury.

Abstract In vitro models serve as indispensable tools for advancing our understanding of biological processes, elucidating disease mechanisms, and establishing screening platforms for drug discovery. Kidneys play an instrumental role in the transport and elimination of drugs and toxins. Nevertheless, despite the well-documented inter-individual variability in kidney function and the multifaceted nature of renal diseases—spanning from their origin, trigger and which segment of the kidney is affected—to presentation, progression and prognosis, few studies take into consideration the variable of sex. Notably, the inherent disparities between female and male biology warrants a more comprehensive representation within in vitro models of the kidney. The omission of sex as a fundamental biological variable carries the substantial risk of overlooking sex-specific mechanisms implicated in health and disease, along with potential differences in drug responsiveness and toxicity profiles between sexes. This review emphasizes the importance of incorporating cellular, biological and functional sex-specific features of renal activity in health and disease in in vitro models. For that, we thoroughly document renal sex-specific features and propose a strategic experimental framework to integrate sex-based differences into human kidney in vitro models by outlining critical design criteria to elucidate sex-based features at cellular and tissue levels. The goal is to enhance the accuracy of models to unravel renal mechanisms, and improve our understanding of their impact on drug efficacy and safety profiles, paving the way for a more comprehensive understanding of patient-specific treatment modalities.

Abstract Tartrazine (E102) is a controversial coloring agent whose potential impacts on human health are not fully understood. Our study reveals the vascular disrupting effects of tartrazine (TTZ) on developing zebrafish embryos in vivo and on human umbilical vein endothelial cells in vitro. The dye was shown to cause dose-dependent hemorrhages in zebrafish embryos. Analyzing transgenic zebrafish harboring fluorescent endothelial cells revealed that TTZ treatment disrupted cell organization into vessels in both the sub-intestinal vein and the brain area. Assays on human umbilical vein endothelial cells demonstrated that TTZ inhibited endothelial proliferation, tube formation, and migration in a dose-dependent manner. Taken together, our results indicate for the first time that TTZ can affect endothelial cell properties, possibly by disrupting Rho family GTPase pathways which control the cytoskeleton. Our finding provides a credible explanation for many reported human health impacts and offers prospective applications for biomedicine.

In many medical settings, medications are typically administered in the morning or evening, aligning with patients’ daily routines. This practice does not stem from chronotherapy, which involves scheduling drug administration to enhance its effectiveness, but rather from the way clinical operations are structured. The timing of drug administration can significantly affect a medication’s effectiveness and side effects, with the impact varying by up to ten times based on circadian rhythms. Disorders such as major depression, bipolar disorder, and schizophrenia are linked to disruptions in these rhythms. Recent studies have found that circadian dysfunctions, including genetic and neurohumoral changes, underlie many psychiatric conditions. Issues such as an altered glucocorticoid rhythm due to impaired HPA axis function, disturbed melatonin balance, and sleep disturbances have been noted in psychotic disorders. Furthermore, mood disorders have been associated with changes in the expression of circadian rhythm genes such as Clock, Bmal1, and Per. Considering that the absorption, biodistribution, effects on target organs, half-life, metabolism, and elimination of drugs are all influenced by the body’s circadian rhythms, this narrative review explores the optimal timing of medication administration to maximize efficacy and minimize side effects in the treatment of psychiatric disorders. By closely monitoring circadian variations in cortisol, melatonin, and key clock genes, as well as by deepening our understanding of the metabolisms and pharmacokinetics of antipsychotic medications, we propose a chronotherapy approach for psychiatric patients that could significantly enhance patient care.

Abstract Background Biosimilar etanercept presents itself as an innovative therapeutic opportunity for inflammatory and autoimmune diseases, however, its efficacy, safety, and immunogenicity in relation to the reference biological agent for the treatment of rheumatoid arthritis is still questioned. With this in mind, this study aimed to verify the efficacy, safety, and immunogenicity of the use of the biosimilar etanercept in relation to the reference biologic in patients over 18 years of age with rheumatoid arthritis. Methods A systematic review with meta-analysis was performed in accordance with the parameters of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) selecting only Phase III randomized clinical trials. The search strategy was constructed with the MeSH terms “Etanercept”, “Biological Products”, “Arthritis, Rheumatoid”, “Biosimilar Pharmaceuticals” and was performed in Medline via PubMed, Embase, the Cochrane Library, Web of Science, EBSCO and Lilacs in January 2023. The analysis measures were relative risk (RR) for dichotomous data and mean difference (MD) for continuous data. The statistical analysis for preparing meta-analyses was developed by the Review Manager 5.1.4 software. Results This systematic review selected 6 eligible studies with a sample population of n = 2355. The main efficacy outcomes showed that both drugs did not present statistically significant differences in ACR20, ACR50, and ACR70 responses within 6 months (RR 1.00; 95% CI = 0.94 to 1.07; RR 1.09; 95% CI = 0.94 to 1.26; RR 1.04; 95% CI = 0.82 to 1.31, respectively), with I 2 ranging from 55 to 63% and 0.04 ≤ P ≥ 0.08. Adverse events were mostly mild or moderate, and serious adverse events were not statistically significant. Regarding immunogenicity, only 5.4% of the ADA-positive biosimilar group had positive neutralizing antibodies. Conclusions Thus, this review found that biosimilar etanercept had efficacy, safety, and immunogenicity similar to those for the biological reference. Systematic review registration This systematic review was registered on the PROSPERO platform under number CRD42020166610.

Abstract The ToxiLaus study aims at evaluating the impact of environmental toxic species on health and diseases’ onset and development. Specifically, the ubiquitous presence of trace elements (TEs) in the environment urges for a better characterization of their influence on human organism. In its primary phase, the ToxiLaus study focused on measuring the urinary concentrations of 23 TEs in the baseline samples from the CoLaus|PsyCoLaus population-based cohort, using inductively coupled plasma mass spectrometry (ICP-MS). Statistical analyses were carried out on 5866 participants, investigating links between TEs concentrations and smoking status, metabolic syndrome and body mass index (BMI). Smoking status was associated with Cd, Zn, Pb, Mo and Hg (respectively OR = 3.64, 1.42, 1.20, 0.69 and 0.58) while metabolic syndrome was associated with Zn and Cd (OR = 1.81 and 1.24 respectively). Concentrations of Zn, Hg, Co, Ni, Cu, Mo, As, Sn, Tl, Fe where significantly different (p

Abstract Early and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions.

Abstract Natural hybridisation in plants can impact genetic and morphological diversity, including the emergence of better-adapted new populations and the potential extinction of some lineages involved in this intricate process. Under progressive global warming, species often need to migrate to newly suitable areas, which may be an additional challenge for species with low dispersal ability. Throughout the search for new environments, previously allopatric lineages can come into secondary contact and eventually hybridise if reproductive isolation is incomplete. Here, we focused on two taxa representing the natural herbaceous component of southern South American lowland grasslands. We aimed to evaluate the impact of contact zones and potential hybridisation on the evolutionary relationships and population dynamics. We used single nucleotide polymorphisms and morphological data of multiple individuals from allopatric and contact zones between taxa to shed light on hybridisation patterns and demographic scenarios. Our results indicated that the contact zones impact taxa’s genetic and morphological diversity, and each contact zone had different patterns of genetic diversity and morphology, constituting stable populations that potentially reflect hybridisation events occurring at distinct evolutionary times.

Abstract Deep brain stimulation is a well-established treatment for improving motor symptoms in Parkinson’s disease. However, persistent non-motor symptoms, such as excessive daytime sleepiness, remain a significant challenge and necessitate further investigation. In this study, we conducted repeated measurements of daytime sleepiness using a modified multiple sleep latency test in a healthy monkey (macaca fascicularis), which was later rendered parkinsonian through MPTP administration. Deep brain stimulation targeting the lateral hypothalamic area revealed frequency-dependent modulation of both sleepiness level and core body temperature. High-frequency stimulation (80 Hz) increased sleepiness in the healthy state, while low-frequency stimulation (20 Hz) promoted wakefulness in the parkinsonian state. These findings suggest a promising therapeutic approach for addressing sleep/wake disturbances, not only in Parkinson’s disease but also in other severe sleep disorders.

Abstract Vaccine hesitancy (VH) is an issue for healthcare students, influenced by safety concerns and misinformation. The need for better communication training and understanding sociocultural factors in VH was highlighted in a European University Alliance seminar. Practical exercises like simulation role-playing, interprofessional collaboration, and digital literacy may improve vaccine education.

Abstract In PDAC patients, ctDNA detection’s prognostic significance needs validation especially in resected patients. This study investigated ctDNA kinetics in portal and peripheral blood before and after resection, and whether tissue mobilization during surgery influences ctDNA detection. In this single-center prospective cohort, portal and peripheral blood were drawn during pancreaticoduodenectomy before and after tissue mobilization, during 12 postoperative months and were associated with overall survival (OS), recurrence-free survival (RFS) and CA19-9 (secondary endpoints). Tumor mutations were identified using next-generation-sequencing and ctDNA detected by digital droplet PCR. From 2018 to 2022, 34 patients were included. The 2-year RFS and OS were 47.6%(95%CI[29.5; 63.6]) and 65.7%(95%CI[46.5; 79.4]) respectively. Intraoperatively, ctDNA detection in portal or peripheral blood was associated with worse RFS (HR[95%CI]3.26[1.26; 8.45],p = 0.010) and OS (HR[95%CI]5.46[1.65;18.01],p = 0.002). Portal vein sampling did not improve ctDNA detection. CtDNA levels were increased by 2.5-fold (p = 0.031) in peripheral blood after tissue mobilization but not significantly linked to RFS or OS. Detecting ctDNA intraoperatively was correlated with poorer RFS (HR [95% CI] 3.26 [1.26;8.45], p = 0.010) and 0S (HR [95% CI] 5.46 [1.65;18.01], p = 0.002). Portal vein sampling did not improve ctDNA detection. Tissue mobilization increases ctDNA levels. Intraoperative detection of ctDNA is associated with a worse prognosis.

We examined the emergence and characteristics of oxacillinase-484–producing Enterobacterales in France during 2012–2023. Genomic analysis identified 2 predominant sequence types in Escherichia coli: ST410 and ST1722. Plasmid analysis revealed that blaOXA-484 genes were carried mostly on an IncX3-type plasmid associated with genetic elements including insertion sequences IS3000 and ISKpn19.

Abstract Opioid prescription records in existing electronic health record (EHR) databases are a potentially useful, high-fidelity data source for opioid use-related risk phenotyping in genetic analyses. Prescriptions for codeine derived from EHR records were used as targeting traits by screening 16 million patient-level medication records. Genome-wide association analyses were then conducted to identify genomic loci and candidate genes associated with different count patterns of codeine prescriptions. Both low- and high-prescription counts were captured by developing 8 types of phenotypes with selected ranges of prescription numbers to reflect potentially different levels of opioid risk severity. We identified one significant locus associated with low-count codeine prescriptions (1, 2 or 3 prescriptions), while up to 7 loci were identified for higher counts (≥ 4, ≥ 5, ≥6, or ≥ 7 prescriptions), with a strong overlap across different thresholds. We identified 9 significant genomic loci with all-count phenotype. Further, using the polygenic risk approach, we identified a significant correlation (Tau = 0.67, p = 0.01) between an externally derived polygenic risk score for opioid use disorder and numbers of codeine prescriptions. As a proof-of-concept study, our research provides a novel and generalizable phenotyping pipeline for the genomic study of opioid-related risk traits.

Abstract Rice (Oryza sativa L.) producers in the Mid-south are experiencing difficulties with herbicide-resistant weeds such as barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.]. As a result, methods that can alter E. crus-galli ecology are needed. This research evaluated the ecological implications of rice cultivar and row widths on crop and E. crus-galli growth. Overall, for E. crus-galli, as the row width increased, greater density, panicle counts, and seed production occurred. Echinochloa crus-galli density was 120% greater in a 38-cm row width than the 13-cm row width at the preflood rice stage. Reduced early-season rice canopy coverage in the wider row widths allowed for increased E. crus-galli densities. At the preharvest stage, E. crus-galli panicle counts were similar for the 13- and 19-cm rows. Row width did not affect rice yield, indicating wider row widths could be feasible agronomically, but additional weed management efforts would be needed because greater ecological advantages were obtained in narrower rows. Less E. crus-galli seed production occurred in competition with hybrid cultivars compared to inbred cultivars. Overall, the standard row width (19-cm) and hybrid cultivars would provide the greatest ecological advantage over E. crus-galli.

Abstract Recent advances in deep learning and natural language processing (NLP) have broadened opportunities for automatic text processing in the medical field. However, the development of models for low-resource languages like French is challenged by limited datasets, often due to legal restrictions. Large-scale training of medical imaging models often requires extracting labels from radiology text reports. Current methods for report labeling primarily rely on sophisticated feature engineering based on medical domain knowledge or manual annotations by radiologists. These methods can be labor-intensive. In this work, we introduce a BERT-based approach for the efficient labeling of French mammogram image reports. Our method leverages both the expansive scale of existing rule-based systems and the precision of radiologist annotations. Our experimental results showcase the superiority of the proposed approach. It was initially fine-tuned on a limited dataset of radiologist annotations. Then, it underwent training on annotations generated by a rule-based labeler. Our findings reveal that our final model, MammoBERT, significantly outperforms the rule-based labeler while simultaneously reducing the necessity for radiologist annotations during training. This research not only advances the state of the art in medical image report labeling but also offers an efficient and effective solution for large-scale medical imaging model development.

Abstract The Harpy Eagle (Harpia harpyja) is an iconic species that inhabits forested landscapes in Neotropical regions, with decreasing population trends mainly due to habitat loss, and currently classified as vulnerable. Here, we report on a chromosome-scale genome assembly for a female individual combining long reads, optical mapping, and chromatin conformation capture reads. The final assembly spans 1.35 Gb, with N50scaffold equal to 58.1 Mb and BUSCO completeness of 99.7%. We built the first extensive transposable element (TE) library for the Accipitridae to date and identified 7,228 intact TEs. We found a burst of an unknown TE ~ 13–22 million years ago (MYA), coincident with the split of the Harpy Eagle from other Harpiinae eagles. We also report a burst of solo-LTRs and CR1 retrotransposons ~ 31–33 MYA, overlapping with the split of the ancestor to all Harpiinae from other Accipitridae subfamilies. Comparative genomics with other Accipitridae, the closely related Cathartidae and Galloanserae revealed major chromosome-level rearrangements at the basal Accipitriformes genome, in contrast to a conserved ancient genome architecture for the latter two groups. A historical demography reconstruction showed a rapid decline in effective population size over the last 20,000 years. This reference genome serves as a crucial resource for future conservation efforts towards the Harpy Eagle.

Abstract Background Miscommunications account for up to 80% of preventable medical errors. Mnemonics like I-PASS (Illness severity, Patient summary, Actions list, Situation awareness, Synthesis) have demonstrated a positive impact on reducing error rates. Currently, physicians at our hospital do not follow a specific structure during hand-offs. We aimed to compare current hand-offs without prior training to a gold standard and the I-PASS tool in terms of content and sequence. Methods This study is a secondary analysis of data collected during a simulation study of a Friday evening hand-off to the night resident at University Hospitals of Geneva. Thirty physicians received a hand-off of four patients and managed two other patients through nursing pages at the start of the night shift, generating six sign-outs each, totaling 177 sign-outs. A focus group of three senior doctors defined the gold standard (GS) by consensus on the essential content of each sign-out. The analysis focused on the rates of relevance (ratio of information considered relevant by the GS) and completeness (proportion of transmitted elements out of all expected elements of the GS), and the distribution and sequence of the first four I-PASS categories. Results Relevance and completeness rates were 37.2% ± 0.07 and 51.9% ± 0.1, respectively, with no significant difference between residents and supervisors. There was a positive correlation between total hand-off time and relevance (residents: R2 = 0.62; supervisors: R2 = 0.67) and completeness (residents: R2 = 0.32; supervisors: R2 = 0.56). The distribution of I-PASS categories was highly skewed in both the GS (I = 2%, P = 72%, A = 17%, S = 9%) and participants (I = 6%, P = 73%, A = 14%, S = 7%), with significant differences in categories A (p = 0.046) and I (p ≤ 0.001). Sequences of I-PASS categories generally followed a P-A-S-I pattern. The first S category was frequently absent, and only one participant began by announcing the case severity as suggested by I-PASS. Conclusion We identified gaps between current medical sign-outs in our institution's general internal medicine division and the I-PASS structure. We recommend implementing the I-PASS mnemonic, emphasizing the "I" category at the start and the "S" category to anticipate and prevent complications. Future studies should assess the impact of this recommendation, adapt the mnemonic elements to the context, and introduce specific hand-off training for senior medical students.

Abstract The goal of this study is to evaluate the impact of pulsed lighting on the reading performance of young adults with dyslexia. A total of 42 participants were recruited, including individuals diagnosed with developmental dyslexia and adults without reported reading difficulties. The severity of each participant’s reading deficit was assessed on a continuous scale using a reading impairment score, derived from four reading tests: an isolated-word reading test, a pseudoword reading test, and two reading fluency tests. The impairment score ranged from 0 (no impairment) to 4 (severe impairment across all tests). To examine the potential effect of pulsed lighting, we measured (1) sentence reading speed, expressed as a reading accessibility index (ACC), and (2) text comprehension, expressed as a comprehension score. These measures were taken under three lighting conditions: standard lighting, pulsed lighting, and a combination of the two. Linear mixed-effects models were applied to assess the effects of lighting on ACC and comprehension, controlling for the reading impairment score. We found no effect of lighting conditions on either ACC or comprehension, except in the most impaired readers, who showed a small but significant increase of 7% in ACC. However, even with pulsed lighting, impaired readers did not reach the performance level of skilled adult readers. In conclusion, the study did not demonstrate a clear positive impact of pulsed lighting on the reading skills of adults with dyslexia.

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1–like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human–animal interactions in periurban settings.

Abstract Antimicrobial-resistant bacteria have been an increasing problem in human medicine and animal husbandry since the introduction of antimicrobials on the market in the 1940s. Over the last decades, efforts to reduce antimicrobial usage in animal husbandry have been shown to limit the development of resistant bacteria. Despite this, antimicrobial-resistant bacteria are still commonly detected and isolated worldwide. In this study, we investigated the presence of antimicrobial-resistant bacteria in bovine milk samples using a multiple approach based on culturing and amplicon sequencing. We first enriched milk samples obtained aseptically from bovine udders in the presence of two antimicrobials commonly used to treat mastitis and then described the resistant microbiota by amplicon sequencing and isolate characterization. Our results show that several commensal species and mastitis pathogens harbor antimicrobial resistance and dominate the enriched microbiota in milk in presence of antimicrobial agents. The use of the two different antimicrobials selected for different bacterial taxa and affected the overall microbial composition. These results provide new information on how different antimicrobials can shape the microbiota which is able to survive and reestablish in the udder and point to the fact that antimicrobial resistance is widely spread also in commensal species.

Abstract This study was conducted to determine the heterogeneity of the quantitative and qualitative properties of fodder growth in cultivated hydroponic wheat fodder (HWF) in the growth tray area and to evaluate the impact on the environment. HWF was grown using nutrient film technique. Yield productivity (YP) of HWF in the growth tray area was divided into four characteristic zones (A, B, C, and D). The most fertile zone A accounted for only 22.3 ± 4.2% of the entire growth tray area, while zone B accounted for 44.7 ± 4.0%. Zones C and D, which accounted for 28.0 ± 1.3% and 5.0 ± 0.3% area, respectively, pose various problems for forage production, i.e., they negatively impact the quantity and quality of HWF, as well as the environment. If all areas in the growth tray support the highest fodder YP (zones A and B), then one kg of dry wheat grains will yield about 6–7 kg of HWF (consisting of 10.7–12.4% dry matter, 17.3–17.5% crude protein, 1.8–2.3% starch, 13.1–14.4% crude fiber, and 4.5–4.6% ether extract). Results of life cycle assessment show that HWF with YPs of 3–5 kg from one kg of dry grains (zones C and D) has the most adverse impact on the environment (150 and 220 kg CO2eq t−1). Under optimum conditions (zone A), CO2eq varied from 94 to 115 kg CO2eq t−1 of feed. Environmentally, HWF production had the most impact on marine aquatic ecotoxicity, abiotic depletion, global warming potential, and freshwater aquatic ecotoxicity.

Abstract Mechanical ventilation in myasthenic crisis is not standardized and is at high risk of failure. We investigated liberation from mechanical ventilation during myasthenic crisis using a prolonged spontaneous breathing trials (SBT) and sequential pulmonary function tests (PFT). In this retrospective monocenter study, we included patients admitted for a first episode of myasthenic crisis between January 2001 and January 2018. The primary outcome was the incidence of weaning failure upon first extubation in our cohort of patients with MC. Secondary objectives were to determine risk factors and outcome associated with weaning failure upon first extubation in MC. We also compared the characteristics of patients with prolonged weaning. 126 episodes of MC were analyzed. Patient’s age was 64 [42–76] years with 72/126 (56.5%) being women. The median delay between weaning initiation and first extubation was 6 [3–10] days and the median total length of MV was 14 [10–23] days. 118/126 (93.7%) patients underwent prolonged SBT of 8 h or more prior to first extubation. The overall weaning failure rate was 18/126 (14.3%). Extubation was more often successful when the factor precipitating the myasthenic crisis was identified (86/108 (79.6%) vs. 8/18 (44.4%); p = 0.004), whereas PFT was similar in failure or successes. Most weaning failures upon first extubation attempt (11/18; 61%) were attributed to an insufficient stabilization of myasthenia gravis. Duration of mechanical ventilation, an infectious trigger and maximal inspiratory pressure upon intubation were independent risk factors for prolonged weaning. In myasthenic crisis, a standardized protocol including prolonged SBT and respiratory function tests might improve the success of first extubation without prolonging mechanical ventilation. The results of this single center study warrant further evaluation in interventional trials.

Background: Clinical reasoning (CR) is fundamental in medical education. However, the Italian curriculum has not incorporated a structured CR format yet. Therefore, we introduced the Clinical Case Discussions (CCD), to medical students attending the University of Bologna as a tool for developing CR abilities. CCDs are a case-based peer-teaching format, simulating the diagnostic process using published patient cases. Methods: Students of all clinical years of the University of Bologna Medical School were invited to voluntarily participate in a two-day CCD training program. They completed pre- and post-training questionnaires assessing their expectations before and impressions after the training and comparing learning outcomes to their usual classes. Results: Twenty-one students participated in this pilot program. Before the training, more than half of the participants expressed either interest or a strong interest in all proposed learning objectives. Afterward, 84.6% of the students stated that the training much exceeded (63.5%) or exceeded (23.1%) their expectations considering its utility for their future medical activities. A total of 92.3% strongly agreed (84.6%) or agreed (7.7%) to have improved their CR. Conclusions: Although this pilot program had some intrinsic limitations, the students’ positive feedback on this CCD format (combining the benefits of case-based learning and peer teaching) encourages further research on its potential role in the Italian curriculum.

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6500 SARS-CoV-2 Alpha genomes (B.1.1.7) across 7 months within Thuringia while collecting patients’ isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are subclusters. Mobile service data can indicate these clusters’ spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept was successfully implemented as a proof-of-concept for a mobility-guided sampling strategy in response to the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.

BackgroundMobile health apps have shown promising results in improving self-management of several chronic diseases in patients. We have developed a mobile health app (Cardiomeds) dedicated to patients with heart failure (HF). This app includes an interactive medication list; daily self-monitoring of symptoms, weight, blood pressure, and heart rate; and educational information on HF delivered through various formats. ObjectiveThis study aimed to perform a mixed methods usability study of Cardiomeds. MethodsSmartphone users with HF were recruited from the HF outpatient clinic at the University Hospital of Geneva. The usability test was conducted in 2 stages, with modifications made to the app after the first stage to address major usability issues. Each stage required 10 participants to perform 14 tasks, such as entering vital signs, entering a new medication and time of intake, or finding information about HF. Each task was timed, sessions were recorded, and all data were anonymized. After completing the tasks, patients completed the System Usability Scale 10-item questionnaire and answered 5 open questions about their perceptions of Cardiomeds. ResultsTwenty patients with HF, 75% (15/20) of whom were men, with a mean age of 55 years, were included in this study. The average time to complete all 14 tasks was 18 (SD 5.7) minutes. Manual medication entry was the most time-consuming task, taking an average of 154.40 (SD 68.08) seconds in the first stage, 103.10 (SD 42.76) seconds in the second stage, and 128 (SD 63) seconds overall. The mean overall success rate was 77% (SD 0.23%) for the first stage and 94% (SD 0.07%) for the second stage. A total of 30% (3/10) of participants in the first stage completed all tasks without any help compared with 50% (5/10) of participants during the second stage. The average System Usability Scale score was 80% (SD 17%), showing a slight increase from 79% (SD 16%) in the first stage to 80% (SD 28%) in the second stage, which qualifies the app as “good” in terms of usability. Between the 2 stages, part of the app interface was redesigned to address the key issues identified in the first stage. Despite these improvements, problems related to guidance were frequent and comprised 36% (8/22) of the problems in the first stage and 40% (6/15) in the second stage. In response to open questions, 85% (17/20) of the participants responded that they would like to use the app when it became available. ConclusionsThe usability test indicated that Cardiomeds is a suitable and user-friendly app for patients with HF. The app will be further tested in a randomized clinical trial (2022-00731) after acute HF hospitalization to assess its impact on patients’ knowledge about HF, self-care, and quality of life.

Objectives Diabetes distress can negatively affect the well-being of individuals with type 1 diabetes (T1D). Voice-based (VB) technology can be used to develop inexpensive and ecological tools for managing diabetes distress. This study explored the competencies to engage with digital health services, needs and preferences of individuals with T1D or caring for a child with this condition regarding VB technology to inform the tailoring of a co-designed tool for supporting diabetes distress management.Design We used a mixed methods design. We performed a qualitative reflexive thematic analysis of semistructured interviews of people living with T1D or caring for a child with T1D, complemented by quantitative analysis (descriptive statistics).Setting 12 adults living with T1D who attended diabetes centres or cared for a child with this condition participated in semistructured interviews to collect opinions about voice technology. They also responded to three questionnaires on sociodemographics and diabetes management, diabetes distress and e-health literacy.Outcome measures Main: Patient experiences and perceptions derived from the coded transcriptions of interview data. Secondary: Quantitative data generated from Socio-Demographic and Diabetes Management questionnaire; Problem Areas in Diabetes Scale and e-Health Literacy Questionnaire.Results Five major themes were generated from the participants’ interview responses: (1) Experience of T1D, (2) Barriers to VB technology use, (3) Facilitators of VB technology, (4) Expectations of VB technology management in T1D, (5) Role of healthcare professionals in implementing VB technology for T1D. Most participants expressed a favourable view of voice technology for diabetes distress management. Trust in technology and healthcare professionals emerged as the predominant sentiment, with participants’ current device type impacting anticipated barriers to adopting new technologies.Conclusion The results highlighted positive participant views towards VB technology. Device use, previous experience and health professional endorsement were influential facilitators of novel VB digital health solutions. Further research involving younger people with T1D could further contribute to the successful development of these tools.Trial registration number ClinicalTrials.gov, NCT05517772.

Most biomedical research on animals is based on the handful of the so-called standard model organisms, i.e. laboratory mice, rats or Drosophila, but the keys to some important biomedical questions may simply not be found in these. However, compared with the high number of molecules originating from plants in clinical use, and with the countless unique adaption mechanisms that animals have developed over the course of evolution to cope with environmental constrains, there is still few investigations on wild animals with biomedical objectives, and field studies are far fewer. A major limitation is insufficient funding, the main causes of which we analyze. We argue, however, that fieldwork is a key driver in generating new scientific knowledge as part of a One Health approach, by observing/documenting and understanding the diverse and largely unexplored biological processes evolved by animals adapted to unusual environmental conditions, which would be extreme conditions for humans. These conditions do not only refer to extreme temperatures, since lack of food or water, high pressures or lack of oxygen, are clearly extreme constraints. To conduct this research, there are serious limitations we propose to address. Specific techniques and methods are requested, not only to work in extreme environments, but also to minimize the ecological footprint of field work. The erosion of biodiversity is a major threat. The reduction of animal disturbance, a key issue, requires specific technologies and expertise. An ethical approach is requested, for the sake of transparency and to comply with the Nagoya Protocol on genetic resources. An interdisciplinary expertise and a meticulous planning are requested to overcome the field constraints and interface the associated laboratory work. We recommend focusing on the major threats to global human health today, which wild animals appear to resist particularly well, such as antibioresistance and diseases associated with lifestyle and senescence.

Background The impact of disease activity and treatment on fertility outcomes in patients with spondyloarthritis (SpA) has been little explored. This study aimed to describe median time to pregnancy (TTP) in women with SpA and the factors influencing TTP in this population.Methods This prospective observational multicentre (63 centres) French cohort (GR2 study—NCT02450396) included consecutive women with a diagnosis of SpA (according to their rheumatologist) who wanted to become pregnant between 2015 and 2021. TTP (in months) was the main outcome criterion, prospectively calculated from the date of study inclusion to the date of conception. Data on demographics, disease characteristics, disease activity, severity and treatment were prospectively collected at inclusion and each year thereafter until pregnancy occurred. TTP and its associated factors were estimated by survival analysis (Shared Frailty Cox models), with a random centre effect and multiple imputation to address missing data.Results We analysed 88 women included before conception. Among them, 56 (63.6%) became pregnant during follow-up. Median TTP was 16.1 (95% CI (12.2 to 25.3)) months. Mean preconceptional Bath Ankylosing Spondylitis Disease Activity Index at inclusion was 2.9 (±SD 2.1). Patients were treated with TNF inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), conventional synthetic disease-modifying antirheumatic drugs and glucocorticoids in 61 (69.3%), 23 (26.1%), 12 (13.6%) and 8 (9.1%) cases, respectively. The multivariate model found a significant association between TTP and age (HR) (per year) 1.22 95% CI (1.08 to 1.40); p

Introduction The megalencephaly capillary malformation polymicrogyria (MCAP syndrome) results from mosaic gain-of-function PIK3CA variants. The main clinical features are macrocephaly, somatic overgrowth, neurodevelopmental delay and brain anomalies. Alpelisib (Vijoice) is a recently FDA-approved PI3Kα-specific inhibitor for patients with PIK3CA-related overgrowth spectrum (PROS). During its development, in patients with the MCAP subgroup of PROS, there was no specific, standardised evaluation of the effect on neuro-cognitive functioning. Moreover, it remains unknown if the molecule crosses the blood-brain barrier. Our objective is to evaluate the efficacy of a 24 month treatment with alpelisib on adaptive behaviour in patients with MCAP syndrome.Methods and analysis SESAM is an industry-sponsored two-period multicentre French academic phase II trial, with a 6-month double-blind, placebo-controlled period followed by an open-label period. The primary endpoint is a ≥4-point improvement in the Vineland II Adaptive Behaviour Scale (VABS), 24 months after treatment initiation. Secondary objectives are safety, VABS improvement at 6 months, impact on the quality of life, epilepsy and hypotonia. 20 patients aged 2 to 40 years with an MCAP diagnosis and neurodevelopmental disorders of various degrees, will be followed monthly in local centres, centrally assessed (clinical, biological, neuropsychological and functional evaluation) at baseline and every 6 months. Patients will be evaluated by volumetric MRI at baseline and at 24 months. An optional lumbar puncture will be performed to investigate blood-brain barrier crossing. Inclusions were completed by April 2024, with the end of follow-up in November 2026.Given the efficacy of alpelisib in patients with PROS, if the drug crosses the blood-brain barrier, we can expect a clinical benefit for patients with neurocognitive disorders.Ethics and dissemination Ethical approval was given by CPP Sud-Ouest et Outre-Mer I (reference: 2022-500197-34-01). Findings from this study will be disseminated via publication, reports and conference presentations.Trial registration number NCT05577754

Introduction Children represent a large and vulnerable patient group. However, the evidence base for most paediatric diagnostic and therapeutic procedures remains limited or is often inferred from adults. There is an urgency to improve paediatric healthcare provision based on real-world evidence generation. Digital transformation is a unique opportunity to shape a data-driven, agile, learning healthcare system and deliver more efficient and personalised care to children and their families. The goal of Paediatric Personalized Research Network Switzerland (SwissPedHealth) is to build a sustainable and scalable infrastructure to make routine clinical data from paediatric hospitals in Switzerland interoperable, standardised, quality-controlled, and ready for observational research, quality assurance, trials and health-policy creation. This study describes the design, aims and current achievements of SwissPedHealth.Methods and analysis SwissPedHealth was started in September 2022 as one of four national data streams co-funded by the Swiss Personalized Health Network (SPHN) and the Personalized Health and Related Technologies (PHRT). SwissPedHealth develops modular governance and regulatory strategies and harnesses SPHN automatisation procedures in collaboration with clinical data warehouses, the Data Coordination Center, Biomedical Information Technology Network, and other SPHN institutions and funded projects. The SwissPedHealth consortium is led by a multisite, multidisciplinary Steering Committee, incorporating patient and family representatives. The data stream contains work packages focusing on (1) governance and implementation of standardised data collection, (2) nested projects to test the feasibility of the data stream, (3) a lighthouse project that enriches the data stream by integrating multi-omics data, aiming to improve diagnoses of rare diseases and 4) engagement with families through patient and public involvement activities and bioethics interviews.Ethics and dissemination The health database regulation of SwissPedHealth was approved by the ethics committee (AO_2022-00018). Research findings will be disseminated through national and international conferences and publications in peer-reviewed journals, and in lay language via online media and podcasts.

Obiectivele cercetării au constat în monitorizarea concentrațiilor de radon în diverse tipuri de locuințe în principalele zone geografice ale Republicii Moldova, în localitățile rurale și urbane. Metode. Pentru măsurarea concentrațiilor de radon în locuințe au fost utilizate detectoarele RADTRAK2+, fiind plasate în încăpere pentru o perioadă de 3 luni. Citirea detectoarelor s-a efectuat în laboratorul RADONOVA din Uppsala, Suedia. Prelucrarea statistică a datelor s-a efectuat în baza programului computerizat SPSS, efectuându-se analiza descriptivă. A fost efectuată analiza corelațională/regresională a concentrațiilor de radon și factorii de mediu (temperatura/umiditatea aerului). S-a efectuat calcularea riscului pentru sănătate a expunerii la radon prin calcularea dozelor efective, utilizând formulele propuse de Comisia Internațională de Protecție Radiologică. În baza rezultatelor obținute s-a efectuat cartografierea concentrațiilor de radon pe teritoriul țării cu evidențierea localităților cu risc sporit de expunere la radon. Cartografierea s-a realizat conform metodologiei științifice de cercetare a Centrului Comun de Cercetare (Joint Research Center) din cadrul Comisiei Europene. S-a utilizat caroiajul stabilit în sistemul Lambert-GISCO, potrivit căruia teritoriul Republicii Moldova este reprezentat prin 336 de celule cu laturile 10 x 10 km2. Rezultate. În urma prelucrării statistice a datelor colectate, s-au obținut următoarele rezultate pentru o distribuție uniformă a valorilor, astfel se înregistrează valori maxime de 1160 Bq/m3 pentru zona de Centru, 1260 Bq/m3 pentru zona de Nord și 950 Bq/m3 pentru zona de Sud. Concentrația medie a radonului în aerul din interior constituie 211,67 Bq/m3; 240,55 Bq/m3 și 285,57 Bq/m3 pentru Centru, Nord și, respectiv, zona de Sud, ceea ce demonstrează că valorile medii ale radonului nu au depășit valorile de referință pe țară (300 Bq/m3). Cota parte a locuințelor care au depășit nivelul de referință a radonului (300 Bq/m3) a constituit 25,3% pentru zona Centru, 31,06% – Nord și 38,58% – Sud. Conform rezultatelor obținute în baza măsurării concentrației radonului pentru municipiul Bălți, Chișinău și Cahul, se constată că valorile medii înregistrate nu depășesc valoarea de referință a concentrației radonului de 300 Bq/m3. Concluzii. Expunerea populației la radon, care reprezintă o sursă naturala radioactivă, prezintă pericol pentru sănătatea publică. Expunerea cronică la gazul nominalizat radioactiv contribuie la declanșarea cancerului bronhopulmonar. Cele expuse prevăd un control strict al expunerii populației la radon prin implementarea cerințelor de monitorizare a concentrațiilor de radon în locuințe. În caz de depășire a valorilor în comparație cu cele de referință (300 Bq/m3), se impune implementarea măsurilor de ventilare artificială intensă, aerisirea permanentă a încăperilor, utilizarea membranelor antiradon, ermetizarea fisurilor din pereți și pardosea, etc.

We designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: (1) primary sulfonamide group recognizing carbonic anhydrases (CA), (2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and (3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification. Our designed prodrug candidates bearing moderately active pre-vinylsulfone esters or weakly active carbamates optimized for mild covalent modification activity to avoid toxic non-specific modifications and selectively target CAIX. The lead inhibitors reached 2 pM affinity, the highest among known CAIX inhibitors. The strategy could be used for any disease drug target protein bearing a His residue in the vicinity of the active site.

Macrophages are integral part of the body's defense against pathogens and serve as vital regulators of inflammation. Adaptor molecules, featuring diverse domains, intricately orchestrate the recruitment and transmission of inflammatory responses through signaling cascades. Key domains involved in macrophage polarization include Toll-like receptors (TLRs), Src Homology2 (SH2) and other small domains, alongside receptor tyrosine kinases, crucial for pathway activation. This review aims to elucidate the enigmatic role of macrophage adaptor molecules in modulating macrophage activation, emphasizing their diverse roles and potential therapeutic and investigative avenues for further exploration.

Objectives To assess the incidence of hospital admissions for covid-19 disease in pregnant women, severity of covid-19 disease, and medical treatment provided to pregnant women with moderate to severe covid-19 during the first 10 months of the pandemic.Design Individual patient data meta-analysis of population based cohorts in International Obstetric Survey Systems.Setting 10 European countries with national or regional surveillance within the International Obstetric Survey Systems (INOSS) collaboration using aligned definitions and case report forms: Belgium, France (regional), Italy, the Netherlands, Denmark, Finland, Iceland, Norway, Sweden (regional), and the UK. The dominant variant of the SARS-CoV-2 virus was the wild-type variant in all countries during the study period (1 March 2020 to 31 December 2020).Participants The source population was 1.7 million women giving birth (maternities) from 1 March 2020 to 31 December 2020; pregnant women were included if they were admitted to hospital and had a positive polymerase chain reaction test for the SARS-CoV-2 virus ≤7 days before hospital admission, during admission, or up to two days after giving birth. We further categorised the hospital admission in two groups; covid-19 admission (hospital admission due to covid-19 or with reported symptoms of covid-19 disease) or non-covid-19 admission (admission to hospital for obstetric healthcare or no symptoms of covid-19 disease).Main outcome measures Incidence of hospital admissions for covid-19 per 1000 maternities, frequency of moderate to severe covid-19 disease, and number of women who received specific medical treatment for SARS-CoV-2 infection. Moderate to severe covid-19 disease was defined as maternal death, admission to an intensive care unit, or need for respiratory support.Results Among 1.7 million maternities, 9003 women were included in the study: 2350 (26.1%) were admitted to hospital because of covid-19 disease or had symptoms of disease. The pooled incidence of hospital admissions for covid-19 per 1000 maternities was 0.8 (95% confidence interval (CI) 0.5 to 1.2, τ2=0.44), ranging from no hospital admissions in Iceland to 1.7 in France and 1.9 in the UK. 13 women died due to covid-19. Among 2219 women admitted to hospital for covid-19 in countries with complete information on respiratory support, 820 women (39.5%, 95% CI 34.6% to 44.4%, τ2=0.02) had moderate to severe covid-19 disease. At most, 16.8% (95% CI 7.7% to 32.9%, I2=81.8%, τ2=0.7) of women with moderate to severe covid-19 received specific medical treatment for SARS-CoV-2 infection with corticosteroids, although 66.6% (59.4% to 73.2%, I2=50.1, τ2=0.06) were given thromboprophylaxis.Conclusions Population based surveillance in 10 European countries during the first 10 months of the covid-19 pandemic showed variations in the risk of hospital admissions for covid-19 in pregnant women. This finding indicates that national public health policies likely had a substantial and previously unrecognised role in protecting pregnant women. Few pregnant women with moderate to severe covid-19 were given specific medical treatment for SARS-CoV-2 disease, even when there were no or minor safety concerns. Lessons for future pandemics include the importance of rapid, robust surveillance systems for maternal and perinatal health, and of including use for pregnant women early in the development and testing of medicines and vaccines for public health emergencies.

Esse artigo reflete sobre o avanço das tecnologias da informação e da comunicação (TIC), especialmente a neurotecnologia, a tecnologia aplicada ao ramo da Medicina chamado Neurologia, seus benefícios e a incerteza dos riscos que podem advir de sua implementação. Assim, são abordadas a necessidade de observância da ética e da dignidade da pessoa humana, como pressupostos de condutas médicas, além do respeito aos dados neuronais obtidos. Em se tratando de TIC, aborda-se a proteção do meio ambiente digital no Brasil como elemento da proteção ambiental na Constituição Federal brasileira. Conclui que nesse contexto, o princípio da precaução é relevante, já que não há certeza do impacto causado pela neurotecnologia podendo eles gerarem danos importantes a diretos fundamentais: exemplo é o caso da Neuralink, que comprovou ter procedido a implante de microchip neuronal em paciente humano. O método de aproximação é o hipotético dedutivo e a pesquisa é de natureza bibliográfica.

The aim of this brief report is to evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2-I) effects on patients with both refractory ascites and type 2 diabetes mellitus (T2D). We consecutively recruited all the diabetic patients with refractory ascites due to decompensated liver cirrhosis admitted between February and May 2023 at the Internal Medicine Unit of the University Hospital of Palermo. Clinical and laboratory data were collected after starting SGLT2-I therapy. SGLT2-I use was associated with a reduction/resolution of ascites and with an improvement in serum albumin and sodium levels and estimated glomerular filtration rate. SGLT2-I might represent a valid therapeutic option in the treatment of patients with refractory ascites and T2D, as already hypothesized by other research groups.

This descriptive study aims to determine the digital competence level of faculty members who teach in the health sciences, empirically considering possible contextual aspects. Two data collection instruments were used: a self-reflection questionnaire to assess digital competence, and a survey querying demographics and aspects of teaching and learning context. In total, 306 health sciences faculty members from six universities voluntarily participated the study. The results revealed that a majority of the faculty members have intermediate (integrator or expert) level of digital competence, which is described as being aware of the potential use of digital technology in teaching and having a personal repertoire for its use under various circumstances. Age, digital teaching experience, perception of work environment, and previous teaching experience in fully- or partially-online courses were identified as influencing factors for digital competence. Faculty members in health sciences were able to integrate digital technologies in their teaching practices. Health education institutions may facilitate the use of digital technologies in teaching and learning environments. Moreover, institutions or stakeholders should consider that digital competence requires practice and experience in meaningfully-designed digital environments and tools.

BackgroundSmartphones and wearables are revolutionizing the assessment of cognitive and motor function in neurological disorders, allowing for objective, frequent, and remote data collection. However, these assessments typically provide a plethora of sensor-derived measures (SDMs), and selecting the most suitable measure for a given context of use is a challenging, often overlooked problem. ObjectiveThis analysis aims to develop and apply an SDM selection framework, including automated data quality checks and the evaluation of statistical properties, to identify robust SDMs that describe the cognitive and motor function of people with multiple sclerosis (MS). MethodsThe proposed framework was applied to data from a cross-sectional study involving 85 people with MS and 68 healthy participants who underwent in-clinic supervised and remote unsupervised smartphone-based assessments. The assessment provided high-quality recordings from cognitive, manual dexterity, and mobility tests, from which 47 SDMs, based on established literature, were extracted using previously developed and publicly available algorithms. These SDMs were first separately and then jointly screened for bias and normality by 2 expert assessors. Selected SDMs were then analyzed to establish their reliability, using an intraclass correlation coefficient and minimal detectable change at 95% CI. The convergence of selected SDMs with in-clinic MS functional measures and patient-reported outcomes was also evaluated. ResultsA total of 16 (34%) of the 47 SDMs passed the selection framework. All selected SDMs demonstrated moderate-to-good reliability in remote settings (intraclass correlation coefficient 0.5-0.85; minimal detectable change at 95% CI 19%-35%). Selected SDMs extracted from the smartphone-based cognitive test demonstrated good-to-excellent correlation (Spearman correlation coefficient, |ρ|>0.75) with the in-clinic Symbol Digit Modalities Test and fair correlation with Expanded Disability Status Scale (EDSS) scores (0.25≤|ρ|0.75) for mobility test SDMs. Overall, correlations were similar when smartphone-based tests were performed in a clinic or remotely. ConclusionsReported results highlight that smartphone-based assessments are suitable tools to remotely obtain high-quality SDMs of cognitive and motor function in people with MS. The presented SDM selection framework promises to increase the interpretability and standardization of smartphone-based SDMs in people with MS, paving the way for their future use in interventional trials.