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Abstract Diabetic foot infection imposes a significant burden and is the major cause of nontraumatic limb amputation. Adequate patient management with effective antibiotic therapy is crucial. This retrospective cohort study aimed to characterize the microbiology and resistance patterns of moderate to severe neuropathic diabetic foot infection in patients hospitalized at a tertiary referral hospital between January 2020 and June 2023. Deep tissue specimens from ulcers were collected for culture. Sixty inpatients were included (62% male, mean age 59.1 ± 11.5 years). Osteomyelitis was present in 90% of the patients. Among 102 microorganisms (average of 1.91 ± 1.25 pathogens per patient), 60.8% were gram-positive bacteria, 31.4% were gram-negative, 3.92% were anaerobic bacteria, and 3.92% were fungi. Staphylococcus aureus (19%) and Enterococcus faecium (17%) were the most common. Pseudomonas aeruginosa (8%) and bacteria of the Enterobacterales family (24%) accounted for all the isolated gram-negative bacteria. Sixteen percent of Staphylococcus aureus and 67% of coagulase-negative Staphylococci were resistant to methicillin. Resistance to ampicillin was found in 11% of Enterococci. All Pseudomonas aeruginosa isolates were sensitive to piperacillin-tazobactam, ceftazidime, or cefepime. Among the Enterobacterales, resistance rates were 35% for piperacillin-tazobactam, 38% for ceftazidime, 21% for cefepime, and 13% for carbapenems. Although the prevalence of methicillin-resistant staphylococci was lower than that in other studies, carbapenem resistance among gram-negative bacteria warrants attention. This study highlights the importance of understanding local epidemiology for effective diabetic foot infection management and resistance mitigation.

Abstract Background Endometriosis, defined as the presence of endometrial-like tissue outside of the uterus, is one of the most prevalent gynecological disorders. Although different theories have been proposed, its pathogenesis is not clear. Novel studies indicate that the gut microbiome may be involved in the etiology of endometriosis; nevertheless, the connection between microbes, their dysbiosis, and the development of endometriosis is understudied. This case–control study analyzed the gut microbiome in women with and without endometriosis to identify microbial targets involved in the disease. Methods A subsample of 1000 women from the Estonian Microbiome cohort, including 136 women with endometriosis and 864 control women, was analyzed. Microbial composition was determined by shotgun metagenomics and microbial functional pathways were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Partitioning Around Medoids (PAM) algorithm was performed to cluster the microbial profile of the Estonian population. The alpha- and beta-diversity and differential abundance analyses were performed to assess the gut microbiome (species and KEGG orthologies (KO)) in both groups. Metagenomic reads were mapped to estrobolome-related enzymes’ sequences to study potential microbiome-estrogen metabolism axis alterations in endometriosis. Results Diversity analyses did not detect significant differences between women with and without endometriosis (alpha-diversity: all p-values > 0.05; beta-diversity: PERMANOVA, both R 2 0.05). No differential species or pathways were detected after multiple testing adjustment (all FDR p-values > 0.05). Sensitivity analysis excluding women at menopause (> 50 years) confirmed our results. Estrobolome-associated enzymes’ sequence reads were not significantly different between groups (all FDR p-values > 0.05). Conclusions Our findings do not provide enough evidence to support the existence of a gut microbiome-dependent mechanism directly implicated in the pathogenesis of endometriosis. To the best of our knowledge, this is the largest metagenome study on endometriosis conducted to date.

Measures of physical growth, such as weight and height have long been the predominant outcomes for monitoring child health and evaluating interventional outcomes in public health studies, including those that may impact neurodevelopment. While physical growth generally reflects overall health and nutritional status, it lacks sensitivity and specificity to brain growth and developing cognitive skills and abilities. Psychometric tools, e.g., the Bayley Scales of Infant and Toddler Development, may afford more direct assessment of cognitive development but they require language translation, cultural adaptation, and population norming. Further, they are not always reliable predictors of future outcomes when assessed within the first 12–18 months of a child’s life. Neuroimaging may provide more objective, sensitive, and predictive measures of neurodevelopment but tools such as magnetic resonance (MR) imaging are not readily available in many low and middle-income countries (LMICs). MRI systems that operate at lower magnetic fields (< 100mT) may offer increased accessibility, but their use for global health studies remains nascent. The UNITY project is envisaged as a global partnership to advance neuroimaging in global health studies. Here we describe the UNITY project, its goals, methods, operating procedures, and expected outcomes in characterizing neurodevelopment in sub-Saharan Africa and South Asia.

Abstract Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15 + macrophages, PRDM16 + dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand–receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Abstract Background Bariatric surgery leads to weight loss and to cardiometabolic risk improvement. Although prediabetes remission after bariatric surgery is biologically plausible, data on this topic is scarce. We aimed to assess prediabetes remission rate and clinical predictors of remission in a 4 year follow up period. Methods Observational longitudinal study including patients with obesity and prediabetes who had undergone bariatric surgery in our centre. Prediabetes was defined as having a baseline glycated haemoglobin (A1c) between 5.7% and 6.4% and absence of anti-diabetic drug treatment. We used logistic regression models to evaluate the association between the predictors and prediabetes remission rate. Results A total of 669 patients were included, 84% being female. The population had a mean age of 45.4 ± 10.1 years-old, body mass index of 43.8 ± 5.7 kg/m2, and median A1c of 5.9 [5.8, 6.1]%. After bariatric surgery, prediabetes remission rate was 82%, 73%, 66%, and 58%, respectively in the 1st, 2nd, 3rd, and 4th years of follow-up. Gastric sleeve (GS) surgery was associated with higher prediabetes remission rate than Roux-en-Y gastric bypass surgery in the 3rd year of follow-up. Men had a higher remission rate than women, in the 1st and 3nd years of follow-up in the unadjusted analysis. Younger patients presented a higher remission rate comparing to older patients in the 3rd year of follow-up. Conclusion We showed a high prediabetes remission rate after bariatric surgery. The remission rate decreases over the follow-up period, although most of the patients maintain the normoglycemia. Prediabetes remission seems to be more significant in patients who had undergone GS, in male and in younger patients.

Introduction: The COVID-19 pandemic has led to a worldwide lockdown, which affected physical exercise habits, as well as having a detrimental effect on psychological health and follow-up visits of patients submitted to bariatric surgery. The aim of this study was to evaluate the impact of COVID-19 lockdown on the 2-year weight loss of patients submitted to bariatric surgery in our center. Methods: This was an observational study comparing the weight loss of patients who underwent bariatric surgery from January to March 2020 with a control group submitted to surgery between January and March 2017. Percentage of total weight loss (% TWL) and excess weight loss (% EWL) were assessed 6, 12, and 24 months after surgery. Results: A total number of 203 patients were included in this study, 102 had bariatric surgery during the selected period in 2020 and 101 underwent surgery during the same period in 2017. There was no statistically significant difference in weight loss between the 2017 and 2020 groups which was reported as % TWL (mean 27.08 ± 7.530 vs. 28.03 ± 7.074, 33.87 ± 8.507 vs. 34.07 ± 8.979 and 34.13 ± 9.340 vs. 33.98 ± 9.993; p = 0.371) and % EWL (mean 66.83 ± 23.004 vs. 69.71 ± 17.021, 83.37 ± 24.059 vs. 84.51 ± 21.640 and 83.47 ± 24.130 vs. 84.27 ± 23.651; p = 0.506) at 6, 12, and 24 months post-surgery. Conclusion: Despite social limitations imposed by the COVID-19 lockdown, we found no significant difference between weight loss at 2 years postoperatively in the 2020 group when compared with a control group who underwent bariatric surgery in 2017. These results show that the outcomes of bariatric surgery during the COVID-19 lockdown were comparable with those recorded before the pandemic, supporting the efficacy of bariatric procedures’ metabolic effects during the first 2 years after surgery, regardless of lifestyle habits.

Introduction: Three years after the beginning of the SARS-CoV-2 pandemic, the safety and efficacy of COVID-19 vaccination in liver cirrhosis (LC) patients remain controversial. We aimed to study the safety, immunological, and clinical responses of LC patients to COVID-19 vaccination. Methods: Prospective multicentric study in adults with LC eligible for COVID-19 vaccination, without prior known infection. Patients were followed up until the timing of a booster dose, SARS-CoV-2 infection, or death. Spike-protein immunoglobulin G antibody titers for SARS-CoV-2 at 2 weeks, 3 months, and 6 months postvaccination were assessed. Antibody titers 200 BAU/mL at 3 months. Conclusion: COVID-19 vaccines in patients with LC were safe, without serious adverse events. The humoral and clinical responses were similar to the reported for the general population. Humoral response was adversely impacted by older age and adenovirus vector vaccines and unrelated to the liver disease severity.

Abstract Urban vegetable gardens are very often a feature of cities that want to offer their citizens a more sustainable lifestyle by producing their own food products. However, cities can have significant pollution levels (or pollution hotspots) due to specific sources of pollution, such as traffic. Among the various pollutants, microplastics (MPs) are emerging as a consensual concern due to the awareness of the environmental contamination, their bioaccumulation potential and human intake, and, consequently unknown human health impacts. The present study compared the content of MPs in lettuce plants cultivated in Lisbon urban gardens with those cultivated in a rural area, as well as samples bought in supermarkets. Microplastics were detected in all washed leaves, with mean levels ranging from 6.3 ± 6.2 to 29.4 ± 18.2 MPs/g. Lettuce grown in urban gardens from areas with high traffic density showed higher MPs levels. Weak positive Spearman’s rank correlations were found between MPs content and concentrations of Cu and S (determined by Particle Induced X-Ray Emission, PIXE), suggesting a possible role of traffic contribution to MPs levels, as both elements are considered traffic-source tracers. These results contribute to shed light on the MP contamination of vegetables grown in such urban environments, that may represent a potential MP exposure route through the dietary intake, corresponding to a 70% increase in annual MP intake compared to lettuces bought in supermarkets.

Aim: The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves’ disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves’ disease. Methods: Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models. Results: We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th–75th percentiles 1.5–5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classifica tion as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not s ignificantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04–2.49) and with larger nodules (OR 2.96, 95%CI 1.08– 8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis. Conclusion: Patients with Graves’ disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.

Summary: Background: Magnetic Resonance (MR) imaging is key for investigation of suspected newborn brain abnormalities. Access is limited in low-resource settings and challenging in infants needing intensive care. Portable ultralow field (ULF) MRI is showing promise in bedside adult brain imaging. Use in infants and children has been limited as brain-tissue composition differences necessitate sequence modification. The aim of this study was to develop neonatal-specific ULF structural sequences and test these across a range of gestational maturities and pathologies to inform future validation studies. Methods: Prospective cohort study within a UK neonatal specialist referral centre. Infants undergoing 3T MRI were recruited for paired ULF (64mT) portable MRI by convenience sampling from the neonatal unit and post-natal ward. Key inclusion criteria: 1) Infants with risk or suspicion of brain abnormality, or 2) preterm and term infants without suspicion of major genetic, chromosomal or neurological abnormality. Exclusions: presence of contra-indication for MR scanning. ULF sequence parameters were optimised for neonatal brain-tissues by iterative and explorative design. Neuroanatomic and pathologic features were compared by unblinded review, informing optimisation of subsequent sequence generations in a step-wise manner. Main outcome: visual identification of healthy and abnormal brain tissues/structures. ULF MR spectroscopy, diffusion, susceptibility weighted imaging, arteriography, and venography require pre-clinical technical development and have not been tested. Findings: Between September 23, 2021 and October 25, 2022, 102 paired scans were acquired in 87 infants; 1.17 paired scans per infant. Median age 9 days, median postmenstrual age 40+2 weeks (range: 31+3–53+4). Infants had a range of intensive care requirements. No adverse events observed. Optimised ULF sequences can visualise key neuroanatomy and brain abnormalities. In finalised neonatal sequences: T2w imaging distinguished grey and white matter (7/7 infants), ventricles (7/7), pituitary tissue (5/7), corpus callosum (7/7) and optic nerves (7/7). Signal congruence was seen within the posterior limb of the internal capsule in 10/11 infants on finalised T1w scans. In addition, brain abnormalities visualised on ULF optimised sequences have similar MR signal patterns to 3T imaging, including injury secondary to infarction (6/6 infants on T2w scans), hypoxia-ischaemia (abnormal signal in basal ganglia, thalami and white matter 2/2 infants on T2w scans, cortical highlighting 1/1 infant on T1w scan), and congenital malformations: polymicrogyria 3/3, absent corpus callosum 2/2, and vermian hypoplasia 3/3 infants on T2w scans. Sequences are susceptible to motion corruption, noise, and ULF artefact. Non-identified pathologies were small or subtle. Interpretation: On unblinded review, optimised portable MR can provide sufficient contrast, signal, and resolution for neuroanatomical identification and detection of a range of clinically important abnormalities. Blinded validation studies are now warranted. Funding: The Bill and Melinda Gates Foundation, the MRC, the Wellcome/EPSRC Centre for Medical Engineering, the MRC Centre for Neurodevelopmental Disorders, and the National Institute for Health Research (NIHR) Biomedical Research Centres based at Guy’s and St Thomas’ and South London & Maudsley NHS Foundation Trusts and King's College London.

Introdução: Os cuidados de saúde primários (CSP) são responsáveis pela resposta a situações de diagnóstico e tratamento de patologias do foro psiquiátrico bem como a referenciação de determinados casos para nível hospitalar. A Lei da Saúde Mental (Lei nº 36/98) determina os princípios da política de saúde mental e regulamenta o internamento compulsivo de pessoas com doença mental, sendo da responsabilidade do médico de família a identificação dessas situações e a ativação do Mandado de Condução ao Serviço de Urgência. Descrição do caso: O caso refere-se a uma utente do sexo feminino, de 50 anos de idade, com antecedentes psiquiátricos de tentativa de suicídio e seguida em consulta de psiquiatria. Em consulta programada de psiquiatria a utente refere quadro de ansiedade e agitação noturna, tendo sido realizado ajuste terapêutico com reavaliação posterior. Por manter queixas é novamente realizada alteração do plano terapêutico. Posteriormente recorre aos CSP em consulta do dia com a médica de família, onde refere incumprimento terapêutico bem como agravamento sintomático associado a irritabilidade e alucinações auditivas na forma de voz única com instruções para realizar atos de auto e hetero-agressividade; fora encaminhada e avaliada no serviço de urgência, com novo ajuste terapêutico e indicação para antecipação de consulta de psiquiatria para reavaliação do quadro. Em consulta subsequente com a médica de família apura-se ideação suicida, auto e hetero-agressividade associadas a pseudo-alucinações acústico-verbais, tendo sido proposta nova ida a SU, que a utente recusou. Pelo contexto, a médica de família aciona o Mandado de Condução que a utente compreende e aceita. Durante o internamento foi realizado novo plano terapêutico, observando-se remissão da ideação auto e hetero-agressiva e das pseudo-alucinações auditivas, bem como eutimização do humor e redução da anedonia e cognições de cariz depressivo. Comentário: Este caso clínico representa a gestão partilhada de utentes com patologia psiquiátrica entre os CSP e a psiquiatria e ainda a importância da vigilância da resposta terapêutica, reforçando a necessidade de aperfeiçoamento na articulação entre os diversos níveis de cuidados com o objetivo de garantir partilha de informação mais eficaz e a melhor prestação de cuidados aos utentes de foro psiquiátrico.

Abstract This work introduces a new alternative to obtain strut-and-tie models using the hybrid topology optimization method, which is already proposed in the technical literature and is refined here to use polygonal finite elements and accelerate the solution of the material nonlinearity problem. In this method, concrete is approached as a continuum, using polygonal two-dimensional finite elements, and steel bars as truss elements, using one-dimensional finite elements with two nodes. For a closer representation of reality, an orthotropic constitutive model for concrete was implemented considering different compression and tensile stiffness values, which is one of the advantages of the model. Further, the hybrid method limits the final layout of steel bars, thereby generating better structures from a constructive point of view, while allowing greater freedom for the shape and concrete strut slope. However, this method is more complex, and it increases the computational cost, which was substantially minimized through the implementation of an algorithm. Results obtained for some domains were very close to the results of other methodologies; however, small differences were noted that may be relevant to the final result. Other domains showed results with greater differences, thereby significantly changing the final strut-and-tie model and presenting a new structural design alternative.

Industrial., commercial, and residential facilities are progressively adopting automation and generation capabilities. By having flexible demand and renewable energy generation, traditional passive customers are becoming active participants in electric power system operations. Through profound coordination among grid operators and active customers, the facilities' capability for demand response (DR) and distributed energy resource (DER) management will be valuable asset for ancillary services (ASs). To comply with the increasing demand and flexible energy, utilities urgently require standards, regulations, and programs to efficiently handle load-side resources without trading off stability and reliability. This study reviews different types of customers' flexibilities for DR, highlighting their capabilities and limitations in performing local ancillary services (LASs), which should benefit the power grid by profiting from it through incentive mechanisms. Different financial incentives and techniques employed around the world are presented and discussed. The potential barriers in technical and regulatory aspects are successfully identified and potential solutions along with future guidance are discussed.

Abstract Background Low Magnesium (Mg) dietary intake has been associated with increased risk of type 2 diabetes mellitus (T2DM). Furthermore, in patients with T2DM, hypomagnesemia is associated with worst glycaemic control. Bariatric surgery (BS) remains the most effective treatment in severe obesity and also provides resolution/improvement of T2DM. Our aim is to evaluate the association between Mg supplementation post-BS and Mg serum levels with diabetes status after BS. Methods We performed an observational study on patients with obesity and T2DM who underwent BS. Data was assessed pre-BS and one-year post-BS. Results We included a total of 403 patients with T2DM. At baseline, 43.4% of the patients had Mg deficiency. Pre-BS, patients with Mg deficiency had poorer glycaemic control – HbA1c 7.2 ± 1.6% vs 6.4 ± 1.0% (p

Starting from an analysis of the scientific and political uses of the concept of informal care, this paper raises questions and launches the debate on the causes and effects of its uses. Recognizing the diversity and the contradictions found across the use of the term, it explains how its predominant use in Europe can be problematic. First, although it is widely recognized that care is provided primarily by women, this gender dimension is not emphasized in a concept that obscures the sexual division. Second, it does not render explicit that informal care is work, despite being unpaid. Third, the allusion to informality is likely to generate confusion with informal employment of care workers. Finally, studies often focus exclusively on care provided by family members, without distinguishing the spaces in which the work takes place and the social relationships it involves, namely the family or community. In Europe, where documents from (non)governmental organizations focus mainly on long-term care related to demographic aging, it is the care crisis of formal care provision systems, faced with financial fragility, reduction in funds and insufficient supply to meet the demand, that brings informal care to the political and scientific agendas. This paper argues that it is necessary to define conceptual boundaries that allow international studies on the dimension and value of this care work to be compared. It also advocates the importance of making visible that this is work, unpaid and female-dominated, since this view supports action guidelines more focused on social transformation and empowerment.

ABSTRACT Objective: To evaluate the association between the patients’ characteristics and the development of endocrine toxicity and to assess the association between endocrine-related adverse effects (ERAE) development and mortality. Subjects and methods: A retrospective observational study was conducted in 98 patients submitted to immunotherapy in our centre since its introduction in 2015 until March 2021. We excluded patients for which data regarding the corticotroph axis evaluation was missing. We used linear and logistic regression models to address our aims. Results: We observed a significant negative association between ERAE development and death (OR 0.32; p = 0.028). We detected no associations between ERAE and the following characteristics: age at immune checkpoint inhibitors (ICI) initiation, sex, diabetes mellitus, medical history, immunotherapy duration and ICI type. Conclusion: The development of an ERAE may be associated with a better overall survival rate in advanced oncologic disease, supporting the role of an unleashed immune system response to malignant cells.