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Purpose Bangladesh has experienced a rapid epidemiological transition from communicable to non-communicable diseases (NCDs) in recent decades. There is, however, limited evidence about multidimensional determinants of NCDs in this population. The BangladEsh Longitudinal Investigation of Emerging Vascular and nonvascular Events (BELIEVE) study is a household-based prospective cohort study established to investigate biological, behavioural, environmental and broader determinants of NCDs.Participants Between January 2016 and March 2020, 73 883 participants (aged 11 years or older) were recruited from 30 817 households across urban, urban-poor (‘slum’) and rural settings in Bangladesh. A structured questionnaire was administered by trained personnel recording participants’ demographic, socioeconomic, behavioural, medical, environmental and other factors. Anthropometric measurements and blood pressure were recorded for each participant. Biological specimens were collected and aliquoted for long-term storage and analysis.Findings to date Of the 73 883 study participants (mean [SD] baseline age: 39 [15] years), 43 470 (59%) were females, and 38 848 (52%) had no or only primary-level education. Focusing only on the 65 822 adult participants aged 20–79 years at baseline, 15 411 (23%) reported being diagnosed with hypertension; 10 578 (16%) with type 2 diabetes and 7624 (12%) with hypercholesterolaemia. Age and sex-standardised prevalences of these conditions were much higher in urban than slum and rural settings. Overall, the mean (SD) body mass index (BMI) was 25 (5) kg/m2, with 10 442 (16%) participants aged 20–79, classified as obese (ie, BMI≥30 kg/m2). Mean BMI was also higher in urban than slum and rural areas.Future plans The collection of information during the baseline visit was completed in 2020. Regular longitudinal follow-up is ongoing for ascertainment and adjudication of a range of fatal and non-fatal health outcomes among participants. This cohort will provide a powerful resource to investigate multidimensional determinants of incident NCDs across diverse settings in Bangladesh, helping to advance scientific discovery and public health action in an archetypal low-middle-income country with pressing public health needs.

BackgroundAlthough commercially developed automated insulin delivery (AID) systems have recently been approved and become available in a limited number of countries, they are not universally available, accessible, or affordable. Therefore, open-source AID systems, cocreated by an online community of people with diabetes and their families behind the hashtag #WeAreNotWaiting, have become increasingly popular. ObjectiveThis study focused on examining the lived experiences, physical and emotional health implications of people with diabetes following the initiation of open-source AID systems, their perceived challenges, and their sources of support, which have not been explored in the existing literature. MethodsWe collected data from 383 participants across 29 countries through 2 sets of open-ended questions in a web-based survey on their experience of building and using open-source AID systems. Narratives were thematically analyzed, and a coding framework was identified through iterative alignment. ResultsParticipants consistently reported improvements in glycemia, physical health, sleep quality, emotional impact on everyday life, and quality of life. Knowledge of open-source AID systems was largely obtained through the #WeAreNotWaiting community, which was also the primary source of practical and emotional support. The acquisition of the components to build an open-source AID system and the technical setup were sometimes problematic. ConclusionsThe #WeAreNotWaiting movement represents a primary example of how informed and connected patients proactively address their unmet needs, provide peer support to each other, and obtain results through impactful, user-driven solutions. Alongside providing evidence on the safety and efficacy of open-source AID systems, this qualitative analysis helps in understanding how patients’ experiences and benefits range from psychosocial improvements to a reduction in the burden of managing diabetes. International Registered Report Identifier (IRRID)RR2-10.2196/15368

Abstract Antibiotic‐resistant enterococci represent a significant global health challenge. Unfortunately, most β‐lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides are conjugated to examples from each of the four classes of β‐lactam antibiotics. Remarkably, the β‐lactam–peptide conjugates gained an up to 1000‐fold increase in antimicrobial activity against vancomycin‐susceptible and vancomycin‐resistant enterococci. Even against β‐lactam‐resistant Gram‐negative strains, the conjugates are found to be effective despite their size exceeding the exclusion volume of porins. The extraordinary gain of activity can be explained by an altered mode of killing. Of note, the conjugates showed a concentration‐dependent activity in contrast to the parent β‐lactam antibiotics that exhibited a time‐dependent mode of action. In comparison to the parent β‐lactams, the conjugates showed altered affinities to the penicillin‐binding proteins. Furthermore, it is found that peptide conjugation also resulted in a different elimination route of the compounds when administered to rodents. In mice systemically infected with vancomycin‐resistant enterococci, treatment with a β‐lactam–peptide conjugate reduced bacterial burden in the liver compared to its originator. Therefore, peptide modification of β–lactam antibiotics represents a promising platform strategy to broaden their efficacy spectrum, particularly against enterococci.

This study investigates the effects of press channel length on the quality of wood pellets, focusing on key aspects such as density, radial porosity distribution, and mechanical stability, both at the time of delivery and during storage. Wood pellets were produced using press channels with diameter-to-length (D/L) ratios of 1:3, 1:4, and 1:5 to evaluate how variations in die geometry influence pellet quality. Micro-computed tomography (μCT) analysis indicates that the D/L ratio of the press channel significantly impacts the porosity within the pellets. Short press channels are associated with great variability in the radial porosity distribution of the wood pellets, while longer press channels lead to uniformly low porosity over the radius. Furthermore, pellets produced with longer press channels exhibit a smoother surface with fewer cracks and greater resistance to structural degradation under varying humidity conditions. Although high-density pellets show improved mechanical strength and recovery potential in humid environments, remaining damage in the form of cracks and alterations in radial porosity distribution lead to reduced strength compared to their initial state.

The research station at Prince Leopold Island (PLI), initiated in 1975, was the first seabird monitoring site created in the Canadian Arctic. The island supports 150 000 breeding pairs of seabirds, principally thick-billed murres (Uria lomvia Linnaeus 1758), black-legged kittiwakes (Rissa tridactyla Linnaeus 1758) and northern fulmars (Fulmarus glacialis Linnaeus 1761), along with ∼70 pairs of glaucous gulls (Larus hyperboreus Gunnerus 1767) and several thousand black guillemots (Cepphus grylle Linnaeus 1758). Baseline observations of seabird breeding biology were made during 1975–1977. Subsequent monitoring has taken place in 22 of the 47 seasons, with work during 2001–2003 replicating the original baseline studies. Population trends of breeding seabirds have shown kittiwakes (sharply) and murres (gradually) increasing, while gulls (definitely) and fulmars (likely) have declined. The most striking scientific findings from PLI were related to the effect of annual ice break-up on seabird phenology, clutch size, and reproductive success. For contaminant research, PLI has become one of the core monitoring sites in Canada and internationally, documenting dramatic changes in concentrations of various contaminants in the Arctic marine environment. Given the international impact of research and monitoring at PLI for almost five decades, the continuation of seabird research at PLI, the most important seabird colony in the Canadian Arctic, is essential.

The Coats Island field station in northern Hudson Bay, Canada, was established by the Canadian Wildlife Service in 1984 to monitor the thick-billed murre (Uria lomvia, akpa, [Graphic: see text]) population in the context of harvest management and federal responsibilities under the Migratory Birds Convention Act. The long-term monitoring program has continued annually for 34 of the last 39 years, making it the most frequently monitored seabird colony in the Canadian Arctic. In the 1990s, the focus of efforts at the site shifted from population monitoring and harvest management to long-term monitoring of murres as an indicator of environmental change. In addition to informing harvest management of murres in Canada, long-term monitoring and research at Coats Island have helped to establish thick-billed murres as an indicator species for Arctic seabirds, identified major shifts in the marine prey communities of Hudson Bay, enabled the assessment of international agreements on reducing contaminants in Arctic wildlife, and improved the understanding of the effects of climate change on Arctic marine birds. Coats Island has developed into an essential research site for all aspects of murre ecology and served as a training site for new generations of Arctic ecologists.

BackgroundDespite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF).Methods24 anesthetized pigs with experimental acute lung injury were ventilated for 18 h according to one of three strategies: 1) Open lung approach (OLA), 2) ARDS Network high-PEEP/FIO2 strategy (HighPEEP), or 3) low-PEEP/FIO2 strategy (LowPEEP). Total MP was assessed as the sum of energy dissipated to overcome airway resistance and energy temporarily stored in the elastic lung tissue per minute. The distribution of pulmonary perfusion was determined by positron emission tomography. Regional PBF and MP, assessed in three iso-gravitational regions of interest (ROI) with equal lung mass (ventral, middle, and dorsal ROI), were compared between groups.ResultsMP was higher in the LowPEEP than in the OLA group, while CO did not differ between groups. After 18 h, regional PBF did not differ between groups. During LowPEEP, regional MP was higher in the ventral ROI compared to OLA and HighPEEP groups (2.5 ± 0.3 vs. 1.4 ± 0.4 and 1.6 ± 0.3 J/min, respectively, P < 0.001 each), and higher in the middle ROI compared to the OLA group (2.5 ± 0.4 vs. 1.6 ± 0.5 J/min, P = 0.04). MP in the dorsal ROI did not differ between groups (1.4 ± 0.9 vs. 1.4 ± 0.5 vs. 1.3 ± 0.8 J/min, P = 0.916). Total MP was independently associated with CO [0.34 (0.09, 0.59), P = 0.020]. Regional MP was positively associated with PBF irrespective of the regions [0.52 (0.14, 0.76), P = 0.01; 0.49 (0.10, 0.74), P = 0.016; 0.64 (0.32, 0.83), P = 0.001 for ventral, middle, and dorsal ROI, respectively]. Subgroup analysis revealed a significant association of MP and CO only in the OLA group as well as a significant association between MP with regional PBF only in the HighPEEP group.ConclusionIn this model of acute lung injury in pigs ventilated with either open lung approach, high, or low PEEP tables recommended by the ARDS network, MP correlated positively with CO and regional PBF, whereby these clinically relevant lung-protective ventilation strategies influenced the associations.

Introdução/Objetivo: A Síndrome POEMS (Polineuropatia; Organomegalia; Endocrinopatia; Distúrbio monoclonal de células plasmáticas e alterações cutâneas) é um processo paraneoplásico de causa desconhecida, onde ocorre superprodução de citocinas inflamatórias, dentre as quais, o VEGF é a que melhor se relaciona com atividade de doença. Existem dois critérios obrigatórios que a compõem: polineuropatia e a presença de distúrbio monoclonal das células plasmáticas. Esse trabalho possui como objetivo demonstrar um caso atípico de POEMS, onde um dos critérios obrigatórios não está presente. Material e métodos: Trata-se de um relato de caso sobre Síndrome POEMS. Resultados: F.V.S, feminina, 49 anos, branca, casada, evangélica, manicure, natural da Paraíba e residente do Rio de Janeiro, refere que em novembro de 2022, iniciou quadro de paresia e parestesias de caráter ascendente em membros inferiores até nível dos joelhos. Em janeiro de 2023, apresentou hiperemia e turvação visual, sendo diagnosticada com papiledema, realizando punção lombar, com melhora parcial do quadro. Nos meses subsequentes, evoluiu com perda ponderal (20 kgs em 7 meses), aumento do volume abdominal e foi diagnosticada com hipotireoidismo. Deu entrada no Hospital Universitário Gaffrée e Guinle em fevereiro de 2024 para dar seguimento à investigação. Realizou Tomografia Computadorizada de Tórax/Abdome e Pelve, com evidência de lesão esclerótica em esterno, ascite volumosa e hepatoesplenomegalia; Eletroneuromiografia demonstrou neuropatia sensitivo motora de natureza desmielinizante e sinais de lesão axonal secundária; Eletroforese de proteínas séricas e urinárias e Imunofixação de proteínas séricas e urinárias apresentaram resultados negativos; Cadeias leves livres sem a presença de pico monoclonal; Biópsia de Medula Óssea: infiltrado de plasmócitos correspondendo a 10% de celularidade, com leve predomínio de cadeia leve lambda. Ao exame físico apresenta raynaud em ambas as mãos. Neurológico: Marcha talonante; Arreflexia global; Sensibilidade superficial = hipoestesia tátil abaixo dos joelhos, hiperalgesia dolorosa abaixo dos joelhos; Sensibilidade profunda = apalestesia distal em membros inferiores. A paciente foi encaminhada para a Hematologia e iniciou tratamento com VCD – Bortezomibe; Dexametasona e Ciclofosfamida dia 3 de maio de 2024. Evoluiu com redução do volume abdominal – última paracentese no dia 2 de maio de 2024. Dosagem de VEGF com valor de 1540,1 pg/mL. Nova eletroforese de proteínas séricas e urinárias, imunofixação de proteínas séricas e urinárias e dosagem de cadeias leves livres não demonstraram, novamente, presença do pico monoclonal. Foi encaminhada para realização de transplante de células hematopoiéticas. Segue em acompanhamento também com a Neurologia, atualmente em uso de topiramato para a Síndrome de hipertensão intracraniana. Discussão: Diante do exposto, trata-se de um caso atípico de POEMS, pois há ausência de gamopatia monoclonal a despeito da presença de plasmocitose na medula óssea e resposta ao tratamento instituído. Conclusão: A Síndrome POEMS é uma entidade rara, e muitas vezes subdiagnosticada. Casos atípicos (sem a presença de polineuropatia ou distúrbio de células plasmáticas monoclonais) já foram relatados. Caso esses pacientes desenvolvam sintomas graves, como ascite refratária, deve-se considerar tratamento de forma semelhante aos casos típicos.

Immunofluorescence localises proteins via fluorophore-labelled antibodies. However, some proteins evade detection due to antibody-accessibility issues or because they are naturally low abundant or antigen density is reduced by the imaging method. Here, we show that the fusion of the target protein to the biotin ligase TurboID and subsequent detection of biotinylation by fluorescent streptavidin offers an ‘all in one’ solution to these restrictions. For all proteins tested, the streptavidin signal was significantly stronger than an antibody signal, markedly improving the sensitivity of expansion microscopy and correlative light and electron microscopy. Importantly, proteins within phase-separated regions, such as the central channel of the nuclear pores, the nucleolus, or RNA granules, were readily detected with streptavidin, while most antibodies failed. When TurboID is used in tandem with an HA epitope tag, co-probing with streptavidin and anti-HA can map antibody-accessibility and we created such a map for the trypanosome nuclear pore. Lastly, we show that streptavidin imaging resolves dynamic, temporally, and spatially distinct sub-complexes and, in specific cases, reveals a history of dynamic protein interaction. In conclusion, streptavidin imaging has major advantages for the detection of lowly abundant or inaccessible proteins and in addition, provides information on protein interactions and biophysical environment.

Tuberculous paradoxical reaction presents as clinical deterioration during appropriate tuberculosis therapy and is a separate entity from treatment failure and drug resistance. We describe a case of central nervous system paradoxical reaction following tuberculous meningoencephalitis treatment in an immunocompromised patient with systemic lupus erythematosus.

Background Clinical trials comparing the efficacy of ocrelizumab (OCR) with other disease-modifying therapies (DMTs) other than interferon (IFN) β-1a in relapsing multiple sclerosis (RMS) are lacking. Objectives To compare the treatment effect of OCR vs six DMTs’ (IFN β-1a, glatiramer acetate, fingolimod, dimethyl fumarate, teriflunomide, natalizumab) treatment pathways used in clinical practice by combining clinical trial and real-world data. Methods Patient-level data from OPERA trials and open-label extension phase, and from the German NeuroTransData (NTD) MS registry, were used to build 1:1 propensity score-matched (PSM) cohorts controlling for seven baseline covariates, including brain imaging activity. Efficacy outcomes were time to first relapse and time to 24-week confirmed disability progression over 5.5 years of follow-up. Intention-to-treat analysis using all outcome data irrespective of treatment switch was applied. Results The analyses included 611 OPERA patients and 7141 NTD patients. We built 12 paired-matched cohorts (six for each outcome, two for each DMT) to compare efficacy of OCR in OPERA with each DMT treatment pathway in NTD. Post-matching, baseline covariates and PS were well balanced (standardized mean difference