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Introduction and objectives: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. Methods: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. Results: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1 612 851.54 up to EUR 6 587 360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. Conclusions: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals. Resumo: Introdução e objetivos: A insuficiência cardíaca (IC) é uma síndrome clínica associada a uma elevada morbidade, mortalidade e despesa com custos de saúde. A dapagliflozina demonstrou ser eficaz na redução do risco de morte e hospitalização em doentes com IC, independentemente da fração de ejeção do ventrículo esquerdo. Este artigo visa projetar o potencial impacto da dapagliflozina na redução dos custos relacionados com hospitalizações subsequentes por IC em hospitais portugueses. Métodos: Foi recolhido, e posteriormente analisado de forma agregada em clusters, o número total de hospitalizações por IC, hospitalizações subsequentes por IC e duração média de internamento dos doentes com diagnóstico primário de IC em seis hospitais portugueses, entre janeiro de 2019 e dezembro de 2021. Os custos relacionados com hospitalizações subsequentes por IC foram calculados de acordo com a legislação portuguesa e tendo em consideração três abordagens – conservadora, média e complexa. A projeção da redução de custos teve por base as reduções do risco relativo (RRR) de hospitalizações por IC (hIC) reportadas nos ensaios clínicos com dapagliflozina. Resultados: Considerando uma RRR de 26% do risco de hospitalização subsequente por IC, com base no valor reportado na análise agregada dos estudos DAPA-HF e DELIVER relativa à RRR de hIC, a nossa projeção indica que a utilização da dapagliflozina resulta numa redução de custos. De acordo com a nossa projeção a redução de custos oscila entre €1,612,851.54 e €6,587,360.09, entre 2019 e 2021, ao considerar todos os hospitais envolvidos e as diferentes abordagens metodológicas. A projeção aponta para um resultado similar tendo por base uma RRR de 24%, resultante da ponderação das subanálises de DAPA-HF e DELIVER, juntamente com dados epidemiológicos do estudo PORTHOS. Conclusões: Nesta projeção, a utilização de dapagliflozina, em todos os doentes hospitalizados por IC que sejam elegíveis, está associada a uma redução direta significativa nos custos hospitalares. Estes dados reforçam a ideia de que, para além da melhoria nos resultados de saúde relacionados com a IC, a dapagliflozina pode ter um impacto significativo nos hospitais portugueses ao nível dos custos de saúde.

Background: Schizophrenia is a severe psychiatric condition that affects approximately 24 million people worldwide. The complex pathophysiology of schizophrenia presents various challenges for researchers and doctors. Therefore, it is crucial to curate robust pharmacotherapy for patients with schizophrenia to ease their symptoms. Establishing proper standards for patient care requires an ammunition of research studies done on the disease and its therapy, upon which health-care practitioners can rely for future patient care. Unfortunately, there is a void of adequate research studies done on understanding the prescription patterns of schizophrenia in India, especially in rural areas. To improve patient outcomes, there is a need for increased research on this particular subject. Aim: The aim of this study was to assess the prescription pattern of antipsychotics in patients with schizophrenia at a tertiary care hospital in rural Karnataka. Setting and Design: This is an observational study carried out in MVJ Medical College and Research Hospital, Bengaluru, India. Materials and Methods: The study included a total of 139 inpatients, regardless of their age and sex, who had been diagnosed with schizophrenia. The study was conducted for a period of 6 months, from February 2022 to July 2022. Data collection involved a case record form (CRF) designed for assessing treatment patterns. An investigator was assigned to the Department of Psychiatry, where patients with schizophrenia were discovered and after reviewing their medication chart, necessary data were filled into the CRF. The obtained data were then compiled and assessed. Results: Paranoid schizophrenia was the major subclass (90.0%). The prescription pattern showed that second-generation antipsychotics (SGAs) were prescribed more than first-generation antipsychotics (FGAs), 112 (81.29%) and 41 (29.5%) prescriptions, respectively. In SGAs, tablet olanzapine received the most prescriptions which was 42 (30.22%). Tablet haloperidol was the major FGA to be prescribed receiving 18 prescriptions (12.95%). This study also included the assessment of combination drugs which showed that tablet risperidone + tablet trihexyphenidyl was the most prescribed combination drug 118 (78.43%). Conclusion: Our study showed that our findings aligned with several similar studies and also differed from a few, underscoring the need for further research and individualized treatment approaches to manage this complex psychiatric disorder.

Multiplex spatial proteomic methodologies can provide a unique perspective on the molecular and cellular composition of complex biological systems. Several challenges are associated to the analysis of imaging data, specifically in regard to the normalization of signal-to-noise ratios across images and subtracting background noise. However, there is a lack of user-friendly solutions for denoising multiplex imaging data that can be applied to large datasets. We have developed PENGUIN –Percentile Normalization GUI Image deNoising: a straightforward image preprocessing tool for multiplexed spatial proteomics data. Compared to existing approaches, PENGUIN distinguishes itself by eliminating the need for manual annotation or machine learning models. It effectively preserves signal intensity differences while reducing noise, improving downstream tasks such as cell segmentation and phenotyping. PENGUIN's simplicity, speed, and intuitive interface, available as both a script and a Jupyter notebook, make it easy to adjust image processing parameters, providing a user-friendly experience. We further demonstrate the effectiveness of PENGUIN by comparing it to conventional image processing techniques and solutions tailored for multiplex imaging data.

Abstract Background Wearable-generated data yield objective information on physical activity and sleep variables, which, are in turn, related to the phenomenology of depression. There is a dearth of wearable-generated data regarding physical activity and sleep variables among youth with clinical depression. Methods Longitudinal (up to 24 months) quarterly collections of wearable-generated variables among adolescents diagnosed with current/past major depression. Latent class analysis was employed to classify participants on the basis of wearable-generated: Activity, Sleep Duration, and Sleep efficiency. The Patient Health Questionnaire adapted for adolescents (PHQ-9-A), and the Ruminative Response Scale (RRS) at study intake were employed to predict class membership. Results Seventy-two adolescents (72.5% girls) were recruited over 31 months. Activity, Sleep Duration, and Sleep efficiency were reciprocally correlated, and wearable-generated data were reducible into a finite number (3 to 4) of classes of individuals. A PHQ-A score in the clinical range (14 and above) at study intake predicted a class of low physical activity (Acceleration) and a class of shorter Sleep Duration. Limitations Limited power related to the sample size and the interim nature of this study. Conclusions This study of wearable-generated variables among adolescents diagnosed with clinical depression shows that a large amount of longitudinal data is amenable to reduction into a finite number of classes of individuals. Interfacing wearable-generated data with clinical measures can yield insights on the relationships between objective psychobiological measures and symptoms of adolescent depression, and may improve clinical management of depression.

Abstract Background As food insecurity and healthcare costs are linked, healthcare entities (i.e., providers, healthcare systems, insurers) are increasingly interested in identifying and providing solutions to address food insecurity among their patients. Home-delivered meals are one long-standing solution to address food insecurity among homebound older adults. However, there is limited evidence about what mode of delivery is most effective in promoting community independence, reducing healthcare utilization, and improving quality of life as well as how these outcomes may vary as a function of people’s preferences for how meals are delivered to them. Methods With extensive stakeholder input, we designed and implemented a pragmatic randomized comparative effectiveness study in which we will enroll 2300 older adults on waiting lists at home-delivered meals programs across the country and randomize them to receive for 6 months, either (1) weekday lunchtime meals delivered by a local volunteer or driver who also provides socialization and wellness checks or (2) biweekly delivery of 10 frozen meals to participants’ homes. Participant data will be combined with Centers for Medicare and Medicaid Services (CMS) data to calculate post-randomization institutional vs. community days. Baseline and 3-month surveys will evaluate secondary outcomes (e.g., food insecurity, loneliness, quality of life) and exploratory outcomes (e.g., nutritional risk). To examine heterogeneity of treatment effects, we will test for interactions between the two types of meal delivery and participants’ preferred mode of meal delivery as well as participants’ living arrangements. Discussion This research will be the first to prospectively evaluate the comparative effectiveness of the two predominant meal delivery options. The knowledge generated from this research will be of value to healthcare providers, health systems, payers, community-based organizations, older adults, and their families, because it will identify the mode of meal delivery that best meets homebound older adults’ needs and promotes community independence. In addition, the experience of working closely with stakeholders in designing and conducting this trial will be useful to researchers seeking to engage with stakeholders in the development and evaluation of complex social service interventions while balancing regulatory, resource, and human subjects research considerations. Trial registration ClinicalTrials.gov. NCT05357261 . Registered on May 02, 2022

Pesticide misuse by farmers poses hazards to human, animal, and environmental health. [Objective] This study aimed to document potential pesticide formulation misuse in agricultural farms. [Methodology] Inadequate storage practices, incorrect pesticide selection, and pesticide formulation overuse were documented through interviews and photographs on 13 agricultural farms from the Cartago and Guanacaste provinces of Costa Rica between August 2022 and April 2023. [Results] Storage room characteristics in many farms do not comply with safety standards prescribed by the Costa Rican Ministry of Agriculture and Livestock. Different active ingredients with herbicidal, fungicidal, insecticidal, and bactericidal properties are used in crop species for which they are not recommended. These substances include those from the carbamate, pyridine, cyclohexanedione, pyrethroid, conazole, benzothiazinone, oxadiazine, and phthalimide chemical groups in Cartago province, and from the neonicotinoid and pyrethroid chemical groups in Guanacaste province. Many pesticide formulations are utilized in quantities exceeding the manufacturers' recommendations. Among these formulations were bifenthrin, captan, oxamyl, cypermethrin, mancozeb, dimethoate, and deltamethrin in Cartago province, and imidacloprid in Guanacaste province. [Conclusions] These substances and their secondary metabolites have the potential to move across different environmental compartments such as water, soil, and air, thereby negatively affecting the health of community members rather than just the farmers applying these formulations. Well-established pesticide education programs based on on-site visits to farmers can enhance awareness about implementing good practices and ensure rational use of these substances, with positive results in non-target organisms such as humans and ecosystem service providers as well as natural and anthropogenic ecosystems.

Abstract Background: Takotsubo syndrome is characterized by transient regional systolic dysfunction, left ventricular (LV) dilatation, and edema, often occurring without obstructive coronary artery disease. The mechanisms underlying this stress-induced condition, especially the role of mechanical dyssynchrony in affecting systolic function, remain poorly understood. Methods: In our study, we evaluated global LV function and mechanical dyssynchrony in 24 Takotsubo patients compared to 20 controls by analyzing pressure-volume loops and time-varying elastance. Additionally, we monitored changes in LV segmental volume and internal flow. Results: Here we show a significant reduction in global myocardial contractility and pronounced mechanical dyssynchrony in Takotsubo syndrome, particularly in the mid and apical LV segments, without disturbances in electrical conduction. Conclusions: Our findings reveal substantial mechanical dyssynchrony in Takotsubo patients, characterized by increased internal flow and a shortened systolic ejection time. This indicates a mechanical basis for the inefficient LV function in Takotsubo syndrome, independent of electrical conduction abnormalities.

Abstract Over the past five decades, a large number of wild animals have been individually identified by various observation systems and/or temporary tracking methods, providing unparalleled insights into their lives over both time and space. However, so far there is no comprehensive record of uniquely individually identified animals nor where their data and metadata are stored, for example photos, physiological and genetic samples, disease screens, information on social relationships. Databases currently do not offer unique identifiers for living, individual wild animals, similar to the permanent ID labelling for deceased museum specimens. To address this problem, we introduce two new concepts: (1) a globally unique animal ID (UAID) available to define uniquely and individually identified animals archived in any database, including metadata archived at the time of publication; and (2) the digital ‘home’ for UAIDs, the Movebank Life History Museum (MoMu), storing and linking metadata, media, communications and other files associated with animals individually identified in the wild. MoMu will ensure that metadata are available for future generations, allowing permanent linkages to information in other databases. MoMu allows researchers to collect and store photos, behavioural records, genome data and/or resightings of UAIDed animals, encompassing information not easily included in structured datasets supported by existing databases. Metadata is uploaded through the Animal Tracker app, the MoMu website, by email from registered users or through an Application Programming Interface (API) from any database. Initially, records can be stored in a temporary folder similar to a field drawer, as naturalists routinely do. Later, researchers and specialists can curate these materials for individual animals, manage the secure sharing of sensitive information and, where appropriate, publish individual life histories with DOIs. The storage of such synthesized lifetime stories of wild animals under a UAID (unique identifier or ‘animal passport’) will support basic science, conservation efforts and public participation.

Cushing's disease (CD) is characterized by distinct syndromic features, often accompanied by obesity and depression. However, considering its gradual onset of symptoms, it is usually associated with diagnostic delays. In rare instances, CD may lead to severe infections due to the observed immunosuppression in affected individuals. We present a rare case of an undiagnosed CD in a 20-year-old male with a medical history of depression and obesity, complicated by severe COVID-19 infection. He presented to the Emergency Room with respiratory distress, hypertensive crisis, and fever, ultimately receiving the diagnosis of SARS-CoV-2 pneumonia. The patient required mechanical ventilation and intensive care unit (ICU) admission due to severe acute respiratory distress syndrome (ARDS). During ICU care, he received remdesivir and dexamethasone, subsequently developing severe hyperglycemia and worsened hypertension, requiring insulin and multiple antihypertensive agents to manage metabolic disruption. Upon physical examination, classic signs of hypercortisolism were noted. Subsequent laboratory tests and pituitary magnetic resonance imaging confirmed the diagnosis of CD. The patient underwent surgical resection with significant improvements in body composition and metabolic parameters postoperatively. After surgery, remission of hypercortisolism was evident, accompanied by notable improvements in mood and overall health. This case underscores the importance of recognizing hypercortisolism in the context of metabolic, physical, and mood changes. Timely diagnosis of CD is crucial to mitigate complications such as severe opportunistic infections and their outcomes.

Abstract The Kunming-Montreal Global Biodiversity Framework (GBF) aims to halt global biodiversity loss. However, its implementation process will need strategic financing particularly to address the divide between the Global North and Global South. Highly migratory marine vertebrates (henceforth marine megafauna) connect distant ecosystems providing ecosystem services across jurisdictions with considerably different conservation interests and economic ability to pay for biodiversity protection. Although such migratory behaviour presents a specially challenging case for protection, because it provides a direct link between developed and less-developed countries it can provide a key to unlock the potential for financial support for implementing the GBF and shed light on a nature-based solution for how Official Development Assistance (ODA) could be deployed. Such ODA could ensure the global protection of these charismatic and threatened species, while contributing to the financing of the GBF. Our work emphasises the economic value of marine megafauna ecosystem services provided “on the move” across jurisdictions and highlights the economic value of conserving marine megafauna, our global heritage.

Abstract Fish age and growth data are crucial for understanding vital species’ traits and their populations. Boarfish is a pelagic species widely distributed in the Northeast Atlantic that is one of the most discarded non-commercial species on the Portuguese coast. Due to its potential valorisation as a new fishery in the Northeast Atlantic, boarfish has become object of interest in several published studies. However, since no age standard protocol has been implemented for boarfish, studies have used a variety of different otolith preparation techniques to estimate age, leading to contradicting and discrepant results. This research aims to consolidate biological insights into boarfish age and growth, lay the foundation for a standardized ageing protocol and serve as a benchmark study for the Portuguese west coast before commercial exploitation. Through the comparison of two otolith ageing methodologies, this study recommends using whole otoliths as the best method, revealing a maximum age of 15 years. The growth pattern estimated, indicated a biphasic growth pattern, with a faster initial growth rate that slows down at 2.4 years, the moment of change, when energy is allocated for sexual maturation. This finding was corroborated by a maturity ogive and analysis of fish size and otolith length relationship.

Abstract Background Although depression is the leading cause of disability worldwide, treatment coverage for the condition is inadequate. Supply-side barriers (e.g. shortage of specialist mental health professionals) and demand-side barriers (e.g. lack of awareness about depression) lead to limited availability of evidence-based interventions, poor demand for care, and low levels of adherence to care. The aim of our study is to examine if the addition of a community intervention delivered by community volunteers enhances the population-level impact of an evidence based psychosocial intervention (Healthy Activity Program [HAP]) in routine primary care by increasing demand for HAP and improving HAP adherence and effectiveness. Methods A hybrid type 2 effectiveness implementation cluster randomised controlled trial will be implemented in the state of Goa, India. Twenty-eight clusters of villages and their associated public sector health centres will be randomly allocated through restricted randomisation. Clusters will be randomly allocated to the ‘Community Model’ or ‘Facility Model’ arms. All clusters will offer the HAP and clusters in the ‘Community Model’ arm will additionally receive activities delivered by community volunteers (“Sangathis”) to increase awareness about depression and support demand for and adherence to HAP. The primary outcomes are Contact Coverage (Patient Health Questionnaire [PHQ-9] score > 4 as a proportion of those screened) and Effectiveness Coverage (mean PHQ-9 score amongst those who score ≥ 15 at baseline, i.e. those who have moderately severe to severe depression) at 3 months post-recruitment. Additional outcomes at 3 and 6 months will assess sustained effectiveness, remission, response to treatment, depression awareness, social support, treatment completion, and activation levels. Economic and disability outcomes will be assessed to estimate incremental cost-effectiveness ratios. Implementation will be evaluated through process data and qualitative data informed by the RE-AIM framework. A minimum of 79488 primary care attenders will be screened for the Contact Coverage outcome, and 588 individuals with PHQ-9 ≥ 15 will be recruited for the Effectiveness Coverage outcome. Discussion If effective, our community intervention will have relevance to India’s Ayushman Bharat universal healthcare programme which is scaling up care for depression in primary care, and also to other low- and middle- income countries. Trial registration Registered on ClincalTrials.gov ( NCT05890222 .) on 12/05/2023.

Abstract Background High rates of labour augmentation with oxytocin have been found in some low- and lower-middle-income countries, causing potential perinatal harm. It is critical to understand the reasons for this overuse. Aim was to explore factors that shape practices around using oxytocin for labour augmentation in a high-volume labour ward in Dar es Salaam, Tanzania. Methods Mixed-methods data collection was conducted from March 2021 to February 2022, including structured observations of 234 births, 220 h of unstructured labour ward observations and 13 individual in-depth interviews with birth attendants. Thematic network analysis and descriptive statistics were used to analyse data. We used a time-lens to understand practices of oxytocin for labour augmentation in time-pressured labour wards. Results Birth attendants constantly had to prioritise certain care practices over others in response to time pressure. This led to overuse of oxytocin for augmentation to ensure faster labour progression and decongestion of the, often overburdened, ward. Simultaneously, birth attendants had little time to monitor foetal and maternal condition. Surprisingly, while oxytocin was used in 146 out of 234 (62.4%) structured labour observations, only 9/234 (4.2%) women had active labour lasting more than 12 h. Correspondingly, 21/48 (43.8%) women who were augmented with oxytocin in the first stage of labour had uncomplicated labour progression at the start of augmentation. While the partograph was often not used for decision-making, timing of starting oxytocin often correlated with natural cycles of ward-rounds and shift-turnovers instead of individual women’s labour progression. This resulted in co-existence of ‘too early’ and ‘too late’ use of oxytocin. Liberal use of oxytocin for labour augmentation was facilitated by an underlying fear of prolonged labour and low alertness of oxytocin-related risks. Conclusions Time scarcity in the labour ward often made birth attendants deviate from clinical guidelines for labour augmentation with oxytocin. Efforts to navigate time pressure resulted in too many women with uncomplicated labour progression receiving oxytocin with little monitoring of labour. Fear of prolonged labour and low alertness to oxytocin-mediated risks were crucial drivers. These findings call for research into safety and benefits of oxytocin in low-resource settings and interventions to address congestion in labour wards to prevent using oxytocin as a time-management tool.

Scholarship on feedback format tends to demonstrate that students prefer video feedback; however, the characteristics of study participants are often absent. This study builds on the scholarship of feedback practice mediated by technology and feedback literacy in intercultural contexts. A mixed methods approach examined international postgraduate students' experience of, preferences for and attitudes towards three feedback formats: text, audio and video. Eighty-four participants in an Australian university completed a survey, and twelve participated in semi-structured phone interviews. The participants were mainly women from India, aged between 25 and 34 years old and declared English as a second language. Participants scored their experience with video, audio and written feedback. Written feedback was ranked first, followed by video and audio feedback. Participants reported that written feedback allows students to easily locate areas that need improvement. The role of the disciplinary traditions and respondents' educational background is discussed to make sense of the results.

OBJECTIVE: The goal of this study was to examine whether neural sensitivity to negative peer evaluation conveys risk for depression among youth with a history of anxiety. We hypothesized that brain activation in regions that process affective salience in response to rejection, relative to acceptance, from virtual peers would predict depressive symptoms 1 year later and would be associated with ecological momentary assessment (EMA) reports of peer connectedness. METHOD: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA. RESULTS: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC; β = .39, p = .010) activation to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly negatively correlated with EMA reports of connectedness with peers in daily life (r = - .71, p