The interplay between birth weight and obesity in determining childhood and adolescent cardiometabolic risk.

BACKGROUND: Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations. METHODS: We used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels. FINDINGS: BW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (ßadj [95% CI per SD] for obesity: -0.12 [-0.15, -0.08]; normal weight: -0.04 [-0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: -0.11 [-0.14, -0.08]; normal weight: -0.02 [-0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: -0.12 [-0.16, -0.08]; normal weight: -0.06 [-0.11, -0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05). INTERPRETATION: We identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD. FUNDING: Novo Nordisk Foundation (NNF15OC0016544, NNF0064142 to T.H., NNF15OC0016692 to T.H. and A.K., NNF18CC0033668 to S.E.S, NNF18SA0034956 to C.E.F., NNF20SA0067242 to DCA, NNF18CC0034900 to NNF CBMR), The Innovation Fund Denmark (0603-00484B to T.H.), The Danish Cardiovascular Academy (DCA) and the Danish Heart Foundation (HF) (PhD2021007-DCA to P.K.R, 18-R125-A8447-22088 (HF) and 21-R149-A10071-22193 (HF) to M.A.V.L., PhD2023009-HF to L.A.H), EU Horizon (668031, 847989, 825694, 964590 to A.K.), Innovative Health Initiative (101132901 for A.K.), A.P. Møller Foundation (19-L-0366 to T.H.), The Danish National Research Foundation, Steno Diabetes Center Sjælland, and The Region Zealand and Southern Denmark Health Scientific Research Foundation.

Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases.

The rising prevalence of liver diseases related to obesity and excessive use of alcohol is fuelling an increasing demand for accurate biomarkers aimed at community screening, diagnosis of steatohepatitis and significant fibrosis, monitoring, prognostication and prediction of treatment efficacy. Breakthroughs in omics methodologies and the power of bioinformatics have created an excellent opportunity to apply technological advances to clinical needs, for instance in the development of precision biomarkers for personalised medicine. Via omics technologies, biological processes from the genes to circulating protein, as well as the microbiome - including bacteria, viruses and fungi, can be investigated on an axis. However, there are important barriers to omics-based biomarker discovery and validation, including the use of semi-quantitative measurements from untargeted platforms, which may exhibit high analytical, inter- and intra-individual variance. Standardising methods and the need to validate them across diverse populations presents a challenge, partly due to disease complexity and the dynamic nature of biomarker expression at different disease stages. Lack of validity causes lost opportunities when studies fail to provide the knowledge needed for regulatory approvals, all of which contributes to a delayed translation of these discoveries into clinical practice. While no omics-based biomarkers have matured to clinical implementation, the extent of data generated has enabled the hypothesis-free discovery of a plethora of candidate biomarkers that warrant further validation. To explore the many opportunities of omics technologies, hepatologists need detailed knowledge of commonalities and differences between the various omics layers, and both the barriers to and advantages of these approaches.

Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

SARS-CoV-2 Specific Nanobodies Neutralize Different Variants of Concern and Reduce Virus Load in the Brain of h-ACE2 Transgenic Mice.

Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis.

Altered glucagon and GLP-1 responses to oral glucose in children and adolescents with obesity and insulin resistance.

CONTEXT: Pediatric obesity is characterized by insulin resistance, yet it remains unclear whether insulin resistance contributes to abnormalities in glucagon and incretin secretion. OBJECTIVE: To examine whether fasting and stimulated glucagon, GLP-1, and GIP concentrations differ between children and adolescents with obesity and insulin resistance (OIR), obesity and normal insulin sensitivity (OIS), and controls with normal weight (NW). METHODS: 80 (34 boys) children and adolescents, aged 7-17 years with OIR (n=22), OIS (n=22), and NW (n=36) underwent an oral glucose tolerance test with measurements of serum insulin, plasma glucose, glucagon, total GLP-1, and total GIP. Homeostatic model assessment of insulin resistance (HOMA-IR), single point insulin sensitivity estimator (SPISE), Matsuda index, insulinogenic index (IGI), and oral disposition index (ODI) were calculated. RESULTS: Fasting concentrations of glucagon and GLP-1 were higher in the OIR-group, with no significant differences for GIP. The OIR-group had higher glucagon total area under the curve (tAUC0-120) and lower GLP-1 incremental AUC (iAUC0-120), with no significant differences for GIP iAUC0-120. Higher fasting glucagon was associated with higher HOMA-IR, lower Matsuda index, lower SPISE, higher IGI, and higher plasma alanine transaminase, whereas higher fasting GLP-1 was associated with higher HOMA-IR, lower Matsuda index, and lower ODI. Higher glucagon tAUC0-120 was associated lower SPISE and lower Matsuda index, whereas lower GLP-1 iAUC0-120 was associated with a higher HOMA-IR, lower Matsuda index, and lower ODI. CONCLUSIONS: The OIR-group had elevated fasting concentrations of glucagon and GLP-1, and higher glucagon, but lower GLP-1 responses during an OGTT compared to the OIS- and NW-groups. In contrast, the OIS-group had similar hormone responses to the NW-group.

Trophic morphology and diet of the endangered fish Tlaloc hildebrandi (Cyprinodontiformes: Profundulidae) / Morfología trófica y dieta de Tlaloc hildebrandi (Cyprinodontiformes: Profundulidae), especie amenazada de extinción

Abstract Introduction: Tlaloc hildebrandi is a freshwater killifish, endemic to Southern Mexico and under threat of extinction; the knowledge of the trophic morphology and diet is needed by conservation managers. Objective: To analyse and describe the anatomy of the visceral skeleton, visceral musculature, digestive tract and its adjoining glands of T. hildebrandi; as well as its diet. Methods: We performed the trophic anatomy on 20 adult specimens of both sexes, through manual dissection; as well as gut content analysis in 60 individuals to describe the diet. Results: As notable characters of the visceral skeleton of T. hildebrandi we found the posterior notch of the premaxillary, the presence of the "coronoid cartilage", the tricuspid shape of the gill rakers of the first branchial arch, and the presence of the coronomeckelian bone; some outstanding characters of the visceral musculature are the origin of the retractor dorsalis muscle from the first four vertebral centra, and the division of the pharyngoclavicularis externus muscle into two sections. The notable characters of the digestive tube are the absence of stomach and pyloric caeca, and the presence of the "intestinal valve". Insects (IVI = 66.6 %) and ostracods (13 % IVI) were the dominant prey items of the Tlaloc hildebrandi diet; larvae and adults of the family Chironomidae were the most dominant insects in the diet (53 % IVI). Conclusions: The organization of the digestive system of T. hildebrandi corresponds to the general morphologic pattern of the Cyprinodontiformes; however, we register as new information for these fish, the presence of the "coronoid cartilage" and the "intestinal valve". The structures of the trophic morphology and the components of the diet, confirms us that T. hildebrandi is a carnivorous-insectivorous fish.

Resumen Introducción: Tlaloc hildebrandi es un killi de agua dulce, endémico del sur de México y bajo amenaza de extinción; el conocimiento de la morfología trófica y la dieta son necesarios para los administradores de la conservación. Objetivo: Analizar y describir la anatomía del esqueleto visceral, la musculatura visceral, el tracto digestivo y las glándulas adyacentes de T. hildebrandi; así como los componentes de su dieta. Métodos: Mediante la técnica del descarnado manual, realizamos la descripción de la anatomía trófica en 20 especímenes adultos de ambos sexos, y el análisis del contenido estomacal en 60 individuos para describir la dieta. Resultados: Como caracteres sobresalientes del esqueleto visceral de T. hildebrandi está la escotadura posterior del premaxilar, la presencia del "cartílago coronoides", la forma tricúspide de las branquiespinas del primer arco branquial y la presencia del hueso coronomeckeliano; como caracteres de la musculatura visceral sobresalen el origen del músculo retractor dorsalis de los cuatro primeros centros vertebrales, y la división del músculo pharyngoclavicularis externus en dos secciones. Los caracteres notables del tubo digestivo son la ausencia de estómago y de ciegos pilóricos y la presencia de la "válvula intestinal". Los insectos (IVI = 66.6 %) y ostrácodos (13 % IVI) fueron los componentes dominantes de la dieta de T. hildebrandi; particularmente las larvas y adultos de la familia Chironomidae fueron los insectos más abundantes en la dieta (53 % IVI). Conclusiones: La organización del sistema digestivo de T. hildebrandi corresponde al patrón morfológico general de los Cyprinodontiformes, sin embargo, se registra como nueva información para estos peces, la presencia del cartílago coronoides y la válvula intestinal. Las estructuras de la morfología trófica y los componentes de la dieta nos confirman que T. hildebrandi es un pez carnívoro-insectívoro.

Disentangling the intersection of inequities with health and malaria exposure: key lessons from rural communities in Northern Borneo.

BACKGROUND: The increasing incidence of Plasmodium knowlesi malaria poses a significant challenge to efforts to eliminate malaria from Malaysia. Macaque reservoirs, outdoors-biting mosquitoes, human activities, and agricultural work are key factors associated with the transmission of this zoonotic pathogen. However, gaps in knowledge regarding reasons that drive malaria persistence in rural Kudat, Sabah, Northern Borneo remain. This study was conducted to address this knowledge gap, to better understand the complexities of these entangled problems, and to initiate discussion regarding new countermeasures to address them. This study aims to highlight rural community members' perspectives regarding inequities to health relating to P. knowlesi malaria exposure. METHODS: From January to October 2022, a study using qualitative methods was conducted in four rural villages in Kudat district of Sabah, Malaysia. A total of nine in-depth interviews were conducted with community and faith leaders, after the completion of twelve focus group discussions with 26 photovoice participants. The interviews were conducted using the Sabah Malay dialect, audio-recorded, transcribed, and translated into English. The research team led the discussion and analysis, which was approved by participants through member checking at the community level. RESULTS: Participants identified disparity in health as a key issue affecting their health and livelihoods. Injustice in the social environment was also identified as a significant challenge, including the importance of listening to the voices of affected communities in disentangling the social and economic phenomena that can impact malaria control. Specific concerns included inadequate access to health-related resources and degradation of the environment. Participants recommended improving access to water and other necessities, increasing the availability of malaria control commodities in healthcare facilities, and developing sustainable programs to reduce socioeconomic disparities. CONCLUSION: Inequities to health emerged as a key concern for malaria control in rural Kudat, Sabah. A locally targeted malaria programme cantered on improving the social and economic disparities associated with health outcomes, could be a potential strategy for malaria prevention in such areas. Community-level perspectives gathered from this study can be used as a foundation for future discussions and dialogues among policymakers and community members for achieving greater transparency, improving social equity, and interoperability in addressing P. knowlesi malaria control.

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

Exploring barriers to and facilitators of malaria prevention practices: a photovoice study with rural communities at risk to Plasmodium knowlesi malaria in Sabah, Malaysia.

BACKGROUND: The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human settlements. This study aims to explore the barriers and facilitators related to prevention of mosquito bites among rural communities living in Sabah, Malaysia using the participatory visual method, photovoice. METHODS: From January through June 2022, 26 participants were recruited from four villages in Kudat, Sabah, using purposive sampling. Participants were male and female villagers, aged > 18 years old. After photovoice training in the villages, participants documented facilitators of and barriers related to avoiding mosquito bites using their own smartphone cameras, and provided narratives for their photos. Twelve Focus Group Discussions (FGDs) sessions in three rounds were held to share and discuss the photos, and to address challenges to the avoidance of mosquito bites. All discussions were conducted in the Sabah Malay dialect, and were video and audio recorded, transcribed, and analyzed using reflexive thematic analysis. The Ideation Model, a meta-theoretical model of behaviour change, underpinned this study. RESULTS: The most common types of barriers identified by participants included (I) intrapersonal factors such as low perceived threat of malaria, (II) livelihood and lifestyle activities consisting of the local economy and socio-cultural activities, and (III) physical and social environment. The facilitators were categorized into (I) intrapersonal reasons, including having the opportunity to stay indoors, especially women who are housewives, (II) social support by the households, neaighbours and healthcare workers, and (III) support from healthcare services and malaria awareness program. Participants emphasized the importance of stakeholder's support in implementing feasible and affordable approaches to P. knowlesi malaria control. CONCLUSION: Results provided insights regarding the challenges to preventing P. knowlesi malaria in rural Kudat, Sabah. The participation of communities in research was valuable in expanding knowledge of local challenges and highlighting possible ways to overcome barriers. These findings may be used to improve strategies for zoonotic malaria control, which is critical for advancing social change and minimizing health disparities in malaria prevention.

Seeing malaria through the eyes of affected communities: using photovoice to document local knowledge on zoonotic malaria causation and prevention practices among rural communities exposed to Plasmodium knowlesi malaria in Northern Borneo Island.

BACKGROUND: Many rural communities in Malaysian Borneo and Southeast Asia are at risk of Plasmodium knowlesi malaria. Multiple factors contribute to infection, however, a deep understanding of illness causation and prevention practices among at-risk communities remains limited. This study aims to document local knowledge on malaria causation and preventive practices of rural communities in Sabah, Malaysia, using photovoice-a participatory research method. METHODS: From January to June 2022, a photovoice study was conducted with rural communities in Matunggong subdistrict, Malaysia, to explore their experiences with and local knowledge of non-human primate malaria and prevention practices. The study included (1) an introductory phase in which participants were introduced to the photovoice method; (2) a documentation phase in which participants captured and narrated photos from their communities; (3) a discussion phase in which participants discussed photos and relevant topics through a series of three focus group discussions (FGDs) per village; and (4) a dissemination phase where selected photos were shared with key stakeholders through a photo exhibition. A purposively selected sample of 26 participants (adults > 18 years old, male, and female) from four villages participated in all phases of the study. The study activities were conducted in Sabah Malay dialect. Participants and the research team contributed to data review and analyses. RESULTS: Rural communities in Sabah, Malaysia possess local knowledge that attributes non-human primate malaria to natural factors related to the presence of mosquitoes that bite humans and which carry "kuman-malaria" or malaria parasite. Participants revealed various preventive practises ranging from traditional practises, including burning dried leaves and using plants that produce foul odours, to non-traditional approaches such as aerosols and mosquito repellents. By engaging with researchers and policymakers, the participants or termed as co-researchers in this study, showcased their ability to learn and appreciate new knowledge and perspectives and valued the opportunity to share their voices with policymakers. The study successfully fostered a balance of power dynamics between the co-researchers, research team members and policymakers. CONCLUSION: There were no misconceptions about malaria causation among study participants. The insights from study participants are relevant because of their living experience with the non-human malaria. It is critical to incorporate rural community perspectives in designing locally effective and feasible malaria interventions in rural Sabah, Malaysia. Future research can consider adapting the photovoice methodology for further research with the community toward building locally tailored-malaria strategies.

Racial/ethnic and Gender Inequalities in Third Grade Children's Self-perceived STEM Competencies.

Studies have sought to understand the underrepresentation of women and racial/ethnic minority groups in STEM, but less attention has been paid to primary school students. Using data from a nationally-representative sample, this study identified factors influencing US third-grade children's self-perceived competencies in math and science, while controlling for their actual abilities. Results indicate that girls had degraded self-perceptions of their math competencies compared to boys, but similar self-rated science competencies. Black students exhibited buoyed self-perceived math competencies, while Hispanic and indigenous students underestimated their science competencies. Students who reported being satisfied with parental attention, friends, and neighborhood had higher self-perceived competencies in both math and science.

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland.

Background: The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population. Methods: Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact. Findings: We identified a novel variant in the known MODY gene HNF1A with an allele frequency of 1.9% in the Greenlandic Inuit and absent elsewhere. Functional assays indicate that it prevents normal splicing of the gene. The variant caused lower 30-min insulin (ß = -232 pmol/L, ßSD = -0.695, P = 4.43 × 10-4) and higher 30-min glucose (ß = 1.20 mmol/L, ßSD = 0.441, P = 0.0271) during an oral glucose tolerance test. Furthermore, the variant was associated with type 2 diabetes (OR 4.35, P = 7.24 × 10-6) and HbA1c (ß = 0.113 HbA1c%, ßSD = 0.205, P = 7.84 × 10-3). The variant explained 2.5% of diabetes variance in Greenland. Interpretation: The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive TBC1D4 variant, we show that close to 1 in 5 cases of diabetes (18%) in Greenland are associated with high-impact genetic variants compared to 1-3% in large populations. Funding: Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.

Estenosis laringotraqueal posintubación por COVID-19 en dos hospitales / Post-intubation laryngotracheal stenosis due to COVID 19 in two hospitals

Introducción: la infección por COVID-19 ha dejado más 400 millones de personas infectadas hasta la fecha, y entre un 10 %-15 % requiere intubación orotraqueal. Esto ha desencadenado una ola de secuelas en la vía aérea a largo plazo, que han aumentado la morbimortalidad posinfecciosa. El objetivo de este trabajo fue describir las características demográficas, clínicas y los posibles factores de riesgo de los pacientes con estenosis laringotraqueal (ELT) posintubación por COVID-19 en el Hospital Universitario Clínica San Rafael y el Hospital Militar Central en Bogotá, Colombia. Materiales y métodos: estudio observacional descriptivo de serie de casos retrospectiva que recolectó datos sociodemográficos, comorbilidades, tiempos de intubación, características de estenosis, resultados de estudios endoscópicos, manejos ofrecidos y resultados. Resultados: se registraron 25 pacientes, 15 hombres (60 %) y 10 mujeres (40 %), con tiempos de intubación promedio de 15,7 días. Los subsitios más comprometidos fueron la tráquea (68,2 %) y la subglotis-tráquea (22,7%). La mayoría de pacientes requirió más de una intervención. La dilatación con balón y traqueostomía fueron los procedimientos más realizados. Conclusiones: la ELT es una complicación de la intubación orotraqueal que, asociada con la vasculitis, inflamación y necrosis coagulativa de la vía aérea, ha aumentado en los casos de infección grave por COVID-19

Introduction: COVID-19 infection has left more than 400 million people infected to date, and between 10%-15% require orotracheal intubation. This has triggered a wave of long-term airway sequelae, which have increased post-infectious morbidity and mortality. Objectives: To describe the demographic and clinical characteristics and possible risk factors of patients with laryngotracheal stenosis (LTE) post-intuba-tion by COVID19 at the Hospital Universitario Clínica San Rafael and the Hospital Militar Central in Bogotá, Colombia. Methods: Descriptive observational study of retrospective case series, collecting socio-demographic data, comorbidities, intu-bation times, stenosis characteristics, results of endoscopic studies, management offered and results. Results: 25 patients were collected, 15 men (60%) and 10 wo-men (40%), with average intubation times of 15.7 days. The most compromised subsites were the trachea (68.2%) and subglottis-trachea (22.7%). Most patients re-quired more than one intervention. Balloon dilation and tracheostomy were the most performed procedures. Conclusions: LTE is a complication of orotracheal intuba-tion, associated with vasculitis, inflammation and coagulative necrosis of the airway, has increased in cases in severe COVID-19 infection.

Generating Trust in Participatory Research on Plasmodium knowlesi Malaria: A Study with Rural Community Gatekeepers during the COVID-19 Pandemic.

BACKGROUND: Plasmodium knowlesi malaria is a zoonotic infection that affects rural communities in South East Asia. Although the epidemiology of the disease has been extensively researched, the voices of individuals within affected communities often go unheard. Here, we describe a study that explores the importance of gatekeepers in conducting research among rural communities, their perspectives on the challenges encountered when attempting to avoid malaria infection, and their views on participatory research. METHODS: Between 1 November 2021 and 28 February 2022, we conducted a study in Kudat district, Sabah, using a multi-method design. All participants consented to the study, which included health care workers (HCWs) (n = 5), community leaders (n = 8), and faith leaders (n = 1). We conducted interviews, transect walks, and observations with gatekeepers to ensure data trustworthiness. All interviews were conducted in the Sabah Malay dialect. The sessions were audio- and video-recorded, transcribed into English and analyzed using thematic analysis. RESULTS: Between 2017 and 2021, the number of cases of P. knowlesi malaria detected in humans ranged from 35 to 87 in villages under the care of the Lotong primary health care clinic. The challenges in controlling malaria include social norms, lifestyles, socioeconomic factors, environmental factors, and limitations of basic resources. Critical discussions regarding participation with the gatekeepers identified that face-to-face interviews were preferable to online discussions, and influenced willingness to participate in future research. CONCLUSION: This study was conducted among village gatekeepers during the COVID-19 pandemic and generated information to drive methodological changes, opening up new ideas by sharing perspectives on challenges in P. knowlesi malaria control among vulnerable communities. The study generated trust in the community and expanded knowledge regarding participation that is critical for future community-based studies.

The use of leg elevation in the treatment of chronic peripheral oedema.

Chronic peripheral oedema is a common long-term condition, with conflicting evidence on how it is best managed. It is crucial to establish the cause of the oedema to decide on the most appropriate intervention for its management. If the oedema is not managed, it can lead to unwanted complications for the service user. The District Nurse (DN) is pivotal in the management of patients with long-term conditions, both directly and indirectly. It is important that a multi-disciplinary approach is used, although nurses are now more autonomous due to advances in practice. The present study focuses on leg elevation as a form of intervention in the treatment of chronic peripheral oedema. As with any intervention, there are some risks with leg elevation that must be considered. This should be disseminated and monitored effectively.

Disseminated juvenile xanthogranulomas with ocular involvement: A case report and literature review.

Cutaneous juvenile xanthogranuloma is an uncommon disorder usually arising during infancy. Systemic involvement of juvenile xanthogranuloma remains rare, and there are no published guidelines to date on screening extracutaneous manifestations in these patients. Ocular involvement is the most common extracutaneous manifestation of juvenile xanthogranuloma. We present the case of an infant with disseminated juvenile xanthogranulomas and associated ocular involvement and present a review of literature, focusing on identifying risk factors for ocular and systemic involvement in disseminated cases.

Successful pilot application of multi-attribute utility analysis concepts in evaluating academic-clinical partnerships in the United States: a case report.

Strong partnerships between academic health professions programs and clinical practice settings, termed academic-clinical partnerships, are essential in providing quality clinical training experiences. However, the literature does not operationalize a model by which an academic program may identify priority attributes and evaluate its partnerships. This study aimed to develop a values-based academic-clinical partnership evaluation approach, rooted in methodologies from the field of evaluation and implemented in the context of an academic Doctor of Physical Therapy clinical education program. The authors developed a semi-quantitative evaluation approach incorporating concepts from multi-attribute utility analysis (MAUA) that enabled consistent, values-based partnership evaluation. Data-informed actions led to improved overall partnership effectiveness. Pilot outcomes support the feasibility and desirability of moving toward MAUA as a potential methodological framework. Further research may lead to the development of a standardized process for any academic health profession program to perform a values-based evaluation of their academic-clinical partnerships to guide decision-making.

Lifestyle school-based intervention to increase the proportion of adolescents free of components of the metabolic syndrome in an andean region of Peru. / Intervención educativa basada en estilos de vida para incrementar la proporción de adolescentes libres de componentes del síndrome metabólico en una región altoandina del Perú.

OBJECTIVE.: To estimate the impact of a school-based nutritional and healthy lifestyle intervention to increase the proportions of adolescents free of components of the metabolic syndrome. MATERIALS AND METHODS.: We conducted a pre-experimental study in a representative sample of adolescents from two schools in a high Andean district of Peru (Cajamarca city); 388 students completed the intervention and the baseline and post-intervention measurement. The intervention had nine thematic modules; each module was developed in an educational session of 45 minutes every two weeks. We used the National Cholesterol Education Program Expert Panel and Adult Treatment Panel III criteria for metabolic syndrome. We used paired proportions comparison (McNemar test) to determine the impact of the intervention. RESULTS.: At baseline, 20.4% (95% CI: 16.2 to 24.5) students had no metabolic syndrome components, post-intervention this proportion increased to 32,5% (95% CI: 27.7 to 37.3), the difference in proportions was 12.1% (95% CI: 7.5 to 16.8; p<0.001). The prevalence of metabolic syndrome was 4.6% (95% CI: 2.4 to 6.9) at baseline, while post-intervention was 2.3% (95%CI: 0.7 to 3.9). During the analysis of components, the greatest reduction was observed in the proportion of hypertriglyceridemia (difference in proportions: 21.9%, 95%CI: 16.9 to 26.9, p <0.001); we also found a significant reduction in arterial hypertension (difference in proportions: 3.1%, 95% CI: 0.6 to 5.6, p=0.025). In the other components, there were no significant differences. CONCLUSIONS.: The school-based intervention increased in 59.3% the proportion of students free of any component of the metabolic syndrome.

OBJETIVO.: Estimar el efecto de una intervención educativa basada en nutrición y estilos de vida saludables para incrementar la proporción de adolescentes libres de componentes del síndrome metabólico. MATERIALES Y MÉTODOS.: Se realizó un estudio preexperimental en una muestra representativa de adolescentes de dos escuelas de un distrito altoandino del Perú (ciudad de Cajamarca); 388 estudiantes completaron la intervención, así como la medición basal y la posintervención. La intervención tuvo nueve ejes temáticos, cada uno fue desarrollado en una sesión educativa de 45 min cada dos semanas. Se usó los criterios del National Cholesterol Education Program Expert Panel and Adult Treatment Panel III para el síndrome metabólico. Se realizó la comparación de proporciones pareadas (prueba de McNemar) para determinar el impacto de la intervención. RESULTADOS.: En la medición basal, el 20,4% (IC95%: 16,2 a 24,5) no tenía componentes de SM, posintervención dicha proporción se incrementó a 32,5% (IC95%: 27,7 a 37,3), la diferencia de proporciones fue 12,1% (IC95%: 7,5 a 16,8; p<0,001). La prevalencia de síndrome metabólico fue 4,6% (IC95%: 2,4 a 6,9) basalmente; posintervención fue 2,3% (IC95%: 0,7 a 3,9). La diferencia de proporciones fue 2,3%, (IC95%: 0,3 a 3,2; p=0,022). Entre los componentes, la mayor reducción fue en la proporción de hipertrigliceridemia (diferencia de proporciones: 21,9%, IC95%: 16,9 a 26,9; p<0,001), también se observó una reducción significativa de la hipertensión arterial (diferencia de proporciones: 3,1%, IC95%: 0,6 a 5,6; p=0,025). En los demás componentes no hubo diferencias significativas. CONCLUSIONES.: La intervención educativa incrementó en un 59,3% la proporción de estudiantes libres de algún componente del síndrome metabólico.

Intervención educativa basada en estilos de vida para incrementar la proporción de adolescentes libres de componentes del síndrome metabólico en una región altoandina del Perú / Lifestyle school-based intervention to increase the proportion of adolescents free of components of the metabolic syndrome in an andean region of Peru

RESUMEN Objetivo. Estimar el efecto de una intervención educativa basada en nutrición y estilos de vida saludables para incrementar la proporción de adolescentes libres de componentes del síndrome metabólico. Materiales y métodos. Se realizó un estudio preexperimental en una muestra representativa de adolescentes de dos escuelas de un distrito altoandino del Perú (ciudad de Cajamarca); 388 estudiantes completaron la intervención, así como la medición basal y la posintervención. La intervención tuvo nueve ejes temáticos, cada uno fue desarrollado en una sesión educativa de 45 min cada dos semanas. Se usó los criterios del National Cholesterol Education Program Expert Panel and Adult Treatment Panel III para el síndrome metabólico. Se realizó la comparación de proporciones pareadas (prueba de McNemar) para determinar el impacto de la intervención. Resultados. En la medición basal, el 20,4% (IC95%: 16,2 a 24,5) no tenía componentes de SM, posintervención dicha proporción se incrementó a 32,5% (IC95%: 27,7 a 37,3), la diferencia de proporciones fue 12,1% (IC95%: 7,5 a 16,8; p<0,001). La prevalencia de síndrome metabólico fue 4,6% (IC95%: 2,4 a 6,9) basalmente; posintervención fue 2,3% (IC95%: 0,7 a 3,9). La diferencia de proporciones fue 2,3%, (IC95%: 0,3 a 3,2; p=0,022). Entre los componentes, la mayor reducción fue en la proporción de hipertrigliceridemia (diferencia de proporciones: 21,9%, IC95%: 16,9 a 26,9; p<0,001), también se observó una reducción significativa de la hipertensión arterial (diferencia de proporciones: 3,1%, IC95%: 0,6 a 5,6; p=0,025). En los demás componentes no hubo diferencias significativas. Conclusiones. La intervención educativa incrementó en un 59,3% la proporción de estudiantes libres de algún componente del síndrome metabólico.

ABSTRACT Objective. To estimate the impact of a school-based nutritional and healthy lifestyle intervention to increase the proportions of adolescents free of components of the metabolic syndrome. Materials and methods. We conducted a pre-experimental study in a representative sample of adolescents from two schools in a high Andean district of Peru (Cajamarca city); 388 students completed the intervention and the baseline and post-intervention measurement. The intervention had nine thematic modules; each module was developed in an educational session of 45 minutes every two weeks. We used the National Cholesterol Education Program Expert Panel and Adult Treatment Panel III criteria for metabolic syndrome. We used paired proportions comparison (McNemar test) to determine the impact of the intervention. Results. At baseline, 20.4% (95% CI: 16.2 to 24.5) students had no metabolic syndrome components, post-intervention this proportion increased to 32,5% (95% CI: 27.7 to 37.3), the difference in proportions was 12.1% (95% CI: 7.5 to 16.8; p<0.001). The prevalence of metabolic syndrome was 4.6% (95% CI: 2.4 to 6.9) at baseline, while post-intervention was 2.3% (95%CI: 0.7 to 3.9). During the analysis of components, the greatest reduction was observed in the proportion of hypertriglyceridemia (difference in proportions: 21.9%, 95%CI: 16.9 to 26.9, p <0.001); we also found a significant reduction in arterial hypertension (difference in proportions: 3.1%, 95% CI: 0.6 to 5.6, p=0.025). In the other components, there were no significant differences. Conclusions. The school-based intervention increased in 59.3% the proportion of students free of any component of the metabolic syndrome.

Development, implementation and evaluation of an optimized cross-sectoral rehabilitation program after acute hip fracture surgery: A mixed-methods study.

Fall-related hip fracture (HF) is a frequent trauma in Scandinavia with a yearly incidence of 8,000 among ≥65-year-old citizens in Denmark. The rising incidence and global predictions are alarming since a HF is a major, and potentially fatal, trauma to the citizen, requiring acute surgery, a multimodal approach and post-operative crosssectoral rehabilitation. However, continuity of the rehabilitation program is frequently interrupted in the transition between sectors, compromising optimal recovery of frail citizens. Thus, there is a need to develop and implement optimized cross-sectoral rehabilitation after HF. The purpose of this explorative study was to develop, implement and evaluate an optimized cross-sectoral rehabilitation program (OCRP) after HF surgery using validated theoretical frameworks. OCRP was developed, implemented and evaluated in one municipality using a pragmatic user-centered approach, quantitative and qualitative data collection and theoretical frameworks including the Behavior Change Wheel (BCW) and RE-AIM. Results of OCRP showed optimized rehabilitation based on motivated health professionals, high patient satisfaction and tendencies of improved levels of physical function. No re-referrals to rehabilitation were reported after OCRP. The BCW, RE-AIM and user-centered approach to program development, implementation and evaluation are useful to apply in program development and evaluation processes across sectors, professions, and medical specialties.