Characterisation of the Novel HLA-DRB1*16:79 Allele Using Short- and Long-Read Sequencing Technologies.

The novel HLA-DRB1*16:79 allele, first described in an individual from Brazil.

Prospective Variation of Cytokine Trends during COVID-19: A Progressive Approach from Disease Onset until Outcome.

COVID-19 is characterized by pronounced hypercytokinemia. The cytokine switch, marked by an imbalance between pro-inflammatory and anti-inflammatory cytokines, emerged as a focal point of investigation throughout the COVID-19 pandemic. However, the kinetics and temporal dynamics of cytokine release remain contradictory, making the development of new therapeutics difficult, especially in severe cases. This study collected serum samples from SARS-CoV-2 infected patients at 72 h intervals and monitored them for various cytokines at each timepoint until hospital discharge or death. Cytokine levels were analyzed based on time since symptom onset and patient outcomes. All cytokines studied prospectively were strong predictors of mortality, particularly IL-4 (AUC = 0.98) and IL-1ß (AUC = 0.96). First-timepoint evaluations showed elevated cytokine levels in the mortality group (p < 0.001). Interestingly, IFN-γ levels decreased over time in the death group but increased in the survival group. Patients who died exhibited sustained levels of IL-1ß and IL-4 and increased IL-6 levels over time. These findings suggest cytokine elevation is crucial in predicting COVID-19 mortality. The dynamic interplay between IFN-γ and IL-4 highlights the balance between Th1/Th2 immune responses and underscores IFN-γ as a powerful indicator of immune dysregulation throughout the infection.

Characterisation of the novel HLA-C*01:273 allele, first identified in a Brazilian individual.

The novel HLA-C*01:273 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-A*33:01:21 allele, first identified in a Brazilian individual.

The novel HLA-A*33:01:21 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-B*18:243 allele using short- and long-read sequencing technologies.

The novel HLA-B*18:243 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-DRB1*03:215 allele using short- and long-read sequencing technologies.

The novel HLA-DRB1*03:215 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-C*15:274 allele using short and long-read sequencing technologies.

The novel HLA-C*15:274 allele, first described in a potential bone marrow donor from Brazil.

Characterisation of the novel HLA-C*08:275 allele, first identified in a Brazilian individual.

The novel HLA-C*08:275 allele, first described in a potential bone marrow donor from Brazil.

Reducing Physical Restraint Use in the Medical Behavioral Unit.

OBJECTIVES: Children with behavioral health conditions often experience agitation when admitted to children's hospitals. Physical restraint should be used only as a last resort for patient agitation because it endangers the physical and psychological safety of patients and employees. At the medical behavioral unit (MBU) in our children's hospital, we aimed to decrease the weekly rate of physical restraint events per 100 MBU patient-days, independent of patient race, ethnicity, or language, from a baseline mean of 14.0 to <10 within 12 months. METHODS: Using quality improvement methodology, a multidisciplinary team designed, tested, and implemented interventions including a series of daily deescalation huddles led by a charge behavioral health clinician that facilitated individualized planning for MBU patients with the highest behavioral acuity. We tracked the weekly number of physical restraint events per 100 MBU patient-days as a primary outcome measure, weekly physical restraint event duration as a secondary outcome measure, and MBU employee injuries as a balancing measure. RESULTS: Our cohort included 527 consecutive patients hospitalized in the MBU between January 2021 and January 2023. Our 2021 baseline mean of 14.0 weekly physical restraint events per 100 MBU patient-days decreased to 10.0 during our 2022 intervention period from January through July and 4.1 in August, which was sustained through December. Weekly physical restraint event duration also decreased from 112 to 67 minutes without a change in employee injuries. CONCLUSIONS: Multidisciplinary huddles that facilitated daily deescalation planning safely reduced the frequency and duration of physical restraint events in the MBU.

Diversity and distribution of iron-oxidising bacteria belonging to Gallionellaceae in different sites of a hydroelectric power plant.

Iron (Fe) is the fourth most abundant element on the planet, and iron-oxidising bacteria (FeOB) play an important role in the biogeochemical cycle of this metal in nature. FeOB stands out as Fe oxidisers in microaerophilic environments, and new members of this group have been increasingly discussed in the literature, even though their isolation can still be challenging. Among these bacteria is the Gallionellaceae family, mainly composed of neutrophilic FeOB, highlighting Gallionella ferruginea, and nitrite-oxidiser genera. In the previous metagenomic study of the biofilm and sediments of the cooling system from the Irapé hydroelectric power plant (HPP-Irapé), 5% of the total bacteria sequences were related to Gallionellaceae, being 99% unclassified at genus level. Thus, in the present study, a phylogenetic tree based on this family was constructed, in order to search for shared and unique Gallionellaceae signatures in a deep phylogenetic level affiliation and correlated them with geomorphologic characteristics. The results revealed that Gallionella and Ferrigenium were ubiquitous reflecting their ability to adapt to various locations in the power plant. The cave was considered a hotspot for neutrophilic FeOB since it harboured most of the Gallionellaceae diversity. Microscopic biosignatures were detected only in the CS1 sample, which presented abundance of the stalk-forming Ferriphaselus and of the sheath-forming Crenothrix. Further studies are required to provide more detailed insights on Gallionellaceae distribution and diversity patterns in hydroelectric power plants, particularly its biotechnological potential in this industry.

Feeding laying hens with lactobacilli improves internal egg quality and animal health.

Feeding animals with lactobacilli strains is a biotechnological strategy to improve production, food quality, and animal health. Thus, this study aimed to select new lactic acid bacteria (LAB) able to improve laying hens health and egg production. Forty Bovans White layers (two days old) were randomly divided into four experimental groups that receive an oral gavage with saline solution (control group) or with one of the three lactobacilli selected (KEG3, TBB10, and KMG127) by their antagonistic activity against the foodborne pathogen Bacillus cereus GGD_EGG01. 16 S rRNA sequencing identified KEG3 as Lentilactobacillus sp., and TBB10 and KMG127 as Lactiplantibacillus sp. The data showed that feeding birds with LAB increased weight uniformity and improved the internal quality of the eggs (high yolk index and Haugh unit) compared with the control group (p < 0.05). Beta-diversity analysis showed that LAB supplementation modifies the cecal microbiota of laying hens. The prokaryotic families Bacteroidaceae, Ruminococcaceae, Rikenellaceae, and Lactobacillaceae were most important to the total dissimilarity of the cecal microbial community (calculated by SIMPER test). At end of in vivo experiments, it was possible to conclude that the feed of laying hens with Lentilactobacillus sp. TBB10 and Lentilactobacillus sp. KEG3 can be an important biotechnological tool for improving food quality and animal health.

Characteristics, disposition, and outcomes of children hospitalized for mental health boarding at a children's hospital.

Increasingly, youth experiencing mental health crises present to acute care medical hospitals and "board" on medical units due to inpatient psychiatric bed shortages. We conducted a retrospective cohort study of children experiencing mental health boarding at a US children's hospital from October 2020 to September 2022. We examined associations between patients' characteristics and their disposition and outcomes. Our cohort included 1891 boarding hospitalizations: 53.9% transferred to an inpatient psychiatric hospital and 46.1% discharged home. Characteristics associated with not being transferred to an inpatient psychiatric hospital included age <13 years (adjusted odds ratio [aOR] 0.6; 95% confidence interval [CI]: 0.4-0.7), disruptive or aggressive behavior (aOR 0.6; 95% CI: 0.4-0.8), psychosis (aOR 0.5; 95% CI: 0.3-0.8), COVID-19 infection (aOR 0.3; 95% CI: 0.2-0.6), or a complex chronic medical condition (aOR 0.8; 95% CI: 0.6-1.0). Our findings suggest that certain populations of children experiencing mental health boarding face disparate access to inpatient psychiatric care.

Models of KPTN-related disorder implicate mTOR signalling in cognitive and overgrowth phenotypes.

KPTN-related disorder is an autosomal recessive disorder associated with germline variants in KPTN (previously known as kaptin), a component of the mTOR regulatory complex KICSTOR. To gain further insights into the pathogenesis of KPTN-related disorder, we analysed mouse knockout and human stem cell KPTN loss-of-function models. Kptn -/- mice display many of the key KPTN-related disorder phenotypes, including brain overgrowth, behavioural abnormalities, and cognitive deficits. By assessment of affected individuals, we have identified widespread cognitive deficits (n = 6) and postnatal onset of brain overgrowth (n = 19). By analysing head size data from their parents (n = 24), we have identified a previously unrecognized KPTN dosage-sensitivity, resulting in increased head circumference in heterozygous carriers of pathogenic KPTN variants. Molecular and structural analysis of Kptn-/- mice revealed pathological changes, including differences in brain size, shape and cell numbers primarily due to abnormal postnatal brain development. Both the mouse and differentiated induced pluripotent stem cell models of the disorder display transcriptional and biochemical evidence for altered mTOR pathway signalling, supporting the role of KPTN in regulating mTORC1. By treatment in our KPTN mouse model, we found that the increased mTOR signalling downstream of KPTN is rapamycin sensitive, highlighting possible therapeutic avenues with currently available mTOR inhibitors. These findings place KPTN-related disorder in the broader group of mTORC1-related disorders affecting brain structure, cognitive function and network integrity.

Increased interregional virus exchange and nucleotide diversity outline the expansion of chikungunya virus in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil.

Rare genetic variants impact muscle strength.

Muscle strength is highly heritable and predictive for multiple adverse health outcomes including mortality. Here, we present a rare protein-coding variant association study in 340,319 individuals for hand grip strength, a proxy measure of muscle strength. We show that the exome-wide burden of rare protein-truncating and damaging missense variants is associated with a reduction in hand grip strength. We identify six significant hand grip strength genes, KDM5B, OBSCN, GIGYF1, TTN, RB1CC1, and EIF3J. In the example of the titin (TTN) locus we demonstrate a convergence of rare with common variant association signals and uncover genetic relationships between reduced hand grip strength and disease. Finally, we identify shared mechanisms between brain and muscle function and uncover additive effects between rare and common genetic variation on muscle strength.

The impact of rare protein coding genetic variation on adult cognitive function.

Compelling evidence suggests that human cognitive function is strongly influenced by genetics. Here, we conduct a large-scale exome study to examine whether rare protein-coding variants impact cognitive function in the adult population (n = 485,930). We identify eight genes (ADGRB2, KDM5B, GIGYF1, ANKRD12, SLC8A1, RC3H2, CACNA1A and BCAS3) that are associated with adult cognitive function through rare coding variants with large effects. Rare genetic architecture for cognitive function partially overlaps with that of neurodevelopmental disorders. In the case of KDM5B we show how the genetic dosage of one of these genes may determine the variability of cognitive, behavioral and molecular traits in mice and humans. We further provide evidence that rare and common variants overlap in association signals and contribute additively to cognitive function. Our study introduces the relevance of rare coding variants for cognitive function and unveils high-impact monogenic contributions to how cognitive function is distributed in the normal adult population.

Increased interregional virus exchange and nucleotide diversity outline the expansion of the chikungunya virus ECSA lineage in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as Yellow Fever, Zika, Chikungunya, and Dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus (CHIKV) across the country since its first detection in 2014 in Northeast Brazil. Faced with this scenario, on-site training activities in genomic surveillance carried out in partnership with the National Network of Public Health Laboratories have led to the generation of 422 CHIKV genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These new genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersion dynamics of the CHIKV East-Central-South-African (ECSA) lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C>T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving CHIKV ECSA lineage genetic diversity in Brazil.

[Position of the international forum of internal medicine on habits, lifestyle changes and a healthy environment for the prevention of cardiovascular diseases]. / Posicionamiento del foro Internacional de Medicina Interna sobre Hábitos, modificaciones del Estilo de Vida y Ambiente Saludable para la Prevención de Enfermedades Cardiovasculares.

Cardiovascular diseases (CVD), mainly ischemic heart disease and stroke, is the main cause of death worldwide and each year more people die from CVD than from any other cause. These data call for a paradigm shift, where health promotion and cardiovascular prevention will acquire a central role in health policies. From this perspective, dedicating time during the consultation to promoting the acquisition of heart-healthy habits would be indicated in all individuals, regardless of cardiovascular risk classification, the role of the internist being fundamental. This position document from the International Forum of Internal Medicine (FIMI) presents the main indications regarding changes in lifestyle and acquisition of healthy habits to prevent CVD. The different sections will address topics including: nutrition, physical activity, sedentary lifestyle, obesity, smoking, alcohol consumption, sleep, stress, environmental problems related to CVD and specific conditions in women. A section is included about starting CVD promotion and prevention measures at an early age, childhood and adolescence, also mentioning epigenetic aspects related to CVD. Social determinants in CVD are also taken into account, since some of these aspects, such as low socioeconomic level, modify cardiovascular risk and should be taken into account.

Las enfermedades cardiovasculares (ECV), principalmente la cardiopatía isquémica y el accidente cerebrovascular (ACV), constituyen la principal causa de muerte a nivel mundial y cada año mueren más personas por ECV que por cualquier otra causa. Estos datos requieren la necesidad de un cambio de paradigma, en donde la promoción de la salud y la prevención cardiovascular adquieran un papel central en las políticas sanitarias. Desde esta perspectiva, dedicar tiempo durante la consulta en promocionar la adquisición de hábitos cardiosaludables estaría indicado en todos los individuos, independientemente de la clasificación de riesgo cardiovascular, siendo fundamental el rol del médico internista en su función de médico de cabecera. En este documento de posicionamiento del Foro Internacional de Medicina Interna (FIMI) se presentan algunas pautas para recomendar e indicar modificaciones en el estilo de vida y adquisición de hábitos saludables para prevenir la ECV, que tienen el objetivo de ser una herramienta practica para el médico internista. Las diferentes secciones abordaran temas que incluyen: nutrición, actividad física, sedentarismo, obesidad, hábito tabáquico, consumo de alcohol, sueño, estrés, problemas ambientales relacionados a la ECV y condiciones específicas en la mujer. Se incluyó un apartado acerca de comenzar las medidas de promoción y prevención de ECV en edades tempranas, infancia y adolescencia, mencionando además aspectos epigenéticos relacionados a la ECV. Se tienen en cuenta además los determinantes sociales en ECV, ya que algunos de estos aspectos, como el bajo nivel socioeconómico, modifican el riesgo cardiovascular y debieran ser tenidos en cuenta.

Position of the international forum of internal medicine on habits, lifestyle changes and a healthy environment for the prevention of cardiovascular diseases.

Cardiovascular diseases (CVD), mainly ischemic heart disease and stroke, is the main cause of death worldwide and each year more people die from CVD than from any other cause. These data call for a paradigm shift, where health promotion and cardiovascular prevention will acquire a central role in health policies. From this perspective, dedicating time during the consultation to promoting the acquisition of heart-healthy habits would be indicated in all individuals, regardless of cardiovascular risk classification, the role of the internist being fundamental. This position document from the International Forum of Internal Medicine (FIMI) presents the main indications regarding changes in lifestyle and acquisition of healthy habits to prevent CVD. The different sections will address topics including: nutrition, physical activity, sedentary lifestyle, obesity, smoking, alcohol consumption, sleep, stress, environmental problems related to CVD and specific conditions in women. A section is included about starting CVD promotion and prevention measures at an early age, childhood and adolescence, also mentioning epigenetic aspects related to CVD. Social determinants in CVD are also taken into account, since some of these aspects, such as low socioeconomic level, modify cardiovascular risk and should be taken into account.

Las enfermedades cardiovasculares (ECV), principalmente la cardiopatía isquémica y el accidente cerebrovascular (ACV), constituyen la principal causa de muerte a nivel mundial y cada año mueren más personas por ECV que por cualquier otra causa. Estos datos requieren la necesidad de un cambio de paradigma, en donde la promoción de la salud y la prevención cardiovascular adquieran un papel central en las políticas sanitarias. Desde esta perspectiva, dedicar tiempo durante la consulta en promocionar la adquisición de hábitos cardiosaludables estaría indicado en todos los individuos, independientemente de la clasificación de riesgo cardiovascular, siendo fundamental el rol del médico internista en su función de médico de cabecera. En este documento de posicionamiento del Foro Internacional de Medicina Interna (FIMI) se presentan algunas pautas para recomendar e indicar modificaciones en el estilo de vida y adquisición de hábitos saludables para prevenir la ECV, que tienen el objetivo de ser una herramienta practica para el médico internista. Las diferentes secciones abordaran temas que incluyen: nutrición, actividad física, sedentarismo, obesidad, hábito tabáquico, consumo de alcohol, sueño, estrés, problemas ambientales relacionados a la ECV y condiciones específicas en la mujer. Se incluyó un apartado acerca de comenzar las medidas de promoción y prevención de ECV en edades tempranas, infancia y adolescencia, mencionando además aspectos epigenéticos relacionados a la ECV. Se tienen en cuenta además los determinantes sociales en ECV, ya que algunos de estos aspectos, como el bajo nivel socioeconómico, modifican el riesgo cardiovascular y debieran ser tenidos en cuenta.