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.

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.

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.

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.

Impact of the COVID-19 Pandemic on Patient- and Family-Centered Care and on the Mental Health of Health Care Workers, Patients, and Families.

During the COVID-19 pandemic, hospitals around the world were forced to reorganize their processes in an attempt to contain the spread of the virus while still providing adequate care to patients. In the Pediatric Intensive Care Unit (PICU) setting, changes in family visitation protocols and restrictions on parent chaperones during hospitalization, as well as other changes, interfered with care. Based on a narrative review of the literature, supported by the authors' observations in practice, we aimed to describe the impact of the pandemic on patient and family-centered care (PFCC) in the PICU environment, especially regarding the presence of family members, family support, and communication with patients and their families, as well as the effects of changes in these practices on the mental health of those involved. In this context, several strategies were used to sustain PFCC, and, despite many challenges, attempts were made to achieve the bare-minimum goals of humanized care for patients, families, and providers alike.

Intelligence quotient (IQ) as a predictor of epilepsy surgery outcome.

INTRODUCTION: About one-third of patients with epilepsy have a refractory form which is associated with important economic and psychosocial burden. Most of these patients also suffer from comorbidities. One of the most frequent is cognitive impairment. Resective surgery or neuromodulation techniques may improve seizure control. Several factors have been proposed as potential predictors of the success of surgery regarding seizure frequency. We aimed to study preoperative cognitive performance as a predictor of the epilepsy surgery outcome. METHODS: In this ambispective study we studied total intelligence quotients (IQ) measured before surgery with the Wechsler Adult Intelligence Scale (WAIS) as a potential predictor of Engel Class at 1 year after surgery. Then we included IQ in a multivariate model and tested its performance. RESULTS: Preoperative IQ was a significant and independent predictor of the Engel Class at 1 year after surgery (OR 0.94; CI 0.90-0.98; p = 0.007). The multivariate model including the age at epilepsy onset, education level, sex, and the type of surgery (resective versus palliative surgery) showed an area under the ROC curve of 0.85. CONCLUSIONS: A low intelligence level may constitute a marker of worse prognosis after epilepsy surgery. However, other predictors should also be considered when evaluating surgical candidates.

Phenothiazinium dyes for photodynamic treatment present lower environmental risk compared to a formulation of trifloxystrobin and tebuconazole.

The widespread use of conventional chemical antifungal agents has led to worldwide concern regarding the selection of resistant isolates. In this scenario, antimicrobial photodynamic treatment (APDT) has emerged as a promising alternative to overcome this issue. The technique is based on the use of a photosensitizer (PS) and light in the presence of molecular oxygen. Under these conditions, the PS generates reactive oxygen species which damage the biomolecules of the target organism leading to cell death. The great potential of APDT against plant-pathogenic fungi has already been reported both in vitro and in planta, indicating this control measure has the potential to be widely used in crop plants. However, there is a lack of studies on environmental risk with ecotoxicological assessment of PSs used in APDT. Therefore, this study aimed to evaluate the environmental toxicity of four phenothiazinium PSs: i) methylene blue (MB), ii) new methylene blue N (NMBN), iii) toluidine blue O (TBO), and iv) dimethylmethylene blue (DMMB) and also of the commercial antifungal NATIVO®, a mixture of trifloxystrobin and tebuconazole. The experiments were performed with Daphnia similis neonates and zebrafish embryos. Our results showed that the PSs tested had different levels of toxicity, with MB being the less toxic and DMMB being the most. Nonetheless, the environmental toxicity of these PSs were lower when compared to that of NATIVO®. Furthermore, estimates of bioconcentration and of biotransformation half-life indicated that the PSs are environmentally safer than NATIVO®. Taken together, our results show that the toxicity associated with phenothiazinium PSs would not constitute an impediment to their use in APDT. Therefore, APDT is a promising approach to control plant-pathogenic fungi with reduced risk for selecting resistant isolates and lower environmental impacts when compared to commonly used antifungal agents.

Intestinal polyparasitism and levels of mucosal anthelmintic SIgA in children from endemic areas in Northeastern Brazil.

Interactions between parasites during co-infections are often complex and can impact immunization and treatment programmes, as well as disease outcomes and morbidity. However, little is known about these interactions and the mechanisms involved. In this study, a coproparasitological survey was carried out in school-age children living in endemic areas of parasitic infection in the state of Sergipe, Northeastern Brazil. Anti-helminth-specific and total secretory immunoglobulin-A (SIgA) levels were measured in stool and saliva samples and were compared in children presenting monoparasitism, polyparasitism (helminths and/or intestinal protozoa) and no infections. The survey showed that protozoa were more prevalent than helminths, and that there was a high frequency of polyparasitism in the studied population, mainly from combinations of protozoan species. Although less frequent, combinations between species of protozoa and helminths were also observed. The levels of salivary SIgA in these co-infected individuals were lower than the average observed in infections with helminths alone. Although the children participating in this survey were asymptomatic, and it was, therefore, not possible to evaluate the impact of salivary SIgA reduction on the diseases, and the study highlights the need for further investigations of co-infections by intestinal parasites and the effects on immune response induced by the interactions between different parasites.

Ultrastructure of the gill ciliary epithelium of Limnoperna fortunei (Dunker 1857), the invasive golden mussel.

BACKGROUND: Limnoperna fortunei is a freshwater bivalve mollusc originally from southern Asia that invaded South America in the 1990's. Due to its highly efficient water pumping and filtering, and its capacity to form strong adhesions to a variety of substrates by byssus thread, this invasive species has been able to adapt to several environments across South America, causing significant ecological and economic damages. By gaining a deeper understanding of the biological and ecological aspects of L. fortunei we will be able to establish more effective strategies to manage its invasion. The gills of the mollusc are key structures responsible for several biological functions, including respiration and feeding. In this work, we characterized the ultrastructure of L. fortunei gills and its ciliary epithelium using light microscopy, transmission and scanning electron microscopies. This is the first report of the morphology of the epithelial cells and cilia of the gill of L. fortunei visualized in high resolution. RESULTS: The analysis showed highly organized and abundant ciliary structures (lateral cilia, laterofrontal cirri and frontal cilia) on the entire length of the branchial epithelium. Mitochondria, smooth endoplasmic reticulum and glycogen granules were abundantly found in the epithelial cells of the gills, demonstrating the energy-demanding function of these structures. Neutral mucopolysaccharides (low viscosity mucus) were observed on the frontal surface of the gill filaments and acid mucopolysaccharides (high viscosity mucus) were observed to be spread out, mainly on the lateral tract. Spherical vesicles, possibly containing mucus, could also be observed in these cells. These findings demonstrate the importance of the mucociliary processes in particle capture and selection. CONCLUSIONS: Our data suggest that the mechanism used by this mollusc for particle capture and selection could contribute to a better understanding of key aspects of invasion and also in the establishment of more efficient and economically viable strategies of population control.