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A discinesia ciliar primária é uma síndrome autossómica recessiva, de clínica muito variável. Se associada a situs inversus, sinusite crónica e bronquiectasias, denomina-se Síndrome de Kartagener. A sua clínica pode ser muito variável e inespecífica, incluindo dificuldade respiratória neonatal. Descrevemos um caso de Síndrome de Kartagener num bebé de um ano, que se manifestou aos seis dias com dificuldade respiratória, de agravamento progressivo. Este caso representa o paradigma da importância da atuação do Médico de Família, na valorização dos sinais e sintomas, que permitiu o diagnóstico precoce de uma síndrome pouco prevalente.

Facades are systems fixed externally to the building that perform the function of protecting the internal environment, thermal comfort and control lighting. The degradation of facades occurs due to the action of agents and mechanisms that are capable of causing alterations in the chemical and physical characteristics of materials. It depends on factors such as orientation, degree of exposure to agents and construction processes. Because the facades have different exposure conditions, degradation manifests itself heterogeneously. Given the need to understand the evolutionary behavior of degradation, we propose to characterize degradation based on its velocity as a function of increasing age of buildings. This new index helps in the study of degradation, since unlike the FGD (general degradation factor), it considers the age factor of the sample. This research was applied in 306 samples of facades located in Brasilia, Brazil. Degradation is quantified by the degradation measurement method (DMM). The speed of the degradation consists of quantifying the degradation of each sample over a year. For the quantification of the speed, three characteristic intervals are adopted (low, medium and high speed). It is observed that, with higher values, degradation becomes widespread. For the high degradation rate, more than half of the samples have a northern orientation. The high percentage of samples with a northern orientation and a high degradation rate shows that this orientation has a higher criticality of degradation.

Marbling is one of the most important beef quality traits. An association between a non-synonymous variant located in EGFLAM (EGF-like fibronectin and laminin G) and marbling in Hanwoo cattle has recently been published. We therefore investigated the association between this SNP (rs109436056 SNP) and marbling in Limousin cattle. A total of 355 animals were phenotyped for marbling and genotyped for this SNP. Significant association (p < 0.05) was observed, in which genotype CC exhibited higher marbling. This SNP could be used for the genetic improvement of marbling in Limousin cattle., (© 2024 Stichting International Foundation for Animal Genetics. Published by John Wiley & Sons Ltd.)

Research Highlights: Supplementation with CuNP in feed and water reduced Salmonella Enteritidis count.Supplementation with CuNP did not affect intestinal integrity of broilers.CuNP did not affect weight gain or total lactic acid bacterial counts.The results demonstrate the potential of CuNP as alternative antimicrobials.

The mammalian cortex is comprised of cells classified into types according to shared properties. Defining the contribution of each cell type to the processes guided by the cortex is essential for understanding its function in health and disease. We used transcriptomic and epigenomic cortical cell type taxonomies from mouse and human to define marker genes and putative enhancers and created a large toolkit of transgenic lines and enhancer AAVs for selective targeting of cortical cell populations. We report evaluation of fifteen new transgenic driver lines, two new reporter lines, and >800 different enhancer AAVs covering most subclasses of cortical cells. The tools reported here as well as the scaled process of tool creation and modification enable diverse experimental strategies towards understanding mammalian cortex and brain function.

Bioinformatic pipelines are becoming increasingly complex with the ever-accumulating amount of Next-generation sequencing (NGS) data. Their orchestration is difficult with a simple Bash script, but bioinformatics workflow managers such as Nextflow provide a framework to overcome respective problems. This study used Nextflow to develop a bioinformatic pipeline for detecting expression quantitative trait loci (eQTL) using a DSL2 Nextflow modular syntax, to enable sharing the huge demand for computing power as well as data access limitation across different partners often associated with eQTL studies. Based on the results from a test run with pilot data by measuring the required runtime and computational resources, the new pipeline should be suitable for eQTL studies in large scale analyses., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Background: Artificial intelligence, particularly deep learning (DL), has immense potential to improve the interpretation of transthoracic echocardiography (TTE). Mitral regurgitation (MR) is the most common valvular heart disease and presents unique challenges for DL, including the integration of multiple video-level assessments into a final study-level classification., Methods: A novel DL system was developed to intake complete TTEs, identify color MR Doppler videos, and determine MR severity on a 4-step ordinal scale (none/trace, mild, moderate, and severe) using the reading cardiologist as a reference standard. This DL system was tested in internal and external test sets with performance assessed by agreement with the reading cardiologist, weighted κ, and area under the receiver-operating characteristic curve for binary classification of both moderate or greater and severe MR. In addition to the primary 4-step model, a 6-step MR assessment model was studied with the addition of the intermediate MR classes of mild-moderate and moderate-severe with performance assessed by both exact agreement and ±1 step agreement with the clinical MR interpretation., Results: A total of 61 689 TTEs were split into train (n=43 811), validation (n=8891), and internal test (n=8987) sets with an additional external test set of 8208 TTEs. The model had high performance in MR classification in internal (exact accuracy, 82%; κ=0.84; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR) and external test sets (exact accuracy, 79%; κ=0.80; area under the receiver-operating characteristic curve, 0.98 for moderate or greater MR). Most (63% internal and 66% external) misclassification disagreements were between none/trace and mild MR. MR classification accuracy was slightly higher using multiple TTE views (accuracy, 82%) than with only apical 4-chamber views (accuracy, 80%). In subset analyses, the model was accurate in the classification of both primary and secondary MR with slightly lower performance in cases of eccentric MR. In the analysis of the 6-step classification system, the exact accuracy was 80% and 76% with a ±1 step agreement of 99% and 98% in the internal and external test set, respectively., Conclusions: This end-to-end DL system can intake entire echocardiogram studies to accurately classify MR severity and may be useful in helping clinicians refine MR assessments., Competing Interests: Dr Poterucha owns stock in Abbott Laboratories and Baxter International with research support provided to his institution from the Amyloidosis Foundation, American Heart Association (awards 933452 and 23SCISA1077494; https://doi.org/10.58275/AHA.23SCISA1077494.pc.gr.172160), Eidos Therapeutics, Pfizer, Edwards Lifesciences, and Janssen. Dr Hahn reports speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, Medtronic, Philips Healthcare, and Siemens Healthineers; she has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Anteris, Edwards Lifesciences, Medtronic and Novartis; she is chief scientific officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored valve trials, for which she receives no direct industry compensation. Dr Einstein reports receiving authorship fees from Wolters Kluwer Healthcare—UpToDate and serving on a scientific advisory board for Canon Medical Systems; his institution has grants/grants pending from Attralus, BridgeBio, Canon Medical Systems, GE HealthCare, Intellia Therapeutics, Ionis Pharmaceuticals, Neovasc, Pfizer, Roche Medical Systems, and W.L. Gore & Associates. The other authors report no conflicts.

Clear renal cell carcinoma (RCC) is the most common primary renal tumor originating within the renal cortex. It is responsible for 75% to 85% of all primary renal neoplasms. Multiple risk factors are associated with the development of RCC, the most common being smoking. On some occasions, RCC has been linked to some autoimmune conditions, but data is limited. Especially, its association with glomerulonephritis (GN) is rare in literature and not fully understood. In this case report, we discuss a presentation of RCC associated with crescentic GN., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharieh et al.)

Background: Several guidelines recommend the use of different classifiers to determine the risk of recurrence (ROR) and treatment decisions in patients with HR+HER2- breast cancer. However, data are still lacking for their usefulness in Latin American (LA) patients. Our aim was to evaluate the comparative prognostic and predictive performance of different ROR classifiers in a real-world LA cohort., Methods: The Molecular Profile of Breast Cancer Study (MPBCS) is an LA case-cohort study with 5-year follow-up. Stages I and II, clinically node-negative HR+HER2- patients (n = 340) who received adjuvant hormone therapy and/or chemotherapy, were analyzed. Time-dependent receiver-operator characteristic-area under the curve, univariate and multivariate Cox proportional hazards regression (CPHR) models were used to compare the prognostic performance of several risk biomarkers. Multivariate CPHR with interaction models tested the predictive ability of selected risk classifiers., Results: Within this cohort, transcriptomic-based classifiers such as the recurrence score (RS), EndoPredict (EP risk and EPClin), and PAM50-risk of recurrence scores (ROR-S and ROR-PC) presented better prognostic performances for node-negative patients (univariate C-index 0.61-0.68, adjusted C-index 0.77-0.80, adjusted hazard ratios [HR] between high and low risk: 4.06-9.97) than the traditional classifiers Ki67 and Nottingham Prognostic Index (univariate C-index 0.53-0.59, adjusted C-index 0.72-0.75, and adjusted HR 1.85-2.54). RS (and to some extent, EndoPredict) also showed predictive capacity for chemotherapy benefit in node-negative patients (interaction P = .0200 and .0510, respectively)., Conclusion: In summary, we could prove the clinical validity of most transcriptomic-based risk classifiers and their superiority over clinical and immunohistochemical-based methods in the heterogenous, real-world node-negative HR+HER2- MPBCS cohort., (© The Author(s) 2024. Published by Oxford University Press.)

Understanding interactions within and between species is crucial to ecological research. However, for cetaceans such interactions can be difficult to observe in the field. Photographs offer an opportunity to study intra- and inter-specific interactions, by capturing 'snapshots' of their occurrence over space and time. At-surface and underwater photographs of bottlenose dolphins ( Tursiops aduncus ) inhabiting Ponta do Ouro Partial Marine Reserve (PPMR), Mozambique, were used to examine evidence of interactions with other dolphins, predators and ectoparasites. Intra-specific scarring levels significantly differed by sex and age class, with males displaying more scarring than females. Similarly, adults had more scarring than juveniles or calves. Shark bites significantly differed in their distribution across dolphin body areas, with the dorsal side being more frequently wounded than the ventral side. The presence of barnacles was exclusive to fluke, dorsal and pectoral fins, and showed strong seasonal trends. Overall, this study demonstrates the value of photographs for examining marine ecological interactions. It provides the first insights regarding dolphin social behaviour, predation risk and health for this population. These in turn will support future research into the population dynamics and conservation of the PPMR dolphins, which is urgently required in the face of locally increasing anthropogenic pressures., Competing Interests: The authors declare no competing financial or nonfinancial interests that are directly or indirectly related to this work., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Benign essential blepharospasm (BEB) is the most common adult-onset focal facial dystonia and its treatment of choice is periodic application of botulinum toxin (BtA). It has a higher incidence in middle and late adulthood, especially in women between 40 and 60 years of age., Objective: To carry out the translation and cross-cultural adaptation of the CDQ24 questionnaire in its Spanish version in patients diagnosed with BEB who have been treated with BtA in an ophthalmologic center in Bogotá - Colombia., Materials and Methods: Pilot test of validation study and adaptation of a scale assembled in a prospective cohort of the CDQ24 instrument to Spanish in adult patients with primary blepharospasm treated with botulinum toxin in Bogota, Colombia., Results: We obtained a sample of 26 patients to whom the instrument was applied after translation and retranslation of the original document, composed of 19 (73%) women with a median age of 64.5 years; the average time to answer the survey was 4.93 min. The internal consistency of the scale evaluated by Cronbach's Alpha had a total score of 0.78. Criterion validity between the CDQ24 scale and the WHOQOL-BREF quality of life scale was determined by determining correlation between the Emotional Well-Being and Phsychological domains of both scales., Conclusions: The translation and cross-cultural adaptation of the CDQ-24 scale into Spanish allowed the applicability of the instrument to the Spanish-speaking population during the pilot test, which allows us to continue the relevant studies in the study population., (Copyright © 2024 Sociedad Española de Oftalmología. All rights reserved.)

The objective of this study was to synthesize and characterize porous Cellulose Acetate (CA) scaffolds using the electrospinning technique and functionalize the surface of the scaffolds obtained through the dip-coating method with a Hydroxyapatite (HA) nanocomposite and varying concentrations of graphene oxide (GO) for application in tissue engineering regeneration techniques. The scaffolds were divided into four distinct groups based on their composition: 1) CA scaffolds; 2) CAHAC scaffolds; 3) CAHAGOC 1.0% scaffolds; 4) CAHAGOC 1.5% scaffolds. Scaffold analyses were conducted using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy, Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS), and in vitro cell viability assays (WST). For the biological test analysis, Variance (two-way) was used, followed by Tukey's post-test (α = 0.05). The XRD results revealed the predominant presence of CaP phases in the CAHAC, CAHAGOC 1.0%, and CAHAGOC 1.5% groups, emphasizing the presence of HA in the scaffolds. FTIR demonstrated characteristics of cellulose and PO4 bands in the groups containing HA, confirming the presence of CaP in the synthesized materials, as also indicated by XRD. Raman spectroscopy showed the presence of D and G bands, consistent with GO, confirming the successful incorporation of the HAGO nanocomposite into the scaffolds. The micrographs displayed overlapping electrospun fibers, forming the three-dimensional structure in the produced scaffolds. It was possible to observe hydroxyapatite crystals filling some of these pores, creating a suitable structure for cell adhesion, proliferation, and nutrition, as corroborated by the results of in vitro tests. All scaffolds exhibited high cell viability, with significant cell proliferation. Even after 48 h, there was a slight reduction in the number of cells, but a noteworthy increase in cell proliferation was evident in the CAHAGOC 1.5% group after 48 h ( p  < 0.05). In conclusion, it can be affirmed that the produced scaffolds demonstrated physical and biological characteristics and properties capable of promoting cell adhesion and proliferation. Therefore, they represent significant potential for application in tissue engineering, offering a new perspective regarding techniques and biomaterials applied in regenerative therapies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This research focuses on developing MIL-53-type compounds with Fe obtained with ligands derived from PET waste, followed by the controlled addition of hydrofluoric acid (HF). Incorporating HF into the MOF structure induced substantial changes in the material textural properties, resulting in a significant change in CO 2 adsorption. Furthermore, a distinctive structural alteration (breathing effect) was observed in the CO 2 isotherms at different temperatures; these structural changes have not been observed by X-ray diffraction (XRD) because this characterization has been performed at room temperature, whereas the adsorption experiments were conducted at 260, 273, and 303 K and different pressures. Subsequently, DFT studies were performed to investigate the CO 2 -filling mechanisms and elucidate the material respiration effect. This approach offers promising opportunities for sustainable materials with improved gas adsorption properties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Mitochondrial DNA sequences are frequently transferred into the nuclear genome, generating nuclear mitochondrial DNA sequences (NUMTs). Here, we analysed, for the first time, NUMTs in the domestic yak genome. We obtained 499 alignment matches covering 340.2 kbp of the yak nuclear genome. After a merging step, we identified 167 NUMT regions with a total length of ~ 503 kbp, representing 0.02% of the nuclear genome. We discovered copies of all mitochondrial regions and found that most NUMT regions are intergenic or intronic and mostly untranscribed. 98 different NUMT regions from domestic yak showed high homology with cow and/or wild yak genomes, suggesting selection or hybridization between domestic/wild yak and cow. To rule out the possibility that the identified NUMTs could be artifacts of the domestic yak genome assembly, we validated experimentally five NUMT regions by PCR amplification. As NUMT regions show high similarity to the mitochondrial genome can potentially pose a risk to domestic yak DNA mitochondrial studies, special care is therefore needed to select primers for PCR amplification of mitochondrial DNA sequences., (© 2024. The Author(s).)

Objective: To evaluate the association of a validated chest computed tomography (Chest-CT) severity score in COVID-19 patients with their respiratory outcome in the Intensive Care Unit., Methods: A single-center, prospective study evaluated patients with positive RT-PCR for COVID-19, who underwent Chest-CT and had a final COVID-19 clinical diagnosis needing invasive mechanical ventilation in the ICU. The admission chest-CT was evaluated according to a validated Chest-CT Severity Score in COVID-19 (Chest-CTSS) divided into low ≤50% (<14 points) and >50% high (≥14 points) lung parenchyma involvement. The association between the initial score and their pulmonary clinical outcomes was evaluated., Results: 121 patients were clustered into the > 50% lung involvement group and 105 patients into the ≤ 50% lung involvement group. Patients ≤ 50% lung involvement (<14 points) group presented lower PEEP levels and FiO2 values, respectively GEE P = 0.09 and P = 0.04. The adjusted COX model found higher hazard to stay longer on invasive mechanical ventilation HR: 1.69, 95% CI, 1.02-2.80, P = 0.042 and the adjusted logistic regression model showed increased risk ventilator-associated pneumonia OR = 1.85 95% CI 1.01-3.39 for COVID-19 patients with > 50% lung involvement (≥14 points) on Chest-CT at ICU admission., Conclusion: COVID-19 patients with >50% lung involvement on Chest-CT admission presented higher chances to stay longer on invasive mechanical ventilation and more chances to developed ventilator-associated pneumonia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Esper Treml et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The CRISPR/Cas9 technique applied to modify the cattle genome has value in increasing animal health and welfare. Here, we established a simple, fast, and efficient cloning-free CRISPR/Cas9 protocol for large deletions of genomic loci in the frequently used model bovine MDBK cell line. The main advantages of our protocol are as follows: (i) pre-screening of the sgRNA efficiency with a fast and simple cleavage assay, (ii) reliable detection of genomic edits primarily by PCR and confirmed by DNA sequencing, and (iii) single cell sorting with FACS providing specific genetic information from modified cells of interest. Therefore, our method could be successfully applied in different studies, including functional validation of any genetic or regulatory elements., (© 2024. The Author(s).)

Background: Peripheral nerve injury is a recognized complication after reverse shoulder arthroplasty (RSA) that has mainly been studied at the level of the brachial plexus and its proximal branches. However, the impact of RSA on distal peripheral nerves and the influence of elbow and wrist position is not known. This cadaveric study aimed to analyze the effect of RSA implantation and upper limb position on tension in the distal median and radial nerves. The hypothesis was that RSA increased distal nerve tension, which could be further affected by elbow and wrist position., Methods: 12 upper limbs in 9 full fresh-frozen cadavers were dissected. Nerve tension was measured in the median nerve at the level of the proximal arm, elbow, and distal forearm, and in the radial nerve at the level of the elbow, using a customized three-point tensiometer. Measurements were carried out before and after RSA implantation, using a semi-inlay implant (Medacta, Castel San Pietro, Switzerland). Two different configurations were tested, using the smallest and largest available implant sizes. Three upper-limb key positions were considered (plexus at risk, plexus relief, and neutral), from which the effect of elbow and wrist position was further tested., Results: RSA implantation significantly increased median and radial nerve tension throughout the upper limb. The distal nerve segments were particularly dependent on elbow and wrist position. The plexus at risk position induced the most tension in all nerve segments, especially with the large implant configuration. On the other hand, the plexus relief position induced the least amount of tension. Flexing the elbow was the most efficient way to decrease nerve tension in all tested nerve segments and key positions. Wrist flexion significantly decreased nerve tension in the median nerve, whereas wrist extension decreased tension in the radial nerve., Conclusion: RSA significantly increases tension in the median and radial nerves and makes them more susceptible to wrist and elbow positioning. The mechanism behind distal peripheral neuropathy after RSA may thus result from increased compression of tensioned nerves against anatomical fulcrums rather than nerve elongation alone. Elbow flexion was the most effective way to decrease nerve tension, while elbow extension should be avoided when implanting the humeral component. Further studies are needed to assess the ulnar nerve., (© 2024 The Authors.)

The Zika virus (ZIKV) can be vertically transmitted, causing congenital Zika syndrome (CZS) in fetuses. ZIKV infection in early gestational trimesters increases the chances of developing CZS. This syndrome involves several pathologies with a complex diagnosis. In this work, we aim to identify biological processes and molecular pathways related to CZS and propose a series of putative protein and metabolite biomarkers for CZS prognosis in early pregnancy trimesters. We analyzed serum samples of healthy pregnant women and ZIKV-infected pregnant women bearing nonmicrocephalic and microcephalic fetuses. A total of 1090 proteins and 512 metabolites were identified by bottom-up proteomics and untargeted metabolomics, respectively. Univariate and multivariate statistical approaches were applied to find CZS differentially abundant proteins (DAP) and metabolites (DAM). Enrichment analysis (i.e., biological processes and molecular pathways) of the DAP and the DAM allowed us to identify the ECM organization and proteoglycans, amino acid metabolism, and arachidonic acid metabolism as CZS signatures. Five proteins and four metabolites were selected as CZS biomarker candidates. Serum multiomics analysis led us to propose nine putative biomarkers for CZS prognosis with high sensitivity and specificity.

Dietary polyphenol consumption is associated with a wide range of neuroprotective effects by improving mitochondrial function and signaling. Consequently, the use of polyphenol supplementation has been investigated as an approach to prevent neurodevelopmental diseases during gestation; however, the data obtained are still very inconclusive, mostly because of the difficulty of choosing the correct doses and period of administration to properly prevent neurodegenerative diseases without undermining normal brain development. Thus, we aimed to evaluate the effect of naringin supplementation during the third week of gestation on mitochondrial health and signaling in the cerebellum of 21-day-old offspring. The offspring born to naringin-supplemented dams displayed higher mitochondrial mass, membrane potential, and superoxide content in the cerebellum without protein oxidative damage. Such alterations were associated with dynamin-related protein 1 (DRP1) and phosphorylated AKT (p-AKT) downregulation, whereas the sirtuin 3 (SIRT3) levels were strongly upregulated. Our findings suggest that high dietary polyphenol supplementation during gestation may reduce mitochondrial fission and affect mitochondrial dynamics even 3 weeks after delivery via SIRT3 and p-AKT. Although the offspring born to naringin dams did not present neurobehavioral defects, the mitochondrial alterations elicited by naringin may potentially interfere during neurodevelopment and need to be further investigated., (© 2024 International Society for Developmental Neuroscience.)

Background: Rhodnius zeledoni was described from a single specimen. Since its description, doubts have arisen regarding the taxonomic status of this species in relation to Rhodnius domesticus., Methods: The present study reviewed and compared R. zeledoni with R. domesticus based on morphological analysis and head geometric morphometrics., Results: Our analysis revealed the absence of distinctive diagnostic characters between the two species at specific levels. Rhodnius zeledoni and R. domesticus show morphological and morphometric similarity, with only minor differences in coloration observed between them. Contrary to previous statements, our analysis showed that R. zeledoni and R. paraensis are not closely related species, not corroborating previous studies with such an assumption., Conclusions: Therefore, we formally propose R. zeledoni as a junior synonym of R. domesticus., (© 2024. The Author(s).)

We present the case of an elderly man with a small-joint polyarthritis, accompanied by pitting oedema, involving hands and feet, raising clinical suspicion of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). Treatment with corticosteroids was initiated with significant improvement, but unacceptable iatrogeny ensued, and tapering was not possible without disease flare-up. A trial of tocilizumab allowed disease activity control, slow weaning of corticosteroids and, ultimately, its suspension. RS3PE is a rare rheumatological entity, initially thought to be a variant of rheumatoid arthritis (RA), with shared traits with polymyalgia rheumatica (PMR), and other seronegative spondyloarthropathies, thereby implying a shared pathophysiological background. Elevated levels of interleukin 6 (IL-6) are found in patients with RA, have shown to mirror disease activity in PMR and have also been described in the serum and synovial fluid of patients with RS3PE. Tocilizumab, an anti-IL-6 receptor antibody, shows auspicious results in several other rare rheumatic diseases other than RA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increased intestinal permeability and dysbiosis are related to obesity. Nuts can provide nutrients and bioactive compounds that modulate gut microbiota and inflammation, enhancing the beneficial effects of weight loss., Objectives: To evaluate the effect of consuming cashew nuts (Anacardium occidentale L.) and Brazil nuts (Bertholletia excelsa H.B.K) on intestinal permeability and microbiota, fecal SCFAs and pH, inflammation, and weight loss in energy restriction condition., Methods: In this 8-week randomized controlled trial, 40 women with overweight or obesity were assigned to energy-restricted groups (-500 kcal/d): control group (free of nuts) or Brazilian nuts group (BN: 30 g of cashew nuts and 15 g of Brazil nuts per day). Permeability was analyzed by the lactulose/mannitol test and the microbiota by sequencing the 16S gene in the V3-V4 regions. Plasma concentrations of inflammatory cytokines (TNF, IL-6, IL-10, IL-8, IL-17A) and C-reactive protein were analyzed., Results: In total, 25 women completed the intervention. Both groups lost weight without statistical differences. Lactulose excretion increased only in the control group (P < 0.05). The BN consumption increased fecal propionic acid and potentially beneficial bacteria, such as Ruminococcus, Roseburia, strains NK4A214 and UCG-002 from the Ruminococcaceae family, but also Lachnospiraceae family, Bacteroides, and Lachnoclostridium, when compared to the control group. Changes in intestinal permeability were correlated to a greater reduction in body fat (kg), and IL-8, and increases in Ruminococcus abundance., Conclusion: Our findings demonstrate a positive impact of BN consumption within an energy-restricted context, linked to the augmentation of potentially beneficial bacteria and pathways associated with body fat reduction. Besides, BN consumption mitigated increased intestinal permeability, although its capacity to diminish permeability or enhance weight loss proved limited. This trial was registered at the Brazilian Registry of Clinical Trials as ReBEC (ID: RBR-3ntxrm)., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Transfusion-transmitted malaria (TTM) is a public health problem in endemic and nonendemic areas. The Brazilian Ministry of Health (MH) requested the development of a nucleic acid amplification test (NAT) for the detection of Plasmodium spp. in public blood centers to increase blood safety., Study Design and Methods: The new Brazilian NAT kit named NAT PLUS HIV/HBV/HCV/Malaria Bio-Manguinhos was first implemented in HEMORIO, a public blood center in the city of Rio de Janeiro. Since October 1, 2022, this blood center has been testing all its blood donations for malaria in a pool of six plasma samples to detect Plasmodium spp. by real-time polymerase chain reaction (PCR)., Results: Since the implementation of the NAT PLUS platform until February 2023, HEMORIO has successfully received and tested 200,277 donations. The platform detected two asymptomatic donors in the city of Rio de Janeiro, which is a nonendemic region for malaria. Our analyses suggested a malaria from the Amazon region caused by Plasmodium vivax, in the first case, while an autochthonous transmission case by Plasmodium malariae was identified in the rural area of Rio de Janeiro state., Discussion: The NAT PLUS platform detects Plasmodium spp. in plasma samples with sensitivity capable of detecting subpatent infections. This is the first time worldwide that a group developed and implemented molecular diagnosis for Plasmodium spp. to be used by public blood centers to avoid TTM., (© 2024 AABB.)

Background: The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection., Methods: This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model., Results: We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (β= -0.161, p = 0.001). Time of PrEP use was directly associated with CT infection (β = 0.202; p = 0.042) and inversely associated with dysuria (β= -0.121, p = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (β= -0.089, p = 0.005) and NG (β= -0.048, p = 0.002) infections. Foul-smelling discharge was directly associated with CT (β = 0.275, p = 0.004) and NG (β = 0.295, p = 0.037) infection., Conclusion: The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing., (© 2024. The Author(s).)

Bipolar disorder is a leading contributor to disability, premature mortality, and suicide. Early identification of risk for bipolar disorder using generalizable predictive models trained on diverse cohorts around the United States could improve targeted assessment of high risk individuals, reduce misdiagnosis, and improve the allocation of limited mental health resources. This observational case-control study intended to develop and validate generalizable predictive models of bipolar disorder as part of the multisite, multinational PsycheMERGE Network across diverse and large biobanks with linked electronic health records (EHRs) from three academic medical centers: in the Northeast (Massachusetts General Brigham), the Mid-Atlantic (Geisinger) and the Mid-South (Vanderbilt University Medical Center). Predictive models were developed and valid with multiple algorithms at each study site: random forests, gradient boosting machines, penalized regression, including stacked ensemble learning algorithms combining them. Predictors were limited to widely available EHR-based features agnostic to a common data model including demographics, diagnostic codes, and medications. The main study outcome was bipolar disorder diagnosis as defined by the International Cohort Collection for Bipolar Disorder, 2015. In total, the study included records for 3,529,569 patients including 12,533 cases (0.3%) of bipolar disorder. After internal and external validation, algorithms demonstrated optimal performance in their respective development sites. The stacked ensemble achieved the best combination of overall discrimination (AUC = 0.82-0.87) and calibration performance with positive predictive values above 5% in the highest risk quantiles at all three study sites. In conclusion, generalizable predictive models of risk for bipolar disorder can be feasibly developed across diverse sites to enable precision medicine. Comparison of a range of machine learning methods indicated that an ensemble approach provides the best performance overall but required local retraining. These models will be disseminated via the PsycheMERGE Network website., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Recent studies have discussed the role of antibiotic treatment in the conservative management of acute appendicitis and whether antibiotics are a safe option to replace appendicectomy, which has been the gold standard treatment of acute appendicitis for many years. The bibliographic databases Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, Medline, and PubMed comparing conservative versus surgical treatment of acute appendicitis were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-one studies consisting of systematic reviews and meta-analyses involving 44,699 participants were identified. At least 17,865 participants were treated with antibiotics. Our studies compare antibiotic versus appendicectomy among acute appendicitis patients ranging from 7 to 94 years of age. In most studies, patients received parenteral antibiotics for a total of one to three days, and oral antibiotics such as oral cephalosporin plus metronidazole, oral amoxicillin/clavulanate, oral fluoroquinolones plus Tinidazole upon hospital discharge for a total of 7 to 10 days. The total course of antibiotics for both parenteral and oral regimes ranged from 2 to 16 days, with 10 days being the commonest duration. The recurrence rate following initial antibiotic treatment at one-year follow-up ranged from 13% to 38%, while the mean duration of recurrence ranged from three to eight months. The majority of the patients with recurrence underwent appendicectomy, while some patients were either given a repeat or different course of antibiotics due to the possible presence of antibiotic resistance; however, only 2.4% of the patients were successfully treated upon completion of the second course of antibiotics. Most of the studies concluded that appendicectomy remains the gold standard treatment for uncomplicated acute appendicitis, given its higher efficacy and lower complication rates. Although antibiotic treatment cannot be routinely recommended, it can be considered an appropriate alternative in selected patients with uncomplicated appendicitis who wish to avoid surgery and also acknowledge the risk of recurrence and the potential need for subsequent surgery at the same time., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Chin et al.)

We compared the mental health of higher education students with that of nonstudents. Moreover, we examined whether the mental health of students predicts their probability of obtaining a higher education degree, and whether the extent to which mental health affects educational attainment varies by gender. Drawing on a risk and resilience framework, we considered five facets of mental health that may be implicated in distinct ways in the educational attainment process: positive attitude towards life, self-esteem, self-efficacy, negative affectivity, and perceived stress. We used data from a nationally representative panel study from Switzerland ( N students  = 2070, 42.8% male; N nonstudents  = 3755, 45.9% male). The findings suggest that overall, the mental health of higher education students was relatively similar to that of nonstudents, although students exhibited slightly higher self-esteem, slightly weaker self-efficacy, greater negative affectivity, and higher levels of perceived stress. The effects of different facets of mental health on higher education degree attainment were mostly statistically and/or practically insignificant. However, positive attitudes towards life had a substantial positive effect on the probability of being awarded a higher education degree. Mental health was equally important for male and female students' educational attainment., Supplementary Information: The online version of this article (10.1007/s11618-023-01187-3) contains supplementary material, which is available to authorized users., (© The Author(s) 2023.)

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model., (© 2024. The Author(s).)