Interleukin-10 deficiency induces thoracic perivascular adipose tissue whitening and vascular remodeling.

Perivascular adipose tissue (PVAT) is an adipose layer, surrounding blood vessels, with a local modulatory role. Interleukin-10 (IL-10) has been shown to modulate vascular tissue. This study aimed to characterize the endogenous role of IL-10 in vascular remodeling, and PVAT phenotyping. Thoracic aortic segments from control (C57BL/6J) and IL-10 knockout (IL-10-/-) male mice were used. Analyzes of aorta/PVAT morphometry, and elastin, collagen and reticulin deposition were performed. Tissue uncoupling protein 1 (UCP1) was accessed by Western blotting. Endogenous absence of IL-10 reduced total PVAT area (p = 0.0310), and wall/lumen ratio (p = 0.0024), whereas increased vascular area and thickness (p < 0.0001). Total collagen deposition was augmented in IL-10-/-, but under polarized light, the reduction of collagen-I (p = 0.0075) and the increase of collagen-III (p = 0.0055) was found, simultaneously with reduced elastic fibers deposition (p = 0.0282) and increased deposition of reticular fibers (p < 0.0001). Adipocyte area was augmented in the IL-10 absence (p = 0.0225), and UCP1 expression was reduced (p = 0.0420). Moreover, relative frequency of white adipose cells and connective tissue was augmented in IL-10-/- (p < 0.0001), added to a reduction in brown adipose cells (p < 0.0001). Altogether, these data characterize aorta PVAT from IL-10-/- as a white-like adipocyte phenotype. Endogenous IL-10 prevents vascular remodeling and favors a brown-like adipocyte phenotype, suggesting a modulatory role for IL-10 in PVAT plasticity.

Genetic association analysis in sugarcane (Saccharum spp.) for sucrose accumulation in humid environments in Colombia.

BACKGROUND: Sucrose accumulation in sugarcane is affected by several environmental and genetic factors, with plant moisture being of critical importance for its role in the synthesis and transport of sugars within the cane stalks, affecting the sucrose concentration. In general, rainfall and high soil humidity during the ripening stage promote plant growth, increasing the fresh weight and decreasing the sucrose yield in the humid region of Colombia. Therefore, this study aimed to identify markers associated with sucrose accumulation or production in the humid environment of Colombia through a genome-wide association study (GWAS). RESULTS: Sucrose concentration measurements were taken in 220 genotypes from the Cenicaña's diverse panel at 10 (early maturity) and 13 (normal maturity) months after planting. For early maturity data was collected during plant cane and first ratoon, while at normal maturity it was during plant cane, first, and second ratoon. A total of 137,890 SNPs were selected after sequencing the 220 genotypes through GBS, RADSeq, and whole-genome sequencing. After GWAS analysis, a total of 77 markers were significantly associated with sucrose concentration at both ages, but only 39 were close to candidate genes previously reported for sucrose accumulation and/or production. Among the candidate genes, 18 were highlighted because they were involved in sucrose hydrolysis (SUS6, CIN3, CINV1, CINV2), sugar transport (i.e., MST1, MST2, PLT5, SUT4, ERD6 like), phosphorylation processes (TPS genes), glycolysis (PFP-ALPHA, HXK3, PHI1), and transcription factors (ERF12, ERF112). Similarly, 64 genes were associated with glycosyltransferases, glycosidases, and hormones. CONCLUSIONS: These results provide new insights into the molecular mechanisms involved in sucrose accumulation in sugarcane and contribute with important genomic resources for future research in the humid environments of Colombia. Similarly, the markers identified will be validated for their potential application within Cenicaña's breeding program to assist the development of breeding populations.

Influence of empirically derived filtering parameters, ASV, and OTU pipelines on assessing rumen microbial diversity.

Microbes play an important role in human and animal health as well as animal productivity. The host microbial interactions within ruminants play a critical role in animal health and productivity and provide up to 70% of the animal's energy need in the form of fermentation products. As such, many studies have investigated microbial community composition to understand microbial community changes and factors that affect microbial colonization and persistence. The advances in next generation sequencing (NGS) technologies and low cost of sequencing have gravitated many studies to utilize 16S rDNA-based analysis tools for interrogation of microbiomes at a much finer scale than traditional culturing. However, such methods that rely on single base pair differences for bacterial taxa clustering may inflate or underestimate diversity leading to inaccurate identification of bacterial diversity. Therefore, in this study, we sequenced mock communities of known membership and abundance to establish filtration parameters to reduce inflation of microbial diversity due to PCR and sequencing errors. Additionally, we evaluated the effect of the resulting filtering parameters proposed using established bioinformatic pipelines on a study consisting of Holstein and Jersey cattle to identify bread and treatment effects on the bacterial community composition and the impact of the filtering on global microbial community structure analysis and results. Filtration resulted in a sharp reduction in bacterial taxa identified, yet retain most sequencing data (retaining > 79% of sequencing reads) when analyzed using 3 different microbial analysis pipelines (DADA2, Mothur, USEARCH). After filtration, conclusions from α and ß-diversity tests show very similar results across all analysis methods. The mock community-based filtering parameters proposed in this study help provide a more realistic estimation of bacterial diversity. Additionally, the filtration reduced the variation between microbiome analysis methods and help identify microbial community differences that could have been missed due to large animal to animal variation observed in the unfiltered data. As such, we believe, the new filtering parameters described in this study will help obtain diversity estimates closer to realistic values and will improve the ability of detecting microbial community differences and help better understand microbial community changes in 16S rDNA-based studies.

Bulk segregant mapping and transcriptome analyses reveal the molecular mechanisms of spinetoram resistance in Spodoptera frugiperda.

The evolution of resistance to insecticides poses a significant threat to pest management programs. Understanding the molecular mechanisms underlying insecticide resistance is essential to design sustainable pest control and resistance management programs. The fall armyworm, Spodoptera frugiperda, is an important insect pest of many crops and has a remarkable ability to evolve resistance to insecticides. In this study, we employed bulk segregant analysis (BSA) combined with DNA and RNA sequencing to characterize the molecular basis of spinetoram resistance in S. frugiperda. Analysis of genomic data derived from spinetoram selected and unselected bulks and the spinetoram-resistant and susceptible parental strains led to the identification of a three-nucleotide deletion in the gene encoding the nicotinic acetylcholine receptor α6 subunit (nAChR α6). Transcriptome profiling identified the upregulation of few genes encoding detoxification enzymes associated with spinetoram resistance. Thus, spinetoram resistance in S. frugiperda appears to be mediated mainly by target site insensitivity with a minor role of detoxification enzymes. Our findings provide insight into the mechanisms underpinning resistance to spinetoram in S. frugiperda and will inform the development of strategies to control this highly damaging, globally distributed crop pest.

Latin-American guidelines of recommendations at discharge from an acute coronary syndrome.

The diagnostic criteria, treatments at the time of admission, and drugs used in patients with acute coronary syndrome are well defined in countless guidelines. However, there is uncertainty about the measures to recommend during patient discharge planning. This document brings together the most recent evidence and the standardized and optimal treatment for patients at the time of discharge from hospitalization for an acute coronary syndrome, for comprehensive and safe care in the patient's transition between care from the acute event to the outpatient care, with the aim of optimizing the recovery of viable myocardium, guaranteeing the most appropriate secondary prevention, reducing the risk of a new coronary event and mortality, as well as the adequate reintegration of patients into daily life.

Los criterios diagnósticos, los tratamientos en el momento de la admisión y los fármacos utilizados en pacientes con síndrome coronario agudo están bien definidos en innumerables guías. Sin embargo, existe incertidumbre acerca de las medidas para recomendar durante la planificación del egreso de los pacientes. Este documento reúne las evidencias más recientes y el tratamiento estandarizado y óptimo para los pacientes al momento del egreso de una hospitalización por un síndrome coronario agudo, para un cuidado integral y seguro en la transición del paciente entre la atención del evento agudo y el cuidado ambulatorio, con el objetivo de optimizar la recuperación de miocardio viable, garantizar la prevención secundaria más adecuada, reducir el riesgo de un nuevo evento coronario y la mortalidad, así como la adecuada reinserción de los pacientes en la vida cotidiana.

Nutritional value and kinetics of in vitro fermentation of spineless cactus of the genus Nopalea in different phenological phases.

The objective was to evaluate the chemical composition and in vitro fermentation of spineless cactus of the genus Nopalea, F-21 (Nopalea cochenillifera Dyck), IPA-Sertânia (Nopalea cochenillifera Dyck) and Miúda (Nopalea cochenillifera Salm Dyck), in different phenophases. There was no effect (P < 0.05) of the phenological phases of spineless cactus on DM, ash, OM, EE, and CP. Varieties F-21 and Miúda presented higher values of DM and OM, whereas the CP was higher for IPA-Sertânia. The contents of NDF, ADF, and ADL, as well as the fractions of carbohydrates B2 and C were higher in the mature stage, irrespective of the variety. The Miúda variety showed higher levels of NFC and fractions A + B1 and the lower levels of pectin compared to the F-21 and IPA-Sertânia varieties, but not differ of TC to F-21. The volume of gas produced via the degradation of NFC was higher for young phenological phases. The young and intermediate stages showed a higher in vitro digestibility of DM. Based on the results, varieties IPA-Sertânia and Miúda have a high potential for use in animal feed because of their high nutritional quality. Mature cladodes showed a higher fibrous fraction and lower digestibility in all varieties.

Is race adjustment necessary to estimate glomerular filtration rate in South Brazilians?

BACKGROUND AND AIMS: Race coefficients (RC) in equations to estimate glomerular filtration rate (GFR) have been highly questioned. We aimed to evaluate the performance of three equations, namely 2009 Chronic Kidney Disease Epidemiology Collaboration (2009 CKD-EPI), 2021 CKD-EPI, and European Kidney Function Consortium (EKFC) in self-reported Black and White Brazilians. MATERIALS AND METHODS: Our cross-sectional study compared estimated GFR (eGFR) with 51Cr-EDTA measured GFR (mGFR) in healthy adults, patients with type 2 diabetes mellitus with or without chronic kidney disease (CKD), and in non-diabetic individuals with CKD. The performance of these equations was assessed using Bland-Altman plots, Lin's concordance correlation coefficient (CCC), bias, P30, and P15 accuracy. RESULTS: Three hundred six White adults (aged 53 ± 17 years, 55% women, mean mGFR: 83 ± 32 mL/min/1.73 m2) and 48 Black participants (aged 53 ± 17 years, 58% women, mGFR: 90 ± 34 mL/min/1.73 m2) were included. No equation achieved the desirable P30 accuracy value of 90%, neither in White (2009 CKD-EPI:78%, 2021 CKD-EPI:76% and EKFC:77%, p = 0.368) nor in Black volunteers (respective values of 77%, 75%, and 77%; p = 0.882). The 2009 CKD-EPI showed the best performance in Black participants (bias: 4.04; CCC: 0.848), whereas the 2021 CKD-EPI performed better in Whites, with smaller bias (1.45), and better concordance correlation coefficient (0.790). The EKFC presented the worst performance. All equations underdiagnosed advanced CKD in White participants, but not in Black. CONCLUSIONS: The 2021 CKD-EPI does not outperform the 2009 CKD-EPI. Instead, it underestimated the occurrence of CKD in White participants. Thus, we do not recommend replacing the 2009 with the new 2021 CKD-EPI in the Brazilian population.

Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Artificial intelligence for ventricular arrhythmia capability using ambulatory electrocardiograms.

Aims: European and American clinical guidelines for implantable cardioverter defibrillators are insufficiently accurate for ventricular arrhythmia (VA) risk stratification, leading to significant morbidity and mortality. Artificial intelligence offers a novel risk stratification lens through which VA capability can be determined from the electrocardiogram (ECG) in normal cardiac rhythm. The aim of this study was to develop and test a deep neural network for VA risk stratification using routinely collected ambulatory ECGs. Methods and results: A multicentre case-control study was undertaken to assess VA-ResNet-50, our open source ResNet-50-based deep neural network. VA-ResNet-50 was designed to read pyramid samples of three-lead 24 h ambulatory ECGs to decide whether a heart is capable of VA based on the ECG alone. Consecutive adults with VA from East Midlands, UK, who had ambulatory ECGs as part of their NHS care between 2014 and 2022 were recruited and compared with all comer ambulatory electrograms without VA. Of 270 patients, 159 heterogeneous patients had a composite VA outcome. The mean time difference between the ECG and VA was 1.6 years (⅓ ambulatory ECG before VA). The deep neural network was able to classify ECGs for VA capability with an accuracy of 0.76 (95% confidence interval 0.66-0.87), F1 score of 0.79 (0.67-0.90), area under the receiver operator curve of 0.8 (0.67-0.91), and relative risk of 2.87 (1.41-5.81). Conclusion: Ambulatory ECGs confer risk signals for VA risk stratification when analysed using VA-ResNet-50. Pyramid sampling from the ambulatory ECGs is hypothesized to capture autonomic activity. We encourage groups to build on this open-source model. Question: Can artificial intelligence (AI) be used to predict whether a person is at risk of a lethal heart rhythm, based solely on an electrocardiogram (an electrical heart tracing)? Findings: In a study of 270 adults (of which 159 had lethal arrhythmias), the AI was correct in 4 out of every 5 cases. If the AI said a person was at risk, the risk of lethal event was three times higher than normal adults. Meaning: In this study, the AI performed better than current medical guidelines. The AI was able to accurately determine the risk of lethal arrhythmia from standard heart tracings for 80% of cases over a year away-a conceptual shift in what an AI model can see and predict. This method shows promise in better allocating implantable shock box pacemakers (implantable cardioverter defibrillators) that save lives.

Patentometric analysis of the technological development of biotechnology for health in higher education institutions in Rio Grande do Sul.

Biotechnology offers solutions and opportunities to meet various societal demands, thereby contributing to significant scientific advancements. This study aimed to characterize the technological development of biotechnology in the healthcare sector in the state of Rio Grande do Sul, Brazil, from 2016 to 2022 by analyzing patents filed by and granted to public and private Higher Education institutions. For data collection, a quantitative exploratory approach was employed using statistical methods and a patent analysis of institutions in the patent database of the Brazilian National Institute of Industrial Property (INPI), focusing on patents related to the healthcare field. Data were collected in October, November, and December. A total of 580 patent records were collected from the INPI, belonging to Sections A and C of the International Patent Classification (IPC) related to educational institutions. Furthermore, this study highlighted that higher education institutions have a higher number of patents in the healthcare field. These results provide an understanding of the strategic areas for technological development in biotechnology in Rio Grande do Sul, Brazil.

New hard tick (Acari: Ixodidae) reports and detection of Rickettsia in ticks from Sierra Nevada de Santa Marta, Colombia.

The Sierra Nevada de Santa Marta (SNSM), located in northern Colombia, is considered a geographical island with high levels of biodiversity and endemism. However, little is known about tick species and their associated microorganisms at the SNSM. In this study we sampled host-seeking ticks in areas of the town of Minca within the SNSM. We collected 47 ticks identified as Amblyomma pacae, Amblyomma longirostre, Amblyomma ovale, Amblyomma mixtum, Haemaphysalis juxtakochi, Ixodes sp. cf. Ixodes affinis and Ixodes sp. Of these ticks, we tested for Rickettsia spp. by amplifying the gltA, SCA1, and 16S rRNA genes via PCR. Rickettsia amblyommatis was detected in one pool of 3 larvae and in a female of A. pacae. Additonally, we isolated Rickettsia sp. belonging to the group of spotted fevers in larvae of A. longirostre. This study reports new findings of six species of ticks and two species of Rickettsia within the SNSM.

RapidpulseTM cyclic aspiration system for acute ischemic stroke due to large vessel occlusions.

BACKGROUND: The best strategy to achieve optimal reperfusion outcomes during mechanical thrombectomy remains to be defined. The RapidPulseTM Cyclic Aspiration System is a novel technology, delivering high-frequency pulsed vacuum forces to increase the efficiency of aspiration thrombectomy. METHODS: Prospective, multicenter, open-label, core lab-adjudicated, two-arm study comparing safety and efficacy of a feasibility version of the RapidPulseTM system compared with contemporary controls. Primary endpoint was the rate of mTICI ≥ 2c after first-pass effect (FPE). Additional efficacy endpoints were the rates of mTICI ≥ 2b after first pass (modified FPE (mFPE)), last pass with study device defined as frontline technical success, and after all passes including rescue therapy. The primary safety endpoints included symptomatic ICH (sICH) within 24 h post-procedure. RESULTS: Between February 2022 to December 2022, 80 subjects were consented and enrolled in the study (n = 40 treatment arm, n = 40 control arm). In the intent to treat (ITT) population, mean age was 67.8 ± 11.5 years; 19 (47.5%) were male. Median NIHSS score was 16 (IQR: 13-22). Median ASPECTS score was 9 (IQR: 8-10). The rate of mTICI ≥ 2c after first pass was 53.9% in ITT population (60.0% in per-protocol population) versus 38.5% in the corresponding control population. Functional independence (mRS 0-2) at 90 days was achieved in 61.1% (22/36) in the RapidPulseTM arm and 52.8% (19/36) in the control arm. In the RapidPulseTM arm, no sICH within 24 h and no device-related morbidity or mortality occurred. CONCLUSION: Preliminary data suggests RapidPulseTM Aspiration System is highly effective and safe for recanalization of large vessel occlusions.

Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03-1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (ß =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD. Trial Registration: ClinicalTrials.gov: NCT03156504.

Clinical Characteristics and Neuroimaging Correlations in Autoimmune Encephalitis: A Report of Two Cases.

Autoimmune encephalitis is an infrequent pathological occurrence documented within our local context. When clinical suspicion arises, employing electroencephalogram and brain magnetic resonance imaging (MRI) proves valuable. However, for conclusive diagnosis confirmation, lumbar puncture for cerebrospinal fluid (CSF) analysis is indispensable. Managing this condition involves a combination of immunosuppression and, when necessary, tumor resection. We document the initial cases reported in our city, featuring two young patients without significant pre-existing conditions. Patients initially displayed behavioral alterations progressing to altered consciousness, febrile peaks, and challenging epileptic status, requiring intensive care and mechanical ventilation. The diagnosis was made based on MRI and anti-N-methyl-D-aspartate (anti-NMDA) antibodies. Treatment involved intravenous (IV) immunoglobulins, plasmapheresis, and corticosteroids. After discharge, both had cognitive sequelae. Autoimmune encephalitis is a pathological condition that still lacks thorough exploration and reporting. It predominantly affects young patients without a history of acute psychiatric symptoms, necessitating consideration when behavioral alterations emerge. The challenges faced by small cities, including a shortage of technical resources, further impede the timely and precise diagnosis of this intricate condition.

Identifying genetic differences between bipolar disorder and major depression through multiple GWAS.

Background: Accurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A key reason is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Aims: Here, we use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores that may aid early differential diagnosis. Methods: Based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting cohort of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform a variety of GWAS and polygenic risk scores (PRS) analyses. Results: While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distinguish BD from MDD, including BD cases with depressive onset. We replicate our PRS findings, but not signals of individual loci in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our case-case GWAS and that of case-control BD. Conclusions: We find that MDD and BD, including BD with a depressive onset, are genetically distinct. Further, our findings support the hypothesis that Controls - MDD - BD primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BD and, importantly, BD with depressive onset from MDD.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.