Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.122
Filtrar
Mais filtros

Intervalo de ano de publicação
1.
Nature ; 625(7993): 85-91, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38172362

RESUMO

The world's population increasingly relies on the ocean for food, energy production and global trade1-3, yet human activities at sea are not well quantified4,5. We combine satellite imagery, vessel GPS data and deep-learning models to map industrial vessel activities and offshore energy infrastructure across the world's coastal waters from 2017 to 2021. We find that 72-76% of the world's industrial fishing vessels are not publicly tracked, with much of that fishing taking place around South Asia, Southeast Asia and Africa. We also find that 21-30% of transport and energy vessel activity is missing from public tracking systems. Globally, fishing decreased by 12 ± 1% at the onset of the COVID-19 pandemic in 2020 and had not recovered to pre-pandemic levels by 2021. By contrast, transport and energy vessel activities were relatively unaffected during the same period. Offshore wind is growing rapidly, with most wind turbines confined to small areas of the ocean but surpassing the number of oil structures in 2021. Our map of ocean industrialization reveals changes in some of the most extensive and economically important human activities at sea.


Assuntos
Atividades Humanas , Indústrias , Oceanos e Mares , Imagens de Satélites , Humanos , COVID-19/epidemiologia , Aprendizado Profundo , Fontes Geradoras de Energia/estatística & dados numéricos , Abastecimento de Alimentos/estatística & dados numéricos , Sistemas de Informação Geográfica , Mapeamento Geográfico , Atividades Humanas/economia , Atividades Humanas/estatística & dados numéricos , Caça/estatística & dados numéricos , Indústrias/economia , Indústrias/estatística & dados numéricos , Navios/estatística & dados numéricos , Vento
2.
N Engl J Med ; 388(25): 2315-2325, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37224232

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).


Assuntos
Antidepressivos , Transtorno Depressivo Resistente a Tratamento , Eletroconvulsoterapia , Ketamina , Humanos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia/efeitos adversos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/diagnóstico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/terapia , Administração Intravenosa , Transtornos Psicóticos
3.
Nature ; 583(7817): 560-566, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32699397

RESUMO

There are concerns that recent climate change is altering the frequency and magnitude of river floods in an unprecedented way1. Historical studies have identified flood-rich periods in the past half millennium in various regions of Europe2. However, because of the low temporal resolution of existing datasets and the relatively low number of series, it has remained unclear whether Europe is currently in a flood-rich period from a long-term perspective. Here we analyse how recent decades compare with the flood history of Europe, using a new database composed of more than 100 high-resolution (sub-annual) historical flood series based on documentary evidence covering all major regions of Europe. We show that the past three decades were among the most flood-rich periods in Europe in the past 500 years, and that this period differs from other flood-rich periods in terms of its extent, air temperatures and flood seasonality. We identified nine flood-rich periods and associated regions. Among the periods richest in floods are 1560-1580 (western and central Europe), 1760-1800 (most of Europe), 1840-1870 (western and southern Europe) and 1990-2016 (western and central Europe). In most parts of Europe, previous flood-rich periods occurred during cooler-than-usual phases, but the current flood-rich period has been much warmer. Flood seasonality is also more pronounced in the recent period. For example, during previous flood and interflood periods, 41 per cent and 42 per cent of central European floods occurred in summer, respectively, compared with 55 per cent of floods in the recent period. The exceptional nature of the present-day flood-rich period calls for process-based tools for flood-risk assessment that capture the physical mechanisms involved, and management strategies that can incorporate the recent changes in risk.

5.
Curr Issues Mol Biol ; 46(8): 8726-8740, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39194732

RESUMO

This study aimed to evaluate the efficacy of the ethanolic extract of Anadenanthera colubrina in modulating the immune response in the Experimental Autoimmune Encephalomyelitis (EAE) model. The ethanolic extract of the dried bark was analyzed by ESI (+) Orbitrap-MS to obtain a metabolite profile, demonstrating a wide variety of polyphenols, such as flavonoids and phenolic acids. Various parameters were evaluated, such as clinical signs, cytokines, cellular profile, and histopathology in the central nervous system (CNS). The ethanolic extract of A. colubrina demonstrated significant positive effects attenuating the clinical signs and pathological processes associated with EAE. The beneficial effects of the extract treatment were evidenced by reduced levels of pro-inflammatory cytokines, such as IL1ß, IL-6, IL-12, TNF, IFN-γ, and a notable decrease in several cell profiles, including CD8+, CD4+, CD4+IFN-γ, CD4+IL-17+, CD11c+MHC-II+, CD11+CD80+, and CD11+CD86+ in the CNS. In addition, histological analysis revealed fewer inflammatory infiltrates and demyelination sites in the spinal cord of mice treated with the extract compared to the control model group. These results showed, for the first time, that the ethanolic extract of A. colubrina exerts a modulatory effect on inflammatory processes, improving clinical signs in EAE, in the acute phase of the disease, which could be further explored as a possible therapeutic alternative.

6.
Gastroenterology ; 164(3): 344-372, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36822736

RESUMO

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/diagnóstico , Lactoferrina/metabolismo , Lactoferrina/uso terapêutico , Biomarcadores/metabolismo , Proteína C-Reativa/metabolismo , Fezes/química , Complexo Antígeno L1 Leucocitário/metabolismo , Índice de Gravidade de Doença , Colonoscopia
7.
Gastroenterology ; 165(6): 1367-1399, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37981354

RESUMO

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Biomarcadores , Proteína C-Reativa , Fezes , Complexo Antígeno L1 Leucocitário
8.
Clin Gastroenterol Hepatol ; 22(6): 1315-1322.e7, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38191014

RESUMO

BACKGROUND AND AIMS: Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation. METHODS: This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54-70 years of age with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. RESULTS: Sixty-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) vs mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared with mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% confidence interval: 8.3%-27.9%) and secure message outreach (13.1%; 97.5% confidence interval: 3.5%-22.7%) vs mailed letter outreach. CONCLUSIONS: Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting. (ClinicalTrials.gov, Number: NCT05389397).


Assuntos
Colonoscopia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenoma/diagnóstico , California , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/prevenção & controle , Detecção Precoce de Câncer/métodos , Telefone
9.
BMC Plant Biol ; 24(1): 570, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886648

RESUMO

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.


Assuntos
Estudo de Associação Genômica Ampla , Umidade , Saccharum , Sacarose , Saccharum/genética , Saccharum/metabolismo , Colômbia , Sacarose/metabolismo , Polimorfismo de Nucleotídeo Único , Genótipo
10.
Microb Pathog ; 186: 106483, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38092133

RESUMO

Ascariasis is the most prevalent helminth affecting approximately 819 million people worldwide. The acute phase of Ascariasis is characterized by larval migration of Ascaris spp., through the intestinal wall, carried to the liver and lungs of the host by the circulatory system. Most of the larvae subsequently transverse the lung parenchyma leading to tissue injury, reaching the airways and pharynx, where they can be expectorated and swallowed back to the gastrointestinal tract, where they develop into adult worms. However, some larvae are trapped in the lung parenchyma inciting an inflammatory response that causes persistent pulmonary tissue damage long after the resolution of infection, which returns to tissue homeostasis. However, the mechanism by which chronic lung disease develops and resolves remains unknown. Here, using immunohistochemistry, we demonstrate that small fragments and larval antigens of Ascaris suum are deposited and retained chronically in the lung parenchyma of mice following a single Ascaris infection. Our results reveal that the prolonged presence of Ascaris larval antigens in the lung parenchyma contributes to the persistent immune stimulation inducing histopathological changes observed chronically following infection, and clearly demonstrate that larval antigens are related to all phases of tissue adaptation after infection: lung injury, chronic inflammation, resolution, and tissue remodeling, in parallel to increased specific humoral immunity and the recovery of lung function in mice. Additional insight is needed into the mechanisms of Ascaris antigen to induce chronic immune responses and resolution in the host lungs following larval migration.


Assuntos
Ascaríase , Ascaris suum , Humanos , Animais , Camundongos , Ascaríase/patologia , Ascaris suum/fisiologia , Pulmão/patologia , Imunidade , Intestinos/patologia , Larva
11.
Clin Sci (Lond) ; 138(17): 1071-1087, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39136472

RESUMO

Perivascular adipose tissue (PVAT) negatively regulates vascular muscle contraction. However, in the context of obesity, the PVAT releases vasoconstrictor substances that detrimentally affect vascular function. A pivotal player in this scenario is the peptide endothelin-1 (ET-1), which induces oxidative stress and disrupts vascular function. The present study postulates that obesity augments ET-1 production in the PVAT, decreases the function of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, further increasing reactive oxygen species (ROS) generation, culminating in PVAT dysfunction. Male C57BL/6 mice were fed either a standard or a high-fat diet for 16 weeks. Mice were also treated with saline or a daily dose of 100 mg·kg-1 of the ETA and ETB receptor antagonist Bosentan, for 7 days. Vascular function was evaluated in thoracic aortic rings, with and without PVAT. Mechanistic studies utilized PVAT from all groups and cultured WT-1 mouse brown adipocytes. PVAT from obese mice exhibited increased ET-1 production, increased ECE1 and ETA gene expression, loss of the anticontractile effect, as well as increased ROS production, decreased Nrf2 activity, and downregulated expression of Nrf2-targeted antioxidant genes. PVAT of obese mice also exhibited increased expression of Tyr216-phosphorylated-GSK3ß and KEAP1, but not BACH1 - negative Nrf2 regulators. Bosentan treatment reversed all these effects. Similarly, ET-1 increased ROS generation and decreased Nrf2 activity in brown adipocytes, events mitigated by BQ123 (ETA receptor antagonist). These findings place ET-1 as a major contributor to PVAT dysfunction in obesity and highlight that pharmacological control of ET-1 effects restores PVAT's cardiovascular protective role.


Assuntos
Tecido Adiposo , Regulação para Baixo , Endotelina-1 , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2 , Obesidade , Espécies Reativas de Oxigênio , Animais , Endotelina-1/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Masculino , Tecido Adiposo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Bosentana/farmacologia , Dieta Hiperlipídica , Camundongos , Estresse Oxidativo , Receptor de Endotelina A/metabolismo , Receptor de Endotelina A/genética , Enzimas Conversoras de Endotelina/metabolismo , Aorta Torácica/metabolismo , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia
12.
Mol Psychiatry ; 2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882501

RESUMO

Genome-wide association studies (GWAS) of mood disorders in large case-control cohorts have identified numerous risk loci, yet pathophysiological mechanisms remain elusive, primarily due to the very small effects of common variants. We sought to discover risk variants with larger effects by conducting a genome-wide association study of mood disorders in a founder population, the Old Order Amish (OOA, n = 1,672). Our analysis revealed four genome-wide significant risk loci, all of which were associated with >2-fold relative risk. Quantitative behavioral and neurocognitive assessments (n = 314) revealed effects of risk variants on sub-clinical depressive symptoms and information processing speed. Network analysis suggested that OOA-specific risk loci harbor novel risk-associated genes that interact with known neuropsychiatry-associated genes via gene interaction networks. Annotation of the variants at these risk loci revealed population-enriched, non-synonymous variants in two genes encoding neurodevelopmental transcription factors, CUX1 and CNOT1. Our findings provide insight into the genetic architecture of mood disorders and a substrate for mechanistic and clinical studies.

13.
Mol Psychiatry ; 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36991131

RESUMO

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list (Phypergeometric = 1.28E-09 and 4.10E-18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

14.
Mol Psychiatry ; 2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37433967

RESUMO

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

15.
Phys Chem Chem Phys ; 26(7): 6068-6079, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38299458

RESUMO

This work explores the photochemical degradation of cationic species of 7-hydroxy-1-methyl-2H-pyrido[3,4-b]indole or harmol (1C) and the corresponding partially hydrogenated derivative 7-hydroxy-1-methyl-3,4-dihydro-2H-pyrido[3,4-b]indole or harmalol (2C) in aqueous solution. UV-visible absorption and fluorescence emission spectroscopy coupled with multivariate data analysis (MCR-ALS and PARAFAC), HPLC and HRESI-MS techniques were used for both quantitative and qualitative analysis. The formation of hydrogen peroxide reactive oxygen species (ROS) was quantified, and the influence of pH, oxygen partial pressure and photoexcitation source on the photochemical degradation of both compounds was assessed. The potential implications on the biosynthesis of ßCs and their biological role in living systems are discussed.


Assuntos
Alcaloides , Harmalina/análogos & derivados , Harmina/análogos & derivados , Água , Indóis , Concentração de Íons de Hidrogênio
16.
J Dairy Sci ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945268

RESUMO

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.

17.
An Acad Bras Cienc ; 96(1): e20231201, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451600

RESUMO

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.


Assuntos
Academias e Institutos , Biotecnologia , Brasil , Universidades , Bases de Dados Factuais
18.
An Acad Bras Cienc ; 96(3): e20221001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865505

RESUMO

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.


Assuntos
Cactaceae , Fermentação , Valor Nutritivo , Cactaceae/química , Cactaceae/classificação , Cinética , Ração Animal/análise
19.
Chaos ; 34(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38341761

RESUMO

The description of neuronal activity has been of great importance in neuroscience. In this field, mathematical models are useful to describe the electrophysical behavior of neurons. One successful model used for this purpose is the Adaptive Exponential Integrate-and-Fire (Adex), which is composed of two ordinary differential equations. Usually, this model is considered in the standard formulation, i.e., with integer order derivatives. In this work, we propose and study the fractal extension of Adex model, which in simple terms corresponds to replacing the integer derivative by non-integer. As non-integer operators, we choose the fractal derivatives. We explore the effects of equal and different orders of fractal derivatives in the firing patterns and mean frequency of the neuron described by the Adex model. Previous results suggest that fractal derivatives can provide a more realistic representation due to the fact that the standard operators are generalized. Our findings show that the fractal order influences the inter-spike intervals and changes the mean firing frequency. In addition, the firing patterns depend not only on the neuronal parameters but also on the order of respective fractal operators. As our main conclusion, the fractal order below the unit value increases the influence of the adaptation mechanism in the spike firing patterns.


Assuntos
Fractais , Modelos Neurológicos , Potenciais de Ação/fisiologia , Neurônios/fisiologia
20.
Pestic Biochem Physiol ; 202: 105921, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879297

RESUMO

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.


Assuntos
Resistência a Inseticidas , Inseticidas , Spodoptera , Animais , Spodoptera/genética , Spodoptera/efeitos dos fármacos , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Inseticidas/toxicidade , Perfilação da Expressão Gênica , Transcriptoma , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismo , Macrolídeos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA