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The primary objective of this study was to explore the influence of prolonged (24 weeks) supplementary Tai Chi therapy on cognitive capabilities and immune-inflammatory pathways in subjects diagnosed with schizophrenia. A total of 90 individuals who have been clinically diagnosed with schizophrenia were assigned to two treatment groups, namely the Tai Chi treatment (TT) group and the routine treatment (RT) group. Following a 24-week duration of intervention, the data obtained from 32 patients in the TT group and 30 patients in the RT group were meticulously analyzed. At the commencement of the investigation and upon completion of the 24-week intervention, blood samples were gathered, and clinical evaluations were executed. In plasma, the identification of nine cytokines (IL-10, IFN-γ, IL-5, GM-CSF, TNF-α, IL-13, IL-4, IL-2, and IL-12) was conducted using the multiple primer suspension chip method. The clinical evaluations encompassed CGI, WHOQUOL-BREF, SOFS, PSS, BPRS, SAPS, SANS, and RBANS. In comparison to the RT group, the patients in the TT group demonstrated decreased levels of TNF-α and IL-5 (P < 0.05). Moreover, they encountered more pronounced advancements in SAPS, SANS, PSS, SOFS, and RBANS scores (P < 0.05). Additionally, a positive connection was detected between the plasma TNF-α level in the TT group and both the SANS score and the SPFS score (P < 0.05). Tai Chi has been shown to improve clinical symptoms in patients with schizophrenia as an add-on therapy, potentially through its effects on immunomodulatory pathways.
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Background: Benign paroxysmal positional vertigo (BPPV) is a common neurological disorder with a high recurrence rate. Type 2 diabetes mellitus (T2DM) is recognized as a risk factor for BPPV recurrence. However, the genomic association between T2DM and BPPV recurrence remains understudied. Methods: Differential gene expression analysis and weighted gene co-expression network analysis were used to identify shared genes between BPPV recurrence and T2DM. The MCC algorithm was employed to select hub genes from the protein-protein interaction network of the shared genes. The predictive efficacy of hub genes for BPPV recurrence and T2DM was assessed using ROC curve analysis. Genemania database was used to identify downstream targets of hub genes. The immune infiltration landscape of BPPV and T2DM was characterized using the CIBERSORT algorithm. Correlation analysis was performed to explore the relationship between hub genes and immune cells. The expression levels of hub genes in patient blood samples were validated using qPCR. Results: Thirteen shared genes were identified and a protein-protein interaction network was constructed for BPPV recurrence and T2DM. Subsequently, four hub genes were selected, and their expression levels effectively predicted the occurrence of BPPV recurrence and T2DM. These hub genes were highly correlated with immune cell infiltration, indicating a common mechanism underlying recurrent BPPV and T2DM. Finally, the upregulation of hub genes in patients with T2DM comorbid with BPPV recurrence was confirmed in blood samples. These hub genes may serve as predictive biomarkers for assessing the recurrence rate in BPPV patients with comorbid T2DM. Conclusion: We proposed shared gene characteristics between BPPV recurrence and T2DM, revealing an immune-mediated inflammatory regulation as a common pathway and identifying four immune-related biomarkers and potential therapeutic targets for T2DM comorbid with recurrent BPPV.
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Prolamin-based particles loaded with bioactive molecules have attracted widespread attention from scientists due to their novel properties in chemistry, physics, and biology. In the self-assembly process of biopolymer-based nanocapsules, noncovalent interactions are the main driving forces for reducing bulk materials to the nanoscale and controlling the release of bioactive molecules. This article reviews the types of interaction forces, binding strength, binding active sites, molecular orientation, and binding affinity that affect the release profile of bioactive molecules during the preparation of protein stabilizer particles. Different preparation formulations, the use of different biopolymers, the inherent nature of the loaded bioactive molecules, and external factors (including pH, biopolymer concentration, temperature, salt, ultrasonication, and atmospheric cold plasma treatment) lead to different types and strengths of intra- and intermolecular interactions. Strategies, such as pH, ultrasonication, and atmospheric cold plasma, to change the protein conformation are key to improving the binding strength between proteins and bioactive substances or stabilizers. This review provides some guidance for scientists and technicians dedicated to improving loading efficiency, delaying release, enhancing colloidal stability, and exploring the binding behavior among proteins, stabilizers, and bioactive molecules.
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Solar-driven interfacial evaporation is an efficient method for purifying contaminated or saline water. Nonetheless, the suboptimal design of the structure and composition still necessitates a compromise between evaporation rate and service life. Therefore, achieving efficient production of clean water remains a key challenge. Here, a biomimetic dictyophora hydrogel based on loofah/carbonized sucrose@ZIF-8/polyvinyl alcohol is demonstrated, which can serve as an independent solar evaporator for clean water recovery. This special structural design achieves effective thermal positioning and minimal heat loss, while reducing the actual enthalpy of water evaporation. The evaporator achieves a pure water evaporation rate of 3.88 kg m-2 h-1 and a solar-vapor conversion efficiency of 97.16% under 1 sun irradiation. In comparison, the wastewater evaporation rate of the evaporator with ZIF-8 remains at 3.85 kg m-2 h-1 for 30 days, which is 16.3% higher than the light irradiation without ZIF-8. Equally important, the evaporator also showcases the capability to cleanse water from diverse sources of contaminants, including those with small molecules, oil, heavy metal ions, and bacteria, greatly improving the lifespan of the evaporator.
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To evaluate the clinical evidence of platelet-rich plasma (PRP) in the treatment of venous ulcers (VUs). Electronic searches were conducted through the Cochrane Library, Web of Science, Embase and PubMed. AMSTAR-2 was used to assess the methodological quality. The quality of evidence was assessed using the GRADE system. According to AMSTAR-2, the methodological quality of the included reviews was generally inadequate owing to the limitations of entries 2, 4 and 7. Due to bias risk and imprecision, the evidence quality of the outcome measures was inadequate. In conclusion, PRP may have a therapeutic effect on VUs. However, this conclusion must be treated with caution due to methodological flaws of the included systematic reviews and meta-analyses.
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Cancer treatment faces numerous challenges, such as inadequate drug targeting, steep price tags, grave toxic side effects, and limited therapeutic efficacy. Therefore, there is an urgent need for a safe and effective new drug to combat cancer. Microbial polysaccharides, complex and diverse biological macromolecules, exhibit significant microbial variability and uniqueness. Studies have shown that terrestrial microbial polysaccharides possess a wide range of biological activities, including immune enhancement, antioxidant properties, antiviral effects, anti-tumour potential, and hypoglycemic functions. To delve deeper into the structure-activity relationship of these land-based microbial polysaccharides against cancer, we conducted a comprehensive review and analysis of anti-cancer literature published between 2020 and 2024. The anticancer efficacy of terrestrial microbial polysaccharides is influenced by multiple factors, including the microbial species, existing form, chemical structure, and polysaccharide purity. According to the literature, an optimal molecular weight and good water solubility are essential for demonstrating anticancer activity. Furthermore, the addition of mannose and galactose has been found to significantly enhance the anticancer properties of these polysaccharides. These insights will serve as a valuable reference for future research and progress in the field of cancer drug therapy, particularly with regards to terrestrial microbial polysaccharides.
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Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Polissacarídeos/química , Polissacarídeos/uso terapêutico , Polissacarídeos/farmacologia , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/uso terapêutico , Relação Estrutura-Atividade , Animais , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/uso terapêuticoRESUMO
Investigational therapeutics that target toxic species of α-synuclein (αSyn) aim to slow down or halt disease progression in patients with Parkinson's disease (PD). Here this 44-week, randomized, placebo-controlled, double-blind, single-center phase 1 study investigated safety, tolerability and immunogenicity of UB-312, an active immunotherapeutic targeting pathological αSyn, in patients with PD. The primary outcome measures were adverse event frequency and change in anti-αSyn antibody titers in blood and cerebrospinal fluid (CSF). Exploratory outcomes were changes in clinical scales and biomarker-based target engagement as measured by seed amplification assays. Twenty patients were randomized 7:3 (UB-312:placebo) into 300/100/100 µg or 300/300/300 µg (weeks 1, 5 and 13) intramuscular prime-boost dose groups. Safety was similar across groups; adverse events were mostly mild and transient. Two patients experienced three serious adverse events in total, one possibly treatment related; all resolved without sequalae. Anti-αSyn antibodies in serum from 12/13 and CSF from 5/13 patients who received three UB-312 doses confirmed immunogenicity. Mean serum titers (in log-dilution factor) increased from baseline by 1.398 and 1.354, and peaked at week 29 at 2.520 and 2.133, for 300/100/100 µg and 300/300/300 µg, respectively. CSF titers were 0 at baseline and were 0.182 and 0.032 at week 21, respectively. Exploratory analyses showed no statistical differences in clinical scales but a significant reduction of αSyn seeds in CSF of a subset of UB-312-treated patients. These data support further UB-312 development. ClinicalTrials.gov: NCT04075318 .
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A new triterpenoid compound 1* (scandine A1) was obtained from 95% ethanol extract of Uncaria laevigata. Meanwhile, eleven described compounds were also isolated for the first time from Uncaria laevigata. Herein, compound 2 exhibited strong diastolic cardio-cerebrovascular activity (EC50BA = 9.22 µM and EC50CA = 14.65 µM), which was not been previously described. Compound 1* also showed certain diastolic cardio-cerebrovasculary activity. Network pharmacology indicated that the diastolic cardio-cerebrovascular activity of compound 2 was most correlated with the Ras signalling pathway. Molecular docking confirmed that it exhibited strong binding activity with target protein (matrix metalloproteinase inhibitor-1). Moreover, compound 2 demonstrated significant potential on cardio-cerebrovascular activity in vitro. Overall, compounds 1* and 2 with good diastolic cardio-cerebrovascular activity were discovered in this work.
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Simultaneous sensitive and precise determination of multibiomarkers is of great significance for improving detection efficiency, reducing diagnosis and treatment expenses, and elevating survival rates. However, the development of simple and portable biosensors for simultaneous determination of multiplexed targets in biological fluids still faces challenges. Herein, a unique and versatile immobilization-free dual-target electrochemical biosensing platform, which combines distinguishable magnetic signal reporters with buoyancy-magnetism separation, was designed and constructed for simultaneous detection of carcinoembryonic (CEA) and α-fetoprotein (AFP) in intricate biological fluids. To construct such distinguishable magnetic signal reporters with signal transduction, amplification, and output, secondary antibodies of CEA and AFP were respectively functionalized on methylene blue (MB) and 6-(ferrocenyl)hexanethiol (FeC) modified Fe3O4@Au magnetic nanocomposites. Meanwhile, a multifunctional flotation probe with dual target recognition, capture, and isolation capability was prepared by conjugating primary antibodies (Ab1-CEA, Ab1-AFP) to hollow buoyant microspheres. The target antigens of CEA and AFP can trigger a flotation-mediated sandwich-type immunoreaction and capture a certain amount of the distinguishable magnetic signal reporter, which enables the conversion of the target CEA and AFP quantities to the signal of the potential-resolved MB and FeC. Thus, the MB and FeC currents of magnetically adsorbed distinguishable magnetic reporters can be used to determine the CEA and AFP targets simultaneously and precisely. Accordingly, the proposed strategy exhibited a delightful linear response for CEA and AFP in the range of 100 fg·mL-1-100 ng·mL-1 with detection limits of 33.34 and 17.02 fg·mL-1 (S/N = 3), respectively. Meanwhile, no significant nonspecific adsorption and cross-talk were observed. The biosensing platform has shown satisfactory performance in the determination of real clinical samples. More importantly, the proposed approach can be conveniently extended to universal detection just by simply substituting biorecognition events. Thus, this work opens up a new promising perspective for dual and even multiple targets and offers promising potential applications in clinical diagnosis.
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Técnicas Biossensoriais , Antígeno Carcinoembrionário , Técnicas Eletroquímicas , alfa-Fetoproteínas , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/imunologia , Antígeno Carcinoembrionário/análise , Antígeno Carcinoembrionário/imunologia , Técnicas Biossensoriais/métodos , Humanos , Imunoensaio/métodos , Ouro/química , Limite de DetecçãoRESUMO
Plasma membrane proteins mediate important aspects of physiology, including nutrient acquisition, cell-cell interactions, and monitoring homeostasis. The trafficking of these proteins, involving internalisation from and/or recycling back to the cell surface, is often critical to their functions. These processes can vary among different proteins and cell types and states and are still being elucidated. Current strategies to measure surface protein internalisation and recycling are typically microscopy or biochemical assays; these are accurate but generally limited to analysing a homogenous cell population and are often low throughput. Here, we present flow cytometry-based methods involving probe-conjugated antibodies that enable quantification of internalisation or recycling rates at the single-cell level in complex samples. To measure internalisation, we detail an assay where the protein of interest is labelled with a specific antibody conjugated to a fluorescent oligonucleotide-labelled probe. To measure recycling, a specific antibody conjugated to a cleavable biotin group is employed. These probes permit the differentiation of molecules that have been internalised or recycled from those that have not. When combined with cell-specific marker panels, these methods allow the quantitative study of plasma membrane protein trafficking dynamics in a heterogenous cell mixture at the single-cell level. Key features ⢠These assays allow sensitive quantification of internalised or recycled surface molecules using oligonucleotide or cleavable biotin-conjugated probes, respectively, and detected by flow cytometry. ⢠They can be adapted to any membrane protein that transits via the cell surface and for which a specific purified antibody is available. ⢠The dynamics of a cell surface protein can be measured in heterogenous cell populations simultaneously, including various cellular activation states. ⢠The internalisation assay builds upon the method developed by Liu et al. [1,2] and extends its application to heterogenous human peripheral blood mononuclear cells. ⢠These assays have been extensively used on suspension cells but have not been tested on adherent cells.
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The present study aimed to investigate the effect of a blatant activation of age-based stereotype threats (ABST) on time-based prospective memory (TBPM) in older adults. A sample of 74 adults from Hong Kong was randomly assigned to one of the two experimental conditions: the stereotyped condition (n = 36) or the neutral condition (n = 38). Participants were asked to read fictitious news reports related to dementia (stereotyped condition) or the importance of English oral skills (neutral condition). After, all participants performed a TBPM task using the Chinese lexical decision task as an ongoing task block. The results indicate a main effect of ABST on TBPM accuracy. Specifically, older adults under a blatant activation of ABST demonstrated lower TBPM accuracy (p < 0.05, ηp2 = 0.08). Further analyses based on age groups demonstrated that TBPM accuracy was only impaired in older participants (aged 70-80 years) (p < 0.05, ηp2 = 0.19). The study, for the first time, provides evidence that ABST can disrupt TBPM performance in older adults, especially when cues are blatantly activated.
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The first and stereoselective synthesis of xylodonin A and 22-hydroxyxylodonin A, two drimane-type sesquiterpenoid natural products, was developed from the readily available (+)-sclareolide. This route features an allylic oxidation and acid-promoted dehydration for construction of the key intermediate 6-hydroxyisodrimenin. Representative analogues were synthesized, and their previously unknown bioactivities were revealed after biological evaluation. The analogue 19a exhibited cytotoxic activity against liver cancer HepG2 cells (IC50: 8.8 vs 5.9 µM) that was comparable to that of the clinical anticancer drug etoposide with lower toxicity to normal liver HL7702 cells (IC50 > 100 µM).
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Sesquiterpenos , Humanos , Estereoisomerismo , Estrutura Molecular , Células Hep G2 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/síntese químicaRESUMO
Pruritus, also known as itching, is a complex sensation that involves the activation of specific physiological and cellular receptors. The skin is innervated with sensory nerves as well as some receptors for various sensations, and its immune system has prominent neurological connections. Sensory neurons have a considerable impact on the sensation of itching. However, immune cells also play a role in this process, as they release pruritogens. Disruption of the dermal barrier activates an immune response, initiating a series of chemical, physical, and cellular reactions. These reactions involve various cell types, including keratinocytes, as well as immune cells involved in innate and adaptive immunity. Collective activation of these immune responses confers protection against potential pathogens. Thus, understanding the molecular and cellular mechanisms that contribute to pruritus in host skin is crucial for the advancement of effective treatment approaches. This review provides a comprehensive analysis of the present knowledge concerning the molecular and cellular mechanisms underlying itching signaling in the skin. Additionally, this review explored the integration of these mechanisms with the broader context of itch mediators and the expression of their receptors in the skin.
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Prurido , Pele , Humanos , Prurido/genética , Prurido/metabolismo , Queratinócitos , Células Receptoras Sensoriais/metabolismo , Transdução de SinaisRESUMO
Oil palm processing generates substantial waste materials rich in organic content, posing various environmental challenges. Anaerobic digestion (AD), particularly for palm oil mill effluent (POME), offers a sustainable solution, by converting waste into valuable biomethane for thermal energy or electricity generation. The synergistic activities of the AD microbiota directly affect the biomethane production, and the microbial community involved in biomethane production in POME anaerobic digestion has been reported. The composition of bacterial and archaeal communities varies under different substrate and physicochemical conditions. This review discusses the characteristics of POME, explores the microbial members engaged in each stage of AD, and elucidates the impacts of substrate and physicochemical conditions on the microbial community dynamics, with a specific focus on POME. Finally, the review outlines current research needs and provides future perspectives on optimizing the microbial communities for enhanced biomethane production from oil palm wastes.
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Rapeseed (Brassica napus L.) is one of the important oil crops, with a high demand for nitrogen (N). It is essential to explore the potential of rapeseed to improve nitrogen utilization efficiency (NUtE). Rapeseed is an allotetraploid crop with a relatively large and complex genome, and there are few studies on the mapping of genes related to NUtE regulation. In this study, we used the combination of bulk segregant analysis sequencing (BSA-Seq) and RNA sequencing (RNA-Seq) to analyze the N-efficient genotype 'Zheyou 18' and N-inefficient genotype 'Sollux', to identify the genetic regulatory mechanisms. Several candidate genes were screened, such as the high-affinity nitrate transporter gene NRT2.1 (BnaC08g43370D) and the abscisic acid (ABA) signal transduction-related genes (BnaC02g14540D, BnaA03g20760D, and BnaA05g01330D). BnaA05g01330D was annotated as ABA-INDUCIBLE bHLH-TYPE TRANSCRIPTION FACTOR (AIB/bHLH17), which was highly expressed in the root. The results showed that the primary root length of the ataib mutant was significantly longer than that of the wild type under low N conditions. Overexpression of BnaA5.AIB could reduce the NUtE under low N levels in Arabidopsis (Arabidopsis thaliana). Candidate genes identified in this study may be involved in the regulation of NUtE in rapeseed, and new functions of AIB in orchestrating N uptake and utilization have been revealed. It is indicated that BnaA5.AIB may be the key factor that links ABA to N signaling and a negative regulator of NUtE. It will provide a theoretical basis and application prospect for resource conservation, environmental protection, and sustainable agricultural development.
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Brassica napus , Brassica rapa , Brassica napus/genética , RNA-Seq , Brassica rapa/genética , Análise de Sequência de RNA , NitrogênioRESUMO
A new alkaloid 1* (scandine Z) and fourteen known natural products were isolated from 95% ethanol extract of Uncaria laevigata for the first time. Besides compound 1*, these fourteen compounds were firstly isolated from Uncaria laevigata. Excitedly, compound 4 exhibited strong anti-inflammatory activity (IC50 = 8.12 µmol/L), which wasn't described before. Moreover, compound 1* also de--monstrated certain anti-inflammatory activity (IC50 = 10.34 µmol/L). Network pharmacology suggested that compound 4 was involved in the IL-17 signalling pathway and the regulation of inflammation pathway. Molecular docking confirmed that it showed strong binding activity with the target protein (peroxisome proliferator-activated receptor γ, PPAR). Overall, compounds 1* and 4 exhibited strong anti-inflammatory activity and served as lead compounds and anti-inflammatory molecules for further study in vivo.
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Phosphorus modified biochar (P-BC) is an effective adsorbent for wastewater remediation, which has attracted widespread attention due to its low cost, vast source, unique surface structure, and abundant functional groups. However, there is currently no comprehensive analysis and review of P-BC in wastewater remediation. In this study, a detailed introduction is given to the synthesis method of P-BC, as well as the effects of pyrolysis temperature and residence time on physical and chemical properties and adsorption performance of the material. Meanwhile, a comprehensive investigation and evaluation were conducted on the different biomass types and phosphorus sources used to synthesize P-BC. This article also systematically compared the adsorption efficiency differences between P-BC and raw biochar, and summarized the adsorption mechanism of P-BC in removing pollutants from wastewater. In addition, the effects of P-BC composite with other materials (element co-doping, polysaccharide stabilizers, microbial loading, etc.) on physical and chemical properties and pollutant adsorption capacity of the materials were investigated. Some emerging applications of P-BC were also introduced, including supercapacitors, CO2 adsorbents, carbon sequestration, soil heavy metal remediation, and soil fertility improvement. Finally, some valuable suggestions and prospects were proposed for the future research direction of P-BC to achieve the goal of multiple utilization.
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Poluentes Ambientais , Poluentes Químicos da Água , Águas Residuárias , Carvão Vegetal/química , Solo/química , Poluentes Ambientais/análise , Adsorção , Fósforo , Poluentes Químicos da Água/análiseRESUMO
With the pace of life accelerating, multitasking has become the norm in daily life. According to research, multiple cognitive processes, including numerical reasoning, comprehension, and writing, are negatively affected by multitasking. However, only a few studies have investigated the relationship between multitasking and metacognition. In this study, the effect of multitasking on metacognition was examined using a prospective monitoring paradigm (prediction of subsequent recall performance). In Experiment 1, the participants simultaneously studied word pairs (primary task) and differentiated between different sound pitches (secondary task) and then predicted their performance in a subsequent memory test for the studied word pairs (prospective metacognitive monitoring). The accuracy of metacognitive evaluation with multitasking was then compared with that without multitasking. In Experiment 2, sounds and icons of real-life applications were used to improve the ecological validity of the experiment in the secondary task. The results indicated that multitasking impaired metacognition in both artificial and real-life simulated scenarios. In addition, the participants who engaged in more media multitasking in their daily lives exhibited poorer metacognitive monitoring abilities in single tasks.
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Metacognição , Humanos , Estudos Prospectivos , Rememoração Mental , Resolução de Problemas , CompreensãoRESUMO
OBJECTIVES: This study aimed to identify individual-level factors that affect malnutrition outcomes among children and adolescents living with HIV/AIDS in Tanzania. METHODS: We used data from the National AIDS Control Programme. 70,102 participants aged 5 to 19 years attending care and treatment clinics between January to December 2021 were included. Nutritional assessments were performed by anthropometric measurement. Logistic regression models were used to evaluate risk factors. We further estimated marginal prevalence and adjusted predictions by marginal effects. Supplementary analysis assessed the accuracy of the final fitted model. RESULTS: Prevalence of malnutrition for stunting, underweight, wasting, and anthropometric failure (CIAF) were 36.0%, 28.9%, 13.0%, and 48.0%, respectively. Several individual-level factors were significant determinants of malnutrition. Boys, participants aged 15-19 years, those switched to second- or third-line antiretroviral therapy (ART), initiated ART at ages of 5-14 years, ART duration less than 3 years, and were in advanced stages of WHO HIV clinical status had increased adjusted odds ratios and marginal prevalence. The larger AUC values for all models implied importance of identified factors accounted for malnutrition. CONCLUSIONS: On long-term ART, nutritional interventions should be context-specific guidelines to improve growth, especially at ART initiation, ART regimen, and ART duration reckoning with age and sex.