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1.
Child Care Health Dev ; 50(3): e13271, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738842

RESUMO

OBJECTIVE: The aim of this study is to identify the main processes and outcomes related to family-centred care (FCC) in neuromotor and functional rehabilitation of preschool children with cerebral palsy (CP). BACKGROUND: FCC is considered a reference for best practices in child rehabilitation. CP is the most common cause of physical disability in childhood with repercussions on functionality. There is a gap in knowledge of the practical principles of FCC, and it is necessary to develop a reference model for the practice of child rehabilitation professionals. METHODS: In this scoping review, the main databases selected were as follows: LILACS; Pubmed; Embase; The Cochrane Library; CINAHL (EBSCO); Scopus; Web of Science; PEDro (Physiotherapy Evidence Database); Open Gray and other banks of thesis. The terms combined in the search strategy were as follows: 'Family-centered', 'Family-centred' and 'CP'. Inclusion criteria are as follows: studies on preschool-aged children with CP, undergoing family-centred functional therapeutic interventions (FCFTI) with outcomes on bodily structures and functions and/or activities and/or participation. RESULTS: The main participatory care methods identified were home intervention, environmental enrichment, collaborative realistic goal setting, planning of home-based activities and routine, child assessment feedback, family education/training, family coaching, encouraging discussion, observation of therapist and supervised practice. The main relational care qualities identified were as follows: respect, active listening, treat parents as equals, clear language, respect parents' ability to collaborate, demonstrate genuine care for the family, appreciate parents' knowledge and skills, demonstrate competence, experience and commitment. The main outcomes identified in children were improvement in motor and cognitive function and the child's functional ability. The main parentaloutcomes identified were empowerment, feeling of competence, self-confidence, motivation and engagement. CONCLUSION: The main differences in FCFTI programs refer to the parental education/guidance component and the amount of intervention carried out by parents. It is possible that the elements chosen by the therapist in a FCFTI depend on characteristics of the child and caregivers.


Assuntos
Paralisia Cerebral , Humanos , Paralisia Cerebral/reabilitação , Pré-Escolar , Criança , Assistência Centrada no Paciente , Terapia Familiar/métodos , Relações Profissional-Família
2.
J Toxicol Environ Health A ; 87(12): 497-515, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38619158

RESUMO

One prominent aspect of Parkinson's disease (PD) is the presence of elevated levels of free radicals, including reactive oxygen species (ROS). Syagrus coronata (S. coronata), a palm tree, exhibits antioxidant activity attributed to its phytochemical composition, containing fatty acids, polyphenols, and flavonoids. The aim of this investigation was to examine the potential neuroprotective effects of S. coronata fixed oil against rotenone-induced toxicity using Drosophila melanogaster. Young Drosophila specimens (3-4 d old) were exposed to a diet supplemented with rotenone (50 µM) for 7 d with and without the inclusion of S. coronata fixed oil (0.2 mg/g diet). Data demonstrated that rotenone exposure resulted in significant locomotor impairment and increased mortality rates in flies. Further, rotenone administration reduced total thiol levels but elevated lipid peroxidation, iron (Fe) levels, and nitric oxide (NO) levels while decreasing the reduced capacity of mitochondria. Concomitant administration of S. coronata exhibited a protective effect against rotenone, as evidenced by a return to control levels of Fe, NO, and total thiols, lowered lipid peroxidation levels, reversed locomotor impairment, and enhanced % cell viability. Molecular docking of the oil lipidic components with antioxidant enzymes showed strong binding affinity to superoxide dismutase (SOD) and glutathione peroxidase (GPX1) enzymes. Overall, treatment with S. coronata fixed oil was found to prevent rotenone-induced movement disorders and oxidative stress in Drosophila melanogaster.


Assuntos
Transtornos dos Movimentos , Rotenona , Animais , Drosophila melanogaster , Simulação de Acoplamento Molecular , Estresse Oxidativo , Antioxidantes/farmacologia , Óxido Nítrico/metabolismo
4.
Nat Ecol Evol ; 8(5): 901-911, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467713

RESUMO

Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.


Assuntos
Biodiversidade , Inundações , Rios , Árvores , Brasil , Florestas
5.
Lasers Med Sci ; 39(1): 56, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329547

RESUMO

Photobiomodulation (PBM) induced by non-ionizing radiations emitted from low-power lasers and light-emitting diodes (LEDs) has been used for various therapeutic purposes due to its molecular, cellular, and systemic effects. At the molecular level, experimental data have suggested that PBM modulates base excision repair (BER), which is responsible for restoring DNA damage. There is a relationship between the misfunction of the BER DNA repair pathway and the development of tumors, including breast cancer. However, the effects of PBM on cancer cells have been controversial. Breast cancer (BC) is the main public health problem in the world and is the most diagnosed type of cancer among women worldwide. Therefore, the evaluation of new strategies, such as PBM, could increase knowledge about BC and improve therapies against BC. Thus, this work aims to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the mRNA levels from BER genes in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm-2, 0.77 W cm-2) and blue LED (482 J cm-2, 5.35 W cm-2), alone or in combination, and the relative mRNA levels of the APTX, PolB, and PCNA genes were assessed by reverse transcription-quantitative polymerase chain reaction. The results suggested that exposure to low-power red laser and blue LED decreased the mRNA levels from APTX, PolB, and PCNA genes in human breast cancer cells. Our research shows that photobiomodulation induced by low-power red laser and blue LED decreases the mRNA levels of repair genes from the base excision repair pathway in MCF-7 and MDA-MB-231 cells.


Assuntos
Neoplasias da Mama , Terapia com Luz de Baixa Intensidade , Humanos , Feminino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Lasers , Reparo do DNA/genética , Terapia com Luz de Baixa Intensidade/métodos
7.
Farm Hosp ; 48(2): 83-89, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37770284

RESUMO

OBJECTIVES: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. METHODS: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by 2 independent researchers. Experimental and observational studies were eligible for inclusion. RESULTS: Out of the 5791 studies retrieved, after excluding duplicates (n = 1050), conducting title/abstract screening (n = 4741), and full reading (n = 41), only 1 study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to 2 groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. CONCLUSIONS: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only 1 of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs) and decrease the monthly costs of pharmacotherapy. Nevertheless, the impact on patient safety and humanistic outcomes remain unclear.


Assuntos
Desprescrições , Cuidados Paliativos , Idoso , Humanos , Prescrição Inadequada/prevenção & controle , Polimedicação , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
8.
Farm Hosp ; 48(2): T83-T89, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38016841

RESUMO

OBJECTIVES: Patients with life-limiting illnesses are prone to unnecessary polypharmacy. Deprescribing tools may contribute to minimizing negative outcomes. Thus, the aims of the study were to identify validated instruments for deprescribing inappropriate medications for patients with palliative care needs and to assess the impact on clinical, humanistic, and economic outcomes. METHODS: A systematic review was conducted in LILACS, PUBMED, EMBASE, COCHRANE, and WEB OF SCIENCE databases (until May 2021). A manual search was performed in the references of enrolled articles. The screening, eligibility, extraction, and bias risk assessment were carried out by two independent researchers. Experimental and observational studies were eligible for inclusion. RESULTS: Out of the 5,791 studies retrieved, after excluding duplicates (n = 1,050), conducting title/abstract screening (n = 4,741), and full reading (n = 41), only one study met the inclusion criteria. In this included study, a randomized controlled trial was conducted, which showed a high level of bias risk overall. Adults 75 years or older (n = 130) with limited life expectancy and polypharmacy were allocated to two groups [intervention arm (deprescribing); and control arm (usual care)]. Deprescribing was performed with the aid of the STOPPFrail tool. The mean number of inappropriate medications and monthly medication costs were significantly lower in the intervention arm. No statistically significant differences were found in terms of unscheduled hospital presentations, falls, fractures, mortality, and quality of life. CONCLUSIONS: Despite the availability of several instruments to support deprescribing in patients with palliative care needs, only one of them has undergone validation and robust assessment for effectiveness in clinical practice. The STOPPFrail tool appears to reduce the number of inappropriate medications for older people with limited life expectancy (and probably palliative care needs) and decrease the monthly costs of pharmacotherapy. Nevertheless, the impact on patient safety and humanistic outcomes remain unclear.


Assuntos
Desprescrições , Humanos , Idoso , Prescrição Inadequada/prevenção & controle , Cuidados Paliativos , Qualidade de Vida , Polimedicação , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Commun Biol ; 6(1): 1130, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938615

RESUMO

Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution.


Assuntos
RNA Longo não Codificante , Árvores , Florestas , Solo , Temperatura
10.
bioRxiv ; 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37425808

RESUMO

The fruit fly Drosophila melanogaster combines surprisingly sophisticated behaviour with a highly tractable nervous system. A large part of the fly's success as a model organism in modern neuroscience stems from the concentration of collaboratively generated molecular genetic and digital resources. As presented in our FlyWire companion paper 1 , this now includes the first full brain connectome of an adult animal. Here we report the systematic and hierarchical annotation of this ~130,000-neuron connectome including neuronal classes, cell types and developmental units (hemilineages). This enables any researcher to navigate this huge dataset and find systems and neurons of interest, linked to the literature through the Virtual Fly Brain database 2 . Crucially, this resource includes 4,552 cell types. 3,094 are rigorous consensus validations of cell types previously proposed in the hemibrain connectome 3 . In addition, we propose 1,458 new cell types, arising mostly from the fact that the FlyWire connectome spans the whole brain, whereas the hemibrain derives from a subvolume. Comparison of FlyWire and the hemibrain showed that cell type counts and strong connections were largely stable, but connection weights were surprisingly variable within and across animals. Further analysis defined simple heuristics for connectome interpretation: connections stronger than 10 unitary synapses or providing >1% of the input to a target cell are highly conserved. Some cell types showed increased variability across connectomes: the most common cell type in the mushroom body, required for learning and memory, is almost twice as numerous in FlyWire as the hemibrain. We find evidence for functional homeostasis through adjustments of the absolute amount of excitatory input while maintaining the excitation-inhibition ratio. Finally, and surprisingly, about one third of the cell types proposed in the hemibrain connectome could not yet be reliably identified in the FlyWire connectome. We therefore suggest that cell types should be defined to be robust to inter-individual variation, namely as groups of cells that are quantitatively more similar to cells in a different brain than to any other cell in the same brain. Joint analysis of the FlyWire and hemibrain connectomes demonstrates the viability and utility of this new definition. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open source toolchain for brain-scale comparative connectomics.

11.
Clin Pharmacol Ther ; 114(2): 371-380, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150935

RESUMO

Rozibafusp alfa (AMG 570) is a first-in-class bispecific IgG2-peptide fusion designed to inhibit inducible T-cell costimulator ligand (ICOSL) and B-cell activating factor (BAFF). The pharmacokinetics (PK) and pharmacodynamics (PD) of rozibafusp alfa were investigated in two randomized, placebo-controlled clinical studies: a phase Ia single ascending-dose study (7-700 mg subcutaneously (s.c.)) in healthy subjects and a phase Ib multiple ascending-dose study (70-420 mg s.c. every 2 weeks (q2w)) in patients with rheumatoid arthritis. Rozibafusp alfa exhibited nonlinear PK and dose-related and reversible dual-target engagement. Maximal reduction of naïve B cells from baseline (> 40%), reflective of BAFF inhibition, was achieved with rozibafusp alfa exposure (area under the concentration-time curve from time 0 to time infinity (AUCinf ) and AUC within a dosing interval from day 0 to day 14 (AUCtau )) above 51 and 57 days•µg/mL for the single-dose (≥ 70 mg) and multiple-dose studies (≥ 70 mg q2w), respectively. ICOSL receptor occupancy on circulating B cells, a surrogate PD end point for ICOSL inhibition, was directly related to drug concentration. PK/PD analysis showed > 90% RO at rozibafusp alfa ≥ 22.2 µg/mL (≥ 420-mg single dose or ≥ 210 mg q2w multiple dose), with saturation occurring at higher drug concentrations. These results informed the design and dose selection of a phase IIb study assessing the safety and efficacy of rozibafusp alfa in patients with active systemic lupus erythematosus.


Assuntos
Artrite Reumatoide , Lúpus Eritematoso Sistêmico , Humanos , Área Sob a Curva , Artrite Reumatoide/tratamento farmacológico , Fator Ativador de Células B/antagonistas & inibidores , Relação Dose-Resposta a Droga , Ligante Coestimulador de Linfócitos T Induzíveis/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico
12.
J Peripher Nerv Syst ; 28(2): 169-178, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37060329

RESUMO

BACKGROUND AND AIMS: Effective treatments for Charcot-Marie-Tooth (CMT) disease lack. Current treatments, such as ankle and foot surgery/orthoses, analgesics, and physiotherapy, focus on relieving the symptoms. Few randomized controlled trials (RCTs) investigated the effectiveness of exercise in patients with CMT, and a systematic review summarizing the effects of such treatments is outdated. This study aims to systematically review the effects of exercise on muscle strength, function, aerobic capacity, and quality of life in CMT. METHODS: We included RCTs that compared exercise programs against sham exercise, usual care, no exercise, and different exercise programs in individuals diagnosed with CMT. Searches were performed on 10 electronic databases from inception up to July 2021. Authors analyzed titles, abstracts, and full texts and extracted information from the eligible trials. We used the Physiotherapy Evidence Database (PEDro) scale and the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach to evaluate the risk of bias and the certainty of the evidence, respectively. Results were synthesized narratively. RESULTS: Eight citations (six studies; pooled n = 214) met the inclusion criteria. The mean age of participants was 38.49 (±13.02) years, and 83% were diagnosed with CMT1A. The mean PEDro score was 5.25 (range 2-9). Six trials were considered to have a high risk of bias. Moderate-quality evidence suggests that strengthening the ankle dorsiflexors minimizes the progression of weakness at 24 months in children with CMT1A. For other outcomes, quality of the evidence ranged from very low to low. INTERPRETATION: Based on the available, evidence we can only recommend exercise to improve muscle strength in children with CMT. More high quality and robust trials are needed.


Assuntos
Doença de Charcot-Marie-Tooth , Criança , Humanos , Adulto , Pessoa de Meia-Idade , Doença de Charcot-Marie-Tooth/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos , Exercício Físico , Força Muscular/fisiologia , Qualidade de Vida
13.
Sci Rep ; 13(1): 2859, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36801913

RESUMO

In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.


Assuntos
Biodiversidade , Ecossistema , Entropia , Florestas , Plantas , Ecologia , Clima Tropical
14.
ACR Open Rheumatol ; 4(10): 903-911, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35899378

RESUMO

OBJECTIVE: To assess the safety and biological activity of rozibafusp alfa, a first-in-class bispecific antibody-peptide conjugate targeting inducible costimulator ligand (ICOSL) and B cell activating factor (BAFF), in patients with rheumatoid arthritis (RA). METHODS: This phase 1b, double-blind, placebo-controlled, multiple ascending dose study included 34 patients (18-75 years; 82.4% female) with active RA (Disease Activity Score of 28 joints-C-reactive protein [DAS28-CRP] >2.6, on stable methotrexate) randomized 3:1 to receive rozibafusp alfa (n = 26, in four ascending dose cohorts of 70, 140, 210, and 420 mg) or a placebo (n = 8) subcutaneously once every 2 weeks for 10 weeks (six total doses), with 24 weeks of follow-up. The primary end point was the incidence of treatment-emergent adverse events (TEAEs). Additional assessments included serum pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and RA disease activity measures (DAS28-CRP, Patient Global Assessment of Disease, and Physician Global Assessment of Disease). RESULTS: TEAEs occurred in 96.2% and 87.5% of patients receiving rozibafusp alfa and the placebo, respectively; most were mild or moderate in severity. Two (7.7%) patients treated with rozibafusp alfa reported serious TEAEs; none were considered treatment related. Multiple doses of rozibafusp alfa showed nonlinear PK (mean t1/2  = 4.6-9.5 days) and dose-related, reversible PD (>90% ICOSL receptor occupancy in 210- and 420-mg cohorts; reduction in naïve B cells and increase in memory B cells in all cohorts). Five (20%) patients developed anti-rozibafusp alfa antibodies, with no apparent impact on safety. RA disease activity showed greater numerical improvement from baseline with rozibafusp alfa versus the placebo in the 210- and 420-mg cohorts. CONCLUSION: Multiple ascending doses of rozibafusp alfa were well tolerated, with PK and PD reflecting dual ICOSL and BAFF blockade. Findings support further clinical evaluation of rozibafusp alfa in autoimmune disease.

15.
Clin Cosmet Investig Dent ; 14: 103-112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509813

RESUMO

Background: The use of discolored teeth is required to test whitening products, and it is difficult to obtain them, given their scarcity. Objective: To present a technique for in vitro darkening of extracted teeth simulating pulpal necrosis discoloration. Materials and Methods: Hemolysates I and II from human blood were subjected or not to laser irradiation (442 nm) for 1 h. The concentration of oxyhemoglobin (O2Hb) was analyzed by ultraviolet/visible spectroscopy, and the conversion of O2Hb to methemoglobin (MetHb) by transmission spectroscopy was assessed immediately and after 3 and 40 days. For darkening evaluation, bovine incisors were divided into two groups (n = 25), and their pulp chambers were filled with hemolysate solution II (HSII) and hemolysate II solution + laser (HSII+L). After storage in artificial saliva for 40 days at 37°C, color changes were measured by a colorimeter and ΔE was compared with the NBS parameters. Data were analyzed using a mixed linear model (α=5%). Results: HSII+L presented the lowest O2Hb and higher MetHb. The conversion of O2Hb to MetHb in HSII+L was 42% higher than in HSII. Both groups were effective in darkening the teeth, according to the NBS. Darkening stabilized from day 35. HSII promoted a marked color difference. Conclusion: The proposed technique was effective in darkening the extracted teeth simulating necrosis discoloration for in vitro models.

16.
Curr Diabetes Rev ; 18(1): e010521189964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33413064

RESUMO

BACKGROUND: Some authors evaluated the effect of VD on hyperglycemia in T1DM, but the results remain controversial. This study aims to analyze the effects of high-dose VD supplementation on T1DM patients' glycemic levels, maintaining stable doses of insulin. METHODS: Prospective, 12-week clinical trial including 67 T1DM patients, supplemented with high doses of cholecalciferol according to participants' VD value. Patients with VD levels below 30 ng/mL received 10,000 IU/day; those with levels between 30-60 ng/mL received 4,000 IU/day. Patients who had not achieved 25(OH)D levels > 30 ng/ml or presented insulin dose variation during the study were not analyzed. RESULTS: Only 46 out of 67 patients accomplished the criteria at the end of the study. There was no general improvement in the glycemic control evaluated by HbA1c (9.4 ± 2.4 vs 9.4 ± 2.6, p=NS) after VD supplementation. However, a post-hoc analysis, based on HbA1c variation, identified patients who had HbA1c reduced at least 0.6% (group 1, N = 13 (28%)). In addition, a correlation between 25(OH)D levels with HbA1c and total insulin dose at the end of the study was observed (r = -0.3, p<0.05; r=-0.4, p<0.05, respectively), and a regression model demonstrated that 25(OH)D was independent of BMI, duration of T1DM and final total insulin dose, being capable of determining 9.2% of HbA1c final levels (Unstandardized B coefficient = -0.033 (CI 95%: -0.064 to -0.002), r2 = 0.1, p <0.05). CONCLUSION: Our data suggest that VD is not widely recommended for glycemic control. Nevertheless, specific patients might benefit from this approach.


Assuntos
Diabetes Mellitus Tipo 1 , Deficiência de Vitamina D , Diabetes Mellitus Tipo 1/tratamento farmacológico , Suplementos Nutricionais , Controle Glicêmico , Humanos , Estudos Prospectivos , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
17.
Diabetes Metab Syndr ; 16(1): 102358, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34920192

RESUMO

BACKGROUND AND AIMS: Common variants in fat mass and obesity-associated (FTO) gene have been implicated as a susceptibility locus for obesity and type 2 diabetes in different populations. Here, in an indigenous population-based study, we examined whether FTO rs9939609 has a role in susceptibility to glucose intolerance and obesity. METHODS: The study population comprised 949 full Xavante indigenous people (465 men) aged 18-99 years. The participants were submitted to clinical examination, anthropometrical measures and basal and 2-h post 75g oral glucose load capillary glucose measurements. FTO rs9939609 was genotyped and logistic regression was carried out to test the additive effect of the risk allele. RESULTS: The frequency of the minor allele of the FTO rs9939609 (0.06) was lower in Xavante than observed in some populations. A significant association between the variant and overweight was observed (OR = 1.56 (95% CI:1.06-2.29, p = 0.02), using an additive model of inheritance, adjusted by age and gender and considering the family structure. We found no associations with obesity or glucose intolerance. CONCLUSIONS: The FTO rs9939609 is associated with overweight, but not with obesity or glucose intolerance. The low frequency of the A allele suggests that it is not an important risk determinant for these conditions in Xavante indigenous people.


Assuntos
Diabetes Mellitus Tipo 2 , Intolerância à Glucose , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Índice de Massa Corporal , Brasil , Diabetes Mellitus Tipo 2/complicações , Predisposição Genética para Doença , Genótipo , Intolerância à Glucose/complicações , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/genética , Humanos , Povos Indígenas , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polimorfismo de Nucleotídeo Único , Adulto Jovem
18.
Front Immunol ; 12: 782788, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34970265

RESUMO

AMG 966 is a bi-specific, heteroimmunoglobulin molecule that binds both tumor necrosis factor alpha (TNFα) and TNF-like ligand 1A (TL1A). In a first-in-human clinical study in healthy volunteers, AMG 966 elicited anti-drug antibodies (ADA) in 53 of 54 subjects (98.1%), despite a paucity of T cell epitopes observed in T cell assays. ADA were neutralizing and bound to all domains of AMG 966. Development of ADA correlated with loss of exposure. In vitro studies demonstrated that at certain drug-to-target ratios, AMG 966 forms large immune complexes with TNFα and TL1A, partially restoring the ability of the aglycosylated Fc domain to bind FcγRIa and FcγRIIa, leading to the formation of ADA. In addition to ADA against AMG 966, antibodies to endogenous TNFα were also detected in the sera of subjects dosed with AMG 966. This suggests that the formation of immune complexes between a therapeutic and target can cause loss of tolerance and elicit an antibody response against the target.


Assuntos
Anticorpos Biespecíficos/efeitos adversos , Formação de Anticorpos , Complexo Antígeno-Anticorpo/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Tolerância Imunológica , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/farmacocinética , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Biomarcadores/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Antígenos HLA/genética , Antígenos HLA/imunologia , Humanos , Imunoensaio , Isoanticorpos/imunologia , Ligação Proteica/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo
19.
Front Endocrinol (Lausanne) ; 12: 667029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290667

RESUMO

Introduction: While soy is suggested as a possible risk factor, exclusive breastfeeding (EBF) has a likely protective effect in precocious puberty. Our aim was to evaluate the association between both of these variables with central precocious puberty (CPP). Methods: We performed a retrospective, case-control study. A total of 161 girls were divided into two groups: 84 patients diagnosed with CPP composed the case group and 77 patients without the diagnosis of CPP (had gone through normal onset of puberty) were the control group. Results: Our control group had a higher presence of EBF >6 months, which was an important protective factor for CPP (OR: 0.5; IC 95%: 0.3-0.9, p = 0.05) and also correlated negatively with the presence of it (r = -0.2; p < 0.05). Oppositely, the use of soy was significantly higher in the CPP group, (OR: 3.8; IC 95%: 1.5-6, p < 0.05) and positively correlating (r = 0.2; p < 0.01) with the presence of CPP. Duration of soy intake (years) correlated with bone age (r = 0.415; p < 0.05). A logistic regression was performed to evaluate the effects of EBF duration and soy on CPP. The model was significant (x² (2) = 20,715, p = <0.001) and explained 12.2% (Nagelkerke R2) of the variance, correctly classifying 62.5% of cases. EBF was associated with a reduction of likelihood of having CPP [OR = 0,187 (CI = 0.055-0,635); Wald = 7,222, p = 0.007], while soy intake increased the risk [OR = 3.505 (CI) = 1,688-7,279, Wald = 11,319, p = 0.001]. Conclusion: Our data found the use of soy was associated with CPP. Additionally, EBF was pointed as a protective factor. However, future prospective studies are needed to clarify this issue.


Assuntos
Aleitamento Materno/métodos , Glycine max/efeitos adversos , Fatores de Proteção , Puberdade Precoce/prevenção & controle , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Prognóstico , Puberdade Precoce/induzido quimicamente , Puberdade Precoce/patologia , Estudos Retrospectivos
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