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RNA binding proteins (RBPs) are important players in RNA metabolism and gene regulation. In this issue of Genes & Development, Flamand and colleagues (pp. 1002-1015) developed a new method (TRIBE-STAMP) that detects binding events by two distinct RBPs on single mRNA molecules, which they first applied to the YTHDF family of N 6-methyladenosine (m6A) reader proteins. The investigators show that these RBPs largely share a common pool of bound transcripts and that an individual mRNA may be bound by multiple YTHDF proteins throughout its lifetime. This single-molecule technique is an exciting new method to study potential synergy and/or antagonism between different RBPs.
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Regulação da Expressão Gênica , Proteínas de Ligação a RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RNA Mensageiro/metabolismo , RNARESUMO
RNA-binding proteins (RBPs) regulate nearly every aspect of mRNA processing and are important regulators of gene expression in cells. However, current methods for transcriptome-wide identification of RBP targets are limited, since they examine only a single RBP at a time and do not provide information on the individual RNA molecules that are bound by a given RBP. Here, we overcome these limitations by developing TRIBE-STAMP, an approach for single-molecule detection of the target RNAs of two RNA binding proteins simultaneously in cells. We applied TRIBE-STAMP to the cytoplasmic m6A reader proteins YTHDF1, YTHDF2, and YTHDF3 and discovered that individual mRNA molecules can be bound by more than one YTHDF protein throughout their lifetime, providing new insights into the function of YTHDF proteins in cells. TRIBE-STAMP is a highly versatile approach that enables single-molecule analysis of the targets of RBP pairs simultaneously in the same cells.
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Proteínas de Ligação a RNA , RNA , Proteínas de Ligação a RNA/metabolismo , RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma , Processamento Pós-Transcricional do RNARESUMO
The dynamic interaction of RNA-binding proteins (RBPs) with their target RNAs contributes to the diversity of ribonucleoprotein (RNP) complexes that are involved in a myriad of biological processes. Identifying the RNP components at high resolution and defining their interactions are key to understanding their regulation and function. Expressing fusions between an RBP of interest and an RNA editing enzyme can result in nucleobase changes in target RNAs, representing a recent addition to experimental approaches for profiling RBP/RNA interactions. Here, we have used the MS2 protein/RNA interaction to test four RNA editing proteins for their suitability to detect target RNAs of RBPs in planta. We have established a transient test system for fast and simple quantification of editing events and identified the hyperactive version of the catalytic domain of an adenosine deaminase (hADARcd) as the most suitable editing enzyme. Examining fusions between homologs of polypyrimidine tract binding proteins (PTBs) from Arabidopsis thaliana and hADARcd allowed determining target RNAs with high sensitivity and specificity. Moreover, almost complete editing of a splicing intermediate provided insight into the order of splicing reactions and PTB dependency of this particular splicing event. Addition of sequences for nuclear localisation of the fusion protein increased the editing efficiency, highlighting this approach's potential to identify RBP targets in a compartment-specific manner. Our studies have established the editing-based analysis of interactions between RBPs and their RNA targets in a fast and straightforward assay, offering a new system to study the intricate composition and functions of plant RNPs in vivo.
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Arabidopsis , Splicing de RNA , Splicing de RNA/genética , Arabidopsis/genética , Domínio Catalítico , Éxons , RNARESUMO
BACKGROUND: The increased prevalence of obesity, particularly central obesity, is closely associated with many metabolic complexions, including hypertension and diabetes. OBJECTIVES: The present study investigates the cut-off points of some anthropometric measurements such as body mass index [BMI (kg/m2)], waist circumference [WC (cm)], waist-hip ratio (WHR), and waist-height ratio (WHtR) associated with high blood pressure. It determines the risk factors among the Chiru tribe of North East India. METHODS: The cross-sectional study was conducted in four villages in the hilly districts of Manipur. For the present study, 416 Chiru adults (209 males and 207 females) aged 20-79 years were included. Anthropometrics and blood pressure were measured using standard procedures. Statistical methods such as chi-square, Pearson correlation, and multivariate logistic regression were employed. RESULTS: The result indicates that the cut-off values to detect hypertension were 21.83 for BMI, 82.55 for WC, 0.92 for WHR, and 0.53 for WHtR. However, the cut-off values to detect hypertension in females were 23.92 for BMI, 86.48 for WC, 0.94 for WHR, and 0.55 for WHtR. Multivariate logistic regression analysis indicated that hypertension was an independently associated risk factor in both males and females with an age ≥ 50 years (OR = 18.52 and 10.12), physical activity (OR = 0.10 and 0.21), salt intake (OR = 7.81 and 3.36), and smoking (OR = 2.56 and 3.23), respectively. CONCLUSION: It has been concluded that BMI, WC, WHR, and WHtR values can determine hypertension risk in the Chiru population. Age, smoking, physical activity, and salt intake were independent risk factors associated with high blood pressure.
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Índice de Massa Corporal , Hipertensão , Estilo de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Índia/epidemiologia , Hipertensão/epidemiologia , Hipertensão/etnologia , Estudos Transversais , Fatores de Risco , Idoso , Circunferência da Cintura , Relação Cintura-Quadril , Adulto Jovem , Antropometria , Razão Cintura-EstaturaRESUMO
Whole-genome duplication (WGD) plays important roles in plant evolution and function, yet little is known about how WGD underlies metabolic diversification of natural products that bear significant medicinal properties, especially in nonmodel trees. Here, we reveal how WGD laid the foundation for co-option and differentiation of medicinally important ursane triterpene pathway duplicates, generating distinct chemotypes between species and between developmental stages in the apple tribe. After generating chromosome-level assemblies of a widely cultivated loquat variety and Gillenia trifoliata, we define differentially evolved, duplicated gene pathways and date the WGD in the apple tribe at 13.5 to 27.1 Mya, much more recent than previously thought. We then functionally characterize contrasting metabolic pathways responsible for major triterpene biosynthesis in G. trifoliata and loquat, which pre- and postdate the Maleae WGD, respectively. Our work mechanistically details the metabolic diversity that arose post-WGD and provides insights into the genomic basis of medicinal properties of loquat, which has been used in both traditional and modern medicines.
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Eriobotrya/genética , Duplicação Gênica , Poliploidia , Triterpenos/metabolismo , Vias Biossintéticas , Eriobotrya/metabolismo , Genoma de PlantaRESUMO
Anaemia severely impacts physical and mental abilities, raises health risks, and diminishes the quality of life and work capacity. It is a leading cause of adverse pregnancy outcomes and maternal mortality, especially in developing nations like India, where recent data on anaemia from National Family and Health Survey (NFHS-4) (2015-16) and NFHS-5 (2019-21) indicate a tremendous rise. Anaemia is a marker of poor nutrition and health, and socio-economic factors such as gender norms, race, income, and living conditions influence its impact. As a result, there are disparities in how anaemia affects different segments of society. However, existing research on health inequity and anaemia often employs a single-axis analytical framework of social power. These studies operate under the assumption that gender, economic class, ethnicity, and caste are inherently distinct and mutually exclusive categories and fail to provide a comprehensive understanding of anaemia prevalence. Therefore, the study has adopted the theoretical framework of intersectionality and analysed the NFHS-5 (2019-21) data using bivariate cross-tabulations and binary logistic regression models to understand how gender, class, caste, and place of residence are associated with the prevalence of anaemia. The results suggest that the women of Scheduled Tribes (ST) and Scheduled Castes (SC) share a disproportionate burden of anaemia. This study confirms that economic class and gender, geographical location, level of education, and body mass index significantly determine the prevalence of anaemia. The ST and SC women who are economically marginalised and reside in rural areas with high levels of poverty, exclusion, and poor nutritional status have a higher prevalence of anaemia than other population groups. Thus, the study suggests that intersections of multiple factors such as caste, class, gender, and place of residence significantly determine 'who is anaemic in India'.
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BACKGROUND: The haplotypes from Northern, Southern, Eastern, and Western Kazakhstan, analysed for 27 Y-STR loci, have been contributed to the Y-Chromosome STR Haplotype Reference Database, while the genetic profile of Central Kazakhstan remains inadequately explored. AIM: To investigate the genetic diversity of 27 Y-STR loci in the Kazakh populations from Central Kazakhstan. SUBJECTS AND METHODS: A total of 112 unrelated Central Kazakh males were genotyped via the Yfiler Plus kit. Data analysis yielded haplotype and allele frequencies, and forensic parameters. Genetic distances were graphically represented by a multidimensional scaling plot, with genetic linkages further elucidated through Nei's distance dendrograms and Median-joining networks. RESULTS: A total of 102 haplotypes were detected, of which 96 were unique. The haplotype diversity and discrimination capacity were 0.997 and 0.91, respectively. Central Kazakhstan displays a unique cluster in analyses, underscoring its distinct Y-chromosome diversity compared to other Kazakh regions. The analysis of the Naiman tribe, predominantly residing in Central, Southern and Eastern Kazakhstan, revealed three genetic clusters of distinct haplogroups associated with their clans. CONCLUSIONS: The identified haplotypes will enhance the existing reference database for Y-chromosomal studies in Kazakhstan, offering a robust tool for future research in population genetics, forensic science and genetic genealogy.
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Cromossomos Humanos Y , Haplótipos , Repetições de Microssatélites , Polimorfismo Genético , Humanos , Cazaquistão , Cromossomos Humanos Y/genética , Masculino , Frequência do GeneRESUMO
The Talang Mamak tribe is an indigenous tribe that lives in groups (the extended family) in rural locations. All decisions are made after much deliberation. Traditional birth attendants are still used for childbirth. The objective of the study is to analyze the factors that influence reproductive health-needing behavior among Talang Mamak women of reproductive age. With 160 respondents, data was analyzed using logistic regression. The study discovered that education p = 0.001 with PR=4,738, knowledge p = 0.001 with PR=13,800, attitude p= 0.001 with PR=3,133, and tradition p= 0.001 with PR=226.66 are variables that influence the behavior of women of reproductive age toward needing reproductive health services. Among the five variables influencing the outcome, one stands out: tradition, which has an Exp(ß) value of 192.422. The multivariate results show that three variables are included in the modeling: tradition p = 0.001, knowledge p = 0.001, and education p = 0.001. Good traditions, good knowledge, and higher education in the Talang Mamak tribe have a more behavioral probability of needing reproductive health services in women of reproductive age 99%, while another 1% probability by other variables is not examined in this study.
La tribu Talang Mamak est une tribu indigène qui vit en groupes (la famille élargie) dans les zones rurales. Toutes les décisions sont prises après de longues délibérations. Les accoucheuses traditionnelles sont encore utilisées pour l'accouchement. L'objectif de l'étude est d'analyser les facteurs qui influencent le comportement en matière de santé reproductive chez les femmes Talang Mamak en âge de procréer. Avec 160 répondants, les données ont été analysées par régression logistique. L'étude a découvert que l'éducation p = 0,001 avec PR = 4 738, la connaissance p = 0,001 avec PR = 13 800, l'attitude p = 0,001 avec PR = 3 133 et la tradition p = 0,001 avec PR = 226,66 sont des variables qui influencent le comportement des femmes en situation de procréation. âge pour avoir besoin de services de santé reproductive. Parmi les cinq variables influençant le résultat, une se démarque : la tradition, qui a une valeur Exp(ß) de 192,422. Les résultats multivariés montrent que trois variables sont incluses dans la modélisation : tradition p = 0,001, connaissances p = 0,001 et éducation p = 0,001. Les bonnes traditions, les bonnes connaissances et l'enseignement supérieur dans la tribu Talang Mamak ont une probabilité comportementale plus élevée d'avoir besoin de services de santé reproductive chez les femmes en âge de procréer (99 %), tandis qu'une autre probabilité de 1 % selon d'autres variables n'est pas examinée dans cette étude.
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Etnicidade , Serviços de Saúde Reprodutiva , Gravidez , Feminino , Humanos , Reprodução , Escolaridade , Saúde Reprodutiva , Fatores SocioeconômicosRESUMO
INTRODUCTION: Literature examining the connection between obesity and burn injuries is limited. This study is a secondary analysis of a multicenter trial data set to investigate the association between burn outcomes and obesity following severe burn injury. MATERIALS AND METHODS: Body mass index (BMI) was used to stratify patients as normal weight (NW; BMI 18.5-25), all obese (AO; any BMI>30), obese I (OI; BMI 30-34.9), obese II (OII; BMI 35-39.9), or obese III (OIII; BMI>40). The primary outcome examined was mortality. Secondary outcomes included hospital length of stay (LOS), number of transfusions, injury scores, infection occurrences, number of operations, ventilator days, intensive care unit LOS, and days to wound healing. RESULTS: Of 335 patients included for study, 130 were obese. Median total body surface area (TBSA) was 31%, 77 patients (23%) had inhalation injury and 41 patients died. Inhalation injury was higher in OIII than NW (42.1% versus 20%, P = 0.03). Blood stream infections (BSI) were higher in OI versus NW (0.72 versus 0.33, P = 0.03). Total operations, ventilator days, days to wound healing, multiorgan dysfunction score, Acute Physiology and Chronic Health Evaluationscore, hospital LOS, and intensive care unit LOS were not significantly affected by BMI classification. Mortality was not significantly different between obesity groups. Kaplan-Meier survival curves did not significantly differ between the groups (χ2 = 0.025, P = 0.87). Multiple logistic regression identified age, TBSA, and full thickness burn as significant independent predictors (P < 0.05) of mortality; however, BMI classification itself was not predictive of mortality. CONCLUSIONS: No significant association between obesity and mortality was seen after burn injury. Age, TBSA, and percent full- thickness burn were independent predictors of mortality after burn injury, while BMI classification was not.
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Queimaduras , Sepse , Humanos , Queimaduras/complicações , Queimaduras/terapia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/terapia , Transfusão de Sangue , Sepse/complicações , Escores de Disfunção Orgânica , Estudos Retrospectivos , Tempo de InternaçãoRESUMO
Aims: Evaluating the prognostic role of radiomic features in liver-limited metastatic colorectal cancer treated with first-line therapy at baseline and best response among patients undergoing resection. Patients & methods: Among patients enrolled in TRIBE2 (NCT02339116), the association of clinical and radiomic data, extracted by SOPHiA-DDM™ with progression-free and overall survival (OS) in the overall population and with disease-free survival/postresection OS in those undergoing resection was investigated. Results: Among 98 patients, radiomic parameters improved the prediction accuracy of our model for OS (area under the curve: 0.83; sensitivity: 0.85; specificity: 0.73; accuracy: 0.78), but not progression-free survival. Of 46 resected patients, small-distance high gray-level emphasis was associated with shorter disease-free survival and high gray-level zone emphasis/higher kurtosis with shorter postresection OS. Conclusion: Radiomic features should be implemented as tools of outcome prediction for liver-limited metastatic colorectal cancer.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Bevacizumab , Prognóstico , Neoplasias Colorretais/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Retais/tratamento farmacológicoRESUMO
BACKGROUND: Scrub typhus is a significant tropical disease, occurring in rural settings and therefore usually afflicting remote agricultural populations who have lower socioeconomic status and limited access to medical care. A large proportion of the hill tribe people in Thailand are financially poor, have limited education, and do not have adequate health care access. This study aimed to estimate the prevalence of and determine factors associated with scrub typhus exposure among the hill tribe population living in high-incidence areas in northern Thailand. METHODS: A cross-sectional study design was used to gather information from hill tribe people aged 18 years and over living in ten hill tribe villages in Mae Fah Luang, Chiang Rai Province, Thailand. Participants who met the inclusion criteria were invited to participate in the study. A validated questionnaire was used as the research instrument, and 5 mL blood samples were taken. Orientia tsutsugamushi IgM and IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA) and then confirmed by immunofluorescence assay (IFA). Logistic regression was used to detect associations between variables at a significance level of α = 0.05. RESULTS: A total of 485 hill tribe people participated in the study; 57.1% were female, 29.9% were over 60 years of age, 46.4% were from the Akha tribe, and 74.2% had never attended school. The overall prevalence of scrub typhus exposure was 48.0%. In the multivariate model, five variables were found to be associated with scrub typhus exposure. Participants aged over 60 years had a 4.31-fold increased risk (95% CI = 1.73-10.72) of scrub typhus exposure compared to those who were younger than 30 years. Those who were illiterate had a 3.46-fold increased risk (95% CI = 1.93-6.21) of scrub typhus exposure than those who had at least a primary education level. Participants from the Akha tribe had a 2.20-fold increased risk (95% CI = 1.31-3.72) of scrub typhus exposure than those from the Lahu tribe. Subjects who had a history of cutting grass had a 1.85-fold increased risk (95% CI = 1.20-2.84) of scrub typhus exposure. Those who never wore gloves for farming had a 2.12-fold increased risk (95% CI = 1.28-3.49) of scrub typhus exposure than those who wore gloves daily. CONCLUSIONS: There is a high prevalence of scrub typhus exposure among the hill tribe in Thailand. Effective public health interventions to promote scrub typhus awareness and prevention are urgently needed in these populations.
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Tifo por Ácaros , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Incidência , Prevalência , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/diagnóstico , Tailândia/epidemiologia , Orientia tsutsugamushiRESUMO
BACKGROUND: Intimate partner violence (IPV) is a major global public health problem. Women are the principal victims of IPV, and some special populations have been particularly impacted. The Akha and Lahu women are vulnerable populations for IPV due to the modernization and changes of their culture and norms. This study aimed to understand premarriage factors related to IPV, including associated factors, influencers, patterns and impacts, in Akha and Lahu women in Thailand. METHODS: A qualitative method was used to gather information among Akha and Lahu women who had experienced IPV in the previous year and were fluent in Thai. Women who had experienced IPV in the previous year and lived in the border area of Thailand and Myanmar were invited to provide information. A thematic analysis was used to extract information from the participants and develop findings. RESULTS: A total of fifty-two married women were recruited into the study: 46.2% were Akha and 53.8% were Lahu. Those married Akha and Lahu women younger than 39 years found their partner through social media, had conditions before getting married, had high self-confidence, and tended to marry people from different tribes. While those aged 40 years and over met their husbands in village activities, were highly compliant with the norms of their culture, and married men from the same tribe. Three factors were detected as associated factors of IPV: cultural differences between partners from different tribes, substance use, and personality. Differences in age between partners, living in poor family economic status, and poor education were also detected as influencers of IPV. Four patterns of IPV were observed among Akha and Lahu married women: neglect, emotional abuse, verbal abuse, and physical abuse. Several patterns of the impacts were presented: children were neglected, especially in the preparation of daily food, having stress, having poor family relationships, and having children with unsuccessful lives in terms of education and getting a good job. Almost all married Akha and Lahu women had no particular expectations in their lives. CONCLUSION: Akha and Lahu women face IPV problems with several key influences and impacts. Effective implementations are required to monitor and reduce the problem in the Akha and Lahu families, especially where the women are younger than 40 years old and married to men from different tribes.
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Violência por Parceiro Íntimo , Transtornos Relacionados ao Uso de Substâncias , Masculino , Criança , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Tailândia/epidemiologia , Fatores de Risco , Violência por Parceiro Íntimo/psicologia , Grupos Populacionais , Prevalência , Parceiros SexuaisRESUMO
BACKGROUND: The persistently high rates of maternal mortality and morbidity among historically marginalised social groups, such as adolescent Scheduled Castes (SCs) and Scheduled Tribes (STs) in India, can be attributed, in part, to the low utilisation of full antenatal healthcare services. Despite efforts by the Indian government, full antenatal care (ANC) usage remains low among this population. To address this issue, it is crucial to determine the factors that influence the utilisation of ANC services among adolescent SC/ST mothers. However, to date, no national-level comprehensive study in India has specifically examined this issue for this population. Our study aims to address this research gap and contribute to the understanding of how to improve the utilisation of ANC services among adolescent SC/ST mothers in India. DATA AND METHODS: Data from the fourth round of the National Family Health Survey 2015-16 (NFHS-4) was used. The outcome variable was full antenatal care (ANC). A pregnant mother was considered to have 'full ANC' only when she had at least four ANC visits, at least two tetanus toxoid (TT) injections, and consumed 100 or more iron-folic acid (IFA) tablets/syrup during her pregnancy. Bivariate analysis was used to examine the disparity in the coverage of full ANC. In addition, binary logistic regression was used to understand the net effect of predictor variables on the coverage of full ANC. RESULTS: The utilisation of full antenatal care (ANC) among adolescent SC/ST mothers was inadequate, with only 18% receiving full ANC. Although 83% of Indian adolescent SC/ST mothers received two or more TT injections, the utilisation of the other two vital components of full ANC was low, with only 46% making four or more ANC visits and 28% consuming the recommended number of IFA tablets or equivalent amount of IFA syrup. There were statistically significant differences in the utilisation of full ANC based on the background characteristics of the participants. The statistical analysis showed that there was a significant association between the receipt of full ANC and factors such as religion (OR = 0.143, CI = 0.044-0.459), household wealth (OR = 5.505, CI = 1.804-16.800), interaction with frontline health workers (OR = 1.821, CI = 1.241-2.670), and region of residence in the Southern region (OR = 3.575, CI = 1.917-6.664). CONCLUSION: In conclusion, the study highlights the low utilisation of full antenatal care services among Indian adolescent SC/ST mothers, with only a minority receiving the recommended number of ANC visits and consuming the required amount of IFA tablets/syrup. Addressing social determinants of health and recognising the role of frontline workers can be crucial in improving full ANC coverage among this vulnerable population. Furthermore, targeted interventions tailored to the unique needs of different subgroups of adolescent SC/ST mothers are necessary to achieve optimal maternal and child health outcomes.
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Mães Adolescentes , Cuidado Pré-Natal , Criança , Adolescente , Gravidez , Feminino , Humanos , Classe Social , Ácido Fólico , Fatores Socioeconômicos , Ferro , Toxoide Tetânico , Índia/epidemiologiaRESUMO
BACKGROUND: Diabetes mellitus (DM), a significant public health problem across the nations, is among the top ten leading causes of death. More than 370 million indigenous people (referred to as tribal people in India) are spread across 90 countries. India has the largest tribal people of 104 million. Tribal populations are not exceptional to the threat of type 2 DM (T2DM) and other non-communicable diseases, and hence, public health programmes are addressing this problem. This paper reports the systematic review and meta-analysis of the literature on the prevalence of T2DM. METHODS: We conducted a systematic review and meta-analysis of the literature to understand the prevalence of T2DM among the tribal populations of India, following the guidelines of the PRISMA Statement for Reporting Systematic Reviews and Meta-Analysis. The gender-wise prevalence was recalculated by extracting the data wherever possible. Forest plots were depicted based on the prevalence, and other analyses were performed. RESULTS: On initial searches from three databases, 5422 citations were identified, and ultimately 27 studies were included in the review. These studies were undertaken amongst different tribes in different parts of India. The pooled prevalence of T2DM among men, women and combined were 6.04% (95% confidence interval (CI): 5.55% to 6.57%), 6.48% (95% CI: 6.01% to 6.99%) and 4.94% (95% CI: 4.72% to 5.17%), respectively. Considerable heterogeneity was found among these studies. CONCLUSION: This systematic review provides an overview of the prevalence of T2DM among the Indian tribal population. The pooled overall prevalence is slightly lower than the general population. This situation is worrisome as the epidemic of T2DM will affect the poor tribal communities, who can least afford to bear the health care costs. Hence, the public health care services must be strengthened in all tribal areas. This review further warrants establishing surveillance of T2DM in tribal areas.
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Diabetes Mellitus Tipo 2 , Povos Indígenas , População do Sul da Ásia , Feminino , Humanos , Masculino , Diabetes Mellitus Tipo 2/epidemiologia , Índia/epidemiologia , Povos Indígenas/estatística & dados numéricos , Grupos Populacionais , Prevalência , Saúde Pública/estatística & dados numéricos , População do Sul da Ásia/estatística & dados numéricosRESUMO
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, altered neuronal dendritic morphology is a common theme among several neurological disorders and is thought to precede neurodegeneration. We previously found that both TDP-43 overexpression (OE) and knockdown (KD) result in reduced dendritic branching of cortical neurons. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as an approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 RNA targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescues defects in dendritic branching. Finally, we demonstrate, using RNA sequencing, that TDP-43 OE and KD cause similar changes in the abundance of specific messenger RNAs, consistent with their ability to produce similar morphological defects. Our data therefore provide a mechanism by which TDP-43 dysfunction interferes with dendritic branching, and may define pathways for therapeutic intervention in neurodegenerative diseases.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteínas de Ligação a DNA , Dendritos , Regulação da Expressão Gênica/genética , Transdução de Sinais , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dendritos/metabolismo , Dendritos/patologia , Células HEK293 , Humanos , RNA Mensageiro/metabolismo , Ratos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Proteinopatias TDP-43RESUMO
BACKGROUND: Achieving meaningful consent can be challenging, particularly in contexts of diminished literacy, yet is a vital part of participant protection in global health research. METHOD: We explored the challenges and potential solutions of achieving meaningful consent through a qualitative study in a predominantly hill tribe ethnic minority population in northern Thailand, a culturally distinctive population with low literacy. Semi-structured interviews were conducted with 37 respondents who had participated in scrub typhus clinical research, their family members, researchers and other key informants. A thematic analysis was conducted. RESULTS: Our analysis identified four interrelated themes surrounding participants' ability to give consent: varying degrees of research understanding, limitations of using informal translators, issues impacting decisions to join research, and voluntariness of consent. Suggestions for achieving more meaningful consent included the use of formal translators and community engagement with research populations. CONCLUSIONS: Participant's agency in decision making to join research should be supported, but research information needs to be communicated to potential participants in a way that they can understand. We found that improved understanding about the study and its potential benefits and harms goes beyond literacy or translation and requires attention to social and cultural factors.
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Pesquisa Biomédica , Etnicidade , Humanos , Tailândia , Grupos Minoritários , Consentimento Livre e Esclarecido , Pesquisa QualitativaRESUMO
Indigenous communities in the United States experience some of the highest rates of food insecurity and diet-related diseases despite an abundance of food assistance programs and other public health interventions. New approaches that center Indigenous perspectives and solutions are emerging and urgently needed to better understand and address these challenges. This Practice Note shares lessons learned from ongoing collaboration between the Karuk Tribe and University of California, Berkeley researchers and other partners to assess and enhance food sovereignty among Tribes and Tribal communities in the Klamath River Basin. Through two participatory research and extension projects, we demonstrate the importance of centering Indigenous knowledge to strengthen research findings and identify more culturally appropriate solutions to community identified food access, health, and ecosystem challenges. Key findings suggest that approaches to food sovereignty and community health must emanate from the community, be approached holistically, reflect community values and priorities, and center Indigenous land stewardship.
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Ecossistema , Saúde Pública , Estados Unidos , Humanos , Alimentos , DietaRESUMO
To gain insights into the trichurid diversity in pre-Hispanic remains of South American camelids (SACs), as well as into modern SAC populations, a bibliographic search was carried out to find parasitological studies. Results showed that a total of 17 studies were performed at archaeological and paleontological sites, in which a total of 213 samples were examined. The sample set was used as the unit of analysis, and 83% of 52 pre-Hispanic sample sets were positive for parasites. Parasitological studies confirmed the pre-Hispanic presence of diverse trichurids: two Trichuris species and capillariid eggs with morphological differences that allowed them to be assigned to three different species. Currently, the richness of the native trichurid assemblages in SACs has been extended by the inclusion of two species (Trichuris sp. 2 and Capillariinae gen. sp. 1). Modern T. tenuis Chandler, 1930, considered SAC-specific, would have invaded SAC populations during the European colonization. The estimate of regional and temporal trichurid prevalence and paleoecological information allowed us to propose a possible origin for some of them. Although the present analysis is exploratory, it should stimulate future studies about the biogeographic history of SAC helminths, provide relevant information to improve descriptions of the Holocene ecology, and identify threatened helminths.
Assuntos
Helmintos , Nematoides , Parasitos , Animais , Trichuris , América do SulRESUMO
Background: There is a dominant role of informal healthcare providers (IHPs) in the current cultural and sociological context of tribal communities. They outnumber formal health-care providers, thus bridging the gap between existing and nonexisting public health facilities despite not having formal training or accreditation. Objectives: The study examines the role, relevance, and extent of abortion services provided by IHPs- in Jharkhand among three Scheduled Tribe groups. Materials and Methods: Based on in-depth interviews with 15 IHPs and 42 married women among three Scheduled Tribe groups in three districts of Jharkhand, a qualitative study was conducted. Interview guidelines addressed reasons for preferring IHP services, their scope of practice, dissemination, and quality of services. Results: The majority of women seeking abortions used traditional contraceptives, which often resulted in unwanted pregnancies. The economic, cultural, social, access to services, and confidence factors encouraged women to seek abortion services from IHPs. There were differences in the nature of access to abortion services among tribal groups. The Chero and Korwa tribes continued to rely heavily on simpler life technologies that shaped their beliefs and practices regarding reproduction. The Ho tribe, however, preferred to use the formal health-care system since they were close to a more complex society. Conclusion: IHP plays a significant role in the social structure of Tribes, demonstrating their marginalization in access to formal health-care services. Eventually, they replaced traditional healers with their function as physicians.
Assuntos
Aborto Induzido , Acessibilidade aos Serviços de Saúde , Gravidez , Feminino , Humanos , Índia , Gravidez não Desejada , Pessoal de SaúdeRESUMO
BACKGROUND: The East Asian subtropical evergreen broad-leaved forests (EBLFs) harbor remarkable biodiversity. However, their historical assembly remains unclear. To gain new insights into the assembly of this biome, we generated a molecular phylogeny of one of its essential plant groups, the tribe Perseeae (Lauraceae). RESULTS: Our plastid tree topologies were robust to analyses based on different plastid regions and different strategies for data partitioning, nucleotide substitution saturation, and gap handling. We found that tribe Perseeae comprised six major clades and began to colonize the subtropical EBLFs of East Asia in the early Miocene. The diversification rates of tribe Perseeae accelerated twice in the late Miocene. CONCLUSIONS: Our findings suggest that the intensified precipitation in East Asia in the early Miocene may have facilitated range expansions of the subtropical EBLFs and establishment of tribe Perseeae within this biome. By the late Miocene, species assembly and diversification within the EBLFs had become rapid.