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In women who die from cancer, breast cancer is the most common cause of death. The development of small molecular scaffolds as specific Cyclin-dependent kinase (CDK) inhibitors is a promising strategy in the discovery of anti-breast cancer drugs. Isoindolin-1-ones are heterocyclic compounds with useful therapeutic properties. In this study, a library of 48 isoindolinones has been virtually screened by molecular docking that showed high binding affinity up to - 10.1 kcal/mol and conventional hydrogen bonding interactions with active amino acid residues of CDK7. The molecular dynamics simulation (MDS), fragment molecular orbital (FMO), density functional theory (DFT), and pharmacokinetics studies of the best two docked scored ligands 7 and 14 have been studied. Examining the ligand root mean square deviation and hydrogen bonding occupancy of the 100 ns MDS trajectory, both ligands 7 and 14 showed docked pose stability. FMO calculations displayed that LYS139 and LYS41 are majorly contributing to the binding interactions with ligands 7 and 14 in the docked poses. DFT studies of ligands 7 and 14 showed high values of global softness and low values of global hardness and chemical potential thus displaying chemically reactive soft molecules and this influences their anti-cancer activity. Our hits exhibited superior qualities to known CDK7 inhibitors, according to the comprehensive pharmacokinetic parameters that were predicted. The results indicate that isoindolin-1-one moieties are good candidates for anti-cancer action and could serve as effective CDK7 inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00225-0.
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BACKGROUND: Distal radius fractures (DRF) are extremely common in middle-aged and elderly. Certified Hand Therapists (CHT) are experts in managing hand injuries including DRF. PURPOSE: Using qualitative methodology, this study examined practice patterns among CHT and understand prevalent common patterns in managing DRF. STUDY DESIGN: Descriptive qualitative study. METHODS: This study utilized a qualitative descriptive method with an inductive approach to discern the practices of CHT in managing DRF. A purposive sample of practicing CHT was assembled. A semi-structured interview guide facilitated qualitative interviews using open-ended questions to assess practices of CHT in the domains of assessment, interventions, and appropriateness for discharge. Two student physical therapists transcribed the interviews, which were verified by a third rater for accuracy. Thematic content analysis guided the coding and analyses of the interview data. A two-phase coding process was conducted using Nvivo software. Two study authors developed initial codebook and completed subsequent analysis of transcripts. RESULTS: Of the 12 participants, five were PT and seven were OT with an average experience of 14.1 years as a CHT. Practice patterns across domains were largely consistent among CHT. All CHTs reported inquiring about severity of displacement of DRF, orthopedic management, comorbidities, and medical history as well as examining wrist/hand range of motion (ROM), grip strength (GS), and wrist functions (n = 12). A large majority administered outcome measures and performed sensory and integumentary assessment. Patient education regarding injury and exercises was the key element for interventions. Adequate gains in GS, wrist functions, wrist ROM, and ability to use wrist/hand for functional tasks were the key benchmarks for discharge from care. DISCUSSION: Most practice behaviors were common among CHTs while managing DRF. Some variations exist depending whether their primary discipline is PT or OT. The results highlight knowledge-to-action gap, where most CHTs do not integrate fall-risk management in DRF. CONCLUSIONS: This study identified common practice patterns among CHTs in managing DRF while also identifying opportunity to improve practice by integrating assessment of balance and fall-risk.
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The initial phase of the COVID-19 vaccination in Ecuador occurred between April and November 2021. Initially, it focused on priority populations, including health professionals and other front-line workers. During this period, there was limited knowledge about the vaccine's adverse effects. A non-probability, observational study was conducted among university staff in Guayaquil, Ecuador, who received the AstraZeneca vaccine (n = 423) between April and November 2021. This study aimed to compare the acute adverse reactions by doses and to report the incidence of long-term adverse reactions within the AstraZeneca group. As a result, comparing acute adverse reactions between doses, the odds ratio for local pain, headache, muscle pain, fever, and chills are statistically higher after the first dose than the second dose. Survival curves indicated these symptoms appeared mainly within the first 6 h post-vaccination. This is the first pharmacovigilance study from Ecuador that analyzes survival probabilities for the AstraZeneca vaccine's adverse effects.
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Precision nutrition (PN) considers multiple individual-level and environmental characteristics or variables to better inform dietary strategies and interventions for optimizing health, including managing obesity and metabolic disorders. Here, we review the evidence on potential mechanisms-including ones to identify individuals most likely to respond-that can be leveraged in the development of PN interventions addressing obesity. We conducted a review of the literature and included laboratory, animal, and human studies evaluating biochemical and genetic data, completed and ongoing clinical trials, and public programs in this review. Our analysis describes the potential mechanisms related to 6 domains including genetic predisposition, circadian rhythms, physical activity and sedentary behavior, metabolomics, the gut microbiome, and behavioral and socioeconomic characteristics, i.e., the factors that can be leveraged to design PN-based interventions to prevent and treat obesity-related outcomes such as weight loss or metabolic health as laid out by the NIH 2030 Strategic Plan for Nutrition Research. For example, single nucleotide polymorphisms can modify responses to certain dietary interventions, and epigenetic modulation of obesity risk via physical activity patterns and macronutrient intake have also been demonstrated. Additionally, we identified limitations including questions of equitable implementation across a limited number of clinical trials. These include the limited ability of current PN interventions to address systemic influences such as supply chains and food distribution, healthcare systems, racial or cultural inequities, and economic disparities, particularly when designing and implementing PN interventions in low- and middle-income communities. PN has the potential to help manage obesity by addressing intra- and inter-individual variation as well as context, as opposed to "one-size fits all" approaches though there is limited clinical trial evidence to date.
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Dieta , Obesidad , Humanos , Obesidad/prevención & control , Ejercicio Físico , Alimentos , Pérdida de PesoRESUMEN
Oral delivery, while a highly desirable form of nanoparticle-drug administration, is limited by challenges associated with overcoming several biological barriers. Here, the authors study how fluorescent and poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles sized 5 to 50 nm interact with major barriers including intestinal mucus, intestinal epithelium, and stomach acid. From imaging fluorescence correlation spectroscopy studies using quasi-total internal reflection fluorescence microscopy, diffusion of nanoparticles through highly scattering mucus is progressively hindered above a critical hydrodynamic size around 20 nm. By studying Caco-2 cell monolayers mimicking the intestinal epithelia, it is observed that ultrasmall nanoparticles below 10 nm diameter (Cornell prime dots, [C' dots]) show permeabilities correlated with high absorption in humans from primarily enhanced passive passage through tight junctions. Particles above 20 nm diameter exclusively show active transport through cells. After establishing C' dot stability in artificial gastric juice, in vivo oral gavage experiments in mice demonstrate successful passage through the body followed by renal clearance without protein corona formation. Results suggest C' dots as viable candidates for oral administration to patients with a proven pathway towards clinical translation and may generate renewed interest in examining silica as a food additive and its effects on nutrition and health.
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Portadores de Fármacos , Nanopartículas , Humanos , Ratas , Ratones , Animales , Portadores de Fármacos/química , Células CACO-2 , Ratas Sprague-Dawley , Dióxido de Silicio/química , Nanopartículas/químicaRESUMEN
BACKGROUND: Pennsylvania Shoulder Score (PSS) is a patient-reported outcome measure (PROM) that is gaining use when examining shoulder-specific outcomes. To date, a systematic review of the PSS measurement properties has not been published. PURPOSE: To systematically locate, appraise, and synthesize the evidence concerning the measurement properties of the PSS. STUDY DESIGN: Systematic literature review. METHODS: A pair of raters conducted a literature search using pre-defined keywords from 5 databases (PubMed, CINAHL, SPORTdiscus, PsychINFO, Scopus) during the week of October 23, 2022. Critical appraisal of study design for psychometric articles was used to assess methodological quality and risk of bias. Measurement property data were synthesized with pooled estimates for the indices of test-retest reliability (ICC), standard error of measurement (SEM), minimal detectable change (MDC), Cronbach α (CA), effect size (ES), and standardized response means (SRM) calculated from applicable studies. RESULTS: A total of 13 articles met the inclusion criteria for this review. Methodological quality was agreed upon between the 2 raters with a weighted kappa of 0.77, and 9/13 of the articles were rated above 70%. Test-retest reliability of the PSS total score ranged between 0.90 and 0.94, and construct validity was high when compared to other shoulder-specific PROMs (0.75 < r > 0.96). Responsiveness of the PSS was large across all studies with few PSS subscales dropping to moderate. Pooled MDC90 of the total PSS was 12.13 points, and the pooled ES of the total PSS was 0.85. CONCLUSIONS: The scope of this review demonstrates positive measurement properties of the PSS as a reliable, valid, and responsive measurement of shoulder-specific PROM. However, there are few studies examining the measurement properties of the PSS and more research is needed to assess cross-cultural appropriateness and factor analysis of the questions contained in the PSS.
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Proyectos de Investigación , Hombro , Humanos , Reproducibilidad de los Resultados , Pennsylvania , PsicometríaRESUMEN
Post-harvest handling can affect micronutrient retention in biofortified crops through to the point of consumption. Here we conduct a systematic review identifying 67 articles examining the retention of micronutrients in conventionally bred biofortified maize, orange sweet potato, cassava, pearl millet, rice, beans and wheat. Provitamin A crops maintain high amounts compared with non-biofortified counterparts. Iron and zinc crops have more variability in micronutrient retention dependent on processing method; for maximum iron and zinc content, whole grain product consumption such as whole wheat flour or only slightly milled brown rice is beneficial. We offer preliminary suggestions for households, regulatory bodies and programme implementers to increase consumer awareness on best practices for preparing crops to maximize micronutrient content, while highlighting gaps in the literature. Our online, interactive Micronutrient Retention Dashboard ( https://www.cpnh.cornell.edu/mn-retention-db ) offers an at-a-glance view of the compiled minimum and maximum retention found, organized by processing method.
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Hierro , Oligoelementos , Biofortificación , Zinc , Provitaminas , Alimentos Fortificados , Harina , Triticum , Fitomejoramiento , Micronutrientes , Productos Agrícolas , Compuestos OrgánicosRESUMEN
CONTEXT: It is important to understand the sensory acceptability of biofortified food products among target population groups if biofortification is to be realized as a sustainable strategy for mitigation of micronutrient deficiencies, able to be scaled up and applied through programs. OBJECTIVE: This systemic review aims to summarize and synthesize the sensory acceptability of conventionally bred iron-, zinc-, and provitamin A-biofortified food products. DATA SOURCES: MEDLINE (PubMed), AGRICOLA, AgEcon, CABI Abstracts (Web of Science), and organizational websites (eg, those of HarvestPlus and CGIAR and their partners) were searched for relevant articles. No access to any market research that may have been internally conducted for the commercial biofortified food products was available. DATA EXTRACTION: This review identified articles measuring the sensory acceptability of conventionally bred biofortified food products. Extraction of the hedonic ratings of food products was performed. DATA ANALYSIS: An "Acceptability Index %" was defined based on hedonic scoring to determine an overall rating, and used to categorize biofortified food products as "acceptable" (≥70%) or "not acceptable" (<70%). Additionally, this review narratively synthesized studies using methods other than hedonic scoring for assessing sensory acceptability. CONCLUSIONS: Forty-nine studies assessed the acceptability of 10 biofortified crops among children and adults, in mostly rural, low-income settings across Africa, Latin America, and India; food products made from mineral and provitamin A-biofortified food products were generally acceptable. Compared with studies on provitamin-A biofortified food products, few studies (1 to 2 each) on mineral-enhanced crops such as rice, cowpeas, lentils, and wheat were found, limiting the generalizability of the findings. Similarly, few studies examined stored biofortified food products. Few commercial food products have so far been developed, although new varieties of crops are being continuously tested and released globally. Certain crop varieties were found to be acceptable while others were not, suggesting that particular varieties should be prioritized for scale-up. Determining sensory acceptability of biofortified food products is important for informing programmatic scale-up and implementation across diverse populations and settings.
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Introduction: The first COVID-19 wave in Ecuador started in March 2020 and extended until November. Several types of drugs have been proposed as a potential treatment during this period, and some affected people have self-medicated. Method: A retrospective study was conducted with 10,175 individuals who underwent RT-PCR tests for SARS-CoV-2 from July to November 2020. We compared the number of positive and negative cases in Ecuador with symptoms and drug consumption. The Chi-square test of independence compared clinical and demographic data and PCR test results. Odds ratios analyzed drug consumption dynamics. Results: Of 10,175 cases, 570 were positive for COVID-19, while 9,605 were negative. In positive cases, there was no association between the RT-PCR result and sex, age, or comorbidities. When considering demographic data, Cotopaxi and Napo had the highest rates of positive cases (25.7% and 18.8%, respectively). Manabí, Santa Elena, and Guayas regions had fewer than 10% positive cases. The Drug consumption dynamic analysis showed that negative COVID-19 cases presented higher drug consumption than positive cases. In both groups, the most consumed medication was acetaminophen. Acetaminophen and Antihistamines had higher odds of consumption in positive PCR cases than in negative. Symptoms like fever and cough were more related to positive RT-PCR results. Conclusion: The first COVID-19 wave in Ecuador has affected the provinces differently. At a national level, the consumption of drugs has been highly associated with self-medication.
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OBJECTIVE: The objective of this study was to examine measurement properties of the Joint replacement version for Hip Disability and Osteoarthritis Outcome Score (HOOS-JR) using Rasch analysis in patients with osteoarthritis of hip (HOA). DESIGN: Cross-sectional clinical measurement SETTING: Patient outcomes database at a tertiary care hospital PARTICIPANTS: Convenience sampling of patients with HOA scheduled for total hip arthroplasty (N=327) OUTCOME MEASURES AND ANALYSIS: The data for pre-surgery assessments for patients with HOA were extracted from an existing database. Variables extracted included HOOS-JR scores, demographic information (age, sex), health-related data, and anthropometric variables. The assumptions of Rasch model such as the test of fit, fit residuals, ordering of item thresholds, factor structure, DIF, internal consistency and Pearson separation index were examined for the HOOS-JR scores. RESULTS: The HOOS-JR showed adequate overall fit to the Rasch model, logically ordered response thresholds, no floor or ceiling effects, and high internal consistency (Cronbach's alpha of 0.91). The HOOS-JR did not satisfy the assumption of unidimensionality, albeit the violation of this assumption was marginal (6.12% over 5%). Person-item threshold distribution (difference between person and item means were equal to 0.92 which was less than 1 logit unit) confirmed that the HOOS-JR scores were well targeted. CONCLUSIONS: Given that the violation of unidimensionality for HOOS-JR was marginal, we recommend further studies to validate this finding. Results broadly support the use of HOOS-JR for assessing hip health in patients with HOA.
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Artroplastia de Reemplazo de Cadera , Osteoartritis de la Cadera , Humanos , Osteoartritis de la Cadera/cirugía , Estudios Transversales , Reproducibilidad de los Resultados , Dimensión del Dolor/métodos , Medición de Resultados Informados por el PacienteRESUMEN
Background: Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects (NTDs) and other pregnancy complications. Vitamin B12 deficiency is a risk factor for NTDs and may modify folate biomarkers that predict NTD risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. Objectives: This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 households in Southern India. Methods: Women 18 to 49 y who are not pregnant or lactating and reside within the catchment area of our community-based research site in Southern India will be screened and invited to participate in the trial. After informed consent, women and their households will be randomized to receive one of the following 4 interventions: 1) double-fortified salt (DFS; iron, iodine), 2) DFS + folic acid (iron, iodine, folic acid), 3) DFS + vitamin B12 (iron, iodine, vitamin B12), or 4) DFS + folic acid and vitamin B12 (QFS; iron, iodine, folic acid, vitamin B12) for 12 mo. Structured interviews will be conducted by trained nurse enumerators to collect sociodemographic, anthropometric, dietary, health, and reproductive history data. Biological samples will be collected at baseline, midpoint, and endpoint. Whole blood will be analyzed for hemoglobin using Coulter Counter. Total vitamin B12 will be measured by chemiluminescence; red blood cell folate and serum folate will be evaluated using the World Health Organization-recommended microbiologic assay. Conclusions: The results of this randomized trial will help to evaluate the efficacy of QFS to prevent anemia and micronutrient deficiencies. Clinical trial registration numbers: NCT03853304 and Clinical Trial Registry of India REF/2019/03/024479. Registration number: NCT03853304 and REF/2019/03/024479.
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The Tilburg Frailty Indicator (TFI) is a validated tool for determining frailty in older adults. This study examined the validity and accuracy of the TFI Part B (TFI-B) in a North American context. Seventy-two individuals ≥ 65 years of age recruited from a rural geriatric medicine clinic completed a set of self-reported and performance-based measures, including TFI-B. Frailty level was determined using modified Fried's Frailty Phenotype (FFP). Pearson correlation coefficients (r) assessed the concurrent relationships between the TFI-B and other measures. Accuracy of the TFI-B in classifying frailty level was assessed using assessing area under the curve (AUC). The TFI-B scores showed low correlations (r < 0.4) with gait speed and grip, suggesting that the TFI-B did not consider frailty as merely a physical problem. The AUC of 0.82 indicated that the TFI-B scores accurately classified frail versus non-frail individuals. The score of ≥ 5 on the TFI-B scores showed satisfactory sensitivity/specificity (73%/77%) and excellent negative predictive value (91.95%). This indicates that a TFI-B score of < 5 can be used to rule out frailty.
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Fragilidad , Humanos , Anciano , Fragilidad/diagnóstico , Anciano Frágil , Encuestas y Cuestionarios , Evaluación Geriátrica , Psicometría , Reproducibilidad de los ResultadosRESUMEN
Hand masses and infections are commonly encountered by the community orthopaedic specialist, and maintaining an understanding of these ailments is important for diagnosis, treatment, and possible referral to a hand specialist. Hand masses are common, and it is important to provide the community orthopaedic specialist the knowledge needed for appropriate diagnostic workup and treatment as well as an understanding of when to refer to a hand specialist. Hand masses arise from soft tissue or bone. Specific types include ganglion cysts, mucoid cysts, giant cell tumors of the tendon sheath, lipomas, epidermal inclusions cysts, glomus tumors, and malignancies. Hand infections are also common, and their level of acuity can vary. It is important to define which infections necessitate urgent management and are associated with a risk of significant morbidity and mortality. From superficial cellulitis to deep space infections, it is important to provide an understanding of hand anatomy needed for appropriate treatment.
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Ganglión , Neoplasias de los Tejidos Blandos , Cirujanos , Humanos , Mano/patología , Ganglión/diagnóstico , Ganglión/patología , Huesos/patologíaRESUMEN
BACKGROUND: Isoindolin-1-ones are medicinally privileged heterocyclic compounds. Due to the interesting biological activities exhibited by these compounds, several synthetic and medicinal research groups have developed numerous synthetic approaches for these compounds. We have also previously reported two efficient approaches for the synthesis of the isoindolin-1-ones through iodoaminocyclization of alkynyl amides using n-BuLi and phosphazene superbases. OBJECTIVE: This study aimed to construct a medium-size library of multi-substituted 3- methyleneisoindolin-1-ones and study its biological profile, specifically anti-cancer activity. METHODS: Solution phase parallel synthesis was performed for the synthesis of the 3- methyleneisoindolin-1-ones library through n-BuLi-mediated iodoaminocyclization of 2(1- Alkynyl)benzamides. The iodocyclized products were further derivatized through palladiumcatalyzed Sonogashira and Suzuki Miyaura couplings and N-alkylation reactions. In silico evaluation of the physicochemical and ADMET properties was performed to examine the drug-likeness of the library compounds. Selected isoindolin-1-one analogues were evaluated for in vitro antiproliferative activity in various human cancer cell lines (MCF-7, A-549, and U-373 MG). RESULTS: A library of 46 multisubstituted 3-methyleneisoindolin-1-ones has been synthesized. The iodo-isoindolin-1-ones were synthesized in 66-76% yields through n-BuLi-mediated iodoaminocyclization of 2(1-Alkynyl)benzamides. Further diversification afforded the diverse library members in yields of 40-96%. Two of the library compounds exhibited GI50 values of < 10 µM in the human breast cancer cell line (MCF-7). CONCLUSION: Isoindolin-1-one library was constructed through electrophilic cyclization. The diversification was successfully performed through various C-C and C-N bond formation reactions. The anti-proliferative activity of the library members appears to be arising from the interaction of the compounds with the protein kinase drug targets.
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Antineoplásicos , Benzamidas , Humanos , Estructura Molecular , Línea Celular , Ciclización , Antineoplásicos/química , Relación Estructura-Actividad , Proliferación CelularRESUMEN
Background: In 2015, the American Association of Plastic Surgeons (AAPS) published a consensus statement against the routine use of preoperative antibiotic prophylaxis to prevent surgical site infection in clean hand surgery. The American Academy of Orthopaedic Surgeons (AAOS) similarly cited "insufficient evidence" in its Appropriate Use Criteria guidelines to support the use of antibiotics in carpal tunnel surgery. Nonetheless, its administration remains a common practice during clean hand surgery. We sought to evaluate the impact of the above guidelines on preoperative antibiotic administration. Methods: An institutional review board-approved retrospective chart review of consecutive patients with carpal tunnel syndrome treated with open carpal tunnel release (CTR) at our institution was performed in the 2 years before and after publication of AAPS/AAOS guidelines. Patient demographics and surgical outcomes were reviewed. Incidence of antibiotic administration, patient demographics, and surgeon factors were collected. Results: A total of 770 primary open CTR procedures were performed in the studied years. In 2013 and 2014, 83.9% of patients received preoperative antibiotics. In 2017 and 2018, 48.2% of patients received preoperative antibiotics. Of the variables analyzed, immunosuppression, history of diabetes, and poorly controlled diabetes (A1c > 7) were found to be statistically significant in its positive correlation to prophylactic preoperative antibiotic use. Diabetes was not associated with surgical site infections. Conclusion: Patients were more likely to receive preoperative antibiotics before the publication of the AAPS/AAOS clinical practice guidelines. Patients with diabetes regardless of their glycemic control are more likely to receive preoperative antibiotics.
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Síndrome del Túnel Carpiano , Ortopedia , Humanos , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Síndrome del Túnel Carpiano/cirugía , Estudios Retrospectivos , Estados Unidos , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: Description of the condition Malaria, an infectious disease transmitted by the bite of female mosquitoes from several Anopheles species, occurs in 87 countries with ongoing transmission (WHO 2020). The World Health Organization (WHO) estimated that, in 2019, approximately 229 million cases of malaria occurred worldwide, with 94% occurring in the WHO's African region (WHO 2020). Of these malaria cases, an estimated 409,000 deaths occurred globally, with 67% occurring in children under five years of age (WHO 2020). Malaria also negatively impacts the health of women during pregnancy, childbirth, and the postnatal period (WHO 2020). Sulfadoxine/pyrimethamine (SP), an antifolate antimalarial, has been widely used across sub-Saharan Africa as the first-line treatment for uncomplicated malaria sTo examine the effects of folic acid supplementation, at various doses, on malaria susceptibility (risk of infection) and severity among people living in areas with various degrees of malaria endemicity. We will examine the interaction between folic acid supplements and antifolate antimalarial drugs. Specifically, we will aim to answer the following. Among uninfected people living in malaria endemic areas, who are taking or not taking antifolate antimalarials for malaria prophylaxis, does taking a folic acid-containing supplement increase susceptibility to or severity of malaria infection? Among people with malaria infection who are being treated with antifolate antimalarials, does folic acid supplementation increase the risk of treatment failure?Criteria for considering studies for this review Types of studies Inclusion criteria Randomized controlled trials (RCTs) Quasi-RCTs with randomization at the individual or cluster level conducted in malaria-endemic areas (areas with ongoing, local malaria transmission, including areas approaching elimination, as listed in the World Malaria Report 2020) (WHO 2020) Exclusion criteria Ecological studies Observational studies In vivo/in vitro studies Economic studies Systematic literature reviews and meta-analyses (relevant systematic literature reviews and meta-analyses will be excluded but flagged for grey literature screening) Types of participants Inclusion criteria Individuals of any age or gender, living in a malaria endemic area, who are taking antifolate antimalarial medications (inclu
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Anemia , Antimaláricos , Antagonistas del Ácido Fólico , Defectos del Tubo Neural , Niño , Lactante , Embarazo , Recién Nacido , Femenino , Humanos , Preescolar , Antimaláricos/uso terapéutico , Sulfadoxina/uso terapéutico , Pirimetamina/uso terapéutico , Antagonistas del Ácido Fólico/uso terapéutico , Peso al Nacer , Parasitemia/tratamiento farmacológico , Vitaminas , Ácido Fólico/uso terapéutico , Anemia/tratamiento farmacológico , Suplementos Dietéticos , Hierro/uso terapéutico , RecurrenciaRESUMEN
Biofortification increases micronutrient content in staple crops through conventional breeding, agronomic methods, or genetic engineering. Bioaccessibility is a prerequisite for a nutrient to fulfill a biological function, e.g., to be bioavailable. The objective of this systematic review is to examine the bioavailability (and bioaccessibility as a proxy via in vitro and animal models) of the target micronutrients enriched in conventionally biofortified crops that have undergone post-harvest storage and/or processing, which has not been systematically reviewed previously, to our knowledge. We searched for articles indexed in MEDLINE, Agricola, AgEcon, and Center for Agriculture and Biosciences International databases, organizational websites, and hand-searched studies' reference lists to identify 18 studies reporting on bioaccessibility and 58 studies on bioavailability. Conventionally bred biofortified crops overall had higher bioaccessibility and bioavailability than their conventional counterparts, which generally provide more absorbed micronutrient on a fixed ration basis. However, these estimates depended on exact cultivar, processing method, context (crop measured alone or as part of a composite meal), and experimental method used. Measuring bioaccessibility and bioavailability of target micronutrients in biofortified and conventional foods is critical to optimize nutrient availability and absorption, ultimately to improve programs targeting micronutrient deficiency.
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Exposure to dietary aflatoxins has been recognized as a potential threat to child nutrition and growth, in addition to being a known carcinogen. The ability to accurately assess concentration of aflatoxin in the blood of at-risk individuals is therefore very important to inform public health policies and on-the-ground programs around the world. Venous blood is frequently used to quantify biomarkers of exposure such as AFB1-lysine adducts. However, venous blood collection methods are invasive, requiring highly trained staff, which makes this method challenging to implement, especially in resource-limited settings. In contrast, capillary blood collection by fingerprick is less invasive and has the potential for application in point-of-need monitoring. The aim of this exploratory study was to investigate the correlation and interchangeability of capillary and venous human blood samples in the quantification of AFB1-lysine adduct concentration. A total of 72 venous and capillary blood samples were collected from 36 women of reproductive age (16-49 years) in northern Uganda. All sample specimens were analyzed using high-performance liquid chromatography with fluorescence detection. Regression analysis and Bland-Altman analysis were performed to compare AFB1-lysine concentrations between venous and capillary sample pairs. Bland-Altman analysis of albumin-normalized AFB1-lysine data-bias was -0.023 pg/mg-albumin and the 95% limits of agreement were 0.51 to -0.56 pg/mg-albumin for log-transformed data. There was a positive correlation between albumin-normalized venous and capillary AFB1-lysine concentrations with r of 0.71 (p < .0001). A lack of any accepted clinical cutoff for aflatoxin exposure makes definition of an 'acceptable' limit for statistical analysis and comparison of methods challenging. Our data suggests a positive correlation between albumin-normalized AFB1-lysine concentrations in venous and capillary sample pairs, but relatively weak agreement and interchangeability based on Bland-Altman analysis.
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Aflatoxinas , Adolescente , Adulto , Aflatoxina B1 , Albúminas , Biomarcadores , Carcinógenos , Femenino , Humanos , Lisina , Persona de Mediana Edad , Adulto JovenRESUMEN
Background: We catalog and summarize evidence of the analytical performance of portable quantitative and semi-quantitative devices for the assessment of vitamin A status and vitamin A deficiency (VAD) in various biological samples-including whole blood, plasma, serum, and milk-in addition to VAD determination by functional indicators such as pupillary response. Methods: We searched the literature for published research articles, patents, and information from manufacturers of mobile devices, particularly those appropriate for low-resource settings. The included devices were required to be portable (lightweight and ideally not needing a power outlet) and to measure vitamin A as well as define VAD. Eligible studies compared a portable device to a reference standard of high-performance liquid chromatography for blood and milk, or a Goldmann-Weekers dark adaptometer for eyes/vision. Where available, identified devices were compared with reference methods across several performance criteria. When possible, we compared the device's performance reported in published studies against the stated performance criteria from the manufacturers' websites. Results: We catalogued 25 portable devices for measuring vitamin A and/or VAD via biological samples. We also identified 18 comparison studies (plus associated reports) assessing nine methods: the iCheck Fluoro, iCheck Carotene, CRAFTi, Tidbit with or without the HYPER filtration system, custom field-friendly immunoassays, and microfluidic assays for blood; the iCheck Fluoro and iCheck Carotene for milk; and the Scotopic Sensitivity Tester-1 for eye function. Conclusions: The iCheck Fluoro and iCheck Carotene are commercially available for use and are acceptable for measuring vitamin A in blood and milk samples, according to the available validation data. Many of the other identified devices, including other portable fluorometers, photometers, immunoassays, microfluidics-based devices, and dark adaptometers, were proofs of concept and not yet commercially available. Furthermore, none of these other devices included manufacturer-described device performance criteria to compare with descriptions from experimental studies. Several gaps remain, including studies comparing the other portable devices against a reference standard, particularly for functional indicators of vitamin A status/deficiency; available manufacturer-reported device performance criteria against which to compare future results of investigations; and more comprehensive reporting of validation metrics including sensitivity, specificity, precision, and Bland-Altman analysis.