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BACKGROUND: Promoting health via a community approach is one of the most effective strategies for reducing the current incidence of chronic diseases. Primary care (PC), through the implementation of community activities (CA), has the potential to achieve this goal. Yet the implementation of CA at health centers is not standardized and is often thanks only to the voluntariness of health professionals. OBJECTIVE: To ascertain the knowledge, attitudes, and practices of PC professionals regarding the implementation of CA. METHODS: We carried out a cross-sectional study by circulating a self-administered online questionnaire on CA, across the period December 2022 through June 2023 in Galicia (Spain). All health professionals working in the Galician Health Service PC setting were invited to participate. RESULTS: A total of 521 health professionals participated in the study. They included all types of PC health professionals (physicians, general and specialist nurses -midwives, pediatrics, family and community, mental health- and social workers), including residents in training. Only 14.8% and 12.5% of professionals correctly identified CAs and social prescription (SPr) interventions, respectively. Furthermore, 93.9% recognized that the development of CA in health centers was deficient. Despite this, 76.5% showed a good attitude toward participation in CA. CONCLUSIONS: PC professionals find it difficult to identify CA and SPr interventions. Therefore, it is necessary to improve the training of these professionals in the implementation of CA with a view to enhancing population health, reducing the incidence of chronic diseases, and helping lessen the healthcare burden of the health system.
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BACKGROUND: Fetal sex and placental development impact pregnancy outcomes and fetal-maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies. METHODS: Pregnant subjects were recruited in late first trimester (weeks 10-14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas. RESULTS: Methylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood. CONCLUSIONS: Overall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta.
Fetal sex and placenta development affect pregnancy outcomes for both the fetus and mother throughout pregnancy, including risk of miscarriages, preterm birth, preeclampsia, and other outcomes. Epigenetics, the "overlay" of regulatory signals on DNA which affects how DNA is read, is not well understood in early pregnancy when critical placenta developments are happening that affect the rest of pregnancy. Here, we use leftover placenta biopsy samples (n = 56) donated by Cedars-Sinai patients with informed consent to learn about first trimester human placenta DNA methylation differences due to fetal sex. Out of the total 743,461 sites analyzed, we identified 151 sites significantly affected by fetal sex after correcting p-values to reduce false positives (false discovery rate < 0.05). We also performed an analysis to look at multiple sites and identified 11 regions across the genome with significant DNA methylation changes due to fetal sex. Furthermore, because DNA methylation is a regulatory mark on DNA which typically dampens gene expression, we also compared the DNA methylation sex differences to placental RNA-sequencing gene expression analysis using the same tissue from a mostly overlapping patient group (n = 74 total sequenced, n = 51 overlap). We identify 18 genes which show both significant DNA methylation differences and gene expression changes. The most significant gene was transcription factor ZNF300 with higher DNA methylation in males and reduced gene expression in males (and thus higher gene expression in females). This study identifies some sex differences that continue until later pregnancy and others that are unique to first trimester.
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Metilação de DNA , Placenta , Primeiro Trimestre da Gravidez , Caracteres Sexuais , Humanos , Feminino , Gravidez , Masculino , Placenta/metabolismo , AdultoRESUMO
BACKGROUND: In 2020, the prevalence of cancer rose to 844,778 cases among the population aged 0-19 years. Approximately 90% of individuals under 18 years of age reside in low- and middle-income countries, where cancer survivors report adverse outcomes that negatively impact their general health, emotional state, and external factors such as academic performance due to the effect of these outcomes on executive functions. The Wisconsin Cart Sorting Test (WCST) is the gold standard for evaluating executive functioning. Therefore, this article (1) reports the performance of the Wisconsin Card Sorting Test (WCST) in oncopediatric patients from Cali, Colombia; (2) indicates the reliability of the WCST; (3) describes the association between cancer type and executive functioning in patients; (4) describes the differences between patients with various executive deficits and their executive total scores; and (5) describes the association between cancer type and the presence of brain deficits based on the WCST. METHODS: In this cross-sectional observational study, 24 oncopediatric patients were interviewed and evaluated via the WCST. RESULTS: The mean age was 12.08 years (SD 3.98); 20.8% of the patients were women, 70.8% had a primary diagnosis of leukemia, 8% exhibited acquired brain deficits, and more than 75% displayed adequate functional indicators of executive functions. Robust statistics were employed to explore the differences between the types of diagnosis and performance in executive functions, and no statistically significant differences were found (p = 0.156). We found that the WCST has a reliable Cronbach's α of 0.804. Oncopediatric patients without brain deficits presented strong results in terms of executive functions (p = 0.002), with a moderate effect size (0.727). CONCLUSIONS: The WCST is reliable for discriminating executive functioning among pediatric cancer patients. The evidence suggests that there were no differences in the executive functioning of the participants based on the types of cancer being evaluated.
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Persistent trachoma is a growing concern to trachoma control programs globally and programs serving Ethiopia specifically. Persistent trachoma is defined as a district with two or more trachoma impact surveys (TISs) at which the prevalence of trachomatous inflammation-follicular (TF) among children ages 1-9 years is ≥5%, the elimination threshold. Because the global target for trachoma elimination as a public health problem is 2030, research is needed to better characterize persistent trachoma. This study described the epidemiology of ocular Chlamydia trachomatis infection, the causative bacteria of trachoma, in seven contiguous districts experiencing persistent trachoma. In 2019, multistage cluster random sampling TISs were conducted in the seven districts after 10 years of interventions. All individuals ages ≥1 year were examined for trachoma clinical signs by certified graders, and conjunctival swabs were collected from children ages 1-5 years to test for C. trachomatis infection. The district TF prevalence ranged from 11.8% (95% CI:7.6-16.0%) to 36.1% (95% CI:27.4-44.3%). The range of district-level C. trachomatis infection prevalence was between 2.7% and 34.4%. Statistically significant spatial clustering of high-infection communities was observed in the study districts, and children with infection were more likely than those without to be found in households with clinical signs of trachoma and those without latrines. These seven districts appear to constitute a persistent hotspot in Amhara, where an additional 3-5 years or more of interventions will be required. The global program will need to strengthen and enhance intervention strategies within persistent districts if elimination by 2030 is to be achieved.
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Chlamydia trachomatis , Tracoma , Humanos , Tracoma/epidemiologia , Tracoma/microbiologia , Etiópia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Pré-Escolar , Lactente , Feminino , Masculino , Criança , Prevalência , Doenças EndêmicasRESUMO
Chordoma is a malignant bone tumor originating from notochordal remnants, most commonly occurring at the sacrococcygeal junction. We present a case of a 70-year-old male with chronic pain in the lower lumbar spine. MRI performed elsewhere revealed a large tumor that involved S4, S5, and the coccyx with a presacral soft tissue component. The lesion was heterogeneously hyperintense on T2-weighted images with a thick hypointense rim anteriorly. On T1-weighted images, the lesion showed a native hyperintense signal centrally probably due to hemorrhage. Based on this MRI, the diagnosis of chordoma was suggested. A spontaneous marked reduction in size was observed on a 4-week interval MRI performed at our institution before biopsy. Due to spontaneous tumor shrinkage along with peripheral enhancement, a differential diagnosis of infection or bleeding in a retrorectal cyst was proposed. This case teaches us that chordomas may contain a large hemorrhagic component, which is hyperintense on T1-weighted images and shows peripheral rim enhancement. Spontaneous shrinkage of a tumor may occur due to the resolution of a hematoma within weeks. Biopsy is key to obtain the correct diagnosis. Understanding the typical and more rare features of chordomas is key for MSK radiologists as well as pathologists. Chordomas are typically slow-growing tumors, but radiologists should be aware that intratumoral hemorrhage can lead to rapid changes in tumor size, which may be mistaken for either regression or progression of tumor. This case highlights the importance of considering hemorrhagic events within chordomas in the differential diagnosis when observing size fluctuations on imaging.
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After years of programmatic inaccessibility, in 2019-2020 the Sudan Federal Ministry of Health Trachoma Control Program conducted population-based trachoma surveys in three localities (districts) in North Darfur state, Sudan. These baseline surveys were to determine the prevalence of trachomatous inflammation-follicular (TF) among children aged 1-9 years and to further use serological markers to understand the historical trachoma burden within this mass drug administration (MDA)-naive area. Trained and certified graders collected trachoma clinical data, and trained nurses collected dried blood spot (DBS) samples. The DBSs were assayed on a multiplex bead array for antibody responses to the Chlamydia trachomatis antigens Pgp3 and CT694. Across the three localities, 3,613 individuals aged 1-9 years and 3,542 individuals aged ≥15 years were examined for clinical signs, and 8,322 DBSs were collected. The prevalence of TF among children aged 1-9 years was endemic (≥5%) in two localities (El Seraif, 15.6%, and Saraf Omrah, 11.0%) and below the TF elimination threshold (<5%) in the third (Kotom, 1.4%). The Pgp3 seroprevalence among children aged 1-9 years was 34.1% in El Seraif, 35.0% in Saraf Omrah, and 11.0% in Kotom. Locality prevalence results were similar for Pgp3 and CT694. Seroprevalence increased with age in all three localities. Serological data collected within these surveys demonstrate that all three localities have had a long history of exposure to Chlamydia trachomatis and that two of the three localities require MDA to reach elimination as a public health problem threshold.
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Anticorpos Antibacterianos , Antígenos de Bactérias , Chlamydia trachomatis , Administração Massiva de Medicamentos , Tracoma , Humanos , Tracoma/epidemiologia , Sudão/epidemiologia , Criança , Pré-Escolar , Lactente , Chlamydia trachomatis/imunologia , Feminino , Adolescente , Antígenos de Bactérias/imunologia , Masculino , Adulto , Anticorpos Antibacterianos/sangue , Adulto Jovem , Prevalência , Estudos Soroepidemiológicos , Pessoa de Meia-Idade , Teste em Amostras de Sangue SecoRESUMO
INTRODUCTION: Fetal sex affects fetal and maternal health outcomes in pregnancy, but this connection remains poorly understood. As the placenta is the route of fetomaternal communication and derives from the fetal genome, placental gene expression sex differences may explain these outcomes. OBJECTIVES: We utilized next generation sequencing to study the normal human placenta in both sexes in first and third trimester to generate a normative transcriptome based on sex and gestation. STUDY DESIGN: We analyzed 124 first trimester (T1, 59 female and 65 male) and 43 third trimester (T3, 18 female and 25 male) samples for sex differences within each trimester and sex-specific gestational differences. RESULTS: Placenta shows more significant sexual dimorphism in T1, with 94 T1 and 26 T3 differentially expressed genes (DEGs). The sex chromosomes contributed 60.6% of DEGs in T1 and 80.8% of DEGs in T3, excluding X/Y pseudoautosomal regions. There were 6 DEGs from the pseudoautosomal regions, only significant in T1 and all upregulated in males. The distribution of DEGs on the X chromosome suggests genes on Xp (the short arm) may be particularly important in placental sex differences. Dosage compensation analysis of X/Y homolog genes shows expression is primarily contributed by the X chromosome. In sex-specific analyses of first versus third trimester, there were 2815 DEGs common to both sexes upregulated in T1, and 3263 common DEGs upregulated in T3. There were 7 female-exclusive DEGs upregulated in T1, 15 female-exclusive DEGs upregulated in T3, 10 male-exclusive DEGs upregulated in T1, and 20 male-exclusive DEGs upregulated in T3. DISCUSSION: This is the largest cohort of placentas across gestation from healthy pregnancies defining the normative sex dimorphic gene expression and sex common, sex specific and sex exclusive gene expression across gestation. The first trimester has the most sexually dimorphic transcripts, and the majority were upregulated in females compared to males in both trimesters. The short arm of the X chromosome and the pseudoautosomal region is particularly critical in defining sex differences in the first trimester placenta. As pregnancy is a dynamic state, sex specific DEGs across gestation may contribute to sex dimorphic changes in overall outcomes.
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Sequenciamento de Nucleotídeos em Larga Escala , Placenta , Caracteres Sexuais , Humanos , Feminino , Gravidez , Masculino , Placenta/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Adulto , Transcriptoma , Terceiro Trimestre da Gravidez/genética , Análise de Sequência de RNA , Primeiro Trimestre da Gravidez/genética , Primeiro Trimestre da Gravidez/metabolismoRESUMO
Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is characterized by impaired lung development with sustained functional abnormalities due to alterations of airways and the distal lung. Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about the underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of the airways and parenchyma, contributes to late respiratory disease as a result of antenatal stress is unknown. We hypothesized that antenatal endotoxin (ETX) impairs juvenile lung function as a result of altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intraamniotic ETX (10 µg) or saline solution (control) 2 days before term. We performed extensive structural and functional evaluation of the proximal airways and distal lung in 2-week-old rats. Distal lung structure was quantified by stereology. Conducting airway diameters were measured using micro-computed tomography. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. ETX-exposed pups exhibited distal lung simplification, decreased alveolar surface area, and decreased parenchyma-airway attachments. ETX-exposed pups exhibited decreased tracheal and second- and third-generation airway diameters. ETX increased respiratory system resistance and decreased lung compliance at baseline. Only Newtonian resistance, specific to large airways, exhibited increased methacholine reactivity in ETX-exposed pups compared with controls. ETX-exposed pups had a decreased ratio of FEV in 0.1 second to FVC and a normal FEV in 0.1 second, paralleling the clinical definition of dysanapsis. Antenatal ETX causes abnormalities of the central airways and distal lung growth, suggesting that dysanapsis contributes to abnormal lung function in juvenile rats.
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Displasia Broncopulmonar , Ratos , Animais , Feminino , Gravidez , Displasia Broncopulmonar/patologia , Endotoxinas , Cloreto de Metacolina/farmacologia , Microtomografia por Raio-X , Ratos Sprague-Dawley , Animais Recém-Nascidos , Pulmão/patologiaRESUMO
The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal-fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal-fetal health.
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Placenta , Primeiro Trimestre da Gravidez , Terceiro Trimestre da Gravidez , RNA Mensageiro , Transcriptoma , Humanos , Feminino , Gravidez , Terceiro Trimestre da Gravidez/genética , Placenta/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Primeiro Trimestre da Gravidez/genética , Adulto , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.
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Fármacos Anti-HIV , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Raltegravir Potássico/efeitos adversos , Lamivudina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Quimioterapia Combinada , Carga Viral , Resultado do TratamentoRESUMO
IMPORTANCE: Because analytic technologies improve, increasing amounts of data on methylation differences between assisted reproductive technology (ART) and unassisted conceptions are available. However, various studies use different tissue types and different populations in their analyses, making data comparison and integration difficult. OBJECTIVE: To compare and integrate data on genome-wide analyses of methylation differences due to ART, allowing exposure of overarching themes. EVIDENCE REVIEW: All studies undertaking genome-wide analysis of human methylation differences due to ART or infertility in any tissue type across the lifespan were assessed for inclusion. FINDINGS: Seventeen studies were identified that met the inclusion criteria. One study assessed trophectoderm biopsies, 2 first-trimester placenta, 1 first-trimester fetal tissue, 2 term placenta, 7 cord blood, 3 newborn dried blood spots, 1 childhood buccal smears, 1 childhood peripheral blood, and 2 adult peripheral blood. Eleven studies compared tissues from in vitro fertilization (IVF) conceptions with those of unassisted conceptions, 4 compared intracytoplasmic sperm injection with unassisted conceptions, 4 compared non-IVF fertility treatment (NIFT) with unassisted conceptions, 4 compared NIFT with IVF, and 5 compared an infertile population (conceiving via various methods) with an unassisted presumably fertile population. In studies assessing placental tissue, 1 gene with potential methylation changes due to IVF when compared with unassisted conceptions was identified by 2 studies. In blood, 11 potential genes with methylation changes due to IVF compared with unassisted conceptions were identified by 2 studies, 1 of which was identified by 3 studies. Three potentially affected genes were identified by 2 studies involving blood between intracytoplasmic sperm injection and unassisted populations. There were no overlapping genes identified in any tissue type between NIFT and unassisted populations, between NIFT and IVF, or the infertility combined population when compared with the unassisted fertile population. CONCLUSIONS: Comparing studies is challenging due to differing variables between analyses. However, even in similar tissue types and populations, overlapping methylation changes are limited, suggesting that differences due to ART are minimal. RELEVANCE: Information from this systematic review is significant for providers and patients who provide and use ART to understand methylation risks that may be associated with the technology.
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Metilação de DNA , Estudo de Associação Genômica Ampla , Técnicas de Reprodução Assistida , Adulto , Criança , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Fertilização in vitro , Infertilidade/diagnóstico , Infertilidade/genética , Infertilidade/terapia , Placenta/metabolismo , Técnicas de Reprodução Assistida/efeitos adversos , SêmenRESUMO
Breast cancer (BC) is the most frequent malignant neoplasia and leading cause of cancer mortality for women. A timely diagnosis of BC is crucial to ensure the best chances of survival. Among the various screening tools for BC, antibodies directed towards self-antigens or tumor-associated antigens (autoantibodies) have emerged as an alternative to image-based screening modalities. However, little attention has been paid to the global diversity of autoantibodies. This work aimed to analyze the diversity of autoantibodies reactive to antigens expressed by the BC cell line T47D in the sera of Mexican women with BC, benign breast pathology (BBP), or without breast pathology (WBP). We found that the diversity of antibodies in the sera was higher in the BC and BBP groups than in the WBP group. Likewise, the diversity changed with the progression of BC. Our results show and measure the complexity of the antibody response in breast health and disease.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/patologia , Autoanticorpos , Antígenos de NeoplasiasRESUMO
Resumen Objetivo: Identificar factores clínicos y sociodemográficos asociados a la mortalidad en los pacientes internados por pie diabético, en la Unidad de Pie Diabético del Hospital San Juan de Dios de Costa Rica, del año 2017 al 2019. Materiales y métodos: Estudio de cohorte retrospectivo con 238 pacientes, seguidos desde su internamiento hasta la muerte o al 31 de diciembre del 2021 aún vivos. Análisis descriptivo a variables sociodemográficas, clínicas y causas de muerte. Modelo de riesgos proporcionales de Cox para todas las causas de muerte, y otro exclusivo para muerte por causa cardiovascular. Tiempos de supervivencia se analizan por curvas de Kaplan-Meier, con la prueba de log-Rank para comparar curvas. Resultados: Mayoría de los fallecidos eran hombres, no contaban con pareja, residían en zona urbana o predominantemente urbana, de 15 años o más de ser diabéticos, hipertensos, con enfermedad arterial periférica, anemia, hemoglobina glicosilada inadecuada y obesidad. La tasa de mortalidad fue 23,53%, y la principal causa de muerte fue la enfermedad cardiovascular (35,70 %). Las variables asociadas con mortalidad por todas las causas, ajustadas por edad y sexo fueron: ausencia de pareja (HR: 13,09; IC 95 %: 4,04-42,31), obesidad (HR: 2,89; IC 95 %: 1,59-5,27), enfermedad arterial periférica (HR: 2,26; IC 95 %: 1,25-4,09), años de evolución de la diabetes mellitus ≥ 15 años (HR: 1,99; IC 95 %: 1,04-3,82). A su vez, para mortalidad cardiovascular fueron: obesidad (HR: 6,42; IC 95 %: 2,07-19,87), enfermedad arterial periférica (HR: 3,88; IC 95 %: 1,39-10,79) y cardiopatía (HR: 4,11; IC 95 %: 1,62-10,46). Conclusiones: Años de evolución de la diabetes mellitus mayor o igual a 15 años, no contar con pareja; la obesidad y enfermedad arterial periférica se asoció a mortalidad por todas las causas. Respecto a muerte por enfermedad cardiovascular, las variables asociadas fueron obesidad, enfermedad arterial periférica y cardiopatía.
Abstract Objective: To identify clinical and sociodemographic factors associated with mortality in patients hospitalized for diabetic foot, in the Diabetic Foot Unit of the San Juan de Dios Hospital in Costa Rica, from 2017 to 2019. Materials and methods: A retrospective cohort study with 238 patients, followed from hospitalization until death or until December 31, 2021, still alive. A descriptive analysis is made of the sociodemographic, clinical, and cause of death variables. A Cox proportional hazards model is run for all causes of death, and another exclusively for death from cardiovascular causes. Survival times are analyzed using Kaplan-Meier curves, with the log-rank test for comparison. Results: Most of the deceased were men, did not have a partner, lived in urban or predominantly urban areas, were 15 years or older, diabetic, hypertensive, with peripheral arterial disease, anemia, inadequate glycosylated hemoglobin, and obesity. The mortality rate was 23,53%, and cardiovascular disease was the main cause of death (35,70%). The variables associated with all-cause mortality, adjusted for age and sex were: absence of a partner (HR: 13,09; 95% CI: 4,04-42,31), obesity (HR: 2,89; 95% CI %: 1,59-5,27), peripheral arterial disease (HR: 2,26; CI 95%: 1,25-4,09), years of evolution of diabetes mellitus ≥ 15 years (HR: 1,99; CI 95 %: 1,04-3,82). In turn, for cardiovascular mortality were: obesity (HR: 6,42; 95% CI: 2,07-19,87), peripheral arterial disease (HR: 3,88; 95% CI: 1,39-10,79) and heart disease (HR: 4,11; 95% CI: 1,62-10,46). Conclusions: Evolution of diabetes mellitus greater than or equal to 15 years, not having a partner, obesity and peripheral arterial disease were associated with all-cause mortality. Regarding death from cardiovascular disease, the associated variables were obesity, peripheral arterial disease, and heart disease.
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BACKGROUND: The emergency derived from coronavirus disease 2019 (COVID-19) has taught us important lessons in public and environmental health, particularly in the alarming numbers of existing noncommunicable diseases. However, one aspect to which little attention has been paid during the pandemic is mental health and its relationship with the gender perspective, in spite of gender being a determinant associated with health. In contrast, regarding health, few schemes and theories consider health from a positive and comprehensive perspective. METHODS: This study was designed to examine the symptoms of stress and positive coping from a gender perspective. For this, the Stress Symptomatology Inventory, the Positive Coping to Life Scale and a general data questionnaire were applied to 665 individuals underwent the severe acute respiratory syndrome coronavirus 2 test at the Center for Health Studies and Services of the Universidad Veracruzana from July 2020 to November 2021. FINDINGS: We found that women presented more stress symptoms and less positive coping in the factor of positive self-regulation of adverse situations and the factors of self-determination and positive self-regulation of important situations. Moreover, significant differences in the associations of these variables were observed between men and women. CONCLUSIONS: Therefore, the needs of women must be considered in the approach to the emergency department due to COVID-19 and in general in the health-disease process; therefore, not considering a gender approach will continue to deepen inequalities between sexes.
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COVID-19 , Masculino , Humanos , Feminino , COVID-19/epidemiologia , Adaptação Psicológica , SARS-CoV-2 , Saúde Mental , PandemiasRESUMO
Background: The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal- fetal health. Methods: The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Results: Placenta expresses 14,979 mRNAs above sequencing noise (TPM>0.66), with 1,545 stably expressed genes across gestation. Differentially expressed genes account for 86.7% of genes in the full cohort (FDR<0.05). Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR<0.001, fold change>1.5), there are 6,941 differentially expressed protein coding genes (3,206 upregulated in first and 3,735 upregulated in third trimester). Conclusion: This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and stably expressed genes may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers in maternal-fetal disease.
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The acid-base characteristics of tumor cells and the other elements that compose the tumor microenvironment have been topics of scientific interest in oncological research. There is much evidence confirming that pH conditions are maintained by changes in the patterns of expression of certain proton transporters. In the past decade, the voltage-gated proton channel (Hv1) has been added to this list and is increasingly being recognized as a target with onco-therapeutic potential. The Hv1 channel is key to proton extrusion for maintaining a balanced cytosolic pH. This protein-channel is expressed in a myriad of tissues and cell lineages whose functions vary from producing bioluminescence in dinoflagellates to alkalizing spermatozoa cytoplasm for reproduction, and regulating the respiratory burst for immune system response. It is no wonder that in acidic environments such as the tumor microenvironment, an exacerbated expression and function of this channel has been reported. Indeed, multiple studies have revealed a strong relationship between pH balance, cancer development, and the overexpression of the Hv1 channel, being proposed as a marker for malignancy in cancer. In this review, we present data that supports the idea that the Hv1 channel plays a significant role in cancer by maintaining pH conditions that favor the development of malignancy features in solid tumor models. With the antecedents presented in this bibliographic report, we want to strengthen the idea that the Hv1 proton channel is an excellent therapeutic strategy to counter the development of solid tumors.
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Introducción: la adherencia al tratamiento no farmacológico de la diabetes mellitus es un factor clave para evitar o retrasar las complicaciones de esta enfermedad. El cumplimento terapéutico depende de múltiples factores. Objetivo: evaluar la adherencia al tratamiento higiénico dietético en pacientes con diabetes mellitus, sobre todo la nutricional y la actividad física. Se midieron además las variables demográficas y presencia de hipertensión arterial. Metodología: se realizó una entrevista a pacientes adultos de ambos sexos, portadores de diabetes mellitus, que residen en el barrio Sajonia de Asunción, Paraguay, entre mayo y octubre del 2022. Se midieron variables demográficas y clínicas. La adherencia se determinó con el cuestionario de Caro Bautista que consta de 7 preguntas que evalúan las prácticas terapéuticas de los pacientes en la última semana. El estudio contó con la aprobación del Comité de ética de la Facultad de Medicina de la Universidad Privada del Este, Paraguay. Resultados: fueron entrevistados 257 personas con el diagnóstico de diabetes mellitus, con predominio del sexo femenino (61,4%), 73,9% refería tener ingresos propios y 49% padecía también de hipertensión arterial. El cuestionario detectó que 20,1% seguía una dieta saludable toda la semana, 15,5% realizaba ejercicios físicos diariamente y 14,3% realizaba los monitoreos de sangre capilar regularmente. Conclusión: entre 10 y 22% de los pacientes con diabetes mellitus realiza dieta y ejercicios adecuados, así como monitoreo de la glucemia según las recomendaciones de sus médicos.
Introduction: Adherence to non-pharmacological treatment of diabetes mellitus is a key factor in avoiding or delaying the complications of this disease. Treatment compliance depends on multiple factors. Objective: To evaluate adherence to dietary hygienic treatment in patients with diabetes mellitus, especially nutrition and physical activity. Demographic variables and the presence of arterial hypertension were also measured. Methodology: An interview was conducted with adult male and female patients, carriers of diabetes mellitus, residing in the Sajonia neighborhood of Asunción, Paraguay, between May and October 2022. Demographic and clinical variables were measured. Adherence was determined with the Caro Bautista questionnaire, which consists of seven questions that evaluate the therapeutic practices of patients in the last week. The study was approved by the Ethics Committee of the Faculty of Medicine of the Universidad Privada del Este, Paraguay. Results: Two hundred fifty-seven people diagnosed with diabetes mellitus were interviewed, with a predominance of females (61.4%), 73.9% reported having their own income and 49% also suffered from arterial hypertension. The questionnaire detected that 20.1% followed a healthy diet all week, 15.5% performed daily physical exercises, and 14.3% performed capillary blood monitoring regularly. Conclusion: Between 10 and 22% of patients with diabetes mellitus perform adequate diet and exercise, as well as glycemia monitoring according to the recommendations of their physicians.
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OBJECTIVE: To determine whether deoxyribonucleic acid (DNA) methylation alterations exist in the first-trimester human placenta between conceptions using fertility treatments and those that do not and, if so, whether they are the result of underlying infertility or fertility treatments. We also assessed whether significant alterations led to changes in gene expression. DESIGN: We compared DNA methylation of the first-trimester placenta from singleton pregnancies that resulted in live births from unassisted, in vitro fertilization (IVF), and non-IVF fertility treatment (NIFT) conceptions using the Infinium MethylationEPIC BeadChip array. Significant CpG sites were compared with corresponding ribonucleic acid sequencing analysis in similar cohorts to determine whether methylation alterations lead to differences in gene expression. SETTING: Academic medical center. PATIENT(S): A total of 138 singleton pregnancies undergoing chorionic villus sampling resulting in a live birth were recruited for methylation analysis (56 unassisted, 38 NIFT, and 44 IVF conceptions). Ribonucleic acid-sequencing data consisted of 141 subjects (74 unassisted, 33 NIFT, and 34 IVF conceptions) of which 116 overlapped with the methylation cohort. INTERVENTION(S): In vitro fertilization-conceived pregnancy or pregnancy conceived via NIFT, such as ovulation induction and intrauterine insemination. MAIN OUTCOME MEASURE(S): Significant methylation changes at CpG sites after adjustment for multiple comparisons. The secondary outcome was gene expression changes of significant CpG sites. RESULT(S): Of the 741,145 probes analyzed in the placenta, few were significant at Bonferroni <0.05: 185 CpG sites (0.025%) significant in pregnancies conceived with the fertility treatments (NIFT + IVF) vs. unassisted conceptions; 28 in NIFT vs. unassisted; 195 in IVF vs. unassisted; and only 13 (0.0018%) in IVF vs. NIFT conceptions. Of all significant CpG sites combined, 10% (35) were located in genes with suggestive gene expression changes, but none were significant after adjustment for multiple comparisons (ribonucleic acid sequencing false discovery rate <0.05). None of the 13 differentially methylated probes in the IVF vs. NIFT placenta were located in genes with suggestive IVF vs. NIFT gene expression differences. CONCLUSION(S): Underlying infertility is the most significant contributor to the minimal differences in first-trimester placental methylation, and not the specific fertility treatment used, such as IVF.
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Infertilidade , Placenta , Gravidez , Feminino , Humanos , Placenta/metabolismo , Primeiro Trimestre da Gravidez , Metilação de DNA , Infertilidade/diagnóstico , Infertilidade/genética , Infertilidade/terapia , Fertilização in vitro/efeitos adversos , Nascido Vivo , RNA , Expressão GênicaRESUMO
BACKGROUND: Although antiretroviral therapy (ART) is effective in suppressing viral replication, HIV-1 persists in reservoirs and rebounds after ART has been stopped. However, a very few people (eg, elite and post-treatment controllers) are able to maintain viral loads below detection limits without ART, constituting a realistic model for long-term HIV remission. Here, we describe the HIV control mechanisms of an individual who showed exceptional post-treatment control for longer than 15 years. METHODS: We report the case of a Hispanic woman aged 59 years with sexually acquired acute HIV infection, who was included in an immune-mediated primary HIV infection trial involving a short course of ciclosporine A, interleukin-2, granulocyte macrophage colony-stimulating factor, and pegylated interferon alfa, followed by analytical treatment interruption. We did the following viral assays: total and integrated HIV-1 DNA in CD4 T cells and rectal tissue, quantitative viral outgrowth assay, HIV-1 infectivity in peripheral blood mononuclear cells and CD4 T-cell cultures and viral inhibitory activity by natural killer (NK) and CD8 T cells. NK and T-cell phenotypes were determined by flow cytometry. HLA, killer cell immunoglobulin-like receptors, Δ32CCR5, and NKG2C alleles were genotyped. FINDINGS: After ART and immunomodulatory treatment, the person maintained undetectable plasma viral load for 15 years. HIV-1 subtype was CFR_02AG, CCR5-tropic. We found progressive reductions in viral reservoir during the 15-year treatment interruption: total HIV DNA (from 4573·50 copies per 106 CD4 T cells to 95·33 copies per 106 CD4 T cells) and integrated DNA (from 85·37 copies per 106 CD4 T cells to 5·25 copies per 106 CD4 T cells). Viral inhibition assays showed strong inhibition of in vitro HIV replication in co-cultures of CD4 T cells with autologous NK or CD8 T cells at 1:2 ratio (75% and 62%, respectively). Co-cultures with NK and CD8 T cells resulted in 93% inhibition. We detected higher-than-reference levels of both NKG2C-memory-like NK cells (46·2%) and NKG2C γδ T cells (64·9%) associated with HIV-1 control. INTERPRETATION: We described long-term remission in a woman aged 59 years who was treated during primary HIV infection and has maintained undetectable viral load for 15 years without ART. Replication-competent HIV-1 was isolated. NKG2C-memory-like NK cells and γδ T cells were associated with the control viral replication. Strategies promoting these cells could bring about long-term HIV remission. FUNDING: Fondo Europeo para el Desarrollo Regional (FEDER), SPANISH AIDS Research Network (RIS), Fondo de Investigación Sanitaria (FIS), HIVACAT, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CERCA Programme/Generalitat de Catalunya, la Caixa Foundation, and Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
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Infecções por HIV , Soropositividade para HIV , Humanos , Leucócitos Mononucleares , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Carga ViralRESUMO
Breast cancer (BC) is a leading cause of women's morbimortality worldwide. Unfortunately, attempts to predict women's susceptibility to developing BC well before it becomes symptomatic, based on their genetic, family, and reproductive background have proved unsatisfactory. Here we analyze the matching of personality traits and protein serum profiles to predict women's susceptibility to developing cancer. We conducted a prospective study among 150 women (aged 18-70 years), who were distributed into three groups (n = 50): women without breast pathology and women diagnosed with BC or benign breast pathology. Psychological data were obtained through standardized psychological tests and serum protein samples were analyzed through semiquantitative protein immunoblotting. The matching for psychological and immunological profiles was constructed from these data using a mathematical generalized linear model.The model predicted that women who have stronger associations between high-intensity stress responses, emotional containment, and an increased number and reduced variability of serum proteins (detected by IgG autoantibodies) have the greatest susceptibility to develop BC before the disease has manifested clinically. Hence, the present study endorses the possibility of using psychological and biochemical tests in combination to increase the possibility of identifying women at risk of developing BC before the disease shows clinical manifestations. A longitudinal study must be instrumented to test the prediction ability of the instrument in real scenarios. Trial registration: Committee of Ethical Research of the Hospital General de México "Dr. Eduardo Liceaga," Ministry of Health (DI/12/111/03/064).