High-throughput mRNA sequencing of human placenta shows sex differences across gestation.

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.

Serological Responses to Trachoma Antigens prior to the Start of Mass Drug Administration: Results from Population-Based Baseline Surveys, North Darfur, Sudan.

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.

Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia.

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.

High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester.

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 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 (TPM > 0.66), with 10.7% 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 remain 50.1% differentially expressed genes (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 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 for maternal-fetal health.

Efficacy and safety of raltegravir plus lamivudine maintenance therapy.

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.

A systematic review of genome-wide analyses of methylation changes associated with assisted reproductive technologies in various tissues.

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.

Autoantibody Diversity Is Augmented in Women with Breast Cancer and Is Related to the Stage of the Disease.

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.

Mortalidad de pacientes internados por pie diabético en un hospital de Costa Rica (2017-2019) / Mortality of inpatients due to diabetic foot in a hospital in Costa Rica (2017-2019)

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.

Stress symptoms and positive coping during coronavirus disease 2019: The need to look at health from a gender perspective.

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.

High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester.

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.

Role of voltage-gated proton channel (Hv1) in cancer biology.

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.

Adherencia a las medidas higiénico dietéticas de adultos con diabetes mellitus de Asunción en 2022

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.

Infertility and treatments used have minimal effects on first-trimester placental DNA methylation and gene expression.

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.

Immunological and virological findings in a patient with exceptional post-treatment control: a case report.

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.

Psychological suppressive profile and autoantibodies variability in women living with breast cancer: A prospective cross-sectional study.

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).

Your health is in your mouth: A comprehensive view to promote general wellness.

Background: Even though various studies recognize the importance of the oral cavity to have general health, in multidisciplinary professional practice it is almost always excluded and on an individual basis, very commonly neglected. Oral diseases are preventable, still, they are highly prevalent. Although some studies consider oral health within integral health, currently, there is no model in which the mouth is integrated within other levels for the achievement of well-being. The objective of this article was to review the importance of oral health and its connection with well-being and, based on these findings, propose a complex and comprehensive perspective for approach and care. Methods: The databases MEDLINE, PubMed, and Google Scholar were revised for randomized controlled trials and reviews that included search terms related to oral health and its relationship with the general health in its different levels (physical, psychological, social and environmental). Results: The review shows that oral health is critical, as the teeth and mouth are not only an integral part of the body, but also, they also support and enable essential human functions. That is, oral health has a multidimensional nature, as it includes the physical, psychological, social, and environmental domains that are essential for overall health and well-being. Likewise, the mouth is the psychological seat of the first physiological needs and emotional gratifications, with it we take a taste of the world around us. Thus, the mouth plays an important role in the feeling of unity and in the constitution of the self. Based on these results we propose an integrative model in which the mouth is the first step for well-being and from this integrative model we build a multidisciplinary approach which could be used in the clinical practice for the promotion of oral care and general health. Conclusion: The effort on the part of oral health professionals is essential for people's well-being and must be integrated as part of health promotion. Dental treatments alone cannot solve this problem, it requires a comprehensive and approach in which the bio-psychological, behavioral, and socio-environmental determinants are included to face this global oral health challenge. That is, without a comprehensive and multidisciplinary approach to medical science that includes dental and oral health, our public policies cannot provide the best answers to health promotion, disease prevention, early detection, and treatment.

Sex at the interface: the origin and impact of sex differences in the developing human placenta.

The fetal placenta is a source of hormones and immune factors that play a vital role in maintaining pregnancy and facilitating fetal growth. Cells in this extraembryonic compartment match the chromosomal sex of the embryo itself. Sex differences have been observed in common gestational pathologies, highlighting the importance of maternal immune tolerance to the fetal compartment. Over the past decade, several studies examining placentas from term pregnancies have revealed widespread sex differences in hormone signaling, immune signaling, and metabolic functions. Given the rapid and dynamic development of the human placenta, sex differences that exist at term (37-42 weeks gestation) are unlikely to align precisely with those present at earlier stages when the fetal-maternal interface is being formed and the foundations of a healthy or diseased pregnancy are established. While fetal sex as a variable is often left unreported in studies performing transcriptomic profiling of the first-trimester human placenta, four recent studies have specifically examined fetal sex in early human placental development. In this review, we discuss the findings from these publications and consider the evidence for the genetic, hormonal, and immune mechanisms that are theorized to account for sex differences in early human placenta. We also highlight the cellular and molecular processes that are most likely to be impacted by fetal sex and the evolutionary pressures that may have given rise to these differences. With growing recognition of the fetal origins of health and disease, it is important to shed light on sex differences in early prenatal development, as these observations may unlock insight into the foundations of sex-biased pathologies that emerge later in life.

Highly Efficient Autologous HIV-1 Isolation by Coculturing Macrophage With Enriched CD4+ T Cells From HIV-1 Patients.

We described a novel HIV autologous isolation method based in coculturing macrophages and CD4+T-cell-enriched fractions from peripheral blood collected from antiretroviral-treated (ART) HIV patients. This method allows the isolation of high viral titers of autologous viruses, over 1010HIV RNA copies/ml, and reduces the time required to produce necessary amounts for virus for use as antigens presented by monocyte-derived myeloid cells in HIV therapeutic vaccine approaches. By applying these high titer and autologous virus produced in the patient-derived cells, we intended to elicit a boost of the immunological system response in HIV therapeutic vaccines in clinical trials.

Assessment of executive functions and physical activity in girls and boys with normal weight, overweight and obesity.

OBJECTIVE: To evaluate the association between body mass index (BMI) and performance of executive functions (EFs) in girls and boys with 9- and 10-year-old schoolchildren with moderate- to vigorous-intensity physical activity (MVPA) and sedentary behaviour. METHODS: A total of 120 schoolchildren (61 girls and 59 boys) were evaluated anthropometrically. The MVPA was evaluated with a self-report questionnaire. EFs were measured using a neuropsychological battery of Executive Functions and Frontal Lobes-2 (BANFE-2). RESULTS: A high BMI was associated with longer delay in completing inhibitory control tests (p = 0.00, rp  = 0.32) and working memory (p = 0.00, rp  = 0.26). We observed correlations in time (p = 0.00, rp  = -0.43) and hits (p = 0.04, rp  = -0.27) of self-directed signalling test in boys; and girls in alphabetical words order (p = 0.00, rp  = -0.39). Active normal weight schoolchildren (ANw) performed better by successfully completed the working memory tasks (H = 26.97, p = 0.00) than sedentary schoolchildren with overweight and obesity. In addition, overweight-active schoolchildren (AOw) showed better performance on working memory tests in time (p = 0.00) and hits (p = 0.01) than their sedentary peers. Multiple linear regression analysis revealed a significant association between BMI and EFs scores (F = 2.41, df = 98, p = 0.001). CONCLUSIONS: EFs are affected by a high BMI and sedentary behaviour in school children. Boys and girls reflected differences to solve the same challenges. The MVPA has a positive effect on executive control skills mainly in overweight children.