PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.

Congenital diaphragmatic hernia (CDH) is a relatively common and genetically heterogeneous structural birth defect associated with high mortality and morbidity. We describe eight unrelated families with an X-linked condition characterized by diaphragm defects, variable anterior body-wall anomalies, and/or facial dysmorphism. Using linkage analysis and exome or genome sequencing, we found that missense variants in plastin 3 (PLS3), a gene encoding an actin bundling protein, co-segregate with disease in all families. Loss-of-function variants in PLS3 have been previously associated with X-linked osteoporosis (MIM: 300910), so we used in silico protein modeling and a mouse model to address these seemingly disparate clinical phenotypes. The missense variants in individuals with CDH are located within the actin-binding domains of the protein but are not predicted to affect protein structure, whereas the variants in individuals with osteoporosis are predicted to result in loss of function. A mouse knockin model of a variant identified in one of the CDH-affected families, c.1497G>C (p.Trp499Cys), shows partial perinatal lethality and recapitulates the key findings of the human phenotype, including diaphragm and abdominal-wall defects. Both the mouse model and one adult human male with a CDH-associated PLS3 variant were observed to have increased rather than decreased bone mineral density. Together, these clinical and functional data in humans and mice reveal that specific missense variants affecting the actin-binding domains of PLS3 might have a gain-of-function effect and cause a Mendelian congenital disorder.

Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

A critical review to identify data gaps and improve risk assessment of bisphenol A alternatives for human health.

Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).

Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. METHODS: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). RESULTS: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. CONCLUSIONS: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.

High-depth next-generation sequencing panel testing in the evaluation of arteriovenous malformations.

Arteriovenous malformations (AVMs) are vascular lesions in which an overgrowth of blood vessels of varying sizes develops with one or more direct connections between the arterial and venous circulation. We performed a retrospective review of a cohort of 54 patients with AVMs referred to our clinical genomic laboratory for high-depth next-generation sequencing (NGS) panel of Disorders of Somatic Mosaicism (DoSM). Thirty-seven of 54 patients were female (68.5%). Among the 54 cases, 37 (68.5%) cases had pathogenic and/or likely pathogenic (P/LP) variants identified, two cases (3.7%) had variants of uncertain clinical significance, and the remaining 15 cases (27.8%) had negative results. MAP2K1 variants were found in 12 cases, followed by eight cases with KRAS variants and seven with TEK variants, and the remainder being identified in several other genes on the panel. Among the 37 positive cases, 32 cases had somatic alterations only; the remaining five cases had at least one germline P/LP variant, including four cases with PTEN and one with RASA1. Of note, two cases had the unexpected co-existence of two P/LP variants. In summary, this study illustrated the molecular diagnostic yield (68.5%) of this cohort of patients with a clinical indication of AVMs by our high-depth DoSM NGS panel.

Enigma portal: Undifferentiated thyroid malignant neoplasm in a patient with Hashimoto's thyroiditis.

Undifferentiated anaplastic thyroid tumours are uncommon and constitute a diagnostic challenge on fine needle aspiration. A case showing large, single neoplastic cells in a background of Hashimoto's disease is presented.

The effects of preconception and early gestation SARS-CoV-2 infection on pregnancy outcomes and placental pathology.

OBJECTIVE: To evaluate if peri-pregnancy timing of a PCR+ test for SARS-CoV-2 RNA affects pregnancy outcomes and placental pathology. METHODS: This is a retrospective cohort study conducted in a tertiary center. Pregnancy outcomes and placental pathology were compiled for women who tested positive for SARS-CoV-2 RNA from a nasopharyngeal swab assessed by RT-PCR. The population comprised four groups that were PCR+ preconception (T0) or in the 1st (T1), 2nd (T2), or 3rd (T3) trimester of pregnancy. A fifth, control group (TC) tested PCR- for SARS-CoV-2 before delivery. RESULTS: Seventy-one pregnancies were studied. The T0 group exhibited lower gestational ages at delivery, had infants with the lowest birth weights, the highest rate of pregnancy loss before 20 weeks. Features of maternal vascular malperfusion and accelerated villous maturation were prominent findings in the histopathology of placentas from women PCR+ for SARS-CoV-2 RNA, especially in the T0 and the T1 groups. CONCLUSION: Women at highest risk for pregnancy complications are those who test PCR+ for viral RNA preconception or during first trimester of pregnancy.

Sclerosing angiomatoid nodular transformation, a rare splenic tumor with increasing incidence.

SANT (sclerosing angiomatoid nodular transformation) tumor is a rare splenic tumor of unknown etiology and vascular lineage, first described in 2004. Most cases are asymptomatic, although cases of anemia or abdominal pain in association with growth have been described. Spontaneous ruptures have not been described. Radiologically it presents a radial pattern with centripetal filling in dynamic MRI, being a characteristic feature, but not pathognomonic. It may present hypermetabolism in PET-CT. Its incidence is increasing since its description as an independent clinical and histopathological entity, especially in the oncological patients follow-up. Due to its radiological resemblance to metastatic lesions and its growth despite being a vascular lesion, splenectomy is indicated following the principles of oncologic surgery until a definitive diagnosis is made. It presents a benign behavior, requiring neither treatment nor specific subsequent surveillance. Two diagnosed cases of SANT are presented, as well as a review of the clinical, radiological and histopathological characteristics of this little-known splenic lesion.

Incidence, clinical, risk factors and outcomes of Guillain-Barré in Covid-19.

We diagnosed 11 Guillain-Barré syndrome (GBS) cases among 71,904 COVID patients attended at 61 Spanish emergency departments (EDs) during the 2-month pandemic peak. The relative frequency of GBS among ED patients was higher in COVID (0.15‰) than non-COVID (0.02‰) patients (odds ratio [OR] = 6.30, 95% confidence interval [CI] = 3.18-12.5), as was the standardized incidence (9.44 and 0.69 cases/100,000 inhabitant-years, respectively, OR = 13.5, 95% CI = 9.87-18.4). Regarding clinical characteristics, olfactory-gustatory disorders were more frequent in COVID-GBS than non-COVID-GBS (OR = 27.59, 95% CI = 1.296-587) and COVID-non-GBS (OR = 7.875, 95% CI = 1.587-39.09) patients. Although COVID-GBS patients were more frequently admitted to intensive care, mortality was not increased versus control groups. Our results suggest SARS-CoV-2 could be another viral infection causing GBS. ANN NEUROL 2021;89:598-603.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

Clinical Management of Hypertriglyceridemia in the Prevention of Cardiovascular Disease and Pancreatitis.

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well. RECENT FINDINGS: NHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP). Residual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.

Vertical transmission of a large calvarial ossification defect due to heterozygous variants of ALX4 and TWIST1.

ALX4 is a homeobox gene expressed in the mesenchyme of developing bone and is known to play an important role in the regulation of osteogenesis. Enlarged parietal foramina (EPF) is a phenotype of delayed intramembranous ossification of calvarial bones due to variants of ALX4. The contrasting phenotype of premature ossification of sutures is observed with heterozygous loss-of-function variants of TWIST1, which is an important regulator of osteoblast differentiation. Here, we describe an individual with a large cranium defect, with dominant transmission from the mother, both carrying disease causing heterozygous variants in ALX4 and TWIST1. The distinct phenotype of absent superior and posterior calvarium in the child and his mother was in sharp contrast to the other affected maternal relatives with a recognizable ALX4-related EPF phenotype. This report demonstrates comorbid disorders of Saethre-Chotzen syndrome and EPF in a mother and her child, resulting in severe skull defects reminiscent of calvarial abnormalities observed with bilallelic ALX4 variants. To our knowledge this is the first instance of ALX4 and TWIST1 variants acting synergistically to cause a unique phenotype influencing skull ossification.

[Health accounts from past to present for a political arithmeticContas da saúde do passado ao presente para a aritmética política]. / Cuentas de salud del pasado al presente para una aritmética política.

This report traces the progressive expansion of health accounts (HA) to measure national health expenditures, from the first attempts in 1926 by the American Medical Association to the present day. Milestones in the development of A System of Health Accounts (SHA) are covered, from the economic background to initial efforts by a few countries and organizations, to the need for a set of accounting standards for health care systems, and finally, to consolidation with SHA 2011. International organizations, such as the World Health Organization, Organization for Economic Cooperation and Development, Eurostat, the World Bank, and the United States Agency for International Development have been critical to expanding national HA exercises and ensuring that these are standardized, comparable, and become institutionalized. National efforts to track health expenditures have not only enriched collective results, but have become an important component of global leadership, informing policy the world over. More than 100 countries have created HA under the global standard and have gained a better understanding of health spending and financial flows. These results are key for monitoring progress toward national and global initiatives, such as the Sustainable Development Goals and Universal Health Coverage. Challenges remain to be tackled, among them institutionalization and quality of results. Social responsibility for improving data sources and expanding the generation and usability of health accounts are also needed.

Este informe traça a progressiva expansão das contas da saúde para mensurar os gastos nacionais em saúde, das primeiras tentativas em 1926 pela Associação Americana de Medicina aos dias de hoje. Os marcos do desenvolvimento de um sistema de contas da saúde (SHA) são apresentados: dos antecedentes econômicos, esforços iniciais por parte de alguns países e organizações e necessidade de estabelecer um conjunto de normas contábeis para os sistemas de saúde à consolidação do sistema de contas da saúde (SHA) 2011. As organizações internacionais, como Organização Mundial da Saúde, Organização para a Cooperação e Desenvolvimento Econômico, Eurostat, Banco Mundial e Agência dos Estados Unidos para o Desenvolvimento Internacional, têm sido peças fundamentais para expandir os exercícios de contas nacionais da saúde e assegurar sua padronização, equivalência e institucionalização. Os esforços nacionais para monitorar os gastos em saúde não apenas melhoram os resultados coletivos, mas também são um importante componente de liderança global, servindo de base para políticas no mundo todo. Mais de 100 países criaram contas da saúde segundo o padrão global e têm agora um melhor entendimento do gasto em saúde e fluxos financeiros. Esses resultados são essenciais para monitorar o progresso rumo às iniciativas nacionais e globais, como os Objetivos de Desenvolvimento Sustentável e a cobertura universal de saúde. Existem ainda desafios a serem vencidos, como institucionalização e qualidade dos resultados. Também é preciso responsabilidade social para melhorar as fontes de dados e expandir a geração e a usabilidade das contas da saúde.

Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.

BACKGROUND: Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. OBJECTIVES: To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. PATIENTS AND METHODS: HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (≥20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a ≥ 2% threshold to include low-frequency variants. RESULTS: Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P < 0.001). Clustering individuals were younger [adjusted OR (aOR) per year = 0.96, 95% CI 0.95-0.97, P < 0.001] and less likely to include women (aOR = 0.46, 95% CI 0.28-0.75, P = 0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR = 0.93, 95% CI 0.88-0.98, P = 0.003). CONCLUSIONS: Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.

Wolff-Parkinson-White syndrome: De novo variants and evidence for mutational burden in genes associated with atrial fibrillation.

BACKGROUND: Wolff-Parkinson-White (WPW) syndrome is a relatively common arrhythmia affecting ~1-3/1,000 individuals. Mutations in PRKAG2 have been described in rare patients in association with cardiomyopathy. However, the genetic basis of WPW in individuals with a structurally normal heart remains poorly understood. Sudden death due to atrial fibrillation (AF) can also occur in these individuals. Several studies have indicated that despite ablation of an accessory pathway, the risk of AF remains high in patients compared to general population. METHODS: We applied exome sequencing in 305 subjects, including 65 trios, 80 singletons, and 6 multiple affected families. We used de novo analysis, candidate gene approach, and burden testing to explore the genetic contributions to WPW. RESULTS: A heterozygous deleterious variant in PRKAG2 was identified in one subject, accounting for 0.6% (1/151) of the genetic basis of WPW in this study. Another individual with WPW and left ventricular hypertrophy carried a known pathogenic variant in MYH7. We found rare de novo variants in genes associated with arrhythmia and cardiomyopathy (ANK2, NEBL, PITX2, and PRDM16) in this cohort. There was an increased burden of rare deleterious variants (MAF ≤ 0.005) with CADD score ≥ 25 in genes linked to AF in cases compared to controls (P = .0023). CONCLUSIONS: Our findings show an increased burden of rare deleterious variants in genes linked to AF in WPW syndrome, suggesting that genetic factors that determine the development of accessory pathways may be linked to an increased susceptibility of atrial muscle to AF in a subset of patients.

Effect of bowel preparation volume in inpatient colonoscopy. Results of a prospective, randomized, comparative pilot study.

BACKGROUND: Inpatient status has been shown to be a predictor of poor bowel preparation for colonoscopy; however, the optimal bowel preparation regimen for hospitalized patients is unknown. Our aim was to compare the efficacy of bowel preparation volume size in hospitalized patients undergoing inpatient colonoscopy. METHODS: This prospective, single blinded (endoscopist), randomized controlled trial was conducted as a pilot study at a tertiary referral medical center. Hospitalized patients undergoing inpatient colonoscopy were assigned randomly to receive a high, medium, or low-volume preparation. Data collection included colon preparation quality, based on the Boston Bowel Preparation Scale, and a questionnaire given to all subjects evaluating the ability to completely finish bowel preparation and adverse effects (unpleasant taste, nausea, and vomiting). RESULTS: Twenty-five colonoscopies were performed in 25 subjects. Patients who received low-volume preparation averaged a higher mean total BBPS (7.4, SD 1.62), in comparison to patients who received high-volume (7.0, SD 1.41) and medium-volume prep (6.9, SD 1.55), P = 0.77. When evaluating taste a higher score meant worse taste. The low-volume group scored unpleasant taste as 0.6 (0.74), while the high-volume group gave unpleasant taste a score of 2.2 (0.97) and the medium-volume group gave a score of 2.1 (1.36), P < 0.01. CONCLUSION: In this pilot study we found that low-volume colon preparation may be preferred in the inpatient setting due its better rate of tolerability and comparable bowel cleanliness when compared to larger volume preparation, although we cannot overreach any definitive conclusion. Further more robust studies are required to confirm these findings. TRIAL REGISTRATION: The Affect of Low-Volume Bowel Preparation for Hospitalized Patients Colonoscopies. TRIAL REGISTRATION: NCT01978509 (terminated). Retrospectively registered on November 07, 2013.

Response to multiple rapid swallows shows impaired inhibitory pathways in distal esophageal spasm patients with and without concomitant esophagogastric junction outflow obstruction.

Distal esophageal spasm (DES) is a motility disorder characterized by premature contraction of the esophageal body during single swallows. It is thought to be due to impairment of esophageal inhibitory pathways, but studies to support this are limited. The normal response to multiple rapid swallows (MRS) is deglutitive inhibition of the esophageal body during the MRS sequence. Our aim was to compare the response to MRS in DES patients and healthy control subjects. Response to MRS during HRM was evaluated in 19 DES patients (8 with and 11 without concomitant esophagogastric junction outflow obstruction [EGJOO]) and 24 asymptomatic healthy controls. Patients with prior gastroesophageal surgery, peroral endoscopic myotomy, pneumatic dilation, esophageal botulinum toxin injection within 6 months of HRM, opioid medication use, and esophageal stricture were excluded. Response to MRS was evaluated for complete versus impaired inhibition (esophageal body contractility with distal contractile integral [DCI] > 100 mmHg-sec-cm during MRS), presence of post-MRS contraction augmentation (DCI post MRS greater than single swallow mean DCI), and integrated relaxation pressure (IRP). Impaired deglutitive inhibition during MRS was significantly more frequent in DES compared to controls (89% vs. 0%, P < 0.001), and frequency was similar for DES with versus without concomitant EGJOO (100% vs. 82%, P = 0.48). The proportion of subjects with augmentation post MRS was similar for both groups (37% vs. 38%, P = 1.00), but mean DCI post MRS was higher in DES than controls (3360.0 vs. 1238.9, P = 0.009). IRP was lower during MRS compared to single swallows in all patients, and IRP during MRS was normal in 5 of 8 patients with DES and EGJOO. Our study suggests that impaired deglutitive inhibition during MRS is present in the majority of patients with DES regardless of whether they have concomitant EGJOO, and future studies should explore the usefulness of incorporating response to MRS in the diagnosis of DES.

Syphilis Infection Markers Among HIV Positive Individuals In The Mexico City HIV/AIDS Program.

OBJECTIVE: The aim of this study is to evaluate the prevalence of T. pallidum infection markers in HIV-positive individuals receiving highly active antiretroviral therapy (ART) in the Mexico City HIV/AIDS Program, as well as predictive characteristics. METHODS: The reverse serologic algorithm method was used for the T. pallidum diagnosis, and applied to 2,383 HIV-positive individuals. Socio-demographic characteristics, sexual practices, previous syphilis diagnosis, and length of antiretroviral treatment, were evaluated. Variables significantly associated with syphilis markers were analyzed using a logistic regression model. RESULTS: Prevalence of "active or resolved" and "probable active" infection markers were 44.2% and 28.8%, respectively. Predictive factors were: Clinic Specialized Condesa Iztapalapa (CECI), previous syphilis diagnosis, MSM, and receptive sex practices. CONCLUSIONS: The prevalence of T. pallidum infection markers was the highest ever reported in Mexico, and was related to specific sexual practices as well as previous syphilis diagnosis, elements which require preventive measures in the Mexico City HIV/AIDS Program.

Effect of manual and electrical brushing on the enamel of sound primary teeth and teeth with induced white spot lesions.

PURPOSE: To evaluate the effect of different electrical brushing systems on the surface roughness and wear profile of the enamel of sound primary teeth and teeth with induced white spot lesions. METHODS: 45 specimens were obtained from sound primary incisors, and the buccal surface was divided into four parts: sound enamel; enamel with white spot lesions; sound enamel with brushing; and enamel with white spot lesions and brushing. Specimens were randomly divided into three groups (n =15), according to the different brushing systems: Group 1 - Electric rotating toothbrush (Kid's Power Toothbrush - Oral B); Group 2 - Sonic electric toothbrush (Baby Sonic Toothbrush); and Group 3 - Manual toothbrush (Curaprox infantil) (control). The specimens were analyzed for surface roughness and wear profile. Data were analyzed by appropriate statistical tests, with a significance level of 5%. RESULTS: Regarding the surface roughness, no significant difference was observed between the groups. However, with respect to the wear profile, Group 1 caused significantly higher wear in the sound tooth enamel and in the presence of white spot lesions, in comparison to the other brushing systems (2 and 3) (P< 0.05), which did not cause wear. Manual and electric brushing (rotational and sonic) did not increase surface roughness in primary tooth enamel. However, the electric rotational brushing caused significant wear of the sound and demineralized enamel surface of primary teeth. CLINICAL SIGNIFICANCE: None of the toothbrushing systems tested caused significant alterations on sound dental enamel. However, rotational toothbrushing on enamel of primary teeth with white spot lesion increased wear.

Association between personal, medical and positive psychological variables with somatization in university health sciences students.

OBJECTIVE: To measure personal, medical and psychological positive and negative variables and to determine their relation with somatization in a sample of health sciences students. Subjects and methods: A total of 594 (34.43%) of the 1725 health science students of a public university answered an online survey with personal and medical information as well as the following psychological variables: phsychological well-being, five facets mindfulness questionnaire (FFMQ), life satisfaction, depression, and academic stress. Additionally, the presence of 11 somatic symptoms and 11 diseases during the last year was measured. Results: Most students were women (74.06%) who were 19.96 ± 4.28 years old. The global frequency of somatization in the previous year was 66.59%, and the presence of any measured disease 14.75%. With the multivariate analysis, self-acceptance was the most related variable (negatively) with somatization, followed by the sum of diseases, female gender, academic stress, smoking, and depression, in a model with an R-value of 0.634, self-acceptance was also the most related variable (negatively) with depression, being this last the most related variable with academic stress. Conclusions: After analyzing all variables considered in this study, self-acceptance was the most related variable with somatization and depression; this highlights the importance of strengthening the acceptance of the self in the student population in order to prevent these conditions and their consequences.