Gap junction reduction in cardiomyocytes following transforming growth factor- beta treatment and Trypanosoma cruzi infection

Gap junction connexin-43 (Cx43) molecules are responsible for electrical impulse conduction in the heart and are affected by transforming growth factor-beta (TGF-beta). This cytokine increases during Trypanosoma cruzi infection, modulating fibrosis and the parasite cell cycle. We studied Cx43 expression in cardiomyocytes exposed or not to TGF-beta T. cruzi, or SB-431542, an inhibitor of TGF-beta receptor type I (ALK-5). Cx43 expression was also examined in hearts with dilated cardiopathy from chronic Chagas disease patients, in which TGF-beta signalling had been shown previously to be highly activated. We demonstrated that TGF-beta treatment induced disorganised gap junctions in non-infected cardiomyocytes, leading to a punctate, diffuse and non-uniform Cx43 staining. A similar pattern was detected in T. cruzi-infected cardiomyocytes concomitant with high TGF-beta secretion. Both results were reversed if the cells were incubated with SB-431542. Similar tests were performed using human chronic chagasic patients and we confirmed a down-regulation of Cx43 expression, an altered distribution of plaques in the heart and a significant reduction in the number and length of Cx43 plaques, which correlated negatively with cardiomegaly. We conclude that elevated TGF-beta levels during T. cruzi infection promote heart fibrosis and disorganise gap junctions, possibly contributing to abnormal impulse conduction and arrhythmia that characterise severe cardiopathy in Chagas disease

Escabiosis en paciente masculino de 10 años con desnutrición crónica infantil de la amazonia ecuatoriana. Reporte de caso y revisión

Scabies or scabies is an ectoparasitic infection produced by the mite Sarcoptes scabiei var hominis (class Arachnida, subclass Acarina, order Astigmata, family Sarcoptidae). It has a worldwide distribution, with an estimated global prevalence of 300 million cases. It is a disease for which there is universal susceptibility, without significant differences in terms of sex, age, ethnic group or socioeconomic level, although there are predisposing circumstances for its contagion, such as overcrowding, immigration, poor hygiene, malnutrition, dementia and sexual promiscuity.Objective: Early identification of the evolution of scabies for its respective diagnosis and treatment.Description of the case: This case is presented, and a literary review is carried out in order to identify the diagnosis of scabies in a patient with chronic malnutrition.Low-income patient is captured by medical personnel where itching of several weeks of evolution is evidenced where there is evidence of an itchy rash in the abdominal region, in addition to this he presents chronic malnutrition. He is admitted to the dermatology service with nutritional support where he receives treatment for several days which are favorable with an adequate evolution.Conclusions: Scabies in our country Ecuador is endemic, it is a common disease in our Amazon region where most of the people who suffer from it are overcrowded people with low resources who have chronic malnutrition, it is important as doctors to carry out health checks on people vulnerable in rural areasLa escabiosis o sarna es una infección ectoparasitaria producida por el acaro Sarcoptes scabiei var hominis (clase Arachnida, subclase Acarina, orden Astigmata, familia Sarcoptidae). Tiene una distribución mundial, con una prevalencia global estimada de 300 millones de casos. Es una enfermedad para la que hay susceptibilidad universal, sin diferencias significativas en cuanto a sexo, edad, grupo étnico o nivel socioeconómico, aunque existen circunstancias predisponentes para su contagio, como el hacinamiento, la inmigración, la higiene deficiente, la malnutrición, la demencia y la promiscuidad sexual.Objetivo: Identificar de manera temprana la evolución de la escabiosis para su respectivo diagnóstico y tratamiento.Descripción del caso: Se presenta este caso y se realiza un revisión literaria para poder identificar el diagnostico de escabiosis en paciente con desnutrición crónica.Paciente de bajos recursos económicos es captado por personal médico donde se evidencia prurito de varias semanas de evolución donde se evidencia exantema en región abdominal pruriginoso además de ello presenta desnutrición crónica. Es ingresado al servicio de dermatología con apoyo de nutrición donde recibe tratamiento por varios días los cuales son favorables con una evolución adecuada.Conclusiones: La escabiosis en nuestro país Ecuador es endémica, es una enfermedad común en nuestra región amazónica donde la mayoría de las personas que la padecen son personas en hacinamiento con bajos recursos que presentan desnutrición crónica, es importante como médicos realizar controles sanitarios a las personas vulnerables de las zonas rurales

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Background: Intraoperative recognition of the local anatomy of the posterior cruciate ligament (PCL) is difficult for many surgeons, and correct positioning of the graft can be challenging

Can We Use SE-specific Sentiment Analysis Tools in a Cross-Platform Setting?

In this paper, we address the problem of using sentiment analysis tools 'off-the-shelf,' that is when a gold standard is not available for retraining. We evaluate the performance of four SE-specific tools in a cross-platform setting, i.e., on a test set collected from data sources different from the one used for training. We find that (i) the lexicon-based tools outperform the supervised approaches retrained in a cross-platform setting and (ii) retraining can be beneficial in within-platform settings in the presence of robust gold standard datasets, even using a minimal training set. Based on our empirical findings, we derive guidelines for reliable use of sentiment analysis tools in software engineering.Comment: 12 page

Characterization of the oral fungal microbiota in smokers and non-smokers

This study aimed to assess the effect of smoking on the biodiversity of the oral fungal microbiota of healthy young subjects, using an improved culture method that assesses both total and pathogenic viable fungi. Forty individuals (20 smokers and 20 non‐smokers) were selected. All individuals presented fungal growth (100% for molds and 92.5% for yeasts), a prevalence higher than previously reported. The most commonly occurring molds were Penicillium sp., Aspergillus sp., and Cladosporium sp. Smokers presented significantly higher levels of yeasts and pathogenic molds than did non‐smokers. No differences in fungal prevalence and diversity were observed in smokers and non‐smokers following a 30‐wk observation period. In conclusion, tobacco smoking may alter the oral mycobiota and facilitate colonization of the oral cavity with yeasts and pathogenic molds. The effect of chronic fungal colonization on the oral health of tobacco smokers cannot be neglected

A Comparison of Botulinum Toxin A and Intralesional Steroids for the Treatment of Plantar Fasciitis: A Randomized, Double- Blinded Study

Plantar fasciitis is the most frequent cause of chronic heel pain. This pathology generally presents in patients who are 40 years of age or older, overweight, sedentary, or engage in intense physical activity. 14,32 Because of its anatomic orientation and its tensile strength, the plantar fascia functions to prevent foot collapse. It is a piece of thick connective tissue that originates at the base of the calcaneus and extends distally to the phalanges. Stretching of the plantar fascia prevents the displacement of the calcaneus and the metatarsals and helps to maintain the medial longitudinal arch. The plantar fascia simulates a cable between the calcaneus and the metatarsophalangeal joints. The windlass mechanism described by Hicks 13 for the action of the plantar fascia explains that during dorsiflexion of the toes, the length of the plantar fascia is effectively shortened, causing an elevation of the arch. Extension of the toes increases the arc of tension with the metatarsophalangeal joints, similar to an axis or anchor point. Shortening of the plantar fascia that results from dorsiflexion of the hallux is the essence of the reel mechanism. When a complete fasciotomy is performed, this mechanism is lost, decreasing the stability of the arch and interfering with stability during the terminal stance phase. Methods: The patients were randomly divided into 2 groups according to the treatment received. The patients were evaluated over 6 months. The evaluation scores included the Visual Analog Scale (VAS), Maryland Foot and Ankle, Foot and Ankle Disability Index (FADI), and American Orthopaedic Foot and Ankle Society (AOFAS) score. Moreover, patients were instructed to perform plantar fascia stretching exercises over the course of the study. The final number of patients was 36, of whom 19 received BTX-A (10 men and 9 women) and 17 (6 men and 11 women) received steroids. Results: When compared to patients who received steroids, the patients who received BTX-A exhibited more rapid and sustained improvement over the duration of the study. Conclusion: A combination of BTX-A and plantar fascia stretching exercises yielded better results for the treatment of plantar fasciitis than intralesional steroids. Level of Evidence: Level I, therapeutic studies

Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.

Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children

Central and peripheral GLP-1 systems independently suppress eating

The anorexigenic peptide glucagon-like peptide-1 (GLP-1) is secreted from gut enteroendocrine cells and brain preproglucagon (PPG) neurons, which, respectively, define the peripheral and central GLP-1 systems. PPG neurons in the nucleus tractus solitarii (NTS) are widely assumed to link the peripheral and central GLP-1 systems in a unified gut–brain satiation circuit. However, direct evidence for this hypothesis is lacking, and the necessary circuitry remains to be demonstrated. Here we show that PPGNTS neurons encode satiation in mice, consistent with vagal signalling of gastrointestinal distension. However, PPGNTS neurons predominantly receive vagal input from oxytocin-receptor-expressing vagal neurons, rather than those expressing GLP-1 receptors. PPGNTS neurons are not necessary for eating suppression by GLP-1 receptor agonists, and concurrent PPGNTS neuron activation suppresses eating more potently than semaglutide alone. We conclude that central and peripheral GLP-1 systems suppress eating via independent gut–brain circuits, providing a rationale for pharmacological activation of PPGNTS neurons in combination with GLP-1 receptor agonists as an obesity treatment strategy

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin