Smc3 dosage regulates B cell transit through germinal centers and restricts their malignant transformation.

During the germinal center (GC) reaction, B cells undergo extensive redistribution of cohesin complex and three-dimensional reorganization of their genomes. Yet, the significance of cohesin and architectural programming in the humoral immune response is unknown. Herein we report that homozygous deletion of Smc3, encoding the cohesin ATPase subunit, abrogated GC formation, while, in marked contrast, Smc3 haploinsufficiency resulted in GC hyperplasia, skewing of GC polarity and impaired plasma cell (PC) differentiation. Genome-wide chromosomal conformation and transcriptional profiling revealed defects in GC B cell terminal differentiation programs controlled by the lymphoma epigenetic tumor suppressors Tet2 and Kmt2d and failure of Smc3-haploinsufficient GC B cells to switch from B cell- to PC-defining transcription factors. Smc3 haploinsufficiency preferentially impaired the connectivity of enhancer elements controlling various lymphoma tumor suppressor genes, and, accordingly, Smc3 haploinsufficiency accelerated lymphomagenesis in mice with constitutive Bcl6 expression. Collectively, our data indicate a dose-dependent function for cohesin in humoral immunity to facilitate the B cell to PC phenotypic switch while restricting malignant transformation.

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.

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.

A One Health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of Spain, 2003 to 2022.

IntroductionMycobacterium caprae is a member of the Mycobacterium tuberculosis complex (MTBC) not routinely identified to species level. It lacks specific clinical features of presentation and may therefore not be identified as the causative agent of tuberculosis. Use of whole genome sequencing (WGS) in the investigation of a family microepidemic of tuberculosis in Almería, Spain, unexpectedly identified the involvement of M. caprae.AimWe aimed to evaluate the presence of additional unidentified M. caprae cases and to determine the magnitude of this occurrence.MethodsFirst-line characterisation of the MTBC isolates was done by MIRU-VNTR, followed by WGS. Human and animal M. caprae isolates were integrated in the analysis.ResultsA comprehensive One Health strategy allowed us to (i) detect other 11 M. caprae infections in humans in a period of 18 years, (ii) systematically analyse M. caprae infections on an epidemiologically related goat farm and (iii) geographically expand the study by including 16 M. caprae isolates from other provinces. Integrative genomic analysis of 41 human and animal M. caprae isolates showed a high diversity of strains. The animal isolates' diversity was compatible with long-term infection, and close genomic relationships existed between isolates from goats on the farm and recent cases of M. caprae infection in humans.DiscussionZoonotic circulation of M. caprae strains had gone unnoticed for 18 years. Systematic characterisation of MTBC at species level and/or extended investigation of the possible sources of exposure in all tuberculosis cases would minimise the risk of overlooking similar zoonotic events.

The Impact of Periventricular Leukoaraiosis in Post-stroke Oropharyngeal Dysphagia: A Swallowing Biomechanics and MRI-Based Study.

Oropharyngeal dysphagia is a highly prevalent post-stroke complication commonly associated with topographically specific gray-matter damage. In contrast, the role of damage to the extensive white matter brain network (leukoaraiosis) in post-stroke oropharyngeal dysphagia has not yet been clarified. We aim to assess the role of leukoaraiosis in post-stroke oropharyngeal dysphagia. We designed a cross-sectional study and retrospectively collected from our database patients with dysphagia affected by a recent stroke and on whom both a brain 1.5 T-MRI and a videofluoroscopy had been performed. Leukoaraiosis was assessed in brainstem and in cerebral regions (periventricular or deep) with Fazekas scale. Penetration-Aspiration-Scale and time to laryngeal vestibule closure and to upper esophageal sphincter opening were analyzed. Study population (n = 121; 57% men, 75.5 ± 9.4y) presented mostly supratentorial ischemic PACI-type strokes. Of the patients, 86% had unsafe swallows (PAS = 3.97 ± 2.04); 94.2% had cerebral leukoaraiosis (Fazekas = 3.36 ± 1.7) and 42.1% had brainstem-leukoaraiosis, hypertension being the main risk factor. We found both significant positive associations between degree of periventricular-leukoaraiosis and total-leukoaraiosis and presence of risk of aspirations (p = 0.016 and p = 0.023, respectively); and a correlation between periventricular-leukoaraiosis and PAS scale severity (r = 0.179, p = 0.049). No correlations/associations were found between stroke volume and dysphagia in this study. Our study supports a role for leukoaraiosis in the pathophysiology of dysphagia. Stroke is associated with chronic short-connection/circuit injury and damage to periventricular white matter long connections is a relevant neuro-pathophysiological mechanism contributing to impaired safety of swallow in post-stroke oropharyngeal dysphagia patients.

Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values.

BACKGROUND: active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. OBJECTIVES: to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. METHODS: a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. RESULTS: ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). CONCLUSIONS: esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.

Mutations in the COL18A1 gen associated with knobloch syndrome and structural brain anomalies: a novel case report and literature review of neuroimaging findings.

. COL18A1 gene mutations have been associated with Knobloch syndrome, which is characterized by ocular and brain abnormalities. Here we report a 4.5 years-old male child with autism and two novel COL18A1 mutations (NM_030582.4: c.1883_1891dup and c.1787C>T). Hypermetropic astigmatism, but not brain migration disorders, was observed. However, an asymmetric pattern of cerebellar perfusion and a smaller arcuate fascicle were found.  Low levels of collagen XVIII were also observed in the patient´s serum. Thus, biallelic loss-of-function mutations in COL18A1 may be a new cause of autism  without the brain malformations typically reported in patients with Knobloch syndrome.

Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola.

BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). RESULTS: In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations-L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance-D435Y plus L452P and L430P plus S493L-. CONCLUSION: Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains.

Self-rated health among people living with HIV in Spain in 2019: a cross-sectional study.

BACKGROUND: HIV infection has become a chronic disease and well-being of people living with HIV (PLHIV) is now of particular concern. The objectives of this paper were to describe self-rated health among PLHIV, on ART and on ART virally suppressed and to analyse its determinants. METHODS: Data were obtained from a second-generation surveillance system based on a cross-sectional one-day survey in public hospitals. Epidemiological and clinical data were collected among HIV-infected inpatients and outpatients receiving HIV-related care the day of the survey in 86 hospitals in 2019. Self-rated health was measured using a question included in the National Health Survey: "In the last 12 months, how would you rate your health status?" an ordinal variable with five categories (very good, good, moderate, bad and very bad). For the analysis, these responses were dichotomized into two categories: 1 = very good/good and 0 = moderate, bad or very bad health status. Factors associated with very good/good self-rated health were estimated using logistic regression. RESULTS: Of 800 PLHIV, 67.5% perceived their health as very good/good, 68.4% among PLHIV on ART and 71.7% of those virally suppressed. Having university education (adjusted odds ratio (aOR):2.1), being unemployed (aOR:0.3) or retired (aOR:0.2), ever being diagnosed of AIDS (aOR:0.6), comorbidities (aOR:0.3), less than 2 year since HIV diagnosis (aOR:0.3) and not receiving ART (aOR:0.3) were associated with good self-rated health. Moreover, among PLHIV on ART, viral load less than 200 copies (aOR:3.2) were related to better perceived health. Bad adherence was inversely associated with good self-rated health among PLHIV on ART (aOR:0.5) and of those virally suppressed (aOR:0.4). CONCLUSIONS: Nearly seven in 10 PLHIV in Spain considered their health status as very good/good, being higher among virally suppressed PLHIV. Both demographic and clinical determinants affect quality of life.

Development and Evaluation of a Telematics Platform for Monitoring of Patients in Ambulatory Major Surgery.

BACKGROUND: Ambulatory surgical procedures (ambulatory major surgery [AMS]), to which many people turn, do not require hospital admission. Patients may continue with their recovery from home on the same day they had surgery. OBJECTIVE: The main purpose of this article is to provide a technological solution that may enable nurses to control the evolution of a large number of patients in real time. METHODS: Java and Microsoft Band 2 SDK were used to program the mobile application (app), in contrast, Java, Hibernate, JSP, and Struts2 were used for the web app. The World Health Organization Quality Of Life (WHOQOL) and the System Usability Scale (SUS) questionnaires were applied for assessment purposes. IBM SPSS Statistics Data Editor was used for statistical analysis. Each test lasted 2 weeks, and the test itself involved completing the questionnaire about the patient's health using the mobile app. The average age of the individuals who took part in the study was 42.30 years, with a standard deviation of 17.63 years. RESULTS: The tests involved in this system were conducted at the Ambulatory Major Surgery Unit in the Basurto Hospital, Basque Country, Spain on 20 participants with an average of 42.30 years and a standard deviation of 17.63 years. The application obtained a good score on the SUS ( \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$\overline{X}$$ \end{document} = 89.87 of 100, σ = 9.14). Using the WHOQOL questionnaire, the results were found better in the case of the patients' group than in the control group. CONCLUSION: Using a developed multiplatform mobile app, patients noted an improvement in the care provided in the case of day surgery. The web platform accessed by nurses to make consultations has been integrated into the app service provider, while the bracelet sends the data to the app which receives it and then sends it on to the database. Healthcare staff then check patients' condition.

Oral Application of Recombinant Bacillus subtilis Spores to Dogs Results in a Humoral Response against Specific Echinococcus granulosus Paramyosin and Tropomyosin Antigens.

Bacillus subtilis is known as an endospore- and biofilm-forming bacterium with probiotic properties. We have recently developed a method for displaying heterologous proteins on the surface of B. subtilis biofilms by introducing the coding sequences of the protein of interest into the bacterial genome to generate a fusion protein linked to the C terminus of the biofilm matrix protein TasA. Although B. subtilis is a regular component of the gut microflora, we constructed a series of recombinant B. subtilis strains that were tested for their ability to be used to immunize dogs following oral application of the spores. Specifically, we tested recombinant spores of B. subtilis carrying either the fluorescent protein mCherry or else selected antigenic peptides (tropomyosin and paramyosin) from Echinococcus granulosus, a zoonotic intestinal tapeworm of dogs and other carnivores. The application of the recombinant B. subtilis spores led to the colonization of the gut with recombinant B. subtilis but did not cause any adverse effect on the health of the animals. As measured by enzyme-linked immunosorbent assay and immunoblotting, the dogs were able to develop a humoral immune response against mCherry as well as against E. granulosus antigenic peptides. Interestingly, the sera of dogs obtained after immunization with recombinant spores of E. granulosus peptides were able to recognize E. granulosus protoscoleces, which represent the infective form of the head of the tapeworms. These results represent an essential step toward the establishment of B. subtilis as an enteric vaccine agent.

Extravasation accidents with liposomal/liposomal pegylated anthracyclines treated with dexrazoxane: an overview and outcomes.

The extravasation of chemotherapeutic agents is a challenge for oncologic care teams. The management of nonliposomal (conventional) anthracyclines is well established in clinical practice guidelines, including general measures and specific antidotes, such as dexrazoxane. However, there is little scientific evidence on the management of liposomal and pegylated liposomal anthracyclines. The aim of this paper was to review the scientific literature on the extravasation of liposomal and pegylated liposomal anthracyclines and determine the clinical impact of this type of extravasation, focusing on dexrazoxane. The literature was searched using two databases: PubMed and Embase. Three searches were conducted, using liposomal anthracycline extravasation, pegylated liposomal anthracycline extravasation, and liposomal doxorubicin extravasation as keywords, respectively. Seven articles fulfilled the study eligibility criteria and included seventeen cases in humans. Extravasation occurred with three drugs: liposomal doxorubicin in nine (53%) patients, liposomal daunorubicin in four (23.5%) patients, and pegylated liposomal doxorubicin in four (23.5%) patients. General measures for extravasations were applied in all patients, but only three patients received dexrazoxane. All cases were completely resolved at 2-3 months, except for one patient, in whom dexrazoxane was not used. In animals, dexrazoxane decreased both the frequency of wounds produced by pegylated liposomal doxorubicin and their extent. The pharmacokinetic profiles of liposomal and pegylated liposomal anthracyclines differ from those of conventional anthracyclines, modifying their effectiveness and safety. General measures may be inadequate to heal areas affected by extravasation, which may require the administration of dexrazoxane. However, each case should be evaluated individually for the administration of dexrazoxane in off-label use until scientific evidence is available on its effectiveness and safety as an antidote for these formulations of anthracyclines.

Chronic hepatitis B genotype E in African migrants: response to nucleos(t)ide treatment in real clinical practice.

BACKGROUND: Hepatitis B virus (HBV) genotype E is a poorly studied genotype that almost exclusively occurs in African people. It seems to harbour intrinsic potential oncogenic activity and virological characteristics of immune scape but a paucity of information is available on clinical and virological characteristic of HBV genotype E-infected patients as well as on the efficacy of anti-HBV drugs for such patients. The increasing flow of migrants from high endemic HBV sub-Saharan Africa, where genotype E is the predominant one, to Western countries makes improving such knowledge critical in order to deliver proper medical care. METHODS: Prospective observational study of naïve patients of sub-Saharan origin treated for chronic HBV genotype E infection at a Tropical Medicine clinic sited in Spain from February 2004 to January 2018. The aim of the study was to describe the response of chronic HBV genotype E infection to nucleos(t)ide analogues (NA), entecavir or tenofovir, in real clinical practice. RESULTS: During the study period, 2209 sub-Saharan patients were assisted at our Tropical Medicine Unit and 609 (27.6%) had chronic HBV (CHB) infection. Genotype information was available for 55 naïve patients initiating treatment with NA (entecavir or tenofovir), 43 (84.3%) of them being genotype E, although 15 were excluded because they did not meet study inclusion criteria. Thus, a total of 28 CHB genotype E patients were included and followed for 24 months at least. Twenty-one patients were in HBeAg-negative chronic hepatitis phase and 7 patients in HBeAg-positive chronic hepatitis phase. After one year of treatment, among those with good adherence, 89.4% (17/19) of the HBeAg-negative patients and 80% of the HBeAg-positive ones had undetectable viral loads. Response rates reached 100% in both groups after 15-18 months of follow-up. Out of the 7 HBeAg-positive patients, 6 (85.7%) presented HBeAg loss in a median time of 31.8 months. Neither serious adverse effects nor hepatocarcinoma cases happened during the study period. CONCLUSIONS: HBV genotype may influence disease progression and antiviral response. Our study provides precious information on the efficacy and safety of NA treatment for CHB genotype E infection, a fairly unknown genotype with and increasing epidemiological impact.

Cord Blood Biomarkers of Cardiac Dysfunction and Damage in Term Growth-Restricted Fetuses Classified by Severity Criteria.

OBJECTIVE: To assess cardiovascular function and damage in term small-for-gestational-age (SGA) and intrauterine growth-restricted (IUGR) fetuses by echocardiography and biomarkers in cord blood. METHODS: This was a cohort study including 60 normal fetuses and 47 term small fetuses subclassified as small for gestational age (SGA) with estimated fetal weight (EFW) between the 3rd and 9th centiles and normal fetoplacental Doppler (n = 14) or intrauterine growth restriction (IUGR, n = 33) if EFW <3rd centile or EFW <10th centile together with cerebroplacental ratio <5th and/or mean uterine artery pulsatility index >95th centile. Fetal echocardiography included left myocardial performance index (MPI) and annular plane systolic excursion. Fetal B-type natriuretic peptide (BNP), troponin-I, heart-type fatty acid-binding proteins (H-FABP), and homocysteine concentrations were measured in cord blood collected at delivery. RESULTS: Both SGA and IUGR cases presented echocardiographic signs of systolic and diastolic dysfunction with increased MPI (mean controls 0.43 [SD 0.12], SGA 0.47 [0.03], and IUGR 0.57 [0.08], p < 0.01) and decreased mitral annular plane systolic excursion (controls 6.0 mm [1.0], SGA 5.5 mm [0.6], and IUGR 4.9 mm [0.8], p = 0 01). IUGR fetuses presented increased levels of cord blood BNP (controls 17.2 pg/mL [11.5], SGA 22.4 pg/mL [10.7], and IUGR 31.2 pg/mL [26.8], p < 0.01). Troponin I was increased in both SGA and IUGR cases (controls 0.004 ng/mL [0.007], SGA 0.012 ng/mL [0.02], and IUGR 0.018 ng/mL [0.05], p < 0.01). H-FABP and homocysteine showed similar values among groups. CONCLUSIONS: Cardiac dysfunction and cell damage is a common feature of term SGA and IUGR fetuses despite of the severity criteria for perinatal outcome. Further research is needed to evaluate the potential long-term consequences on their cardiovascular system.

Practical aspects of high resolution esophageal manometry.

High resolution esophageal manometry (HRM) is currently under development as can be seen in the various Chicago classifications. In order to standardize criteria in certain practical aspects with limited scientific evidence, the First National Meeting for Consensus in High Resolution Manometry of the Spanish Digestive Motility Group took place, bringing together a wide group of experts. The proposals were based on a prior survey composed of 47 questions, an exhaustive review of the available literature and the experience of the participants. Methodological aspects relating to the poorly defined analysis criteria of certain new high resolution parameters were discussed, as well as other issues previously overlooked such as spontaneous activity or secondary waves. Final conclusions were drawn with practical applications.

Successful intestinal Echinococcus multilocularis oncosphere invasion and subsequent hepatic metacestode establishment in resistant RccHan™:WIST rats after pharmacological immunosuppression.

Susceptibility/resistance to larval Echinococcus multilocularis infection varies greatly depending on host species and strains. Whereas several mice strains and non-human primates are highly susceptible to alveolar echinococcosis, rats and most of humans are considered as more resistant. In this study, we aimed to elucidate factors responsible for host resistance in rats (Experiments A-D). (A) The parasite establishment was not observed in immunocompetent Wistar rats orally inoculated with sodium hypochlorite resistant eggs with/without pig bile, or activated/non-activated oncospheres (NAO). Peritoneal inoculation with NAO or metacestode tissue allowed the parasite establishment in rats. (B) T-cell-deficient athymic nude rats showed complete resistance against the metacestode establishment after oral inoculation with parasite eggs. This finding suggests that T-cell-independent parasite clearance occurred in the animals during early phase of the parasite invasion. Finally, Wistar rats that received pharmacological immunosuppression using either dexamethasone (DMS) alone or methotrexate (MTX) i.p. alone or a combination of these compounds were orally inoculated with the parasite's eggs. As a result (D), successful establishment of metacestode with protoscoleces was observed in all 3 rats treated with DMS (s.c.) alone or in all 6 rats treated with DMS (s.c.) plus MTX but not in 8 rats with MTX alone, suggesting that factors affected by DMS treatment are responsible to regulate the parasite invasion and establishment.

In vivo viability of Echinococcus multilocularis eggs in a rodent model after different thermo-treatments.

Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a serious and emerging zoonotic disease in many parts of the northern hemisphere. Humans but also primates and other accidental hosts can acquire the infection by the ingestion of eggs excreted by the carnivore definitive hosts, e.g. after hand contact with egg-contaminated environments or by consumption of contaminated food or beverages. The goal of this study was to develop a sensitive in vivo method to determine the viability of E. multilocularis eggs and to establish suitable conditions (optimal temperature, exposure time and humidity) for their (prophylactic) inactivation. The sensitivity of a rodent model was evaluated and, conclusively, C57Bl/6 mice were most susceptible to subcutaneous inoculation of small numbers of sodium hypochlorite-resistant oncospheres, even more than to oral inoculation of mature eggs. In the second part of the study, various combinations of exposure temperature (between 45 °C and 80 °C), times (between 30 min and 180 min) and relative humidity (70% vs. suspended in water) were tested. After heat treatment in an incubator, the sodium hypochlorite resistance test was used to assess in vitro egg viability at the time of inoculation. Subsequently, the infectivity of the oncospheres was evaluated by subcutaneous inoculation in mice. Eggs exposed to increasing temperatures were more resistant to heat if suspended in water as compared to eggs exposed on a filter paper at 70% relative humidity. As survival of eggs in water droplets on the vegetables cannot be excluded, further experiments were performed with eggs suspended in water only. Eggs were infectious after heat exposure at 65 °C for up to 120 min, however, no echinococcosis developed after treatment of the eggs at 65 °C for 180 min or at 70, 75 and 80 °C for 7.5, 15 or 30 min.

Reducing Health Risk Factors in Workplaces of Low and Middle-Income Countries.

OBJECTIVE: To reduce risk factors in workplace settings in low- and middle-income countries. DESIGN AND SAMPLE: Workplace interventions were utilized as part of the Community Interventions for Health program, a nonrandomized, controlled study undertaken in three communities in China, India, and Mexico. Exactly, 45 industrial, 82 health and 101 school workplace settings with a target population of 15,726. Two independent cross-sectional surveys of workers were conducted at baseline and follow-up, after 18-24 months of intervention activities. MEASURES: Culturally appropriate interventions to reduce tobacco use, increase physical activity, and improve dietary intake were delivered in the intervention areas. RESULTS: Exactly, 12,136 adults completed surveys at baseline, and 9,786 at follow-up. In the intervention group, the prevalence of tobacco use reduced significantly in men (-6.0%, p < .001) and the proportion eating five portions of fruit and vegetables daily increased (+6.9%, p < .001) compared with the control group. There were no significant differences between the groups for changes in physical activity or prevalence of overweight. CONCLUSIONS: Workplace interventions improved risk factors in China, India, and Mexico.

Hypercontractile esophagus: Clinical context and motors findings in high resolution manometry.

BACKGROUND: Hypercontractile esophagus (HE) is a primary hypercontractile disorder of the esophageal musculature not frequently seen in the general population. It is characterized by the presence of at least one contraction with a very high amplitude and duration (DCI > 8,000 mmHg/s/cm) in patients with esophageal symptoms. The aim of our study was to assess the clinical context and manometric characteristics in patients with HE using highresolution manometry (HRM). METHODS: We thoroughly reviewed the clinical features and manometric findings of a total of 720 patients with esophageal symptoms that were attended in the Department of Gastroenterology of our hospital between June 2011 and June 2013. RESULTS: We found seven patients that met criteria for HE according to the Chicago Classification (2012). All of the patients were women (100%). Mean age was 64 years old. Most frequent symptoms were: Chest pain, dysphagia and heartburn.In one patient (14%) the HE was related to a gastroesophageal reflux disease (GERD) and gastroesophageal junction (GEJ) outflow obstruction. Three patients (43%) had more than one hypercontractile contraction in the study. Four patient (57%) hade multipeaked pattern (Jackhammer esophagus) and y two of them were synchronized with respiration. Two patients (29%) were diagnosed with hiatus hernias. Integrated relaxation pressure (IRP) was not higher in hypercontractile contractions than in normal contractions. Only one patient presented a slight alteration of the relaxation (IRP-4s = 15 mmHg) with normal peristalsis, GEJ outflow obstruction and not multipeakeded pattern. One patient presented pathological acid exposure (PAE) in 24-hours pH-metry. CONCLUSIONS: HE is a rare disorder and HRM is essential for its correct diagnosis and characterization. The treatment of HE should achieve the disappearance or at least improvement of the patient´s symptoms and avoid unnecessary diagnostic testing.

Identifying endosymbiont bacteria associated with free-living amoebae.

The association between free-living amoebae and pathogenic bacteria is an issue that has gained great importance due to the environmental and health consequences that it implies. In this paper, we analyse the techniques to follow an epidemiological study to identify associations between genera, species, genotypes and subgenotypes of amoebae with pathogenic bacteria, analysing their evolution and considering their usefulness. In this sense, we highlight the combination of microscopic and molecular techniques as the most appropriate way to obtain fully reliable results as well as the need to achieve the standardization of these techniques to allow the comparison of both environmental and clinical results.