A decade of collaboration in medicines regulation: healthcare professionals engaging with the European Medicines Agency.

The article shows that the input given by healthcare professionals (HCPs) adds value to the regulatory processes surrounding the development, authorisation, and monitoring of a medicine, but is also an instrument for accountability, trust, mutual exchange as well as an insight into the public health issues that matter most to one of the key stakeholder groups the Agency works with. We highlight the role of HCPs in the EU regulatory process and take stock of the first 10 years of the Framework for Interaction with HCPs to describe how practises have evolved over this time to meet the goals of informing, consulting and improving trust in the EU regulatory system. We will analyse what led European Medicines Agency (EMA) to develop this framework through to the next steps and where the interaction might lead in the future.

An action-concept processing advantage in a patient with a double motor cortex.

Patients with atrophy in motor brain regions exhibit selective deficits in processing action-related meanings, suggesting a link between movement conceptualization and the amount of regional tissue. Here we examine such a relation in a unique opposite model: a rare patient with a double cortex (due to subcortical band heterotopia) in primary/supplementary motor regions, and no double cortex in multimodal semantic regions. We measured behavioral performance in action- and object-concept processing as well and resting-state functional connectivity. Both dimensions involved comparisons with healthy controls. Results revealed preserved accuracy in action and object categories for the patient. However, unlike controls, the patient exhibited faster performance for action than object concepts, a difference that was uninfluenced by general cognitive abilities. Moreover, this pattern was accompanied by heightened functional connectivity between the bilateral primary motor cortices. This suggests that a functionally active double motor cortex may entail action-processing advantages. Our findings offer new constraints for models of action semantics and motor-region function at large.

Meta-Analysis of Reversal Agents for Severe Bleeding Associated With Direct Oral Anticoagulants.

BACKGROUND: Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding. OBJECTIVES: The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding. METHODS: The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model. RESULTS: The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used. CONCLUSIONS: The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.

Effect of Modified Lemaire Anterolateral Extra-articular Tenodesis on the Magnetic Resonance Imaging Maturity Signal of Anterior Cruciate Ligament Hamstring Graft.

BACKGROUND: Lateral extra-articular tenodesis (LET) is one of the most widely used procedures to restore anterolateral stability. Clinical outcomes after the addition of LET to anterior cruciate ligament (ACL) reconstruction (ACLR) have been widely investigated; however, the potential influence of LET on the ACL ligamentization process has not been examined. PURPOSE/HYPOTHESIS: The purpose was to use 10-month postoperative magnetic resonance imaging (MRI) scans to determine whether the maturity of grafts after hamstring autograft ACLR was affected by concomitant LET. The hypothesis was that when modified Lemaire lateral extra-articular tenodesis (MLLET) was performed, the MRI parameters of ACL graft maturity would be modified. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The study included patients treated between December 2017 and December 2018 who had undergone anatomic 3-strand hamstring tendon autograft ACLR, with or without concomitant MLLET, and had undergone MRI 10 months postoperatively. Thus, the study included 30 patients who had isolated ACLR and 22 patients who had ACLR plus MLLET. The 2 groups were comparable based on all criteria analyzed. To evaluate graft maturity, the signal-to-noise quotient (SNQ) was measured in 3 regions of interest of the proximal, midsubstance, and distal ACL graft. Lower SNQ ratios indicate less water content and, theoretically, better maturity and healing of the graft. RESULTS: The mean ± SD for SNQ was 4.62 ± 4.29 (range, 3.12-6.19) in the isolated ACLR group and 7.59 ± 4.68 (range, 4.38-8.04) in the ACLR plus MLLET group (P = .012). Upon comparing the mean values of the 3 portions between the 2 groups, we found a significant difference between the 2 groups for the proximal and middle portions (P = .007 and P = .049, respectively) but no difference in the distal portion (P = .369). CONCLUSION: At the 10-month follow-up, hamstring tendon autografts for anatomic ACLR with MLLET did not show the same MRI signal intensity compared with isolated hamstring anatomic ACLR.

The vancomycin soaking technique: no differences in autograft re-rupture rate. A comparative study.

PURPOSE: The main aim of this study was to evaluate the re-rupture risk after an anterior cruciate ligament reconstruction (ACL-R) using the vancomycin soaking technique and to compare it with the re-rupture risk in patients on whom this technique was not utilized. The secondary purpose was to compare the functional outcomes of those two subsets of patients operated on for ACL-R. The hypotheses are that the vancomycin soaking technique does not affect the re-rupture risk or the functional outcomes. MATERIAL AND METHODS: A retrospective historical cohort study was conducted. Two groups were compared in terms of the re-rupture rate (traumatic or atraumatic) and functional outcomes (International Knee Documentation Committee (IKDC), Tegner, and Lysholm). Group 1 consisted of patients that received pre-operative IV antibiotics. In group 2, the patients received pre-operative IV antibiotics along with a graft that had been presoaked in a vancomycin solution. A minimum follow-up of five years was required. RESULTS: There were 17 patients that suffered a re-rupture in group 1 (4.7%) and 15 in group 2 (3.9%) (n.s.). IKDC was 82.0 in group 1 and 83.9 in group 2 (p = 0.049); Tegner scored 4 in both groups (n.s.) and Lysholm was 90.3 in group 1 and 92.0 in group 2 (p = 0.015). CONCLUSION: The vancomycin soaking technique for ACL autografts is a safe procedure for the daily clinical practice, in terms of re-ruptures. Moreover, it does not impair functional outcomes after an ACL-R.

Integrative and Conjugative Elements of Helicobacter pylori Are Hypothetical Virulence Factors Associated With Gastric Cancer.

Helicobacter pylori is a bacteria with high genome plasticity that has been associated with diverse gastric pathologies. The genetic diversity of this bacteria has limited the characterization of virulence factors associated with gastric cancer (GC). To identify potentially helpful disease biomarkers, we compared 38 complete genomes and 108 draft genomes of H. pylori isolated worldwide from patients with diverse gastric pathologies and 53 draft genomes of H. pylori isolated from Mexican patients with GC, intestinal metaplasia, gastritis, peptic ulcer, and dyspepsia. H. pylori strains isolated from GC were 3-11 times more likely to harbor any of seven genes encoded within an integrative and conjugative element (ICE) than H. pylori isolated from subjects with other gastric pathologies. We tested the cytopathic effects on AGS cells of selected H. pylori strains with known cytotoxin-associated gene pathogenicity island (cag-PAI) and ICE status (H. pylori strains 29CaP, 29CaCe, 62A9, 7C, 8822, and 26695) and the histopathological damage of H. pylori 29CaP and 62A9 in a mouse model. H. pylori 29CaP, which harbors a complete ICEHptfs3 but lacks cag-PAI, elicited distinctive morphology changes and higher histopathological scores compared with other H. pylori strains carrying cag-PAI and hybrid ICE with incomplete TFSS. The presence of intact segments of ICE regions might be a risk factor to develop GC that needs to be addressed in future studies.

Effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute myocardial infarction-Results of the Chymase Inhibitor in Adverse Remodeling after Myocardial Infarction (CHIARA MIA) 2 trial.

BACKGROUND: Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). METHODS: In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. RESULTS: Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ±â€¯5.4%, placebo: 4.0% ±â€¯5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ±â€¯13.3 mL/m2, placebo: 5.1 ±â€¯18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ±â€¯11.2 mL/m2, placebo: 0.6 ±â€¯14.8 mL/m2, P = .56) were observed in both treatment arms. CONCLUSION: Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

The Menisco-Tibio-Popliteus-Fibular Complex: Anatomic Description of the Structures That Could Avoid Lateral Meniscal Extrusion.

PURPOSE: To analyze, quantify, and redefine the anatomy of the peripheral attachments of the lateral meniscal body to further understand how the structures might play a part in preventing meniscal extrusion and how it might be applied to surgical techniques. METHODS: Ten nonpaired fresh-frozen cadaveric knees without prior injury, a surgical history, or gross anatomic abnormality were included. There were 5 right and 5 left knees, and 50% were from male donors and 50% were from female donors. All the dissections were performed by a group of 3 experts in knee surgery (2 knee surgeons and 1 anatomy professor who oversaw the design of the dissection protocol and guided this protocol). The main peripheral structures associated with the lateral meniscus body were dissected to determine the insertion, size, thickness, and location of the lateral meniscotibial ligament (LMTL), popliteofibular ligament (PFL), and popliteomeniscal ligament (PML). The distance to various landmarks in the lateral compartment was also determined using an electronic caliper. Moreover, a histopathologic study was carried out. RESULTS: The average thickness of the LMTL was 0.62 ± 0.18 mm (95% confidence interval [CI], 0.49-0.75 mm); that of the PFL-PML area was 1.05 ± 0.27 mm (95% CI, 0.85-1.24 mm). The anteroposterior distance measured 15.80 ± 4.80 mm (95% CI, 12.40-19.30 mm) for the LMTL and 10.40 ± 1.70 mm (95% CI, 9.21-11.63 mm) for the PFL-PML area. The anteroposterior distance of the whole menisco-tibio-popliteus-fibular complex (MTPFC) was 28.20 ± 4.95 mm (95% CI, 24.70-31.70 mm). The average distance from the MTPFC to the posterior horn of the lateral meniscal root was 29.30 ± 2.29 mm (95% CI, 27.60-30.90 mm), whereas that to the anterior horn was 32.00 ± 4.80 mm (95% CI, 28.60-35.50 mm). The average distance from the tibial insertion of the LMTL to the articular surface was 5.59 ± 1.22 mm (95% CI, 4.72-6.46 mm). In all the anatomic components of the knee, a consistent morphologic and histologic pattern was observed between the fibers of the LMTL, PFL, and PML and those of the lateral meniscal body, making up the proposed MTPFC. CONCLUSIONS: A consistent anatomic pattern has been identified between the lateral meniscal body and the LMTL, PFL, and PML, forming an interconnected complex that would seem appropriate to denominate the MTPFC. A precise study of this region and appropriate nomenclature for it could contribute to a better understanding of the mechanism of lateral meniscal injuries at this level, as well as the development of surgical techniques to treat these lesions and prevent extrusion. CLINICAL RELEVANCE: This study contributes to the understanding of the lateral meniscal body attachments and the functions they serve. This will lead to improvements in the treatment of lesions in this region, including the development of surgical techniques.

Translation of gastric disease progression at gene level expression.

Helicobacter pylori is associated with the development of several lesions in the human stomach. This chronic infection produces gastritis, which can progress to intestinal metaplasia and gastric cancer. To date, there is very little information regarding gene-expression in the different phases of progression caused by chronic H. pylori infection. In this study, we performed a genome-wide gene-expression analysis in gastric biopsies of patients chronically infected with H. pylori, using the potential of high-throughput technologies that have not been fully exploited in this area. Here we illustrate the potential correlation of H. pylori infection with the gene expression changes in follicular gastritis, chronic gastritis and intestinal metaplasia. We also suggest its potential as biomarkers of each condition. An exploratory set of 21 biopsies from patients with follicular gastritis, chronic gastritis, and intestinal metaplasia were analyzed by gene-expression microarrays in order to identify the biological processes altered in each lesion. The microarray data was corroborated by real-time PCR, while 79 Formalin-Fixed Paraffin-Embeded samples were analyzed by immunohistochemistry. Follicular gastritis exhibited significant enrichment in genes associated with glutamate signaling, while chronic gastritis showed a down-regulation in metallothionein 1 and 2 and in oxidative phosphorylation-related genes, which could be associated with the chronic infecton of H. pylori. Intestinal metaplasia exhibited an over-expression of gastrointestinal stem cell markers, such as LGR5 and PROM1, as well as messenger RNA and nucleic acid metabolism-related genes. The gene-expression patterns found in this study provide new comparative information about chronic gastritis, follicular gastritis and intestinal metaplasia that may play an important role in the development of gastric cancer.

Error Measurement Between Anatomical Porcine Spine, CT Images, and 3D Printing.

RATIONALE AND OBJECTIVES: 3D printers are increasingly used in medical applications such as surgical planning, creation of implants and prostheses, and medical education. For the creation of reliable 3D printed models of the vertebral column, processing must be performed on CT images. This processing must be assessed and validated so that any error of the printed model can be recognized and minimized. MATERIAL AND METHODS: In order to perform this validation, 10 CT scans of porcine lumbar spinal vertebra were used, which were then dissected and scanned again. CT image processing was performed to obtain a mesh and perform 3D printing. RESULTS: There was no statistical difference among the four different levels of vertebrae measurements (first CT images, second CT images, anatomical piece of porcine bone and 3D printing of porcine bone; One Way repeated measure ANOVA, F < F_crit, p value > α = 0.05). The Intraclass Correlation also revealed a mean intraclass correlation coefficient (3,1) = 0.9553, which describes the reliability of all four levels in addition to the reliability of the data between porcine samples subjected to different levels of measurement. This shows that the average error is less than 1 mm. CONCLUSIONS: The measurements of models created with 3D printers using the pipeline described in this paper have an average error of 0.60 mm with CT images and 0.73 mm with anatomical piece. Thus, 3D printed models accurately reflect in vivo bones and provide accurate 3D impressions to assist in surgical planning.

Visual analysis of automated segmentation in the diagnosis of focal cortical dysplasias with magnetic resonance imaging.

Focal cortical dysplasias (FCDs) are a frequent cause of epilepsy. It has been reported that up to 40% of them cannot be visualized with conventional magnetic resonance imaging (MRI). The main objective of this work was to evaluate by means of a retrospective descriptive observational study whether the automated brain segmentation is useful for detecting FCD. One hundred and fifty-five patients, who underwent surgery between the years 2009 and 2016, were reviewed. Twenty patients with FCD confirmed by histology and a preoperative segmentation study, with ages ranging from 3 to 43 years (14 men), were analyzed. Three expert neuroradiologists visually analyzed conventional and advanced MRI with automated segmentation. They were classified into positive and negative concerning visualization of FCD by consensus. Of the 20 patients evaluated with conventional MRI, 12 were positive for FCD. Of the negative studies for FCD with conventional MRI, 2 (25%) were positive when they were analyzed with automated segmentation. In 13 of the 20 patients (with positive segmentation for FCD), cortical thickening was observed in 5 (38.5%), while pseudothickening was observed in the rest of patients (8, 61.5%) in the anatomical region of the brain corresponding to the dysplasia. This work demonstrated that automated brain segmentation helps to increase detection of FCDs that are unable to be visualized in conventional MRI images.

Use of Three-dimensional Printing in Orthopaedic Surgical Planning.

BACKGROUND: Three-dimensional (3D) printing is a technique based on overlapping layers of a material (eg, plastic, clay, and metal). The widespread implementation of 3D printers has resulted in a notable increase in use. Fields such as construction, engineering, and medicine benefit from this technique. AIM: The use of 3D printed scale models permits better surgical planning and results. METHODS: The models were created based on CT images of seven patients (age range, 5 to 61 years) with different pathologies who were candidates for surgery. RESULTS: Surgical time decreased as a result of detailed surgical planning with printed models. This technique also was associated with a decrease in bleeding, a reduction in the amount of anesthesia required, and greater precision. In some patients, a change in surgical strategy was noted, thus allowing for a reduction in the number of surgeries and the aggressiveness of surgery. Finally, the preoperative practice (virtual and physical osteotomies using cutting tools) that was performed in two cases allowed the surgeon to evaluate the different approach alternatives and establish the best strategy. CONCLUSIONS: The use of 3D-printed anatomic models has improved surgical planning, especially for patients in whom the conventional techniques are insufficient for establishing a proper strategy. The extra information provided by 3D-printed models can lead to a better intervention strategy, which is beneficial for patients because it decreases the risks, procedure times, and recovery times.

Study of Resting-State Functional Connectivity Networks Using EEG Electrodes Position As Seed.

Electroencephalography (EEG) is the standard diagnosis method for a wide variety of diseases such as epilepsy, sleep disorders, encephalopathies, and coma, among others. Resting-state functional magnetic resonance (rs-fMRI) is currently a technique used in research in both healthy individuals as well as patients. EEG and fMRI are procedures used to obtain direct and indirect measurements of brain neural activity: EEG measures the electrical activity of the brain using electrodes placed on the scalp, and fMRI detects the changes in blood oxygenation that occur in response to neural activity. EEG has a high temporal resolution and low spatial resolution, while fMRI has high spatial resolution and low temporal resolution. Thus, the combination of EEG with rs-fMRI using different methods could be very useful for research and clinical applications. In this article, we describe and show the results of a new methodology for processing rs-fMRI using seeds positioned according to the 10-10 EEG standard. We analyze the functional connectivity and adjacency matrices obtained using 65 seeds based on 10-10 EEG scheme and 21 seeds based on 10-20 EEG. Connectivity networks are created using each 10-20 EEG seeds and are analyzed by comparisons to the seven networks that have been found in recent studies. The proposed method captures high correlation between contralateral seeds, ipsilateral and contralateral occipital seeds, and some in the frontal lobe.

Causes of Death in Patients with Venous Thromboembolism Anticoagulated with Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

Death is more frequent than nonfatal recurrent venous thromboembolism (VTE) and major bleeding after acute VTE. The analysis of the causes of death is fundamental to explore new strategies to reduce mortality rates in these patients. The authors performed a meta-analysis to analyze mortality and independently adjudicated causes of death in anticoagulated patients due to VTE, and to evaluate potential differences between different anticoagulant schemes. They searched MEDLINE and CENTRAL, from January 1, 2000, to January 31, 2017, and performed additional searches in Web sites of regulatory agencies, clinical trial registers, and conference proceedings. Two investigators independently selected studies and extracted the data. Study quality was assessed with the Cochrane Collaboration's tool for assessing the risk of bias in randomized studies. Seven prospective randomized trials in 29,844 patients (22,025 patient-year follow-up) were included, comparing dabigatran, rivaroxaban, apixaban, and edoxaban with the standard anticoagulant treatment of VTE. A total of 718 patients died during the follow-up (3.4% per year; 95% confidence interval [CI]: 2.3-4.8). The most frequent causes of death were cancer (42%), followed by VTE (20%), infections (13%), hemorrhage (6%), heart disease (4%), and stroke (2%). There were no differences in the overall survival and causes of death according to the anticoagulant type. Concomitant active cancer during the study was significantly associated with death (odds ratio: 15.2; 95% CI: 9.2-25.1). Cancer is the leading cause of death in contemporary VTE trials. Interventions beyond anticoagulation, particularly in patients with active cancer, are needed.

Derechos Sexuales y Reproductivos durante la atención de la gestación, parto y lactancia: La situación de Chile / The exercise of Sexual and Reproductive Rights during parental care, delivery and breast feeding: the situation in Chile

Este artículo busca analizar la situación actual sobre la atención en salud materna y del recién nacido en nuestro país, con enfoque de derechos humanos, de acuerdo a lo que la literatura y las diversas agencias internacionales vienen proponiendo desde hace algunos años.(AU)

Enfrentamiento práctico del paciente con síndrome de boca urente, una propuesta para el estudio y tratamiento / Burning mouth syndrome

El Síndrome de Boca Urente (SBU) clásicamente se define como un dolor oral quemante sin hallazgos en el examen físico o de laboratorio. Muchas veces puede ser asociado a procedimientos dentales o alteraciones psiquiátricas pero en En la gran mayoría de los casos, no existe un fenómeno relacionado. Sin embargo, no existe consenso en su evaluación clínica, lo que se refleja en lo heterogéneo de los estudios de prevalencia, patogenia y tratamiento. Es por esto que muchas veces, representa un desafío el diagnóstico y tratamiento, especialmente cuando especialmente cuando existe un serio deterioro de la calidad de vida, sin una causa identificable. Este artículo tiene como objetivo contribuir en la identificación de causas y en la definición de pautas para el diagnostico y manejo clínico del SBU, proponiendo un esquema de estudio y manejo en base a la revisión de la literatura y la experiencia clínica.

Classically, we can define Burning-Mouth Syndrome (BMS) as burnish oral pain with no physical or laboratory findings; often can be associated with dental procedures or psychiatric disorders but in general, there is no related phenomenon. Even today there is confusion and ignorance of this syndrome, being reflected in the heterogeneity of the studies of prevalence, pathogenesis and treatment. This is why, in clinical practice, study and treatment are challenging, especially when we are faced with a patient who feels seriously impaired in his quality of life and does not find the cause. This article attempts to contribute to the understanding of the BMS, proposing a study and management scheme based on literature review and clinical experience.

[Diagnóstico tardío de psoriasis: motivos y consecuencias]. / Late diagnosis of psoriasis: Reasons and consequences.

BACKGROUND: Psoriasis is an autoimmune skin disease that may be associated with articular manifestations, and the most common clinical presentation is the variety "in plaques". In Mexico, in the Centro Dermatológico Pascua, it is the eighth leading cause of consultation. The aim of this study was to determine the diagnostic process of patients in a reference center for diseases of the skin. METHODS: Performing an analytical cross-sectional study that included 100 patients where the diagnostic process was questioned, clinimetric scales were applied and evaluated anthropometric. RESULTS: It was found that 70% of patients had taken over a month to get medical care (median: 3 months; IQR: 11 months), having consulted in 61% to a general physician as a doctor of first contact and 89% being diagnosed by a dermatologist. Eighty-eight percent of the patients were overweight or obese. We found as a factor of delay, a partnership with the variable of having an Institutional Medical Service (p = 0.019; U = 695.5). CONCLUSION: it is necessary to design a system to shorten the diagnostic process, not only in psoriasis, in addition to emphasizing dermatological education.

Health risks from exposure to untreated wastewater used for irrigation in the Mezquital Valley, Mexico: A 25-year update.

Wastewater reuse for agriculture is common worldwide; wastewater treatment, however, is rare in many countries, leading to high potential for exposure to harmful pathogens. Mexico City, one of the largest producers of untreated wastewater for agricultural use worldwide, was the site of key epidemiologic studies conducted in the 1990s. We both reviewed the literature on and conducted a cross-sectional study of diarrheal risk and wastewater contamination to provide an updated assessment of health risks and to inform an upcoming update of the 2006 WHO guidelines on wastewater reuse. We surveyed communities in the Mezquital Valley that use wastewater for irrigation and communities that use well water to compare the prevalence of self-reported diarrheal disease in children under five years old. Wastewater, well water, household environmental samples, and stool samples were collected and analyzed. Communities exposed to wastewater had a higher one-week prevalence of diarrhea (10%) compared to unexposed communities (5%). This association remained in an adjusted modified Poisson regression model (PR = 2.31, 95% CI 1.00, 5.31), but not when limited to households engaged in agriculture. Water quality indicators document differences between irrigation water from the two community groups. These results are in agreement with 25 population studies identified by our review that were conducted since or not included in the 2006 WHO guidelines and show consistent negative impacts of wastewater exposure on health. While overall diarrheal prevalence has declined when compared to studies conducted over 25 years ago in the same region, the association of diarrheal disease and wastewater exposure has remained and possibly increased. With rising urbanization worldwide, attention to these risks and wastewater treatment is becoming increasingly important.

Genetic Alterations in Gastric Cancer Associated with Helicobacter pylori Infection.

Gastric cancer is a world health problem and depicts the fourth leading mortality cause from malignancy in Mexico. Causation of gastric cancer is not only due to the combined effects of environmental factors and genetic variants. Recent molecular studies have transgressed a number of genes involved in gastric carcinogenesis. The aim of this review is to understand the recent basics of gene expression in the development of the process of gastric carcinogenesis. Genetic variants, polymorphisms, desoxyribonucleic acid methylation, and genes involved in mediating inflammation have been associated with the development of gastric carcinogenesis. Recently, these genes (interleukin 10, Il-17, mucin 1, ß-catenin, CDX1, SMAD4, SERPINE1, hypoxia-inducible factor 1 subunit alpha, GSK3ß, CDH17, matrix metalloproteinase 7, RUNX3, RASSF1A, TFF1, HAI-2, and COX-2) have been studied in association with oncogenic activation or inactivation of tumor suppressor genes. All these mechanisms have been investigated to elucidate the process of gastric carcinogenesis, as well as their potential use as biomarkers and/or molecular targets to treatment of disease.