Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage.

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.

Reactive infectious mucocutaneous eruption due to COVID-19 with erythema-multiforme-like lesions and myeloid cells.

Reactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16-year-old male with COVID-19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non-segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID-19-related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.

Neutrophilic fixed drug eruption, a histopathologic variant or an expected finding?-A report of two cases and review of the literature.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by recurrent circumscribed lesions at the same location upon re-exposure to the culprit medication, resulting in distinct postinflammatory hyperpigmentation. Histopathologically, FDE demonstrates a predominantly lymphocytic interface or lichenoid infiltrate with basal cell vacuolar changes and keratinocyte dyskeratosis/apoptosis. The term "neutrophilic fixed drug eruption" has been used to describe cases in which the inflammatory infiltrate is predominantly neutrophilic. The infiltrate can extend deeper in the dermis, potentially mimicking a neutrophilic dermatosis such as Sweet syndrome. We present two cases and review the literature to discuss the possibility that a neutrophilic inflammatory infiltrate may be an expected finding in FDE, rather than a histopathologic variant.

Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview.

Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC is a complex disease with tumor heterogeneity, rapidity, and dynamics of the tumor microenvironment that result in resistance to existing therapy. Targeting a single cell-signaling pathway is unlikely to treat or prevent BC. Curcumin (a natural yellow pigment), the principal ingredient in the spice turmeric, is well-documented for its diverse pharmacological properties including anti-cancer activity. However, its clinical application has been limited because of its low solubility, stability, and bioavailability. To overcome the limitation of curcumin, several modified curcumin conjugates and curcumin mimics were developed and studied for their anti-cancer properties. In this review, we have focused on the application of curcumin mimics and their conjugates for breast cancer.

Comparative assessment of water quality indices-a case study to evaluate water quality for drinking water supply and irrigation in Northern Mexico.

Water quality indices (WQIs) are numerical measures used by researchers and water managers to communicate water quality status to the public. This study analyzes the official databases from the CONAGUA monitoring network of the main tributary rivers in the middle basin of the San Pedro-Mezquital River in Durango, Mexico, for a 6-year period (2013-2018). We applied three WQIs to 432 data (18 sampling sites, four samples per year, 6 years): Canadian Council of Ministers of the Environment (CCME) WQI, National Sanitation Foundation (NSF) WQI, and Secretariat of Urban Development and Ecology (SEDUE) WQI. The Canadian index proved to be a flexible, appropriate, and rigorous methodology for assessing water quality based on its use. Results classify the water quality in the studied reservoirs as good, while river water was rated for public use, as marginal to very poor. No statistical significant differences in the quality of water between the rainy (June-October) and dry (November-May) seasons were found. However, tendency shows that in the rainy season the water quality was lower, mainly attributed to agricultural runoffs and bank erosion. The main contamination problem was the presence of fecal coliforms in high concentrations, which is associated to the high population density in the area, low sanitation efficiency, and multiple non-point discharges.

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

INTRODUCTION: rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. MATERIAL AND METHODS: this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.

SARS-CoV-2 Reinfection among Healthcare Workers in Mexico: Case Report and Literature Review.

Since the onset of the COVID-19 pandemic, there have been multiple questions regarding reinfections associated with SARS-CoV-2. Healthcare workers on duty, due to overexposure in environments where there are more cases of COVID-19, are more prone to become infected by this virus. Here, we report 4 cases that meet the definition of clinical reinfection by SARS-CoV-2, as well as a literature review on this subject; all occurred in healthcare workers in Acapulco Guerrero, Mexico who provide their services in a hospital that cares for patients with COVID-19. The time between the manifestation of the first and second infection for each case was 134, 129, 107 and 82 days, all patients presented symptomatology in both events. The time between remission of the first infection and onset of second infection was 108, 109, 78 and 67 days for each case, while the time to confirmation by reverse transcription polymerase chain reaction (RT-PCR) between infections was 134, 124, 106 and 77 days. In two of the four cases the reinfection resulted in a more severe case, while in the remaining two cases the manifestation of symptoms and complications was similar to that presented in the first infection. Given this scenario, greater care is needed in the management of the pandemic caused by SARS-CoV-2 to protect healthcare workers and the general public from risks and complications caused by a possible reinfection by SARS-CoV-2.

From the handling of an outbreak by an unknown pathogen in Wuhan to the preparedness and response in the face of the emergence of Covid-19 in Mexico.

On December 31, 2019, the Chinese health authorities informed the international community, through the mechanisms established by the World Health Organization (WHO), of a pneumonia epidemic of unknown etiology in Wuhan, Hubei Province. The first cases were reported early in that month and were linked to a history of having visited a market where food and live animals are sold. On January 7, 2020, isolation and identification of the culprit pathogen was achieved using next-generation sequencing, while the number of affected subjects continued to rise. The publication of full-genomes of the newly identified coronavirus (initially called 2019-nCoV, now called SARS-CoV2) in public and private databases, of standardized diagnostic protocols and of the clinical-epidemiological information generated will allow addressing the Public Health Emergency of International Concern (PHEIC), declared on January 30 by the WHO. With this document, we intend to contribute to the characterization of the pneumonia epidemic, now designated coronavirus disease (Covid-19) review the strengths Mexico has in the global health concert and invite health professionals to join the preparedness and response activities in the face of this emergency.

El 31 de diciembre de 2019, las autoridades chinas de salud informaron a la comunidad internacional, a través de los mecanismos establecidos por la Organización Mundial de la Salud (OMS), de una epidemia de neumonía con etiología desconocida en Wuhan, provincia de Hubei. Los primeros casos se notificaron a inicios de ese mes y se vincularon al antecedente de visitar un mercado de comida y animales vivos. El 7 de enero de 2020 se logró el aislamiento y reconocimiento del patógeno responsable mediante secuenciación de siguiente generación, mientras el número de afectados continuaba en ascenso. La publicación de genomas completos del nuevo coronavirus identificado (inicialmente denominado 2019-nCoV, ahora designado SARS-CoV2) en bases de datos públicas y privadas, de protocolos diagnósticos estandarizados y de la información clínica epidemiológica generada permitirá atender la Emergencia de Salud Pública de Importancia Internacional (ESPII) declarada el 30 de enero por la OMS. Con este documento pretendemos aportar a la caracterización de la epidemia de neumonía, ahora llamada enfermedad por coronavirus (Covid-19), revisar las fortalezas que tiene México en el concierto de la salud global e invitar a los profesionales de la salud a incorporarse a las actividades de preparación y respuesta ante esta emergencia.

Errores más comunes al redactar artículos médicos originales.

One of the skills that is more in need to be strengthened in the medical area is the dissemination of knowledge. For this reason, it is necessary to provide elements that promote training in scientific writing. Identifying the most common problems when writing medical original articles for publication will provide useful resources that should contribute to the generation of knowledge. There are multiple reasons that intervene for an original article not to be accepted in a medical journal, among which failure to follow instructions for authors and methodological, design and structural problems stand out. However, the aspect that most influences and that is seldom pointed out, is inadequate writing of research manuscripts, which becomes evident in the different sections that make up manuscripts. All the above-mentioned factors are the responsibility of the authors, and therefore must be taken care of properly. The purpose of this article is to identify the most common mistakes when writing original medical manuscripts, which, if avoided, will increase the possibility for research papers to be accepted for publication.

Una de las habilidades que más requiere ser fortalecida en el área médica es la difusión de conocimiento, por tal motivo, es necesario brindar elementos que promuevan la capacitación en redacción científica. Identificar cuáles son los problemas más comunes al redactar artículos médicos originales para su publicación proporcionará recursos útiles que contribuyan a la generación de conocimiento. Existen diversos motivos que intervienen para que un artículo original no sea aceptado en una revista médica, entre los que destacan falta de apego a las instrucciones para autores, problemas metodológicos y de diseño, así como de estructura, sin embargo, el aspecto que más influye y pocas veces se señala, es la redacción inadecuada de los escritos de investigación, la cual se hace patente en las diferentes secciones que componen los manuscritos. Todos los factores mencionados son responsabilidad de los autores, por lo que deben ser atendidos apropiadamente. El presente escrito tiene como objetivo señalar los errores más comunes al redactar escritos médicos originales, los cuales, de ser evitados, incrementarán la posibilidad de que sus trabajos de investigación sean aceptados para su publicación.

Algoritmo diagnóstico para la confirmación de casos de sarampión y rubéola en México.

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Debido a la implementación exitosa de las estrategias de eliminación del sarampión y la rubéola, México enunció la interrupción de la transmisión endémica del sarampión en 1996 y de la rubéola en 2008. Después de un proceso de verificación, la región de las Américas fue declarada libre de rubéola y del síndrome de rubéola congénita en 2015 y del sarampión en 2016. Para mantener el estatus de eliminación en México es esencial continuar con la vigilancia por laboratorio en el marco de la Red Mundial de Laboratorios de Sarampión y Rubéola. El Instituto de Diagnóstico y Referencia Epidemiológicos, a través de la Red Nacional de Laboratorios de Salud Pública, garantiza resultados oportunos y confiables ante la posible reintroducción de estos y otros patógenos emergentes.

Diagnostic algorithm for the confirmation of cases of measles and rubella in Mexico.

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Mitral valve navigator. A new diagnostic tool for effective regurgitant orifice quantification in mitral regurgitation.

INTRODUCTION: Mitral regurgitation severity assessment is usually carried out using qualitative, semiquantitative, and quantitative parameters. The mitral valve navigation (MVN) tool allows to measure the mitral effective regurgitant orifice (MERO) from 3D echo datasets. Our aim was to validate the MVN as a new tool to quantify MERO. A secondary aim was to assess the intra- and interobserver variability. METHODS: This is a retrospective study in which consecutive subjects undergoing a transoesophageal echocardiogram for more than mild mitral regurgitation evaluation were included. MERO measurement obtained by means of 3D color Doppler was used as the gold standard method for comparison. In every patient, MERO was also obtained using the MVN tool. RESULTS: Fifty-nine consecutive patients were analyzed (47.5% female; mean age 50.8 years). Mitral regurgitation was moderate in 23 (39%) and severe in 36 (61%) patients. Forty patients (67.8%) had a primary and 19 (32.2%) a secondary mitral regurgitation. The intraclass correlation coefficient (ICC) between 3D color Doppler and MVN was excellent (ICC: 0.95; 95% CI: 0.82 to 0.98; P < 0.001) in the total group and for patients with primary and secondary mitral regurgitation. Intra- and interobserver agreements were also good. CONCLUSIONS: Mitral valve navigator shows an excellent accuracy for measuring MERO when the transoesophageal 3D color Doppler is used as the reference method, either primary or secondary mitral regurgitation. Intraobserver reproducibility and interobserver reproducibility are also excellent. These findings make this software a good alternative method to measure mitral regurgitation severity.

Pharmacokinetics of Miltefosine in Children and Adults with Cutaneous Leishmaniasis.

An open-label pharmacokinetics (PK) clinical trial was conducted to comparatively assess the PK and explore the pharmacodynamics (PD) of miltefosine in children and adults with cutaneous leishmaniasis (CL) in Colombia. Sixty patients, 30 children aged 2 to 12 years and 30 adults aged 18 to 60 years, were enrolled. Participants received miltefosine (Impavido) at a nominal dose of 2.5 mg/kg/day for 28 days. Miltefosine concentrations were measured in plasma and peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry of samples obtained during treatment and up to 6 months following completion of treatment, when therapeutic outcome was determined. Fifty-two patients were cured, 5 pediatric patients failed treatment, and 3 participants were lost to follow-up. Leishmania (Viannia) panamensis predominated among the strains isolated (42/46; 91%). Noncompartmental analysis demonstrated that plasma and intracellular miltefosine concentrations were, overall, lower in children than in adults. Exposure to miltefosine, estimated by area under the concentration-time curve and maximum concentration, was significantly lower in children in both the central and intracellular compartments (P < 0.01). Leishmania persistence was detected in 43% of study participants at the end of treatment and in 27% at 90 days after initiation of treatment. Clinical response was not dependent on parasite elimination. In vitro miltefosine susceptibility was similar for Leishmania strains from adults and children. Our results document PK differences for miltefosine in children and adults with cutaneous leishmaniasis that affect drug exposure and could influence the outcome of treatment, and they provide bases for optimizing therapeutic regimens for CL in pediatric populations. (This study has been registered at ClinicalTrials.gov under identifier NCT01462500.).

Evaluation of a hearing screening questionnaire for use with Ecuadorian school-aged children.

OBJECTIVE: The purpose of this study was to evaluate the accuracy of a teacher-administered hearing screening questionnaire to detect hearing loss among first-grade Ecuadorian children in public schools. DESIGN: A cross-sectional design was used to compare screening results from the teacher-administered questionnaire and pure-tone audiometry. STUDY SAMPLE: Children were randomly selected from 117 schools. The study was conducted in two phases to accommodate different school calendars in the country. Data for both screening methods were available for 4616 children. RESULTS: For Phase 1, almost 90% who failed the questionnaire passed audiometry; and, 85% who failed audiometry passed the questionnaire. A revised questionnaire was used for Phase 2 and 70% who failed the questionnaire passed audiometry; and 85% who failed audiometry, passed the questionnaire. Of the 27 children identified in Phase 2 as having hearing loss at the time screening was done, 88.9% failed audiometry, but only 22.2% failed the questionnaire. CONCLUSIONS: Because there was little agreement between the questionnaire and the audiometry, it was recommended that the questionnaire not be used to screen Ecuadorian children for hearing loss. The results of this evaluation of the school hearing screening program provided the Ecuadorian government with important information to guide policy decisions.

Sixteen years follow-up results of a randomized phase II trial of neoadjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) compared with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) in stage III breast cancer: GOCS experience.

Neoadjuvant chemotherapy (NAC) allows direct evaluation of the tumor's sensitivity to therapy, eradication of micrometastatic disease and the possibility of performing breast conserving surgery. The aim of this study was to describe long-term results of NAC in stage III breast cancer patients. We evaluated 126 patients that participated in a phase II randomized trial of neoadjuvant FAC compared with CMF. Chemotherapy was administered for three cycles prior to definitive surgery and radiotherapy, and then for six cycles as adjuvant. Median follow-up was 4.5 years (range 0.2-16.4). Objective response rate (OR) was similar in both groups (61 % for FAC, 66 % for CMF, P = NS). There were no differences in median disease free survival (DFS) or overall survival (OS) (5.1 vs 3.3 years and 6.7 vs 6.3 years for FAC and CMF, respectively). After 16 years of follow-up, 53 patients are still alive. Multivariate analysis showed that the number of pathologically involved lymph nodes (pLN) was the only factor associated with both, DFS and OS (P = 0.0003 and P = 0.0005, respectively). Both regimens were well tolerated, CMF had higher incidence of grade 3-4 leukopenia, thrombocytopenia, and stomatitis, whereas alopecia was more common in FAC. To the best of our knowledge, this is the first study to report long-term outcomes of FAC and CMF in the neoadjuvant setting. Within the sensitivity of our study, both regimens showed similar OR, long-term toxicity, DFS, and OS rate at 16 years. After 5 years, the hazard of death seems to decline. The prolonged follow-up of this study provides a unique opportunity to evaluate factors that predict long-term outcomes. After 16 years of follow-up, the number of pLN remains the most powerful predictor of survival.

Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members.

IMPORTANCE: Sickle cell disease (SCD) is a life-threatening genetic disorder affecting nearly 100,000 individuals in the United States and is associated with many acute and chronic complications requiring immediate medical attention. Two disease-modifying therapies, hydroxyurea and long-term blood transfusions, are available but underused. OBJECTIVE: To support and expand the number of health professionals able and willing to provide care for persons with SCD. EVIDENCE REVIEW: Databases of MEDLINE (including in-process and other nonindexed citations), EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, TOXLINE, and Scopus were searched using prespecified search terms and keywords to identify randomized clinical trials, nonrandomized intervention studies, and observational studies. Literature searches of English-language publications from 1980 with updates through April 1, 2014, addressed key questions developed by the expert panel members and methodologists. FINDINGS: Strong recommendations for preventive services include daily oral prophylactic penicillin up to the age of 5 years, annual transcranial Doppler examinations from the ages of 2 to 16 years in those with sickle cell anemia, and long-term transfusion therapy to prevent stroke in those children with abnormal transcranial Doppler velocity (≥200 cm/s). Strong recommendations addressing acute complications include rapid initiation of opioids for treatment of severe pain associated with a vasoocclusive crisis, and use of incentive spirometry in patients hospitalized for a vasoocclusive crisis. Strong recommendations for chronic complications include use of analgesics and physical therapy for treatment of avascular necrosis, and use of angiotensin-converting enzyme inhibitor therapy for microalbuminuria in adults with SCD. Strong recommendations for children and adults with proliferative sickle cell retinopathy include referral to expert specialists for consideration of laser photocoagulation and for echocardiography to evaluate signs of pulmonary hypertension. Hydroxyurea therapy is strongly recommended for adults with 3 or more severe vasoocclusive crises during any 12-month period, with SCD pain or chronic anemia interfering with daily activities, or with severe or recurrent episodes of acute chest syndrome. A recommendation of moderate strength suggests offering treatment with hydroxyurea without regard to the presence of symptoms for infants, children, and adolescents. In persons with sickle cell anemia, preoperative transfusion therapy to increase hemoglobin levels to 10 g/dL is strongly recommended with a moderate strength recommendation to maintain sickle hemoglobin levels of less than 30% prior to the next transfusion during long-term transfusion therapy. A strong recommendation to assess iron overload is accompanied by a moderate strength recommendation to begin iron chelation therapy when indicated. CONCLUSIONS AND RELEVANCE: Hydroxyurea and transfusion therapy are strongly recommended for many individuals with SCD. Many other recommendations are based on quality of evidence that is less than high due to the paucity of clinical trials regarding screening, management, and monitoring for individuals with SCD.

2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance.

Obesity-related systemic inflammation contributes to develop insulin resistance. The main factors involved in the relationship of obesity with systemic inflammation and insulin resistance have not been completely elucidated. Microbiota includes around 1013 to 1014 microbes harboring the human gut, which are clustered in approximately a thousand different bacterial species. Several studies suggest that imbalance in the intestinal bacterial population could result in obesity, systemic inflammation and metabolic dysfunction. Here, we review the main bacterial groups observed in obesity as well as their possible role in increasing the intestinal permeability and lipopolysaccharide-related endotoxemia. Furthermore, we point out the role of intestinal dysbiosis in the inflammatory activation of macrophages with the ability to infiltrate in the visceral adipose tissue and induce insulin resistance. Finally, we discuss the apparent beneficial use of prebiotics and probiotics in ameliorating both systemic inflammation and metabolic dysfunction. Present information may be useful in the future design of novel therapies focused on treating obesity and insulin resistance by restoring the gut microbiota balance.

Self-sealing atrio-oesophageal fistula as a complication of pulmonary vein isolation: a case report.

Background: Atrio-oesophageal fistulas (AEFs) are an uncommon complication of pulmonary vein ablation, and its diagnosis is challenging. Multidisciplinary interventions and diagnostic imaging are usually required and may play a role in the initial assessment. Case summary: A 69-year-old female with atrial fibrillation who had undergone recent pulmonary vein ablation consulted with unspecific symptoms and sudden hemiparesis. Brain imaging showed pneumocephalus and acute infarcts. Chest computed tomography (CT) was highly suspicious for AEF. Surgical exploration revealed a swollen mediastinum attached to the right inferior pulmonary vein. Discussion: Non-specific symptoms after pulmonary vein ablation should prompt the suspicion of complications. In the presence of fever or neurological deficit, AEF must be suspected and assessed with a contrast-enhanced chest CT, which has become the gold standard. In brain imaging, pneumocephalus and multiple punctate acute infarcts might also indicate the presence of this complication.

Characterization of Homicides in Mexico: Analysis of 2015-2022.

BACKGROUND: In Mexico, homicides are the leading cause of death among men aged 15 to 44 years; however, despite their increase in recent decades, the study of this issue is insufficient, given its magnitude and impact. Therefore, this study aimed to characterize the spatial and temporal patterns and associated factors of homicides in Mexico from 2015 to 2022. METHODS: An analytical cross-sectional study was conducted, analyzing death records from the National Institute of Statistics and Geography's general mortality databases. Simple frequencies and incidence rates per 100,000 inhabitants by sex, year, and state of the Mexican Republic were calculated. Mortality was evaluated by age groups and geographic areas, and bivariate logistic regression models with sociodemographic variables were performed. RESULTS: Records of 229,182 homicides in Mexico were analyzed, with a median age of 33 years, interquartile range 18. A total of 203,898 (88.96%) were men and 25,284 (11.04%) were women. The majority of deaths occurred in public places and were caused by firearms; women had a higher percentage of homicides at home. States with high incidence rates for both sexes were Chihuahua, Zacatecas, Michoacán, Colima, and Estado de México. The total years of life lost were 9.19 million years. The national incidence of homicides in men showed an upward trend from 2015 to 2019; however, in the case of women, this incidence increased in various age groups during the study period. Occupation, education, marital status, and place of occurrence had significant associations in the logistic regression models. CONCLUSIONS: This study provides a spatial-temporal characterization of homicides in Mexico between 2015 and 2022, highlighting the high incidence in men and the upward trend in certain age groups among women. These findings underscore the need for preventive measures and public policies to address this issue in a multisectoral manner.