Carbapenem-Resistant Gram-Negative Bacilli Characterization in a Tertiary Care Center from El Bajio, Mexico.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a major public health concern. We aimed to evaluate the prevalence of CR-GNB and the frequency of carbapenemase-encoding genes in a tertiary referral center from El Bajio, Mexico. A cross-sectional study was conducted between January and October 2022; Gram-negative bacilli (GNB) were screened for in vitro resistance to at least one carbapenem. CR-GNB were further analyzed for carbapenemase-production through phenotypical methods and by real-time PCR for the following genes: blaKPC, blaGES, blaNDM, blaVIM, blaIMP, and blaOXA-48. In total, 37 out of 508 GNB were carbapenem-resistant (7.3%, 95% CI 5.2-9.9). Non-fermenters had higher rates of carbapenem resistance than Enterobacterales (32.5% vs. 2.6%; OR 18.3, 95% CI 8.5-39, p < 0.0001), and Enterobacter cloacae showed higher carbapenem resistance than other Enterobacterales (27% vs. 1.4%; OR 25.9, 95% CI 6.9-95, p < 0.0001). Only 15 (40.5%) CR-GNB had a carbapenemase-encoding gene; Enterobacterales were more likely to have a carbapenemase-encoding gene than non-fermenters (63.6% vs. 30.8%, p = 0.08); blaNDM-1 and blaNDM-5 were the main genes found in Enterobacterales; and blaIMP-75 was the most common for Pseudomonas aeruginosa. The mcr-2 gene was harbored in one polymyxin-resistant E. cloacae. In our setting, NDM was the most common carbapenemase; however, less than half of the CR-GNB showed a carbapenemase-encoding gene.

Crossing the cervicothoracic junction: an evaluation of radiographic alignment, functional outcomes, and patient-reported outcomes.

OBJECTIVE: There is currently no consensus regarding the appropriate lower instrumented vertebra (LIV) for multilevel posterior cervical fusion (PCF) constructs between C7 and crossing the cervicothoracic junction (CTJ). The goal of the present study was to compare postoperative sagittal alignment and functional outcomes among adult patients presenting with cervical myelopathy undergoing multilevel PCF terminating at C7 versus spanning the CTJ. METHODS: A single-institution retrospective analysis (January 2017-December 2018) was performed of patients undergoing multilevel PCF for cervical myelopathy that involved the C6-7 vertebrae. Pre- and postoperative cervical spine radiographs were analyzed for cervical lordosis, cervical sagittal vertical axis (cSVA), and first thoracic (T1) vertebral slope (T1S) in two randomized independent trials. Modified Japanese Orthopaedic Association (mJOA) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores were used to compare functional and patient-reported outcomes at the 12-month postoperative follow-up. RESULTS: Sixty-six consecutive patients undergoing PCF and 53 age-matched controls were included in the study. There were 36 patients in the C7 LIV cohort and 30 patients in the LIV spanning the CTJ cohort. Despite significant correction, patients undergoing fusion remained less lordotic than asymptomatic controls, with a C2-7 Cobb angle of 17.7° versus 25.5° (p < 0.001) and a T1S of 25.6° versus 36.3° (p < 0.001). The CTJ cohort had superior alignment corrections in all radiographic parameters at the 12-month postoperative follow-up compared with the C7 cohort: increase in T1S (ΔT1S 14.1° vs 2.0°, p < 0.001), increase in C2-7 lordosis (ΔC2-7 lordosis 11.7° vs 1.5°, p < 0.001), and decrease in cSVA (ΔcSVA 8.9 vs 5.0 mm, p < 0.001). There were no differences in the mJOA motor and sensory scores between cohorts pre- and postoperatively. The C7 cohort reported significantly better PROMIS scores at 6 months (22.0 ± 3.2 vs 11.5 ± 0.5, p = 0.04) and 12 months (27.0 ± 5.2 vs 13.5 ± 0.9, p = 0.01) postoperatively. CONCLUSIONS: Crossing the CTJ may provide a greater cervical sagittal alignment correction in multilevel PCF surgeries. However, the improved alignment may not be associated with improved functional outcomes as measured by the mJOA scale. A new finding is that crossing the CTJ may be associated with worse patient-reported outcomes at 6 and 12 months of postoperative follow-up as measured by the PROMIS, which should be considered in surgical decision-making. Future prospective studies evaluating long-term radiographic, patient-reported, and functional outcomes are warranted.

Psychosocial burden of recurrent uncomplicated urinary tract infections.

Introduction: Urinary tract infections (UTI) are a leading cause of bacterial infections in women. Despite acute treatment, 30-50% of women who have a UTI will experience a recurrence within 6-12 months. In this review, the focus will be on the personal psychosocial impacts of recurrent UTI. Methods: A PubMed/MEDLINE literature search was carried out from 2000 to 2020 in order to identify any recent high-quality meta-analyses or systematic reviews on these topics. Results: One systematic review was found appropriate for this manuscript. Concerning impact on quality of life (QoL) and daily activities, a reduced quality of both intimate and social relationships, self-esteem, and capacity for work was found due to recurrent UTI. Social function was substantially more reduced than physical function. In one study, the greatest reduction overall was in mental role functioning, whereas in another study, mental health reductions were not substantially greater than those of physical health. About one third of women suffered from UTI very often or often after sexual intercourse, and more than half of the patients stated that sexual relations were negatively influenced by UTI. Data from the GESPRIT study suggest that prophylaxis for recurrent UTI is underutilized, because less than 40% of the study population were offered prophylaxis after experiencing three UTI per year, despite all surveyed participants being willing to undertake at least one of the prophylactic measures listed in the survey. Conclusions: Little data on the psychosocial impact of recurrent UTI are available. Therefore, future studies must also incorporate QoL assessments as key outcome measures.

An application of interactive fuzzy optimization model for redesigning supply chain for resilience.

Supply chain disruptions compel professionals all over the world to consider alternate strategies for addressing these issues and remaining profitable in the future. In this study, we considered a four-stage global supply chain and designed the network with the objectives of maximizing profit and minimizing disruption risk. We quantified and modeled disruption risk as a function of the geographic diversification of facilities called supply density (evaluated based on the interstage distance between nodes) to mitigate the risk caused by disruptions. Furthermore, we developed a bi-criteria mixed-integer linear programming model for designing the supply chain in order to maximize profit and supply density. We propose an interactive fuzzy optimization algorithm that generates efficient frontiers by systematically taking decision-maker inputs and solves the bi-criteria model problem in the context of a realistic example. We also conducted disruption analysis using a discrete set of disruption scenarios to determine the advantages of the network design from the bi-criteria model over the traditional profit maximization model. Our study demonstrates that the network design from the bi-criteria model has a 2% higher expected profit and a 2.2% lower profit variance under disruption than the traditional profit maximization solution. We envisage that this model will help firms evaluate the trade-offs between mitigation benefits and mitigation costs.

A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance.

OBJECTIVES: Uncomplicated urinary tract infections (uUTIs) are a common problem in female patients. Management is mainly based on empirical prescribing, but there are concerns about overtreatment and antimicrobial resistance (AMR), especially in patients with recurrent uUTIs. METHODS: A multidisciplinary panel of experts met to discuss diagnosis, treatment, prevention, guidelines, AMR, clinical trial design and the impact of COVID-19 on clinical practice. RESULTS: Symptoms remain the cornerstone of uUTI diagnosis, and urine culture is necessary only when empirical treatment fails or rapid recurrence of symptoms or AMR is suspected. Specific antimicrobials are first-line therapy (typically nitrofurantoin, fosfomycin, trimethoprim/sulfamethoxazole and pivmecillinam, dependent on availability and local resistance data). Fluoroquinolones are not first-line options for uUTIs primarily due to safety concerns but also rising resistance rates. High-quality data to support most non-antimicrobial approaches are lacking. Local AMR data specific to community-acquired uUTIs are needed, but representative information is difficult to obtain; instead, identification of risk factors for AMR can provide a basis to guide empirical antimicrobial prescribing. The COVID-19 pandemic has impacted the management of uUTIs in some countries and may have long-lasting implications for future models of care. CONCLUSION: Management of uUTIs in female patients can be improved without increasing complexity, including simplified diagnosis and empirical antimicrobial prescribing based on patient characteristics, including a review of recent antimicrobial use and past pathogen resistance profiles, drug availability and guidelines. Current data for non-antimicrobial approaches are limited. The influence of COVID-19 on telehealth could provide an opportunity to enhance patient care in the long term.

Pulmonary Large Cell Neuroendocrine Carcinoma Associated With Lambert-Eaton Syndrome.

Lambert-Eaton syndrome is a rare paraneoplastic disorder of the neuromuscular junction, characterized by impaired release of acetylcholine, which causes proximal muscle weakness, depressed tendon reflexes, and autonomic changes. Most cases of Lambert-Eaton syndrome present in small-cell lung carcinoma, and only a few cases have been reported in other lung subtypes. Herein, we report a case of 69 years old male patient with Lambert-Eaton syndrome as a rare association with a pulmonary large-cell neuroendocrine carcinoma, which presented 5 months before neoplasm diagnosis. A lobectomy was auspiciously performed. A review of the literature is also presented.

Current Clinical Applications of Intracranial Vessel Wall MR Imaging.

Intracranial vessel wall MR imaging (VWI) is increasingly being used as a valuable adjunct to conventional angiographic imaging techniques. This article will provide an updated review on intracranial VWI protocols and image interpretation. We review VWI technical considerations, describe common VWI imaging features of different intracranial vasculopathies and show illustrative cases. We review the role of VWI for differentiating among steno-occlusive vasculopathies, such as intracranial atherosclerotic plaque, dissections and Moyamoya disease. We also highlight how VWI may be used for the diagnostic work-up and surveillance of patients with vasculitis of the central nervous system and cerebral aneurysms.

A systematic literature review of quantitative models for sustainable supply chain management.

Supply chain management is the basis for the execution of operations, being considered as the core of the business function in the 21st century. On the other hand, at present, factors such as the reduction of natural resources, the search for competitive advantages, government laws and global agreements, have generated a greater interest in the sustainable development, which, in order to achieve it, industries need to rethink and plan their supply chain considering a path of sustainability. So sustainable supply chain management emerges as a means to integrate stakeholders' concern for profit and cost reduction with environmental and social requirements, attracting significant interest among managers, researchers and practitioners. The main objective of this study is to provide a synthesis of the key elements of the quantitative model offerings that use sustainability indicators in the design and management of forward supply chains. To achieve this objective, we developed a systematic literature review that includes seventy articles published during the last decade in peer-reviewed journals in English language. In addition a 4 W's analysis (When, Who, What, and Where) is applied and three structural dimensions are defined and grouped by categories: Supply chain management, modeling and sustainability. As part of the results we evidenced a continuous growth in the scientific production of this type of articles, with a predominance of deterministic mathematical programming models with an environmental economic perspective. Finally, we identified research gaps, highlighting the lack of integral inclusion of a life cycle analysis in the design of supply chain networks.

Prenatal indole-3-carbinol administration activates aryl hydrocarbon receptor-responsive genes and attenuates lung injury in a bronchopulmonary dysplasia model.

Hyperoxia-hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia-hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway (Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia-hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia-hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup's lungs and hence attenuates lung damage caused by hyperoxia-hypoxia exposure in newborns.

Metastatic colorectal micropapillary carcinoma presenting as lymphangitic lung carcinomatosis.

Pulmonary lymphangitic carcinomatosis denotes the infiltration of tumor cells into the lung parenchymal lymphatic channels. Breast, lung, stomach, and colon adenocarcinoma are the most common origin of this invasion pattern. The micropapillary variant of colorectal adenocarcinoma has a high rate of lymph node metastases and poor overall survival. A 49 year-old man with a 6 months history of persistent cough and a relevant occupational chemical exposure had a computed tomography that showed bilateral interstitial lung infiltrates. The lung biopsy demonstrated a micropapillary adenocarcinoma with diffusely obstruction of the lung parenchymal lymphatics. The immunohistochemistry confirmed a colorectal origin. The colonoscopy evidenced a mass with identical morphology. Colorectal micropapillary carcinoma with metastatic lung lymphangitic carcinomatosis can occur, as a persistent cough, as presenting symptom in extraordinarily rare cases. To the best of our knowledge, this is the first case of an alive patient with colorectal metastatic micropapillary carcinoma presenting with lymphangitic lung carcinomatosis.

Risk factors and predisposing conditions for urinary tract infection.

Understanding individual and population-specific risk factors associated with recurrent urinary tract infections (UTIs) can help physicians tailor prophylactic strategies. Frequent intercourse, vulvovaginal atrophy, change of the local bacterial flora, history of UTIs during premenopause or in childhood, family history, and a nonsecretor blood type are substantiated risk factors for recurrent uncomplicated UTIs. This is a narrative review based on relevant literature according to the experience and expertise of the authors. Asymptomatic bacteriuria is generally benign; however, during pregnancy it is more common and is associated with an increased likelihood of symptomatic infection, which may harm the mother or fetus. Screening of pregnant women and appropriate treatment with antimicrobials must be balanced with the potential for adverse treatment-related outcomes; appropriate prophylaxis should be considered where possible. High-quality data are currently lacking on risks related to asymptomatic bacteriuria in pregnancy and further data in this hard-to-study population should be a primary concern for researchers. Incomplete voiding represents the primary risk factor for UTIs associated with conditions such as urinary incontinence and prolapse. Correcting the presence of residual urine remains the most effective prophylaxis in these populations. Bladder function alters throughout life; however, changes in function may be particularly profound in clinical populations at high risk of UTIs. Patients with neurogenic bladder will also likely have other evolving medical issues which increase the risk of UTIs, such as repeated catheterization and increasing residual urine volume. More aggressive antimicrobial prophylactic strategies may be appropriate in these patients. Again, the paucity of data on prophylaxis in these high-risk patients requires the attention of the research community.

Prevention of recurrent urinary tract infections: bridging the gap between clinical practice and guidelines in Latin America.

The branches of the immune system work in concert to defend against pathogens and prevent tissue damage due to excessive inflammation. Uropathogens in general, and uropathogenic Escherichia coli (UPEC) in particular, have evolved a diverse range of virulence mechanisms to avoid detection and destruction by the mucosal immune system of the urinary tract. Research towards a vaccine active against UPEC continues but has yet to be successful. Orally administered immunomodulatory bacterial lysates both stimulate and modulate the immune response in the urinary tract via the integrated mucosal immune system. The 2018 European Association of Urology (EAU) guidelines on treating acute uncomplicated cystitis recommend aiming for rapid resolution of symptoms, reduction of morbidity, and prophylaxis against reinfection. Recommended short-term antibiotic therapy has the advantage of good compliance, low cost, few adverse events, and low impact on bacterial flora. Antibiotic treatment of asymptomatic bacteriuria is only indicated during pregnancy and before invasive interventions. For recurrent infection, prophylaxis using behavioral modification and counseling should be employed first, then nonantibiotic prophylaxis, and, finally, low-dose continuous or postcoital antibiotic prophylaxis. The 2018 EAU guidelines give a strong recommendation for the oral bacterial lysate immunomodulator OM-89. All other nonantibiotic prophylactic strategies require more data, except for topical estrogen for postmenopausal women. For last-resort antibiotic prophylaxis, nitrofurantoin or fosfomycin trometamol are recommended. Guidelines for Latin America are currently being drafted, taking into account the unique ethnicity, availability of medicines, prevalence of antibiotic resistance, and healthcare practices found throughout the region.

Extracellular matrix and fibroblast injection produces pterygium-like lesion in rabbits.

BACKGROUND: Translational research to develop pharmaceutical and surgical treatments for pterygium requires a reliable and easy to produce animal model. Extracellular matrix and fibroblast are important components of pterygium. The aim of this study was to analyze the effect of the subconjunctival injection of fibroblast cells (NIH3T3 cell line) and exogenous extracellular matrix in rabbits in producing a pterygium-like lesion. METHODS: Six 3-month-old white New Zealand rabbits were injected with 20,000 NIH3T3 cells and 5 µL of Matrigel in the right conjunctiva, and with only 5 µL of Matrigel in the left conjunctiva. The eyes were photographed under a magnification of 16× using a 12-megapixel digital camera attached to the microscope on day 1, 3 and 7. Conjunctival vascularization was measured by analyzing images to measure red pixel saturation. Area of corneal and conjunctival fibrovascular tissue formation on the site of injection was assessed by analyzing the images on day 3 and 7 using area measurement software. Histopathologic characteristics were determined in the rabbit tissues and compared with a human primary pterygium. RESULTS: The two treatments promoted growth of conjunctival fibrovascular tissue at day 7. The red pixel saturation and area of fibrovascular tissue developed was significantly higher in right eyes (p < 0.05). Tissues from both treatments showed neovascularization in lesser extent to that observed in human pterygium. Acanthosis, stromal inflammation, and edema were found in tissues of both treatments. No elastosis was found in either treatment. CONCLUSIONS: Matrigel alone or in combination with NIH3T3 cells injected into the rabbits' conjunctiva can promote tissue growth with characteristics of human pterygium, including neovascularization, acanthosis, stromal inflammation, and edema. The combination of Matrigel with NIH3T3 cells seems to have an additive effect on the size and redness of the pterygium-like tissue developed.

Financial risk of increasing the follow-up period of breast cancer treatment currently covered by the Social Protection System in Health in México.

BACKGROUND: The objective of this work is to estimate the financial impact of increasing the monitoring period for breast cancer, which is financed by the Sistema de Protección Social en Salud (SPSS-Social Protection System in Health). METHODS: A micro-simulation model was developed to monitor a cohort of patients with breast cancer, and also an estimation was made on the probability of surviving the monitoring period financed by the SPSS. Using the Monte Carlo simulation, the maximum expected cost was estimated to broaden such monitoring. Morbimortality information of the Ministry of Health and cases of breast cancer treated by the SPSS were used. RESULTS: Between 2013 and 2026, the financial resources to provide monitoring during 10 years to women diagnosed with breast cancer would reach up to $3607.40 million pesos on a base scenario, $4151.79 million pesos on the pessimistic scenario and $3414.85 million pesos on an optimistic scenario. In the base scenario, additional expenditure represents an annual increase of 9.1% of resources allocated to treating this disease, and 3.0% of the availability of the resources for the Fondo de Protección contra Gastos Catastróficos (FPGC-Fund for Protection against Catastrophic Expenditure). CONCLUSIONS: Increasing monitoring for patients with breast cancer would not represent a financial risk to the sustainability of the FPGC, and could increase patients survival and life quality.

Extracellular matrix and fibroblast injection produces pterygium-like lesion in rabbits

BACKGROUND: Translational research to develop pharmaceutical and surgical treatments for pterygium requires a reliable and easy to produce animal model. Extracellular matrix and fibroblast are important components of pterygium. The aim of this study was to analyze the effect of the subconjunctival injection of fibroblast cells (NIH3T3 cell line) and exogenous extracellular matrix in rabbits in producing a pterygium-like lesion. METHODS: Six 3-month-old white New Zealand rabbits were injected with 20,000 NIH3T3 cells and 5 µL of Matrigel in the right conjunctiva, and with only 5 µL of Matrigel in the left conjunctiva. The eyes were photographed under a magnification of 16× using a 12-megapixel digital camera attached to the microscope on day 1,3 and 7. Conjunctival vascularization was measured by analyzing images to measure red pixel saturation. Area of corneal and conjunctival fibrovascular tissue formation on the site of injection was assessed by analyzing the images on day 3 and 7 using area measurement software. Histopathologic characteristics were determined in the rabbit tissues and compared with a human primary pterygium. RESULTS: The two treatments promoted growth of conjunctival fibrovascular tissue at day 7. The red pixel saturation and area of fibrovascular tissue developed was significantly higher in right eyes (p < 0.05). Tissues from both treatments showed neovascularization in lesser extent to that observed in human pterygium. Acanthosis, stromal inflammation, and edema were found in tissues of both treatments. No elastosis was found in either treatment. CONCLUSIONS: Matrigel alone or in combination with NIH3T3 cells injected into the rabbits' conjunctiva can promote tissue growth with characteristics of human pterygium, including neovascularization, acanthosis, stromal inflammation, and edema. The combination of Matrigel with NIH3T3 cells seems to have an additive effect on the size and redness of the pterygium-like tissue developed.

Una nueva forma de aprender patología: laboratorio virtual de patología / A novel approach to learn pathology: virtual pathology laboratory

INTRODUCCIÓN: Aprender patología es un reto que requiere el desarrollo de habilidades para la identificación de estados anormales del cuerpo humano, trastornos funcionales y causas que los producen. MATERIAL Y MÉTODOS: El objetivo de este estudio fue evaluar si la incorporación de recursos en línea con imágenes digitales, diapositivas y un sistema de gestión de aprendizaje proporciona una enseñanza práctica y efectiva para los estudiantes de medicina, dentro y fuera del aula. El estudio se realizó durante 2015, con una muestra de 83 estudiantes del curso de Patología II. Se utilizó un instrumento para medir el grado de satisfacción del alumno, mediante una escala Likert del 1 al 5, que va de totalmente en desacuerdo hasta totalmente de acuerdo. Se utiliza un acercamiento cuantitativo para realizar un análisis descriptivo de las valoraciones otorgadas. RESULTADOS: Con una media del 4,78, los alumnos indican una clara aceptación por el Laboratorio virtual de patología, basándose en la calidad de los casos e imágenes disponibles. Además, respecto a si la enseñanza mediante la exposición a casos clínicos con soporte de imágenes digitalizadas les ha sido útil para su formación práctica en la medicina, se obtuvo una media de 4,48. CONCLUSIONES: Las respuestas obtenidas por los estudiantes indican que la propuesta tiene ventajas considerables, como facilidad en el acceso a las imágenes y la información, fomento del aprendizaje autodirigido y colaborativo, así como apoyo a la construcción del conocimiento; sin embargo, aún existen retos y limitaciones propias del formato, como una menor interacción directa con el profesor

INTRODUCTION: Learning pathology is a challenge that requires the development of skills for the identification of abnormal states in the human body, as well as its functional disorders and causes. MATERIAL AND METHODS: This study assesses whether an online approach, that combines digital images, online slides and a learning management system, provides a practical and effective teaching method for medical students, both inside and outside the classroom. In 2015, an online survey was conducted with a sample of (83) students of the Pathology class, in order to assess student satisfaction with a Virtual Pathology Lab. A 1 to 5 Likert scale was used, where 1 meant total disagreement, and 5 for total agreement. The selected method is quantitative to provide a descriptive analysis of student perceptions. RESULTS: A mean score of 4.78 was obtained, indicating a clear acceptance of the Virtual Pathology Lab, based on the quality of the cases and images available. As regards students' beliefs that learning with clinical cases, digital images, and digitalised slides has been useful for their medical practical training, a mean score of 4.48 media was achieved. CONCLUSIONS: The responses by students indicate considerable advantages, including that all students have easy access to images and course information. It favours self-directed, as well as collaborative learning. However, there are still few limitations inherent to the format, such as less direct interaction with the teacher

Does nitrogen fertilization history affects short-term microbial responses and chemical properties of soils submitted to different glyphosate concentrations?

The use of nitrogen (N) fertilizer and glyphosate-based herbicides is increasing worldwide, with agriculture holding the largest market share. The agronomic and socioeconomic utilities of glyphosate are well established; however, our knowledge of the potential effects of glyphosate applied in the presence or absence of long-term N fertilization on microbial functional activities and the availability of soil nutrients remains limited. Using an ex situ approach with soils that did (N+) or did not (N0) receive synthetic N fertilization for 6 years, we assessed the impact of different rates (no glyphosate, CK; field rate, FR; 100 × field rate, 100FR) of glyphosate application on biological and chemical parameters. We observed that, after immediate application (1 day), the highest dose of glyphosate (100FR) negatively affected the alkaline phosphatase (AlP) activity in soils without N fertilization history and decreased the cation exchange capacity (CEC) in N0 compared to CK and FR treatments with N+. Conversely, the 100FR application increased nitrate (NO3-) and available phosphorus (PO43-) regardless of N fertilization history. Then, after 8 and 15 days, the N+\100FR and N+\FR treatments exhibited the lowest values for dehydrogenase (DH) and AlP activities, respectively, while urease (URE) activity was mainly affected by N fertilization. After 15 days and irrespective of N fertilization history, the FR glyphosate application negatively affected the degradation of carbon substrates by microbial communities (expressed as the average well color development, AWCD). By contrast, the 100FR treatment positively affected AWCD, increasing PO43- by 5 and 16% and NO3- by 126 and 119% in the N+ and N0 treatments, respectively. In addition, the 100FR treatment resulted in an increase in the average net nitrification rate. Principal component analysis revealed that the 100FR glyphosate treatment selected microbial communities that were able to metabolize amine substrates. Overall, the lack of N fertilization in the 6 past years combined with the highest glyphosate application rate (100FR) induced the highest values of AWCD, functional diversity, NO3-, PO43- and nitrification. We concluded that the intensive use of N fertilization for 6 years may change the non-target effects of glyphosate application on enzyme activities. The functional activities, nitrification and nutrient contents were increased by glyphosate only when applied at 100 times the field application rate.

At 10 years of chlormadinone use in Latin America: a review.

Chlormadinone acetate (CMA) is a progesterone derivative (17α-acetoxy-6-chloro-4,6-pregnadiene-3,20-dione), first synthesized in 1961. It was used as progestin-based hormone replacement therapy; since 1999 it was first used for oral contraception combined with ethinyl estradiol (EE). CMA exerts a potent progestagenic effect, about one third higher than that observed with endogenous progesterone. CMA is also an anti-estrogen, showing no androgenic effects (at birth control dose). Unlike progesterone, it has a mild glucosteroidal effect with no anti-mineralocorticoid effect at all. These biological actions have allowed CMA to have a role for therapeutic use in dysmenorrhea, hyperandrogenism, and as a contraceptive agent. In addition, CMA has exhibited beneficial neuroendocrine effects on women's mood. CMA-EE combination has shown excellent contraceptive efficacy, high tolerability, and compliance due to its risk-benefit profile, having additional benefits on skin and hair, such as reduction of seborrhea and acne. Metabolic tolerance of CMA has been demonstrated in several clinical studies. Currently, CMA is formulated to be taken as oral caplets in a 21 caplets package containing 0.03 mg/EE and 2 mg CMA per pill with/without seven placebo additional pills. Another presentation has 24 caplets containing 0.02 mg/EE and 2 mg CMA plus four placebo pills.

[Resistance to thyroid hormone and Hashimoto's thyroiditis]. / Resistencia a hormonas tiroideas y tiroiditis de Hashimoto.

BACKGROUND: Resistance to thyroid hormone (RTH) is a rare condition characterized by elevation of thyroid stimulating hormone (TSH) and thyroid hormones (TH). Its association with Hashimoto's thyroiditis was described in 1993 and occurs in 1 of 1.3 million births. CLINICAL CASE: We present a female patient with a family history of hypothyroidism. The patient's condition began in 2008 with symptoms of hyperthyroidism, elevated triiodothyronine (T3), thyroxine (T4) and TSH levels. Thyroid scan showed hypermetabolic activity and she was positive for anti-peroxidase antibodies (anti-TPO). After administration of thiamazole, TSH increased. In 2009 she was diagnosed with clinical hypothyroidism, high levels of TSH, and normal T3 and T4 levels. Levothyroxine was prescribed but TSH increased and she presented clinical signs of hyperthyroidism. Patient abandoned treatment after 1 month. Her symptoms fluctuated among hyperthyroidism, euthyroidism and hypothyroidism. In 2010 she presented tachycardia, weight loss, and high T3, T4 and TSH levels. Thyrotropin-secreting adenoma (TSHoma) was suspected and ruled out by magnetic resonance imaging (MRI). Thyrotropin releasing hormone (TRH) test was performed. TSH increased and the α-subunit of pituitary hormones retained low levels. CONCLUSIONS: RTH diagnosis requires exclusion of a TSHoma because both present a similar pattern according to thyroid tests. The association between Hashimoto's thyroiditis and RTH is not well known. This pathological condition has a mutated TRß gene in 75% of the cases.