Clostridial Myonecrosis: A Comprehensive Review of Toxin Pathophysiology and Management Strategies.

Clostridial myonecrosis, commonly known as gas gangrene (GG), is a rapidly progressing and potentially fatal bacterial infection that primarily affects muscle and soft tissue. In the United States, the incidence of GG is roughly 1000 cases per year, while, in developing countries, the incidence is higher. This condition is most often caused by Clostridium perfringens, a Gram-positive, spore-forming anaerobic bacterium widely distributed in the environment, although other Clostridium species have also been reported to cause GG. The CP genome contains over 200 transport-related genes, including ABC transporters, which facilitate the uptake of sugars, amino acids, nucleotides, and ions from the host environment. There are two main subtypes of GG: traumatic GG, resulting from injuries that introduce Clostridium spores into deep tissue, where anaerobic conditions allow for bacterial growth and toxin production, and spontaneous GG, which is rarer and often occurs in immunocompromised patients. Clostridium species produce various toxins (e.g., alpha, theta, beta) that induce specific downstream signaling changes in cellular pathways, causing apoptosis or severe, fatal immunological conditions. For example, the Clostridium perfringens alpha toxin (CPA) targets the host cell's plasma membrane, hydrolyzing sphingomyelin and phosphatidylcholine, which triggers necrosis and apoptosis. The clinical manifestations of clostridial myonecrosis vary. Some patients experience the sudden onset of severe pain, swelling, and muscle tenderness, with the infection progressing rapidly to widespread tissue necrosis, systemic toxicity, and, if untreated, death. Other patients present with discharge, pain, and features of cellulitis. The diagnosis of GG primarily involves clinical evaluation, imaging studies such as X-rays, computer tomography (CT) scans, and culture. The treatment of GG involves surgical exploration, broad-spectrum antibiotics, antitoxin, and hyperbaric oxygen therapy, which is considered an adjunctive treatment to inhibit anaerobic bacterial growth and enhance the antibiotic efficacy. Early recognition and prompt, comprehensive treatment are critical to improving the outcomes for patients affected by this severe and life-threatening condition.

Refractive Errors of School Children from Economically Disadvantaged Areas in Northwest México.

Background: Refractive errors, including myopia, hyperopia, and astigmatism, are the leading causes of visual impairment in school-aged children and can significantly impact their academic performance and quality of life. This study aimed to assess the prevalence of refractive errors among school children from economically disadvantaged areas in Northwest México, using a consistent methodology to facilitate comparison with global data. Methods: We adopted the Refractive Error Study in Children (RESC) protocol by the World Health Organization to examine the prevalence of myopia, hyperopia, and astigmatism. The study comprised a systematic sampling of children aged 6 to 18 years from diverse schools in Northwest México. Trained optometrists conducted visual acuity testing and autorefraction, while ophthalmologists performed cycloplegic refraction to ensure accuracy. Results: The study found a myopia (SE ≤-1.50 D at least one eye) prevalence of 14.55% (95% CI: 13.27-15.91), with a higher incidence in females (6.92%) compared to males (6.00%) in at least one eye. Hyperopia (SE ≥ +1.00 D at least one eye) was less common, at 3.23% (95% CI: 2.61-3.95), with a slightly higher occurrence in males in at least one eye. Astigmatism (Cylinder ≥ 0.75 D at least one eye) was present in 18.63% (95% CI: 17.21-20.12) of the students in at least one eye, with no significant difference between genders. These findings are consistent with other studies in regions such as Puerto Rico and Iran, indicating widespread refractive error issues among schoolchildren. Conclusions: The high prevalence of refractive errors, particularly myopia and astigmatism, highlights the critical need for regular vision screenings in schools and the implementation of public health interventions to provide corrective eyewear. Our study confirms the importance of utilizing standardized methodologies like the RESC protocol to compare refractive error prevalence across different geographical and socio-economic contexts, thereby informing global public health strategies.

Radiation and Chemical Program Research for Multi-Utility and Repurposed Countermeasures: A US Department of Health and Human Services Agencies Perspective.

Although chemical and radiological agents cause toxicity through different mechanisms, the multiorgan injuries caused by these threats share similarities that convene on the level of basic biological responses. This publication will discuss these areas of convergence and explore "multi-utility" approaches that could be leveraged to address common injury mechanisms underlying actions of chemical and radiological agents in a threat-agnostic manner. In addition, we will provide an overview of the current state of radiological and chemical threat research, discuss the US Government's efforts toward medical preparedness, and identify potential areas for collaboration geared toward enhancing preparedness and response against radiological and chemical threats. We also will discuss previous regulatory experience to provide insight on how to navigate regulatory paths for US Food and Drug Administration (FDA) approval/licensure/clearance for products addressing chemical or radiological/nuclear threats. This publication follows a 2022 trans-agency meeting titled, "Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures," sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Discussions from this meeting explored the overlapping nature of radiation and chemical injury and spurred increased interest in how preparedness for one threat leads to preparedness for the other. Herein, subject matter experts from the NIAID and the Biomedical Advanced Research and Development Authority (BARDA), a part of the Administration for Strategic Preparedness and Response (ASPR), summarize the knowledge gained from recently funded biomedical research, as well as insights from the 2022 meeting. These topics include identification of common areas for collaboration, potential use of biomarkers of injury to identify injuries caused by both hazards, and common and widely available treatments that could treat damage caused by radiological or chemical threats.

Barriers to early diagnosis and management of oral cancer in Latin America and the Caribbean.

OBJECTIVE: This study aimed to explore perceived barriers to early diagnosis and management of oral cancer, as well as potential pathways for improvement in Latin America and the Caribbean (LAC). METHODS: This cross-sectional study used a self-administered online questionnaire created via the Research Electronic Data Capture platform. The survey was distributed to health professionals trained in Oral Medicine, Oral Pathology, Oral and Maxillofacial Surgery, and Dentists with clinical and academic expertise in oral potentially malignant disorder (OPMD) and oral cancer. Data obtained were systematically organized and analyzed descriptively using Microsoft Excel. RESULTS: Twenty-three professionals from 21 LAC countries participated. Major barriers included the limited implementation of OPMD and oral cancer control plans (17.4%), low compulsory reporting for OPMD (8.7%) and oral cancer (34.8%), unclear referral pathways for OPMD (34.8%) and oral cancer (43.5%), and a shortage of trained professionals (8.7%). Participants endorsed the utility of online education (100%) and telemedicine (91.3%). CONCLUSION: The survey highlights major perceived barriers to early diagnosis and management of OPMD and oral cancer in LAC, as well as potential avenues for improvement.

Krokodil-Associated Cutaneous Ulceration, Cardiac Arrhythmia and Thrombi.

Krokodil, the street name for desomorphine, has emerged as a deadly and alarming drug phenomenon in recent years. This report delves into the intricate relationship between krokodil abuse, its adverse effects on the skin and its profound impact on cardiovascular events. Our patient developed a non-healing cutaneous ulceration associated with an acute onset of cardiac arrhythmia, as well as bilateral upper extremity acute deep-vein thrombosis. LEARNING POINTS: The use of Krokodil can lead to chronic non-healing ulcerations.It is important to be aware that new cardiac arrhythmias can arise in individuals using krokodil.Acute bilateral upper extremity thrombosis can occur as a complication in patients using krokodil.

Development of purpura fulminans by Candida glabrata and Mucormycosis infection post-surgery.

Purpura fulminans (PF) is a disorder with multifactorial causes that lead to acute localize skin microvasculature thrombosis. PF can be classified as one of the manifestations of disseminated vascular coagulation (DIC). Although, there are three types of PF including hereditary (autosomal dominant) due to mutations in single nucleotide polymorphisms (PROC and PROS1) and serpin family C member 1 (SERPINC1) genes. Idiopathic or acquired type of PF is complex and the pathophysiology is ambiguous, however, low levels of protein C and S were observed. The acute infectious form of PF occurs post-bacterial infection (e.g., Neisseria). The clinical presentation is limited to skin findings or systematic manifestation (shock, disseminated intravascular coagulation, or death). We are presenting two cases of PF sharing similar clinical manifestations developed within 12 h post-operatively with distinct micro-organisms infection. The first patient's wound culture grew fluffy mold, and the sequencing confirmed a Mucormycosis, Absidia corymbifera species, while the second patient was infected by cutaneous Candida glabrata which led to the development of PF. Our findings suggest that surgery can trigger local immunological responses in susceptible individuals such as concealed protein C and S deficiency or microorganism toxins that initiated the rapidly developing of PF in those patients.

National sex- and age-specific burden of blindness and vision impairment by cause in Mexico in 2019: a secondary analysis of the Global Burden of Disease Study 2019.

Background: Reliable national estimations for blindness and vision impairment are fundamental to assessing their burden and developing public health policies. However, no comprehensive analysis is available for Mexico. Therefore, in this observational study we describe the national burden of blindness and vision loss by cause and severity during 2019. Methods: Using public data from the Global Burden of Disease (GBD) study 2019, we present national prevalence and years lived with disability (YLDs) counts and crude and age-standardized rates (per 100,000 people) of total, severity- and cause-specific blindness and vision impairment with 95% uncertainty intervals (UIs) by sex and age group. Findings: In Mexico, the burden of blindness and vision impairment was estimated at 11.01 million (95% UI, 9.25-13.11) prevalent cases and 384.96 thousand (259.57-544.24) YLDs during 2019. Uncorrected presbyopia caused the highest burden (6.06 million cases, 4.36-8.08), whereas severe vision loss and blindness affected 619.40 thousand (539.40-717.73) and 513.84 thousand (450.59-570.98) people, respectively. Near vision loss and refraction disorders caused 78.7% of the cases, whereas neonatal disorders and age-related macular degeneration were among the least frequent. Refraction disorders were the main cause of moderate and severe vision loss (61.44 and 35.43%), and cataracts were the second most frequent cause of blindness (26.73%). Females suffered an overall higher burden of blindness and vision impairment (54.99% and 52.85% of the total cases and YLDs), and people >50 years of age suffered the highest burden, with people between 70 and 74 years being the most affected. Interpretation: Vision loss represents a public health problem in Mexico, with women and older people being the most affected. Although the causes of vision loss contribute differentially to the severity of visual impairment, most of the impairment is avoidable. Consequently, a concerted effort at different levels is needed to alleviate this burden. Funding: This study received no funding.

Doxorubicin Activity Is Modulated by Traditional Herbal Extracts in a 2D and 3D Multicellular Sphere Model of Leukemia.

The modulation of the tumor microenvironment by natural products may play a significant role in the response of tumor cells to chemotherapy. In this study, we evaluated the effect of extracts derived from P2Et (Caesalpinia spinosa) and Anamú-SC (Petiveria alliacea) plants, previously studied by our group, on the viability and ROS levels in the K562 cell line (Pgp- and Pgp+), endothelial cells (ECs, Eahy.926 cell line) and mesenchymal stem cells (MSC) cultured in 2D and 3D. The results show that: (a) the two botanical extracts are selective on tumor cells compared to doxorubicin (DX), (b) cytotoxicity is independent of the modulation of intracellular ROS for plant extracts, unlike DX, (c) the interaction with DX can be influenced by chemical complexity and the expression of Pgp, (d) the 3D culture shows a greater sensitivity of the tumor cells to chemotherapy, in co-treatment with the extracts. In conclusion, the effect of the extracts on the viability of leukemia cells was modified in multicellular spheroids with MSC and EC, suggesting that the in vitro evaluation of these interactions can contribute to the comprehension of the pharmacodynamics of the botanical drugs.

Prior viral infection determines the mode and severity of monkeypox virus.

OBJECTIVES: Monkeypox (MPox) is a zoonotic virus in the genus Orthopoxvirus. It is transmitted from animal to human, and between humans. The clinical presentations vary, starting with a prodrome phase to different skin findings and systemic complications. METHODS: We present two distinctive cases of MPox co-infected with other viruses (hepatitis C virus [HCV] and HIV) by clinical and histopathological analysis. RESULTS: Surprisingly, the MPox patient with a history of HCV developed different skin pathological characteristics (less severe inflammatory changes than the classic patient with HCV or MPox alone). In contrast, patients living with HIV presenting with MPox had severe inflammatory cutaneous changes and distortion of the skin architecture. CONCLUSION: Our findings strongly suggest that MPox infections likely occur in the presence of one or more previous other viral infections, and the prior infection with specific microbes determines the severity of MPox infection.

JAPANESE ENCEPHALITIS VIRUS TRIGGERED OVERLAPPING MILLER FISHER SYNDROME WITH BICKERSTAFF ENCEPHALITIS IN A YOUNG FILIPINO CRUISE LINE WORKER.

Japanese encephalitis virus is an RNA flavivirus and one of the rare pathogens that can cause encephalitis. The main vector is the Culex tritaeniorhynchus mosquito. The virus is very close in pathophysiology and structure to the West Nile and St. Louis encephalitis viruses. It is endemic in Asia and Western Pacific areas, mostly during the summer; only a few cases have been reported outside those regions. We present the case of a young Filipino cruise line male worker with signs and symptoms of Japanese encephalitis concomitantly with Miller Fisher syndrome and Bickerstaff brainstem encephalitis. The patient developed obtundation, ataxia, areflexia, flaccid paralysis, and ophthalmoplegia, which were preceded by a few days of constitutional symptoms (fever, malaise, fatigue and anorexia). Physical examination showed various stages of erythema nodosum on the lower extremities. Analysis of cerebrospinal fluid was positive for anti-GQ1b, West Nile IgG and Japanese encephalitis IgM. Despite the neurological complications and bradyarrhythmia occurring during hospitalization, the patient recovered completely under our regimen. LEARNING POINTS: Insidious onset of bilateral paralysis preceded by fever is most likely encephalitis.Japanese encephalitis virus led to the development of variant forms of Guillain-Barré syndrome in our patient.Supportive care resulted in significant recovery despite the severity of the condition.

A Novel Framework for Generating Personalized Network Datasets for NIDS Based on Traffic Aggregation.

In this paper, we addressed the problem of dataset scarcity for the task of network intrusion detection. Our main contribution was to develop a framework that provides a complete process for generating network traffic datasets based on the aggregation of real network traces. In addition, we proposed a set of tools for attribute extraction and labeling of traffic sessions. A new dataset with botnet network traffic was generated by the framework to assess our proposed method with machine learning algorithms suitable for unbalanced data. The performance of the classifiers was evaluated in terms of macro-averages of F1-score (0.97) and the Matthews Correlation Coefficient (0.94), showing a good overall performance average.

Pneumocystis jirovecii pneumonia and deep vein thrombosis in a patient with glioblastoma multiforme.

We present a case of disseminated Pneumocystis jirovecii pneumonia in a patient with a medical history of glioblastoma multiforme associated with acute deep-vein thrombosis. The patient presented to the emergency department with clinical features of pulmonary infection, and the chest images showed pneumonia. Antibiotics were initiated (azithromycin, cefepime, and vancomycin) and the patient was transferred to the ward for further management, where the condition of the patient continued to worsen over the second day. The patient developed bilateral lower extremity swelling and the doppler ultrasound revealed bilateral lower extremity acute deep vein thrombosis. Laboratory results showed pancytopenia and transaminitis. However, a repeated chest X-ray showed ground-glass changes and interstitial infiltrates, suggestive of atypical infection. We indeed identified D-glucan which hints to a disseminated form of Pneumocystis jirovecii pneumonia infection in this patient. We further confirmed the Pneumocystis jirovecii pneumonia by polymerase chain reaction test from the fluid obtained via bronchoalveolar lavage. We, therefore, initiated intravenous trimethoprim/ sulfamethoxazole treatment with an anticoagulant, and the patient's condition improved. Our findings strongly suggest a possible link between Pneumocystis jirovecii pneumonia infection and thrombogenesis, with impact in medical practice.

Revisión narrativa: unidad de ortogeriatría, la propuesta para reducir los desenlaces adversos en adultos mayores con fracturas de cadera por fragilidad / Narrative review: Orthogeriatrics unit, the proposal to reduce adverse outcomes in older adults with fragility fractures

Introducción Las fracturas de cadera son un problema de salud pública debido a su asociación con altas tasas de mortalidad a un año, deterioro funcional y empeoramiento de la calidad de vida. Un enfoque multidisciplinario mejora los resultados de los pacientes adultos mayores con fracturas por fragilidad. Objetivo Realizar una revisión narrativa para evaluar la evidencia de las unidades de ortogeriatría como estrategia para reducir desenlaces adversos en adultos mayores con fracturas de cadera por fragilidad. Materiales y métodos Se realizó una búsqueda de la literatura en las siguientes bases de datos: PubMed,Cochrane y Scielo, con los términos: "hip fracture" or "fragility fracture" AND "multidisciplinary team" or "Geriatric co management" or AND "orthogeriatric" or "ortho-geriatric". Resultados El manejo por ortogeriatría reduce el tiempo de evaluación pre-quirúrgico, complicaciones postoperatorias y la estancia hospitalaria. La valoración interdisciplinaria ha demostrado ser eficaz para disminuir el deterioro funcional, la mortalidad intrahospitalaria, la mortalidad a los 30 días y el riesgo de institucionalización en comparación con otros modelos de atención. Estos factores impactan sobre la optimización de recursos disminuyendo los costos en salud. Conclusión Los servicios de ortogeriatría son el modelo ideal para tratar las fracturas de cadera por fragilidad en adultos mayores. En Colombia se deben implementar más unidades de ortogeriatría para mejorar la atención intrahospitalaria, crear programas de seguimiento y rehabilitación.

Introduction Hip fracture is a public health problem due to its association with high mortality rates at one year, functional decline and worsening of quality of life. A multidisciplinary approach improves outcomes for elderly patients with fragility fracture. Objective To carry out a narrative review to evaluate the evidence of orthogeriatric units as a strategy to reduce adverse outcomes in older adults with fragility hip fractures. Material and Methods A literature search was carried out in the following databases: PubMed, Cochrane and Scielo, with the terms: "hip fracture" or "fragility fracture" AND "multidisciplinary team" or "Geriatric co management" or AND "orthogeriatric" or "ortho-geriatric". Results Care by orthogeriatrics reduces pre-operative surgical time, postoperative complications and hospital stay. Interdisciplinary assessment has been shown to be effective in reducing functional decline, in-hospital mortality, 30-day mortality, and the risk of institutionalization compared to other models of care. These factors impact on the optimization of resources, reducing health costs. Conclusion Orthogeriatric services are the ideal model to treat fragility fractures in older adults. In Colombia, more orthogeriatric units should be implemented to improve in-hospital care, create follow-up and rehabilitation programs.

Refractive Error of Students (15- to 18-year-olds) in Northwest Mexico.

SIGNIFICANCE: We assessed the prevalence of refractive error in a sample of children of Northern Mexico using the Refractive Error Study in Children protocol of the World Health Organization, which allows for the comparison with other global studies. PURPOSE: Uncorrected refractive error is the main cause of visual impairment in children. The purpose of this study was to assess the refractive error and visual dysfunctions of students (15 to 18 years old) in the upper-middle school system of Sinaloa, Mexico. METHODS: A total of 3468 students in Sinaloa's high school system participated in the study from 2017 to 2019. Optometrists and student clinicians from the Optometry Program of the Autonomous University of Sinaloa conducted the testing. Tests included visual acuities and static retinoscopy. We did not use a cycloplegic agent. RESULTS: The results showed a high prevalence of uncorrected refractive errors. Myopia, defined as a refractive error ≤-0.50 D, had a prevalence of 36.11% (95% confidence interval, 33.47 to 38.83%); hyperopia, defined as a refractive error ≥+2.00 D, had a prevalence of 1.49% (95% confidence interval, 0.09 to 2.33%); and astigmatism, defined as a refractive error with a cylinder ≥0.75 D, had a prevalence of 29.17% (95% confidence interval, 26.60 to 31.76%). We found a significant effect of sex on visual acuity. CONCLUSIONS: Our results are consistent with a high prevalence of myopia reported in adolescents worldwide and in Mexico's northern regions. The results suggest that students attending high school and entering universities should be required to have an optometric eye examination. Additional studies are needed to investigate the prevalence of refractive errors in children in Mexico.

A delayed treatment model for the evaluation of scopolamine for VX nerve agent intoxication.

Most research on medical countermeasures for nerve agent exposure assumes a military scenario, in which (autoinjector) treatment is envisaged to be available immediately. In a civilian setting however, treatment is delayed until arrival of first-aid responders. This may significantly affect treatment efficacy and the requirements for secondary intensive care. The aim of the current study was to develop a guinea pig model to evaluate the efficacy of delayed treatment following nerve agent exposure. We identified a trigger-to-treat based on a progressive stage of the toxidrome following VX exposure, which was associated with the subsiding of clonic movements. This paradigm resulted in treatment consistently being administered between 15 and 25 min post-exposure. Using the model, we investigated the potential for the anticholinergic scopolamine to act as a delayed treatment either as a standalone treatment, or as an adjunct to delayed treatment with Standard of Care (SOC), containing atropine, 2-PAM, and midazolam. The study provides a framework for a small animal model for evaluating the efficacy of treatment administered at a specific stage of the toxidrome, when immediate treatment is absent. As an adjunct, scopolamine treatment did not result in improved survival, but did show a beneficial effect on recovery, in terms of general posture. As a standalone treatment, scopolamine showed a significant, dose-responsive, beneficial effect on survival and recovery. These promising results warrant additional studies to investigate which observed physiological improvements are relevant for the recovery process and residual injury.

3D Multicellular Spheroid for the Study of Human Hematopoietic Stem Cells: Synergistic Effect Between Oxygen Levels, Mesenchymal Stromal Cells and Endothelial Cells.

INTRODUCTION: The human bone marrow microenvironment is composed of biological, chemical and physical factors that act in a synergistic way to modulate hematopoietic stem cell biology, such as mesenchymal stromal cells (MSCs), endothelial cells (ECs) and low oxygen levels; however, it is difficult to mimic this human microenvironment in vitro. METHODS: In this work, we developed 3D multicellular spheroid (3D-MS) for the study of human hematopoietic stem cells (HSCs) with some components of perivascular niche. HSCs were isolated from umbilical cord blood, MSCs were isolated from human bone marrow and a microvasculature EC line (CC-2811, Lonza®) was used. For the formation of a 3D structure, a magnetic levitation culture system was used. Cultures were maintained in 21%, 3% and 1% O2 for 15 days. Culture volume, sphericity index and cell viability were determined. Also, human HSC proliferation, phenotype and production of reactive oxygen species were evaluated. RESULTS: After 15 days, 3D-MS exhibited viability greater than 80%. Histology results showed structures without necrotic centers, and higher cellular proliferation with 3% O2. An increase in the expression of the CD34 antigen and other hematopoietic antigens were observed to 1% O2 with MSCs plus ECs and low ROS levels. CONCLUSION: These findings suggest that 3D-MS formed by MSCs, ECs and HSCs exposed to low concentrations of oxygen (1-3% O2) modulate human HSC behavior and mimics some features of the perivascular niche, which could reduce the use of animal models and deepen the relationship between the microenvironment of HSC and human hematological diseases development.

High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections.

Severe COVID-19 disease is associated with an increase in pro-inflammatory markers, such as IL-1, IL-6, and tumor necrosis alpha, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells, which increase the susceptibility to bacterial and fungal infections. One such opportunistic fungal infection is mucormycosis. Initially, it was debated whether a person taking immunosuppressants, such as corticosteroids, and monoclonal antibodies will be at higher risk for COVID-19 or whether the immunosuppresive state would cause a more severe COVID-19 disease. However, immunosuppressants are currently continued unless the patients are at greater risk of severe COVID-19 infection or are on high-dose corticosteroids therapy. As understood so far, COVID-19 infection may induce significant and persistent lymphopenia, which in turn increases the risk of opportunistic infections. It is also noted that 85% of the COVID-19 patients' laboratory findings showed lymphopenia. This means that patients with severe COVID-19 have markedly lower absolute number of T lymphocytes, CD4+T and CD8+ T cells and, since the lymphocytes play a major role in maintaining the immune homeostasis, the patients with COVID-19 are highly susceptible to fungal co-infections. This report is intended to raise awareness of the importance of early detection and treatment of mucormycosis and other fungal diseases, such as candidiasis, SARS-CoV-2-associated pulmonary aspergillosis, pneumocystis pneumonia and cryptococcal disease, in COVID-19 patients, to reduce the risk of mortality.

TRPM8 Channel Promotes the Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells.

Various families of ion channels have been characterized in mesenchymal stem cells (MSCs), including some members of transient receptor potential (TRP) channels family. TRP channels are involved in critical cellular processes as differentiation and cell proliferation. Here, we analyzed the expression of TRPM8 channel in human bone marrow MSCs (hBM-MSCs), and its relation with osteogenic differentiation. Patch-clamp recordings showed that hBM-MSCs expressed outwardly rectifying currents which were increased by exposure to 500 µM menthol and were partially inhibited by 10 µM of BCTC, a TRPM8 channels antagonist. Additionally, we have found the expression of TRPM8 by RT-PCR and western blot. We also explored the TRPM8 localization in hBM-MSCs by immunofluorescence using confocal microscopy. Remarkably, hBM-MSCs treatment with 100 µM of menthol or 10 µM of icilin, TRPM8 agonists, increases osteogenic differentiation. Conversely, 20 µM of BCTC, induced a decrease of osteogenic differentiation. These results suggest that TRPM8 channels are functionally active in hBM-MSCs and have a role in cell differentiation.

Comportamiento de reingreso a 30 días en un centro de reemplazos articulares. Estudio de cohorte longitudinal / 30 days re-admission in an articular Joint Arthroplasty center. A cohort Study

Introducción Los reemplazos articulares son calificados como procedimientos seguros y exitosos para el tratamiento de la osteoartrosis severa de cadera y rodilla alrededor del mundo. Las tasas de reingreso en los primeros 30 días y las complicaciones se han descrito como una medida para evaluar estándares de calidad. En Colombia no se conoce el comportamiento de éstos estándares. Este estudio pretende aportar información de un centro especializado en reemplazos articulares en Bogotá DC, Colombia, Suramérica. Materiales & Métodos Se realizó un estudio observacional prospectivo de una cohorte de 1.126 pacientes con 626 reemplazos totales de cadera (RTC) y 500 de rodilla (RTR), operados entre los años 2011-2015 en el Hospital Universitario San Ignacio de Bogotá DC, Colombia. Se reportan las tasas de reingreso a 30 días y las complicaciones. Se analiza mediante un modelo de regresión las asociaciones entre variables sociodemográficas y clínicas con el reingreso y las complicaciones. Resultados El 71% de los pacientes fueron mujeres, el promedio de edad de 63 años en los hombres y 65 años en mujeres. La estancia hospitalaria promedio fue de 3,5 días (DE:0,81-6,29). La tasa de reingreso a 30 días por cualquier causa fue 10,8% y la tasa de complicaciones asociadas al procedimiento fue 5,8%, se requirió reintervención quirúrgica en 1,5% de los pacientes. Se encontró asociación estadísticamente significativa entre el índice de Charlson mayor a 2 (OR=2,33[IC95% 1,3-4,18], p=0.004) y el reingreso a 30 días. La principal complicación en RTC fue luxación (1,4%) y en RTR infección de sitio quirúrgico (4%). Se encontró una asociación significativa entre complicaciones a 30 días con los días de hospitalización (OR=1,17[IC95% 1,09-1,25], p=0,00); y con el cirujano 4 en RTR (OR=2,28[IC95% 1,29-4,01], p=0,04); las demás variables no mostraron diferencias significativas. No se aprecian grandes diferencias con lo reportado en la literatura, asociación con estancia hospitalaria y experiencia del cirujano. Discusión La experiencia del cirujano y la aplicación de guías clínicas que optimicen los procesos intrahospitalarios y regulen los días de estancia hospitalaria, se relacionan con un mejor desenlace en la evolución de los pacientes en cuanto al número de complicaciones y reingresos a 30 días.

Background Joint replacements are always defined as safe and successful procedures for the treatment of severe osteoarthritis of the hip and knee around the world. Rates of readmission within initial post surgical 30 days and complications are described as a measure to assess quality standards. In Colombia the behavior of the standards are mainly unknown. Aim of study is to provide information from a specialized in joint replacements center in Colombia. Methods A prospective observational study was carried out on a cohort of 1,126 patients with 626 total hip replacements (THR) and 500 knee replacements (TKR), who underwent surgery between 2011-2015 at a University Hospital in Bogotá, Colombia. 30-day readmission rates and complications were reported. The associations between sociodemographic and clinical variables with readmission and complications were analyzed using a regression model. Results 71% of the patients were women, the average age was 63 years for men and 65 years for women. The mean hospital stay was 3.5 days (SD: 0.81-6.29). The 30-day readmission rate for any cause was 10.8% and the rate of complications associated with the procedure was 5.8%. Additional surgical procedures were required in 1.5% of the patients. A statistically significant association was found between the Charlson index greater than 2 (OR=2.33 [95% CI 1.3-4.18], p=0.004) and readmission at 30 days. The main complication in THR was dislocation (1.4%) and surgical site infection (4%) in TKR. A significant association was found between complications at 30 days and days of hospitalization (OR=1.17 [95% CI 1.09-1.25], p=0.00); and with surgeon 4 in TKR (OR=2.28 [95% CI 1.29-4.01], p=0.04); the other variables did not show significant differences. No differences were found with what is reported in the literature, association with hospital stay and experience of the surgeon. Discussion The surgeon's experience and the application of clinical guidelines that optimize in-hospital processes and regulate the days of hospital stay are related to a better outcome in the evolution of patients in terms of the number of complications and readmissions after 30 days.