Adoptive T cell therapy for solid tumors: current landscape and future challenges.

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate the antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR) gene-modified T cells, and therapy with tumor-infiltrating lymphocytes (TILs). The outstanding results of CAR-T cells in some hematologic malignancies have launched the investigation of ACT in patients with refractory solid malignancies. However, certain characteristics of solid tumors, such as their antigenic heterogeneity and immunosuppressive microenvironment, hamper the efficacy of antigen-targeted treatments. Other ACT modalities, such as TIL therapy, have emerged as promising new strategies. TIL therapy has shown safety and promising activity in certain immunogenic cancers, mainly advanced melanoma, with an exciting rationale for its combination with immune checkpoint inhibitors. However, the implementation of TIL therapy in clinical practice is hindered by several biological, logistic, and economic challenges. In this review, we aim to summarize the current knowledge, available clinical results, and potential areas of future research regarding the use of T cell therapy in patients with solid tumors.

Urinary excretion of calcium, phosphate, magnesium, and uric acid in healthy infants and young children. Influence of feeding practices in early infancy.

BACKGROUND: Reference values for urinary calcium (Ca) and other solutes/creatinine (Cr) ratios in infants and young children are scarce. Its variation with type of lactation administered, breastfed (BF) or formula (F), is incompletely known. METHODS: A total of 511 spot urine samples from 136 children, aged 6 days to < 5 years, was collected. Urine was collected no fasting in infants < 18 months and first morning fasting in children aged 2.5-4 years. Urinary osmolality, Cr, urea, Ca, phosphate (P), magnesium (Mg), and uric acid (UA) were determined. Values are expressed as solute-to-Cr ratio. RESULTS: Urinary values were grouped according to the child's age: 6-17 days (G1), 1-5 months (G2), 6-12 months (G3), 13-18 months (G4), and 2.5-4 years (G5). G1 was excluded; Ca/Cr and UA/Cr (95th percentile) decreased with age (G2 vs. G5) from 1.64 to 0.39 and 2.33 to 0.83 mg/mg, respectively. The P/Cr median rises significantly with age from 0.31 (G2) to 1.66 mg/mg (G5). Mg/Cr was similar in all groups (median 0.20, 95th percentile 0.37 mg/mg). Ca/Cr (95th percentile) of BF infants was 1.80 mg/mg (< 3 months) and 1.63 mg/mg (3-5 months), much higher than F infants (0.93 and 0.90 mg/mg, respectively). P/Cr and P/Ca were lower in BF infants. CONCLUSIONS: Values for urinary Ca/Cr, P/Cr, Mg/Cr, and UA/Cr in infants and children < 5 years were updated. BF infants < 6 months showed higher Ca/Cr and lower P/Cr than F infants. New cutoff values to diagnose hypercalciuria in infants < 6 months, according to the type of lactation, are proposed.

Determinantes de la gestión del riesgo en salud en el Régimen Subsidiado en Colombia: estudio cualitativo

Introducción: El Régimen Subsidiado (RS) del sistema de salud colombiano tiene problemáticas estructurales que no han sido solucionadas y son pocos los estudios que profundizan en la explicación de estas. Objetivo: Explorar la experiencia en la dirección estratégica y gestión operativa y financiera de este régimen, sus aspectos operativos y de gestión del riesgo en esta población, así como las diferencias percibidas frente al Régimen Contributivo. Metodología: Estudio cualitativo. Se utilizó el análisis del discurso desde la perspectiva sociohermenéutica como técnica analítica. Se entrevistaron diez participantes, entre directivos de aseguradoras del RS y gestores del sistema de salud. Las entrevistas fueron grabadas y anonimizadas, previo consentimiento informado. Resultados: Emergen tres patrones discursivos que explican la gestión del riesgo en el RS y su diferenciación con el contributivo. Estos patrones se conectan por medio del rol de los determinantes sociales de la salud como ordenador principal de los procesos de salud-enfermedad y de atención en este régimen. A su vez, estas condiciones de vida son las que determinan de manera importante el perfil epidemiológico, acceso, costo de la atención y en general la forma cómo se consumen los servicios de salud por la población afiliada. Discusión: La literatura del aseguramiento en salud reporta que la gestión del riesgo es una función central y supone un ejercicio estratégico para el adecuado manejo de la siniestralidad para optimizar el uso de la Unidad de Pago por Capitación (UPC) asignada. Los hallazgos muestran que los determinantes sociales de la salud no están siendo tenidos en cuenta como ordenador para la atención, por lo tanto, la gestión del riesgo se centra en la atención de patologías en estados avanzados. Conclusiones: los actores perciben que en general, la situación de salud de los afiliados en este régimen es más grave, más complicada y con mayor carga, lo cual genera una tensión en materia de suficiencia de la unidad per cápita. Existe una ausencia discursiva sobre el rol del modelo de atención y su correlación con las necesidades de esta población.

Introduction: The subsidized regime (SR) of the Colombian health system has structural problems that have not yet been resolved and there is a lack of studies that allow the understanding of most of them. The aim of this study was to explore with stakeholders of the subsidized regime the experience about strategic, financial, and health risk management and the differences perceived with the contributory regime. Methods: A qualitative study was performed; the analytic technique used was the discourse analysis under socio-hermeneutic perspective. 10 participants were interviewed, among them directors of insurance companies of SR and health care system managers. The interviews were recorded, prior informed consent, and analyzed according to the discourse analysis. Finding: Three discursive patterns emerged that explain risk management in SR and its differentiation from contributory regime. These patterns are connected through the role of the social determinants of health as the main axis that explain the health-disease and care processes in this regimen. At the same time, these living conditions are what determine the epidemiological profile, access, cost of care and, in general, the way in which health services are consumed by the affiliated population. Discussion: The health insurance literature reports that risk management is a central function, and it is a strategic exercise for the proper management of claims to optimize the use of resources, however, the findings show that the social determinants of health are not being taken into account as a key element for healthcare organization, therefore, risk management focuses on care for pathologies in advanced stages. Conclusions: The actors perceive that the health situation in this regime is more severe, more complicated and with a greater burden disease, which generates a tension in terms of sufficiency of the Per Capita Unit. There is a discursive absence on the role of the care model and its correlation with the needs of this population.

BRAF Inhibitors in Metastatic Colorectal Cancer and Mechanisms of Resistance: A Review of the Literature.

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.

A One Health approach based on genomics for enhancing the Salmonella enterica surveillance in Colombia.

Objectives: This study aimed to provide evidence of the domestic benefits of introducing an integrative genomic analysis from the One Health approach in the national surveillance of Salmonella enterica between 1997-2017 in Colombia. Methods: Data on Salmonella from clinical laboratory-based surveillance between 1997-2017 and from a national cross-sectional study at chicken retail stores in Colombia were compared using a phenotypic, molecular, and genomic approaches. Additional analysis by serovar using single nucleotide polymorphism was developed to increase the resolution of the relatedness between the interfaces. Results: Locally, the diversity and pathogenic factors of the prevalent S. enterica serovars associated with foodborne disease in Colombia were described using laboratory, pulse field gel electrophoresis, and whole genome sequencing data. For example, the resolution of pulse field gel electrophoresis allowed the description of two main foodborne clusters of Salmonella Enteritidis isolates, which were expanded to eight foodborne clades using whole genome sequencing. Likewise, virulence factors and antimicrobial resistance determinants, and mobile genetic elements that converged in the foodborne clades should be considered a public health concern in Colombia. All results by serovar were compiled in an interactive easy to share report. Conclusion: Whole genome sequencing is a technology that provides a precise assessment of emerging foodborne risks such as the Salmonella foodborne clades, but it requires an integrative and continued collaboration between the stakeholders across the One Health sectors to promote appropriated actions and policies in public health.

Worldwide risk assessment of phthalates and bisphenol A in humans: The need for updating guidelines.

Phthalates and bisphenol A (BPA) are compounds widely used as raw materials in the production of plastics, making them ubiquitous in our daily lives. This results in widespread human exposure and human health hazards. Although efforts have been conducted to evaluate the risk of these compounds in diverse regions around the world, data scattering may mask important trends that could be useful for updating current guidelines and regulations. This study offers a comprehensive global assessment of human exposure levels to these chemicals, considering dietary and nondietary ingestion, and evaluates the associated risk. Overall, the exposure daily intake (EDI) values of phthalates and BPA reported worldwide ranged from 1.11 × 10-7 to 3 700 µg kg bw-1 d-1 and from 3.00 × 10-5 to 6.56 µg kg bw-1 d-1, respectively. Nevertheless, the dose-additive effect of phthalates has been shown to increase the EDI up to 5 100 µg kg bw-1 d-1, representing a high risk in terms of noncarcinogenic (HQ) and carcinogenic (CR) effects. The worldwide HQ values of phthalates and BPA ranged from 2.25 × 10-7 to 3.66 and from 2.74 × 10-7 to 9.72 × 10-2, respectively. Meanwhile, a significant number of studies exhibit high CR values for benzyl butyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP). Moreover, DEHP has shown the highest maximum mean CR values for humans in numerous studies, up to 179-fold higher than BBP. Despite mounting evidence of the harmful effects of these chemicals at low-dose exposure on animals and humans, most regulations have not been updated. Thus, this article emphasizes the need for updating guidelines and public policies considering compelling evidence for the adverse effects of low-dose exposure, and it cautions against the use of alternative plasticizers as substitutes for phthalates and BPA because of the significant gaps in their safety.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005-2019: Observational analysis.

INTRODUCTION: The introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. METHODS: A total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates - ARR) of VTs between the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods. RESULTS: The findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. CONCLUSIONS: Our results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods.

Zoonoses in a changing world.

Animals are continuously exposed to pathogens but rarely get infected, because pathogens must overcome barriers to establish successful infections. Ongoing planetary changes affect factors relevant for such infections, such as pathogen pressure and pathogen exposure. The replacement of wildlife with domestic animals shrinks the original host reservoirs, whereas expanding agricultural frontiers lead to increased contact between natural and altered ecosystems, increasing pathogen exposure and reducing the area where the original hosts can live. Climate change alters species' distributions and phenology, pathogens included, resulting in exposure to pathogens that have colonized or recolonized new areas. Globalization leads to unwilling movement of and exposure to pathogens. Because people and domestic animals are overdominant planetwide, there is increased selective pressure for pathogens to infect them. Nature conservation measures can slow down but not fully prevent spillovers. Additional and enhanced surveillance methods in potential spillover hotspots should improve early detection and allow swifter responses to emerging outbreaks.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Multipopulation evaluation of the internal morphology of mandibular first premolars from different South American countries. A micro-computed tomography study.

OBJECTIVE: To evaluate and compare several anatomical parameters of mandibular first premolars from individuals from different Latin American countries using micro-computed tomography. DESIGN: Five hundred extracted mandibular first premolars from Brazilian, Argentinian, Chilean, Colombian, and Ecuadorian individuals were scanned using micro-computed tomography (n = 100 teeth/country). Root canal configurations were classified according to established parameters. Analyses also included: canal volume and surface area, structure model index, distances from the apical foramen to the root apex or the cementoenamel junction, major/minor apical canal diameters, canal orifice shape, and prevalence of ramifications. RESULTS: A single root was the most common anatomy in all countries (range, 97%-100%). Vertucci's type-I canal was the most frequent configuration (range, 36%-66%), followed by C-shaped and type-V canals. The oval-shaped canal orifice was the most predominant in all countries (range, 34%-58%), followed by the circular shape (range, 16%-47%). C-shaped canals occurred in all subpopulations (range, 14%-26%), always associated with radicular grooves. Ranges for canal ramifications were as follows: accessory canals, 36%-73%; lateral canals, 4%-12%; and apical delta, 4%-14% of the teeth. Many anatomic parameters differed significantly between countries (P < .05). CONCLUSIONS: Vertucci's types-I and -V, and C-shaped canals were the most prevalent configurations in the subpopulations investigated. Accessory canals and several complex anatomies were found, with some significantly different frequencies between countries.

Adsorptive removal of ciprofloxacin and sulfamethoxazole from aqueous matrices using sawdust and plastic waste-derived biochar: A sustainable fight against antibiotic resistance.

We produced carbon-negative biochar from the pyrolysis of sawdust biomass alone (SB) and from the co-pyrolysis of sawdust and plastic waste (SPB). The co-pyrolysis approach in this study was driven by several hypothetical factors, such as increased porosity, surface chemistry, stability, as well as waste management. We applied pyrolyzed and co-pyrolyzed biochars for the removal of ciprofloxacin (CFX) and sulfamethoxazole (SMX). Due to its more alkaline and amorphous nature, SB showed better removal efficiencies compared to SPB. The maximum removals of CFX and SMX with SB were observed as ∼95% and >95%, respectively whereas with SPB were 58.8%, and 34.9%, respectively. The primary mechanisms involved in the adsorption process were H-bonding, electrostatic and π-π electron donor-acceptor interactions. Homogenously and heterogeneously driven adsorption of both antibiotics followed the pseudo-second-order kinetic model, implying electron sharing/transfer (chemisorption) mediated adsorption. The work is highly pertinent in the context of emerging concerns related to drivers that promote antimicrobial resistance.

Effect of receiving a customizable brochure on breast cancer patients' knowledge about their diagnosis and treatment: A randomized clinical trial.

BACKGROUND: Patients' lack of knowledge about their own disease may function as a barrier to shared decision-making and well-being. This study aimed to evaluate the impact of written educational materials on breast cancer patients. METHODS: This multicenter, parallel, unblinded, randomized trial included Latin American women aged ≥18 years with a recent breast cancer diagnosis yet to start systemic therapy. Participants underwent randomization in a 1:1 ratio to receive a customizable or standard educational brochure. The primary objective was accurate identification of molecular subtype. Secondary objectives included identification of clinical stage, treatment options, participation in decision-making, perceived quality of information received, and illness uncertainty. Follow-up occurred at 7-21 and 30-51 days post-randomization. CLINICALTRIALS: gov identifier: NCT05798312. RESULTS: One hundred sixty-five breast cancer patients with a median age of 53 years and 61 days from diagnosis were included (customizable: 82; standard: 83). At first available assessment, 52%, 48%, and 30% identified their molecular subtype, disease stage, and guideline-endorsed systemic treatment strategy, respectively. Accurate molecular subtype and stage identification were similar between groups. Per multivariate analysis, customizable brochure recipients were more likely to identify their guideline-recommended treatment modalities (OR: 4.20,p = 0.001). There were no differences between groups in the perceived quality of information received or illness uncertainty. Customizable brochure recipients reported increased participation in decision-making (p = 0.042). CONCLUSIONS: Over one third of recently diagnosed breast cancer patients are incognizant of their disease characteristics and treatment options. This study demonstrates a need to improve patient education and shows that customizable educational materials increase patients' understanding of recommended systemic therapies according to individual breast cancer characteristics.

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3.

BACKGROUND: EMPOWER-Lung 3, a randomized 2:1 phase 3 trial, showed clinically meaningful and statistically significant overall survival improvement with cemiplimab plus platinum-doublet chemotherapy versus placebo plus chemotherapy for first-line treatment of advanced non-small cell lung cancer. This study evaluated patient-reported outcomes (PROs). METHODS: PROs were assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks) for the first six doses, and then at start of every three cycles, using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer Module (QLQ-LC13) questionnaires. Prespecified analyses included a longitudinal mixed-effect model comparing treatment arms and a time to definitive clinically meaningful deterioration (TTD) analysis performed for global health status/quality of life (GHS/QoL) and all scales from the questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and proportional hazards model. RESULTS: A total of 312 patients were assigned to receive cemiplimab plus platinum-doublet chemotherapy and 154 to receive placebo plus chemotherapy; 391 (83.9%) were male and the median age was 63.0 years (range, 25-84). For pain symptoms (EORTC QLQ-C30), a statistically significant overall improvement from baseline (-4.98, 95% confidence interval [CI] -8.36 to -1.60, p = .004) and a statistically significant delay in TTD (hazard ratio, 0.39; 95% CI, 0.26-0.60, p < .0001) favoring cemiplimab plus chemotherapy were observed. Statistically significant delays in TTD, all favoring cemiplimab plus chemotherapy, were also observed in functioning and symptom scales. A significant overall improvement from baseline in GHS/QoL was seen for cemiplimab plus chemotherapy compared with nonsignificant overall change from baseline for placebo plus chemotherapy (1.69, 95% CI, 0.20-3.19 vs. 1.08, 95% CI, -1.34 to 3.51; between arms, p = .673). No analyses yielded statistically significant PRO results favoring placebo plus chemotherapy for any QLQ-C30 or QLQ-LC13 scale. CONCLUSION: Cemiplimab plus chemotherapy resulted in significant overall improvement in pain symptoms and delayed TTD in cancer-related and lung cancer-specific symptoms and functions.

Differences in Virulence Factors and Antimicrobial Susceptibility of Uropathogenic Enterococcus spp. Strains in a Rural Area of Uganda and a Spanish Secondary Hospital.

Enterococcus faecalis and Enterococcus faecium have become two of the most important agents of nosocomial diseases due to their constantly growing resistance. Enterococcal infections are associated with biofilms, which are intrinsically sensitive to antimicrobials. The main goal of this study was to compare and relate their capacity to form biofilm and their antimicrobial sensitivity, as well as their virulence factors and their implicated genes, of strains isolated from patients with urinary tract infection (UTI) in a rural hospital in Uganda and a secondary hospital in Spain. A prospective study was conducted with 104 strains of E. faecalis and E. faecium isolated from patients with suspected UTI and who presented leukocyturia at the Saint Joseph Kitgum hospital (Uganda) and at the Hospital Universitario Principe de Asturias (Spain). All microorganisms were identified in Spain by MALDI-TOF mass spectrometry. Antimicrobial susceptibility studies were carried out using the Vitek® 2 system (Biomériux, France). The biofilm formation capacity was studied by photospectrometry. Phenotypic and genotypic virulence factors were studied in all cases by PCR or expression techniques. In Uganda, we found a higher incidence of E. faecium (65.3%, n = 32), contrary to the situation found in Spain where most of the bacteria found belonged to E. faecalis (92.7%, n = 51). All E. faecalis strains were found to have very low levels of resistance to ampicillin, imipenem, and nitrofurantoin. However, E. faecium exhibited more than 25% resistance to these antibiotics. Although the esp gene has been shown in the results obtained to be an important initial agent in biofilm formation, we have also demonstrated in this study the intervention of other genes when esp is not present, such as the ace1 gene. No statistically significant relationships were found between the presence of agg and gelE genes and increased biofilm formation. The significant difference between the incidence of E. faecalis and E. faecium and biofilm formation, between samples from Spain and Uganda, shows us very different profiles between countries.

Occupational exposure to pesticides and symptoms of depression in agricultural workers. A systematic review.

BACKGROUND: The use of pesticides can result in harm to both the environment and human health. There is a growing concern in the field of occupational health about the impact on the mental health of agricultural workers. OBJECTIVES: The objective of this review was to systematize scientific evidence from the last ten years on the impact of occupational exposure to pesticides on the development of depression symptoms in agricultural workers. METHODS: We conducted a comprehensive search in the PubMed and Scopus databases from 2011 to September 2022. Our search included studies in English, Spanish, and Portuguese that examined the association between occupational exposure to pesticides and symptoms of depression in agricultural workers, following the guidelines recommended by the PRISMA statement and the PECO strategy (Population, Exposure, Comparison, and Outcomes). RESULTS: Among the 27 articles reviewed, 78% of them indicated a link between exposure to pesticides and the incidence of depression symptoms. The pesticides most frequently reported in the studies were organophosphates (17 studies), herbicides (12 studies), and pyrethroids (11 studies). The majority of the studies were rated as having intermediate to intermediate-high quality, with the use of standardized measures to assess both exposure and effect. CONCLUSION: The updated evidence presented in our review indicates a clear association between pesticide exposure and the development of depressive symptoms. However, more high-quality longitudinal studies are necessary to control for sociocultural variables and utilize pesticide-specific biomarkers and biomarkers of depression. Given the increased use of these chemicals and the health risks associated with depression, it is crucial to implement more stringent measures to monitor the mental health of agricultural workers regularly exposed to pesticides and to enhance surveillance of companies that apply these chemicals.

Enterobacter cloacae Infection After Surgical Treatment of Ankle Fractures, a Multicenter Observational Study.

BACKGROUND: Infection is one of the challenging complications after open reduction and internal fixation for ankle fractures. Previously published case series conclude that Staphylococcus aureus is the most frequent causative microorganism. An unexpected increase in Enterobacter cloacae infections after this surgery was observed in a preliminary analysis of data at the promoting center of the study. In traumatology, its incidence has been reported in chronic osteomyelitis, prosthetic infections, septic osteoarthritis, open fractures in children and adults, and fractures other than the ankle. Because of this unexpected finding, we decided to perform this study to analyze the demographic and microbiological variables of acute osteosynthesis infection after ankle fracture and determine the distinctive features of the patients with E cloacae infection. METHODS: We performed a retrospective multicenter study including 4 university hospitals. All patients diagnosed with acute osteosynthesis infection after ankle fracture fixation between January 2015 and December 2018 were included. We analyzed demographic data, type of fracture, surgical technique, and microorganisms responsible for the infection. We performed a descriptive statistical analysis of the variables. Univariate and multivariate regression analysis were performed to compare patients with E cloacae infection to patients with infection caused by other microorganisms. RESULTS: A total of 65 patients were included. A predominance of polymicrobial infections (24.62%), followed by infections caused by S aureus (23.07%) and E cloacae (23.07%) was observed. When E cloacae isolated in polymicrobial infections were added, the incidence of E cloacae as a causative microorganism increased to 32.3%. Patients with E cloacae infection were older (64/53, P = .008) and had a higher requirement of negative-pressure therapy after surgical debridement (71%/40%, P = .017). CONCLUSION: A high incidence of E cloacae infections was observed. Patients with E cloacae infection were generally older and required a higher use of negative-pressure therapy after debridement. LEVEL OF EVIDENCE: Level V, mechanism-based reasoning.

Infections in patients with adverse reactions to the use of unknown modeling substances for soft tissue enhancement in Cali, Colombia.

The infiltration of foreign materials not approved for medical purposes or of modeling substances used in soft tissue to modify the anatomical appearance for aesthetic purposes represents a serious health problem. These procedures lead to the development of delayed complications, including infections. The objective of this study was to characterize infections in patients with adverse reactions to the use of modeling substances in Cali, Colombia. A cross-sectional and descriptive study was used to determine the frequency of bacterial and fungal infections associated with complications from and adverse reactions to the use of modeling substances in 113 patients. We identified microorganisms in 22 patients and a frequency of 68.1% monomicrobial infections and 31.8% polymicrobial infections. The microorganisms identified in our study included Bacillus cereus, Mycobacterium fortuitum, and Pseudomonas stutzeri, among other microorganisms. The presence of adverse effects derived from the use of illegal modeling substances has been demonstrated; among these effects, infections occur with high frequency and place the health of the patient at risk and increase problems in health care.

Population structure of Neisseria meningitidis ST-9493 identified in Colombian isolates.

INTRODUCTION: Neisseria meningitidis is associated with invasive infections causing high mortality rates. The objective of this study was to describe the population structure of Colombian invasive isolates with ST-9493, a potentially emerging clonal group in the country. METHODS: The complete genomes of 34 invasive isolates of serogroup B with ST-9493 and its variants at one or two loci were sequenced by Illumina to describe the phenotypic and genotypic characteristics of these isolates. RESULTS: The relationship of a clonal group associated with ST-136 CC41/44 was phylogenetically established, identifying two main clades composed of isolates from an outbreak or endemic. The most frequent alleles and peptides included porA 17, porB 44, fHbp 2.24, NHBA 10, and the FetA F5-17 variant. Most of the isolates were susceptible to the antibiotics evaluated. CONCLUSION: This study shows that meningococcal isolates with ST-9493 are an autochthonous clonal group with population dynamics and the capacity to cause endemic and epidemic meningococcal disease in Colombia.

The effect on handgrip strength of low-frequency percutaneous electric stimulation applied to the median and cubital nerves: A randomized, double-blind controlled trial.

Percutaneous electrical nerve stimulation (PENS) consists of applying an electric current of <1,000 Hz to different neuromuscular structures through acupuncture needles. Currently, there is controversy surrounding the effect of PENS on muscle strength in the scientific literature. The main objective was to assess the effect of PENS applied to the median and cubital nerves on the maximum handgrip strength (MHS) compared to sham stimulation, as well as to determine the safety of the intervention. A parallel, randomized, double-blind controlled trial in a sample of 20 healthy subjects. Participants were randomly allocated in the experimental (n = 10) and control (n = 10) groups. A blinded researcher measured MHS. Measurements of MHS of the dominant hand were taken at four time points: preintervention, immediately postintervention, 24 hr after the intervention, and at a 10-day follow-up. A 10-Hz percutaneous electrical current stimulation was employed. The control group also received the same puncture method but with no electric stimulation. Compared to baseline, the MHS decreased 10.4% (SEM = 3.2, p = .02) in the PENS group at 24 hr postintervention, with no differences observed between baseline and at 10 days postintervention. No changes in grip strength were observed at any time point in the sham group. To sum up, PENS decreased MHS at 24 hr postintervention, which does not persist 10 days after the stimulation. PENS can be considered a safe technique. Trials with larger sample sizes are required to corroborate the findings of this study. Clinical Trials Registration: NCT, NCT04662229, filed on March 12th of 2020.