Hydraulic recharge and element dynamics during salinization in an overexploited coastal aquifer of the world's driest zone: Atacama Desert.

The management of water resources in hyper-arid coastal regions is a challenging task because proper information regarding groundwater recharge and water budget is needed for maintaining the hydraulic balance in optimal conditions, avoiding salinization and seawater intrusion. Thus, this article deals with the estimation of the hydraulic recharge and the study of the effects of salinization on the dynamics of trace elements in an alluvial aquifer located in the world's driest zone, the northern Atacama Desert. The result of stable water isotopes (δD and δ18O) and tritium (3H) indicated that groundwater in the area is not recent, whereas 14C results estimated a groundwater residence time ranging between 11,628 and 16,067 yBP. The estimation of the artificial recharge coming from the urban water-supply-system leaks and wastewater/river-water/groundwater infiltration during irrigation was about 19.84 hm3/year, which represents an annual negative water balance of 177 hm3/year for the aquifer. The groundwater salinization triggered by seawater intrusion (up to 32.6 %) has caused the enrichment of Li, Rb, Ca, Ba, and Sr in groundwater by cationic exchange, where the excess of aqueous Na is exchanged by these elements in the aquifer sediments. Other elements such as B, Se, Si, and Sb are enriched in groundwater by ionic strength and/or anionic exchange during salinization. The heightened B concentrations derived from the B-rich alluvial sediments were higher than the limit suggested by international guidelines, representing a risk to consumers. Vanadium seems to be unaffected by salinization, whereas Pb, Mo, As, U, and Zr did not show a clear behavior during saline intrusion. Finally, this article highlights the consequences of conducting improper water management in coastal hyper-arid regions with exacerbated agriculture.

Trace elements and heavy metal(loid)s triggering ecological risks in a heavily polluted river-reservoir system of central Mexico: Probabilistic approaches.

The contamination of trace elements and heavy metal(loid)s in water bodies has emerged as a global environmental concern due to their high toxicity at low concentrations to both biota and humans. This study aimed to evaluate the ecological risk associated with the occurrence and spatial distribution of Mn, Fe, Co, Cd, Ni, Zn, Sb, As, Tl, Cu, Pb, U, and V in the heavily polluted waters of an important river-reservoir system (Atoyac River Basin) in central Mexico, using two-level tired probabilistic approaches: Risk Quotient based on Species Sensitivity Distribution (RQSSD) and Joint Probability Curves (JPCs). The concentrations of these elements varied widely, ranging from 0.055 µg L-1 to 9200 µg L-1 and from 0.056 µg L-1 to 660 µg L-1, in both total and dissolved fractions, respectively. Although geogenic and anthropogenic sources contribute to the presence of these elements in waters, the discharge of untreated or poorly treated industrial wastewater is the main source of contamination. In this regard, the RQSSD results indicated high ecological risk for Mn, Fe, Co, Ni, Zn, and Sb, and medium or low ecological risk for As, Tl, U, and V at almost all sampling sites. The highest RQSSD values were found downstream of a large industrial corridor for Co, Zn, Tl, Pb, and V, with Tl, Pb, and V escalating to higher risk levels, highlighting the negative impact of industrial contamination on biota. The JPC results for these elements are consistent with the RQSSD approach, indicating an ecological risk to species from Mn, Fe, Co, Ni, Zn, and Sb in waters of the Atoyac River Basin. Therefore, the results of this study offer a thorough assessment of pollution risk, providing valuable insights for legislators on managing and mitigating exposure.

Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent.

Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%, p < 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%, p = 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.

Potential ecological risk assessment of microplastics in environmental compartments in Mexico: A meta-analysis.

Microplastic (MP) environmental contamination has been widely studied in Mexico. However, the evaluation of the associated risk to MPs in environmental compartments is scarce. Therefore, this study addresses this issue using diverse indicators such as the Pollution Load Index (PLI), the Polymer Risk Index (PRI), and the Potential Ecological Risk Index (PERI). The results of a meta-analysis revealed high MP contamination levels in most of the studied compartments, which included marine and estuarine waters, beach sand, freshwater, sediments, and biota. Regarding the risk assessment indicators, PLIs indicated low (56%), dangerous (22%), moderate (12%), and high (10%) levels across compartments. Meanwhile, PRIs displayed concerning values, with 36%, 35%, 20%, and 9% exhibiting dangerous, high, moderate, and low levels, respectively. Thus, high PRI values emphasized the significant rise in MP pollution, largely attributed to high-hazard polymer compositions. Otherwise, PERIs showed low (56%), very dangerous (29%), moderate (6%), high (5%), and dangerous (4%) levels. Thus, the ecological risk in Mexico is widespread and mainly linked to MP abundance, polymer type, environmental matrix, and characteristics of organisms. This study represents the first attempt at MP ecological risk assessment in Mexico, providing crucial insights for developing mitigation strategies to address concerns about MP contamination.

Breast Metastasis From Cutaneous Melanoma: Beyond the Infiltrating Ductal Carcinoma.

Breast metastases of extramammary origin are an extremely rare entity. Solid organ metastases to the breast include malignant melanoma, epithelial carcinoma (adenocarcinoma and squamous cell carcinoma of the lung and gastrointestinal tract), and sarcoma. A breast neoplasm can be caused by a primary tumor, in-transit metastasis, breast metastasis, and skin metastasis. A 42-year-old female patient presented with a hyperpigmented lesion on the first finger of her left hand. An incisional biopsy was carried out, reporting pigmented epithelioid melanoma. Amputation of the finger was performed, as well as an axillary sentinel lymph node excision. Later during the treatment and follow-up by medical oncology, a breast tumor was located, followed by a protocol and the approach of possible differential diagnoses. Finally, it was characterized as metastatic cutaneous melanoma. The therapeutic approach regarding the possible origin of the metastatic neoplastic character of breast tumors culminated in this case in the palliative treatment with immunotherapy of cutaneous malignant melanoma. The diagnosis of breast metastases from cutaneous malignant melanoma is a real challenge, so an extensive history and high clinical suspicion are crucial in order to provide adequate treatment, despite the gloomy prognosis.

Acute Glomerulonephritis as a Paraneoplastic Syndrome Secondary to Urachal Adenocarcinoma: An Unknown Entity.

Urachal carcinoma is an uncommon malignancy with a peculiar biomolecular characterization and therefore a complex approach. It was incorporated by the World Health Organization in 2004 in the tumors of the urinary system classification. This neoplasm is generally diagnosed in advanced stages. The standard treatment is surgical, however, due to the rarity and relatively late clinical manifestation of urachal carcinomas, the survival data are mostly case reports, as well as information about medical-surgical treatment based on evidence. The data used were extracted from both the physical and electronic clinical records. Among atypical presentations reported in the literature, we report a case of urachal adenocarcinoma with simultaneous glomerulonephritis as a paraneoplastic syndrome of which there is no report to date. Surgery was carried out in our patient, unfortunately with lifetime morbidity from kidney function replacement secondary to kidney function damage by glomerulonephritis, despite previous immunosuppression treatment for rapidly progressive glomerulonephritis. It is worth mentioning that if the initial diagnosis represents a clinical challenge, treatment is even more complex, given the little information that currently exists about it. Urachal carcinoma is a diagnostic and treatment challenge. Up to now, surgery has been the treatment of choice in localized or locally advanced disease, however, with a high morbidity for the patient.

Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics.

BACKGROUND: Chronic Kidney Disease (CKD) and Metabolic dysfunction-associated steatohepatitis (MASH) are metabolic fibroinflammatory diseases. Combining single-cell (scRNAseq) and spatial transcriptomics (ST) could give unprecedented molecular disease understanding at single-cell resolution. A more comprehensive analysis of the cell-specific ligand-receptor (L-R) interactions could provide pivotal information about signaling pathways in CKD and MASH. To achieve this, we created an integrative analysis framework in CKD and MASH from two available human cohorts. RESULTS: The analytical framework identified L-R pairs involved in cellular crosstalk in CKD and MASH. Interactions between cell types identified using scRNAseq data were validated by checking the spatial co-presence using the ST data and the co-expression of the communicating targets. Multiple L-R protein pairs identified are known key players in CKD and MASH, while others are novel potential targets previously observed only in animal models. CONCLUSION: Our study highlights the importance of integrating different modalities of transcriptomic data for a better understanding of the molecular mechanisms. The combination of single-cell resolution from scRNAseq data, combined with tissue slide investigations and visualization of cell-cell interactions obtained through ST, paves the way for the identification of future potential therapeutic targets and developing effective therapies.

Arsenic and fluoride in groundwater triggering a high risk: Probabilistic results using Monte Carlo simulation and species sensitivity distribution.

The widespread presence of arsenic (As) and fluoride (F-) in groundwater poses substantial risks to human health on a global scale. These elements have been identified as the most prevalent geogenic contaminants in groundwater in northern Mexico. Consequently, this study aimed to evaluate the human health and ecological risks associated with the content of As and F- in the Meoqui-Delicias aquifer, which is in one of Mexico's most emblematic irrigation districts. Concentrations of As and F- were measured in 38 groundwater samples using ICP-MS and ion chromatography, respectively. Overall, these elements showed a similar trend across the aquifer, revealing a positive correlation between them and pH. The concentration of As and F- in the groundwater ranged from 5.3 µg/L to 303 µg/L and from 0.5 mg/L to 8.8 mg/L, respectively. Additionally, the levels of As and F- surpassed the established national standards for safe drinking water in 92% and 97% of samples, respectively. Given that groundwater is used for both agricultural purposes and human activities, this study also assessed the associated human health and ecological risks posed by these elements using Monte Carlo simulation and Species Sensitivity Distribution. The findings disclosed a significant noncarcinogenic health risk associated with exposure to As and F-, as well as an unacceptable carcinogenic health risk to As through water consumption for both adults and children. Furthermore, a high ecological risk to aquatic species was identified for F- and high to medium risks for As in the sampling sites. Therefore, the findings in this study provide valuable information for Mexican authorities and international organizations (e.g., WHO) about the adverse effects that any exposure without treatment to groundwater from this region represents for human health.

Multicenter Study on the Frequency of Low Bone Mineral Density in Young Women With Breast Cancer and Associated Factors.

INTRODUCTION: Young women with breast cancer (BC) may experience bone mineral density (BMD) loss secondary to cancer treatment effects on estrogen levels. Studies assessing BMD in BC patients have had a limited representation of young women. This multicenter retrospective study analyzed the frequency of low BMD and associated factors in this age group. METHODS: Women diagnosed with stage 0-III BC at ≤40 years, treated with chemotherapy and/or endocrine therapy between 2010 and 2020 at 5 Mexican BC referral centers were eligible. Demographic, clinical and treatment data were collected, as well as bone dual-energy X-ray absorptiometry (DEXA) results. Low BMD was defined as lumbar or femoral neck T-score < -1.0 or Z-score ≤ -2.0. RESULTS: A total of 1259 patients were included; median age at diagnosis was 36 years (21-40). Overall, 93% received chemotherapy and 65% endocrine therapy (tamoxifen was received at some point by 61%, aromatase inhibitors by 17%, and GnRH agonists/bilateral oophorectomy by 21%). DEXA scans were documented in 254 (20%), of which 163 (64%; 95% confidence interval [CI] 58%-70%) had a low BMD report. Low BMD was associated with receiving aromatase inhibitors (Odds ratio [OR] 1.92; 95% CI 1.13-3.24), and GnRH agonists/bilateral oophorectomy (OR 2.25; 95% CI 1.21-4.21). CONCLUSION: The suboptimal frequency of BMD monitoring observed displays an alarming disregard for bone health in young patients. Thus, a high proportion of women with low BMD are potentially being missed and precluded from the opportunity to receive timely interventions. Particular focus should be put on BMD monitoring among patients treated with aromatase inhibitors, GnRH agonists or bilateral oophorectomy.

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.

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.

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.

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.

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.

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.