Oculopharyngeal Muscular Dystrophy: A Case Report From Puerto Rico.

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset inherited skeletal myopathy. The diagnosis is based on a clinical presentation of blepharoptosis, dysphagia, and a positive family history of the disease in patients past 40 years of age. A 57-year-old male patient presented with ptosis without lid crease, adult-onset dysphagia, and bilateral pseudophakia. The patient underwent ptosis repair of upper eyelids via frontalis slings with silicone rods. His mother was subsequently found to have ptosis, dry eyes, and anorexia due to dysphagia, thus suggesting a probable family history. Based on the comprehensive ophthalmic evaluation, and based on his ptosis, dysphagia, and family history, the patient was diagnosed with OPMD.

TCF1-positive and TCF1-negative TRM CD8 T cell subsets and cDC1s orchestrate melanoma protection and immunotherapy response.

BACKGROUND: Melanoma, the most lethal form of skin cancer, has undergone a transformative treatment shift with the advent of checkpoint blockade immunotherapy (CBI). Understanding the intricate network of immune cells infiltrating the tumor and orchestrating the control of melanoma cells and the response to CBI is currently of utmost importance. There is evidence underscoring the significance of tissue-resident memory (TRM) CD8 T cells and classic dendritic cell type 1 (cDC1) in cancer protection. Transcriptomic studies also support the existence of a TCF7+ (encoding TCF1) T cell as the most important for immunotherapy response, although uncertainty exists about whether there is a TCF1+TRM T cell due to evidence indicating TCF1 downregulation for tissue residency activation. METHODS: We used multiplexed immunofluorescence and spectral flow cytometry to evaluate TRM CD8 T cells and cDC1 in two melanoma patient cohorts: one immunotherapy-naive and the other receiving immunotherapy. The first cohort was divided between patients free of disease or with metastasis 2 years postdiagnosis while the second between CBI responders and non-responders. RESULTS: Our study identifies two CD8+TRM subsets, TCF1+ and TCF1-, correlating with melanoma protection. TCF1+TRM cells show heightened expression of IFN-γ and Ki67 while TCF1- TRM cells exhibit increased expression of cytotoxic molecules. In metastatic patients, TRM subsets undergo a shift in marker expression, with the TCF1- subset displaying increased expression of exhaustion markers. We observed a close spatial correlation between cDC1s and TRMs, with TCF1+TRM/cDC1 pairs enriched in the stroma and TCF1- TRM/cDC1 pairs in tumor areas. Notably, these TCF1- TRMs express cytotoxic molecules and are associated with apoptotic melanoma cells. Both TCF1+ and TCF1- TRM subsets, alongside cDC1, prove relevant to CBI response. CONCLUSIONS: Our study supports the importance of TRM CD8 T cells and cDC1 in melanoma protection while also highlighting the existence of functionally distinctive TCF1+ and TCF1- TRM subsets, both crucial for melanoma control and CBI response.

Proceedings of the second international meeting on endemic mycoses of the Americas (IMEMA) and first international symposium on implantation mycoses (ISIM).

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25-27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

The cholera toxin B subunit induces trained immunity in dendritic cells and promotes CD8 T cell antitumor immunity.

Introduction: Innate immune training is a metabolic, functional, and epigenetic long-term reprogramming of innate cells triggered by different stimuli. This imprinting also reaches hematopoietic precursors in the bone marrow to sustain a memory-like phenotype. Dendritic cells (DCs) can exhibit memory-like responses, enhanced upon subsequent exposure to a pathogen; however, whether this imprinting is lineage and stimulus-restricted is still being determined. Nevertheless, the functional consequences of DCs training on the adaptive and protective immune response against non-infectious diseases remain unresolved. Methods: We evaluated the effect of the nontoxic cholera B subunit (CTB), LPS and LTA in the induction of trained immunity in murine DCs revealed by TNFa and LDH expression, through confocal microscopy. Additionally, we obtained bone marrow DCs (BMDCs) from mice treated with CTB, LPS, and LTA and evaluated training features in DCs and their antigen-presenting cell capability using multiparametric cytometry. Finally, we design an experimental melanoma mouse model to demonstrate protection induced by CTB-trained DCs in vivo. Results: CTB-trained DCs exhibit increased expression of TNFa, and metabolic reprogramming indicated by LDH expression. Moreover, CTB training has an imprint on DC precursors, increasing the number and antigen-presenting function in BMDCs. We found that training by CTB stimulates the recruitment of DC precursors and DCs infiltration at the skin and lymph nodes. Interestingly, training-induced by CTB promotes a highly co-stimulatory phenotype in tumor-infiltrating DCs (CD86+) and a heightened functionality of exhausted CD8 T cells (Ki67+, GZMB+), which were associated with a protective response against melanoma challenge in vivo. Conclusion: Our work indicates that CTB can induce innate immune training on DCs, which turns into an efficient adaptive immune response in the melanoma model and might be a potential immunotherapeutic approach for tumor growth control.

Genetic diversity of P1/pathogenic Leptospira species hosted by bats worldwide.

INTRODUCTION: Bats are a diverse group of mammals that have unique features allowing them to act as reservoir hosts for several zoonotic pathogens such as Leptospira. Leptospires have been classified into pathogenic, intermediate, and saprophytic groups and more recently into clades P1, P2, S1, and S2, being all the most important pathogenic species related to leptospirosis included within the P1/pathogenic clade. Leptospira has been detected from bats in several regions worldwide; however, the diversity of leptospires harboured by bats is still unknown. AIM: The aim of the present study was to determine the genetic diversity of Leptospira spp. harboured by bats worldwide. METHODS: A systematic review was conducted on four databases to retrieve studies in which Leptospira was detected from bats. All studies were screened to retrieve all available Leptospira spp. 16S rRNA sequences from the GenBank database and data regarding their origin. Sequences obtained were compared with each other and reference sequences of Leptospira species and analysed through phylogenetic analysis. RESULTS: A total of 418 Leptospira spp. 16S rRNA sequences isolated from 55 bat species from 14 countries were retrieved from 15 selected manuscripts. From these, 417 sequences clustered within the P1/pathogenic group, and only one sequence clustered within the P2/intermediate group. Six major clades of P1/pathogenic Leptospira spp. were identified, three of them composed exclusively of sequences obtained from bats. CONCLUSION: We identified that bats harbour a great genetic diversity of Leptospira spp. that form part of the P1/pathogenic clade, some of which are closely related to leptospirosis-associated species. This finding contributes to the knowledge of the diversity of leptospires hosted by bats worldwide and reinforces the role of bats as reservoirs of P1/pathogenic Leptospira spp.

The impact of policy and policy communication on COVID-19 vaccination inequalities among Venezuelan refugees and migrants in Colombia: a comparative cross-sectional interrupted time-series analysis.

INTRODUCTION: Equitable access to vaccines for migrants and refugees is necessary to ensure their right to health and to achieve public health goals of reducing vaccine-preventable illness. Public health policies require regulatory frameworks and communication to effect uptake of effective vaccines among the target population. In Colombia, the National COVID-19 Vaccination Plan implicitly included Venezuelan refugees and migrants; however, initial communication of the policy indicated that vaccine availability was restricted to people with regular migration status. We estimated the impact of a public announcement, which clarified access for refugees and migrants, on vaccination coverage among Venezuelans living in Colombia. METHODS: Between 30 July 2021 and 5 February 2022, 6221 adult Venezuelans participated in a cross-sectional, population-based health survey. We used a comparative cross-sectional time-series analysis to estimate the effect of the October 2021 announcement on the average biweekly change in COVID-19 vaccine coverage of Venezuelans with regular and irregular migration status. RESULTS: 71% of Venezuelans had an irregular status. The baseline (preannouncement) vaccine coverage was lower among people with an irregular status but increased at similar rates as those with a regular status. After the announcement, there was a level change of 14.49% (95% CI: 1.57 to 27.42, p=0.03) in vaccination rates among individuals with irregular migration status with a 4.61% increase in vaccination rate per biweekly period (95% CI: 1.71 to 7.51, p=0.004). By February 2022, there was a 26.2% relative increase in vaccinations among individuals with irregular migration status compared with what was expected without the announcement. CONCLUSION: While there was no policy change, communication clarifying the policy drastically reduced vaccination inequalities across migration status. Lessons can be translated from the COVID-19 pandemic into more effective global, regional and local public health emergency preparedness and response to displacement.

Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Are the Chicago 3.0 manometric diagnostics consistent with Chicago 4.0?

There is little information on the degree of concordance between the results obtained using the Chicago 3.0 (CCv3.0) and Chicago 4.0 (CCv4.0) protocols to interpret high-resolution manometry (HRM) seeking to determine the value provided by the new swallowing maneuvers included in the last protocol. This is a study of diagnostic tests, evaluating concordance by consistency between the results obtained by the CCv3.0 and CCv4.0 protocols, in patients undergoing HRM. Concordance was assessed with the kappa test. Bland-Altman scatter plots, and Lin's correlation-concordance coefficient (CCC) were used to assess the agreement between IRP measured with swallows in the supine and seated position or with solid swallows. One hundred thirty-two patients were included (65% women, age 53 ± 17 years). The most frequent HRM indication was dysphagia (46.1%). Type I was the most common type of gastroesophageal junction. The most frequent CCv4.0 diagnoses were normal esophageal motility (68.9%), achalasia (15.5%), and ineffective esophageal motility (IEM; 5.3%). The agreement between the results was substantial (Kappa 0.77 ± 0.05), with a total agreement of 87.9%. Diagnostic reclassification occurred in 12.1%, from IEM in CCv3.0 to normal esophageal motility in CCv4.0. Similarly, there was a high level of agreement between the IRP measured in the supine compared to the seated position (CCC0.92) and with solid swallows (CCC0.96). In conclusion, the CCv4.0 protocol presents a high concordance compared to CCv3.0. In the majority of manometric diagnoses there is no reclassification of patients with provocation tests. However, the more restrictive criteria of CCv4.0 achieve a better reclassification of patients with IEM.

Adverse events during the COVID-19 pandemic in Ecuador: high frequency of healthcare-associated infections and increasing hospital stay and costs.

Background: The COVID-19 pandemic generated high workloads given the high volume of seriously ill patients; conditions that could increase the risk of adverse events (AE). This study analyzed the frequency of AE in patients with COVID-19 and their effect on mortality, hospital stay and costs. Methods: This retrospective cohort study included in-patients with COVID-19 at a single hospital between March 2020-June 2021. Exposure was the occurrence of at least one AE. Hospital stay, costs and death were considered outcomes. Clinical information and direct costs were obtained from medical and billing records. Generalized linear models were used to estimate the association measures. Results: 405 patients were included, 55.8% (n=226) men, median age 56 years (IQR: 41.0-70.0) and with a history of hypertension (26.2%; n=106), diabetes mellitus (13.8%; n=56) and obesity (13.8%; n=56). The incidence of AE was 13.3% (n=54), 29 patients presented more than one AE, for a total of 70 events. Most events (74.3%; n=52) were preventable and the most frequent were healthcare-associated infections (50%; n=35), phlebitis (14.3%; n=10) and pressure ulcers (12.9%; n=9). AE prolonged hospital stay (change rate: 1.57; 95%CI: 1.26-1.95; P=0.001) and increased direct healthcare costs (change rate: 1.20; 95% CI: 1.03-1.39, P=0.019). Likewise, the risk of death was 56% higher in patients with AE. Conclusion: Pandemics are unexpected events that present challenges to safe healthcare. Improving quality policies, monitoring compliance with protocols and providing ongoing education are strategies to prevent AE such as healthcare-associated infections, which increase hospital costs and stay.

Costo-efectividad de la calidad del control prenatal con respecto al bajo peso al nacer en el Cauca / Antenatal control quality cost-effectiveness regarding low birth weight in Cauca

Antecedentes: El departamento del Cauca en Colombia es multiétnico, multicultural y biodiverso, también con grandes diferencias en bajo peso al nacer (BPN), mortalidad perinatal y mortalidad neonatal tardía entre municipios. Objetivo: Determinar la relación de costo-efectividad del control prenatal (CPN) cuando ha tenido buena calidad frente al que ha tenido calidad deficiente con respecto al BPN en el departamento del Cauca entre 2018 y 2020. Método: Evaluación económica con diseño epidemiológico de una cohorte histórica desde la perspectiva de la institución pagadora. Se calculó la razón incremental de costo-efectividad (RICE), análisis de sensibilidad e impacto presupuestal. Resultados: La incidencia de BPN fue del 8,3% (348/4182). La calidad deficiente en el CPN incrementó el riesgo de BPN (OR: 3,38; IC95%: 1,05-8,2) y la buena calidad tuvo una mejor relación de costo-efectividad (RICE: USD 2727,75), con posición dominante frente a la calidad deficiente (6,14 veces el PIB per cápita de ahorro) y con un impacto presupuestal de USD 2.904.392. Conclusiones: La buena calidad del CPN en el departamento del Cauca durante 2018-2020 fue costo-efectiva y dominante por ser de menor costo y mayor efectividad.

Background: The department of Cauca in Colombia is multiethnic, multicultural, and biodiverse, also with large differences in low birth weight (LBW), perinatal mortality, and late neonatal mortality among municipalities. Objective: To determine the cost-effectiveness relationship of antenatal care (ANC) when it has had good quality compared to that which has had poor quality with respect to low birth weight in the department of Cauca between 2018 and 2019. Method: Economic evaluation with epidemiological cohort design historical from the perspective of the payer institution. Incremental cost-effectiveness ratio (RICE), sensitivity analysis, and budgetary impact were calculated. Results: The incidence of LBW was 8.3% (348/4182). Poor quality in ANC increased the risk of LBW (OR: 3.38; CI95%: 1.05-8.2), good quality had a better cost-effectiveness ratio (RICE: USD 2727.75), with dominant position against poor quality (6.14 times the GDP/capita savings) with a budgetary impact of USD 2,904,392. Conclusions: The good quality of the ANC in the department of Cauca during 2018-2020 was cost-effective and dominant because it is lower cost and more effective.

A systematic review of the evaluation of agricultural policies: Using prisma.

Background: The food security of each country depends on agricultural development, which is sensitive to the implementation of agricultural public policies. These must evolve as new ruralities arise, with new phenomena, such as climate change, ecosystem services, changes in consumer preferences, globalization, sustainability and ecological awareness. Hence, of ex-ante and ex-post evaluations of agricultural policies, are important because they provide timely information to government entities. There are different methodologies for policy evaluation, which have evolved over time. Aims: This systematic review aims to identify manuscript that systematically review methodologies, policies and variables evaluated during the last 50 years to determine whether a policy has been efficient. To assess the quality of the included manuscript and to describe the measures and domains identified. Methods: EBSCO, Dialnet, SciELO, Scopus, Science Direct, Dimensions and Web of Science were searched. A total of 154 manuscript were identified, the review was finalized by reviewing the title, and abstract and the review was finalized by reviewing the title, abstract and full text, resolving disagreements. Of these 154 manuscripts, 37 met the criteria and were included in the analysis. PRISMA checklists were used to evaluate the methodology. Outcomes and results: It were found that there are few studies on the design of evaluation methodologies for agricultural policies in the literature. Research shows that the latest policy evaluation proposals present more complex methodologies involving tools such as machine learning and agent-based modelling (ABM). On the other hand, the issue of sustainability as a policy is seen in the agri-environmental policy evaluation. Conclusions and implications: The evolution of agricultural policy methodologies can be observed at the beginning with the use of quantitative methodologies, such as matrices, statistics and econometrics. With the emergence of new variables, such as agri-environmental variables, citizen participation and market opening, methodologies have become more comprehensive, combining qualitative and quantitative variables. Methodologies were identified that evaluate robust agricultural policies and others that focus on the evaluation of one or two policies. These studies are important for research that focuses not only on the evaluation of agricultural policies but also on their design and implementation processes.

CXCR5 and TIM-3 expressions define distinct exhausted T cell subsets in experimental cutaneous infection with Leishmania mexicana.

T-cell exhaustion is a key stage in chronic infections since it limits immunopathology, but also hinders the elimination of pathogens. Exhausted T (Tex) cells encompass dynamic subsets, including progenitor cells that sustain long-term immunity through their memory/stem like properties, and terminally-differentiated cells, resembling the so-called Tex cells. The presence of Tex cells in chronic leishmaniasis has been reported in humans and murine models, yet their heterogeneity remains unexplored. Using flow cytometry, we identified Tex cells subtypes based on PD-1, CXCR5 and TIM-3 expressions in draining lymph nodes (dLNs) and lesion sites of C57BL/6 mice infected with L. mexicana at 30-, 60- and 90-days post-infection. We showed that infected mice developed a chronic infection characterized by non-healing lesions with a high parasite load and impaired Th1/Th2 cytokine production. Throughout the infection, PD-1+ cells were observed in dLNs, in addition to an enhanced expression of PD-1 in both CD4+ and CD8+ T lymphocytes. We demonstrated that CD4+ and CD8+ T cells were subdivided into PD-1+CXCR5+TIM-3- (CXCR5+), PD-1+CXCR5+TIM-3+ (CXCR5+TIM-3+), and PD-1+CXCR5-TIM-3+ (TIM-3+) subsets. CXCR5+ Tex cells were detected in dLNs during the whole course of the infection, whereas TIM-3+ cells were predominantly localized in the infection sites at day 90. CXCR5+TIM-3+ cells only increased at 30 and 60 days of infection in dLNs, whereas no increase was observed in the lesions. Phenotypic analysis revealed that CXCR5+ cells expressed significantly higher levels of CCR7 and lower levels of CX3CR1, PD-1, TIM-3, and CD39 compared to the TIM-3+ subset. CXCR5+TIM-3+ cells expressed the highest levels of all exhaustion-associated markers and of CX3CR1. In agreement with a less exhausted phenotype, the frequency of proliferating Ki-67 and IFN-γ expressing cells was significantly higher in the CXCR5+ subset within both CD4+ and CD8+ T cells compared to their respective TIM-3+ subsets, whereas CD8+CXCR5+TIM-3+ and CD8+TIM-3+ subsets showed an enhanced frequency of degranulating CD107a+ cells. In summary, we identified a novel, less-differentiated CXCR5+ Tex subset in experimental cutaneous leishmaniasis caused by L. mexicana. Targeting these cells through immune checkpoint inhibitors such as anti-PD-1 or anti PD-L1 might improve the current treatment for patients with the chronic forms of leishmaniasis.

Reparación del músculo pronador cuadrado en fracturas de radio distal tratadas con fijación interna por abordaje palmar: una revisión sistemática y metaanálisis / Repair of the pronator quadratus muscle in distal radius fractures treated with internal fixation through a palmar approach: a systematic review and meta-analysis

Introducción: el músculo pronador cuadrado funciona como un estabilizador dinámico de la articulación radiocubital distal. Su reparación posterior a la fijación interna con placa de bloqueo volar en fracturas distales del radio es controvertida. Objetivo: determinar si la reparación del músculo pronador cuadrado influye en los resultados clínicos y funcionales de pacientes con fractura de radio distal que se sometieron a reducción abierta y fijación interna con placa de bloqueo volar. Materiales y métodos: se realizó una revisión sistemática y metanálisis. Las bases de datos analizadas fueron PubMed/Medline, Embase y Bireme/Lilacs (búsqueda realizada hasta el 20 de febrero del año 2023). Los términos de búsqueda fueron: distal radius fracture AND volar plate AND pronator quadratus. Se determinó la calidad metodológica según el manual de revisiones Cochrane. Resultados: en total se incluyeron 4 ensayos clínicos aleatorizados de adecuada calidad metodológica, lo cual corresponde al análisis de 213 participantes. Existen mejores resultados en la puntuación DASH a los 12 meses de seguimiento en el grupo de no reparación del músculo pronador cuadrado DM 2,8 [IC 95%: 0,51;5,10]. No hubo diferencias significativas al año de seguimiento en las puntuaciones de dolor, rangos de movilidad de la muñeca, fuerza de agarre e incidencia de complicaciones. Conclusión: no existe evidencia que sustente la reparación rutinaria del músculo pronador cuadrado posterior a la fijación interna con placa de bloqueo volar en las fracturas de radio distal. (AU)

Introduction: the pronator quadratus muscle functions as a dynamic stabilizer of the distal radioulnar joint, and its repair after internal fixation with volar locking plate in distal radius fractures is controversial. Objective: to determine whether the repair of the pronator quadratus muscle influences the clinical and functional outcomes of patients with distal radius fracture who underwent open reduction and internal fixation with volar locking plate. Materials and methods: a systematic review and meta-analysis were conducted. The analyzed databases were Pubmed/Medline, Embase, and Bireme/Lilacs (search performed until February 20th, 2023). The search terms were distal radius fracture AND volar plate AND pronator quadratus. Methodological quality was determined according to the Cochrane Reviewer's Handbook. Results: a total of 4 randomized clinical trials of adequate methodological quality, corresponding to the analysis of 213 participants, were included. Better DASH scores were observed at 12 months of follow-up in the non-repair group of the pronator quadratus muscle, with a mean difference of 2.8 [95% CI 0.51; 5.10]. There were no significant differences at one-year follow-up in pain scores, wrist mobility ranges, grip strength, and incidence of complications. Conclusion: there is no evidence to support routine repair of the pronator quadratus muscle after internal fixation with volar locking plate in distal radius fractures. (AU)

Genome-Scale Metabolic Reconstruction, Non-Targeted LC-QTOF-MS Based Metabolomics Data, and Evaluation of Anticancer Activity of Cannabis sativa Leaf Extracts.

Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly Cannabis sativa, leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that C. sativa can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of C. sativa is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.

Zoonotic febrile illnesses misdiagnosed as COVID-19: a review of reported clinical cases.

COVID-19 is a zoonotic coronavirus disease caused by SARS-CoV-2. Its fast spreading by aerosol transmission has made it a highly contagious disease, causing the most recent 2020 pandemic. Although it mainly affects the respiratory system, atypical forms of the disease have been described, including developing an undifferentiated febrile illness without respiratory symptoms, that can represent a diagnostic challenge, mainly in tropical areas where several zoonotic febrile diseases are circulating. Thus, despite the broad clinical spectrum of COVID-19, in the tropics, other zoonotic etiologies should always be considered as differential diagnoses. According to our case reports review, eight different zoonotic febrile diseases misdiagnosed as COVID-19 have been reported in the available scientific literature of four databases. These were only suspected due to the epidemiological history. Thus, making a complete and detailed clinical history of a febrile patient in the tropics is essential to suspect the etiology and request the necessary confirmatory tests. Therefore, COVID-19 must be included as a differential diagnosis of undifferentiated febrile illness in the tropics, but other zoonotic infectious diseases must not be ruled out.

HIV infection and engagement in the care continuum among migrants and refugees from Venezuela in Colombia: a cross-sectional, biobehavioural survey.

BACKGROUND: Venezuela has experienced substantial human displacement since 2015. To inform HIV programmes and treatment distribution, we aimed to estimate HIV prevalence and associated indicators among migrants and refugees from Venezuela residing in Colombia, the largest receiving country. METHODS: We conducted a biobehavioural, cross-sectional survey using respondent-driven sampling among Venezuelan people aged 18 years or older who had arrived in Colombia since 2015 and resided in four cities (ie, Bogotá, Soacha, Soledad, and Barranquilla). Participants completed sociobehavioural questionnaires and rapid HIV and syphilis screening with laboratory-based confirmatory testing, CD4 cell counts, and viral load quantification. Policies related to migration status affect access to insurance and HIV services in Colombia, as in many receiving countries, so we provided legal assistance and navigation support to participants with HIV for sustained access to treatment. Population-based estimates were weighted for the complex sampling design. Penalised multivariable logistic regression analysis was used to identify correlates of viral suppression (HIV-1 RNA <1000 copies per mL). FINDINGS: Between July 30, 2021, and Feb 5, 2022, 6506 participants were recruited through respondent-driven sampling, of whom 6221 were enrolled. 4046 (65·1%) of 6217 were cisgender women, 2124 (34·2%) of 6217 were cisgender men, and 47 (0·8%) of 6217 were transgender or non-binary people. 71 (1·1%) of all 6221 participants had laboratory-confirmed HIV infection, resulting in a weighted population HIV prevalence of 0·9% (95% CI 0·6-1·4). Among participants living with HIV, 34 (47·9%) of 71 had been previously diagnosed with HIV and 25 (35·7%) of 70 had viral suppression. Individuals with irregular migration status compared with individuals with regular migration status (adjusted odds ratio 0·3, 95% CI 0·1-0·9) and with a most recent HIV test in Colombia compared with a most recent test in Venezuela (0·2, 0·1-0·8) were less likely to have suppressed viral loads. INTERPRETATION: HIV prevalence among migrants and refugees from Venezuela in Colombia suggests the HIV epidemic is close to being generalised, which could be addressed by the inclusion of migrants and refugees from Venezuela in local HIV services, improved access to and navigation support for HIV testing and care, and coordination with humanitarian programmes. There is an association between migration status and viral suppression, conferring both clinical and epidemiological implications. Therefore, legal support and access to insurance might lead to early detection of HIV and timely treatment for people with irregular migration status. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Three-dimensional neuroimmune co-culture system for modeling Parkinson's disease microenvironmentsin vitro.

Parkinson's disease (PD) is a complex and multifaceted neurodegenerative disorder that results from multiple environmental factors and multicellular interactions. Although several PD neuropathologies have been identified and described, the thorough understanding of PD pathophysiology and research has been largely limited by the absence of reliablein vitromodels that truly recapitulate PD microenvironments. Here, we propose a neuroimmune co-culture system that models PD neuropathologies by combining relevant multicellular interactions with environments that mimic the brain. This system is composed of: (i) 3D bioprinted cultures of mature human dopaminergic (DA) neurons grown on extracellular matrix (ECM)-derived scaffolds doped with electroconductive nanostructures, and (ii) a direct co-culture of human astrocytes and differentiated monocytes that models neuroinflammatory responses. When co-cultured in a transwell format, these two compartments recreate relevant multicellular environments that model PD pathologies after exposure to the neurotoxin A53Tα-synuclein. With immunofluorescent staining and gene expression analyses, we show that functional and mature DA 3D networks are generated within our ECM-derived scaffolds with superior performance to standard 2D cultures. Moreover, by analyzing cytokine secretion, cell surface markers, and gene expression, we define a human monocyte differentiation scheme that allows the appearance of both monocyte-derived macrophages and dendritic cell phenotypes, as well as their optimal co-culture ratios with human astrocytes to recreate synergistic neuroinflammatory responses. We show that the combined response of both compartments to A53Tα-synuclein stimulates the formation of intracellularα-synuclein aggregates, induces progressive mitochondrial dysfunction and reactive oxygen species production, downregulates the expression of synaptic, DA, and mitophagy-related genes, and promotes the initiation of apoptotic processes within the DA networks. Most importantly, these intracellular pathologies were comparable or superior to those generated with a rotenone-stimulated 2D control that represents the current standard forin vitroPD models and showed increased resilience towards these neurotoxic insults, allowing the study of disease progression over longer time periods than current models. Taken together, these results position the proposed model as a superior alternative to current 2D models for generating PD-related pathologiesin vitro.

Pyrethroid genetic resistance in the dengue vector (Aedes aegypti) in Posadas, Argentina.

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

The Economic Evaluation of Mastitis Control Strategies in Holstein-Friesian Dairy Herds.

The economic evaluation of mastitis control is challenging. The objective of this study was to perform the economic evaluation of mastitis control, under different intervention scenarios, quantifying the total cost of mastitis caused by S. aureus in Holstein cows in Argentina. A model was set for a dairy herd of Holstein cows endemically infected with S. aureus. A basic mastitis control plan including proper milking procedures, milking machine test, dry cow therapy, and treatment for clinical mastitis, was compared against other more complex and costly interventions, such as segregation and culling of chronically infected cows. Sensitivity analysis was performed by modifying the intramammary infection transition probabilities, economic parameters, and efficacy of treatment strategies. The basic mastitis control plan showed a median total cost of USD88.6/cow per year, which was close to the infected cows culling scenarios outputs. However, the segregation scenario was the most efficient, in which the total cost was reduced by about 50%. Such cost was more sensitive to probabilities and efficacy than the economic parameters. The model is flexible and can be customized by producers and veterinarians according to different control and herd settings.

Qualitative assessment of the impacts of the COVID-19 pandemic on migration, access to healthcare, and social wellbeing among Venezuelan migrants and refugees in Colombia.

Background: Colombia hosts a large number of Venezuelan migrants and refugees who are uniquely vulnerable and have been markedly impacted by the COVID-19 pandemic. It is necessary to understand their experiences to inform future policy decisions both in Colombia and during disease outbreaks in other humanitarian contexts in the future. As part of a larger study focused on HIV among Venezuelans residing in Colombia, qualitative interviews were conducted to understand this population's experiences and access to healthcare. Methods: Interviews were conducted with Venezuelan migrants and refugees as well as stakeholders such as care providers, humanitarian workers, and government officials. Interviews were recorded, transcribed, and coded using thematic content analysis. Select quotes were translated and edited for length and/or clarity. Results: Venezuelan migrants and refugees reported high levels of housing instability, job instability, increased barriers to accessing healthcare, and complications in engaging in the HIV care continuum, among other impacts of the COVID-19 pandemic. Stakeholders reported complications in provision of care and obtaining medicines, difficulty maintaining contact with patients, increased discrimination and xenophobia targeting Venezuelan migrants and refugees, increased housing instability among Venezuelan migrants and refugees, and other impacts as a result of the COVID-19 pandemic. Conclusions: This study demonstrates the unique impacts of the COVID-19 pandemic among Venezuelans residing in Colombia by both compounding extant vulnerabilities and introducing new challenges, such as high rates of eviction. Colombia has enacted increasingly inclusive migration policies for Venezuelan refugees and migrants within the country; findings from this study underscore the necessity for such policies both in and outside of the Colombian context.