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Hantavirus Pulmonary Syndrome (HPS), characterized by its high fatality rate, poses a significant public health concern in Argentina due to the increasing evidence of person-to-person transmission of Andes virus. Several orthohantaviruses were described in the country, but their phylogenetic relationships were inferred from partial genomic sequences. The objectives of this work were to assess the viral diversity of the most prevalent orthohantaviruses associated with HPS cases in the Central-East (CE) region of Argentina, elucidate the geographic patterns of distribution of each variant and reconstruct comprehensive phylogenetic relationships utilizing complete genomic sequencing. To accomplish this, a detailed analysis was conducted of the geographic distribution of reported cases within the most impacted province of the region. A representative sample of cases was then selected to generate a geographic map illustrating the distribution of viral variants. Complete viral genomes were obtained from HPS cases reported in the region, including some from epidemiologically linked cases. The phylogenetic analysis based on complete genomes defined two separate clades in Argentina: Andes virus in the Southwestern region and Andes-like viruses in other parts of the country. In the CE region, Buenos Aires virus and Lechiguanas virus clearly segregate in two subclades. Complete genomes were useful to distinguish person-to-person transmission from environmental co-exposure to rodent population. This study enhances the understanding of the genetic diversity, geographical spread, and transmission dynamics of orthohantaviruses in Central Argentina and prompt to consider the inclusion of Buenos Aires virus and Lechiguanas virus in the species Orthohantavirus andesense, as named viruses.

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Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.

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Background: Snake envenomation is a medical condition with high morbidity and mortality in southwestern Colombia. Objectives: To describe the characteristics of the envenomation caused by Viperidae snakes view in a highly complex hospital in Southwestern Colombia. Methods: A cross-sectional study was carried out. Patients treated for Viperidae snake envenomation from 2001 to 2020 in a Hospital Fundación Valle del Lili, Cali, Colombia, were studied. Results: Twenty-eight patients were included. Envenomation was caused by the genera Bothrops, Bothriechis, Porthidium, and Bothrocophias. The median age was 37.7 (±20.6), and they were predominantly male (19, 68%). Bites occurred on the upper extremities in 16 (57%) patients. Pain (23, 81%) and edema (22, 78%) were the most common clinical symptoms. Thirteen (46%) patients presented coagulopathy. Prolonged prothrombin and activated partial thromboplastin times were common: (22, 78% and 15, 53%, respectively). Twenty (71%) patients were treated with polyvalent antivenom (median dose of 6 (2-15) vials). The median time between the accident and antivenom administration was 9 h (5.5-17). Door-to-needle time was 37.5 (0-62) min. Eighteen (64%) patients were admitted to the intensive care unit. Three (11%) patients had serum sickness. Seven (25%) developed infectious complications, four (14%) had surgery, one (3%) had compartment syndrome, one (3%) underwent amputation of the affected limb, and one (3%) patient died. Conclusions: Local manifestations and coagulopathy were common clinical features. Polyvalent antivenom was an effective treatment for disease control. Significant complications were associated with delays in seeking medical care.

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INTRODUCTION: Bothriechis schlegelii is a Crotaline viperid species of Central America and Northern South America. The characteristics of its envenomation have not been well established. We present clinical characteristics of human cases evaluated and treated in a hospital in southwestern Colombia. METHODS: We evaluated data from patients who suffered Bothriechis schlegelii envenomation and were seen at Fundación Valle del Lili Hospital, Cali, Colombia between 2011 and 2022. RESULTS: Eight patients were included, with a median age of 24 years. Snakebites occurred in rural areas. Six (75%) patients were bitten on the upper extremities in relation to the arboreal habits of this animal. The most common symptoms were pain and edema (N = 8, 100%), ecchymoses (N = 2, 25%), and paresthesia (N = 2, 25%). The most common systemic findings were hypofibrinogenemia (N = 8, 100%) and prolonged prothrombin time in five patients (N = 5, 62.5%). All were treated with polyvalent antivenom for Colombian snakes, with a good response and outcome. CONCLUSIONS: Most bite sites from B. schlegelii were on the upper limbs. All patients had both local manifestations, including edema, pain, and systemic effects with hypofibrinogenemia, but none had systemic bleeding. Every patient received antivenom and had favorable outcomes.

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PURPOSE: This study aims to evaluate the ocular surface characteristics in children diagnosed with uveitis and explore the association between uveitis and dry eye disease (DED). METHODS: We included 84 children, 42 with uveitis and 42 healthy children. We performed the OSDI questionnaire and several ocular surface tests, including osmolarity, NITBUT, Schirmer test, and vital staining. We used Fisher's exact test and Mann-Whitney to compare variables and a binomial logistic regression to determine the factors associated with DED. RESULTS: The difference in the prevalence of DED between uveitis (54.8%) and healthy (31%) groups was statistically significant (p < 0.05). Most patients with uveitis had mixed DED, and none of the healthy subjects had a severe form of the disease. There were no statistically significant differences in most of the tear film tests. However, all parameters tended to worsen in the uveitis group, and lipid layer thickness was thinner (p < 0.036). The uveitis group exhibited significantly more symptoms (p < 0.05). In the multivariate logistic regression, uveitis was associated with an odds ratio (OR) of 3.0 (95% CI: 1.07-8.42, p < 0.05) for DED. CONCLUSIONS: Our findings demonstrate a significantly higher prevalence of DED in children with uveitis compared to their healthy counterparts. Furthermore, our analysis indicates that the risk of DED in pediatric patients with uveitis is threefold higher than in healthy children. Therefore, it is crucial for clinicians to vigilantly monitor the development of DED in pediatric patients with uveitis and consider the implementation of preventive treatments.

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BACKGROUND: Glucocorticoid (GR) and mineralocorticoid (MR) receptors are highly expressed in cardiac tissue, and both can be activated by corticosteroids. MR activation, in acute myocardial infarction (AMI), worsens cardiac function, and increase NHE activity contributing to the deleterious process. In contrast, effects of GR activation are not fully understood, probably because of the controversial scenario generated by using different doses or potencies of corticosteroids. AIMS: We tested the hypothesis that an acute dose of hydrocortisone (HC), a low-potency glucocorticoid, in a murine model of AMI could be cardioprotective by regulating NHE1 activity, leading to a decrease in oxidative stress. MATERIALS AND METHODS: Isolated hearts from Wistar rats were subjected to regional ischemic protocol. HC (10 nmol/L) was added to the perfusate during early reperfusion. Infarct size and oxidative stress were determined. Isolated papillary muscles from non-infarcted hearts were used to evaluate HC effect on sodium-proton exchanger 1 (NHE1) by analysing intracellular pH recovery from acute transient acidosis. RESULTS: HC treatment decreased infarct size, improved cardiac mechanics, reduced oxidative stress after AMI, while restoring the decreased level of the pro-fusion mitochondrial protein MFN-2. Co-treatment with the GR-blocker Mifepristone avoided these effects. HC reduced NHE1 activity by increasing the NHE1 pro-inhibiting Ser648 phosphorylation site and its upstream kinase AKT. HC restored the decreased AKT phosphorylation and anti-apoptotic BCL-2 protein expression detected after AMI. CONCLUSIONS: Our results provide the first evidence that acute HC treatment during early reperfusion induces cardioprotection against AMI, associated with a non-genomic HC-triggered NHE1 inhibition by AKT and antioxidant action that might involves mitochondrial dynamics improvement.

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Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease caused by orthohantaviruses in the Americas. In Argentina, since 1995, several reservoirs and virus variants have been described, but the northeastern and central endemic zones in the country include an area without human or rodent infections, despite sharing rodent species with areas with that disease. The aim of this study was to search for orthohantavirus in rodent communities that inhabit this area, which borders two endemic areas of HPS. Small rodents were captured in June of 2022 through a total effort of 644 trap nights distributed in five grids located in the Iberá National Park, Corrientes, Northeastern Argentina. All rodents were sexed, weighed, and the species was recorded. Blood samples were extracted to detect ANDV-specific immunoglobulin G (IgG), and to extract the RNA virus. Trimmed sequences were mapped against reference sequences from GenBank. We captured a total of 36 Oligoryzomys flavescens and 15 Oxymycterus rufus. We detected the O. flavescens species infected with Lechiguanas orthohantavirus in the camping area of the National Park. A nucleotide comparison with previously published sequences shows a 98.34% similarity to the virus obtained from a human case of HPS reported in the adjacent Misiones province. This study demonstrated, for the first time, that O. flavescens is a host of the Lechiguanas orthohantavirus in this zone and contributes to closing information gaps on the distribution of orthohantavirus in Argentina. Additionally, the high similarity with the hantavirus found in the human case of Misiones suggests that the reservoir in that province would also be O. flavescens (not previously confirmed). This information permits us to focus on the preventive measurements to protect the human population.

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This study is based on the premise that the application of chemical synthesis strategies to structurally modify commercial drugs by complexation with biometals is a valid procedure to improve their biological effects. Our purpose is to synthesize a compound with greater efficacy than the original drug, able to enhance its antihypertensive and cardiac pharmacological activity. Herein, the structure of the coordination compound of Zn(II) and the antihypertensive drug olmesartan, [Zn(Olme)(H2O)2] (ZnOlme), is presented. After 8 weeks of treatment in SHR male rats, ZnOlme displayed a better blood pressure-lowering activity compared with olmesartan, with a noticeable effect even in the first weeks of treatment, while ZnCl2 showed similar results than the control. ZnOlme also reduced left ventricle (LV) weight and left ventricle/tibia length ratio (LV/TL), posterior wall thickness (PWT), and intraventricular septum in diastole (IVSd) suggesting its potential to prevent LV hypertrophy. Besides, ZnOlme reduced interstitial fibrosis (contents of collagen types I and III, responsible for giving rigidity and promoting vascular elasticity, respectively). The recovery of heart function was also evidenced by fractional shortening (diastolic left ventricular/systolic left ventricular) diameter determinations. Furthermore, ZnOlme increased the antioxidant capacity and prevented cardiac oxidative stress: it enhanced the reduction of reactive oxygen species generation, exerted a significant decrease in lipid peroxidation and enhanced glutathione contents in heart tissues compared to the control, Zn, and olmesartan treatments. Our results demonstrate that continuous oral administration of ZnOlme causes a better antihypertensive effect and grants enhancement of cardioprotection through antioxidant activity, in combination with hemodynamic improvement.

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BACKGROUND: the antihypertensive drug α-methyldopa (MD) stands as one of the extensively used medications for managing hypertension during pregnancy. Zinc deprivation has been associated with many diseases. In this context, the synthesis of a Zn coordination complex [Zn(MD)(OH)(H2O)2]·H2O (ZnMD) provide a promising alternative pathway to improve the biological properties of MD. METHODS: ZnMD was synthesized and physicochemically characterized. Fluorescence spectral studies were conducted to examine the binding of both, the ligand and the metal with bovine serum albumin (BSA). MD, ZnMD, and ZnCl2 were administered to spontaneous hypertensive rats (SHR) rats during 8 weeks and blood pressure and echocardiographic parameters were determined. Ex vivo assays were conducted to evaluate levels of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO). Cross-sectional area (CSA) and collagen levels of left ventricular cardiomyocytes were also assessed. Furthermore, the expression of NAD(P)H oxidase subunits (gp91phox and p47phox) and Superoxide Dismutase 1 (SOD1) was quantified through western blot analysis. RESULTS: The complex exhibited a moderate affinity for binding with BSA showing a spontaneous interaction (indicated by negative ΔG values) and moderate affinity (determined by affinity constant values). The binding process involved the formation of Van der Waals forces and hydrogen bonds. Upon treatment with MD and ZnMD, a reduction in the systolic blood pressure in SHR was observed, being ZnMD more effective than MD (122 ± 8.1 mmHg and 145 ± 5.6 mmHg, at 8th week of treatment, respectively). The ZnMD treatment prevented myocardial hypertrophy, improved the heart function and reduced the cardiac fibrosis, as evidenced by parameters such as left ventricular mass, fractional shortening, and histological studies. In contrast, MD did not show noticeable differences in these parameters. ZnMD regulates negatively the oxidative damage by reducing levels of ROS and lipid peroxidation, as well as the cardiac NAD(P)H oxidase, and increasing SOD1 expression, while MD did not show significant effect. Moreover, cardiac nitric oxide levels were greater in the ZnMD therapy compared to MD treatment. CONCLUSION: Both MD and ZnMD have the potential to be transported by albumin. Our findings provide important evidence suggesting that this complex could be a potential therapeutic drug for the treatment of hypertension and cardiac hypertrophy and dysfunction.

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Previous research conducted in central-east region of Argentina recorded potential orthohantavirus host rodents in diverse environments, but no research has focused particularly on islands, the environments that present the greatest risk to humans. For this reason, the aims of this research were to determine the orthohantavirus host in the rodent community focused on islands of Paraná River Delta, central-east region of Argentina, to identify temporal and spatial factors associated with orthohantavirus prevalence variations, to compare the functional traits of seropositive and seronegative rodents, and to explore the association between orthohantavirus prevalence and rodent community characteristics between August 2014 and May 2018. With a trapping effort of 14,600 trap-nights, a total of 348 sigmodontine rodent specimens belonging to seven species were captured 361 times. The overall antibody prevalence was 4.9%. Particularly, 14.9% of Oligoryzomys flavescens and 1.5% of Oxymycterus rufus, mainly reproductively active adult males, had antibodies against orthohantavirus. Even though O. flavescens inhabit all islands, our results suggest spatial heterogeneity in the viral distribution, with two months after periods of low temperature presenting increases in seroprevalence. This could be a response to the increased proportion of adults present in the rodent population. In addition, an association was found between the high seroprevalence and the diversity of the rodent assemblage. We also found 1.5% of O. rufus exposed to orthohantavirus, which shows us that further investigation of the ecology of the virus is needed to answer whether this species act as a spillover or a new competent host.

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Abstract Background: Determining the effect of reopening schools on pediatric SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection rates increased the need to share the experience of governments in many geographic regions for better future decision-making in similar health emergencies. Methods: Through a prospective study based on a population-based cohort, students from 18,988 schools in the State of Mexico who began returning to school were followed. Daily sanitation filters were implemented in each school and district liaisons were informed on a daily basis through a negative network. Identified cases were confirmed by reverse transcriptase-polymerase chain reaction. Simple case frequencies, percentages, and incidences of COVID-19 were estimated. State incidences were compared with the national incidence. Results: A total of 3,586 cases were confirmed; 2,048 (57.1%) were children. Twenty-four (0.6%) were hospitalized for moderate to severe COVID-19; nine (37.5%) died, and only one was a schoolchild. From week 36, an average infection rate of 0.36 was observed. The highest infection rate in schoolchildren was observed in epidemiologic week 40 (1.01); from this week on, a decrease in the number of cases was observed until week 50. Conclusions: The use of non-pharmaceutical interventions has more advantages than limitations, as long as the strategies are homogeneous and properly implemented to ensure adequate control of infections.

Resumen Introducción: La determinación del efecto de reabrir las escuelas sobre las tasas de infección pediátrica por SARS-CoV-2 (síndrome respiratorio agudo grave coronavirus 2) incrementó la necesidad de trasmitir la experiencia de los gobiernos de muchas regiones geográficas para mejores decisiones futuras en emergencias sanitarias similares. Métodos: Mediante un estudio prospectivo basado en una cohorte poblacional se dio seguimiento a los alumnos de 18,988 escuelas del Estado de México que iniciaron con el regreso a clases. Se implementaron filtros sanitarios diarios en cada escuela y cotidianamente se informaban a los enlaces jurisdiccionales a través de una red negativa. Los casos identificados eran confirmados a través de RT-PCR (reacción en cadena de la polimerasa con transcriptasa inversa). Se estimaron frecuencias simples de casos, porcentajes e incidencias de COVID-19. Las incidencias del estado se compararon con la incidencia nacional. Resultados: Un total de 3,586 casos fueron confirmados; 2,048 (57.1%) correspondieron a niños. Veinticuatro (0.6%) fueron hospitalizados por COVID-19 moderado a grave; nueve (37.5%) fallecieron, y solamente una correspondió a un escolar. A partir de la semana 36 se observó una tasa promedio de infecciones de 0.36. En la semana epidemiológica 40 se observó la mayor tasa de infección en escolares (1.01); a partir de esta semana se observa un declive de los casos hasta la semana 50. Conclusiones: La implementación de intervenciones no farmacéuticas tiene más ventajas que limitaciones, siempre y cuando las estrategias sean homogéneas y correctamente ejecutadas, lo que asegurará un adecuado control en los contagios.

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BACKGROUND: Determining the effect of reopening schools on pediatric SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection rates increased the need to share the experience of governments in many geographic regions for better future decision-making in similar health emergencies. METHODS: Through a prospective study based on a population-based cohort, students from 18,988 schools in the State of Mexico who began returning to school were followed. Daily sanitation filters were implemented in each school and district liaisons were informed on a daily basis through a negative network. Identified cases were confirmed by reverse transcriptase-polymerase chain reaction. Simple case frequencies, percentages, and incidences of COVID-19 were estimated. State incidences were compared with the national incidence. RESULTS: A total of 3,586 cases were confirmed; 2,048 (57.1%) were children. Twenty-four (0.6%) were hospitalized for moderate to severe COVID-19; nine (37.5%) died, and only one was a schoolchild. From week 36, an average infection rate of 0.36 was observed. The highest infection rate in schoolchildren was observed in epidemiologic week 40 (1.01); from this week on, a decrease in the number of cases was observed until week 50. CONCLUSIONS: The use of non-pharmaceutical interventions has more advantages than limitations, as long as the strategies are homogeneous and properly implemented to ensure adequate control of infections.

INTRODUCCIÓN: La determinación del efecto de reabrir las escuelas sobre las tasas de infección pediátrica por SARS-CoV-2 (síndrome respiratorio agudo grave coronavirus 2) incrementó la necesidad de trasmitir la experiencia de los gobiernos de muchas regiones geográficas para mejores decisiones futuras en emergencias sanitarias similares. MÉTODOS: Mediante un estudio prospectivo basado en una cohorte poblacional se dio seguimiento a los alumnos de 18,988 escuelas del Estado de México que iniciaron con el regreso a clases. Se implementaron filtros sanitarios diarios en cada escuela y cotidianamente se informaban a los enlaces jurisdiccionales a través de una red negativa. Los casos identificados eran confirmados a través de RT-PCR (reacción en cadena de la polimerasa con transcriptasa inversa). Se estimaron frecuencias simples de casos, porcentajes e incidencias de COVID-19. Las incidencias del estado se compararon con la incidencia nacional. RESULTADOS: Un total de 3,586 casos fueron confirmados; 2,048 (57.1%) correspondieron a niños. Veinticuatro (0.6%) fueron hospitalizados por COVID-19 moderado a grave; nueve (37.5%) fallecieron, y solamente una correspondió a un escolar. A partir de la semana 36 se observó una tasa promedio de infecciones de 0.36. En la semana epidemiológica 40 se observó la mayor tasa de infección en escolares (1.01); a partir de esta semana se observa un declive de los casos hasta la semana 50. CONCLUSIONES: La implementación de intervenciones no farmacéuticas tiene más ventajas que limitaciones, siempre y cuando las estrategias sean homogéneas y correctamente ejecutadas, lo que asegurará un adecuado control en los contagios.

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BACKGROUND: Hantavirus Pulmonary Syndrome (HPS) is a rodent-borne zoonosis in the Americas, with up to 50% mortality rates. In Argentina, the Northwestern endemic area presents half of the annually notified HPS cases in the country, transmitted by at least three rodent species recognized as reservoirs of Orthohantavirus. The potential distribution of reservoir species based on ecological niche models (ENM) can be a useful tool to establish risk areas for zoonotic diseases. Our main aim was to generate an Orthohantavirus risk transmission map based on ENM of the reservoir species in northwest Argentina (NWA), to compare this map with the distribution of HPS cases; and to explore the possible effect of climatic and environmental variables on the spatial variation of the infection risk. METHODS: Using the reservoir geographic occurrence data, climatic/environmental variables, and the maximum entropy method, we created models of potential geographic distribution for each reservoir in NWA. We explored the overlap of the HPS cases with the reservoir-based risk map and a deforestation map. Then, we calculated the human population at risk using a census radius layer and a comparison of the environmental variables' latitudinal variation with the distribution of HPS risk. RESULTS: We obtained a single best model for each reservoir. The temperature, rainfall, and vegetation cover contributed the most to the models. In total, 945 HPS cases were recorded, of which 97,85% were in the highest risk areas. We estimated that 18% of the NWA population was at risk and 78% of the cases occurred less than 10 km from deforestation. The highest niche overlap was between Calomys fecundus and Oligoryzomys chacoensis. CONCLUSIONS: This study identifies potential risk areas for HPS transmission based on climatic and environmental factors that determine the distribution of the reservoirs and Orthohantavirus transmission in NWA. This can be used by public health authorities as a tool to generate preventive and control measures for HPS in NWA.

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We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.

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The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients.

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Hypertension is the most common cause of left ventricular hypertrophy, contributing to heart failure progression. Candesartan (Cand) is an angiotensin receptor antagonist widely used for hypertension treatment. Structural modifications were previously performed by our group using Zinc (ZnCand) as a strategy for improving its pharmacological properties. The measurements showed that ZnCand exerts a stronger interaction with the angiotensin II receptor, type 1 (AT1 receptor), reducing oxidative stress and intracellular calcium flux, a mechanism implied in cell contraction. These results were accompanied by the reduction of the contractile capacity of mesangial cells. In vivo experiments showed that the complex causes a significant decrease in systolic blood pressure after 8 weeks of treatment in spontaneously hypertensive rats (SHR). The reduction of heart hypertrophy was evidenced by echocardiography, the histologic cross-sectional area of cardiomyocytes, collagen content, the B-type natriuretic peptide (BNP) marker and connective tissue growth factor (CTGF) and the matrix metalloproteinase 2 (MMP-2) expression. Besides, the complex restored the redox status. In this study, we demonstrated that the complexation with Zn(II) improves the antihypertensive and cardiac effects of the parental drug.

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This scoping review examined the relationship between Dry Eye Disease (DED) and Uveitis. We searched Pubmed, Embase, and LILACS databases for articles in which at least one patient had DED and uveitis concomitantly. The search produced 2381 records, and 24 studies were included in the qualitative synthesis. We concluded that DED and uveitis of any etiology could appear concomitantly in patients of any age. However, both diseases seem to coexist more frequently in middle-aged women and cases of anterior uveitis. Therefore, it is crucial that ophthalmologists actively look for the coexistence of ocular surface abnormalities, especially in patients with these characteristics. Future studies should establish and quantify the risk factors and pathophysiological mechanisms of this coexistence to achieve an early diagnosis of both etiologies and comprehensive management of these patients.

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Cutaneous lupus erythematosus (CLE) is a common disease that may appear as a separate entity from systemic lupus erythematosus (SLE), precede SLE development, or occur as a manifestation of this systemic disease. It has a complex pathophysiology that involves genetic, environmental, and immune-mediated factors creating a self-amplification pro-inflammatory cycle. CLE is characterized by prominent type I interferons (IFNs) inflammation which are considered as the first precursors of the inflammatory cascade generated within the pathophysiology of CLE. TNF-α enhances the production of antibodies through the activation of B cells, and favors the expression of surface nuclear antigens on keratinocytes. UV light exposure favors keratinocyte apoptosis or necroptosis, which results in the release of multiple proinflammatory cytokines, including IL-6, IL-1α, IL-1ß, TNF-α, IFNs, and CXCL10. Serum levels of IL-17 are elevated in patients with ACLE, SCLE, and DLE. Evidence suggests IL-22 plays a role primarily in tissue repair rather than in inflammation. High expression of BAFF and its receptors have been found in lesioned keratinocytes of patients with CLE, and patients with CLE have lower serum levels of the regulatory cytokines TGF-ß and IL-10. The chemokines CXCL9 and CXCL10 (CXCR3 ligands) have an increased expression among these patients, and their expression is correlated with IFNs levels. CXCR3 ligands recruit cytotoxic type I cells through this receptor, further supporting the death of keratinocytes via necroptosis with the subsequent release of eNAs perpetuating the inflammatory cycle. Interface dermatitis is characterized by the presence of CXCR3-positive lymphocytes. This review describes the leading cytokines and chemokines present in the circulation and skin that play a fundamental role in the pathogenesis of CLE.

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Abstract Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight native rodent species have been identified as HPS virus reservoirs in Argentina. The aim of this work was to detect the orthohantavirus genotypes present in a rodent commu-nity that inhabits a zone where a fatal HPS case occurred within an endemic locality of Central Argentina. We captured 27 rodents with a trapping effort of 723 trap nights. We detected 14.3% of infected Akodon azarae with the Pergamino genotype. This result expands the known distribution of this orthohantavirus. Although the Pergamino genotype has not been associated with human cases, the information about its distribution is relevant for risk assessment against potential changes in the virus infectivity.

Resumen El síndrome pulmonar por hantavirus (SPH) es una enfermedad infecciosa emergente en América. Ocho especies de roedores nativos han sido identificadas como reservorios del virus causante del SPH en la Argentina. El objetivo de este trabajo fue detectar los genotipos de orthohantavirus presentes en una comunidad de roedores que habita en una zona donde ocurrió un caso fatal de SPH, en una localidad endémica de Argentina central. Se capturaron 27 individuos con un esfuerzo de 723 trampas-noche. Se detectó un 14,3% de Akodon azarae infectados con el genotipo pergamino. Este resultado amplía el conocido rango de distribución de este orthohantavirus. A pesar de que el genotipo pergamino no ha sido asociado con casos humanos hasta el momento, la información sobre su distribución es relevante para analizar el riesgo ante un potencial cambio en la infectividad del virus.

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We describe a patient in Argentina with severe acute respiratory syndrome coronavirus 2 infection and hantavirus pulmonary syndrome (HPS). Although both coronavirus disease and HPS can be fatal when not diagnosed and treated promptly, HPS is much more lethal. This case report may contribute to improved detection of co-infections in HPS-endemic regions.

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