Reevaluation of the Toxoplasma gondii and Neospora caninum genomes reveals misassembly, karyotype differences, and chromosomal rearrangements.

Neospora caninum primarily infects cattle, causing abortions, with an estimated impact of a billion dollars on the worldwide economy annually. However, the study of its biology has been unheeded by the established paradigm that it is virtually identical to its close relative, the widely studied human pathogen Toxoplasma gondii By revisiting the genome sequence, assembly, and annotation using third-generation sequencing technologies, here we show that the N. caninum genome was originally incorrectly assembled under the presumption of synteny with T. gondii We show that major chromosomal rearrangements have occurred between these species. Importantly, we show that chromosomes originally named Chr VIIb and VIII are indeed fused, reducing the karyotype of both N. caninum and T. gondii to 13 chromosomes. We reannotate the N. caninum genome, revealing more than 500 new genes. We sequence and annotate the nonphotosynthetic plastid and mitochondrial genomes and show that although apicoplast genomes are virtually identical, high levels of gene fragmentation and reshuffling exist between species and strains. Our results correct assembly artifacts that are currently widely distributed in the genome database of N. caninum and T. gondii and, more importantly, highlight the mitochondria as a previously oversighted source of variability and pave the way for a change in the paradigm of synteny, encouraging rethinking the genome as basis of the comparative unique biology of these pathogens.

Molecular detection of coccidian Apicomplexa Parasites isolated from wild crab-eating and pampas foxes through novel TaqMan™ probes: a contribution to their molecular epidemiology.

Neospora caninum, Toxoplasma gondii and Hammondia spp. are coccidian parasites similar in morphology. Molecular techniques are necessary to detect parasite DNA isolated from stool samples in wild canids because they were reported as definitive hosts of N. caninum life cycle. The objective of this study was to develop a highly sensitive and accurate molecular method for the identification of coccidian Apicomplexa parasites in crab-eating fox (Cerdocyon thous) and pampas fox (Lycalopex gymnocercus). Tissue samples from road-killed animals (pampas fox = 46, crab-eating fox = 55) and feces (pampas fox = 84, crab-eating fox = 2) were collected, and species were diagnosed through molecular assay. PCR was used for the amplification of a fragment of the coccidian Apicomplexa nss-rRNA gene. Additionally, we developed a novel real-time PCR TaqMan™ probe approach to detect T. gondii- Hammondia spp. and N. caninum. This is the first report of N. caninum DNA in pampas fox feces (n = 1), thus it was also detected from pampas fox tissues (n = 1). Meanwhile, T. gondii was found in tissues of pampas (n = 1) and crab-eating (n = 1) foxes and H. triffittae in one crab-eating fox tissue. Despite the low percentage (2.5%) of positive samples, the molecular method developed in this study proved to be highly sensitive and accurate allowing to conduct an extensive monitoring analysis for these parasites in wildlife.

Isolation and molecular characterization of four novel Neospora caninum strains.

Neospora caninum causes neosporosis, a leading cause of bovine abortion worldwide. Uruguay is a developing economy in South America that produces milk to feed seven times its population annually. Naturally, dairy production is paramount to the country's economy, and bovine reproductive failure impacts it profoundly. Recent studies demonstrated that the vast majority of infectious abortions in dairy cows are caused by N. caninum. To delve into the local situation and contextualize it within the international standing, we set out to characterize the Uruguayan N. caninum strains. For this, we isolated four distinct strains and determined by microsatellite typing that these represent three unique genetic lineages, distinct from those reported previously in the region or elsewhere. An unbiased analysis of the current worldwide genetic diversity of N. caninum strains known, whereby six typing clusters can be resolved, revealed that three of the four Uruguayan strains group closely with regional strains from Argentina and Brazil. The remaining strain groups in an unrelated genetic cluster, suggesting multiple origins of the local strains. Microsatellite typing of N. caninum DNA from fetuses opportunistically collected from local dairy farms correlated more often with one of the isolates. Overall, our results contribute to further understanding of genetic diversity among strains of N. caninum both regionally and worldwide.

Insights into the Cell Division of Neospora caninum.

Neospora caninum is an apicomplexan protozoan parasite responsible for causing neosporosis in a range of animal species. It results in substantial economic losses in the livestock industry and poses significant health risks to companion and wild animals. Central to its survival and pathogenicity is the process of cell division, which remains poorly understood in this parasite. In this study, we explored the cell division of Neospora caninum using a combination of modern and classic imaging tools, emphasizing its pivotal role in perpetuating the parasite's life cycle and contributing to its ability to persist within host organisms. We described the intricacies of endodyogeny in Neospora caninum, detailing the dynamics of the cell assembly and the nuclear division by ultrastructure expansion microscopy and regular confocal microscopy. Furthermore, we explored the centrosome dynamics, the centrioles and the apicoplast through the advancement of the cell cycle. Our analysis described with unprecedented detail, the endodyogeny in this parasite. By advancing our understanding of these molecular mechanisms, we aimed to inspire innovative strategies for disease management and control, with the ultimate goal of mitigating the devastating impact of neosporosis on animal health and welfare.

Co-circulation of Hepatitis E Virus (HEV) Genotype 3 and Moose-HEV-Like Strains in Free-Ranging-Spotted Deer (Axis axis) in Uruguay.

Hepatitis E caused by hepatitis E virus (HEV) is considered an emerging foodborne zoonosis in industrialized, non-endemic countries. Domestic pigs and wild boars are considered the main reservoir of HEV. However, HEV can also infect an ever-expanding host range of animals, but they exact role in transmitting the virus to other species or humans is mostly unknown. In this work, we investigated the spread of HEV in free-living and captive spotted deer (Axis axis) from Uruguay in a 2-year period (2020-2022) and examined the role of this invasive species as a new potential reservoir of the virus. In addition, with the aim to gain new insights into viral ecology in the context of One Health, by using camera trapping, we identified and quantified temporal and spatial coexistence of spotted deer, wild boars, and cattle. In free-living animals, we detected an anti-HEV seropositivity of 11.1% (6/54). HEV infection and viral excretion in feces were assessed by RT-PCR. Thirteen of 19 samples (68.4%) had HEV RNA. Six samples were amplified using a broadly reactive RT-PCR and sequenced. No captive animal showed evidence of HEV infection. Additionally, HEV RNA was detected in a freshwater pond shared by these species. Phylogenetic and p-distance analysis revealed that zoonotic HEV genotype 3 strains circulate together with unclassified variants related to moose HEV whose potential risk of transmission to humans and other domestic and wild animals is unknown. The data presented here suggest that spotted deer (A. axis) may be a novel host for zoonotic HEV strains.

Genetic variability highlights the invasion route of the Lutzomyia longipalpis complex, the main vector of Visceral Leishmaniasis in Uruguay.

In the Americas, the sandfly Lutzomyia longipalpis is the main vector of the parasitic protozoa Leishmania infantum, the etiological agent of visceral leishmaniasis (VL). The Lu. longipalpis species complex is currently discontinuously distributed across the Neotropical region, from Mexico to the north of Argentina and Uruguay. During its continental spreading, it must have adapted to several biomes and temperature amplitudes, when founder events should have contributed to the high genetic divergence and geographical structure currently observed, reinforcing the speciation process. The first report of Lu. longipalpis in Uruguay was in 2010, calling the attention of Public Health authorities. Five years later, the parasite Le. infantum was recorded and in 2015 the first case of VL in canids was reported. Hitherto seven human cases by VL have been reported in Uruguay. Here, we publish the first DNA sequences from the mitochondrial genes ND4 and CYTB of Lu. longipalpis collected in Uruguay, and we used these molecular markers to investigate their genetic variability and population structure. We described four new ND4 haplotypes in a total of 98 (4/98) and one CYTB in a total of 77 (1/77). As expected, we were able to establish that the Lu. longipalpis collected in two localities (i.e. Salto and Bella Unión) from the north of Uruguay are closely related to the populations from neighbouring countries. We also propose that the possible route for the vector arrival to the region may have been through vegetation and forest corridors of the Uruguay River system, as well as it may have benefited from landscape modifications generated by commercial forestation. The ecological-scale processes shaping Lu. longipalpis populations, the identification of genetically homogeneous groups and the gene flow among them must be carefully investigated by using highly sensible molecular markers (i.e. genome wide SNPs) since it will help to the understanding of VL transmission and contribute to the planification of public policies on its control.

Alternative beliefs in psychedelic drug users.

Previous research has suggested that classical psychedelics can foster significant and enduring changes in personality traits and subjective wellbeing. Despite the lack of evidence for adverse effects on mental health stemming from psychedelic use, concerns persist regarding the capacity of these substances to modulate information processing and attitudes towards factual data. The aim of the present study was to investigate the propensity for accepting alternative facts and the general treatment of knowledge within a sample of 392 participants, 233 of whom reported at least a single incidence of psychedelic use in their lifetime. To do this, we leveraged step-wise methods of linear modelling investigating effects of demographics, psychiatric conditions and concomitant drug use. Our findings revealed a moderate positive association between psychedelic use and beliefs in alternative facts, as well as the specific belief that facts are politically influenced. However, no links were found for favouring intuition over evidence when confirming facts. Among other investigated drugs, only alcohol was negatively associated with beliefs in alternative facts. Taken together, our results support the link between psychedelic use and non-conformist thinking styles, which can be attributed to the psychological effects of the drugs themselves, but may also mirror a common trait related to unconventional beliefs and illicit substance use.

New insights into phenotype and genotype relationships in Neospora caninum.

The successful isolation of four new Neospora caninum strains from different regions and with different backgrounds (obtained from an abortion storm or congenitally infected and asymptomatic calves) allowed us previously to characterize natural isolates, finding differences in phenotype and microsatellites. Given the variability observed, we wondered in this work whether these differences had consequences in virulence, invasion and vertical transmission using cell cultures and murine neosporosis models. In addition, we performed the genomic analysis and SNP comparative studies of the NcURU isolates. The results obtained in this work allowed us to establish that NcURU isolates are of low virulence and have unique phenotypic characteristics. Likewise, sequencing their genomes has allowed us to delve into the genetic singularities underlying these phenotypes, as well as the common mutated genes. This work opens a new perspective for diagnostic purposes and formulating possible vaccines based on attenuated strains.

Trypanosoma cruzi Isolates Naturally Adapted to Congenital Transmission Display a Unique Strategy of Transplacental Passage.

Chagas disease is mainly transmitted by vertical transmission (VT) in nonendemic areas and in endemic areas where vector control programs have been successful. For the present study, we isolated natural Trypanosoma cruzi strains vertically transmitted through three generations and proceeded to study their molecular mechanism of VT using mice. No parasitemia was detected in immunocompetent mice, but the parasites were able to induce an immune response and colonize different organs. VT experiments revealed that infection with different strains did not affect mating, pregnancy, or resorption, but despite low parasitemia, VT strains reached the placenta and resulted in higher vertical transmission rates than strains of either moderate or high virulence. While the virulent strain modulated more than 2,500 placental genes, VT strains modulated 150, and only 29 genes are shared between them. VT strains downregulated genes associated with cell division and replication and upregulated immunomodulatory genes, leading to anti-inflammatory responses and tolerance. The virulent strain stimulated a strong proinflammatory immune response, and this molecular footprint correlated with histopathological analyses. We describe a unique placental response regarding the passage of T. cruzi VT isolates across the maternal-fetal interphase, challenging the current knowledge derived mainly from studies of laboratory-adapted or highly virulent strains. IMPORTANCE The main findings of this study are that we determined that there are Trypanosoma cruzi strains adapted to transplacental transmission and completely different from the commonly used laboratory reference strains. This implies a specific strategy for the vertical transmission of Chagas disease. It is impressive that the strains specialized for vertical transmission modify the gene expression of the placenta in a totally different way than the reference strains. In addition, we describe isolates of T. cruzi that cannot be transmitted transplacentally. Taken together, these results open up new insights into the molecular mechanisms of this insect vector-independent transmission form.

A holstein heifer infected with Neospora caninum NcUru3 congenitally transmits this strain to a viable offspring although infection does not protect her from aborting by a different N. caninum genotype in the subsequent gestation.

Neospora caninum is a leading cause of bovine abortion worldwide. Although the genetic diversity of this apicomplexan parasite has long been recognized, there is little information on whether infection with different genotypes results in different clinical outcomes or whether infection by a given genotype impairs protective immunity against abortion induced by different genotypes. Here, we provide evidence supporting that natural subclinical infection with isolate NcUru3 of N. caninum in a pregnant heifer did not provide protection against abortion caused by a different N. caninum genotype in the subsequent gestation. A Holstein heifer delivered a healthy calf congenitally infected with N. caninum. Specific anti-N. caninum IgG was detected by indirect ELISA in sera obtained from the dam at calving and the calf before ingestion of colostrum, indicating in utero exposure to the parasite in the latter. A N. caninum strain named NcUru3 was isolated and characterized by multilocus microsatellite typing from the brain of this neonate euthanized at 9 days of age. Sixty days after calving, the cow got pregnant, although she aborted spontaneously at ~6 months of gestation. Pathologic examination of the aborted fetus and placenta revealed typical lesions of neosporosis, including encephalitis, myocarditis, hepatitis, myositis, and placentitis. Neospora caninum DNA was amplified from the fetal brain, heart, kidney, and placenta, and multilocus microsatellite typing revealed a genotype that differed from isolate NcUru3 at the level of microsatellite marker 6A (MS6A). Serum obtained from the dam at the time of abortion had IgG that cross-recognized isolate NcUru3, as demonstrated by immunoblotting, indicating that the humoral immune response did not prevent the other genotype from infecting the fetus and inducing fetoplacental lesions and abortion. This is the first description of one same dam transmitting two N. caninum genotypes to her offspring in subsequent gestations.

Bovine Polyomavirus-1 (Epsilonpolyomavirus bovis): An Emerging Fetal Pathogen of Cattle That Causes Renal Lesions Resembling Polyomavirus-Associated Nephropathy of Humans.

Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.

Diagnostic Investigation of 100 Cases of Abortion in Sheep in Uruguay: 2015-2021.

The aim of this work was to identify causes of abortion through laboratory investigations in sheep flocks in Uruguay. One hundred cases of abortion, comprising 58 fetuses, 36 fetuses with their placentas, and 6 placentas were investigated in 2015-2021. Cases were subjected to gross and microscopic pathologic examinations, and microbiological and serological testing for the identification of causes of abortion, including protozoal, bacterial, and viral pathogens. An etiologic diagnosis was determined in 46 (46%) cases, including 33 (33%) cases caused by infectious pathogens, as determined by the detection of a pathogen along with the identification of fetoplacental lesions attributable to the detected pathogen. Twenty-seven cases (27%) were caused by Toxoplasma gondii, 5 (5%) by Campylobacter fetus subspecies fetus, and 1 (1%) by an unidentified species of Campylobacter. Fourteen cases (14%) had inflammatory and/or necrotizing fetoplacental lesions compatible with an infectious etiology. Although the cause for these lesions was not clearly identified, T. gondii was detected in 4 of these cases, opportunistic bacteria (Bacillus licheniformis, Streptococcus sp.) were isolated in 2 cases, and bovine viral diarrhea virus 1 subtype i (BVDV-1i) was detected in another. Campylobacter jejuni was identified in 1 (1%) severely autolyzed, mummified fetus. BVDV-2b was identified incidentally in one fetus with an etiologic diagnosis of toxoplasmosis. Microscopic agglutination test revealed antibodies against ≥1 Leptospira serovars in 15/63 (23.8%) fetuses; however, Leptospira was not identified by a combination of qPCR, culture, fluorescent antibody testing nor immunohistochemistry. Neospora caninum, Chlamydia abortus, Chlamydia pecorum, Coxiella burnetii and border disease virus were not detected in any of the analyzed cases. Death was attributed to dystocia in 13 (13%) fetuses delivered by 8 sheep, mostly from one highly prolific flock. Congenital malformations including inferior prognathism, a focal hepatic cyst, and enterohepatic agenesis were identified in one fetus each, the latter being the only one considered incompatible with postnatal life. Toxoplasmosis, campylobacteriosis and dystocia were the main identified causes of fetal losses. Despite the relatively low overall success rate in establishing an etiologic diagnosis, a systematic laboratory workup in cases of abortion is of value to identify their causes and enables zoonotic pathogens surveillance.

[Study on most common overnight urological service consultations.] / Principales consultas urológicas a la guardia de un hospital de alta complejidad.

INTRODUCTION: In Argentina, our institutionhas a urology resident on call who handles requests to the single radio during nighttime. Few studies address this important issue that provides useful information to promote education and optimize hospital dynamics. OBJECTIVE: To describe the characteristics of the calls received in the urology radio during night shifts. MATERIALS AND METHODS: During the night shifts, all calls to the radio were recorded during the period between June and July 2019. We determined: time, source, sex, and age of the patient, reason for the call and classified the calls according to: calls for immediate resolution (which required urological instrumental intervention, bladder catheterization or lavage, etc.), unnecessary calls (wrong number), and the number of emergencies that require calling a superior for immediate surgical resolution. RESULTS: We registered a total of 325 calls, most of them male patients. The main reason for calling was for placement, replacement, or washing of the urinary catheter or suprapubic catheter. We obtained 139 calls that required urological intervention. The highest number of calls was from the emergency department (119), followed by the Internal Medicine staff (47). Most of them (242) did not require patient admission. The total of unnecessary calls was three, corresponding to wrong number. CONCLUSION: This study helped us to characterize the calls to the Urology radio from other services and emergency department, allowing us to identify the most common problems and educate based on this.

INTRODUCCIÓN: En Argentina nuestra institución cuenta con un residente de guardia activa de urología que se ocupa de las llamadas al radio único durante la noche. Existen pocos trabajos que tratan este tema que resulta importante, ya que brinda información útil para promover educación y optimizar la dinámica hospitalaria.OBJETIVO: Describir las características de las llamadas al radio de urología durante la guardia.MATERIALES Y MÉTODOS: Durante la guardia activa, se registraron llamadas al radio durante el período comprendido en junio y julio de 2019. Determinamos:  hora, fuente, sexo y edad del paciente, motivo de la llamada y los clasificamos según: llamadas para guardia inmediata (que necesitó intervención instrumental urológica como sonda, talla o lavado vesical, etc.), llamadas innecesarias (número equivocado) y número de urgencias que requieren llamar a médico urólogo de pasiva para guardia quirúrgica inmediata.RESULTADOS: Se recopilaron un total de 325 llamadas, la mayoría de pacientes de sexo masculino. El principal motivo de la llamada fue para colocación, recambio o lavado de sonda vesical y/o talla vesical. Obtuvimos 139 llamadas que requirieron intervención urológica. El mayor número de llamadas fue de la Guardia externa (119), seguidos de Clínica Médica (47). La mayoría de las llamadas (242) no fueron ingresos. El total de llamadas innecesarias fueron 3 que corresponden al número equivocado.CONCLUSIÓN: Este trabajo permitió detallar las llamadas al radio de Urología provenientes de otros servicios y guardia externa, pudiendo identificar las problemáticas más comunes y educar en base a esto.

[Reducing the impact of COVID-19 on radiation oncology units of developing countries: A rapid review and expert consensus]. / Reduciendo el impacto de COVID-19 sobre la radioterapia oncológica en países en desarrollo: revisión rápida y consenso de expertos.

OBJECTIVE: To generate recommendations on the management of radiotherapeutic treatments during the pandemic, adapted to a country with limited health resources. METHODS: We did a rapid review of the literature, searching for papers that describe any measures to reduce the risk of COVID-19 infection, as well as management guidelines to reduce the workload, in radiotherapy units. The following conditions were included in the scope of this review: gynecological tumors, breast cancer, gastrointestinal tumors, genitourinary tumors, head and neck tumors, skin cancer, tumors of the central nervous system, and lymphomas. An expert group discussed online the extracted data and drafted the recommendations. Using a modified Delphi method, the consensus was reached among 14 certificated radio-oncologists. The quality of the evidence that supported the recommendations on treatment schedules was assessed. RESULTS: A total of 57 documents were included. Of these, 25 provided strategies to reduce the risk of infection. Recommendations for each condiction were extracted from the remaining documents. The recommendations aim to establish specific parameters where treatments can be omitted, deferred, prioritized, and shortened. Treatment schemes are recommended for each condition, prioritizing hypo-fractionated schemes whenever possible. CONCLUSIONS: We propose strategies for the management of radiotherapy services to guarantee the continuity of high-quality treatments despite the health crisis caused by COVID-19.

OBJETIVO: Establecer recomendaciones para la toma de decisiones de manejo en radioterapia durante la pandemia de COVID-19, adaptadas a un país con recursos de salud limitados. MÉTODOS: A través de una revisión rápida de la literatura se buscaron publicaciones que describieran medidas para reducir el riesgo de infección por COVID-19, así como también pautas de manejo para reducir la carga de trabajo en las unidades de radioterapia. Se incluyeron en el alcance de esta revisión las siguientes patologías: tumores ginecológicos, cáncer de mama, tumores gastrointestinales, tumores genitourinarios, tumores de cabeza y cuello, cáncer de piel, tumores del sistema nervioso central y linfomas. Un grupo de expertos discutió en línea los datos extraídos y redactó las recomendaciones. Mediante un método Delphi modificado, se evaluó el consenso entre 14 radio-oncólogos certificados. Se evaluó la calidad de la evidencia que sustentó las recomendaciones sobre esquemas de tratamiento. RESULTADOS: Se incluyeron un total de 57 documentos. De 25 trabajos se extrajeron las estrategias para reducir el riesgo de infección. De los restantes, se obtuvieron las recomendaciones para cada patología. Las recomendaciones están orientadas a establecer escenarios específicos donde se pueden omitir, diferir, priorizar y acortar los tratamientos. En el ítem de acortar se recomiendan esquemas de tratamiento para cada patología, priorizando los esquemas hipofraccionados cuando fue posible. CONCLUSIÓN: Se plantean estrategias para la gestión de los servicios de radioterapia con el objetivo de garantizar que los tratamientos de alta calidad para pacientes oncológicos sigan entregándose, pese a la crisis sanitaria ocasionada por COVID-19.

Evaluation of the Biases in the Studies that Assess the Effects of the Great Recession on Health. A Systematic Review.

BACKGROUND: Our main objective was to evaluate the fundamental biases detected in studies assessing the effects the Great Recession had on health for the case of Spain. As secondary objectives we presented methods to control these biases and to discuss the results of the studies in question if they had controlled for them. METHODS: We carried out a systematic review of the literature published up to June 2018. We evaluated the biases that could have happened in all the eligible studies. RESULTS: From the review, we finally selected 53 studies. Of the studies we reviewed, 60.38% or 32 out of 53, were evaluated as having a high risk of bias. The main biases our review revealed were problems with evaluation, time bias, lack of control of unobserved confounding, and non-exogeneity when defining the onset of the Great Recession. CONCLUSIONS: The results from the studies that controlled the biases were quite consistent. Summing up, the studies reviewed found that the Great Recession increased the risk of declaring poor self-rated health and the deterioration of mental health. Both the mortality rate and the suicide rate may well have increased after the Great Recession, probably after a three- to four-year delay.

Genomic Characterization and Seroprevalence Studies on Alphaviruses in Uruguay.

Alphaviruses (Togaviridae) are arboviruses frequently associated with emerging infectious diseases. In this study, we aimed to investigate the presence of alphaviruses in Uruguay by detecting the viral genome in mosquitoes and neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for alphavirus genome detection. Serologic studies were performed on 425 horse sera by plaque reduction neutralization test (PRNT80) against Venezuelan equine encephalitis virus (VEEV) subtype IAB, Pixuna virus (PIXV), Rio Negro virus (RNV), western equine encephalitis virus (WEEV), and Madariaga virus (MADV). Mosquitoes belonging to six genera were captured and 82.9% were identified as Culex pipiens. Two Cx. pipiens pools collected in Fray Bentos and Las Toscas localities were alphavirus positive, and phylogenetic analyses showed that the sequences grouped into two different clusters: the lineage I of eastern equine encephalitis virus and RNV (VEEV complex), respectively. Plaque reduction neutralization test assays showed antibodies against strains of the VEEV complex, MADV, and WEEV. Rio Negro virus was the most geographically widespread virus, showing higher seroprevalences (up to 20%). Seroprevalences against VEEV IAB ranged between 4.6% and 13%; antibodies against PIXV, WEEV, and MADV were less frequent (3-4%). In conclusion, RNV exhibited the highest seroprevalence in horses, a wide geographical distribution, and viral genome was detected in Cx. pipiens mosquitoes. Madariaga virus had a low seroprevalence in equines, but an epizootic lineage typical of North America was detected in Cx. pipiens mosquitoes. Taken together, our results show that alphaviruses are present in Uruguay with variable occurrence and geographical distribution being a potential threat for human and equine health.

Manejo multidisciplinario de las metástasis cerebrales: una revisión actualizada y un cambio de paradigma / Multidisciplinary management of brain metastases: An updated review and paradigm shift

Introducción: Las metástasis cerebrales (MC) representan una problemática importante de la salud pública, en promedio el 30% de los pacientes oncológicos desarrollarán MC siendo importante causa de morbilidad, ansiedad y mortalidad. El tratamiento con radioterapia, cirugía y sistémico son los pilares para el tratamiento y han tenido una evolución importante en la última década. Propósito de la revisión: Se proporciona información actualizada en relación a epidemiología, diagnóstico, pronóstico y tratamiento de metástasis cerebrales desde un enfoque multidisciplinariopara lograr individualizar su abordaje con el objetivo de proporcionar control oncológico y calidad de vida. También se discuten el acceso a nuevas terapias sistémicas, técnicas quirúrgicas y disponibilidad de tecnología para ofrecer técnicas avanzadas de radioterapia.Men saje principal: Conocer mutaciones específicas y receptores diana de los tumores permite elegir quimio-inmunoterapia o terapias dirigidas actuales que ofrecen mejor potencial de control tanto a nivel sistémico como intracraneal. La secuenciación de los tratamientos sistémicos y locales (cirugía, radio-cirugía, radioterapia holocraneal) deben ser discutidos desde un enfoque multidisciplinario Conclusión: Es importante poder estimar el pronóstico de los pacientes con MC, esto determinarla conducta terapéutica que puede variar desde cuidados sintomáticos hasta tratamientos más agresivos como resección neuroquirúrgica o radiocirugía.

In troduction:Brain metastases (BMs) represent a significant public health problem. An average of 30% of cancer patients develop BM, which is a significant cause of morbidity, anxiety, and mortality. Radio-therapy, surgery, and systemic treatment are the mainstays of treatment and have evolved significantly in the last decade.Pu rpose of the review: Updated information on the epidemiology, diagnosis, prognosis, and treatment of brain metastases from a multidisciplinary approach is provided to enable an individualized approach aimed at cancer control and quality of life. Access to new systemic therapies, surgical techniques, and availability of technology for advanced radiotherapy techniques are also discussed.Mai n message: Knowledge of specific mutations and targets of tumor receptors allows the selection of chemoimmunotherapy or current targeted therapies that offer better control potential at the systemic and intracranial levels. The sequence of systemic and local treatments (surgery, radiosurgery, whole brain radiation therapy) should be discussed as part of a multidisciplinary approach.C o nclusion: It is essential to estimate the prognosis of patients with BM, given that this will determine the therapeuticbehavior that can range from symptomatic care to more aggressive treatments such as neurosurgical resection or radiosurgery

Riesgo de infección por SARS-CoV-2 en trabajadores sanitarios altamente expuestos / Risk of sars-cov-2 infection in highly exposed health workers

Objetivos: El presente estudio permite establecer el perfil de trabajador más susceptible a la infección por SARS-CoV-2, describir la seroprevalencia y conocer la presencia de anosmia y/o disgeusia. Material y Métodos: Se realizó un estudio epidemiológico descriptivo, transversal y retrospectivo durante 263 días en una UCI de un hospital terciario. Se incluyeron 146 trabajadores de 11 categorías distintas. Se consultaron los resultados de las pruebas diagnósticas de infección y se realizó una entrevista telefónica. Resultados: 56 trabajadores se infectaron (39,4%). El riesgo de infección en sanitarios fue superior (OR 3,38). El personal de enfermería y el trabajo a turnos presentó una tasa de infección más elevada (p= 0, 000). Se detectaron anticuerpos Anti SARS-CoV-2 (AntiN) IgG durante más de 4 meses. El 38,1% desarrolló anosmia y/o disgeusia con una recuperación de 117,41 días de media. Conclusiones: Los datos obtenidos pueden resultar de interés para la evaluación del riesgo ocupacional frente al SARS-CoV-2 en el ámbito sanitario. (AU)

Objectives: The present study makes it possible to establish the profile of the worker most susceptible to SARS-CoV-2 infection, describe seroprevalence and determine the presence of anosmia and / or dysgeusia. Material and Methods: A descriptive, cross-sectional, and retrospective epidemiological study was carried out for 263 days in an ICU of a tertiary hospital. One hundred forty-six workers from 11 different categories were included. The results of the diagnostic tests for infection were consulted, and a telephone interview was carried out. Results: Fifty-six workers were infected (39.4%). The risk of infection in healthcare workers was higher (OR 3.38). Nursing staff and shift workers had a higher infection rate (p = 0, 000). Anti SARS-CoV-2 (AntiN) IgG antibodies were detected for more than four months. 38.1% developed anosmia and/or dysgeusia with a recovery of 117.41 days on average. Conclusions: The data obtained may be of interest for assessing occupational risk against SARS-CoV-2 in the health field. (AU)

Enfermedad por picaduras, la gran olvidada en el algoritmo diagnóstico / Stinging disease, the great forgotten in the diagnostic algorithm

La fiebre botonosa mediterránea es una enfermedad zoonótica febril aguda causada por Rickettsia conorii y transmitida a los humanos por la garrapata marrón Rhipicephalus sanguineus.Todo el mundo es susceptible a las picaduras de garrapata, diversos estudios demuestran que el porcentaje de seropositividad es más elevado en los residentes del medio rural. La mayoría de las veces, al realizar el diagnóstico diferencial de exantema generalizado pruriginoso (causa alérgica, medicamentosa, infecciones bacterianas, virales, fúngicas, estrés…) dejando a un lado las enfermedades por picaduras. Se debe cambiar esa mentalidad dado que el aumento de este tipo de enfermedades es exponencial. Se ha de tener en cuenta que dentro de los riesgos biológicos se encuentran las picaduras y no todas son vánales, requiriendo en nuestro día a día como médicos del trabajo: correcta anamnesis, seguimiento, diagnóstico y tratamiento. Un diagnóstico y tratamiento tardío lleva a un aumento de sintomatología en fase avanzada. (AU)

Mediterranean spotted fever is an acute febrile zoonotic zoonotic disease caused by Rickettsia conorii and transmitted to humans by the brown tick Rhipicephalus sanguineus.Everyone is susceptible to tick bites, but studies show that the rate of seropositivity is higher in rural residents. Most of the time, when making the differential diagnosis of pruritic generalised exanthema (allergic cause, medication, bacterial, viral, fungal infections, stress, etc.), we leave aside diseases caused by bites. We must change this mentality as the increase in this type of disease is exponential. It must be borne in mind that among the biological risks are stings and not all of them are viral, requiring in our day-to-day work as occupational physicians: correct anamnesis, monitoring, diagnosis and treatment. Late diagnosis and treatment leads to an increase in symptoms at an advanced stage. (AU)

Radioterapia hipofraccionada para cáncer de próstata localizado ¿Menos tiempo de tratamiento es mejor? / Hypofractionated radiotherapy for localized prostate cancer ¿Is less treatment time better?

Introducción: El hipofraccionamiento moderado (hRt) en cáncer de próstata, consisten en dismi-nuir el tiempo total de tratamiento con radioterapia, lo que mejora la adherencia terapéutica y opti-miza recursos tecnológicos. En cáncer de próstata, existe evidencia robusta con datos maduros a 5 años de seguimiento, donde se evidenció que hRtno es inferior al tratamiento con fraccionamiento estándar en control oncológico, con menor o igual toxicidad aguda y tardía. Se hace una revisión de la evidencia, dosis de tolerancia, contorneo de volúmenes objetivo (GTV-CTV-PTV) / órganos de ries-go, planificación y reproducibilidad del hRt en cáncer de próstata localizado.

Introduction: Moderate hypofractionation (hRt) in prostate cancer consists of reducing the total time of treatment with radiotherapy, which improves therapeutic adherence and optimizes technolog-ical resources. In prostate cancer, there is robust evidence with mature data at 5 years of follow-up, where it was evidenced that hRt is not inferior to treatment with standard fractionation in oncological control, with less or equal acute and late toxicity. A review of the evidence, tolerance dose, contouring of target volumes (GTV-CTV-PTV) / organs at risk, planning and reproducibility of hRt in localized prostate cancer is made.