Molecular detection and phylogenetic analysis of Anaplasma platys-like and Candidatus Anaplasma boleense strains from Argentina.

The present study aimed at the molecular detection of Anaplasma spp. in different samples obtained from cattle, goats and free-living Rhipicephalus microplus ticks from Argentina. DNA of members of the Anaplasmataceae family was detected by different PCR assays. The phylogenetic analyses of the obtained partial DNA sequences of the 16 S rDNA gene resulted in the identification of two different Anaplasma spp.: (I) Anaplasma platys-like bacteria (in blood sample from cattle and pools of R. microplus larvae and (II) Candidatus Anaplasma boleense (in blood samples from goats and one pool of R. microplus larvae of R. microplus). Candidatus A. boleense was found in two provinces that belong to different biogeographic regions, which leads to the conclusion that this bacterium may be widely distributed in Argentina. Interestingly, both Anaplasma spp. were found in the same R. microplus population in Chaco province, indicating that these two strains of Anaplasma are circulating in the same tick population. The results of this work represent the first report of the circulation of A. platys-like bacteria and Ca. A. boleense in domestic ruminants and free-living R. microplus ticks in Argentina. Further studies to determine the prevalence of infection, dispersion, clinical impact, transmission routes and cross-reactivity in serological tests of both Anaplasma species are needed.

Assessing the validity of self-report of psychopathy short-form (SRP-SF) in incarcerated offenders from Chile and Uruguay.

Psychopathy remains a relatively unexplored concept in Latin America. The abbreviated Self-Report Psychopathy Scale (SRP-SF) seems promising in this under-resourced context. However, the SRP-SF should be tested for measurement invariance to achieve meaningful comparison across countries in Latin America. Therefore the aims of this study were to examine the underlying factor structure of the SRP-SF in incarcerated adult male offenders from Uruguay (n = 331) and Chile (n = 208), to examine the measurement invariance of the SRP-SF across countries, and to assess the utility of SRP-SF to classify first time offenders from offenders with criminal history. Findings showed a good fit for the four-factor model in Uruguay, and both Chile and Uruguay showed invariance. Conversely, the Interpersonal and Affective factors were not associated with criminal history in the Uruguayan sample. Therefore, more studies are needed before using the SRP-SF as screening tool to classify first-time offenders and reoffenders in different countries in Latin America.

Severe COVID-19 in patients with immune-mediated rheumatic diseases: a stratified analysis from the SORCOM multicenter registry.

OBJECTIVES: To evaluate risk factors for severe Coronavirus Disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis. METHODS: An observational, cross-sectional multicenter study was performed. Patients from 10 Rheumatology departments in Madrid who presented with SARS-CoV-2 infection between Feb 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (sociodemographic, clinical and treatments), using logistic regression analyses. RESULTS: 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age and comorbidities such as diabetes mellitus, hypertension and obesity were associated with severe COVID-19. Corticosteroid doses over 10 mg/day, rituximab, sulfasalazine and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, p<0.001), although there were no differences in overall severity in the multivariate analysis. CONCLUSIONS: This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-TNF therapy were not associated with worse outcomes.

Decision trees for COVID-19 prognosis learned from patient data: Desaturating the ER with Artificial Intelligence

ObjectivesTo present a model that enhances the accuracy of clinicians when presented with a possibly critical Covid-19 patient. MethodsA retrospective study was performed with information of 5,745 SARS-CoV2 infected patients admitted to the Emergency room of 4 public Hospitals in Madrid belonging to Quiron Salud Health Group (QS) from March 2020 to February 2021. Demographics, clinical variables on admission, laboratory markers and therapeutic interventions were extracted from Electronic Clinical Records. Traits related to mortality were found through difference in means testing and through feature selection by learning multiple classification trees with random initialization and selecting the ones that were used the most. We validated the model through cross-validation and tested generalization with an external dataset from 4 hospitals belonging to Sanitas Hospitals Health Group. The usefulness of two different models in real cases was tested by measuring the effect of exposure to the model decision on the accuracy of medical professionals. ResultsOf the 5,745 admitted patients, 1,173 died. Of the 110 variables in the dataset, 34 were found to be related with our definition of criticality (death in <72 hours) or all-cause mortality. The models had an accuracy of 85% and a sensitivity of 50% averaged through 5-fold cross validation. Similar results were found when validating with data from the 4 hospitals from Sanitas. The models were found to have 11% better accuracy than doctors at classifying critical cases and improved accuracy of doctors by 12% for non-critical patients, reducing the cost of mistakes made by 17%.

Compassionate Use of Tocilizumab in Severe SARS-CoV2 Pneumonia. When late administration is too late.

IntroductionTocilizumab is an interleukin 6 receptor antagonist which has been used for the treatment of severe SARS-CoV-2 pneumonia (SSP), aiming to ameliorate the cytokine release syndrome (CRS) -induced acute respiratory distress syndrome (ARDS). However, there is no data about the best moment for its administration along the course of the disease. MethodsWe provided tocilizumab on a compassionate-use basis to patients with SSP hospitalized (excluding intensive care and intubated cases) who required oxygen support to have a saturation >93%. Primary endpoint was intubation or death after 24 hours of its administration. Patients received at least one dose of 400 mg intravenous tocilizumab during March 8-2020, through April 20-2020. FindingsA total of 207 patients were studied and 186 analysed. The mean age was 65 years and 68% were male. A co-existing condition was present in 68 % of cases. At baseline, 114 (61%) required oxygen support with FiO2 >0.5 % and 72 (39%) [≤]0.5%. Early administration of tocilizumab, when the need of oxygen support was still below FiO2 [≤]0.5%, was significantly more effective than given it in advanced stages (FiO2 >0.5 %), achieving lower rates of intubation or death (13% vs 37% repectively, p<0{middle dot}001). InterpretationThe benefit of tocilizumab in severe SARS-Cov-2 pneumonia is only expected when it is administrated before the need of high oxygen support. FundingNone.

Benznidazole/Poloxamer 407 Solid Dispersion as a New Strategy to Improve the Treatment of Experimental Trypanosoma cruzi Infection.

Benznidazole and nifurtimox are the only drugs specifically approved for the treatment of Chagas disease. Both compounds are given orally in tablets, but occasionally are ineffective and cause adverse effects. Benznidazole, the first-line treatment in many countries, is a compound with low solubility in water that is administered at high doses for long periods of time. To improve its solubility, we developed a new liquid formulation on the basis of solid dispersions (SD) using the amphiphilic polymer poloxamer 407. Herein we present data on its trypanocidal performance in mouse models of acute and chronic Trypanosoma cruzi infection. SD at doses of 60 or 15 mg/kg per day given with different administration schedules were compared with the commercial formulation (CF; 50 mg/kg per day) and vehicle. The SD performance was assessed by direct parasitemia, total anti-T. cruzi antibodies, and parasitic burden in tissues after 4 or 6 mo posttreatment. The efficacy of the SD was equivalent to the CF but without manifest side effects and hepatotoxicity. Considering our previous data on solubility, together with these on efficacy, this new liquid formulation represents a promising alternative for the treatment of Chagas disease, particularly in cases when dosing poses a challenge, as in infants.

COVID-19 Outcomes in 4712 consecutively confirmed SARS-CoV2 cases in the city of Madrid.

There is limited information describing features and outcomes of patients requiring hospitalization for COVID19 disease and still no treatments have clearly demonstrated efficacy. Demographics and clinical variables on admission, as well as laboratory markers and therapeutic interventions were extracted from electronic Clinical Records (eCR) in 4712 SARS-CoV2 infected patients attending 4 public Hospitals in Madrid. Patients were stratified according to age and stage of severity. Using multivariate logistic regression analysis, cut-off points that best discriminated mortality were obtained for each of the studied variables. Principal components analysis and a neural network (NN) algorithm were applied. A high mortality incidence associated to age >70, comorbidities (hypertension, neurological disorders and diabetes), altered vitals such as fever, heart rhythm disturbances or elevated systolic blood pressure, and alterations in several laboratory tests. Remarkably, analysis of therapeutic options either taken individually or in combination drew a universal relationship between the use of Cyclosporine A and better outcomes as also a benefit of tocilizumab and/or corticosteroids in critically ill patients. We present a large Spanish population-based study addressing factors influencing survival in current SARS CoV2 pandemic, with particular emphasis on the effectivity of treatments. In addition, we have generated an NN capable of identifying severity predictors of SARS CoV2. A rapid extraction and management of data protocol from eCR and artificial intelligence in-house implementations allowed us to perform almost real time monitoring of the outbreak evolution.

Cytomegalovirus infection associated with severe intraocular inflammation in an HIV patient: a case report.

This is a report of a case of severe intraocular inflammation associated with cytomegalovirus in an untreated HIV+ patient with a marked CD4+ T-cell depletion. The atypical presentation shown could confuse and delay the diagnosis. Early suspicion and appropriate treatment (ganciclovir, valganciclovir, HAART) increase the likelihood of a favourable outcome.

Seroprevalencia de Toxoplasma gondii en cabras (Aegagrus hircus) y gallinas (Gallus gallus domesticus) de zonas semirrurales de la provincia de Salta, Argentina y su importancia como zoonosis / Seroprevalence of Toxoplasma gondii in goats (Aegagrus hircus) and chickens (Gallus gallus domesticus) from semi-rural areas of provincia de Salta, Argentina and its importance as a zoonosis

El propósito de este estudio fue determinar la seroprevalencia de anticuerpos anti-Toxoplasma gondii en ganado caprino, caninos y gallinas pertenecientes a Unidades Familiares Productivas (UFP) de zonas semirrurales de la provincia de Salta. Se recolectaron muestras de sangre de cabras en edad reproductiva y de gallinas para detectar anticuerpos anti-Toxoplasma gondii, mediante las técnicas de Hemaglutinación Indirecta. En 206 muestras de cabras, la seroprevalencia de anticuerpos frente a T. gondii en el departamento de La Caldera fue de 12,1% en Vaqueros, 2,9% en La Calderilla y de 1,5% en La Caldera. En el departamento de Los Andes, fue de 0% en Cavy y en Antofasilla, las dos en Tolar Grande. En el departamento de Cerrillos, fue de 5,3% en La Isla. En el departamento Rosario de Lerma fue de 1,0% en San Bernardo de las Zorras y en el departamento de La Viña fue de 6,3% en Coronel Moldes. En el departamento Capital, la seroprevalencia fue del 3,4% en Acceso Norte. En cabras (n = 206), la seroprevalencia frente a T. gondii fue del 32,5%. Existe asociación entre cabras seropositivas y ocurrencia de abortos. En caninos (n=19) la prevalencia de anticuerpos antitoxoplásmicos fue del 21,05%. Las UFP presentaban condiciones y sistemas de manejo disímiles, por lo que el tipo de explotación, sistema de manejo y la presencia de hospedero definitivo influirían en la presentación de T. gondii en el ganado. El conocimiento del estado de situación de esta infección nos permitió mejorar las medidas de prevención y de tratamiento en las poblaciones humanas y caprinas, con el consiguiente incremento de la eficiencia productiva

Los acuerdos de maternidad subrogada: nuevos retos en la protección de los derechos de la mujer y la infancia / Surrogacy Motherhood Agreements: new challenges in the protection of the rights of women and children / Acordos sobre Maternidade Subrogada: novos desafios na proteção dos direitos da mulher e da infância

Los avances en materia de reproducción humana asistida, junto a la relativización de las fronteras, suponen un reto continuo para la ciencia, la ética y el derecho. Un ejemplo de tal situación es la maternidad subrogada, cuya prohibición en algunos países no impide que recurran a ella ciudadanos afectados por tal prohibición en otros Estados cuya práctica está permitida. Tampoco impide que se pretenda el reconocimiento de efectos jurídicos sobre los bebes nacidos sobre aquellos acuerdos. Junto a cuestiones de salud, la protección de los derechos de mujeres y niños, se erigen en los argumentos de referencia que sustentan la nulidad de los acuerdos de gestación subrogada, siendo paradójico que esos mismos argumentos se conviertan en el cauce que va abriendo paso al reconocimiento de efectos jurídicos.

Advances in assisted human reproduction, by the relativization of borders, pose a continuing challenge to science, ethics and law. An example of such a situation is surrogacy, which ban in some countries does not preclude having recourse to citizens affected by such a ban in other States whose practice is permitted. It does not prevent the recognition of legal effects on babies born to those agreements were intended. Along with issues of health, protection of the rights of women and children are erected in reference arguments that support the nullity of surrogacy agreements, being paradoxical that the same arguments become the channel that is making its way to recognition of legal effects.

Os avanços na reprodução humana assistida, pela relativização das fronteiras, constituem um desafio contínuo até a ciência, ética e direito. Um exemplo de tal situação é sub-rogação, que proíbem, em alguns países não exclui recorrer aos cidadãos afectados por essa proibição, em outros Estados cuja prática é permitida. Não impede o reconhecimento de efeitos jurídicos sobre os bebês nascidos de tais acordos se destinavam. Juntamente com as questões de saúde, a protecção dos direitos das mulheres e crianças, são erguidas em argumentos de referência que suportam a nulidade dos acordos de sub-rogação, sendo paradoxal que os mesmos argumentos se tornar o canal que está a fazer o seu caminho para reconhecimento de efeitos jurídicos.

Presencia de infección por Trypanosoma cruzi Y Toxoplasma gondii en perros domésticos de localidades rurales en el noroeste argentino / Infection by Trypanosoma cruzi and Toxoplasma gondii in domestic dogs from rural localities in Northwest Argentina

Las zoonosis causadas por los parásitos Trypanosoma cruzi y Toxoplasma gondii son prevalentes en la Argentina y los perros cumplen el papel de reservorio además de padecer las enfermedades. Se considera una buena alternativa conocer la seroprevalencia de estas zoonosis en los perros debido a que son un reflejo de lo que ocurre en la población humana y en el ambiente. Nos propusimos conocer la seroprevalencia de infección por T. gondii y T. cruzi en caninos en cuatro zonas rurales de la provincia de Salta. Para la detección de anticuerpos anti-T. gondii se utilizó Hemaglutinación Indirecta (HAI) y para la detección de anticuerpos anti-T. cruzi, además de HAI, se usó Enzimoinmunoanálisis (ELISA). Fueron muestreados 209 canes y los resultados serológicos indicaron la presencia de anticuerpos anti-T. gondii en la localidad de La Unión, departamento Rivadavia en 18,2% (4/22), en San Carlos con 20,5% (8/39), en Cafayate con 13,1 % (11/84) y en Embarcación departamento General San Martín con 23.4% (15/64). Los anticuerpos anti-T cruzi sólo estuvieron presentes en los perros de la localidad de San Carlos con 28,2% (11/39). La frecuente seroprevalencia a T. gondii, encontrada en los perros de todas las localidades muestreadas sugiere contaminación ambiental por este parásito en la zona. El hallazgo de perros infectados por T. cruzi, en la localidad de San Carlos, nos sugiere la posibilidad de transmisión activa del parásito en un pasado reciente y nos alerta sobre la posibilidad de reservorio

Hepatotoxicity in mice of a novel anti-parasite drug candidate hydroxymethylnitrofurazone: a comparison with Benznidazole.

BACKGROUND: Treatment of Chagas disease, caused by Trypanosoma cruzi, relies on nifurtimox and benznidazole (BZL), which present side effects in adult patients, and natural resistance in some parasite strains. Hydroxymethylnitrofurazone (NFOH) is a new drug candidate with demonstrated trypanocidal activity; however, its safety is not known. METHODS: HepG2 cells dose response to NFOH and BZL (5-100 µM) was assessed by measurement of ROS, DNA damage and survival. Swiss mice were treated with NFOH or BZL for short-term (ST, 21 d) or long-term (LT, 60 d) periods. Sera levels of cellular injury markers, liver inflammatory and oxidative stress, and fibrotic remodeling were monitored. RESULTS: HepG2 cells exhibited mild stress, evidenced by increased ROS and DNA damage, in response to NFOH, while BZL at 100 µM concentration induced >33% cell death in 24 h. In mice, NFOH ST treatment resulted in mild-to-no increase in the liver injury biomarkers (GOT, GPT), and liver levels of inflammatory (myeloperoxidase, TNF-α), oxidative (lipid peroxides) and nitrosative (3-nitrotyrosine) stress. These stress responses in NFOH LT treated mice were normalized to control levels. BZL-treated mice exhibited a >5-fold increase in GOT, GPT and TNF-α (LT) and a 20-40% increase in liver levels of MPO activity (ST and LT) in comparison with NFOH-treated mice. The liver inflammatory infiltrate was noted in the order of BZL>vehicle≥NFOH and BZL>NFOH≥vehicle, respectively, after ST and LT treatments. Liver fibrotic remodeling, identified after ST treatment, was in the order of BZL>vehicle>NFOH; lipid deposits, indicative of mitochondrial dysfunction and in the order of NFOH>vehicle>BZL were evidenced after LT treatment. CONCLUSIONS: NFOH induces mild ST hepatotoxicity that is normalized during LT treatment in mice. Our results suggest that additional studies to determine the efficacy and toxicity of NFOH are warranted.

Use of clomipramine as chemotherapy of the chronic phase of Chagas disease.

Chagas infection is a major endemic disease affecting Latin American countries. The persistence of Trypanosoma cruzi generates a chronic inflammatory reactivity that induces an immune response directed to the host's tissues. The effectiveness of the treatment in the chronic phase is still unsatisfactory due, amongst other reasons, to the collateral effects of the drugs used. We investigated the effect of clomipramine, a tricyclic antidepressant that, when used as a treatment of T. cruzi-chronically infected mice, inhibits trypanothione reductase, an exclusive and vital enzyme of T. cruzi. Clomipramine improved survival (P<0.05) by diminishing the parasite intensity as demonstrated by PCR studies in the heart and skeletal muscle, and significantly prevented the evolution to fibrosis of the inflammatory infiltrates. Clomipramine could be a good candidate for the treatment of chronic Chagas disease.

Congenital Chagas disease involves Trypanosoma cruzi sub-lineage IId in the northwestern province of Salta, Argentina.

Trypanosoma cruzi is genetically classified into six discrete phylogenetic lineages on the basis of different genetic markers. Identifying lineages circulating among humans in different areas is essential to understand the molecular epidemiology of Chagas disease. In the present study, 18 T. cruzi isolates from congenitally infected newborns in the northwestern province of Salta-Argentina were studied by multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD). All isolates were typed by MLEE and RAPD as belonging to T. cruzi IId. Analysis of minor variants of TcIId using probes hybridizing with hypervariable domains of kDNA minicircles, detected three variants with a similar distribution among the isolates. Our findings confirm the presence of T. cruzi IId among congenitally infected newborns in northwestern Argentina and support the assumption that human infection by T. cruzi in the Southern Cone countries of Latin America is due principally to T. cruzi II.

Use of the polymerase chain reaction (PCR) for early evaluation of etiological treatment in young adults, chronically infected with Trypanosoma cruzi

Foi realizado o tratamento etiológico com benznidazol, no Estado de Salta, Argentina, em 14 pacientes infectados crônicos por Trypanosoma cruzi, de 18 a 30 anos de idade, com Reação em Cadeia da Polimerase (PCR) positiva. Um grupo controle de cinco pacientes, da mesma idade, também com PCR positiva, não recebeu tratamento. O seguimento após tratamento foi realizado com PCR e sorologia convencional. Após 6 meses de tratamento foi observada negativização da PCR de 14/16 (85,7por cento) nos pacientes tratados versus 20por cento no grupo controle (p=0,001). A sorologia foi positiva em todos os pacientes depois do tratamento. Os resultados da PCR pós-tratamento, podem ser um indício de cura no tratamento de infectados chagásicos crônicos, adultos jovens.

Chagas disease in rural areas of Chaco Province, Argentina: epidemiologic survey in humans, reservoirs, and vectors.

We studied the seroprevalence of antibodies against Trypanosoma cruzi in the human population along with domiciliary infestation by triatomine bugs in an area endemic for Chagas disease in the Chaco Province of Argentina. In addition, we carried out parasitologic surveys in patients, dogs, wild mammals, and vectors. The mean seroprevalence in humans was 27.81% (109 of 392) and 24.14% (63 of 261) in 1-15-year-old children. The minimum domiciliary infestation rate was 13.33%, with certain areas reaching 53.85%. The prevalence was 15.09% (16 of 106) in dogs and 35.71% (10 of 28) in opossums. Infection with T. cruzi was detected in 30.10% (59 of 196) of the Triatoma infestans tested. Compared with nationwide studies, our data suggest that 1) there are zones requiring immediate sanitary action, and 2) nationwide estimates are based on very heterogeneous epidemiologic situations. This heterogeneity emphasizes the importance of in-depth studies of restricted areas to provide additional information for a better understanding of the present status of Chagas disease in Argentina.

Determination of aflatoxin B1 in food and feedstuffs in Cuba (1990 through 1996) using an immunoenzymatic reagent kit (Aflacen).

The presence of aflatoxin B1 was analyzed in imported food and feedstuffs of national production in the period of 1990 through 1996, destined to animal and human consumption using an immunoenzymatic reagent kit (Aflacen, Ckure, la Habana, Cuba) with a detection limit of 0.3 microg/kg. It was found that the 17.04% of a total of 4,594 analyzed samples presented aflatoxin B1, and the biggest percentages were in sorghum and peanut with an 83.3 and 40.4%, respectively. The corn, oat, wheat, and soy are fundamental raw ingredients in the elaboration of concentrates. Percentages of contamination with aflatoxin B1 of 23.3, 10.7, 25, and 4.6 were found in corn, oat, wheat, and soy, respectively. Other analyzed foods like rice, beans, and peas presented percentages of contamination with aflatoxin B1 inferior to 5% of the analyzed samples. It was found that more than 455 samples surpassed the value of 10 microg/kg. Corn and peanut products present a high demand in population showing levels of contamination superior to 50 microg/kg. The 11.3% of the samples contaminated with aflatoxin B1 have values between 1 and 20 microg/kg, where peanut and concentrates show the highest percentages (21.9 and 18.7), respectively. These results show levels of aflatoxin B1 in the population that constitute a great risk for human and animal health.