Attachment styles and associated psychosocial factors in patients at ultra-high risk for psychosis: A systematic review.

BACKGROUND: Patients with an ultra-high risk of psychosis (UHR) are more likely to transition to psychosis. Attachment style has also been associated with psychosis and other symptoms. AIMS: To review attachment styles in UHR patients and to analyze related psychosocial factors. Ours is the first systematic review of attachment in this population. METHOD: We performed a systematic review of attachment and related psychosocial factors in UHR patients following the PRISMA methodology. RESULTS: We identified five studies. The results revealed high rates of insecure attachment in this population (more than 80%). The UHR sample presented high levels of depression, anxiety, social anxiety, emotional reactivity, trauma, and poor mentalization. Premorbid social adjustment was a predictor of improvement in disorganization and negative symptoms. The rate of transition to psychosis was 10%. Attachment patterns accounted for 16.8% of the variance. This vulnerability for psychosis was also associated with poor mentalization. CONCLUSION: Early detection of patients with UHR and insecure attachment is crucial, since early intervention to address symptoms, mentalization, and attachment is feasible and may lead to an improvement in the remaining associated psychosocial related factors (secure style: better global functioning and less affective and anxious symptoms). PROSPERO ID440957.

E-H Bond Cleavage Processes in Reactions of Heterometallic Phosphinidene-Bridged MoRe and MoMn Complexes with Hydrogen and p-Block Element Hydrides.

Reactions of complexes [MoMCp(µ-PMes*)(CO)6] with H2 and several p-block element (E) hydrides mostly resulted in the cleavage of E-H bonds under mild conditions [M = Re (1a) and Mn (1b); Mes* = 2,4,6-C6H2tBu3]. The reaction with H2 (ca. 4 atm) proceeded even at 295 K to give the hydrides [MoMCp(µ-H)(µ-PHMes*)(CO)6]. The same result was obtained in the reactions with H3SiPh and, for 1a, upon reduction with Na(Hg) followed by protonation of the resulting anion [MoReCp(µ-PHMes*)(CO)6]-. The latter reacted with [AuCl{P(p-tol)3}] to yield the related heterotrimetallic cluster [MoReAuCp(µ-PHMes*)(CO)6{P(p-tol)3}]. The reaction of 1a with thiophenol gave the thiolate-bridged complex [MoReCp(µ-PHMes*)(µ-SPh)(CO)6], which evolved readily to the pentacarbonyl derivative [MoReCp(µ-PHMes*)(µ-SPh)(CO)5]. In contrast, no P-H bond cleavage was observed in reactions of complexes 1a,b with PHCy2, which just yielded the substituted derivatives [MoMCp(µ-PMes*)(CO)5(PHCy2)]. Reactions with HSnPh3 again resulted in E-H bond cleavage, but now with the stannyl group terminally bound to M, while 1a reacted with BH3·PPh3 to give the hydride-bridged derivatives [MoReCp(µ-H)(µ-PHMes*)(CO)5(PPh3)] and [MoReCp(µ-H){µ-P(CH2CMe2)C6H2tBu2}(CO)5(PPh3)], which follow from hydrogenation, C-H cleavage, and CO/PPh3 substitution steps. Density functional theory calculations on the PPh-bridged analogue of 1a revealed that hydrogenation likely proceeds through the addition of H2 to the Mo=P double bond of the complex, followed by rearrangement of the Mo fragment to drive the resulting terminal hydride into a bridging position.

Cycloaddition and C-S Bond Cleavage Processes in Reactions of Heterometallic Phosphinidene-Bridged MoRe and MoMn Complexes with Alkynes and Phenyl Isothiocyanate.

Reactions of [MoReCp(µ-PMes*)(CO)6] with internal alkynes RC≡CR yielded the phosphapropenylidene-bridged complexes [MoReCp(µ-κ2P,C:η3-PMes*CRCR)(CO)5] (Mes* = 2,4,6-C6H2tBu3; R = CO2Me, Ph). Terminal alkynes HC≡CR1 gave mixtures of isomers [MoReCp(µ-κ2P,C:η3-PMes*CHCR1)(CO)5] and [MoReCp(µ-κ2P,C:η3-PMes*CR1CH)(CO)5], with the first isomer being major (R1 = CO2Me) or unique (R1 = tBu), indicating the relevance of steric repulsions during the [2 + 2] cycloaddition step between Mo=P and C≡C bonds in these reactions. Similar reactions were observed for [MoMnCp(µ-PMes*)(CO)6]. Addition of ligands to these complexes promoted rearrangement of the phosphapropenylidene ligand into the allyl-like µ-η3:κ1C mode, as shown by the reaction of [MoReCp(µ-κ2P,C:η3-PMes*CHC(CO2Me)}(CO)5] with CN(p-C6H4OMe) to give [MoReCp{µ-η3:κ1C-PMes*CHC(CO2Me)}(CO)5{CN(p-CH4OMe)}2]. The MoRe phosphinidene complex reacted with S=C=NPh to give as major products the phosphametallacyclic complex [MoReCp{µ-κ2P,S:κ2P,S-PMes*C(NPh)S}(CO)5] and its thiophosphinidene-bridged isomer [MoReCp(µ-η2:κ1S-SPMes*)(CO)5(CNPh)]. The first product follows from a [2 + 2] cycloaddition between Mo=P and C=S bonds, with specific formation of P-C bonds, whereas the second one would arise from the alternative cycloaddition involving the formation of P-S bonds, more favored on steric grounds. The prevalence of the µ-η2:κ1S coordination mode of the SPMes* ligand over the µ-η2:κ1p mode was investigated theoretically to conclude that steric congestion favors the first mode, while the kinetic barrier for interconversion between isomers is low in any case.

Reactions of Heterometallic Phosphinidene-Bridged MoMn and MoRe Complexes with Sulfur and Selenium: From Chalcogenophosphinidene- to Trithiophosphonate-Bridged Derivatives.

Reactions of [MoReCp(µ-PR*)(CO)6] with S8 were strongly dependent on experimental conditions (R* = 2,4,6-C6H2tBu3). When using 1 equiv of sulfur, complex [MoReCp(µ-η2:κ1S-SPR*)(CO)6] was slowly formed at 313 K, with a thiophosphinidene ligand unexpectedly bridging the dimetal center in the novel µ-κ1S:η2 coordination mode, as opposed to the µ-κ1P:η2 mode usually found in related complexes. The latter underwent fast decarbonylation at 363 K to give [MoReCp(µ-η2:η2-SPR*)(CO)5], with a six-electron donor thiophosphinidene ligand rearranged into the rare µ-η2:η2 coordination mode. Depending on reaction conditions, reactions with excess sulfur involved the addition of two or three S atoms to the phosphinidene ligand to give new complexes identified as the dithiophosphinidene-bridged complex [MoReCp(µ-η2:κ2S,S'-S2PR*)(CO)5], its dithiophosphonite-bridged isomer [MoReCp(µ-κ2S,S':κ2S,S'-S2PR*)(CO)5], or the trithiophosphonate-bridged derivative [MoReCp(µ-κ2S,S':κ2S,S'-S3PR*)(CO)5], all of them displaying novel coordination modes of their PRS2 and PRS3 ligands, as determined by X-ray diffraction studies. In contrast, the related MoMn complex yielded [MoMnCp(µ-η2:η2-SPR*)(CO)5] under most conditions. A similar output was obtained in reactions with gray selenium for either MoRe or MoMn phosphinidene complexes, which under different conditions only gave the pentacarbonyl complexes [MoMCp(µ-η2:η2-SePR*)(CO)5] (M = Re, Mn), these providing a new coordination mode for selenophosphinidene ligands.

Geographic variation in the altitudinal migration patterns, body size, oxidative status and exploratory behavior in a neotropical bird.

To cope with life in the mountains, populations of the same species can exhibit substantial variability in their altitudinal migration patterns and phenotypes in response to local weather conditions. Studying such variability can provide valuable insights into how local populations respond to environmental challenges, and this information can be useful for conservation efforts in mountain ecosystems. Here, we used δ2H values of feathers and blood to evaluate latitudinal variation in altitudinal migration patterns and its possible links with body size, oxidative status, and exploratory behavior in 72 individuals of rufous-collared sparrow (Zonotrichia capensis) that breed at low and high elevations in the center (~33°) and south (~38°) of Chile. Our results show that both altitudinal migration patterns and oxidative status were significantly influenced by the latitude of breeding sites, while exploratory behavior was associated with elevation. Notably, we found that fast-explorer birds inhabiting low elevations in central Chile displayed higher levels of oxidative damage than slow-explorer birds. These outcomes underscore the possibility of local adaptations in response to diverse local environmental conditions in the Andes. We discuss the implications of latitude, elevation, and environmental temperature in shaping the observed patterns and highlight the significance of identifying local adaptations in mountain birds for better predicting their response to climate change and other challenges stemming from anthropogenic activities.

Two-year evaluation of a multifamily psychoeducational program (PROTEC) in the family burden and prognosis of bipolar patients.

INTRODUCTION: Bipolar disorder causes a significant burden on the lives of patients and their families. The family is one of the targets for therapeutic intervention, related to the prognosis in patients with bipolar disorder. AIM: To assess the effectiveness of a multifamily psychoeducational program for people with bipolar disorder, in the family burden: objective and subjective and in the variables related to the course of the patients with bipolar disorder (symptoms, adherence, functionality, hospitalizations), comparing it with a control group (CG). MATERIALS AND METHODS: A total of 148 relatives of bipolar patients and 148 bipolar patients were recruited. The sample was randomized (experimental group [EG] and CG) and with single-blind evaluations (baseline, at 5 months and one year). Clinical and sociodemographic variables were collected from families and patients (family burden self-report scale, Strauss-Carpenter Scale, Global Assessment of Functioning, Morisky Green adherence Scale). Both, EG and CG received 8 multifamily sessions, applied exclusively on the relatives of patients with bipolar disorder, but in the EG a psychoeducational treatment was carried out and in the CG only playful and current topics were discussed. Bivariate and logistic regression models were used, among others. RESULTS: The caregivers and patients of the EG and CG did not differ in any of the baseline variables (sociodemographic and clinical) (P>.001). In the total sample, the baseline objective burden was light (mean 0.6±0.4) and the subjective ones was medium-moderate (mean 1.1±0.3). During the follow-up, in relation to the variables of the caregivers, there was a greater reduction in the objective burden in the EG compared to the CG (5 months P=.006; one year P=.002). It was found that the objective burden (P=.006) and the subjective burden (P=.003) were significantly reduced over a year in EG but not in the CG. During the follow-up, the patients whose caregivers belonged to the EG showed a greater increase in the frequency of social activity (P=.008), in the work activity (P=.002), and global functioning (P=.002), and reduced their symptoms (P≤.001). Longitudinal analyses, over a year, showed that patients in the EG had a greater improvement in functionality compared to patients in the CG (P=.001). After the intervention, adherence to pharmacological treatment improved more in EG than in the CG (P≤.001). Regarding hospitalizations, any patients in the CG were hospitalized during the 5 months after the intervention, while 27.8% of the patients in the CG were hospitalized (P≤.001); the difference between groups remained significant in the long term (one year: P≤.001; 2 years: P≤.001). There were no significant differences between groups in the pharmacological treatment of the patients in any of the evaluations. CONCLUSIONS: The multifamily psychoeducational intervention group improved the family burden after the intervention. Likewise, bipolar patients, whose families attended the EG, improved significantly, over a year, the functionality, the frequency of social contacts, the work status, the adherence to treatment, and reduced their symptoms. In addition, in the EG, the percentage of hospitalizations during the 2 years of follow-up was significantly reduced.

Randomized placebo-controlled trial of oral tannin supplementation on COVID-19 symptoms, gut dysbiosis and cytokine response.

The clinical study aim was to investigate whether a tannin-based dietary supplementation could improve the efficacy of standard-of-care treatment of hospitalized COVID-19 patients by restoring gut microbiota function. Adverse events and immunomodulation post-tannin supplementation were also investigated. A total of 124 patients receiving standard-of-care treatment were randomized to oral tannin-based supplement or placebo for a total of 14 days. Longitudinal blood and stool samples were collected for cytokine and 16S rDNA microbiome profiling, and results were compared with 53 healthy controls. Although oral tannin supplementation did not result in clinical improvement or significant gut microbiome shifts after 14-days, a reduction in the inflammatory state was evident and significantly correlated with microbiota modulation. Among cytokines measured, MIP-1α was significantly decreased with tannin treatment (p = 0.03) where it correlated positively with IL-1ß and TNF- α, and negatively with stool Bifidobacterium abundance.

In vitro production of infectious Plasmodium falciparum sporozoites.

An effective vaccine is needed for the prevention and elimination of malaria. The only immunogens that have been shown to have a protective efficacy of more than 90% against human malaria are Plasmodium falciparum (Pf) sporozoites (PfSPZ) manufactured in mosquitoes (mPfSPZ)1-7. The ability to produce PfSPZ in vitro (iPfSPZ) without mosquitoes would substantially enhance the production of PfSPZ vaccines and mosquito-stage malaria research, but this ability is lacking. Here we report the production of hundreds of millions of iPfSPZ. iPfSPZ invaded human hepatocytes in culture and developed to mature liver-stage schizonts expressing P. falciparum merozoite surface protein 1 (PfMSP1) in numbers comparable to mPfSPZ. When injected into FRGhuHep mice containing humanized livers, iPfSPZ invaded the human hepatocytes and developed to PfMSP1-expressing late liver stage parasites at 45% the quantity of cryopreserved mPfSPZ. Human blood from FRGhuHep mice infected with iPfSPZ produced asexual and sexual erythrocytic-stage parasites in culture, and gametocytes developed to PfSPZ when fed to mosquitoes, completing the P. falciparum life cycle from infectious gametocyte to infectious gametocyte without mosquitoes or primates.

P-C, P-N, and M-N Bond Formation Processes in Reactions of Heterometallic Phosphinidene-Bridged MoMn and MoRe Complexes with Diazoalkanes and Organic Azides to Build Three- to Five-Membered Phosphametallacycles.

Reactions of the heterometallic MoRe complex [MoReCp(µ-PR*)(CO)6] and its MoMn analogue with some small molecules having N-N multiple bonds, such as diazoalkanes and organic azides, were investigated (R* = 2,4,6-C6H2tBu3). Reactions with excess ethyl diazoacetate proceeded slowly and with concomitant denitrogenation to give complexes [MoMCp(µ-η2P,C:κ2P,O-PR*CHCO2Et)(CO)5], which display a bridging phosphaalkene ligand in a novel µ-η2:κ2 coordination mode, while reactions with other diazoalkanes resulted only in the decomposition of the organic reagent. The MoRe complex reacted with benzyl- or p-tolyl azide at room temperature to give the green complexes [MoReCp(µ-η2P,N:κP,N'2-PR*N3R)(CO)6] [R = Bn, p-tol], which display bridging phosphatriazadiene ligands in a novel 6-electron donor coordination mode as a result of a formal [2 + 1] cycloaddition of the terminal N atom of the azide to the Mo-P double bond of the parent complex, followed by coordination of the distal NR nitrogen to the rhenium center. Denitrogenation was only observed for the p-tolyl azide derivative, which upon heating at 333 K yielded [MoReCp{µ-κP:κN-PR*N(p-tol)}(CO)6], a molecule displaying a bridging phosphaimine ligand in a rare κP:κN coordination mode. Analogous reactions of the MoMn phosphinidene complex proceeded similarly at 273 K to give the phosphatriazadiene-bridged derivatives [MoMnCp(µ-η2P,N:κ2P,N'-PR*N3R)(CO)6], but these were thermally unstable and degraded at room temperature to give the mononuclear triazenylphosphanyl complexes [Mn2(κP,N-PR*NHNNR)(CO)3] as major products, along with small amounts of the phosphaimine-bridged complex [MoMnCp{µ-κP:κN-PR*N(p-tol)}(CO)6] in the case of the p-tolyl azide derivative. The structure of the new complexes was analyzed in light of spectroscopic data and single-crystal diffraction studies on selected examples of each type of complex.

Conciencia transoperatoria en personas operadas mediante craneotomía despierto / Intraoperative awareness in awake craniotomy patients

La craneotomía con paciente despierto (CPD) demanda un manejo multidisciplinario particular debido al componente de conciencia transoperatoria que aporta beneficios en la resección tumoral y preservación neurológica, pero también implica el manejo de los riesgos asociados a la necesidad de cooperación del paciente durante el procedimiento. En este trabajo se describen los beneficios y las complicaciones en pacientes operados bajo la modalidad de CPD. Además, se abordan los retos documentados tanto para el equipo profesional a cargo, como para los pacientes, los cuales tienen un rol activo durante la cirugía. En ese sentido, se exponen los criterios para la selección, preparación psicológica y neuropsicológica tanto previo como durante la cirugía. A su vez, se proponen las consideraciones para lograr un procedimiento exitoso y evitar las posibles secuelas psicológicas a largo plazo, como insumos para la protocolización de este tipo de procedimientos con base en nuestra experiencia.

Awake craniotomy (AC) requires a multidisciplinary management due to trans operative awareness, which benefits the tumor resection and neurologic preservation, but it also implies risks for the patient cooperation during the procedure. This article describes the benefits and complications in patients operated under AC. Besides, it approaches the documented challenges for both the professional team and patients, who have an active role during surgery. In this regard, the criteria for selection and psychological and neuropsychological preparation before and during surgery are set out. It suggests considerations to achieve a successful procedure and to avoid possible long- term psychological sequelae, as a resource for the protocol of this type of procedures based on our experience.

Satisfacción de estudiantes de enfermería con educación virtual y a distancia en pandemia / Nursing students' satisfaction with virtual and distance education in pandemic

INTRODUCCIÓN: En pandemia debido al Coronavirus (SARS-CoV-2), a modo de resguardar la distancia social, la Universidad de Playa Ancha (Valparaíso, Chile) implementó estrategias docentes digitalizadas para procurar el avance curricular de sus estudiantes. En este contexto surge la necesidad de conocer la satisfacción de los estudiantes. OBJETIVO: Determinar la satisfacción de estudiantes de la carrera de enfermería con el proceso educativo en modalidad virtual y a distancia en tiempos de pandemia. METODOLOGÍA: Estudio cuantitativo, descriptivo, de diseño no experimental y transversal. Se aplicó la 'Escala de Satisfacción con la Docencia a Distancia' a una muestra no probabilística y por conveniencia (N=106). Los datos se analizaron mediante estadística descriptiva. RESULTADOS. Para el factor Contribución al Aprendizaje, 10 de 12 reactivos se encuentran por sobre el 52% en ACUERDO. Respecto al factor Relación Organizada, la mayoría de las respuestas están por sobre el 75% en ACUERDO. Para el factor Diagnóstico de Contexto, se evidencia que ningún reactivo llega al 50% en ACUERDO. En relación al factor Participación de los Estudiantes destaca que los reactivos se encuentran por sobre el 76% en ACUERDO. CONCLUSIÓN. Los estudiantes de enfermería evidencian principalmente su satisfacción con las actividades de evaluación de sus asignaturas, con la relación organizada de sus docentes y por su propia participación en el proceso de aprendizaje. Por el contrario, su insatisfacción es debido a la falta de interacción en línea y porque los profesores no les consultan por sus condiciones personales y de trabajo para su aprendizaje con la modalidad virtual en pandemia.

INTRODUCTION: As a result of the Covid-19 pandemic and in order to observe social distancing, Universidad de Playa Ancha (Valparaíso, Chile) implemented digital teaching strategies to keep students' curricular progress going. In this context, the need arises to know the satisfaction of students. OBJECTIVE: To determine nursing students' satisfaction with the online and remote educational process implemented in times of pandemic. METHODOLOGY: This is a quantitative, descriptive, non-experimental and cross-cutting study. The 'Distance Teaching Satisfaction Scale' was applied to a non-probabilistic and convenience sampling (N=106). Data were analyzed using descriptive statistics. RESULTS: For the Learning Contribution factor, 10 of 12 reagents are above 52% in AGREEMENT. Regarding the Organized Relationship factor, most of the responses are above 75% in AGREEMENT. For the Context Diagnosis factor, it is evident that no reagent reaches 50% in AGREEMENT. In relation to the Student Participation factor, it stands out that the reagents are above 76% in AGREEMENT. CONCLUSION. Nursing students mainly show their satisfaction with the evaluation activities of their subjects, with the organized relationship of their teachers and for their own participation in the learning process. On the contrary, their dissatisfaction is due to the lack of online interaction and because teachers do not consult them about their personal and working conditions for their learning with the virtual modality in pandemic.

Factores de riesgo de fracturas no vertebrales en receptores de trasplante renal: ¿Una realidad compleja? / Risk factors for nonvertebral bone fractures in kidney transplant recipients: a complex reality?

RESUMEN Introducción: Las fracturas en el postrasplante renal representan una de las complicaciones que aumentan la morbimortalidad en los pacientes. Objetivo: Determinar los factores de riesgo de trasplante de fracturas no vertebrales en receptores de trasplante renal. Material y métodos: Se analizaron los datos de historias clínicas de 737 pacientes trasplantados renales desde 2009-2015, donde se evaluaron los factores de riesgo de fracturas. Se determinaron como factores generales: edad, sexo; y factores específicos: etiología de la enfermedad renal crónica (ERC), tiempo en diálisis, modalidad de diálisis, características del donante:edad, sexo, tipo de donante vivo y cadavérico (DV, DC), diferentes esquemas de inmunosupresión, rechazos, tratamiento con pulsos de esteroides, uso de bifosfonatos y analitos como parathormona intacta (PTHi), pro-vitamina D (25OHD) y creatininemia (Creats). Criterios de exclusión: pacientes <18 años, retrasplante o trasplantes dobles y menos de 1 año de seguimiento. Resultados: 44 pacientes presentaron 50 fracturas no vertebrales. El 62% de las fracturas se presentaron en los 3 primeros años del trasplante. En el modelo Multivariado se pudo observar que los factores de riesgo generales asociados con riesgo de fracturas fueron la edad avanzada del receptor (aHR por año aumenta 1,03, 95% CI: 1,00-1,05] y el sexo femenino (aHR= 1,60, 95% CI: 0,85-2,99), mientras que los factores de riesgo específicos fueron el tiempo en diálisis (1,07 IC95%:1,02- 1,12), la mayor edad del donante (1,03 IC95:1,00- 1,05) y el déficit de 25OHD (3,17 IC95:1,57- 6,41). Conclusiones: Este estudio permitió evaluar los factores predictivos de fractura en nuestros pacientes con trasplante renal.

ABSTRACT Introduction: Fractures in renal postransplantation represent one of the complications that increase morbidity and mortality in patients. Objective: To determine the risk factors for transplantation of non- vertebral fractures in renal transplant recipients. Methods: The data of clinical histories of 737 renal transplanted patients since 2009 2015 were analyzed, where the risk factors of fractures were evaluated. They were determined as general factors: age, sex; and specific factors: etiology of chronic kidney disease (ERC), dialysis time, dialysis modality, donor characteristics: age, sex, type of donor, living or cadaveric (DV, DC), different immunosuppression treatments, rejections, treatment with steroid pulses, use of bisphosphonates and biochemical parameters like intact parathormone (PTHI), Pro-Vitamin D (25OHD) and Creatininemia (CREATS). Exclusión criteria: patients <18 years, retransplantation or double transplants and follow- up less than 1 year. Results: 44 patients presented 50 non-vertebral fractures. 62% of the fractures were presented in the first 3 years of the transplant. In the multivariate model it was observed that the general risk factors associated with fracture risk were the advanced age of the receptor (aHR per year increases 1.03, 95% CI: 1.00-1.05] and the female sex (aHR = 1.60, 95% CI: 0.85-2.99), while the specific risk factors were dialysis time (1.07 IC95%: 1.02-1.12), the higher age of the donor (1.03 IC95: 1,00-1,05) and the deficit of 25OHD (3.17 IC95: 1.57-6.41). Conclusions: This study allowed to evaluate predictive factors of fracture in our patients with kidney transplantation.

Clinical next generation sequencing in developmental and epileptic encephalopathies: Diagnostic relevance of data re-analysis and variants re-interpretation.

Developmental and epileptic encephalopathies (DEE) are complex pediatric epilepsies, in which heterogeneous pathogenic factors play an important role. Next-generation-sequencing based tools have shown excellent effectiveness. The constant increase in the number of new genotype-phenotype associations suggests the periodic need for re-interpretation and re-analysis of genetic studies without positive results. In this study, we report the diagnostic utility of targeted gene panel sequencing and whole exome sequencing in 55 Argentine subjects with DEE, focusing on the utility of re-interpretation and re-analysis of undetermined and negative genetic diagnoses. The new information in biomedical literature and databases was used for the re-interpretation. For re-analysis, sequencing data processing was repeated using updated bioinformatics tools. Initially, pathogenic variants were detected in 21 subjects (38%). After an average time of 29 months, 25% of the subjects without a genetic diagnosis were re-categorized as diagnosed. Finally, the overall diagnostic yield increased to 53% (29 subjects). In consequence of the re-interpretation and re-analysis, we identified novel variants in the genes: CHD2, COL4A1, FOXG1, GABRA1, GRIN2B, HNRNPU, KCNQ2, MECP2, PCDH19, SCN1A, SCN2A, SCN8A, SLC6A1, STXBP1 and WWOX. Our results expand the diagnostic yield of this subgroup of infantile and childhood seizures and demonstrate the importance of re-evaluation of genetic tests in subjects without an identified causative etiology.

[Disseminated histoplasmosis in a woman with seronegative arthritis]. / Histoplasmosis diseminada en una mujer con artritis seronegativa.

Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.

Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con compromiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.

Histoplasmosis diseminada en una mujer con artritis seronegativa / Disseminated histoplasmosis in a woman with seronegative arthritis

Resumen Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con com promiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.

Abstract Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.

A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis.

INTRODUCTION: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. OBJECTIVES: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. PATIENTS AND METHODS: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. RESULTS: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. CONCLUSIONS: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.

A systematic review of suicide and suicide attempts in adolescents with psychotic disorders.

BACKGROUND: Suicide is the main cause of premature death in patients with psychosis. Therefore, the goal of the present study was to review suicide in adolescents with psychotic disorders by evaluating factors associated with suicidal acts. Ours is the first systematic review of suicide in this population. METHOD: We performed a systematic review of suicide in adolescents (10 to 19 years) with psychotic disorder. RESULTS: We identified 10 studies, only 2 of which were randomized clinical trials. The results revealed high rates of suicidal behaviour in this population: the times of higher risk were the time before admission and the period immediately following discharge. The factors most associated with suicide attempts were depression, distress with psychotic symptoms, fewer negative symptoms at baseline, positive symptoms, and anxiety disorders. Associated factors included previous psychiatric history or psychiatric admissions, female sex, prior suicidal behaviour, family history of completed suicide, and nicotine dependence. LIMITATIONS: Clinical and methodological diversity of the studies. CONCLUSIONS: Adolescents with psychotic disorders had a major risk of suicidal behaviour, and specific factors were associated with the act. Early detection of adolescents with psychosis is vital, since it has been found that early intervention can prevent suicidal acts in young people. However, it is necessary to perform more studies, particularly randomized controlled trials, on suicide and suicide attempts, particularly in adolescents.

Field-Deployable Computer Vision Wood Identification of Peruvian Timbers.

Illegal logging is a major threat to forests in Peru, in the Amazon more broadly, and in the tropics globally. In Peru alone, more than two thirds of logging concessions showed unauthorized tree harvesting in natural protected areas and indigenous territories, and in 2016 more than half of exported lumber was of illegal origin. To help combat illegal logging and support legal timber trade in Peru we trained a convolutional neural network using transfer learning on images obtained from specimens in six xylaria using the open source, field-deployable XyloTron platform, for the classification of 228 Peruvian species into 24 anatomically informed and contextually relevant classes. The trained models achieved accuracies of 97% for five-fold cross validation, and 86.5 and 92.4% for top-1 and top-2 classification, respectively, on unique independent specimens from a xylarium that did not contribute training data. These results are the first multi-site, multi-user, multi-system-instantiation study for a national scale, computer vision wood identification system evaluated on independent scientific wood specimens. We demonstrate system readiness for evaluation in real-world field screening scenarios using this accurate, affordable, and scalable technology for monitoring, incentivizing, and monetizing legal and sustainable wood value chains.

Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: This research aims to study the efficacy of tannins co-supplementation on disease duration, severity and clinical symptoms, microbiota composition and inflammatory mediators in SARS-CoV2 patients. TRIAL DESIGN: This is a prospective, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy of the administration of the dietary supplement ARBOX, a molecular blend of quebracho and chestnut tannins extract and Vit B12, in patients affected by COVID-19. PARTICIPANTS: 18 years of age or older, admitted to Hospital de Clinicas Jose de San Martin, Buenos Aires University (Argentina), meeting the definition of "COVID-19 confirmed case" ( https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion-de-caso ). Inclusion Criteria Participants are eligible to be included in the study if the following criteria apply: 1. Any gender 2. ≥18 years old 3. Informed consent for participation in the study 4. Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: 1. Pregnant and lactating patients 2. Patients who cannot take oral therapy (with severe cognitive decline, assisted ventilation, or impaired consciousness) 3. Hypersensitivity to polyphenols 4. Patients already in ICU or requiring mechanical ventilation 5. Patients already enrolled in other clinical trials 6. Decline of consent INTERVENTION AND COMPARATOR: Experimental: TREATED ARM Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day. Placebo Comparator: CONTROL ARM Participants will receive placebo supply for 14 days. The placebo will be administered with the identical dose as described for the test product. All trial participants will receive standard therapy, which includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy. MAIN OUTCOMES: Primary Outcome Measures: Time to hospital discharge, defined as the time from first dose of ARBOX to hospital discharge [ Time Frame: Throughout the Study (Day 0 to Day 28) ] Secondary Outcome Measures: 28-day all-cause mortality [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Invasive ventilation on day 28 [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion Level of inflammation parameters and cytokines [ Time Frame: day 1-14 ] -mean difference Difference in fecal intestinal microbiota composition and intestinal permeability [ Time Frame: day 1-14 ] Negativization of COVID-PCR at day 14 [ Time Frame: day 14 ]-proportion RANDOMIZATION: Potential study participants were screened for eligibility 24 hours prior to study randomization. Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with tannin or standard treatment plus placebo (control group). BLINDING (MASKING): Study personnel and participants are blinded to the treatment allocation, as both ARBOX and placebo were packed in identical containers. Thus, all the used capsules had identical appearance. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Considering an alpha error of 5%, a power of 80% a sample size of 70 patients per branch was estimated. 140 patients in total. TRIAL STATUS: The protocol version is number V2, dated May 23, 2020. The first patient, first visit was on June 12, 2020; the recruitment end date was October 6, 2020. The protocol was not submitted earlier because the enrollment of some patients took place after the closure of the recruitment on the clinicaltrials platform. In fact, due to the epidemiological conditions, due to the decrease of the cases in Argentina during the summer period, the recruitment stopped t before reaching the number of 140 patients (as indicated in the webpage). However, since there was a new increase in cases, the enrolment was resumed in order to reach the number of patients initially planned in the protocol. The final participant was recruited on February 14, 2021. TRIAL REGISTRATION: ClinicalTrials.gov, number: NCT04403646 , registered on May 27th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Molecular Diagnosis in an Argentinean Mitochondrial Disorders Cohort

Abstract Mitochondrial diseases are multisystemic disorders characterized by an impairment of the mitochondrial respiratory chain. Diagnosis requires an approach that involves a high index of suspicion, molecular techniques and a careful selection of the tissue to be studied. Our goal was to develop and implement local strategies for diagnosing mitochondrial disorders, by standardizing procedures of molecular biology and nucleic acid sequencing. A prospective, analytical, observational study was conducted in a cohort of, a total of 82 patients with suspected mitochondrial disorder who were treated at our hospital between May 2008 and June 2019. We developed molecular diagnostic tools that included classical monogenic techniques and Next Generation Sequencing. We characterized the neurological and extra neurological manifestations noted in our cohort. Following the proposed algorithm, we obtained a molecular diagnostic performance of 54%, identifying mutations in 44 patients. mtDNA mutations were identified in 34 patients. Structural rearrangements in mitochondrial genome were found in 3 and 7 in nuclear genes, respectively. Our results confirm the utility of the proposed algorithm and the molecular tools used, as evidenced by a high diagnostic performance. This is of great value to a more efficient and comprehensive medical care of patients and families affected by mitochondrial disorders.