Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors

Data on the long-term metabolic side-effects associated with antipsychotics are scarce. Prospective longitudinal studies in medication-naive patients with a first episode of psychosis are a valuable source of information as they provide an assessment prior to the antipsychotic exposure and minimize the effect of potential confounding factors. The aim of this study was to assess the course of weight gain and the incidence of metabolic abnormalities during the first 3 yr of antipsychotic treatment. Data were collected from a cohort of 170 first-episode psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine (32%) and risperidone (36%). The dose used was flexible. The initial antipsychotic treatment was changed when required, based on clinical response and tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the total mean weight gain) and then stabilized gradually over time. Total cholesterol, LDL-cholesterol and triglyceride levels followed a similar trajectory with a significant increase only during the first year. No significant changes were detected in the mean values of glycaemic parameters. Two patients with a family history of diabetes developed diabetes type II. At short-term the factors positively associated with weight gain were lower body mass index, male gender and olanzapine treatment. At long-term, functional status and clinical response were the main predictors. The results of our study indicate that the first year of antipsychotic treatment is a critical period for weight gain and metabolic changes. Identification of weight gain patterns may help to inform studies that aim to prevent or mitigate the metabolic adverse events associated with antipsychotic therapy

Investigating mutations in the genes GDF9 and BMP15 in Pelibuey sheep through the amplification-refractory mutation system with tetra-primers

Single Nucleotide Polymorphisms (SNP) or mutations are variations with a broad distribution in the genome and, as part of genetic studies, SNP allow the identification of allelic variants related to characteristics of economic importance in sheep production. However, the identification of SNP and their genotypes through sequencing is expensive, as it requires specialized materials and equipment. The objective of this study was to identify polymorphisms and their genotypes in the growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) genes in Pelibuey sheep using the tetra-primer amplification-refractory mutation system through polymerase chain reaction (T-ARMS-PCR). DNA extraction and amplification of BMP15 and GDF9 were conducted from blood samples contained in WhatmanTM FTATM cards from 60 multiparous Pelibuey ewes with reproductive records. The T-ARMS-PCR methodology allowed the identification of wild-type genotypes and mutated homozygous genotypes in polymorphisms G4 and G6 of GDF9, whereas mutations in the BMP15 gene were not found. These results were confirmed by sequencing. In conclusion, the T-ARMS-PCR methodology allowed the identification of mutated and wild-type genotypes in SNP G4 and G6 of GDF9, although no mutations were found in BMP15 in Pelibuey sheep. This technique was found to be reliable, rapid, and easily applied to identify polymorphic genotypes

Nuevos registros de Scolytinae (Coleoptera: Curculionidae) en bosques templados de Durango

En estudios previos realizados en Durango se han reportado 115 especies de escolitínos, la mayoría en bosques templados cercanos a las carreteras principales. Desde el trabajo publicado por Wood (1982) a la fecha se han agregado solo ocho especies. El presente trabajo se realizó de diciembre de 2019 a noviembre de 2020 utilizando trampas Ecoiapar cebadas con etanol. La mayor riqueza especifica fue de ocho especies en el sitio cuatro, mientras que la menor correspondió al sitio dos con cinco especies. Por otra parte, la mayor abundancia fue en el sitio seis con 119 capturas, siendo Monarthrum tuberculatum la especie más abundante durante el estudio. Se reportan 13 nuevos registros estatales Corthylus burgosi, C. nudus, Hylocurus femineus, Hylurgops longipennis, Monarthrum ca. scutellare, M. dentigerum, M. huachucae, M. tuberculatum, M. xalapensis, Pityophthorus ca. miniatus, P. cacuminatus, P. infulatus, P. virilis, Pseudopityophthorus granulatus, y una para México, Pityophthorus infulatus. Los resultados representan un aumento del 12.17 % de la riqueza conocida para el estado de Durango, respecto a las 115 especies registradas previamente, lo que asciende a un total de 129 especies para el estado.In previous studies carried out in Durango, 115 species of scolitins were reported, the majority in temperate forests, some studies have been carried out near the main roads, since the work published by Wood (1982) to date, only eight species have been added. This work was carried out for a period of one year from december 2019 to November 2020. Ecoiapar traps baited with ethanol were used. The highest specific richness that occurred was eight species in site four, while the lowest corresponded to site two with five species. On the other hand, the highest abundance was from site six with 119 captures, while Monarthrum tuberculatum was the most abundant species during the study. 13 new state records are reported Corthylus burgosi, C. nudus, Hylocurus femineus, Hylurgops longipennis, Monarthrum ca. scutellare, M. dentigerum, M. huachucae, M. tuberculatum, M. xalapensis, Pityophthorus ca. miniatus, P. cacuminatus, P. infulatus, P. virilis, P. granulatus, and one for Mexico Pityophtorus infulatus. The results represent an increase of 12.17% of the known diversity for the state of Durango, compared to the 115 species previously registered, which amounts to a total of 129 species for the state

Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia

This is the peer reviewed version of the following article: Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. Human Mutation (2020): 25 April, which has been published in final form at [https://doi.org/10.1002/humu.24026. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe variants identified in this study are openly available at http://www.lovd.nl/ with reference numbers 0000644164, 0000645396, 0000644166, and 0000405673Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298‐2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation‐specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation‐specific treatments for PKUThis work was funded by grant PI16/00573, B2017/BMD-3721, the Fundación Isabel Gemio and the Fundación La Caixa (LCF/PR/PR16/11110018), an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and the European Regional Development Fun

Efectos de la extracción de chaetomorpha linum y ulva spp sobre el estado ecológico del mar menor durante la primavera y verano de 2022

El Mar Menor a diferencia de otras lagunas costeras es de carácter oligotrófico y en las últimas décadas derivado de presiones agrícolas y urbanas, y una planificación litoral de escasa integración ambiental han desencadenado episodios eutróficos que el sistema ha intentado controlar mediante proliferaciones de medusas, algas, fitoplancton y zooplancton, en un intento de favorecer el sistema de producción primaria de arriba-abajo. El Gobierno de la Región de Murcia durante 2022 realiza una retirada de las algas con el fin de evitar la putrefacción y descomposición en zonas someras que generan fangos, y minimizando la incorporación de nutrientes desde el sediment

The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals

Background: Low-grade inflammation has been repeatedly associated with both excess weight and psychosis. However, no previous studies have addressed the direct effect of body mass index (BMI) on basal serum cytokines in individuals with first-episode psychosis (FEP). Objectives: The aim of this study is to analyze the effect of BMI on basal serum cytokine levels in FEP patients and control subjects, separating the total sample into two groups: normal-weight and overweight individuals. Methods: This is a prospective and open-label study. We selected 75 FEP patients and 75 healthy controls with similar characteristics to patients according to the following variables: sex, age, and cannabis and tobacco consumption. Both controls and patients were separated into two groups according to their BMI: subjects with a BMI under 25 were considered as normal weight and those with a BMI equal to or more than 25 were considered as overweight. Serum levels of 21 cytokines/chemokines were measured at baseline using the Human High Sensitivity T Cell Magnetic Bead Panel protocol from the Milliplex® Map Kit. We compared the basal serum levels of the 21 cytokines between control and patient groups according to their BMI. Results: In the normal-weight group, IL-8 was the only cytokine that was higher in patients than in the control group (p = 0.001), whereas in the overweight group, serum levels of two pro-inflammatory cytokines (IL-6, p = 0.000; IL-1?, p = 0.003), two chemokines (IL-8, p = 0.001; MIP-1?, p = 0.001), four Th-1 and Th-2 cytokines (IL-13, p = 0.009; IL-2, p = 0.001; IL-7, p = 0.001; IL-12p70, p = 0.010), and one Type-3 cytokine (IL-23, p = 0.010) were higher in patients than in controls. Conclusions: Most differences in the basal serum cytokine levels between patients and healthy volunteers were found in the overweight group. These findings suggest that excess weight can alter the homeostasis of the immune system and therefore may have an additive pro-inflammatory effect on the one produced by psychosis in the central nervous system.Funding: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support from MINECO SAF2013-46292-R, Instituto de Salud Carlos III, and Fundación Marqués de Valdecilla. No pharmaceutical company has participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting of the manuscript. We thank the Valdecilla Biobank for blood sampling handling and storage. We also wish to thank the participants and their families for enrolling in this study. The study, designed and directed by B C-F, conformed to international standards for research ethics and was approved by the local institutional review board

Targeting the anion exchanger 2 with specific peptides as a new therapeutic approach in B lymphoid neoplasms

Regulatory T (Treg) cells can weaken antitumor immune responses, and inhibition of their function appears to be a promising therapeutic approach in cancer patients. Mice with targeted deletion of the gene encoding the Cl−/HCO3− anion exchanger AE2 (also termed SLC4A2), a membrane-bound carrier involved in intracellular pH regulation, showed a progressive decrease in the number of Treg cells. We therefore challenged AE2 as a potential target for tumor therapy, and generated linear peptides designed to bind the third extracellular loop of AE2, which is crucial for its exchange activity. Peptide p17AE2 exhibited optimal interaction ability and indeed promoted apoptosis in mouse and human Treg cells, while activating effector T-cell function. Interestingly, this linear peptide also induced apoptosis in different types of human leukemia, lymphoma and multiple myeloma cell lines and primary malignant samples, while it showed only moderate effects on normal B lymphocytes. Finally, a macrocyclic AE2 targeting peptide exhibiting increased stability in vivo was effective in mice xenografted with B-cell lymphoma. These data suggest that targeting the anion exchanger AE2 with specific peptides may represent an effective therapeutic approach in B-cell malignancies

Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia

Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298-2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation-specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation-specific treatments for PKU.This work was funded by grant PI16/00573, B2017/BMD-3721, the Fundación Isabel Gemio and the Fundación La Caixa (LCF/PR/PR16/11110018), an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and the European Regional Development Fund.Peer reviewe

Elaboración de metodologías, materiales y recursos didácticos para la docencia de la filosofía en educación secundaria, estudios de grado y estudios de posgrado

Memoria ID2022-061. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2022-2023

Cuidados enfermeros en la gangrena de Fournier: todo un reto

logía de los HH. UU.Virgen del Rocío (Sevilla). Se muestran los patrones funcionales alterados, siguiendo el modelo de M. Gordon, así como los cuidados enfermeros prestados. Se destaca la necesidad de una buena coordinación entre los equipos de enfermería de hospitalización, hospitalización domiciliaria y atención primaria de salud, pues de ello va a depender en gran medida la buena resolución de la herida quirúrgica y el estado de salud del paciente.We report a case of Fournier's gangrene, an infectious disease of high morbidity and mortality, treated at the Urology Department of the HH. UU. Virgen del Rocío (Sevilla). Altered functional patterns are showed, following the model of M. Gordon and nursing care provided. It highlights the need for good coordination between the nursing teams of hospitalization, hospital care and primary health care, since this will depend largely on the good resolution of the surgical wound and the patient's health status.