Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

Quantitative analysis of protein lipidation and acyl-CoAs reveals substrate preferences of the S-acylation machinery.

Protein palmitoylation or S-acylation has emerged as a key regulator of cellular processes. Increasing evidence shows that this modification is not restricted to palmitate but it can include additional fatty acids, raising the possibility that differential S-acylation contributes to the fine-tuning of protein activity. However, methods to profile the acyl moieties attached to proteins are scarce. Herein, we report a method for the identification and quantification of lipids bound to proteins that relies on hydroxylamine treatment and mass spectrometry analysis of fatty acid hydroxamates. This method has enabled unprecedented and extensive profiling of the S-acylome in different cell lines and tissues and has shed light on the substrate specificity of some S-acylating enzymes. Moreover, we could extend it to quantify also the acyl-CoAs, which are thioesters formed between a fatty acid and a coenzyme A, overcoming many of the previously described challenges for the detection of such species. Importantly, the simultaneous analysis of the lipid fraction and the proteome allowed us to establish, for the first time, a direct correlation between the endogenous levels of acyl-CoAs and the S-acylation profile of its proteome.

Impact of cognitive reserve in clinical, neurocognitive and lifestyle factors in chronic schizophrenia and early stages of schizophrenia.

INTRODUCTION: Although there is evidence that higher cognitive reserve (CR) is a protective factor and it has been related to better prognosis, there have been no studies to date that have explored the CR level and its impact in clinical, neurocognitive and lifestyle outcomes according to the stage of the disease: early stage of psychosis (ESP) or chronic schizophrenia (SCZ). MATERIAL AND METHODS: A total of 60 patients in the ESP and 225 patients with SCZ were enrolled in the study. To test the predictive capacity of CR for each diagnostic group, a logistic regression analysis was conducted. Hierarchical linear regression analyses were performed to explore the associations between CR and different outcomes. The mediation analyses were performed according to the principles of Baron and Kenny. RESULTS: Patients with SCZ showed lower CR than those in the ESP (p<0.001). CR correctly classified 79.6% of the cases (p<0.001; Exp(B)=1.062). In ESP group, CR was related to working memory (p=0.030) and negative symptoms (p=0.027). CR (t=3.925, p<0.001) and cannabis use (t=2.023, p=0.048) explained 26.7% of the variance on functioning (p=0.003). In patients with SCZ, CR predicted all cognitive domains, negative symptoms (R2=0.091, p=0.001) and functioning (R2=0.074, p=0.005). In both ESP and SCZ groups, higher CR was associated with lower body mass index and circumference. In ESP group, the effect of adherence to Mediterranean diet on functioning (p=0.037) was mediated by CR level (p=0.003). CONCLUSIONS: The implications of CR depend on the stage of the disease (ESP vs. SCZ), with a greater effect on neurocognition and negative symptoms in patients with chronic SCZ.

Modulation of D3R Splicing, Signaling, and Expression by D1R through PKA→PTB Phosphorylation.

The D1R and D3R receptors functionally and synergistically interact in striatonigral neurons. Dopaminergic denervation turns this interaction antagonistic, which is correlated with a decrement in D3nf isoform and an increment in D3R membranal expression. The mechanisms of such changes in D3R are attributed to the dysregulation of the expression of their isoforms. The cause and mechanism of this phenomenon remain unknown. Dopaminergic denervation produces a decrement in D1R and PKA activity; we propose that the lack of phosphorylation of PTB (regulator of alternative splicing) by PKA produces the dysregulation of D3R splicing and changes D3R functionality. By using in silico analysis, we found that D3R mRNA has motifs for PTB binding and, by RIP, co-precipitates with PTB. Moreover, D1R activation via PKA promotes PTB phosphorylation. Acute and 5-day D1R blockade decreases the expression of D3nf mRNA. The 5-day treatment reduces D3R, D3nf, and PTB protein in the cytoplasm and increases D3R in the membrane and PTB in the nucleus. Finally, the blockade of D1R mimics the effect of dopaminergic denervation in D1R and D3R signaling. Thus, our data indicate that through PKA→PTB, D1R modulates D3R splicing, expression, and signaling, which are altered during D1R blockade or the lack of stimulation in dopaminergic denervation.

Intestinal permeability and low-grade chronic inflammation in schizophrenia: A multicentre study on biomarkers. Rationale, objectives, protocol and preliminary results.

BACKGROUND: Altered intestinal permeability and low-grade chronic inflammation disrupt the integrity of the blood-brain barrier (microbiota-gut-brain axis), probably playing a role in the pathophysiology of schizophrenia-spectrum disorders. However, studies assessing the microbiota-gut-brain axis are inconsistent. This article describes the rationale, objectives, protocol, and presents descriptive results for a new project. METHODS: The sample of this study came from an observational, cross-sectional and multisite study including four centers in Spain (PI17/00246) recruiting adult patients with DSM-5 schizophrenia-spectrum disorders at any stage of the disease. The aims of the project are to assess the interrelation between intestinal permeability and low-grade chronic inflammation in schizophrenia-spectrum disorders and the role of peripheral biomarkers, diet, exercise, metabolic syndrome, disease severity and functioning as well as cognition. Assessments included the following variables: (1) anthropometric, (2) intestinal permeability, diet, and physical exercise, (3) clinical and functional, (4) neuropsychological and cognitive reserve, and (5) peripheral biomarkers from blood. RESULTS: A total of 646 patients were enrolled (257, 39.7% female). Mean age was 43.2±13.6 years, illness duration 15.1±11.5 years. 55.8% consumed tobacco. Positive PANSS score was 13.68±6.55, and 20.38±8.69 in the negative symptoms. CGI was 4.16±2.22 and GAF was 60.00±14.84. CONCLUSION: The results obtained by this project are expected to contribute toward the understanding of the physiopathology of schizophrenia-spectrum disorders. This will likely aid to personalize treatments in real-world clinical practice, potentially including variables related to intestinal permeability and inflammation.

Orofacial motricity in temporomandibular dysfunctions: an integrative approach to interdisciplinary intervention / Motricidad orofacial en disfunciones temporomandibulares: enfoque integrador en la intervención interdisciplinaria

ABSTRACT Objective: to describe the speech-language therapist role in the interdisciplinary team in the intervention of Orofacial motricity in the temporomandibular dysfunction documented in scientific publications. Methods: the search was conducted in well-known databases using the following terms or terminological associations: Temporomandibular dysfunction (TMD), stomatognathic system and TMD, Mastication, Speech and TMD. Interventions related to voice or temporomandibular joint indemnity were not included. Results: the interventions indicated in the scientific publications are described, giving an account of the role of the speech pathologist in the TMD intervention team. Conclusion: the therapist's intervention in Orofacial Motricity restores the stomatognathic system by addressing its functions. An isolated treatment approach from professionals overlooks the relationship of interdependence between function and structure. An appeal for an integrated and interdisciplinary work model, setting it free from the traditional fragmentary and multidisciplinary model, is made.

RESUMO Objetivo: describir el rol fonoaudiológico en el equipo interdisciplinario para la intervención de la motricidad orofacial en la disfunción temporomandibular documentado en publicaciones científicas. Métodos: la búsqueda se realizó en reconocidas bases datos usando los siguientes términos o asociaciones terminológicas: disfunción temporomandibular; Disfunción Temporo Mandibular; sistema estomatognático y Disfunción Temporo Mandibular; masticación, habla y Disfunción Temporo Mandibular. Se descartaron las intervenciones relacionadas con voz o indemnidad de Articulación Temporo Mandibular. Resultados: se describen las intervenciones señaladas en las publicaciones científicas, dando cuenta del rol del fonoaudiólogo en el equipo de intervención de la Disfunción Temporo Mandibular. Conclusión: la intervención fonoaudiológica en Motricidad Orofacial restablece la estructura abordando sus funciones. Un enfoque de tratamiento aislado de los profesionales desestima la relación de interdependencia entre función y estructura. Se aboga por una modalidad de trabajo integradora e interdisciplinaria, descartando la tradicional modalidad fragmentaria y multidisciplinar.

Consumo de sustancias y diferencias de género en personas afectas de un primer episodio psicótico: impacto en los porcentajes de reingreso / Substance abuse and gender differences in first episode psychosis: impact on hospital readmissions

Introducción. El estudio de diferencias de género en primeros episodios psicóticos (PEPs) ha aportado resultados controvertidos en los últimos años. El consumo de sustancias es la principal comorbilidad en PEPs, y se ha relacionado con un peor pronóstico y con una mayor gravedad sintomática. Objetivos. Explorar las diferencias de género en PEPs en relación con el consumo de sustancias, así como su relación con los reingresos hospitalarios. Metodología. Analítico y prospectivo (18 meses). Resultados. Incluimos 141 pacientes (31,2% mujeres), con una edad media de 26,1 años, mayoritariamente diagnosticadas de trastorno esquizofreniforme (32,6%). Un 58,9% presentan algún consumo problemático de sustancias. Encontramos diferencias significativas de género en la edad de inicio, de ingreso en el programa, el estado civil y la convivencia, y diferencias en el consumo de sustancias actual y la frecuencia de consumo. El género, la duración de la psicosis no tratada, los antecedentes psiquiátricos, la edad de inicio o el consumo de sustancias previo no fueron factores predictores de reingreso. El porcentaje de reingreso hospitalario fue del 24,8%, sin diferencias de género. Entre los motivos más frecuentes de ingreso se encuentran el abandono del tratamiento (66,7%) y el consumo de sustancias (44,4%), siendo mayor en los hombres el consumo de sustancias como motivo de reingreso. Conclusiones. Existen diferencias de género en PEPs. Los hombres inician más tempranamente los síntomas, con peores resultados funcionales. El consumo de sustancias en hombres es mayor y representa un importante motivo de reingreso hospitalario. Intervenciones terapéuticas dirigidas a prevenir su efecto son necesarias desde las primeras fases (AU)

Introduction. There have been controversial results in the study of gender differences in first episode psychosis (FEP). Substance abuse is the main existing comorbidity in FEP, and has been associated with worse prognosis and greater symptom severity. Objectives. To explore gender differences in FEP in relation to drug abuse, and their relationship with hospital readmissions. Methodology. Descriptive and prospective study (18 months). Results. We included 141 patients (31.2% women), aged 26.1 years on average, mostly diagnosed with schizophreniform disorder (32.6%). A percentage of 58.9 had problematic use of drugs. Gender significant differences were found in age of onset, age at entry to the programme, marital status and cohabitation, and percentage differences were revealed in current drug abuse and frequency of consumption. Gender, duration of untreated psychosis, psychiatric history, age of onset and previous drug use were not predictors of re-entry. Hospital readmission rate was 24.8%, with no gender differences. The most common reasons for admission were abandonment of treatment (66.7%) and drug abuse (44.4%). Drug abuse was higher in the men than in the women as a reason for re-admission. Conclusions. There are gender differences in FEP. Men have an earlier onset of symptoms and have worse functional outcomes. Drug abuse in men is higher and represents a major cause of hospital readmission. Therapeutic interventions to prevent the effects of drug abuse are necessary from the early stages of the illness (AU)

Efeito do processo de extrusäo sobre o teor de vitamina A em "snacks" fortificados elaborados a partir de misturas à base de milho, gräo-de-bico, amaranto e pulmäo bovino / Effect of extrusion cooking process on vitamin A concentration in snacks of admixed maize grits, defated chickpea, amaranth and bovine lung

A deficiência de micronutrientes, em especial a vitamina A., representa um sério problema de saúde pública em mais de 75 países em desenvolvimento. Por essa razäo têm surgido várias estratégias entre elas, a fortificaçäo de alimentos a fim de reduzir os efeitos negativos que ocasiona a sua falta. O emprego da extrusäo permite a criaçäo de novos produtos prontos para o consumo que constituem um bom veículo para vários nutrientes. Sabendo da instabilidade da vitamina A frente ao calor, oxigênio, umidade e outros fatores, tem surgido o interesse de estudar seu comportamento durante o processo. Objetivo. O presente trabalho teve como objetivo elaborar um salgadinho ("snacks") a partir de mistura de milho utilizando ingredientes näo tradicionais de alto valor nutritivo tais como farinha de gräo-de-bico, pulmäo bovino e amaranto, fortificados com acetato de vitamina A. Métodos. Estabeleceram-se combinaçöes de umidade e temperaturas ótimas, mais e menos deletérias em relaçäo a vitamina A (13 por cento, 177ºC; 11 por cento, 185ºC; 16 por cento, 130ºC) e que resultaram em textura e aparência adequadas do salgadinho. A dosagem de vitamina A foi realizada tanto nas farinhas como nos extrusados, obtendo assim a sua porcentagem de retençäo após o processo. Resultados. A extrusäo reduziu o teor inicial de vitamina A, entre 40,7 por cento - 66,9 por cento. Näo houveram diferenças significativas entre as condiçöes ótimas e menos deletérias em relaçäo a perda de vitamina A, embora observou-se uma influência clara da umidade e temperatura na concentraçäo final de vitamina A . O tipo de matéria-prima também influenciou na retençäo de vitamina A . Conclusäo. Os resultados obtidos sugerem uma fortificaçäo após o processo de extrusäo a fim de propiciar um salgadinho onde a vitamina A adicionada näo seja atingida pelo processo

Envenenamiento con agentes inhibidores de la colinesterasa / Envenenamiento with inhibiting agents of colinesterasa

Expone que los agentes inhibidores de la colinesterasa son empleados ampliamente tanto en los hogares como en la agricultura para la eliminación de insectos, sin embargo el uso y manejo de este tóxico es delicado y al servicio de urgencias muchos pacientes suelen acudir ya sea por envenenamiento accidental o por la ingesta voluntaria del mismo. Los agentes inhibidores de la colinesterasa se dividen en dos grupos: los carbamatos y los órganos fosforados, presentando ambos tóxicos la misma sintomatología entre los cuales tenemos sialorrea, naúseas, vómitos, miosis, diaforesis, diarrea, etc., la cual se presenta por la estimulación de los ganglios post-sinápticos al inhibirse la acetilcolinesterasa y por consiguiente la persistencia de la acetilcolina a este nivel.