The Use of a Spanish-Translated PrEP Stigma Scale among the Latino Sample of the UNITE Cohort Study.

Pre-Exposure Prophylaxis (PrEP) related stigma is linked to inadequate PrEP uptake, yet there are no validated scales to test this association among Spanish-speaking LSMM. The current study examined if the Spanish-translated PrEP Stigma Scale (PSS) was psychometrically appropriate for implementing in Spanish language dominant Latino/e/x Sexual Minority Men (SMM). Recruitment was conducted using geosocial networking applications, social media sites, and e-mail blasts (N=3,049). First, we utilized Item Response Theory (IRT) modeling to evaluate the reliability of the PSS items and the latent construct across both language groups (nEnglish = 2844 and nSpanish = 205). Subsequently, we applied the PSS scale in a theoretical application by examining its association with key steps in the PrEP uptake cascade (i.e., perceived PrEP candidacy, PrEP willingness, PrEP intentions, and having spoken to provider about PrEP) stratified by language. Results of the IRT analyses provided evidence that the translated version of the PSS was appropriate for use among this sample. Further, among English respondents, PrEP stigma was negatively associated with perceived PrEP candidacy (B=-0.30, p=<.001), PrEP willingness (B=-0.46, p=<.001), and PrEP intentions (B=-0.23, p=.003). PrEP stigma, among Spanish respondents, was not significantly associated with any of the PrEP cascade steps. This study demonstrated that the PSS scale performs adequately for both English and Spanish-speaking Latino SMM. However, researchers and health professionals alike should pay close attention to the nuanced effects in U.S. based English and Spanish language samples as PrEP stigma may impact the PrEP cascade for one language sample and not the other.

Treatment-emergent Candida infections in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis treated with ixekizumab: an integrated safety analysis of 25 clinical studies.

BACKGROUND: This safety analysis investigates treatment-emergent mucosal/cutaneous Candida infections in patients treated with ixekizumab (IXE), an anti-interleukin-17A monoclonal antibody, across the approved indications: psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA). RESEARCH DESIGN AND METHODS: Safety data were pooled from 25 clinical studies. Incidence rates (IRs) are expressed as per 100 patient-years (PY), using the entire duration of exposure. RESULTS: Candida infections had an IR of 1.9 per 100 PY in patients with PsO (N = 6892; total PY = 18025.7), 2.0 per 100 PY in patients with PsA (N = 1401; total PY = 2247.7), and 1.2 per 100 PY in patients with axSpA (N = 932; total PY = 2097.7). The majority of treatment-emergent Candida infections were: (i) experienced only once by patients (IR = 1.3;IR = 1.6;IR = 1.0), (ii) mild/moderate in severity (IR = 0.8/0.9;IR = 1.5/0.4;IR = 0.8/0.5) as opposed to severe (IR = 0.0; IR = 0.0; IR = 0.0), (iii) oral Candida or genital Candida (IR = 0.9/0.6;IR = 1.0/0.7;IR = 0.4/0.6), (iv) marked as recovered/resolved during the studies (89.3%;93.8%;90.3%), (v) not leading to IXE discontinuation (0.0%;0.0%;0.1% discontinued), (vi) managed with topical (34.7%;22.2%;11.5%) or no anti-fungal medications (63.5%;77.8%;80.8%) as opposed to systemic therapies (1.5%;0.0%;7.7%), (vii) typically resolved before next visit. CONCLUSIONS: This integrated safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications. TRIAL REGISTRATION: A comprehensive list of the clinical trials and their registration numbers is reported in Table S1 of the supplemental material.

Ixekizumab (IXE) is a drug approved for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis. IXE belongs to the class of molecules that blocks a protein called interleukin-17A. Since interleukin-17A is involved in the defense against fungi, the clinical use of this class of drug has the potential to increase the risk of developing fungal infections, such as Candida infections.Therefore, researchers collected safety data from 25 clinical studies comprising 9225 adult patients treated with IXE: 6892 with psoriasis, 1401 with psoriatic arthritis, and 932 with axial spondyloarthritis. Researchers looked at the rate of new cases of Candida infections, the so-called incidence rate, and found that 1.9 per 100 patient-years experienced at least 1 Candida infection in the psoriasis group, 2.0 per 100 patient-years in the psoriatic arthritis group, and 1.2 per 100 patient-years in the axial spondyloarthritis group.Across indications, the majority of Candida infections (i) were experienced only once by patients, (ii) were mild or moderate in severity, (iii) involved infections caused by superficial skin fungus in the mouth or genitals, (iv) were considered recovered/resolved during the studies, (v) did not lead to IXE discontinuation, (vi) were managed with topical anti-fungal medications or no medications, and (vii) were typically resolved before next visit.In conclusion, this safety analysis shows that the risk of developing Candida infections is low with IXE, and the severity is mild-to-moderate in most instances across the approved IXE indications.

In-hospital unfavorable outcomes of MIS-C during 2020-2022: a systematic review.

Studies on the severity in multisystem inflammatory syndrome in children (MIS-C) show heterogeneous results and may not reflect a global perspective. This systematic review aims to estimate the frequency of in-hospital unfavorable outcomes in patients with MIS-C over the 3 years since the onset of the SARS-CoV-2 pandemic. A systematic search was conducted in Medline, Scopus, Embase, Cochrane, Web of Science, Scielo, and preprint repositories until December 15, 2022. Study selection and data extraction were evaluated independently. The primary outcomes were intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death. Additionally, we evaluated cardiovascular-related outcomes. We performed a random-effects model meta-analysis and assessed the certainty of the evidence. Fifty-seven studies (n = 13 254) were included. The frequency of ICU admission was 44.7% (95% CI 38.8-50.7), 11.9% for IMV (95% CI 9.6-14.4), and 2.0% for death (95% CI 1.3-3.0). The requirement of vasoactive/inotropic drugs was 40.1% (95% CI 35.9-44.4), 7.9% for coronary aneurysm (95% CI 4.1-12.7), 30.7% for decreased left ventricle ejection fraction (LVEF) (95% CI 26.3-35.4), and 29.7% for myocarditis (95% CI 18.4-42.4). We assess the included evidence as being of very low certainty. Finally, excess COVID-19 mortality by country and the diagnostic criteria for MIS-C (CDC compared to WHO) were associated with a higher frequency of ICU admissions. The year of study conduction (2022 compared to 2020) was associated with a lower frequency of IMV. CONCLUSION: The frequency of in-hospital unfavorable outcomes in patients with MIS-C was high. Well-designed studies are needed to explore other heterogeneity sources. PROTOCOL REGISTRATION: CRD42021284878. WHAT IS KNOWN: • Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious condition linked to SARS-CoV-2. Studies on the severity of MIS-C show heterogeneous results. These findings may not be representative of the reality in other regions, making it challenging to draw generalizable conclusions. WHAT IS NEW: • Over the 3 years since the onset of the SARS-CoV-2 pandemic, our systematic review has shown that the frequency of in-hospital unfavorable outcomes in patients with MIS-C is high, with a very low certainty of the evidence. Our results reflect the reality from a global perspective, across different countries with varying income levels. • The main sources of heterogeneity in the frequency of severe outcomes could be explained by the excess mortality due to COVID-19 in each country, the type of diagnostic criteria for MIS-C, and the year the study was conducted.

Study of Potential Blocking Peptides Targeting the SARS-CoV-2 RBD/hACE2 Interaction.

BACKGROUND/OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, was declared a public health emergency in early 2020. The infection initiates when the receptor-binding domain (RBD) of the viral spike protein binds to human angiotensin-converting enzyme 2 (ACE2). Despite the success of vaccination efforts, the emergence of new variants highlights the ongoing need for treatments targeting these evolving strains. In silico methods previously identified peptides BP2, BP9, and BP11 as being capable of disrupting the RBD-ACE2 interaction, though their efficacy has not been experimentally validated until now. METHODS: In this study, these peptides were recombinantly produced in the yeast Komagataella phaffii, and the activity was assessed in vitro using binding assays with multiple RBD variants and the inhibition of the RBD-ACE2 interaction. RESULTS: The production yield for BP2, BP9, and BP11 was 14.34, 4.01, and 1.35 mg per culture liter, respectively. Noteworthy, the three BPs interacted with the RBD of SARS-CoV-2 variants of concern, with BP2 showing higher recognition. Finally, the BPs showed an RBD/hACE2 interaction blocking capacity with IC50 values between 1.03 and 5.35 nM, with BP2 showing the lowest values among the evaluated peptides. CONCLUSIONS: These results demonstrate that BP2, specifically, is a promising candidate for the development of novel therapeutic interventions targeting SARS-CoV-2 and other coronaviruses that use hACE2 for cellular entry.

Non-Coding RNAs and Innate Immune Responses in Cancer.

Non-coding RNAs (ncRNAs) and the innate immune system are closely related, acting as defense mechanisms and regulating gene expression and innate immunity. Both are modulators in the initiation, development and progression of cancer. We aimed to review the major types of ncRNAs, including small interfering RNAs (siRNAs), microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), and long non-coding RNAs (lncRNAs), with a focus on cancer, innate immunity, and inflammation. We found that ncRNAs are closely related to innate immunity, epigenetics, chronic inflammation, and cancer and share properties such as inducibility, specificity, memory, and transfer. These similarities and interrelationships suggest that ncRNAs and modulators of trained immunity, together with the control of chronic inflammation, can be combined to develop novel therapeutic approaches for personalized cancer treatment. In conclusion, the close relationship between ncRNAs, the innate immune system, and inflammation highlights their importance in cancer pathways and their potential as targets for novel therapeutic strategies.

Traumatic middle meningeal arteriovenous fistulas (MMAVFs): an exploratory systematic review.

This study aims to systematically review case reports and case series in order to compare the postoperative course of conservative, endovascular and surgical treatments for traumatic dural arteriovenous fistulas predominantly supplied by the middle meningeal artery (MMAVFs), which usually occur following head trauma or iatrogenic causes. We conducted a comprehensive search of PubMed, Embase, Scopus, Web of Science, and Google Scholar until June 23rd, 2024. Three cohorts were defined based on the treatment modality employed. The primary outcomes were the rates of overall obliteration and postoperative complications, with all-cause mortlality considered as secondary outcome. A total of 61 studies encompassing 78 pooled MMAVFs were included in the qualitative analysis. The predominant demographic consisted of males (53.9%) with a median age of 50.5 (IQR: 33.5-67.5) years. The main etiologies for fistula formation were head trauma (75.6%), cranial neurosurgical procedures (11.5%) and endovascular embolization (8.97%). Venous drainage patterns were categorized as follows based on anatomical confluence: Class I (16.7%), II (14.1%), III (12.8%), IV (14.1%), V (7.7%), and VI (3.9%). Regarding treatment efficacy, the overall obliteration rate was 89.74%, achieved through endovascular (95.83%), surgical (64.29%) or conservative (93.75%) approaches. In terms of safety, the overall postoperative complication rate was 6.49% with an all-cause mortality rate of 8.97%, predominantly observed in the surgical group (35.71%). Our systematic review highlights the challenging management of traumatic MMAVFs, frequently associated with head injuries. Endovascular therapy has emerged as the predominant treatment modality, demonstrating markedly higher rates of fistula obliteration, reduced all-cause mortality, and fewer postoperative complications.

Evidence of Internal Structure Validity, Measurement Invariance, Convergent Validity, Clinical Validity, and Reliability of the Woman Abuse Screening Tool in Peruvian Women.

Intimate partner violence (IPV) is the most common type of violence committed against women and results in serious personal, familial, social, and economic consequences; thus, there is a need to detect IPV early. One test for detecting IPV is the Woman Abuse Screening Tool (WAST). The objective of the study was to obtain evidence of the validity of the WAST in terms of its internal structure, measurement invariance, convergent validity, clinical validity, and reliability. A total of 670 women who have or have had a heterosexual relationship participated in the study. The first stage included 513 adult women who partook of health services (M age = 35.5 years, SD age = 10 years). The second stage included 160 women, 80 diagnosed with IPV (M age = 34.2 years, SD age = 11.8 years) and 80 who were not (M age = 31.8 years, SD age = 11.5 years). We used multivariate and receiver operating characteristic curve analyses. We found evidence that the WAST demonstrates a one-dimensional structure; evidence of measurement invariance regarding cohabitation with the partner, length of the relationship, and age; evidence of convergent validity in terms of correlations with emotional dependence, self-compassion, expressive suppression, anxiety, and depression; and evidence of clinical validity in terms of the high probability of detecting positive cases of IPV. These properties support the use of the WAST for detecting possible cases of IPV, which will allow timely intervention. This instrument can also be used in larger studies on IPV in the Spanish-speaking population.

Knowledge of dementia and Alzheimer's disease among healthcare professionals in Peru.

BACKGROUND: Primary care physicians and other healthcare providers report feeling unprepared to treat persons with dementia (PWD), especially in developing countries OBJECTIVE: We aimed to assess the knowledge of dementia and Alzheimer's disease (AD) among health professionals in both primary and tertiary care in Peru. METHODS: We conducted an in-person and virtual survey of healthcare professionals trained in Peru throughout the year 2020. The survey was developed based on a previously published one and reviewed by an expert panel. We compared groups using a Chi-squared test. A Bonferroni corrected p-value of 0.008 was used for statistical significance. RESULTS: Out of 804 surveys, we excluded 56 due to incomplete data. A total of 41.6% of respondents were doctors and 21.8%, nurses. One fifth of participants did not recognize AD as a cause of dementia and over half considered "senile dementia" a valid clinical entity. Scores were higher among those with postgraduate training, multiple patients with dementia, or those who had practiced for over 10 years. CONCLUSION: There is a low level of knowledge of dementia and AD among health professionals in Peru, which worsens outside of Lima. Pernicious ideas, such as senile dementia, are still significantly present among respondents.

ANTECEDENTES: Los médicos de primer nivel de atención y otros profesionales de la salud no se consideran cómodos tratando pacientes con demencia, especialmente en países en vías de desarrollo. OBJETIVO: Buscamos evaluar el conocimiento sobre demencia y enfermedad de Alzheimer entre profesionales de la salud en centros de atención primaria y terciaria en Perú.: MéTODOS: Realizamos una encuesta virtual y presencial a trabajadores de la salud entrenados en Perú en el año 2020. La encuesta fue desarrollada con base en una previamente publicada y revisada por un panel de expertos. Comparamos los grupos por medio de una prueba de Chi-cuadrado. Un valor de p de 0.008, obtenido por una corrección de Bonferroni, fue usado para determinar la significancia estadística. RESULTADOS: De 804 encuestados, excluimos 56 debido a datos incompletos. En total, 41.6% de los encuestados eran médicos y 21.8%, enfermeras. Un quinto no reconocía a la enfermedad de Alzheimer como una causa de demencia, y más de la mitad consideraban a la "demencia senil" una entidad clínica válida. Los puntajes fueron mayores para aquellos con entrenamiento de posgrado, experiencia con pacientes con demencia, o más de 10 años de experiencia. CONCLUSIóN: Existe un bajo nivel de conocimiento sobre demencia y enfermedad de Alzheimer entre profesionales de la salud en Perú. Este es aún más bajo fuera de Lima. Ideas dañinas como la "demencia senil" aún están significativamente presentes entre los encuestados.

Potential of mesenchymal stromal/stem cells and spermatogonial stem cells for survival and colonization in bull recipient testes after allogenic transplantation.

Stem cell transplantation into seminiferous tubules of recipient testis could become a tool for fertility restoration, genetic improvement, or conservation of endangered species. Spermatogonial stem cells (SSCs) are primary candidates for transplantation; however, limited abundance, complexity for isolation and culture, and lack of specific markers have limited their use. Mesenchymal stromal/stem cells (MSCs) are multipotent progenitors that are simple to isolate and culture and possess specific markers for identification, and immune evasive and migratory capacities. The objective of the present study was to evaluate the potential for survival and colonization in seminiferous tubules of two different concentrations of bovine fetal adipose tissue-derived MSCs (AT-MSCs), native of pre-induced, and to compare the fate of bovine adult peripheral blood-derived MSCs (PB-MSCs) and SSCs after allogenic transplantation in testis of recipient bulls. In experiment 1, AT-MSCs at two concentrations (1x107 and 2x107; n = 3) or pre-exposed to 2 µM testosterone and 1 µM retinoic acid (RA) for 14 days (n = 5) were evaluated. In experiment 2, adult PB-MSCs and SSCs (4x107 cells each) pre-exposed to Sertoli cell conditioned media (SCs/CM; n = 4) for 14 days were compared. Each cell type was separately labelled with PKH26 and then transplanted into testes of 8-month-old recipient bulls. Four weeks (Exp. 1) and two weeks (Exp. 2) after transplantation, testicular tissue was processed for confocal microscopy detection of PKH26-positive cells. Mean number of PKH26-positive cells were higher (P < 0.05) in testis transplanted with 2x107 AT-MSCs in the proximal (6.7 ± 3.7) and medial (6.6 ± 3.2) sections compared to testis transplanted with 1x107 AT-MSCs (proximal: 1.9 ± 1; medial: 1.9 ± 1) sections or pre-induced AT-MSCs (proximal: 4.7 ± 5.6; medial: 3.8 ± 4.1). In Exp. 2, mean number of PKH26-positive SSCs in medial testicular section (22.5 ± 1.3) were higher (P < 0.05) compared to respective section in PB-MSCs group (17 ± 4.2). Thus, in vivo data indicates that a higher number of transplanted AT-MSCs resulted in more cells surviving and colonizing seminiferous tubules; however, pre-induction with testosterone and RA did not improve these capacities. SSCs displayed a greater capacity for survival and colonization in recipient seminiferous tubules; however, PB-MSCs were observed in all sections of testis after two weeks of transplantation.

Stability, Balance, and Physical Variables in Patients with Bilateral Hemophilic Arthropathy of the Ankle versus Their Healthy Peers: A Case-Control Study.

(1) Background: The recurrence of hemarthrosis in patients with hemophilia triggers a pathophysiological process of degenerative, progressive, and irreversible joint destruction. This hemophilic arthropathy is characterized by chronic pain, muscle atrophy, loss of mobility, and proprioceptive alterations. As the same joint undergoes repeated hemarthrosis, the function of the mechanical receptors deteriorates, causing a pathophysiological modulation and deterioration of the musculoskeletal system. The objective was to analyze the differences in stability and balance, as well as in ankle dorsal flexion, functionality, and muscle strength, between patients with bilateral hemophilic arthropathy and their healthy peers. (2) Methods: A cross-sectional descriptive case-control study was performed. Twenty-two participants were recruited: 10 adult patients with bilateral hemophilic arthropathy of the knee and ankle and 12 healthy subjects. The variables were balance (Rs Scan pressure platform), ankle dorsiflexion range of motion (Leg Motion), functionality (2-Minute Walk Test), and ankle dorsal strength (dynamometry). (3) Results: Statistically significant differences (p < 0.05) were found in the balance without visual support in the Max-Y variable (MD = 2.83; CI95%: 0.33;5.33; Effect size (d) = 0.67), ankle dorsiflexion (MD = 16.00; CI95%: 14.30; 20.0; d = 7.46), and strength of the ankle flexor muscles (MD = 128.50; CI95%: 92.50; 153.60; d = 2.76). (4) Conclusions: Ankle range of motion in dorsal flexion, functionality, and muscle strength in dorsal flexion is poorer in patients with bilateral lower limb hemophilic arthropathy than in their healthy peers. Patients with bilateral hemophilic ankle arthropathy have statistically poorer stability and balance without visual support than their healthy peers.

Subcutaneous vs intravenous abatacept in rheumatoid arthritis-interstitial lung disease. National multicentre study of 397 patients.

BACKGROUND: Evidence on abatacept (ABA) utility for rheumatoid arthritis (RA) - associated interstitial lung disease (ILD) is growing. Clinical trials have shown equivalence in subcutaneous (SC) and intravenous (IV) administration of ABA for articular manifestations. However, this has not been studied in respiratory outcomes. OBJECTIVE: To compare the effectiveness of ABA in RA-ILD patients according to the route of administration. METHODS: National retrospective multicentre study of RA-ILD patients on treatment with ABA. They were divided into 2 groups: a) IV, and b) SC. The following outcomes were analysed from baseline to final follow-up using linear mixed models: a) forced vital capacity (FVC), b) diffusing capacity of the lungs for carbon monoxide (DLCO), c) chest high resolution computed tomography (HRCT), d) dyspnoea, e) RA activity, and f) sparing corticosteroids effect. RESULTS: A total of 397 patients were included (94 IV-ABA and 303 SC-ABA), median follow-up of 24 [10-48] months. After adjustment for possible confounders, FVC and DLCO remained stable during the first 24 months without differences between IV-ABA and SC-ABA (p = 0.6304 and 0.5337). Improvement/ stability of lung lesions in HRCT was observed in 67 % of patients (75 % IV-ABA, 64 % SC-ABA; p = 0.07). Dyspnoea stabilized/ improved in 84 % of patients (90 % IV-ABA, 82 % SC-ABA; p = 0.09). RA - disease activity improved in both groups. No statistically significant differences regarding any of the variables studied between the two groups were found. ABA was withdrawn in 87 patients (21.9 %), 45 % IV-ABA and 37 % SC-ABA (p = 0.29). ILD worsening and articular inefficacy were the most common reasons for ABA discontinuation. CONCLUSION: In patients with RA-ILD, ABA seems to be equally effective regardless of the route of administration.

Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes.

The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.

Novel human recombinant N-acetylgalactosamine-6-sulfate sulfatase produced in a glyco-engineered Escherichia coli strain.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by mutations in the gene encoding the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), resulting in the accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). Previously, it was reported the production of an active human recombinant GALNS (rGALNS) in E. coli BL21(DE3). However, this recombinant enzyme was not taken up by HEK293 cells or MPS IVA skin fibroblasts. Here, we leveraged a glyco-engineered E. coli strain to produce a recombinant human GALNS bearing the eukaryotic trimannosyl core N-glycan, Man3GlcNAc2 (rGALNSoptGly). The N-glycosylated GALNS was produced at 100 mL and 1.65 L scales, purified and characterized with respect to pH stability, enzyme kinetic parameters, cell uptake, and KS clearance. The results showed that the addition of trimannosyl core N-glycans enhanced both protein stability and substrate affinity. rGALNSoptGly was capture through a mannose receptor-mediated process. This enzyme was delivered to the lysosome, where it reduced KS storage in human MPS IVA fibroblasts. This study demonstrates the potential of a glyco-engineered E. coli for producing a fully functional GALNS enzyme. It may offer an economic approach for the biosynthesis of a therapeutic glycoprotein that could prove useful for MPS IVA treatment. This strategy could be extended to other lysosomal enzymes that rely on the presence of mannose N-glycans for cell uptake.

Factors that indicate performance on the MoCA 7.3 in healthy adults over 50 years old.

Human aging is a physiological, progressive, heterogeneous global process that causes a decline of all body systems, functions, and organs. Throughout this process, cognitive function suffers an incremental decline with broad interindividual variability.The first objective of this study was to examine the differences in the performance on the MoCA test (v. 7.3) per gender and the relationship between the performance and the variables age, years of schooling, and depressive symptoms .The second objective was to identify factors that may influence the global performance on the MoCA test (v. 7.3) and of the domains orientation, language, memory, attention/calculation, visuospatial and executive function, abstraction, and identification.A cross-sectional study was carried out in which five hundred seventy-three (573) cognitively healthy adults ≥ 50 years old were included in the study. A sociodemographic questionnaire, the GDS-15 questionnaire to assess depression symptoms and the Spanish version of the MoCA Test (v 7.3) were administered. The evaluations were carried out between the months of January and June 2022. Differences in the MoCA test performance per gender was assessed with Student's t-test for independent samples. The bivariate Pearson correlation was applied to examine the relationship between total scoring of the MoCA test performance and the variables age, years of schooling, and depressive symptoms. Different linear multiple regression analyses were performed to determine variables that could influence the MoCA test performance.We found gender-related MoCA Test performance differences. An association between age, years of schooling, and severity of depressive symptoms was observed. Age, years of schooling, and severity of depressive symptoms influence the MoCA Test performance, while gender does not.

Identification of Orthosteric and Allosteric Pharmacological Chaperones for Mucopolysaccharidosis Type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB) is an autosomal inherited disease caused by mutations in gene encoding the lysosomal enzyme N-acetyl-alpha-glucosaminidase (NAGLU). These mutations result in reduced NAGLU activity, preventing it from catalyzing the hydrolysis of the glycosaminoglycan heparan sulfate (HS). There are currently no approved treatments for MPS IIIB. A novel approach in the treatment of lysosomal storage diseases is the use of pharmacological chaperones (PC). In this study, we used a drug repurposing approach to identify and characterize novel potential PCs for NAGLU enzyme. We modeled the interaction of natural and artificial substrates within the active cavity of NAGLU (orthosteric site) and predicted potential allosteric sites. We performed a virtual screening for both the orthosteric and the predicted allosteric site against a curated database of human tested molecules. Considering the binding affinity and predicted blood-brain barrier permeability and gastrointestinal absorption, we selected atovaquone and piperaquine as orthosteric and allosteric PCs. The PCs were evaluated by their capacity to bind NAGLU and the ability to restore the enzymatic activity in human MPS IIIB fibroblasts These results represent novel PCs described for MPS IIIB and demonstrate the potential to develop novel therapeutic alternatives for this and other protein deficiency diseases.

Comparison of the Stress and Anxiety to Viral Epidemic-9 and SAVE-6 scales among healthcare workers in Peru.

Introduction: Peru is a country that has a high incidence of viral outbreaks and epidemics, which is why it is necessary to validate a scale that measures anxiety and stress in professionals who are on the front lines of these events. Therefore, our objective was to validate the Peruvian-Spanish version of the Stress and Anxiety to Viral Epidemics-9 items (SAVE-9) scale and to concurrently compare its validity and internal consistency with the SAVE-6 scale among healthcare workers (HCWs). Materials and methods: We conducted a cross-sectional study based on data collected from a self-reported survey in paper-and-pencil format between April and July 2023. A total of 203 HCWs participated in the research. We developed a confirmatory factor analysis (CFA) and item response theory (IRT). We calculated Cronbach's α coefficient and McDonald's ω to assess the internal consistency of the scales. Results: The results show that SAVE-9 (a two-factor model) and SAVE-6 (a one-factor model) provided an excellent fit in the confirmatory factor analysis. Both scales demonstrated strong internal consistency (Cronbach's α 0.85 and 0.86, respectively). Significant correlations were found between the SAVE-9 and SAVE-6 scales and Generalized Anxiety Disorder-7 items scale (r = 0.44 and r = 0.38, respectively, p < 0.001) as well as the Patient Health Questionnaire-9 items (r = 0.39 and r = 0.35, respectively, p < 0.001). The optimal cutoff points for SAVE-9 and SAVE-6 were identified for assessing anxiety, aligned with a GAD-7 score ≥5 points. Conclusion: The Peruvian-Spanish SAVE-9 and SAVE-6 scales are reliable and valid rating scales to assess the anxiety response of HCWs in response to viral epidemics. Though COVID-19 is diminished, these scales will be useful for other viral epidemics in the future.

Targeting Neutrophil Extracellular Trap Formation: Exploring Promising Pharmacological Strategies for the Treatment of Preeclampsia.

Neutrophils, which constitute the most abundant leukocytes in human blood, emerge as crucial players in the induction of endothelial cell death and the modulation of endothelial cell responses under both physiological and pathological conditions. The hallmark of preeclampsia is endothelial dysfunction induced by systemic inflammation, in which neutrophils, particularly through the formation of neutrophil extracellular traps (NETs), play a pivotal role in the development and perpetuation of endothelial dysfunction and the hypertensive state. Considering the potential of numerous pharmaceutical agents to attenuate NET formation (NETosis) in preeclampsia, a comprehensive assessment of the extensively studied candidates becomes imperative. This review aims to identify mechanisms associated with the induction and negative regulation of NETs in the context of preeclampsia. We discuss potential drugs to modulate NETosis, such as NF-κß inhibitors, vitamin D, and aspirin, and their association with mutagenicity and genotoxicity. Strong evidence supports the notion that molecules involved in the activation of NETs could serve as promising targets for the treatment of preeclampsia.