Public interest in drug-related problems reflected in information search trends: an infodemiological study.

BACKGROUND: The analysis of how people search and "navigate" the internet to obtain health-related information and how they communicate and share this information can provide valuable knowledge about the disease patterns behaviour and health habits of populations. OBJECTIVE: To determine the population's interest in drug-related problems through information search trends. METHOD: A descriptive ecological correlational study, based on obtaining Google Trends data. VARIABLES STUDIED: relative search volume (RSV), evolution over time, milestones and seasonality. RESULTS: The most searched topic was drug overdose, with mean RSV of 56.25 ± 0.65. The highest increase occurred in the contraindication topic (R2 = 0.87, p < 0.001). The main milestone was observed in the drug overdose topic in July 2018 (RSV = 100). A very close relationship was found between adverse drug reaction and contraindication (R = 0.89, p < 0.001). Slight seasonality was noted in the adverse drug reaction (augmented Dickey-Fuller test [ADF] = -1.96), contraindication (ADF = -2.66) and drug interaction (ADF = -1.67) topics, but did not show an epidemiological trend. CONCLUSIONS: The greatest public interest was found in the drug overdose and contraindication topics, which showed a stronger upward trend, although the seasonality study did not show any very notable data or demonstrate epidemiological information search behaviour. The main milestone observed was due to media factors related to the consumption of narcotics. There was a clear difference in English-speaking countries in the use of the drug overdose topic. A correlation between the adverse drug reaction and contraindication topics was confirmed.

Trends and seasonality of information searches, carried out through Google, on metabolic syndrome and occupational health: infodemiological study

Objetivo: Este estudio tuvo como objetivo analizar y relacionar el interés de la población, a través de tendencias de búsqueda de información, sobre el Síndrome Metabólico (MS) con la Salud Laboral (OH).Método: Estudio ecológico y correlacional del Volumen Relativo de Búsqueda (RSV) obtenido de la consulta de Google Trends, segmentado en 3 períodos buscados relacionados con la antigüedad; fecha de consulta: 30 de sep-tiembre de 2023.Resultados: La media más baja del RSV fue para el tema MS (2,23 ± 0,87), aunque hubo una correlación positiva en el RSV entre MS y OH (R = 0,56; p < 0,05). Se observó asociación (p < 0,05) entre los 3 períodos estudiados, excepto para los temas Hipertensión y Obesidad Central, pero significativamente menor en el período actual para los Temas MS y OH. Se encontró una estacionalidad moderada en el tema MS (KPSS = 0,14; p > 0,05), y se demostraron diferen-cias significativas en la búsqueda de información entre países desarrollados y no desarrollados (p > 0,05).Conclusiones: A través de sus búsquedas de información, toda la población demostró tener un menor conocimien-to sobre la MS que sobre las enfermedades que la componen. Se encontró relación entre las búsquedas de infor-mación realizadas sobre MS y OH. El estudio de las tendencias de búsqueda de información puede proporcionar información útil sobre el interés de la población por los datos de enfermedades, así como permitiría gradualmente analizar diferencias en popularidad, o interés incluso entre distintos países. (AU)

Objective: This study aimed to analyse and relate the population interest through information search trends, on Metabolic Syndrome (MS) with the Occupational Health (OH).Method: Ecological and correlational study of the Relative Search Volume (RSV) obtained from Google Trends que-ry, segmented into 3 searched periods concerning antiquity; date of query: September 30, 2023.Results: The lowest mean of the RSV was for the MS Topic (2.23 ± 0.87), albeit there was a positive correlation in the RSV amid MS and OH (R = 0.56; p < 0.05). Association (p < 0.05) was observed between the 3 periods under study, except for the Hypertension and Central Obesity topics, but significantly lower in the current period for the MS and OH Topics. Moderate seasonality was found in the MS topic (KPSS = 0.14; p > 0.05), and significant differences were demonstrated in the information search between developed and undeveloped countries (p > 0.05).Conclusions: Through their information searches, the whole population showed to have a dearth of knowledge of MS than of its component diseases. A relationship was found between the information searches carried out on MS and OH. The study of information search trends may provide useful information on the population’s interest in the disease data, as well as would gradually allow the analysis of differences in popularity, or interest even between different countries. (AU)

Population Interest in Information on Obesity, Nutrition, and Occupational Health and Its Relationship with the Prevalence of Obesity: An Infodemiological Study.

OBJECTIVE: To identify and analyze population interest in obesity, nutrition, and occupational health and safety and its relationship with the worldwide prevalence of obesity through information search trends. METHOD: In this ecological study, data were obtained through online access to Google Trends using the topics "obesity", "nutrition", and "occupational health and safety". Obesity data were obtained from the World Health Organization (WHO) website for crude adult prevalence and estimates by region. The variables studied were relative search volume (RSV), temporal evolution, milestone, trend, and seasonality. The temporal evolution of the search trends was examined by regression analysis (R2). To assess the relationship between quantitative variables, the Spearman correlation coefficient (Rho) was used. Seasonality was verified using the augmented Dickey-Fuller (ADF) test. RESULTS: The RSV trends were as follows: obesity (R2 = 0.04, p = 0.004); nutrition (R2 = 0.42, p < 0.001); and occupational health and safety (R2 = 0.45, p < 0.001). The analysis of seasonality showed the absence of a temporal pattern (p < 0.05 for all terms). The associations between world obesity prevalence (WOP) and the different RSVs were as follows: WOP versus RSV obesity, Rho = -0.79, p = 0.003; WOP versus RSV nutrition, Rho = 0.57, p = 0.044; and WOP versus RSV occupational health and safety, Rho = -0.93, p = 0.001. CONCLUSIONS: Population interest in obesity continues to be a trend in countries with the highest prevalence, although there are clear signs popularity loss in favor of searches focused on possible solutions and treatments, with a notable increase in searches related to nutrition and diet. Despite the fact that most people spend a large part of their time in the workplace and that interventions including various strategies have been shown to be useful in combating overweight and obesity, there has been a decrease in the population's interest in information related to obesity in the workplace. This information can be used as a guide for public health approaches to obesity and its relationship to nutrition and a healthy diet, approaches that are of equal utility and applicability in occupational health.

Computer programs used in the field of hospital pharmacy for the management of dangerous drugs: systematic review of literature.

Background: This review wants to highlight the importance of computer programs used to control the steps in the management of dangerous drugs. It must be taken into account that there are phases in the process of handling dangerous medicines in pharmacy services that pose a risk to the healthcare personnel who handle them. Objective: To review the scientific literature to determine what computer programs have been used in the field of hospital pharmacy for the management of dangerous drugs (HDs). Methods: The following electronic databases were searched from inception to July 30, 2021: MEDLINE (via PubMed), Embase, Cochrane Library, Scopus, Web of Science, Latin American and Caribbean Literature in Health Sciences (LILACS) and Medicine in Spanish (MEDES). The following terms were used in the search strategy: "Antineoplastic Agents," "Cytostatic Agents," "Hazardous Substances," "Medical Informatics Applications," "Mobile Applications," "Software," "Software Design," and "Pharmacy Service, Hospital." Results: A total of 104 studies were retrieved form the databases, and 18 additional studies were obtained by manually searching the reference lists of the included studies and by consulting experts. Once the inclusion and exclusion criteria were applied, 26 studies were ultimately included in this review. Most of the applications described in the included studies were used for the management of antineoplastic drugs. The most commonly controlled stage was electronic prescription; 18 studies and 7 interventions carried out in the preparation stage focused on evaluating the accuracy of chemotherapy preparations. Conclusion: Antineoplastic electronic prescription software was the most widely implemented software at the hospital level. No software was found to control the entire HD process. Only one of the selected studies measured safety events in workers who handle HDs. Moreover, health personnel were found to be satisfied with the implementation of this type of technology for daily work with these medications. All studies reviewed herein considered patient safety as their final objective. However, none of the studies evaluated the risk of HD exposure among workers.

Alfabetización para la salud del personal técnico en cuidados auxiliares de enfermería y del personal no sanitario perteneciente a la plantilla laboral de cuatro hospitales españoles / Health literacy of nursing auxiliary care technicians and non-health personnel belonging to the workforce of four Spanish hospitals

Objetivo: Estimar el grado de alfabetización para la salud (AS) de las técnicas en cuidados auxiliares de enfermería (TCAE) y del personal no sanitario perteneciente a la plantilla laboral de 4 hospitales españoles.Método: Estudio descriptivo-correlacional, siendo la población diana las TCAE a quienes se preguntó, mediante formulario online HLS-EU-Q16 (Health Literacy Survey - European Union), con escala Likert de 4 valores (de 1 muy fácil a 4 muy difícil). Resultados: Respondieron 477 profesionales. Los resultados para la AS global fueron: media 1,95 ± 0,03 y mediana 1,94. El nivel de alfabetización en salud (NAS) demostró AS suficiente en 293 (61,43%) individuos. La mediana sobre la AS de los 3 componentes del cuestionario fue: cuidado sanitario = 2, prevención de enfermedades = 2 y promo-ción de la salud = 1,75. El ítem sobre sobre la manera de abordar problemas de salud mental es el que presentó mayor dificultad con media de 2,45 ± 0,04 y mediana igual a 2. No hubo diferencias significativas entre TCAE y el personal no sanitario.Conclusiones: El grado de AS de las TCAE resultó ser bueno, tanto a nivel global como en las dimensiones de aten-ción y cuidado sanitario, prevención de enfermedades y promoción de la salud. Asimismo, el nivel de alfabetización en salud que se obtuvo resultó ser suficiente en la mayoría de ellas. No se encontró diferencias con el personal no sanitario perteneciente a la plantilla laboral de 4 hospitales estudiados (AU)

Objetive: To estimate the degree of health literacy (HL) of nursing auxiliary care technicians (NACT) and non-health personnel belonging to the workforce of 4 Spanish hospitals.Method: A descriptive-correlational research, with NACT as target population. They were asked, using the online form HLS-EU-Q16 (Health Literacy Survey - European Union), with a Likert scale of 4 values (from 1 very easy to 4 very difficult).Results: 477 professionals answered the form. The results for global SA were: mean 1.95 ± 0.03 and median 1.94. The health literacy level (HLL) demonstrated sufficient HL in 293 (61.43%) individuals. The median on the HL for the 3 components of the questionnaire was: health care = 2, disease prevention = 2 and health promotion = 1.75. The item about how to deal with mental health problems showed the greatest difficulty with a mean of 2.45 ± 0.04 and a median equal to 2. There were no significant differences between NACT and non-health personnel. Conclusions: The HL grade of the NACTs turned out to be good, both globally and in the dimensions of attention and health care, disease prevention and health promotion. Likewise, the level of health literacy obtained turned out to be enough in most of them. No differences were found with the non-health personnel belonging to the workforce of the 4 hospitals researched (AU)

Occupational Health Applied Infodemiological Studies of Nutritional Diseases and Disorders: Scoping Review with Meta-Analysis.

(1) Objective: to identify and review existing infodemiological studies on nutritional disorders applied to occupational health and to analyse the effect of the intervention on body mass index (BMI) or alternatively body weight (BW); (2) Methods: This study involved a critical analysis of articles retrieved from MEDLINE (via PubMed), Embase, Cochrane Library, PsycINFO, Scopus, Web of Science, Latin American, and Caribbean Health Sciences Literature (LILACS) and Medicina en Español (MEDES) using the descriptors "Nutrition Disorders, "Occupational Health" and "Infodemiology", applying the filters "Humans" and "Adult: 19+ years". The search was conducted on 29 May 2021; (3) Results: a total of 357 references were identified from the bibliographic database searches; after applying the inclusion and exclusion criteria, a total of 11 valid studies were obtained for the review. Interventions could be categorised into (1) interventions related to lifestyle, physical activity, and dietary changes through education programmes, (2) interventions associated with lifestyle, physical activity, and dietary changes through the use of telemonitoring systems or self-help applications, (3) interventions tied to lifestyle, physical activity, and dietary changes through control and/or social network support groups, and (4) interventions linked to changes in the work environment, including behavioural change training and work environment training tasks. The meta-analysis demonstrated that the heterogeneity present when analysing the results for BMI was 72% (p < 0.01), which decreased to 0% (p = 0.57) when analysing the outcomes for weight, in which case the null hypothesis of homogeneity could be accepted. In all instances, the final summary of the effect was on the decreasing side for both BMI and BW; (4) Conclusions: Despite the high heterogeneity of the results reported, the trend shown in all cases indicates that the intervention methodologies implemented by empowering individuals through Web 2.0 technologies are positive in terms of the problem of overweight. Further implementation of novel strategies to support individuals is needed to overcome obesity, and, at least in the early studies, these strategies seem to be making the necessary change.

BACE2 beyond ß-processing of APP, its neuroprotective role in cerebrovascular endothelium.

Several proteases are involved in the proteolytic processing of the amyloid precursor protein (APP) generating the amyloidogenic Aß peptide, which can act as the triggering pathological effector of Alzheimer's disease (AD). Among these proteases, the ß-site amyloid precursor protein cleaving enzyme 2 (BACE2) is of particular interest because it was first proposed as an alternative ß-secretase to its homolog BACE1; however, accumulating evidence suggests that BACE2 acts as a non-amyloidogenic α-secretase and exerts neuroprotective effects. In this issue of J Neurochem, Katusic et al. present an interesting article reporting that BACE2 plays a role in preservation of cerebral vascular endothelial nitric oxide synthase (eNOS) function, thus exerting protective functions. Their data support that the process is mediated by the large soluble non-amyloidogenic APP fragment sAPPα through the γ-aminobutyric acid type B receptor 1, which enhances the expression of a major transcription factor for eNOS gene expression in endothelial cells, the Krüppel-like factor 2. These protective functions of BACE2 contrast with the pathogenic role of BACE1 as a key player in the AD amyloidogenic pathway. Indeed, many efforts have been invested in BACE1 inhibitors as potential disease modifiers for AD. Unfortunately, the results in clinical trials have been disappointing. In this scenario, a better understanding of the functions of BACE2, as well as the selectivity of BACE1 inhibitors with respect to other ß-secretases (mainly BACE2), is crucial for the development of new therapeutic agents. Furthermore, specific cellular targeting should also be considered to improve such therapies due to the diverse balance of secretases targeting APP and the complex cross-talk between them and the generated APP fragments.

Occupational Health of Health-Care Workers with Overnutrition: Scoping Review with Meta-Analysis.

(1) Objective: To review the scientific literature on the impact of interventions to enhance the occupational health of health-care workers with overnutrition. (2) Methods: Scoping review with meta-analysis. Data were obtained by consulting the following bibliographic databases: MEDLINE (via PubMed), Embase, Cochrane Library, Scopus, Web of Science, Latin American and Caribbean Literature on Health Sciences (LILACS), and Medicina en Español (MEDES). The terms used as descriptors and as text in the title and abstract fields of the records were "health workers", "overnutrition", and "occupational health", using the filters "human", "adult": 19+ years", and "clinical trial". The search update date was January 2023. The documentary quality of the articles was evaluated using the CONSORT questionnaire and the presence of bias was assessed using the Rob 2.0 tool. (3) Results: From the 611 digitally retrieved references, 17 clinical trials were selected after applying the inclusion and exclusion criteria. CONSORT scores ranged from a minimum of 14.6% to a maximum of 91.7%, with a median of 68.8%. According to the SIGN criteria, this review provided "1" evidence with a grade B recommendation. Six different types of intervention were tested, grouped into strategies ranging from a single intervention to a combination of four interventions. The summary effect of the meta-analysis showed significant weight loss, but no association with reduced body mass index. (4) Conclusions: While workplace interventions have been shown to be potentially effective, and strategies using different types of interventions have been proven to be useful in tackling overnutrition, an effective and sustainable solution for changing the behavior of health professionals to tackle overweight and obesity has yet to be identified.

No evidence for cognitive decline or neurodegeneration in strain-matched Grin3a knockout mice.

N-methyl-D-aspartate (NMDA) receptor (NMDAR) dysregulation is thought to contribute to impaired cognition and neurodegeneration in a variety of brain disorders. In a recent article, Zhong et al. proposed that deficiency of the NMDAR subunit GluN3A may be a primary pathogenic factor in sporadic Alzheimer´s disease (AD) based on evidence for degenerative excitotoxicity and cognitive impairment in aging mice lacking GluN3A. Because the result appeared to be at odds with earlier work where genetic GluN3A deletion enhanced learning in younger mice, we have now compared wild-type and GluN3A knockout mice at later life stages using a congenic mouse strain. Rather than age-dependent cognitive decline or neurodegeneration, we find that the enhanced performance of young adult GluN3A knockouts in memory tasks persists during aging. In sum, our analysis does not support the hypothesis that GluN3A loss underlies cognitive impairment in AD..

Suitability of indexing terms in the MEDLINE bibliographic database on drug-related problems.

BACKGROUND: For years, there has been controversy about the meaning of medication-related problems (MRPs). This has led several authors to attempt to redefine and classify this term with the aim of using it correctly in the healthcare setting. So far without achieving the desired objective, resulting in erroneous results in the sources of information and thus in malpractice in the sector. OBJECTIVE: To describe and analyze the appropriateness of the existing indexing of scientific publications in the MEDLINE bibliographical database with respect to drug-related problems (DRPs) and to determine whether the descriptors used fulfilled the function of suitably representing this concept. METHODS: A descriptive study was conducted, using the following search terms: Medication Errors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Contraindications, Drug. The sample size was calculated by estimating population parameters in an infinite population (expected value = 0.05; precision of interval = 0.05; level of confidence = 0.95) and the selection method was simple random sampling without replacement, taking the total number of bibliographical references in the database as the basis. The agreement of the indexing with DRPs was evaluated with the coefficient of determination (R2), and the Cohen kappa coefficient was used for the association between the definition of the descriptors and the objective of the article. RESULTS: The 1930 records analyzed showed a total of 2888 different major topics. These major topics were present, with at least one of the five descriptors studied, in 482 (25.0%; 95% CI 23.0-27.0) documentary files, with statistically significant differences between the two phases analyzed (χ2 = 183.8; degrees of freedom (df) = 1; p < 0.001): 1st phase, 295 (13.3%; 95% CI 13.7-16.9) and 2nd phase, 187 (9.7%; 95% CI 8.4-11.0). Overall scientific output with the five descriptors showed a coefficient of determination (R2) of 0.9 (p < 0.001) and the relationship between the objective of the study and the definitions of the five descriptors was 0.9 (p < 0.001). CONCLUSIONS: There was a very good direct exponential trend of the overall scientific output retrieved with the terms associated with DRPs, although the progression of the five descriptors separately did not show a growth model conforming to expectations. There was a moderate agreement between the objective of the study and the definition of each of the five descriptors used and a low relationship between the objective of the study and the concept of DRPs used for this investigation. It is essential to have a descriptor that unifies the terminological diffusion that has existed up till now, since process (causes) and effects (outcomes) have been mixed together under the various definitions and classifications of DRPs found in the studies.

Validity of CSF alpha-synuclein to predict psychosis in prodromal Alzheimer's disease.

Background: Alzheimer's disease (AD) accompanied by psychotic symptoms (PS) has a poor prognosis and may be associated with imbalances in key neural proteins such as alpha-synuclein (AS). Aim: The aim of the study was to evaluate the diagnostic validity of AS levels in the cerebrospinal fluid (CSF) as a predictor of the emergence of PS in patients with prodromal AD. Materials and methods: Patients with mild cognitive impairment were recruited between 2010 and 2018. Core AD biomarkers and AS levels were measured in CSF obtained during the prodromal phase of the illness. All patients who met the NIA-AA 2018 criteria for AD biomarkers received treatment with anticholinesterasic drugs. Follow-up evaluations were conducted to assess patients for the presence of psychosis using current criteria; the use of neuroleptic drugs was required for inclusion in the psychosis group. Several comparisons were made, taking into account the timing of the emergence of PS. Results: A total of 130 patients with prodromal AD were included in this study. Of these, 50 (38.4%) met the criteria for PS within an 8-year follow-up period. AS was found to be a valuable CSF biomarker to differentiate between the psychotic and non-psychotic groups in every comparison made, depending on the onset of PS. Using an AS level of 1,257 pg/mL as the cutoff, this predictor achieved at least 80% sensitivity. Conclusion: To our knowledge, this study represents the first time that a CSF biomarker has shown diagnostic validity for prediction of the emergence of PS in patients with prodromal AD.

ADAM10 Gene Variants in AD Patients and Their Relationship to CSF Protein Levels.

ADAM10 is the main α-secretase acting in the non-amyloidogenic processing of APP. We hypothesized that certain rare ADAM10 variants could increase the risk for AD by conferring the age-related downregulation of α-secretase. The ADAM10 gene was sequenced in 103 AD cases (82% familial) and 96 cognitively preserved nonagenarians. We examined rare variants (MAF < 0.01) and determined their potential association in the AD group with lower CSF protein levels, as analyzed by means of ELISA, and Western blot (species of 50 kDa, 55 kDa, and 80 kDa). Rare variants were found in 15.5% of AD cases (23% early-onset, 8% late-onset) and in 12.5% of nonagenarians, and some were group-specific. All were intronic variants except Q170H, found in three AD cases and one nonagenarian. The 3'UTR rs74016945 (MAF = 0.01) was found in 6% of the nonagenarians (OR 0.146, p = 0.057). Altogether, ADAM10 total levels or specific species were not significantly different when comparing AD with controls or carriers of rare variants versus non-carriers (except a Q170H carrier exhibiting low levels of all species), and did not differ according to the age at onset or APOE genotype. We conclude that ADAM10 exonic variants are uncommon in AD cases, and the presence of rare intronic variants (more frequent in early-onset cases) is not associated with decreased protein levels in CSF.

Antibiotic Infographics Available on the Internet: Documentary Quality, Purpose, and Appropriateness as Educational Tools on Antimicrobial Resistance.

Antimicrobial resistance is a major threat to global health in the 21st century. In the age of the internet and social media, infographics may constitute an effective educational resource for transmitting complete messages about antibiotics and antimicrobial resistance and driving behavioural change. We aimed to evaluate the infographics on antibiotics available on the internet in terms of their documentary quality, purpose, and appropriateness as educational tools for explaining the strategic lines defined in the World Health Organization Global Action Plan on Antimicrobial Resistance (GAP-AMR) and for conveying the One Health concept. We obtained the infographics for this cross-sectional study on 4 March 2021 by searching the terms "infographic" and "antibiotic" in Google Images. We verified infographic documentary quality by analysing the image, authorship, title, structure, date, and licence. To evaluate the purpose, we determined whether it coincided with one of the strategic objectives set out in the GAP-AMR. The degree of appropriateness depended on the type of key awareness message on antibiotic use. After obtaining these results, we performed a cross-sectional evaluation to determine how successfully these infographics conveyed the One Heath concept. We selected 247 infographics from 518 references. Of the included infographics, 97 (39%) were produced by public institutions; 58 (23%) read from left to right; 142 (57%) had an educational purpose; 156 (63%) focused on humans; 140 (57%) were subject to copyright; and 97 (39%) had no licence of any type. Almost one quarter (n = 57; 23%) included no key message on proper use of antibiotics. Infographics that included an author/promoter had a significantly higher mean number of messages that those without disclosure of authorship (1.67 vs. 0.50; p < 0.001). The infographics on antibiotics available on the internet are of moderate general quality. Most are produced by public institutions and have a clear and readable layout, but very few have a Creative Commons license to enable their reuse as informative material. The most common purpose is to improve awareness and understanding of antimicrobial resistance; few infographics focus on the remaining four strategic objectives of the GAP-AMR. It would be useful for authors of educational infographics on antibiotics to promote key messages related to antimicrobial resistance and the One Health concept, in accordance with the first objective of the WHO GAP-AMR.

Transient Changes in the Plasma of Astrocytic and Neuronal Injury Biomarkers in COVID-19 Patients without Neurological Syndromes.

The levels of several glial and neuronal plasma biomarkers have been found to increase during the acute phase in COVID-19 patients with neurological symptoms. However, replications in patients with minor or non-neurological symptoms are needed to understand their potential as indicators of CNS injury or vulnerability. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), and total Tau (T-tau) were determined by Single molecule array (Simoa) immunoassays in 45 samples from COVID-19 patients in the acute phase of infection [moderate (n = 35), or severe (n = 10)] with minor or non-neurological symptoms; in 26 samples from fully recovered patients after ~2 months of clinical follow-up [moderate (n = 23), or severe (n = 3)]; and in 14 non-infected controls. Plasma levels of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), were also determined by Western blot. Patients with COVID-19 without substantial neurological symptoms had significantly higher plasma concentrations of GFAP, a marker of astrocytic activation/injury, and of NfL and T-tau, markers of axonal damage and neuronal degeneration, compared with controls. All these biomarkers were correlated in COVID-19 patients at the acute phase. Plasma GFAP, NfL and T-tau levels were all normalized after recovery. Recovery was also observed in the return to normal values of the quotient between the ACE2 fragment and circulating full-length species, following the change noticed in the acute phase of infection. None of these biomarkers displayed differences in plasma samples at the acute phase or recovery when the COVID-19 subjects were sub-grouped according to occurrence of minor symptoms at re-evaluation 3 months after the acute episode (so called post-COVID or "long COVID"), such as asthenia, myalgia/arthralgia, anosmia/ageusia, vision impairment, headache or memory loss. Our study demonstrated altered plasma GFAP, NfL and T-tau levels in COVID-19 patients without substantial neurological manifestation at the acute phase of the disease, providing a suitable indication of CNS vulnerability; but these biomarkers fail to predict the occurrence of delayed minor neurological symptoms.

Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation.

In Alzheimer's disease (AD), the reduction in acetylcholinesterase (AChE) enzymatic activity is not paralleled with changes in its protein levels, suggesting the presence of a considerable enzymatically inactive pool in the brain. In the present study, we validated previous findings, and, since inactive forms could result from post-translational modifications, we analyzed the glycosylation of AChE by lectin binding in brain samples from sporadic and familial AD (sAD and fAD). Most of the enzymatically active AChE was bound to lectins Canavalia ensiformis (Con A) and Lens culinaris agglutinin (LCA) that recognize terminal mannoses, whereas Western blot assays showed a very low percentage of AChE protein being recognized by the lectin. This indicates that active and inactive forms of AChE vary in their glycosylation pattern, particularly in the presence of terminal mannoses in active ones. Moreover, sAD subjects showed reduced binding to terminal mannoses compared to non-demented controls, while, for fAD patients that carry mutations in the PSEN1 gene, the binding was higher. The role of presenilin-1 (PS1) in modulating AChE glycosylation was then studied in a cellular model that overexpresses PS1 (CHO-PS1). In CHO-PS1 cells, binding to LCA indicates that AChE displays more terminal mannoses in oligosaccharides with a fucosylated core. Immunocytochemical assays also demonstrated increased presence of AChE in the trans-Golgi. Moreover, AChE enzymatic activity was higher in plasmatic membrane of CHO-PS1 cells. Thus, our results indicate that PS1 modulates trafficking and maturation of AChE in Golgi regions favoring the presence of active forms in the membrane.

Interés poblacional, a través de las tendencias de búsqueda de información, sobre acoso laboral y sexual en España y su asociación con los datos de búsqueda mundiales / Population interest, through search trends related to workplace and sexual harassment in Spain and its relationship with global search data

Introducción: Analizar y relacionar el interés poblacional, a través de las tendencias de búsqueda de información, sobre acoso laboral (AL) y sexual (AS) en España y su asociación con los datos de búsqueda mundiales. Método: Estudio ecológico, los datos se obtuvieron mediante acceso online a Google Trends, utilizándose los términos «acoso laboral» y «acoso sexual» como tema. Variables estudiadas: volumen de búsqueda relativo (VBR), hito, tendencia y estacionalidad. Fecha consulta 14/01/2022. Resultados: A nivel mundial, mediana del VBR para AL = 25 y para AS = 37 con tendencia para AL de R2 = 0,04 y AS de R2 = 0,43. Se observó un hito de VBR = 100 en noviembre de 2017 en AS. A nivel español mediana del VBR para AL = 21 y para AS = 8 con tendencia para AL de R2 = 0,38 y AS de R2 = 0,06, observándose un hito de VBR = 100 en febrero de 2005 en AL. Conclusiones: Si bien las tendencias sobre AL y AS presentaron una línea decreciente fue a partir de noviembre de 2017 cuando se observó un cambio de modelo en las búsquedas sobre AS. El movimiento MeToo fue el principal responsable de este cambio, siendo incluso el principal hito observado en la tendencia de AS a nivel español y, en mayor medida, a nivel mundial (AU)

Apolipoprotein E imbalance in the cerebrospinal fluid of Alzheimer's disease patients.

OBJECTIVE: The purpose of this study was to examine the levels of cerebrospinal fluid (CSF) apolipoprotein E (apoE) species in Alzheimer's disease (AD) patients. METHODS: We analyzed two CSF cohorts of AD and control individuals expressing different APOE genotypes. Moreover, CSF samples from the TgF344-AD rat model were included. Samples were run in native- and SDS-PAGE under reducing or non-reducing conditions (with or without ß-mercaptoethanol). Immunoprecipitation combined with mass spectrometry or western blotting analyses served to assess the identity of apoE complexes. RESULTS: In TgF344-AD rats expressing a unique apoE variant resembling human apoE4, a ~35-kDa apoE monomer was identified, increasing at 16.5 months compared with wild-types. In humans, apoE isoforms form disulfide-linked dimers in CSF, except apoE4, which lacks a cysteine residue. Thus, controls showed a decrease in the apoE dimer/monomer quotient in the APOE ε3/ε4 group compared with ε3/ε3 by native electrophoresis. A major contribution of dimers was found in APOE ε3/ε4 AD cases, and, unexpectedly, dimers were also found in ε4/ε4 AD cases. Under reducing conditions, two apoE monomeric glycoforms at 36 kDa and at 34 kDa were found in all human samples. In AD patients, the amount of the 34-kDa species increased, while the 36-kDa/34-kDa quotient was lower compared with controls. Interestingly, under reducing conditions, a ~100-kDa apoE complex, the identity of which was confirmed by mass spectrometry, also appeared in human AD individuals across all APOE genotypes, suggesting the occurrence of aberrantly resistant apoE aggregates. A second independent cohort of CSF samples validated these results. CONCLUSION: These results indicate that despite the increase in total apoE content the apoE protein is altered in AD CSF, suggesting that function may be compromised.

Serum angiotensin-converting enzyme 2 as a potential biomarker for SARS-CoV-2 infection and vaccine efficacy.

Various species of the SARS-CoV-2 host cell receptor, the angiotensin-converting enzyme 2 (ACE2), are present in serum, which may result from virus entry and subsequent proteolytic processing of the membrane receptor. We have recently demonstrated changes of particular ACE2 species in virus infected humans, either cleaved fragments or circulating full-length species. Here, we further explore the potential of serum ACE2 as a biomarker to test SARS-CoV-2 infection and vaccine efficacy in virus susceptible transgenic K18-hACE2 mice expressing human ACE2. First, in serum samples derived from K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2, we observed an increase in the levels of cleaved ACE2 fragment at day 2 post-challenge, which may represent the subsequent proteolytic processing through virus entry. These elevated levels were maintained until the death of the animals at day 6 post-challenge. The circulating full-length ACE2 form displayed a sizable peak at day 4, which declined at day 6 post-challenge. Noticeably, immunization with two doses of the MVA-CoV2-S vaccine candidate prevented ACE2 cleaved changes in serum of animals challenged with a lethal dose of SARS-CoV-2. The efficacy of the MVA-CoV2-S was extended to vaccinated mice after virus re-challenge. These findings highlight that ACE2 could be a potential serum biomarker for disease progression and vaccination against SARS-CoV-2.