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Monkeypox outbreak in Spain: clinical and epidemiological findings in a prospective cross-sectional study of 185 cases.
No full textSince May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports. To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak. We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak. In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in men who have sex with men and are strongly associated with high-risk sexual behaviours. Seventy-six per cent of the patients had other sexually transmitted diseases upon screening. The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterization of the epidemiology of this outbreak has implications for control. What is already known about this topic? Monkeypox eruption is described as consisting of pustules. The roles of HIV and previous smallpox vaccination in the prognosis are unknown. The transmission route was initially described as respiratory droplets and was later suggested to be via sexual contact. What does this study add? Initial lesions at the probable inoculation area were homogeneous and papular (pseudopustules). Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common signs included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Well-controlled HIV and previous smallpox vaccination were not associated with severity. No patient died. The data support the hypothesis of transmission via contact during sex. Although this might change, the outbreak is currently limited mostly to men who have sex with men, with high-risk factors for sexually transmitted diseases
Translation and piloting of the Chinese Mandarin version of an intensive care-specific pressure injury risk assessment tool (the COMHON Index).
No full textTo translate an intensive care-specific pressure injury risk assessment tool (the COMHON Index) from English into Chinese Mandarin. A four-step approach to instrument translation was utilised: 1) English-Mandarin forward-translation by three independent bilinguists; 2) Mandarin-English back-translation by two other independent bilinguists; 3) comparison of forward and back-translations, identification of discrepancies, with required amendments returned to step one; and 4) piloting of the translated instrument. The pilot study was undertaken in a Chinese surgical intensive care unit with a convenience sample of 20 nurses. A five-point ordinal scale (1 = very difficult; 5 = very easy) was used to assess ease-of-use and understanding. Translations were retained where medians ≥ 4 indicated use and understanding was easy to very easy. Five iterations of steps 1 to 3, and two sets of amendments to the original English instrument, were required to achieve translation consensus prior to pilot testing. Subscale scoring, sum scoring, and risk categorisation were documented in most pilot assessments (≥ 80%), but three sum scores were incorrectly tallied. The overall tool and all subscales were easy to use and understand (medians ≥ 4), and most assessments (16/20, 80%) took ≤ 5 min to complete. Thus, translations were retained, with minor amendments made to instrument instructions for scoring and risk categorisation. An easy-to-use Chinese Mandarin intensive care-specific pressure injury risk assessment tool has been introduced through cross-cultural translation. However, it requires further testing of interrater reliability and agreement. A rigorous translation and reporting exemplar is presented that provides guidance for future translations
Association of shivering threshold time with body composition and brown adipose tissue in young adults.
No full textBrown adipose tissue (BAT) increases metabolic heat production in response to cold exposure. Body size and composition are involved in the human cold response, yet the influence of BAT herein have not fully been explored. Here, we aimed to study the association of the cold-induced shivering threshold time with body composition, BAT, the perception of shivering and skin temperature in young adults. 110 young healthy adults (81 females; age = 21.7 ± 2.1 years, BMI = 24.2 ± 4.3 kg/m2) underwent 2 h of individualized cooling, followed by the quantification of BAT using a18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography-computed tomography (PET-CT) scan. Body mass index (BMI), lean mass, fat mass and body surface area (BSA) were also measured. Shivering threshold time was defined as the time until shivering occurred using an individualized cooling protocol. The shivering threshold time was on average 116.1 min for males and 125.8 min for females, and was positively associated to BMI (β = 3.106; R2 = 0.141; p = 0.001), lean mass (β = 2.295; R2 = 0.128; p = 0.001) and fat mass (β = 1.492; R2 = 0.121; p = 0.001) in females, but not in males (all p ≥ 0.409). The shivering threshold time was positively associated with BSA in males (p = 0.047) and females (p = 0.001), but it was not associated with BAT volume or [18F]FDG uptake nor with the perception of shivering and skin temperature perception in both sexes. The shivering threshold time is positively associated with whole-body adiposity and lean mass in females, but not in males. The shivering threshold time was positively associated with BSA, but no association was observed with BAT nor with the perception of shivering or skin temperature. Future research should consider the influence of body composition when applying cooling protocols among individuals with different phenotypical features.This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393) and PTA 12264-I, Retos de la Sociedad (DEP 2016-79512-R) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU 13/03410), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 - Excellence actions: Unit of Excellence on Exercise and Health (UCEES) - and Plan Propio de Investigación 2018: Programa Contratos-Puente, the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF, SOMM17/6107/UGR) - and the Fundación Carolina (C.2016-574,961). BMT, FAM and GSD are supported by individual postdoctoral grants from the Fundación Alfonso Martín Escudero.BMT is also supported by a Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea–NextGenerationEU (RR_C_2021_04).S
Hybrid Fluorescent Mass-Tag Nanotrackers as Universal Reagents for Long-Term Live-Cell Barcoding.
No full textBarcoding and pooling cells for processing as a composite sample are critical to minimize technical variability in multiplex technologies. Fluorescent cell barcoding has been established as a standard method for multiplexing in flow cytometry analysis. In parallel, mass-tag barcoding is routinely used to label cells for mass cytometry. Barcode reagents currently used label intracellular proteins in fixed and permeabilized cells and, therefore, are not suitable for studies with live cells in long-term culture prior to analysis. In this study, we report the development of fluorescent palladium-based hybrid-tag nanotrackers to barcode live cells for flow and mass cytometry dual-modal readout. We describe the preparation, physicochemical characterization, efficiency of cell internalization, and durability of these nanotrackers in live cells cultured over time. In addition, we demonstrate their compatibility with standardized cytometry reagents and protocols. Finally, we validated these nanotrackers for drug response assays during a long-term coculture experiment with two barcoded cell lines. This method represents a new and widely applicable advance for fluorescent and mass-tag barcoding that is independent of protein expression levels and can be used to label cells before long-term drug studies
Association between individual and country-level socioeconomic factors and work participation in peripheral and axial spondyloarthritis: analysis of the asas perspa study
No full textBackground: Work outcomes in spondyloarthritis (SpA) have mostly been studied in axSpA, less in peripheral SpA (pSpA) or PsA. The ASAS-COMOSPA study showed that lower education, female gender and lower healthcare expenditures (HCE) are associated with lower odds of employment in SpA. However, it is unknown whether country-level factors or SpA phenotype (axSpA/pSpA/PsA) modify the effect of individual-level socioeconomic factors.
Objectives: To examine whether associations between socioeconomic factors
and work outcomes differ across SpA phenotype and whether associations for
individual-level socioeconomic factors are modified by country-level factors. Methods: Working age patients (18-65 years) from the ASAS-perSpA (peripheral involvement in SpA) study were included. Associations between individual- (age, gender, education, marital status) and country-level socioeconomic factors .S
The C-terminal domain of Arabidopsis ROS1 DNA demethylase interacts with histone H3 and is required for DNA binding and catalytic activity.
No full textActive DNA demethylation plays an important role in controlling methylation patterns in eukaryotes. In plants, the DEMETER-LIKE (DML) family of 5-methylcytosine DNA glycosylases initiates DNA demethylation through a base excision repair pathway. However, it is poorly understood how these DNA demethylases are recruited to their target loci and the role that histone marks play in this process. Arabidopsis REPRESSOR OF SILENCING 1 (ROS1) is a representative enzyme of the DML family, whose members are uniquely characterized by a basic amino-terminal domain mediating nonspecific binding to DNA, a discontinuous catalytic domain, and a conserved carboxy-terminal domain of unknown function. Here, we show that ROS1 interacts with the N-terminal tail of H3 through its C-terminal domain. Importantly, phosphorylation at H3 Ser28, but not Ser10, abrogates ROS1 interaction with H3. Conserved residues at the C-terminal domain are not only required for H3 interaction, but also for efficient DNA binding and catalytic activity. Our findings suggest that the C-terminal domain of ROS1 may function as a histone reader module involved in recruitment of the DNA demethylase activity to specific genomic regions.S
Technological Advances in the Diagnosis and Management of Tinnitus.
No full textTinnitus disorder is a bothersome perception of a composite noise or tone in the ears in
the absence of an external source, associated with emotional distress, cognitive dysfunction,
and/or autonomic arousal. Tinnitus frequently occurs as a symptom together with other
hearing disorders (high-frequency hearing loss, Meniere’s disease, vestibular schwannoma),
auditory pathway disorders (hyperacusis), mental disorders (anxiety, depression), vascular
risk factors (high blood pressure, dyslipidemia), or neurological disorders (intracranial
hypertension, migraine).J.A.L.-E. has received funded from GNP-182 GENDER-Net Co-Plus Fund including
support from “La Caixa” Foundation (ID 100010434), under agreement LCF/PR/DE18/52010002
and the European Union’s Horizon 2020 Research and Innovation Programme, Grant Agreement
No. 848261. PPC is funded by the Andalusian Health Government (Grant RH-0150-2020).S
Uso concomitante de antivirales de acción directa (AAD) y fármacos con acción sobre el sistema nervioso central: Consideraciones en el perfil actual del paciente con hepatitis C.
No full textOur objective was to determine potential drug interactions (DI) between pangenotypic direct-acting antivirals (pDAA) and concomitant central nervous system (CNS) medication in patients with chronic hepatitis C virus (HCV). Transversal design. Patients aged ≥ 18 years on treatment with pDAA during 2017 were included. The variables collected were comorbidity, concomitant CNS medication and potential DI. The pDAA analyzed were a) Sofosbuvir/Velpatasvir (SOF/VEL), b) Glecaprevir/Pibrentasvir (GLE/PIB) and c) Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX). Descriptive statistical analysis. We recruited 1,170 patients (mean age 60.1 years, 56.4% male). Mean concomitant drug use was 3.2 per patient/year. The percentages of potential / possible DI between the DAAs and the concomitant drugs on the CNS were: 2.7% contraindications, 11.3% significant and 4.2% weak. By pDAA, the percentages were: SOF/VEL (2.7%; 0.0%; 4.4%), GLE/GDP (2.7%; 26.5%; 1.6%) SOF/VEL/VOX (2.7%; 6.8%; 4.4%), respectively. Concomitant CNS medication was used in one third of HCV patients. It is important to select a pDAA with a low rate of potential DI to simplify treatment. SOF/VEL is a good alternative compared with the other pDAA studied, mainly due to the concomitant use of antipsychotics and analgesics
Metallothioneins in Dental Implant Treatment Failure and Periodontitis in Patients with Down's Syndrome: Validation of Results.
No full textMetallothioneins (MTs) are low molecular weight cysteine-rich proteins that can bind up to seven zinc ions. Among their numerous functions, MTs appear to act as protectors against oxidative and inflammatory injury. In our first published study, we reported downregulation of the isoforms MT1B (fold distance (FD) -2. 95; p = 0.0024), MT1F (FD -1.72; p = 0.0276), MT1X (FD -3.09; p = 0.0021), MT1H (FD -2.39; p = 0.0018), MT1M (FD -2.37; p = 0.0092), MT1L (FD -2. 55; p = 0.0048), MT1E (FD -2.71; p = 0.0014), MT2A (FD -2.35; p = 0.0072), MT1G (FD -2.24; p = 0.0118), and MT1A (FD -2.82; p = 0.0023) by comparing Down's syndrome patients with periodontal disease and implant failure to those without periodontal disease and with a positive progression of their implants. In this gene validation study, we intended to verify the results of our first gene expression analysis. Materials and Methods: In our retrospective case-control study, we performed retrotranscription (RT-qPCR) of 11 RNA-to-cDNA samples using the SuperScript™ VILO™ kit (50; reference 1,176,605) from Thermo Fisher. We conducted the study using the real-time PCR technique on the q-PCR ViiA 7 platform from Thermo Fisher. We chose the format of the Taqman Array Plate 16 Plus (reference 4,413,261) from Thermo Fisher, which accommodates 12 genes plus four controls (GAPDH, 18S, ACTB, and HPRT1). We conducted the analysis of the plates using the Thermo Fisher Cloud Web Software. Results: The results obtained through gene validation analysis show that in PD+RI+ patients, the genes encoding the isoforms MT1F (FD 0.3; p = 0.039), MT1X (FD 338; p = 0.0078), MT1E (FD 307; p = 0.0358), and MT2A (FD 252; p = 0.0428) continue to show downregulation, whereas MT1B (FD 2.75; p = 0.580), MT1H (FD 281; p = 0.152), MT1L (FD 354; p = 0.0965), and MT1G (FD 336; p = 0.0749) no longer show statistically significant results.S
APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.
No full textApoE is the major lipid and cholesterol carrier in the CNS. There are three major human polymorphisms, apoE2, apoE3, and apoE4, and the genetic expression of APOE4 is one of the most influential risk factors for the development of late-onset Alzheimer's disease (AD). Neuroinflammation has become the third hallmark of AD, together with Amyloid-β plaques and neurofibrillary tangles of hyperphosphorylated aggregated tau protein. This review aims to broadly and extensively describe the differential aspects concerning apoE. Starting from the evolution of apoE to how APOE's single-nucleotide polymorphisms affect its structure, function, and involvement during health and disease. This review reflects on how APOE's polymorphisms impact critical aspects of AD pathology, such as the neuroinflammatory response, particularly the effect of APOE on astrocytic and microglial function and microglial dynamics, synaptic function, amyloid-β load, tau pathology, autophagy, and cell-cell communication. We discuss influential factors affecting AD pathology combined with the APOE genotype, such as sex, age, diet, physical exercise, current therapies and clinical trials in the AD field. The impact of the APOE genotype in other neurodegenerative diseases characterized by overt inflammation, e.g., alpha- synucleinopathies and Parkinson's disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis, and multiple sclerosis, is also addressed. Therefore, this review gathers the most relevant findings related to the APOE genotype up to date and its implications on AD and CNS pathologies to provide a deeper understanding of the knowledge in the APOE field.S