Assessment, diagnosis and treatment of peristomal skin lesions by remote imaging: An expert validation study

Background: Prevention and treatment of peristomal skin problems should be a priority for nurses caring for ostomates, even when the assessment of lesions must be done remotely. Objective: To measure the level of agreement on assessment, diagnosis and care indications for peristomal skin lesions using remote imaging among nurses in Spain. Design: Prospective observational multicentre study to assess the diagnostic validity and inter- and intraobserver agreement between nurses in peristomal skin lesions. Data were collected between March and October 2019. Settings and Participants: The research sample consisted of a group of 39 nurses with expertise in the care of ostomates. Methods: A panel of experts established a list of 24 common signs/findings, 15 diagnostic options and 35 treatment approaches for peristomal skin lesions. Three expert stoma therapy nurses compiled the clinical cases, which they described thoroughly and documented with photographs. The 39 participating nurses evaluated the cases in two rounds to measure inter and intraobserver agreement. Results: A high or very high level of agreement (κ > 0.61) was observed for the following signs: encrustation, nodules, mucocutaneous separation and varicose veins; for the following diagnoses: mucocutaneous dehiscence, allergic contact dermatitis, encrustation and varicose veins (caput medusae); for the following treatments: recommending a diet rich in vitamin C/blueberries, applying acetic acid dressings, applying cold and topical tacrolimus treatment. Conclusions: The most easily identifiable lesions were those most prevalent and with visible signs. There was a lower level of agreement in identifying lesions for which photographs required additional information (laboratory data, description of signs and symptoms, type of diet and level of self-care). It is important to train nurses caring for ostomates to correctly describe ostomy-related lesions, which is important for nursing records, continuity of care and telehealth care

Supplementary Material: Diagnostic Tests for Differentiation between Cushing´s Syndrome and Non-Neoplastic Hypercortisolism: A Systematic Review and Meta-analysis

Context: Differential diagnosis between Cushing’s syndrome (CS) due to neoplastic endogenous hypercortisolism and non-neoplastic hypercortisolism (NNH, pseudo-Cushing’s syndrome) is crucial. Due to worldwide corticotropin-releasing hormone test CRH shortage, accuracy of alternative tests to Dexamethasone (Dex)-CRH is clearly needed. Objective: Asses the diagnostic accuracy of Dex-CRH, desmopressin stimulation test, midnight serum cortisol (MSC), and late-night salivary cortisol (LNSC) levels to distinguish CS from NNH. Methods: Articles through March 2022 were identified from Scopus, Web of Science, MEDLINE, EMBASE, and PubMed. All steps through the systematic review were performed independently and in duplicate and strictly adhered to the updated PRISMA-DTA checklist. Data Synthesis: A total of 26 articles (2059 patients) were included. Dex-CRH had a pooled sensitivity and specificity of 91% (95%CI 87-94%; I2 0%) and 82% (73-88%; I2 50%), desmopressin test 87% (81-91%; I2 34%) and 91% (85-94%; I2 15%), MSC 91% (85-94%; I2 65%) and 80% (70-88%; I2 70%), and LNSC 78% (66-86%; I2 54%) and 88% (83-92%; I2 36%), respectively. SROC areas under the curve were Dex-CRH 0.949, desmopressin test 0.941, MSC 0.939, and LNSC 0.940 without visual or statistical significance. The overall risk of studies bias was moderate. Conclusion: Dex-CRH, the desmopressin stimulation test, and MSC have similar diagnostic accuracy, with Dex-CRH and MSC having slightly higher sensitivity, and the desmopressin test being more specific. LNSC was the least accurate, probably due to high heterogeneity, intrinsic variability, different assays, and lack of consistent reported cutoffs. Our results should increase clinicians’ confidence when deciding which test to perform when facing this challenging differential diagnosis. Key Words: Cushing’s syndrome, neoplastic endogenous hypercortisolism, non-neoplastic hypercortisolism, pseudoCushing’s, dexamethasone CRH test, desmopressin test, salivary cortisol, midnight serum cortiso

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Role of CB2 cannabinoid receptors in the rewarding, reinforcing, and physical effects of nicotine

This study was aimed to evaluate the involvement of CB2 cannabinoid receptors (CB2r) in the rewarding, reinforcing and motivational effects of nicotine. Conditioned place preference (CPP) and intravenous self-administration experiments were carried out in knockout mice lacking CB2r (CB2KO) and wild-type (WT) littermates treated with the CB2r antagonist AM630 (1 and 3 mg/kg). Gene expression analyses of tyrosine hydroxylase (TH) and α3- and α4-nicotinic acetylcholine receptor subunits (nAChRs) in the ventral tegmental area (VTA) and immunohistochemical studies to elucidate whether CB2r colocalized with α3- and α4-nAChRs in the nucleus accumbens and VTA were performed. Mecamylamine-precipitated withdrawal syndrome after chronic nicotine exposure was evaluated in CB2KO mice and WT mice treated with AM630 (1 and 3 mg/kg). CB2KO mice did not show nicotine-induced place conditioning and self-administered significantly less nicotine. In addition, AM630 was able to block (3 mg/kg) nicotine-induced CPP and reduce (1 and 3 mg/kg) nicotine self-administration. Under baseline conditions, TH, α3-nAChR, and α4-nAChR mRNA levels in the VTA of CB2KO mice were significantly lower compared with WT mice. Confocal microscopy images revealed that CB2r colocalized with α3- and α4-nAChRs. Somatic signs of nicotine withdrawal (rearings, groomings, scratches, teeth chattering, and body tremors) increased significantly in WT but were absent in CB2KO mice. Interestingly, the administration of AM630 blocked the nicotine withdrawal syndrome and failed to alter basal behavior in saline-treated WT mice. These results suggest that CB2r play a relevant role in the rewarding, reinforcing, and motivational effects of nicotine. Pharmacological manipulation of this receptor deserves further consideration as a potential new valuable target for the treatment of nicotine dependence.This study was supported by the following research grants: Ministerio de Ciencia e Innovación (SAF2011-23420 to Jorge Manzanares, SAF2009-10689 to Pere Berbel, and SAF2011-29864 to Rafael Maldonado); Ministerio de Economía y Competitividad, Dirección General de Investigación (PSI2011-24762) to José Miñarro; Generalidad Valenciana, Consejería de Educación (PROMETEO/2009/072) to José Miñarro; Gobierno Catalán (SGR2009-00131) to Rafael Maldonado; ICREA Academia-2008 to Rafael Maldonado; and Instituto de Salud ‘Carlos III’ (FIS), RETICS, Red de Trastornos Adictivos (RD06/0001/1004, RD12/0028/0019 to Jorge Manzanares; RD06/001/0016, RD12/0028/005 to José Miarro; RD06/001/001, RD12/0028/0023 to Rafael Maldonado

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.This research was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red-(CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU; Strategic action of the CIBER of Infectious Diseases (CIBERINFEC) 2022.S

Expansion and application of the PREDA material and its effects on Academic Dishonesty and its attitudes

La Deshonestidad Académica (DA) es una de las grandes dificultades que está teniendo la universidad en la formación de futuros profesionales. El objetivo del trabajo fue ampliar el material PREDA con una nueva unidad sobre el software empleado para la detección del plagio y analizar analizar el efecto de todo el PREDA en la percepción de la DA en estudiantes universitarios. La muestra total es de 472 estudiantes universitarios de la UCM y la UDIMA de 15 asignaturas diferente, tanto de grado como de máster. Los resultados indican que no existe un efecto significativo de las estrategías en la percepción de la DA. Sin embargo, el grupo de estudiantes que se expuso al material diseñado y que fue trabajado en el aula presenta una mejora en la percepción de la DA. El material diseñado puede ser empleado para tratar el tema de la DA al interior del aula.Academic Dishonesty (AD) is one of the great difficulties that the university is having in the training of future professionals. The objective of the work was to expand the PREDA material with a new unit on the software used to detect plagiarism and to analyze the effect of all the PREDA on the perception of AD in university students. The total sample is 472 university students from the UCM and the UDIMA of 15 different subjects, both undergraduate and master's degrees. The results indicate that there is no significant effect of the strategies on the perception of AD. However, the group of students who were exposed to the material designed and worked on in the classroom presented an improvement in the perception of AD. The material designed can be used to deal with the subject of AD in the classroom.Depto. de Investigación y Psicología en EducaciónFac. de EducaciónFALSEVicerrectorado de Calidad - UCMunpu