Conectar
by Eleni Christoforidou, Jordan S. Rowe, Fabio A. Simoes, Raphaelle Cassel, Luc Dupuis, Peter Nigel Leigh, Majid Hafezparast
Impaired cytoplasmic dynein function has been implicated in amyotrophic lateral sclerosis (ALS) pathogenesis, yet the contributions of spinal interneurons to disease phenotypes remain unclear. We tested the hypothesis that hypomorphic dynein function in cholinergic neurons disrupts the development, survival, or positioning of inhibitory interneuron populations in the lumbar spinal cord. Using ChAT-Cre recombination, we generated four mouse genotypes with graded reductions in dynein activity in ChAT+ cells: Dync1h1+/+ (wildtype), Dync1h1−/+ (hemizygous wildtype), Dync1h1+/Loa (heterozygous Loa mutation), and Dync1h1−/Loa (hemizygous Loa). At 52 weeks of age, lumbar spinal cords (L3–L6) were harvested, cryosectioned, and immunostained for ChAT, GAD-67, Parvalbumin, and Calbindin. Cell counts were performed on confocal images from eight sections per mouse (N = 3 male mice/genotype), and radial distances from the central canal were normalised to gray matter width. Angular distributions were analysed via circular statistics. There were no significant genotype-dependent differences in the numbers of ChAT+, GAD-67+, Parvalbumin+, or Calbindin+ cells, nor in ChAT+ subpopulations (motor neurons versus interneurons) or double‐positive interneuron subsets (e.g., ChAT+–GAD-67+, Parvalbumin+–GAD-67+, Parvalbumin+–Calbindin+). Radial positioning relative to the central canal was similarly preserved across all markers and genotypes. Circular‐median tests revealed statistically significant shifts in mean angle for ChAT+, GAD-67+, and certain double‐positive cells, but these amounted to only 5–10° displacements, translating to lateral shifts of ~10–20 µm, well within single laminar bands, and are unlikely to impact circuit connectivity. Despite substantial motor deficits and hallmark TDP-43 pathology previously seen in these models, impaired dynein function does not precipitate interneuron loss or gross migratory defects in the lumbar spinal cord. Instead, our findings suggest that the primary contributions of dynein to ALS-like phenotypes likely arise from functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology rather than from structural alterations or loss of interneuron populations.Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are among the leading non-communicable diseases (NCDs) worldwide. However, diagnosing CRDs in low-income and middle-income countries (LMICs) remains challenging due to limited access to spirometry and trained professionals. Aggravating the burden, CRDs often coexist with other NCDs, increasing healthcare costs, reducing quality of life and elevating mortality. These challenges highlight the need for simple case-finding approaches for CRDs, such as the COPD in Low-Income and Middle-Income Countries Assessment (COLA-6) questionnaire, to support prompt identification and appropriate care within NCD services in LMICs.
To evaluate the discriminative accuracy, feasibility and implementation of the COLA-6 questionnaire in identifying and managing CRDs in Brazilian Primary Healthcare (PHC) services for NCDs.
The Multimorbidity Approach for REspiratory Solutions (MARES) study consists of three work packages to be conducted in PHC services in São Carlos/SP and São Paulo/SP, Brazil.
MARES-1: A cross-sectional observational study enrolling 859 individuals with at least one NCD receiving care in PHC. The COLA-6 questionnaire will be administered by the research team and compared with quality-assured spirometry. The Chronic Airways Assessment Test (CAAT), Asthma Control Questionnaire (ACQ-7) and fractional exhaled nitric oxide (FeNO) will also be assessed. The diagnostic performance of COLA-6 for identifying CRDs—including COPD, asthma, preserved ratio impaired spirometry, restriction and overlaps—will be assessed using area under receiver operating characteristic curves and 95% CIs.
MARES-2: A cross-sectional observational study enrolling 20 healthcare professionals (physicians, physiotherapists, community health agents and nurses) from five PHC services. These professionals will apply the COLA-6 during routine NCD care to a total sample of 1000 patients. Qualitative interviews will be conducted to explore barriers and facilitators to the implementation of COLA-6, using deductive thematic analysis.
MARES-3: A longitudinal, prospective observational study in which patients from MARES-1 and MARES-2 will be reassessed at 6-month follow-up. A total sample of 473 participants with abnormal spirometry, a diagnosis of CRD or high risk for CRDs is expected. Participants will undergo spirometry, and a subset will be interviewed to explore their healthcare experiences through qualitative thematic analysis. Access to diagnostic and treatment services in Brazil will be assessed. Changes in spirometry values, FeNO, CAAT and ACQ-7 scores from baseline to 6 months in patients from MARES-1 will be analysed.
This study has been approved by the Ethics Committees of Federal University of São Carlos and University of Santo Amaro (UNISA). Ethical approval was also granted by the University College London. Results will be disseminated through peer-reviewed medical journals and presentations at international conferences. Results will improve identification of CRDs, addressing a significant gap in current PHC settings.
Dermoscopy has a proved validity in the diagnosis of cutaneous melanoma, which is one of the most aggressive forms of skin cancer. Although some studies have demonstrated a relationship between specific dermoscopic and pathologic melanoma features, there is no solid evidence allowing reliable conclusions. This study will evaluate the evidence regarding this association.
Observational studies eligible for our systematic review will enrol adults with histological cutaneous non-volar melanoma diagnosis and with dermoscopy image analysis. We will search the following databases: PubMed, Embase, Web of Science, MEDLINE and Cochrane Library. We will not impose any language or date restrictions. Outcomes of interest include the association of at least one of the melanoma dermoscopy features (irregular pigmentation, blue-white veil, atypical network, multicomponent pattern, atypical dots and/or globules, regression, peripheral tan structureless area, negative network, shiny white structures, atypical vessels and streaks/pseudopods), with melanoma Breslow index or other histopathology characteristics (melanoma subtype, mitotic index and presence of ulceration). Two reviewers will independently screen and search results, extract data from eligible studies and assess risk of bias. The evidence derived by this study will elucidate the possible link between melanoma dermoscopy and histopathology. If we could predict melanoma thickness based on dermoscopy, we would be able to anticipate melanoma treatment with impact on survival.
Ethical approval is not required because this is a literature-based study. It will be published in scientific Pubmed indexed open access journals to ensure its accessibility.
CRD42024564919.
Asthma is a major personal and public health problem worldwide, with a significant impact on patients’ quality of life and health systems. The prevalence of asthma in children is 9.1% and in adolescents is 11%. Greater literacy among children is related to better asthma control. There are many validated Patient-Reported Outcome Measures (PROMs) related to asthma, but there are only a few, and no gold standard, to measure children and adolescents’ knowledge of asthma. Therefore, the purpose of this systematic review is to evaluate the most suitable asthma self-knowledge PROMs for the paediatric population with asthma.
The inclusion criteria will be children and adolescents diagnosed with asthma (population), validated PROMs about asthma self-knowledge (intervention), between each PROM (comparison) and measurement properties (outcome) (validity, reliability, interpretability and responsiveness). The search process will be conducted in PubMed, Web of Science, EMBASE and SCOPUS. The risk of bias evaluation will be done independently by two authors with the COnsensus-based Standards for the selection of health Measurement INstruments risk of bias checklist, and the quality of evidence will be evaluated based on the Grading of Recommendations Assessment, Development and Evaluation approach.
Ethics approval is not applicable for this study since the data that will be collected are secondary data and are already in the public domain. The results will be disseminated through peer-reviewed publication and conference presentations.
CRD42024577500.
Global organizations have pronounced about the importance of involving people in health care, however, this process is challenging. Given the availability of evidence that addresses people's experiences of involvement in nursing care, it is important to produce recommendations at this point by synthesizing the evidence. So, this review aims to synthesize the available qualitative evidence about people's experiences of their involvement in nursing care in a hospital setting.
Systematic review of qualitative evidence.
This systematic review was conducted according to the JBI methodology for systematic reviews of qualitative evidence. A comprehensive search strategy was conducted in nine databases/resources. The selection process, methodological quality assessment, and data extraction were conducted independently by two reviewers. The data were synthesized using the meta-aggregation approach, and the results were graded according to ConQual.
A total of 75 findings and 141 illustrations were extracted from the 15 included studies. These findings were aggregated into 12 categories and generated into three synthesized findings: (1) People who are hospitalized conceptualize and attribute importance to involvement in nursing care as an active process of participation and monitoring of care, decision-making, opinion, and partnership; (2) The establishment of a relationship between hospitalized people and nurses, trust, communication, and information are essential for participation in care; (3) People's participation in care is affected by the person's own constraints and preference for assuming a passive role, by barriers associated with a lack of information, the organization of care, the relationship established between nurses, and paternalistic attitudes.
People who were admitted to hospital conceptualized and attached importance to this phenomenon, perceived the conditions necessary to promote it, and the barriers they experienced.
This systematic review provides recommendations for nurses' clinical practice (with grade B). It recommends that nurses should establish a partnership relationship with hospitalized people, through trust, communication and information; give people the opportunity to monitor care, participate in decision-making and give their opinion; assess the person's preferences for involvement and other factors; and that the barriers to this process identified here should be assessed and addressed in each context. As such, this review provides very valuable information for nurses' clinical practice and should also be incorporated into health policy.
Protocol Registration: PROSPERO CRD42024506501.
FreshRSS 