Sharada Kunwor, Sami Lama, Surya Raj Niraula
et al.
Introduction: Resilience enables older adults to cope with and adapt to challenges, promoting stability or positive personal growth. In old age, vulnerabilities such as multi morbidity, bereavement, social isolation, and financial constraints elevate mental health risks, including depression and anxiety. Higher trait resilience strongly correlates with improved mental well-being in this population. This study was to assessed resilience and mental well-being among older adults.
Methods: A community-based descriptive cross-sectional study was conducted in Dharan Sub-Metropolitan city. Five wards were randomly selected from twenty. A simple random sampling method was used to choose respondents, with informed consent obtained prior to interviews. Data were collected using a structured questionnaire and analyzed with the Statistical Package for Social Sciences version 11.5. Descriptive and inferential statistics were used.
Result: A total of 166 elderly participants were included in the study, of whom 71 (42.77%) were male and 95 (57.23%) were female. The median resilience score was 69.50 (IQR: 59.25–74.00; 95% CI: 67.70–71.30), and the median mental well-being score was 55.00 (IQR: 52.00–58.00; 95% CI: 54.27–55.73).
Conclusion: The resilience of the elderly participants was moderate to high, and their mental well-being was generally satisfactory.
ObjectiveThis study aimed to enhance the Coma Recovery Scale-Revised (CRS-R) for disorders of consciousness (DoC) by developing a two-dimensional model differentiating cognition and motor function.MethodsWe analyzed 124 DoC patients retrospectively and validated findings using five multicenter datasets (n = 420). CRS-R subscores were decomposed into Consciousness_x (awareness) and Consciousness_y (arousal/motor function) using Projective Non-negative Matrix Factorization. Logistic regression established diagnostic thresholds, evaluated by accuracy, precision, recall, and F1-score.ResultsThe model achieved high accuracy (0.94), precision (0.92), and recall (0.99). Patients with minimally conscious state (MCS) or emerged MCS showed significantly higher scores than vegetative state (VS) patients (p < 0.05). The four-quadrant framework revealed distinct clinical profiles: Quadrant I (high awareness/arousal) identified patients for cognitive rehabilitation; Quadrant II (low awareness/high arousal) suggested arousal-enhancing therapies; Quadrant III (low awareness/arousal) indicated VS requiring basic support; Quadrant IV (high awareness/low arousal) highlighted needs for sensorimotor integration.ConclusionsThe two-dimensionally reduced representation of CRS-R scores maintains diagnostic accuracy while improving DoC classification. The four-quadrant model enables personalized interventions.Trial registrationOur study has been verified by the Chinese Clinical Trial Registry with the registration number: ChiCTR2400085855, and the registration date is June 19, 2024.
Sara Venturini, Saniya Mediratta, Tobias J. Adams
et al.
Objective: For patients undergoing decompressive craniectomy for TBI, cranioplasty facilitates rehabilitation and reintegration into society. Cranioplasty practice is poorly documented globally. Challenges including lack of materials and technical skills disproportionately affect LMICs. This study evaluates global cranioplasty practice and the extent to which barriers preclude patients from accessing cranial reconstruction. Methods: An international survey was disseminated to centres performing cranioplasty for TBI. Survey questions addressed baseline hospital information, cranioplasty indications, barriers and techniques, follow-up. Centres in HICs and LMICs were compared. Results: 101 responses were received (86 individual institutions, 39 countries). Variation in practice was seen globally, and between HICs and LMICs. Autologous bone was the most common material used. Titanium and polymethylmethacrylate were the most used artificial implants. LMIC sites were more likely to store bone flaps in the patient's abdomen, while HICs had more access to 3D printing. Lack of infection and good neurological recovery were the commonest eligibility criteria. Cost of materials/operation and unavailable materials were the commonest barriers. Responders suggested easier access to cheaper materials would significantly improve access. Cranioplasty associated costs were higher than the country's GNI per capita in 7 cases. Less than 50 % of patients without cranioplasty had access to protective equipment. Less than a quarter of respondents stated patients had access to brain injury charities, and over 50 % believed stigma affects their patients. Conclusions: Variation in cranioplasty practice was confirmed. Barriers limiting access were identified, specifically, availability of materials and operation-related costs. These findings can inform context-specific interventions to overcome current challenges.
Surgery, Neurology. Diseases of the nervous system
Abstract Background Abnormal microglial polarization phenotypes contribute to the pathogenesis of Alzheimer’s disease (AD). Circular RNAs (circRNAs) have garnered increasing attention due to their significant roles in human diseases. Although research has demonstrated differential expression of circRNAs in AD, their specific functions in AD pathogenesis remain largely unexplored. Methods CircRNA microarray was performed to identify differentially expressed circRNAs in the hippocampus of APP/PS1 and WT mice. The stability of circAPP was assessed via RNase R treatment assay. CircAPP downstream targets miR-1906 and chloride intracellular channel 1 (CLIC1) were identified using bioinformatics and proteomics, respectively. RT-PCR assay was conducted to detect the expression of circAPP, miR-1906 and CLIC1. Morris water maze (MWM) test, passive avoidance test and novel object recognition task were used to detect cognitive function of APP/PS1 mice. Microglial M1/M2 polarization and AD pathology were assessed using Western blot, flow cytometry and Golgi staining assays. CLIC1 expression and channel activity were evaluated using Western blot and functional chloride channel assays, respectively. The subcellular location of circAPP was assessed via FISH and RT-PCR assays. RNA pull-down assay was performed to detect the interaction of miR-1906 with circAPP and 3’ untranslated region (3’UTR) of CLIC1 mRNA. Results In this study, we identified a novel circRNA, named circAPP, that is encoded by amyloid precursor protein (APP) and is implicated in AD. CircAPP is a stable circRNA that was upregulated in Aβ-treated microglial cells and the hippocampus of APP/PS1 mice. Downregulation of circAPP or CLIC1, or overexpression of miR-1906 in microglia modulated microglial M1/M2 polarization in Aβ-treated microglial cells and the hippocampus of APP/PS1 mice, and improved AD pathology and the cognitive function of APP/PS1 mice. Further results revealed that circAPP was mainly distributed in the cytoplasm, and circAPP could regulate CLIC1 expression and channel activity by interacting with miR-1906 and affecting miR-1906 expression, thereby regulating microglial polarization in AD. Conclusions Taken together, our study elucidates the regulatory role of circAPP in AD microglial polarization via miR-1906/CLIC1 axis, and suggests that circAPP may act as a critical player in AD pathogenesis and represent a promising therapeutic target for AD.
Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology. Diseases of the nervous system
Lorenzo Moccia, Francesca Bardi, Maria Benedetta Anesini
et al.
<b>Background/Objectives:</b> While positive symptoms of schizophrenia are often satisfactorily controlled, negative symptoms are difficult to treat, persisting despite treatment. Different strategies have been devised to deal with this problem. We aimed to review drug treatment for negative symptoms of schizophrenia in controlled trials of marketed drugs. <b>Methods:</b> We searched the PubMed database and the resulting records’ reference lists to identify eligible trials using schizophrenia[ti] AND “negative symptom*”[ti] as a search strategy. We determined eligibility through Delphi rounds among all authors. <b>Results:</b> On 11 February 2025, we identified 1485 records on PubMed and 3 more from reference lists. Eligible were 95 records. Most studies were double-blind, randomized controlled trials, carried-out in add-on in patients stabilized with antipsychotics. Other antipsychotics were the most frequent comparators, followed by antidepressants, and recently, antioxidants are gaining importance in trials. Many trials, especially those conducted in the Western world, found no significant effects compared to placebo, while most Iranian studies were positive, although not with a strong effect size. <b>Conclusions:</b> Current research has contributed little to progress in the treatment of the negative symptoms of schizophrenia. The reason might reside in the absence of knowledge of the mechanisms whereby these symptoms are generated, which prevents us from designing possibly effective treatment strategies, and/or to the chronicity of negative symptoms, as they are the first to be established even when they do not become fully apparent.
Masoumeh Najafi, Amin Jahanbakhshi, Sebastiano Finocchi Ghersi
et al.
The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.
Autophagy dysfunction has been directly linked with the onset and progression of Parkinson’s disease (PD), but the underlying mechanisms are not well understood. High-mobility group A1 (HMGA1), well-known chromatin remodeling proteins, play pivotal roles in diverse biological processes and diseases. Their function in neural cell death in PD, however, have not yet been fully elucidated. Here, we report that HMGA1 is highly induced during dopaminergic cell death in vitro and mice models of PD in vivo. Functional studies using genetic knockdown of endogenous HMGA1 show that HMGA1 signaling inhibition accelerates neural cell death, at least partially through aggravating MPP+-induced autophagic flux reduction resulting from partial block in autophagic flux at the terminal stages, indicating a novel potential neuroprotective role for HMGA1 in dopaminergic neurons death. MicroRNA-103/107 (miR-103/107) family, which is highly expressed in neuron, coordinately ensures proper end-stage autophagy. We further illustrate that MPP+/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced HMGA1 elevation counterparts the effect of miR-103/107 downregulation by directly binding to their promoters, respectively, sustaining their expression in MPP+-damaged MN9D cells and modulates autophagy through CDK5R1/CDK5 signaling pathway. We also find that HMGA1 is a direct target of miR-103/107 family. Thus, our results suggest that HMGA1 forms a negative feedback loop with miR-103/107-CDK5R1/CDK5 signaling to regulate the MPP+/MPTP-induced autophagy impairment and neural cell death. Collectively, we identify a paradigm for compensatory neuroprotective HMGA1 signaling in dopaminergic neurons that could have important therapeutic implications for PD.
Objective: The surgical technique, safety, efficacy, and clinical application value of the intra-neuroendoscopic technique (INET) for the treatment of subacute-chronic and chronic septal subdural hematoma was investigated based on the structure and pathological features of the hematoma wall, and the critical factors of hematoma growth and recurrence were determined, in order to provide reference for clinical drug treatment.Methods: This was non-randomized concurrent control study. A total of 94 patients who met the inclusion criteria were recruited between May 2015 and February 2019 and were divided into the INET treatment group (INET group, 45 cases) and the burr hole drainage (BHD) treatment group (control group, 49 cases). The hematoma fluid components and the morphological structure and pathological characteristics of the hematoma wall were analyzed, and the surgical duration, subdural drainage tube (SDT) placement duration, intracranial infection rate, Bender grade at the 1 month post-operative follow-up and hematoma recurrence rate within the 6 months of post-operative follow-up were compared between the two groups. A multiple logistic regression model was established to analyze the risk factors associated with recurrence within 6 months.Results: Intraoperative endoscopy showed that the adhesion bands that formed early in the hematoma cavity were strip-like and that those that formed late were lock-column-like. The hematoma cavity was divided into different-sized chambers with by these strips/columns. Pathological sections of cyst wall reveled angiogenesis inside the cyst and mucus-like changes, rupture and hemorrhage in the vascular wall. Obvious inflammatory cell infiltration and fibrous connective tissue hyperplasia were observed in the cyst wall. The osmotic pressure of the hematoma fluid was not significantly different from that of the peripheral venous blood [(296.7 ± 10.3) mOsm/kg vs. (291.5 ± 12.4) mOsm/kg, p = 0.68]. However, the D-dimer contents which reflect the severity of fibrinolysis in the hematoma and the proinflammatory cytokine interleukin 6 (IL-6) were significantly higher in the hematoma fluid than in the peripheral venous blood. The surgery duration for the INET group was significantly longer than that for the control group [(60.4 ± 10.6) min vs. (44.1 ± 9.8) min, p = 0.00], but both the hematoma recurrence rate within 6 months of post-operative follow-up (4.4 vs. 24.5%, p = 0.00) and the SDT placement duration [(2.1 ± 0.6) d vs. (3.9 ± 0.7) d, p = 0.00] for the INET group were both lower than those for the control group. The intracranial infection rate did not differ significantly between the two groups (4.4 vs. 10.2%, p = 0.50). The overall effective rate of the Bender grade at 1 month of follow-up did not differ significantly between the two groups (95.6 vs. 87.8%, p = 0.32), but the proportion of patients who recovered to Bender grade 0 with no symptoms was significantly higher in the INET group than in the control group (86.7 vs. 67.3%, p = 0.03). Multiple logistic regression analysis showed that INET surgery [odds ratio (OR) 3.71, 95% confidence interval (CI) 1.31–9.62, p = 0.02], age of 65 years or younger (OR 1.51, 95% CI 1.05–2.87, p = 0.03) and unilateral subdural hematoma (OR 1.76, 95% CI 1.05–3.41, p = 0.02) were independent factors that reduced the post-operative recurrence rate.Conclusion: The INET surgical plan based on the structure and pathological features of the subacute-chronic and chronic subdural hematoma wall can reduce the recurrence rate and improve the clinical prognosis.Trial registration:ClinicalTrials.gov, NCT02515903. Registered 5 August, 2015.
Lotte Haverman, Ron A A Mathôt, Floor Veltkamp
et al.
Introduction Idiopathic nephrotic syndrome (INS) is characterised by a high relapse rate up to 80% after initial response to standard therapy with corticosteroids. Steroid toxicity is common and causes a great burden of disease that negatively influences the health-related quality of life (HRQoL). Recently, studies have shown that levamisole, an anthelminthic drug, significantly improves relapse-free survival in children with frequent relapses or steroid dependency. Compared with other steroid-sparing drugs, levamisole has relatively few side effects. We hypothesise that adding levamisole to standard therapy with corticosteroids in children with a first episode of INS will prevent relapses, decrease cumulative dosage of steroids used and improve HRQoL. This paper presents the study protocol for the LEARNS study (LEvamisole as Adjuvant therapy to Reduce relapses of Nephrotic Syndrome).Methods and analysis An international, double-blind, placebo-controlled randomised trial will be conducted in 20 participating hospitals in the Netherlands and Belgium. Participants (n=92) with a first episode of INS, aged 2–16 years, who achieve remission after 4 weeks of oral prednisolone will be randomly assigned (1:1) to receive either levamisole 2.5 mg/kg alternate day or placebo added to prednisolone (18-week tapering schedule) for a total of 24 weeks. Follow-up will be until 2 years after first presentation. Additionally, parents and/or children will fill out five HRQoL questionnaires. Primary outcome of the LEARNS study is occurrence of relapses within 12 months after first presentation. Secondary outcomes include time to first relapse, cumulative steroid dose after 2 years, safety parameters and quality of life scores.Ethics and dissemination The trial was approved by the Medical Ethical Committee. Results of the study will be published in a peer-reviewed journal.Trial registration number NL6826, 2017-001025-41
Meredith R. Boyd, Cara C. Lewis, Kelli Scott
et al.
Abstract Background Training is a core component in the implementation of empirically supported treatments, especially in the case of psychosocial interventions targeting mental illness. However, common forms of training are relatively ineffective in producing behavioral changes in providers. Trainers are in a strategic position to influence the success of training, but no research, to our knowledge, has explored whether personal characteristics of trainers (e.g., enthusiasm, charisma) increase effectiveness of training empirically supported treatments in the field of mental health. To address this gap, the current study created a measure of trainer characteristics (the Measure of Effective Attributes of Trainers (MEAT)) and assessed preliminary evidence for its reliability and validity by following gold standard measure development procedures. Methods Measure development consisted of three steps: (1) An initial pool of items was generated based on extant literature, input from the target population, and expert input; (2) target users of the measure interacted with the initial item pool to ensure face validity as well as clarity of measure instructions, response options, and items; and (3) a convenience sample viewed training videos and completed the measure resulting from step 2 to establish preliminary evidence of reliability and validity. An exploratory factor analysis was performed on the measure to determine whether latent factors (i.e., subscales of characteristics) underlie the data. Results The final solution consisted of two factors that demonstrated preliminary evidence for structural validity of the measure. The first factor, labeled “Charisma,” contained items related to characteristics that facilitate a positive personal relationship with the trainee (e.g., friendly, warm), and the second factor, labeled “Credibility,” contained items related to characteristics that emphasize the qualification of the trainer (e.g., professional, experienced). There was also evidence for face validity, content validity, reliability, and known groups validity of the measure. Conclusions The MEAT demonstrated preliminary evidence of key psychometric properties. Future research is needed to further explore and contribute to its psychometric evidence, which could be done in conjunction with measures of trainee knowledge, attitudes towards empirically supported treatments, and evaluations of trainee behavior change to delineate key characteristics of trainers to be leveraged for more effective training.
Jens Bunt, Jason M Osinski, Jonathan WC Lim
et al.
Background: Nuclear factor I family members nuclear factor I A and nuclear factor I B play important roles during cerebral cortical development. Nuclear factor I A and nuclear factor I B regulate similar biological processes, as their expression patterns, regulation of target genes and individual knockout phenotypes overlap. We hypothesised that the combined allelic loss of Nfia and Nfib would culminate in more severe defects in the cerebral cortex than loss of a single member. Methods: We combined immunofluorescence, co-immunoprecipitation, gene expression analysis and immunohistochemistry on knockout mouse models to investigate whether nuclear factor I A and nuclear factor I B function similarly and whether increasing allelic loss of Nfia and Nfib caused a more severe phenotype. Results: We determined that the biological functions of nuclear factor I A and nuclear factor I B overlap during early cortical development. These proteins are co-expressed and can form heterodimers in vivo . Differentially regulated genes that are shared between Nfia and Nfib knockout mice are highly enriched for nuclear factor I binding sites in their promoters and are associated with neurodevelopment. We found that compound heterozygous deletion of both genes resulted in a cortical phenotype similar to that of single homozygous Nfia or Nfib knockout embryos. This was characterised by retention of the interhemispheric fissure, dysgenesis of the corpus callosum and a malformed dentate gyrus. Double homozygous knockout of Nfia and Nfib resulted in a more severe phenotype, with increased ventricular enlargement and decreased numbers of differentiated glia and neurons. Conclusion: In the developing cerebral cortex, nuclear factor I A and nuclear factor I B share similar biological functions and function additively, as the combined allelic loss of these genes directly correlates with the severity of the developmental brain phenotype.
Davide Vito MorettiNational Institute for the research and cure of Alzheimer’s disease, S. John of God, Fatebenefratelli, Brescia, Italy Background: An increased electroencephalographic (EEG) upper/lower alpha power ratio has been associated with less regional blood perfusion, atrophy of the temporoparietal region of the brain, and reduction of hippocampal volume in subjects affected by mild cognitive impairment due to Alzheimer’s disease as compared with subjects who do not develop the disease. Moreover, EEG theta frequency activity is quite different in these groups. This study investigated the correlation between biomarkers and memory performance.Methods: EEG α3/α2 power ratio and cortical thickness were computed in 74 adult subjects with prodromal Alzheimer’s disease. Twenty of these subjects also underwent assessment of blood perfusion by single-photon emission computed tomography (SPECT). Pearson’s r was used to assess the correlation between cortical thinning, brain perfusion, and memory impairment.Results: In the higher α3/α2 frequency power ratio group, greater cortical atrophy and lower regional perfusion in the temporoparietal cortex was correlated with an increase in EEG theta frequency. Memory impairment was more pronounced in the magnetic resonance imaging group and SPECT groups.Conclusion: A high EEG upper/low alpha power ratio was associated with cortical thinning and less perfusion in the temporoparietal area. Moreover, atrophy and less regional perfusion were significantly correlated with memory impairment in subjects with prodromal Alzheimer’s disease. The EEG upper/lower alpha frequency power ratio could be useful for identifying individuals at risk for progression to Alzheimer’s dementia and may be of value in the clinical context.Keywords: electroencephalography, perfusion, atrophy, temporoparietal network, memory deficits, hippocampal volume, mild cognitive impairment, Alzheimer’s disease
Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology. Diseases of the nervous system
Abstract Background and Objective: With regard to high prevalence of attention deficit hyperactivity disorder (ADHD) and its being significantly affected by nutritional factors, we aimed to determine the relationship between Ferritin serum level and ADHD. Material and methods: This ex-post- facto (causal comparative research) design study was conducted on 60 children, selected via convenience sampling. Thirty of them were ADHD children diagnosed by a psychiatrist using DSM IV checklist, as a case group, and the rest were healthy ones located in control group. Having their family informed consent, their Ferritin level was measured via ELIZA method. Results: The results show that Ferritin serum level of ADHD children are lower than that of healthy ones. Using t- test, it was indicated that the difference is significant (p= 0.002). Besides, the result of Pearson correlation coefficient showed that there is no significant relation between Ferritin and ADHD. Conclusion: In terms of the results and the importance of this issue, we recommend conducting further controlled research. Keywords: Ferritin, ADHD, Attention Deficit Hyperactivity Disorder
In both humans and rodents, decline in cognitive function is a hallmark of the aging process, the basis for this decrease has yet to be fully characterized. However, using aged rodent models, deficits in auditory processing have been associated with significant decreases in inhibitory signaling attributed to a loss of GABAergic interneurons. Not only are these interneurons crucial for pattern detection and other large-scale population dynamics, but they have also been linked to mechanisms mediating plasticity and learning, making them a prime candidate for study and modelling of modifications to cortical communication pathways in neurodegenerative diseases. Using the rat primary auditory cortex (A1) as a model, we probed the known markers of GABAergic interneurons with immunohistological methods, using antibodies against gamma aminobutyric acid (GABA), parvalbumin (PV), somatostatin (SOM), calretinin (CR), vasoactive intestinal peptide (VIP), choline acetyltransferase (ChAT), neuropeptide Y (NPY) and cholecystokinin (CCK) to document the changes observed in interneuron populations across the rat’s lifespan. This analysis provided strong evidence that several but not all GABAergic neurons were affected by the aging process, showing most dramatic changes in expression of parvalbumin (PV) and somatostatin (SOM) expression. With this evidence, we show how understanding these trajectories of cell counts may be factored into a simple model to quantify changes in inhibitory signalling across the course of life, which may be applied as a framework for creating more advanced simulations of interneuronal implication in normal cerebral processing, normal aging, or pathological processes.
Neurosciences. Biological psychiatry. Neuropsychiatry, Human anatomy
A saúde mental, antes focada principalmente na patologia psiquiátrica, tem como objeto de estudo todo o contexto biopsicossocial no qual o sujeito está inserido. Além disso, mais recentemente, tem surgido maior interesse na investigação das possíveis diferenças entre gêneros. Sobre a mente feminina, é imprescindível que os profissionais da saúde tenham a atenção e o conhecimento necessários sobre os transtornos psíquicos associados ao ciclo reprodutivo, devido tamanha repercussão que causam não somente à paciente. Diversas questões ainda estão em aberto no que se refere a um tema tão amplo quanto à saúde mental da mulher. Neste artigo traremos um breve panorama histórico, atualidades e perspectivas.