Increased expression of heme-binding protein 1 early in Alzheimer's disease is linked to neurotoxicity.

Alzheimer's disease is the most prevalent neurodegenerative disorder leading to progressive cognitive decline. Despite decades of research, understanding AD progression at the molecular level, especially at its early stages, remains elusive. Here, we identified several presymptomatic AD markers by investigating brain proteome changes over the course of neurodegeneration in a transgenic mouse model of AD (3×Tg-AD). We show that one of these markers, heme-binding protein 1 (Hebp1), is elevated in the brains of both 3×Tg-AD mice and patients affected by rapidly-progressing forms of AD. Hebp1, predominantly expressed in neurons, interacts with the mitochondrial contact site complex (MICOS) and exhibits a perimitochondrial localization. Strikingly, wildtype, but not Hebp1-deficient, neurons showed elevated cytotoxicity in response to heme-induced apoptosis. Increased survivability in Hebp1-deficient neurons is conferred by blocking the activation of the mitochondrial-associated caspase signaling pathway. Taken together, our data highlight a role of Hebp1 in progressive neuronal loss during AD progression

Risk assessment of sari fatemeh zahra hospital using failure mode effect analysis, individualized rapid assessment tool, and preliminary hazard analysis

Abstract Background and purpose: Identification of risk in hospital waste management have a major role in reducing the cost of surplus and preventing the spread of diseases. In this quantitative analysis, we aimed at determining waste components, evaluating hospital waste management, and prioritizing the risks in Sari Fatemeh Zahra Hospital. Materials and methods: We performed a descriptive-cross-sectional study in 2015. Tchobanoglous method was used for quantitative-physical analysis of the waste. The individualized rapid assessment tool was applied to evaluate waste management. Preliminary Hazard Analysis and failure mode and effect analysis models were used to identify and prioritize the risks. Results: Total waste production, general waste, infectious wastes, and sharp objects were 1011.54, 600.45, 384.94, and 26.15 kg/day, respectively. Plastics, organic materials, and textiles constituted the highest amount of waste products. According to the individualized rapid assessment tool, the score obtained by the hospital was 82.15% indicating an excellent waste management. In preliminary hazard analysis, failure mode, and effect analysis models, 23 errors were observed, of which 9 had a priority number greater than 100. Conclusion: The models studied showed that mixing the sharp waste material with other garbage, disposal of non-infectious and semi-household waste in infectious bins and vice versa are of high risk and need corrective measures. Keywords: hospital waste management,quantitative analysis, risk assessment,preliminary hazard analysis, Hazard Analysis and Failure mode

Motor complications in Parkinson’s disease:results from 3,343 patients followed for up to 12 years

Background: Motor complications are well recognised in Parkinson’s disease (PD), but their reported prevalence varies and functional impact has not been well studied. Objectives: To quantify the presence, severity, impact and associated factors for motor complications in PD.Methods: Analysis of 3 large prospective cohort studies of recent-onset PD patients followed for up to 12 years. The MDS-UPDRS part 4 assessed motor complications and multivariable logistic regression tested for associations. Genetic risk score (GRS) for Parkinson’s was calculated from 79 single nucleotide polymorphisms. Results: 3,343 cases were included (64.7% male). Off periods affected 35.0% (95% CI 33.0, 37.0) at 4-6 years and 59.0% (55.6, 62.3) at 8-10 years. Dyskinesia affected 18.5% (95% CI 16.9, 20.2) at 4-6 years and 42.1% (38.7, 45.5) at 8-10 years. Dystonia affected 13.4% (12.1, 14.9) at 4-6 years and 22.8% (20.1, 25.9) at 8-10 years. Off periods consistently caused greater functional impact than dyskinesia. Motor complications were more common among those with higher drug doses, younger age at diagnosis, female gender, and greater dopaminergic responsiveness (in challenge tests), with associations emerging 2 to 4 years post-diagnosis. Higher Parkinson’s GRS was associated with early dyskinesia (0.026 ≤ P ≤ 0.050 from 2 to 6 years).Conclusions: Off periods are more common and cause greater functional impairment than dyskinesia. We confirm previously reported associations between motor 4 complications with several demographic and medication factors. Greater dopaminergic responsiveness and a higher genetic risk score are two novel and significant independent risk factors for the development of motor complications

Motor complications in Parkinson's disease: results from 3343 patients followed for up to 12 years

Background Motor complications are well recognized in Parkinson's disease (PD), but their reported prevalence varies and functional impact has not been well studied. Objectives To quantify the presence, severity, impact and associated factors for motor complications in PD. Methods Analysis of three large prospective cohort studies of recent-onset PD patients followed for up to 12 years. The MDS-UPDRS part 4 assessed motor complications and multivariable logistic regression tested for associations. Genetic risk score (GRS) for Parkinson's was calculated from 79 single nucleotide polymorphisms. Results 3343 cases were included (64.7% male). Off periods affected 35.0% (95% CI 33.0, 37.0) at 4–6 years and 59.0% (55.6, 62.3) at 8–10 years. Dyskinesia affected 18.5% (95% CI 16.9, 20.2) at 4–6 years and 42.1% (38.7, 45.5) at 8–10 years. Dystonia affected 13.4% (12.1, 14.9) at 4–6 years and 22.8% (20.1, 25.9) at 8–10 years. Off periods consistently caused greater functional impact than dyskinesia. Motor complications were more common among those with higher drug doses, younger age at diagnosis, female gender, and greater dopaminergic responsiveness (in challenge tests), with associations emerging 2–4 years post-diagnosis. Higher Parkinson's GRS was associated with early dyskinesia (0.026 ≤ P ≤ 0.050 from 2 to 6 years). Conclusions Off periods are more common and cause greater functional impairment than dyskinesia. We confirm previously reported associations between motor complications with several demographic and medication factors. Greater dopaminergic responsiveness and a higher genetic risk score are two novel and significant independent risk factors for the development of motor complications