Amstrupclemmensen2933

Outdoor air pollution is a global health concern, but detailed exposure information is still limited for many parts of the world. In this study, high-resolution exposure surfaces were generated for annual and seasonal fine particulate matter (PM2.5), coarse particulate matter (PM10), and carbon monoxide (CO) for the Greater Beirut Area (GBA), Lebanon, an urban zone with a complex topography and multiple source contributions. Land use regression models (LUR) were calibrated and validated with monthly data collected from 58 locations between March 2017 and March 2018. The annual mean (±1 SD) concentrations of PM2.5, PM10, and CO across the monitoring locations were 68.1 (±15.7) μg/m3, 83.5 (±19.5) μg/m3, and 2.48 (±1.12) ppm, respectively. The coefficients of determination for LUR models ranged from 56 to 67% for PM2.5, 44 to 63% for the PM10 models, and 50 to 60% for the CO. LUR model structures varied significantly by season for both PM2.5 and PM10 but not for CO. Traffic emissions were consistently the main source of CO emissions throughout the year. The relative importance of industrial emissions and power generation sources towards predicted PM levels increased during the hot season while the contribution of the international airport diminished. Moreover, the complex topography of the study area along with the seasonal changes in the predominant wind directions affected the spatial predicted concentrations of all three pollutants. Overall, the predicted exposure surfaces were able to conserve the inter-pollution correlations determined from the field monitoring campaign, with the exception of the cold season. Our pollution surfaces suggest that the entire population of Beirut is regularly exposed to concentrations exceeding the World Health Organization (WHO) air quality standards for both PM2.5 and PM10.Background Checkrein deformity is an uncommon disease with a well-described etiology. It is characterized by a dynamic deformity of the hallux or great toe. We report two cases of checkrein deformity due a fibular graft harvesting in two patients with a mandibular bone defect secondary to an oral cancer treatment. Case report We report two young patients with mandibular cancers that had been treated several years before our visit and were currently free of disease. The patients had a mandibular bone defect due to the maxillofacial treatment, solved with a free fibular graft. The current complaint was a great toe deformity that caused pain and made them walk with difficulties. Diagnosis was a checkrein deformity, and after a surgical release of the flexor hallucis longus tendon, both cases returned to normal activities with no walking limitations. Conclusion Our cases highlight that an accurate patient examination is warranted following these reconstructions as many of them can be misdiagnosed, and a relatively simple surgery can improve the patients' limitations.Environmental toxicants such as phthalate have been involved in multiple health disorders including renal diseases. Oxidative damage is implicated in many alterations caused by phthalate especially the di(2-ethylhexyl) phthalate (DEHP), which is the most useful phthalate. However, information regarding its mechanism of renal damage is lacking. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates gene expression implicated in free radical scavenging and cytoprotection including the antioxidant glutathione (GSH) pathway. The aim of this study was to assess whether DEHP affects the Nrf2 pathway and the GSH concentration. Mice were divided into four groups a control group and three groups treated with DEHP at different concentrations (5, 50, and 200 mg/kg body weight) for 30 days. Our results showed that DEHP altered the normal levels of serum biochemical parameters creatinine (CREA), urea, and lactate dehydrogenase (LDH). This phthalate caused oxidative damage through the induction of lipid peroxidation and protein oxidation as marked by increase of protein carbonyl (PC) and loss of protein-bound sulfhydryls (PSH). Simultaneously, DEHP treatment decreased the protein level of Nrf-2, HO-1, and GCLC (responsible of GSH synthesis) and decreased the GSH level. Inhibition of the Nrf2 pathway is related to the activation of the mitochondrial pathway of apoptosis. Beta-Lapachone in vitro This apoptotic process is evidenced by an upregulation of p53 and Bax protein levels in addition to a downregulation of Bcl-2. Collectively, our data demonstrated that depletion of Nrf2 and GSH was associated with the elevation of oxidative stress and the activation of intrinsic apoptosis in mouse kidney treated with DEHP.The COVID-19 pandemic needs therapies that are presently available and safe. We propose that subjects with metabolic syndrome, old age, and male gender have the greatest morbidity and mortality and have low stress proteins, in particular, low intracellular heme oxygenase (HO-1), making them particularly vulnerable to the disease. Additionally, COVID-19's heme reduction may contribute to even lower HO-1. Low-grade inflammation associated with these risk factors contributes to triggering a cytokine storm that spreads to multi-organ failure and near death. The high mortality of those treated with ventilator assistance may partially be explained by ventilator-induced inflammation. The cytoprotective and anti-inflammatory properties of HO-1 can limit the infection's damage. A paradox of COVID-19 hospital admissions data suggests that fewer cigarette-smokers are admitted compared with non-smokers in the general population. This unexpected observation may result from smoke induction of HO-1. Therapies with anti-viral properties that raise HO-1 include certain anesthetics (sevoflurane or isoflurane), hemin, estrogen, statins, curcumin, resveratrol, and melatonin. Controlled trials of these HO-1 inducers should be done in order to prevent or treat COVID-19 disease.Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome-lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Neuroepithelial cells act as neural stem cells by renewing themselves during embryonic development. These cells are tightly interconnected and make contact with the basement membrane of the neuroepithelium. Under such circumstances, Ca2+ fluorescence recording is a successful method to study physiological properties of the neuroepithelial stem cell. This chapter describes detailed techniques of Ca2+ fluorescence recording from neuroepithelial stem cells.Hereditary transthyretin amyloidosis is caused by pathogenic variants (ATTRv) in the TTR gene. Alongside cardiac dysfunction, the disease typically manifests with a severely progressive sensorimotor and autonomic polyneuropathy. Three different drugs, tafamidis, patisiran, and inotersen, are approved in several countries, including the European Union and the United States of America. By stabilizing the TTR protein or degrading its mRNA, all types of treatment aim at preventing amyloid deposition and stopping the otherwise fatal course. Therefore, it is of utmost importance to recognize both onset and progression of neuropathy as early as possible. To establish recommendations for diagnostic and therapeutic procedures in the follow-up of both pre-symptomatic mutation carriers and patients with manifest ATTRv amyloidosis with polyneuropathy, German and Austrian experts elaborated a harmonized position. This paper is further based on a systematic review of the literature. Potential challenges in the early recognition of disease onset and progression are the clinical heterogeneity and the subjectivity of sensory and autonomic symptoms. Progression cannot be defined by a single test or score alone but has to be evaluated considering various disease aspects and their dynamics over time. The first-line therapy should be chosen based on individual symptom constellations and contra-indications. If symptoms worsen, this should promptly implicate to consider optimizing treatment. Due to the rareness and variability of ATTRv amyloidosis, the clinical course is most importantly directive in doubtful cases. Therefore, a systematic follow-up at an experienced center is crucial to identify progression and reassure patients and carriers.Background Walking dysfunction is common in people with multiple sclerosis (MS). Besides walking speed or endurance, one crucial feature of ambulatory function is the ability to adjust the gait pattern according to walking speed which relies on the integrity of spinal motor centres, their reciprocal connections to supraspinal networks and peripheral sensory input. Objective To investigate the capacity of people with MS to modify their gait pattern in response to changes in walking speed. Methods 3D gait analysis during free treadmill walking was performed in 35 people with MS and 20 healthy controls. Twelve kinematic parameters ranging from basic spatiotemporal measures to complex indicators of intralimb coordination were assessed at different absolute and relative walking speeds. Results Cadence, double-limb support time, trunk movements and especially measures of intralimb coordination demonstrated significantly less speed-dependent modifications in MS than in controls. These limitations were more prominent in subjects with stronger MS-related impairment (worse outcome in clinical walking tests, higher Expanded Disability Status Scale). Conclusion The incapacity to modify specific elements of the walking pattern according to walking speed contributes to gait dysfunction in people with MS limiting activities of daily living. Gait modulation may serve as sensitive marker of walking function in MS. Trial registration Clinicaltrials.gov, NCT01576354; first posted April 12, 2012.Mild cognitive impairment (MCI) is a pre-existing state of Alzheimer's disease (AD). An accurate prediction on the conversion from MCI to AD is of vital clinical significance for potential prevention and treatment of AD. Longitudinal studies received widespread attention for investigating the disease progression, though most studies did not sufficiently utilize the evolution information. In this paper, we proposed a cerebral similarity network with more progression information to predict the conversion from MCI to AD efficiently. First, we defined the new dynamic morphological feature to mine longitudinal information sufficiently. Second, based on the multiple dynamic morphological features the cerebral similarity network was constructed by sparse regression algorithm with optimized parameters to obtain better prediction performance. Then, leave-one-out cross-validation and support vector machine (SVM) were employed for the training and evaluation of the classifiers. The proposed methodology obtained a high accuracy of 92.