ABSTRACT
COVID-19 pandemic has heavily impacted the global community. To curb the viral transmission, travel restrictions have been enforced across the world. The dataset documents the mobility disruptions and the modal shifts that have occurred as a consequence of the restrictive measures implemented in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. An online questionnaire was distributed during the period from the 11st to the 31st of May 2020, with a total of 9 394 respondents. The first part of the survey has characterized the frequency of use of all transport modes before and during the enforcement of the restrictions, while the second part of the survey has dealt with perceived risks of contracting COVID-19 from different transport modes and perceived effectiveness of travel mitigation measures. Overall, the dataset (stored in a repository publicly available) can be conveniently used to quantify and understand the modal shifts and people's cognitive behavior towards travel due to COVID-19. The collected responses can be further analysed by considering other demographic and socioeconomic covariates.
ABSTRACT
The dataset deals with the air quality perceived by citizens before and during the enforcement of COVID-19 restrictions in ten countries around the world: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the United States. An online survey conveniently translated into Chinese, English, Italian, Norwegian, Persian, Portuguese collected information regarding the perceived quality of air pollution according to a Likert scale. The questionnaire was distributed between 11-05-2020 and 31-05-2020 and 9 394 respondents took part. Both the survey and the dataset (stored in a Microsoft Excel Worksheet) are available in a public repository. The collected data offer the people's subjective perspectives related to the objective improvement in air quality occurred during the COVID-19 restrictions. Furthermore, the dataset can be used for research studies involving the reduction in air pollution as experienced, to a different extent, by populations of all the ten countries.
ABSTRACT
OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.
Subject(s)
Atrophy/pathology , Gray Matter/diagnostic imaging , Magnetic Resonance Imaging/methods , Multiple System Atrophy/pathology , Parkinson Disease/classification , Parkinson Disease/diagnostic imaging , Case-Control Studies , Female , Gray Matter/pathology , Humans , Male , Parkinsonian Disorders/pathology , ROC CurveABSTRACT
OBJECTIVES: Parkinson's disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (p<0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (p<0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (p<0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value.
Subject(s)
Humans , Male , Female , Parkinson Disease/classification , Parkinson Disease/diagnostic imaging , Atrophy/pathology , Magnetic Resonance Imaging/methods , Multiple System Atrophy/pathology , Gray Matter/diagnostic imaging , Case-Control Studies , ROC Curve , Parkinsonian Disorders/pathology , Gray Matter/pathologyABSTRACT
Abstract: Morphine is a well-characterized and effective analgesic commonly used to provide pain relief to patients suffering from both acute and chronic pain conditions. Despite its widespread use and effectiveness, one of the major drawbacks of morphine is its relatively short half-life of approximately 4 h. This short half-life often necessitates multiple administrations of the drug each day, which may contribute to both dependence and tolerance to morphine. Here, we tested the analgesic properties of a new polymer form of morphine known as PolyMorphine. This polymer has monomeric units of morphine incorporated into a poly(anhydride-ester) backbone that has been shown to hydrolyze into free morphine in vitro. Using an animal model of chronic pain, the spared nerve injury surgery, we showed that PolyMorphine is able to block spared nerve injury-induced hypersensitivity in mice for up to 24-h post-administration. Free morphine was shown to only block spared nerve injury-induced hypersensitivity for up to 2-h post-injection. PolyMorphine was also shown to act through the mu opioid receptor due to the ability of naloxone (a mu opioid receptor antagonist) to block PolyMorphine-induced analgesia in spared nerve injury animals pretreated with PolyMorphine. Additionally, we observed that PolyMorphine causes similar locomotor and constipation side effects as free morphine. Finally, we investigated if PolyMorphine had any effects in a non-evoked pain assay, conditioned place preference. Pretreatment of spared nerve injury mice with PolyMorphine blocked the development of conditioned place preference for 2-methyl-6-(phenylethynyl)pyridine (MPEP), a short-lasting mGluR5 antagonist with analgesic-like properties. Free morphine does not block the development of preference for MPEP, suggesting that PolyMorphine has longer lasting analgesic effects compared to free morphine. Together, these data show that PolyMorphine has the potential to provide analgesia for significantly longer than free morphine while likely working through the same receptor.
Subject(s)
Analgesics, Opioid/pharmacology , Morphine/pharmacology , Peripheral Nervous System Diseases/drug therapy , Receptors, Opioid, mu/drug effects , Animals , Drug Tolerance/physiology , Mice, Inbred C57BL , Morphine/chemistry , Naloxone/pharmacology , Narcotic Antagonists/pharmacologyABSTRACT
Objective: To summarize the effect of mild hypothermia on function of the organs in patients with multiple organ dysfunction syndrome after cardiopulmonary bypass surgery. Methods: The patients were randomly divided into two groups, northermia group (n=71) and hypothermia group (n=89). We immediately began cooling the hypothermia group when test results showed multiple organ dysfunction syndrome, meanwhile all patients of two groups were drawn blood to test blood gas, liver and kidney function, blood coagulation function, and evaluated the cardiac function using echocardiography from 12 to 36 hours. We compared the difference of intra-aortic balloon pump, extracorporeal membrane oxygenation rate and mortality within one month after intensive care unit admission. Results: Among the 160 patients, 36 died, 10 (11.24%) patients were from the hypothermia group and 26 (36.6%) from the northermia group (P<0.05). In northermia group, 45 (63.38%) patients used intra-aortic balloon pump and 4 (5.63%), extracorporeal membrane oxygenation; in hypothermia group, 35 (39.32%) patients used intra-aortic balloon pump and 2 (2.25%), extracorporeal membrane oxygenationï¼P<0.05). The patients' heart rate decreased significantly in the hypothermia group. The heart rate of hypothermia group is significantly slower than the northermia group at the 36th hour (P<0.05). But the mean arterial pressure of hypothermia group is significantly higher than the northermia group at the 36th hour (P<0.05). In hypothermia group, PO2, SvO2 and lactate were improved significantly compared to pre-cooling (P<0.05), and they were significantly better than the northermia group at the 36th hour (P<0.05%). Prothrombin time and activated partial thromboplastin time have no significantly difference between the two groups (P>0.05). But the platelet count has significantly difference between the two groups at the 36th hour (P<0.05). The aspartate transaminase, alanine transaminase and creatinine were improved significantly in the hypothermia group, and they were significantly better than the northermia group (P<0.05). Conclusion: Mild hypothermia is feasible and safe for patients with multiple organ dysfunction syndrome after cardiopulmonary bypass surgery.
Subject(s)
Cardiopulmonary Bypass/adverse effects , Hypothermia, Induced/methods , Multiple Organ Failure/therapy , Postoperative Care/methods , Arterial Pressure , Blood Coagulation , Cardiopulmonary Bypass/mortality , Heart Rate , Humans , Hypothermia, Induced/mortality , Hypothermia, Induced/statistics & numerical data , Intra-Aortic Balloon Pumping , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Postoperative Period , Prospective StudiesABSTRACT
BACKGROUND AND OBJECTIVE: Recently, we have shown that the Parkinson's disease (PD) susceptibility locus MAPT (microtubule associated protein tau) is associated with parkinsonism in older adults without a clinical diagnosis of PD. In this study, we investigated the relationship between parkinsonian signs and MAPT transcripts by assessing the effect of MAPT haplotypes on alternative splicing and expression levels of the most common isoforms in two prospective clinicopathologic studies of aging. MATERIALS AND METHODS: using regression analysis, controlling for age, sex, study and neuropathology, we evaluated 976 subjects with clinical, genotyping and brain pathology data for haplotype analysis. For transcript analysis, we obtained MAPT gene and isoform-level expression from the dorsolateral prefrontal cortex for 505 of these subjects. RESULTS: The MAPT H2 haplotype was associated with lower total MAPT expression (p = 1.2x10-14) and global parkinsonism at both study entry (p = 0.001) and proximate to death (p = 0.050). Specifically, haplotype H2 was primarily associated with bradykinesia in both assessments (p<0.001 and p = 0.008). MAPT total expression was associated with age and decreases linearly with advancing age (p<0.001). Analysing MAPT alternative splicing, the expression of 1N/4R isoform was inversely associated with global parkinsonism (p = 0.008) and bradykinesia (p = 0.008). Diminished 1N/4R isoform expression was also associated with H2 (p = 0.001). CONCLUSIONS: Overall, our results suggest that age and H2 are associated with higher parkinsonism score and decreased total MAPT RNA expression. Additionally, we found that H2 and parkinsonism are associated with altered expression levels of specific isoforms. These findings may contribute to the understanding of the association between MAPT locus and parkinsonism in elderly subjects and in some extent to age-related neurodegenerative diseases.
Subject(s)
Genetic Association Studies , Genetic Predisposition to Disease , Haplotypes , Parkinsonian Disorders/genetics , tau Proteins/genetics , Age Factors , Aged , Aged, 80 and over , Alternative Splicing , Brain/metabolism , Brain/pathology , Diagnosis , Female , Gene Expression , Genotype , Humans , Male , Parkinson Disease/genetics , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/mortality , Phenotype , Protein Isoforms , Quantitative Trait, HeritableABSTRACT
ABSTRACT Objective: To summarize the effect of mild hypothermia on function of the organs in patients with multiple organ dysfunction syndrome after cardiopulmonary bypass surgery. Methods: The patients were randomly divided into two groups, northermia group (n=71) and hypothermia group (n=89). We immediately began cooling the hypothermia group when test results showed multiple organ dysfunction syndrome, meanwhile all patients of two groups were drawn blood to test blood gas, liver and kidney function, blood coagulation function, and evaluated the cardiac function using echocardiography from 12 to 36 hours. We compared the difference of intra-aortic balloon pump, extracorporeal membrane oxygenation rate and mortality within one month after intensive care unit admission. Results: Among the 160 patients, 36 died, 10 (11.24%) patients were from the hypothermia group and 26 (36.6%) from the northermia group (P <0.05). In northermia group, 45 (63.38%) patients used intra-aortic balloon pump and 4 (5.63%), extracorporeal membrane oxygenation; in hypothermia group, 35 (39.32%) patients used intra-aortic balloon pump and 2 (2.25%), extracorporeal membrane oxygenation( P <0.05). The patients' heart rate decreased significantly in the hypothermia group. The heart rate of hypothermia group is significantly slower than the northermia group at the 36th hour (P <0.05). But the mean arterial pressure of hypothermia group is significantly higher than the northermia group at the 36th hour (P <0.05). In hypothermia group, PO2, SvO2 and lactate were improved significantly compared to pre-cooling (P <0.05), and they were significantly better than the northermia group at the 36th hour (P <0.05%). Prothrombin time and activated partial thromboplastin time have no significantly difference between the two groups (P >0.05). But the platelet count has significantly difference between the two groups at the 36th hour (P <0.05). The aspartate transaminase, alanine transaminase and creatinine were improved significantly in the hypothermia group, and they were significantly better than the northermia group (P <0.05). Conclusion: Mild hypothermia is feasible and safe for patients with multiple organ dysfunction syndrome after cardiopulmonary bypass surgery.
Subject(s)
Humans , Postoperative Care/methods , Cardiopulmonary Bypass/adverse effects , Hypothermia, Induced/methods , Multiple Organ Failure/therapy , Postoperative Period , Blood Coagulation , Cardiopulmonary Bypass/mortality , Prospective Studies , Arterial Pressure , Heart Rate , Hypothermia, Induced/mortality , Hypothermia, Induced/statistics & numerical data , Intra-Aortic Balloon Pumping , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Multiple Organ Failure/bloodABSTRACT
OBJECTIVE: We explore the role of DNA methylation in Alzheimer's disease (AD). To elucidate where DNA methylation falls along the causal pathway linking risk factors to disease, we examine causal models to assess its role in the pathology of AD. METHODS: DNA methylation profiles were generated in 740 brain samples using the Illumina HumanMet450K beadset. We focused our analysis on CpG sites from 11 AD susceptibility gene regions. The primary outcome was a quantitative measure of neuritic amyloid plaque (NP), a key early element of AD pathology. We tested four causal models: (1) independent associations, (2) CpG mediating the association of a variant, (3) reverse causality, and (4) genetic variant by CpG interaction. RESULTS: Six genes regions (17 CpGs) showed evidence of CpG associations with NP, independent of genetic variation - BIN1 (5), CLU (5), MS4A6A (3), ABCA7 (2), CD2AP (1), and APOE (1). Together they explained 16.8% of the variability in NP. An interaction effect was seen in the CR1 region for two CpGs, cg10021878 (P = 0.01) and cg05922028 (P = 0.001), in relation to NP. In both cases, subjects with the risk allele rs6656401(AT) (/) (AA) display more methylation being associated with more NP burden, whereas subjects with the rs6656401(TT) protective genotype have an inverse association with more methylation being associated with less NP. INTERPRETATION: These observations suggest that, within known AD susceptibility loci, methylation is related to pathologic processes of AD and may play a largely independent role by influencing gene expression in AD susceptibility loci.
ABSTRACT
BACKGROUND: During the early phases of a hepatitis C virus (HCV) infection, NK cell activation appears to be critical to the induction of adaptive immune responses that have the potential of clearing the infection. This study aimed to investigate the phenotype and function of NK cells in chronic HCV (CHC) patients, particularly patients who cleared HCV infections spontaneously (SR-HCV). MATERIAL AND METHODS: Peripheral blood NK cells were compared between 36 CHC patients, 12 SR-HCV patients, and 14 healthy controls (HC). The phenotype and function of NK cells were characterized by flow cytometry. In addition, the potential associations between the frequency of NK cell subsets and ALT, AST and HCV viral loads were also analyzed. RESULTS: Our data revealed that the population of CD3-CD56+ NK cells was significantly decreased in CHC and SR-HCV patients compared to levels in HC (P = 0.031, P = 0.014). Interestingly, we found that the levels of the CD158b inhibitory receptor were higher in CHC patients compared to levels observed in HCand SR-HCV subjects (P = 0.018, P = 0.036). In addition, the percentages of the activation receptors NKp30 and NKp46 were significantly decreased in CHC and SR-HCV patients compared to their expression levels in HC (P < 0.05). Moreover, the frequencies of inducible CD107a (but not IFN-γ-secreting) NK cellsfrom both CHC and SR-HCV patients were significantly lower than frequencies observed in controls (P = 0.018, P = 0.027). CONCLUSION: Our data indicated that the higher frequency of inhibitory NK cells combined with fewer activated NK cells may be associated with HCV-related chronic inflammation involved in CHC pathogenesis.
Subject(s)
Adaptive Immunity , Hepatitis C, Chronic/immunology , Killer Cells, Natural/immunology , Lymphocyte Activation , Receptors, KIR2DL3/blood , Adult , Aged , Alanine Transaminase/blood , Biomarkers/blood , Case-Control Studies , Female , Flow Cytometry , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/diagnosis , Humans , Immunophenotyping/methods , Killer Cells, Natural/virology , Lymphocyte Count , Lysosomal Membrane Proteins/blood , Male , Middle Aged , Natural Cytotoxicity Triggering Receptor 1/blood , Natural Cytotoxicity Triggering Receptor 3/blood , Phenotype , Young AdultABSTRACT
Extracellular Ca2+ influx was blocked by L-type Ca2+ channel blocker nifedipine to observe the effects of 15-hydroxyeicosatetraenoic acid on the constriction of rabbit pulmonary artery rings and on the changes of Ca2+ level in the rabbit pulmonary artery smooth muscle cells, and further to investigate the mechanism of the calcium mobilization induced by the 15-HETE under hypoxic conditions. The effect of extracellular Ca2+ on tension of the rabbit PA rings was also studied. Nifedipine (10 µ mol/L) had no effect on 1 µ mol/L 15-hydroxyeicosatetraenoic acid induced vasoconstriction under normoxic and hypoxic conditions. Intracellular Ca2+ increased markedly in the 15-HETE group (cells were exposed to 1 µ mol/L 15-HETE for 8 min during culture) compared to the control group (P < 0.05). The study demonstrated that the 15-HETE could induce the elevation of Ca2+ in the pulmonary artery smooth muscle cells and the elevated calcium came from the release of the intracellular calcium.
ABSTRACT
Multi-state models are appealing tools for analysing data about the progression of a disease over time. In this paper, we consider a multi-state Markov chain with two competing absorbing states: dementia and death and three transient non-demented states: cognitively normal, amnestic mild cognitive impairment (amnestic MCI), and non-amnestic mild cognitive impairment (non-amnestic MCI). The likelihood function for the data is derived and estimates for the effects of the covariates on transitions are determined when the process can be viewed as a polytomous logistic regression model with shared random effects. The presence of a shared random effect not only complicates the formulation of the likelihood but also its evaluation and maximization. Three approaches for maximizing the likelihood are compared using a simulation study; the first method is based on the Gauss-quadrature technique, the second method is based on importance sampling ideas, and the third method is based on an expansion by Taylor series. The best approach is illustrated using a longitudinal study on a cohort of cognitively normal subjects, followed annually for conversion to mild cognitive impairment (MCI) and/or dementia, conducted at the Sanders Brown Center on Aging at the University of Kentucky.