Abstract
HbVar (http://globin.bx.psu.edu/hbvar) is a widely-used locus-specific database (LSDB) launched 20 years ago by a multi-center academic effort to provide timely information on the numerous ...genomic variants leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Here, we report several advances for the database. We made clinically relevant updates of HbVar, implemented as additional querying options in the HbVar query page, allowing the user to explore the clinical phenotype of compound heterozygous patients. We also made significant improvements to the HbVar front page, making comparative data querying, analysis and output more user-friendly. We continued to expand and enrich the regular data content, involving 1820 variants, 230 of which are new entries. We also increased the querying potential and expanded the usefulness of HbVar database in the clinical setting. These several additions, expansions and updates should improve the utility of HbVar both for the globin research community and in a clinical setting.
Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal ...hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers.
Antimicrobial resistance remains a serious problem that results in high mortality and increased healthcare costs globally. One of the major issues is that resistant pathogens decrease the efficacy of ...conventional antimicrobials. Accordingly, development of novel antimicrobial agents and therapeutic strategies is urgently needed to overcome the challenge of antimicrobial resistance. A potential strategy is to kill pathogenic microorganisms via the formation of reactive oxygen species (ROS). ROS are defined as a number of highly reactive molecules that comprise molecular oxygen (O2), superoxide anion (O2•−), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). ROS exhibit antimicrobial actions against a broad range of pathogens through the induction of oxidative stress, which is an imbalance between ROS and the ability of the antioxidant defence system to detoxify ROS. ROS-dependent oxidative stress can damage cellular macromolecules, including DNA, lipids and proteins. This article reviews the antimicrobial action of ROS, challenges to ROS hypothesis, work to solidify ROS-mediated antimicrobial lethality hypothesis, recent developments in antimicrobial agents using ROS as an antimicrobial strategy, safety concerns related to ROS, and future directions in ROS research.
•Reactive oxygen species (ROS) could combat antimicrobial resistance.•ROS are used as an antimicrobial strategy because of their toxicity to a broad range of microbial pathogens.•ROS exert antimicrobial activity via an induction of oxidative stress in microbial cells.•Oxidative stress caused by ROS leads to microbial DNA damage, and ultimately inducing cell death.
AbstractUnder the load and resistance factor design philosophy used in North America, building codes structures are designed using load and resistance factors calibrated to a target reliability ...level. Despite this, few attempts have been made to calibrate resistance factors for timber connections. A calibration process was carried out for the withdrawal resistance of axially loaded self-tapping screws using a database of test results from across Canada. Two load cases were considered, reflecting load combinations and statistics drawn from the 2015 National Building Code of Canada and from a proposal developed to provide greater consistency in reliability outcomes, and the reliability under each case was determined using the first-order reliability method (FORM). Given the low ductility–brittle nature of withdrawal failures, a resistance factor of φ=0.7 was recommended for a target reliability index of β=4.0. The outcomes will assist in the selection of a resistance factor for self-tapping screws for use in the Canadian timber design standard, CSA O86.
Objective
This study examined the differences in 14-year outcomes of persons with schizophrenia with and without family caregiver(s) in a rural community in China.
Methods
All participants with ...schizophrenia (
n
= 510) aged 15 years and older were identified in a 1994 epidemiological investigation of 123,572 people and followed up in 2004 and 2008 in Xinjin County, Chengdu, China.
Results
Individuals without family caregiver in 1994 had significantly higher rate of homelessness (23.8 %) and lower rate of survival (47.5 %) in 2008 than those with family caregivers (5.1 and 70.9 %). Compared with individuals with family caregivers, those without family caregivers were more likely to be male, live alone, have fewer family members, lower family economic status, lower rates of marriage and complete remission, higher mean scores on PANSS and lower mean score on GAF in 2008. The predictors of participants without family caregiver in 2008 included having a small number of family members at baseline and being male.
Conclusions
The absence of a family caregiver is a predictive factor of poorer long-term outcome of persons with schizophrenia in the rural community. The critical role of family caregiving should be incorporated in the planning and delivering of mental health policies and community-based mental health services.
Excretion of hazardous pharmaceutical residues causes the emergence of toxic potential to the environment. Nanomedicine is commonly associated with nanoparticulate drug delivery to offer the improved ...therapeutic effects at a lower dose for disease treatments. Green chemistry aims to reduce or exclude the utilisation or generation of toxic substances in the design, manufacture and application of chemical products. The use of non-toxic and biodegradable materials in pharmaceutical formulations could minimize the adverse effects of pharmaceutical residues entering the environment in the first place. In our study, bovine serum albumin, a non-toxic, biodegradable and biocompatible protein, was used in the formation of nanoparticulate drug delivery systems. Glucose was used instead of glutaraldehyde to modify albumin nanoparticles for berberine delivery in order to prevent the potential toxicity to humans and the environment. These nanoparticles highly inhibited LX-2 cell growth and exhibited stronger caspase 3 activation at a lower dose when compared with free drug
in vitro
. Nanoparticles with berberine at doses of 1 and 2 μg g
−1
could rescue mice from CCl
4
-induced hepatotoxicity
in vivo
. Green glucose-bovine serum albumin nanoparticles could be safe and effective to deliver berberine at low doses in liver fibrosis treatment.
Use of non-hazardous materials in pharmaceutical formulation avoids the emergence of toxic potential to the environment.
Summary
Compound heterozygotes for sickle haemoglobin (HbS) and hereditary persistence of fetal haemoglobin (HPFH) have high fetal haemoglobin (HbF) levels but few, if any, sickle cell ...disease‐related complications. We studied 30 cases of HbS‐HPFH (types 1 and 2), confirmed by molecular analysis, and report the haematological features and change in HbF levels over time. These results were compared to those of patients with sickle cell anaemia or HbS‐β0 thalassaemia, including a subgroup of patients carrying the XmnI polymorphism, known to be associated with elevated HbF. Among the HbS‐HPFH patients, HbF level was 50–90% during infancy and declined steeply within the first few years of life, stabilizing between ages 3 and 5 years, at approximately 30%. Mean HbF of individuals age 5 or older was 31 ± 3%, average haemoglobin concentration was 130 ± 10 g/l and average mean corpuscular volume (MCV) was 75 ± 4 fl. Univariate and multivariate regression analyses significantly associated HbF with age, haemoglobin concentration, and MCV (P < 0·001). There was a strong inverse association between HbF and age (r = −0·9, P < 0·001). Despite having a much higher HbF level, patients with HbS‐HPFH have a similar age‐related pattern of HbF decline and associations as patients with sickle cell anaemia or HbS‐β0 thalassaemia.
To analyze the effect of white matter lesions in different brain regions on regional cortical glucose metabolism, regional cortical atrophy, and cognitive function in a sample with a broad range of ...cerebrovascular disease and cognitive function.
Subjects (n = 78) were recruited for a study of subcortical ischemic vascular disease (SIVD) and Alzheimer disease (AD) contributions to dementia. A new method was developed to define volumes of interest from high-resolution three-dimensional T1-weighted MR images. Volumetric measures of MRI segmented white matter signal hyperintensities (WMH) in five different brain regions were related to regional PET glucose metabolism (rCMRglc) in cerebral cortex, MRI measures of regional cortical atrophy, and neuropsychological assessment of executive and memory function.
WMH was significantly higher in the prefrontal region compared to the other brain regions. In all subjects, higher frontal and parietal WMH were associated with reduced frontal rCMRglc, whereas occipitotemporal WMH was only marginally associated with frontal rCMRglc. These associations were stronger and more widely distributed in nondemented subjects where reduced frontal rCMRglc was correlated with WMH for all regions measured. In contrast, there was no relationship between WMH in any brain region and rCMRglc in either parietal or occipitotemporal regions. WMHs in all brain regions were associated with low executive scores in nondemented subjects.
The frontal lobes are most severely affected by SIVD. WMHs are more abundant in the frontal region. Regardless of where in the brain these WMHs are located, they are associated with frontal hypometabolism and executive dysfunction.
Summary
Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab‐Indian (AI) HBB (β‐globin gene) haplotype. The phenotype of AI SCD in children was described ...as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital‐based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety‐six per cent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co‐inherited α‐thalassaemia and about one‐third had glucose‐6‐phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F‐cells.
Background
Migrant children refer to rural children who accompany one or both parents to urban area. Empirical evidence showed that compared with their urban counterparts, migrant children had poorer ...developmental, emotional and psychological health.
Method
A sample of 1306 migrant children were recruited to examine the characteristics of migrant children and investigate the effects of identity integration, support and socioeconomic factors (e.g. age, gender, type of school, family socioeconomic status, city type) on their subjective wellbeing.
Results
Children with higher levels of identity integration, social support, family socioeconomic status, who attended public school and who lived in the third‐tiered city of Weihai demonstrated better subjective wellbeing. Social support remained a strong predictor for subjective wellbeing, despite a significant mediating effect of identity integration.
Conclusions
These results highlight the need for policymakers and practitioners alike to address individual factors pertaining to psychological adjustments, as well as social determinants of subjective wellbeing in the context of migration.
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