Improving health-care quality in resource-poor settings

Improvements in health-care quality can contribute to healthier populations. However, many global and national health strategies are not sufficiently considering the issues of measuring and improving health-care quality in low-resource settings.1 The barriers to delivering high-quality care are often similar across different health systems. However, the extent and mechanisms through which these barriers affect quality improvement interventions may be different in resource-poor settings.2 Investments in health systems strengthening without continuous quality improvement is thought to be a useless effort.3 Conversely, only focusing on quality improvement in a resource-poor context without engaging the broader health system for support is of limited value. Hence, both areas must be improved simultaneously

Maternal Fish Consumption and Infant Birth Size and Gestation: New York State Angler Cohort Study

BACKGROUND: The scientific literature poses a perplexing dilemma for pregnant women with respect to the consumption of fish from natural bodies of water. On one hand, fish is a good source of protein, low in fat and a rich source of other nutrients all of which have presumably beneficial effects on developing embryos and fetuses. On the other hand, consumption of fish contaminated with environmental toxicants such as polychlorinated biphenyls (PCBs) has been associated with decrements in gestation and birth size. METHODS: 2,716 infants born between 1986–1991 to participants of the New York State Angler Cohort Study were studied with respect to duration of maternal consumption of contaminated fish from Lake Ontario and its tributaries and gestation and birth size. Hospital delivery records (maternal and newborn) were obtained for 92% of infants for the ascertainment of gestation (weeks), birth size (weight, length, chest, and head circumference) and other known determinants of fetal growth (i.e., maternal parity, history of placental infarction, uterine bleeding, pregnancy loss or cigarette smoking and infant's race, sex and presence of birth defect). Duration of maternal fish consumption prior to the index infant's birth was categorized as: none; 1–2, 3–7, 8+ years, while birth weight (in grams), birth length (in centimeters), and head and chest circumference (in centimeters) were left as continuous variables in multiple linear regression models. Birth size percentiles, ponderal indices and head to chest circumference ratios were computed to further assess proportionality and birth size in relation to gestational age. RESULTS: Analysis of variance failed to identify significant mean differences in gestation or any measure of birth size in relation to duration of maternal lifetime fish consumption. Multiple linear regressions identified gestational age, male sex, number of daily cigarettes, parity and placental infarction, as significant determinants of birth size. CONCLUSIONS: The results support the absence of an adverse relation between Lake Ontario fish consumption and reduced birth size as measured by weight, length and head circumference. Biological determinants and maternal cigarette smoking during pregnancy remain important determinants of birth size

Nocturia, Sleep-Disordered Breathing, and Cardiovascular Morbidity in a Community-Based Cohort

Background: Nocturia has been independently associated with cardiovascular morbidity and all-cause mortality, but such studies did not adjust for sleep-disordered breathing (SDB), which may have mediated such a relationship. Our aims were to determine whether an association between nocturia and cardiovascular morbidity exists that is independent of SDB. We also determined whether nocturia is independently associated with SDB. Methodology/Principal Findings: In order to accomplish these aims we performed a cross-sectional analysis of the Sleep Heart Health Study that contained information regarding SDB, nocturia, and cardiovascular morbidity in a middle-age to elderly community-based population. In 6342 participants (age 63±11 [SD] years, 53% women), after adjusting for known confounders such as age, body mass index, diuretic use, diabetes mellitus, alpha-blocker use, nocturia was independently associated with SDB (measured as Apnea Hypopnea index >15 per hour; OR 1.3; 95%CI, 1.2-1.5). After adjusting for SDB and other known confounders, nocturia was independently associated with prevalent hypertension (OR 1.23; 95%CI 1.08-1.40; P = 0.002), cardiovascular disease (OR 1.26; 95%CI 1.05-1.52; P = 0.02) and stroke (OR 1.62; 95%CI 1.14-2.30; P = 0.007). Moreover, nocturia was also associated with adverse objective alterations of sleep as measured by polysomnography and self-reported excessive daytime sleepiness (P<0.05). Conclusions/Significance: Nocturia is independently associated with sleep-disordered breathing. After adjusting for SDB, there remained an association between nocturia and cardiovascular morbidity. Such results support screening for SDB in patients with nocturia, but the mechanisms underlying the relationship between nocturia and cardiovascular morbidity requires further study. MeSH terms: Nocturia, sleep-disordered breathing, obstructive sleep apnea, sleep apnea, polysomnography, hypertension

Phycodnavirus Potassium Ion Channel Proteins Question the Virus Molecular Piracy Hypothesis

Phycodnaviruses are large dsDNA, algal-infecting viruses that encode many genes with homologs in prokaryotes and eukaryotes. Among the viral gene products are the smallest proteins known to form functional K+ channels. To determine if these viral K+ channels are the product of molecular piracy from their hosts, we compared the sequences of the K+ channel pore modules from seven phycodnaviruses to the K+ channels from Chlorella variabilis and Ectocarpus siliculosus, whose genomes have recently been sequenced. C. variabilis is the host for two of the viruses PBCV-1 and NY-2A and E. siliculosus is the host for the virus EsV-1. Systematic phylogenetic analyses consistently indicate that the viral K+ channels are not related to any lineage of the host channel homologs and that they are more closely related to each other than to their host homologs. A consensus sequence of the viral channels resembles a protein of unknown function from a proteobacterium. However, the bacterial protein lacks the consensus motif of all K+ channels and it does not form a functional channel in yeast, suggesting that the viral channels did not come from a proteobacterium. Collectively, our results indicate that the viruses did not acquire their K+ channel-encoding genes from their current algal hosts by gene transfer; thus alternative explanations are required. One possibility is that the viral genes arose from ancient organisms, which served as their hosts before the viruses developed their current host specificity. Alternatively the viral proteins could be the origin of K+ channels in algae and perhaps even all cellular organisms

Demethylation of the Coding Region Triggers the Activation of the Human Testis-Specific PDHA2 Gene in Somatic Tissues

Human PDHA2 is a testis-specific gene that codes for the E1α subunit of Pyruvate Dehydrogenase Complex (PDC), a crucial enzyme system in cell energy metabolism. Since activation of the PDHA2 gene in somatic cells could be a new therapeutic approach for PDC deficiency, we aimed to identify the regulatory mechanisms underlying the human PDHA2 gene expression. Functional deletion studies revealed that the −122 to −6 promoter region is indispensable for basal expression of this TATA-less promoter, and suggested a role of an epigenetic program in the control of PDHA2 gene expression. Indeed, treatment of SH-SY5Y cells with the hypomethylating agent 5-Aza-2′-deoxycytidine (DAC) promoted the reactivation of the PDHA2 gene, by inducing the recruitment of the RNA polymerase II to the proximal promoter region and the consequent increase in PDHA2 mRNA levels. Bisulfite sequencing analysis revealed that DAC treatment induced a significant demethylation of the CpG island II (nucleotides +197 to +460) in PDHA2 coding region, while the promoter region remained highly methylated. Taken together with our previous results that show an in vivo correlation between PDHA2 expression and the demethylation of the CpG island II in testis germ cells, the present results show that internal methylation of the PDHA2 gene plays a part in its repression in somatic cells. In conclusion, our data support the novel finding that methylation of the PDHA2 coding region can inhibit gene transcription. This represents a key mechanism for absence of PDHA2 expression in somatic cells and a target for PDC therapy

Shock wave lithotripsy, for the treatment of kidney stones, results in changes to routine blood tests and novel biomarkers: a prospective clinical pilot-study

From Springer Nature via Jisc Publications RouterHistory: received 2020-04-21, accepted 2020-05-27, registration 2020-05-27, pub-electronic 2020-06-01, online 2020-06-01, collection 2020-12Publication status: PublishedFunder: Institute of Biomedical Science; doi: http://dx.doi.org/10.13039/501100000825Abstract: Background: The number of patients undergoing shock wave lithotripsy (SWL) for kidney stones is increasing annually, and as such the development of post-operative complications, such as haematuria and acute kidney injury (AKI) following SWL, is likely to increase. The aim of the study was to evaluate changes in routine blood and novel biomarkers following SWL, for the treatment of kidney stones. Methods: Twelve patients undergoing SWL for solitary unilateral kidney stones were recruited. From patients (8 males and 4 females) aged between 31 and 72 years (median 43 years), venous blood samples were collected pre-operatively (baseline), at 30, 120 and 240 min post-operatively. Routine blood tests were performed using a Sysmex XE-5000, and Beckman Coulter AU5800 and AU680 analysers. NGAL, IL-18, IL-6, TNF-α, IL-10 and IL-8 concentrations were determined using commercially available ELISA kits. Results: Significant (p ≤ 0.05) changes were observed in several blood parameters following SWL. NGAL concentration significantly increased, with values peaking at 30 min post-treatment (p = 0.033). Although IL-18 concentration increased, these changes were not significant (p = 0.116). IL-6 revealed a statistically significant rise from pre-operative up to 4 h post-operatively (p 0.05). Conclusions: Changes to routine blood tests and specific biomarkers, in the future, may be more useful for clinicians. In turn, identification of a panel of biomarkers could provide valuable data on “normal” physiological response after lithotripsy. Ultimately, studies could be expanded to identify or predict those patients at increased risk of developing post-operative complications, such as acute kidney injury or. These studies, however, need validating involving larger cohorts

The Cognitive Role of the Globus Pallidus interna; Insights from Disease States.

The motor symptoms of both Parkinson's disease and focal dystonia arise from dysfunction of the basal ganglia, and are improved by pallidotomy or deep brain stimulation of the Globus Pallidus interna (GPi). However, Parkinson's disease is associated with a greater degree of basal ganglia-dependent learning impairment than dystonia. We attempt to understand this observation in terms of a comparison of the electrophysiology of the output of the basal ganglia between the two conditions. We use the natural experiment offered by Deep Brain Stimulation to compare GPi local field potential responses in subjects with Parkinson's disease compared to subjects with dystonia performing a forced-choice decision-making task with sensory feedback. In dystonic subjects, we found that auditory feedback was associated with the presence of high gamma oscillations nestled on a negative deflection, morphologically similar to sharp wave ripple complexes described in human rhinal cortex. These were not present in Parkinson's disease subjects. The temporal properties of the high gamma burst were modified by incorrect trial performance compared to correct trial performance. Both groups exhibited a robust low frequency response to 'incorrect' trial performance in dominant GPi but not non-dominant GPi at theta frequency. Our results suggest that cellular processes associated with striatum-dependent memory function may be selectively impaired in Parkinson's disease even if dopaminergic drugs are administered, but that error detection mechanisms are preserved

A primary care database study of asthma among patients with and without opioid use disorders

Substance misuse is associated with poor asthma outcome and death. People with opioid use disorder (OUD) may be at particular risk, however, there have been no case-control studies of asthma care and outcomes in this patient group. A primary care database study of patients with asthma aged 16–65 years was conducted using a matched case-control methodology. The dataset comprised 275,151 adults with asthma, of whom 459 had a clinical code indicating a lifetime history of OUD. Cases with a history of OUD were matched to controls 1:3 by age, gender, smoking status and deprivation index decile. Attendance at annual review (30%) and for immunisation (25%) was poor amongst the overall matched study population (N = 1832). Compared to matched controls, cases were less likely to have attended for asthma review during the previous 12 months (OR = 0.60, 95% CI 0.45–0.80) but had similar immunisation rates. Higher rates of ICS (OR = 1.50, 1.13–1.98) and oral prednisolone use (OR = 1.71, 1.25–2.40) were seen amongst those with a history of OUD and 7.2% had a concurrent diagnosis of COPD (OR = 1.86, 1.12–2.40). We found that people with asthma and a history of OUD have worse outcomes on several commonly measured metrics of asthma care. Further research is required to identify reasons for these findings, the most effective strategies to help this vulnerable group access basic asthma care, and to better understand long-term respiratory outcomes

Early Adverse Events, HPA Activity and Rostral Anterior Cingulate Volume in MDD

Prior studies have independently reported associations between major depressive disorder (MDD), elevated cortisol concentrations, early adverse events and region-specific decreases in grey matter volume, but the relationships among these variables are unclear. In the present study, we sought to evaluate the relationships between grey matter volume, early adverse events and cortisol levels in MDD.Grey matter volume was compared between 19 controls and 19 individuals with MDD using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire. Subjects also provided salivary cortisol samples. Depressed patients showed decreased grey matter volume in the rostral ACC as compared to controls. Rostral ACC volume was inversely correlated with both cortisol and early adverse events.These findings suggest a key relationship between ACC morphology, a history of early adverse events and circulating cortisol in the pathophysiology of MDD

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques