The relationship between rates of hospitalization for ambulatory care sensitive conditions and local access to primary healthcare in Manitoba First Nations communities: Results from the Innovation in Community-based Primary Healthcare Supporting Transformation in the Health of First Nations in Manitoba (iPHIT) study

ObjectivesThe objective of this study was to assess the performance of models of primary healthcare (PHC) delivered in First Nation and adjacent communities in Manitoba, using hospitalization rates for ambulatory care sensitive conditions (ACSC) as the primary outcome.MethodsWe used generalized estimating equation logistic regression on administrative claims data for 63 First Nations communities from Manitoba (1986–2016) comprising 140,111 people, housed at the Manitoba Centre for Health Policy. We controlled for age, sex, and socio-economic status to describe the relationship between hospitalization rates for ACSC and models of PHC in First Nation communities.ResultsHospitalization rates for acute, chronic, vaccine-preventable, and mental health-related ACSCs have decreased over time in First Nation communities, yet remain significantly higher in First Nations and remote non-First Nations communities as compared with other Manitobans. When comparing different models of care, hospitalization rates were historically higher in communities served by health centres/offices, whether or not supplemented by itinerant medical services. These rates have significantly declined over the past two decades.ConclusionLocal access to a broader complement of PHC services is associated with lower rates of avoidable hospitalization in First Nation communities. The lack of these services in many First Nation communities demonstrates the failure of the current Canadian healthcare system to meet the need of First Nation peoples. Improving access to PHC in all 63 First Nation communities can be expected to result in a reduction in ACSC hospitalization rates and reduce healthcare cost.     

Effects of lead,copper, and zinc on the rat's lactate dehydrogenase in vivo and in vitro

Following subacute intoxication of rats with Pb-, Cu-, and Zn-salts (separately or in mixture) for 5 weeks, the chelating agent D-penicillamine was administered for 3 weeks. In the course of the 3-month experiment, lactate dehydrogenase (LDH) was estimated in serum and in cytoplasmic fraction of the kidney. Pb²⁺ treatment resulted in an increase of LDH activity, Cu²⁺ in a slight decrease, whereas Zn²⁺ had no effect, respectively. Mixture of these metals caused a significant rise in the enzymatic activity. Seven weeks after the stoppage of the administration of toxic substances, altered LDH activity, both in serum and in kidney returned to normal. D-penicillamine treatment was found to accelerate a restoration of the enzyme activity.In the experiments in vitro, Cu²⁺ inhibited significantly the kidney LDH activity, Pb²⁺ and Zn²⁺ being 100- and 400-times less efficient, respectively. Cu²⁺ inhibition was reversed by D-penicillamine, whereas inhibition of LDH by Zn²⁺ or Pb²⁺ was irreversible.     

The association between women’s health information use and health care visits

OBJECTIVE: To determine the effect of the type of information sources used on health services use. METHODS: Population-based random-digit dialing survey of 498 women, between December 1999 and January 2000, on use of health information sources and health visits. RESULTS: After adjustment for sociodemographic and medical factors, use of print health media and computer-based resources was associated with 1.9 and 1.6 more visits, respectively compared to non-use (Regression coefficients 1.9; [95% confidence interval {CI} 0.1, 3.7] and 1.6; [95% CI 0.3, 3.0]). CONCLUSIONS: Print health media and computer-based sources are associated with a higher number of health care visits.     

Effects of exogenous sphinganine, sphingosine, and sphingosine-1-phosphate on relaxation and contraction of porcine thoracic aortic and pulmonary arterial rings.

Fumonisin mycotoxicosis in pigs causes a decrease in mean aortic pressure, an increase in mean pulmonary arterial pressure, and increases in serum concentrations of sphinganine (3.2 microM) and sphingosine (1.4 microM). To determine a causal relationship between the hemodynamic changes and sphingolipid alterations, we examined the in vitro effects of sphinganine, sphingosine, and sphingosine-1-phosphate on porcine aortic and pulmonary arterial rings. Both sphinganine and sphingosine relaxed un-contracted and phenylephrine-contracted aortic rings at > or = 10 microM and > or = 1 microM, respectively. Sphingosine (> or = 10 microM) relaxed un-contracted and phenylephrine-contracted pulmonary arterial rings, whereas sphingosine-1-phosphate (10 microM) contracted pulmonary arterial rings. Sphingosine (3 microM) also impaired the contractile response of pulmonary artery rings to 60 mM KCl. The results suggested that the systemic hypotension caused by fumonisin is mediated, in part, by increases in serum sphinganine and sphingosine concentrations, and the pulmonary hypertension is mediated, in part, by increased sphingosine-1-phosphate concentrations.     

Lack of effect of dietary nucleotide supplementation on erythrocyte 2,3-diphosphoglycerate concentration. A study on preterm neonates.

BACKGROUND: Recently we demonstrated an increased 2,3-diphosphoglycerate (2,3-DPG) erythrocyte concentration in rat pups subjected to nucleotide-enriched artificial feeding. DESIGN: The present study was carried out to test the hypothesis that a possible increase in 2,3-DPG concentration can also be obtained in human neonates who are fed nucleotide-enriched formula. Preterm neonates born or referred to the neonatal intensive care unit of the G. Gaslini Hospital, Genoa University, with a gestational age >30 weeks and <37 weeks were enrolled in our randomized trial. Recruitment took place within 48-72 hours from birth. Only newborns of mothers deciding not to breast-feed were eligible to be randomized for the supplemented group (FN) or non-supplemented group (RF). Breast-fed newborns were considered the control group (C). The study window (for supplementation and blood samples) was restricted to the first two weeks following birth (from the 2nd (t1) to the 16th (t2) day of life). At the end of our study, only 21 neonates were eligible for statistical analysis. RESULTS: The stimulating action of dietary nucleotides on 2,3-DPG concentration failed to be demonstrated; increases in 2,3-DPG concentration that were observed in newborns fed with nucleotide supplemented formula (FN) were comparable to those observed in newborns fed with regular formula (RF) and breast-fed newborns. CONCLUSIONS: The EC recommendation for the amount of nucleotides allowed in formula milk does not seem to be high enough to have positive effects on 2,3-DPG synthesis. Whether this possible 'pharmacological' effect can be achieved by a higher intake of ingested nucleotides and/or a change in the proportions of single nucleotides contained in milk formulas remain interesting end points to be elucidated.     

High-Throughput Screening of FDA-Approved Drug Library Reveals Ixazomib Is a Broad-Spectrum Antiviral Agent against Arboviruses

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome β5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses’ life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.     

Mutant huntingtin impairs immune cell migration in Huntington disease

In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed.