RURAL KENTUCKY’S PHYSICIAN SHORTAGE: Strategies for producing, recruiting and retaining primary care providers within a medically underserved region

Examines the inadequate supply of doctors in outlying regions of the Commonwealth. Through literature review, data analysis, personal interviews and other research methods, the UK Center for Excellence in Rural Health-Hazard study concluded that Kentucky needs an additional 600 primary care physicians in order to adequately meet the health care needs of its residents. The findings appear in the October 2005 Journal of the Kentucky Medical Association

Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation

The abnormal accumulation of the microtubule-binding protein tau is associated with a number of neurodegenerative conditions, and correlates with cognitive decline in Alzheimer's disease. The ubiquitin ligase carboxy terminus of Hsp70-interacting protein (CHIP) and the molecular chaperone Hsp90 are implicated in protein triage decisions involving tau, and have consequently been targeted for therapeutic approaches aimed at decreasing tau burden. Here, we present evidence that CHIP binds, ubiquitinates and regulates expression of histone deacetylase 6 (HDAC6). As the deacetylase for Hsp90, HDAC6 modulates Hsp90 function and determines the favorability of refolding versus degradation of Hsp90 client proteins. Moreover, we demonstrate that HDAC6 levels positively correlate with tau burden, while a decrease in HDAC6 activity or expression promotes tau clearance. Consistent with previous research on Hsp90 clients in cancer, we provide evidence that a loss of HDAC6 activity augments the efficacy of an Hsp90 inhibitor and drives client degradation, in this case tau. Therefore, our current findings not only identify HDAC6 as a critical factor for the regulation of tau levels, but also indicate that a multi-faceted treatment approach could more effectively arrest tau accumulation in disease

Use of facility assessment data to improve reproductive health service delivery in the Democratic Republic of the Congo

Background: Prolonged exposure to war has severely impacted the provision of health services in the Democratic Republic of the Congo (DRC). Health infrastructure has been destroyed, health workers have fled and government support to health care services has been made difficult by ongoing conflict. Poor reproductive health (RH) indicators illustrate the effect that the prolonged crisis in DRC has had on the on the reproductive health (RH) of Congolese women. In 2007, with support from the RAISE Initiative, the International Rescue Committee (IRC) and CARE conducted baseline assessments of public hospitals to evaluate their capacities to meet the RH needs of the local populations and to determine availability, utilization and quality of RH services including emergency obstetric care (EmOC) and family planning (FP). Methods: Data were collected from facility assessments at nine general referral hospitals in five provinces in the DRC during March, April and November 2007. Interviews, observation and clinical record review were used to assess the general infrastructure, EmOC and FP services provided, and the infection prevention environment in each of the facilities. Results: None of the nine hospitals met the criteria for classification as an EmOC facility (either basic or comprehensive). Most facilities lacked any FP services. Shortage of trained staff, essential supplies and medicines and poor infection prevention practices were consistently documented. All facilities had poor systems for routine monitoring of RH services, especially with regard to EmOC. Conclusions: Women's lives can be saved and their well-being improved with functioning RH services. As the DRC stabilizes, IRC and CARE in partnership with the local Ministry of Health and other service provision partners are improving RH services by: 1) providing necessary equipment and renovations to health facilities; 2) improving supply management systems; 3) providing comprehensive competency-based training for health providers in RH and infection prevention; 4) improving referral systems to the hospitals; 5) advocating for changes in national RH policies and protocols; and 6) providing technical assistance for monitoring and evaluation of key RH indicators. Together, these initiatives will improve the quality and accessibility of RH services in the DRC - services which are urgently needed and to which Congolese women are entitled by international human rights law

Multi-Sensor PHD: Construction and Implementation by Space Partitioning

International audienceThe Probability Hypothesis Density (PHD) is a well-known method for single-sensor multi-target tracking problems in a Bayesian framework, but the extension to the multi-sensor case seems to remain a challenge. In this paper, an extension of Mahler's work to the multi-sensor case provides an expression of the true PHD multi-sensor data update equation. Then, based on the configuration of the sensors' fields of view (FOVs), a joint partitioning of both the sensors and the state space provides an equivalent yet more practical expression of the data update equation, allowing a more effective implementation in specific FOV configurations

Acute peripheral immune activation alters cytokine expression and glial activation in the early postnatal rat brain.

BACKGROUND:Neuroinflammation can modulate brain development; however, the influence of an acute peripheral immune challenge on neuroinflammatory responses in the early postnatal brain is not well characterized. To address this gap in knowledge, we evaluated the peripheral and central nervous system (CNS) immune responses to a mixed immune challenge in early postnatal rats of varying strains and sex. METHODS:On postnatal day 10 (P10), male and female Lewis and Brown Norway rats were injected intramuscularly with either a mix of bacterial and viral components in adjuvant, adjuvant-only, or saline. Immune responses were evaluated at 2 and 5 days post-challenge. Cytokine and chemokine levels were evaluated in serum and in multiple brain regions using a Luminex multiplex assay. Multi-factor ANOVAs were used to compare analyte levels across treatment groups within strain, sex, and day of sample collection. Numbers and activation status of astrocytes and microglia were also analyzed in the cortex and hippocampus by quantifying immunoreactivity for GFAP, IBA-1, and CD68 in fixed brain slices. Immunohistochemical data were analyzed using a mixed-model regression analysis. RESULTS:Acute peripheral immune challenge differentially altered cytokine and chemokine levels in the serum versus the brain. Within the brain, the cytokine and chemokine response varied between strains, sexes, and days post-challenge. Main findings included differences in T helper (Th) type cytokine responses in various brain regions, particularly the cortex, with respect to IL-4, IL-10, and IL-17 levels. Additionally, peripheral immune challenge altered GFAP and IBA-1 immunoreactivity in the brain in a strain- and sex-dependent manner. CONCLUSIONS:These findings indicate that genetic background and sex influence the CNS response to an acute peripheral immune challenge during early postnatal development. Additionally, these data reinforce that the developmental time point during which the challenge occurs has a distinct effect on the activation of CNS-resident cells

Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response to Plasmodium yoelii, Limits Malaria-Associated Disruption of Intestinal Barrier Integrity and Reduces Parasite Transmission to Anopheles stephensi

An increase in mast cells (MCs) and MCs mediators has been observed in malaria-associated bacteremia, however, the role of these granulocytes in malarial immunity is poorly understood. Herein, we studied the role of mouse MC protease (Mcpt) 4, an ortholog of human MC chymase, in malaria-induced bacteremia using Mcpt4 knockout (Mcpt4(-/-)) mice and Mcpt4(+/+) C57BL/6J controls, and the non-lethal mouse parasite Plasmodium yoelii yoelii 17XNL. Significantly lower parasitemia was observed in Mcpt4(-/-) mice compared with Mcpt4(+/+) controls by day 10 post infection (PI). Although bacterial 16S DNA levels in blood were not different between groups, increased intestinal permeability to FITC-dextran and altered ileal adherens junction E-cadherin were observed in Mcpt4(-/-) mice. Relative to infected Mcpt4(+/+) mice, ileal MC accumulation in Mcpt4(-/-) mice occurred two days earlier and IgE levels were higher by days 8-10 PI. Increased levels of circulating myeloperoxidase were observed at 6 and 10 days PI in Mcpt4(+/+) but not Mcpt4(-/-) mice, affirming a role for neutrophil activation that was not predictive of parasitemia or bacterial 16S copies in blood. In contrast, early increased plasma levels of TNF-alpha, IL-12p40 and IL-3 were observed in Mcpt4(-/-) mice, while levels of IL-2, IL-10 and MIP1 beta (CCL4) were increased over the same period in Mcpt4(+/+) mice, suggesting that the host response to infection was skewed toward a type-1 immune response in Mcpt4(-/-) mice and type-2 response in Mcpt4(+/+) mice. Spearman analysis revealed an early (day 4 PI) correlation of Mcpt4(-/-) parasitemia with TNF-alpha and IFN-gamma, inflammatory cytokines known for their roles in pathogen clearance, a pattern that was observed in Mcpt4(+/+) mice much later (day 10 PI). Transmission success of P. y. yoelii 17XNL to Anopheles stephensi was significantly higher from infected Mcpt4(-/-) mice compared with infected Mcpt4(+/+) mice, suggesting that Mcpt4 also impacts transmissibility of sexual stage parasites. Together, these results suggest that early MCs activation and release of Mcpt4 suppresses the host immune response to P. y. yoelii 17XNL, perhaps via degradation of TNF-alpha and promotion of a type-2 immune response that concordantly protects epithelial barrier integrity, while limiting the systemic response to bacteremia and parasite transmissibility

Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies.

MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 μM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels. The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or β-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page

Skunk River Review September 1993, vol 5

https://openspace.dmacc.edu/skunkriver/1008/thumbnail.jp

Expressions 1988

https://openspace.dmacc.edu/expressions/1031/thumbnail.jp

Family planning in conflict: results of cross-sectional baseline surveys in three African countries

Background: Despite the serious consequences of conflict for reproductive health, populations affected by conflict and its aftermath face tremendous barriers to accessing reproductive health services, due to insecurity, inadequate numbers of trained personnel and lack of supplies. Family planning is often particularly neglected. Methods: In six conflict-affected areas in Sudan, northern Uganda and the Democratic Republic of Congo, household surveys of married or in-union women of reproductive age were conducted to determine baseline measures of family planning knowledge, attitudes and behaviors regarding contraception. Health facility assessments were carried out to assess baseline measures of family planning services availability. Data were double-entered into CSPro 3.2 and exported to SAS 9.2, which was used to calculate descriptive statistics. The studies' purposes were to guide program activities and to serve as a baseline against which program accomplishments could be measured. Results: Knowledge of modern contraceptive methods was low relative to other sub-Saharan African countries, and use of modern methods was under 4% in four sites; in two sites with prior family planning services it was 12% and 16.2%. From 30% to 40% of women reported they did not want a child within two years, however, and an additional 12% to 35% wanted no additional children, suggesting a clear need for family planning services. The health facilities assessment showed that at most only one-third of the facilities mandated to provide family planning had the necessary staff, equipment and supplies to do so adequately; in some areas, none of the facilities were prepared to offer such services. Conclusions: Family planning services are desired by women living in crisis situations when offered in a manner appropriate to their needs, yet services are rarely adequate to meet these needs. Refugee and internally displaced women must be included in national and donors' plans to improve family planning in Africa