Engaging Critical Access Hospitals in Addressing Rural Substance Use

Substance use is a significant public health issue in rural communities. Despite this fact, substance use treatment services are limited in rural areas and residents suffer from significant barriers to care. Critical Access Hospitals (CAHs), frequently the hubs of local systems of care, can play an important role in addressing substance use disorders. To develop a coordinated response to community substance use issues, CAHs must identify and prioritize local needs, mobilize local resources and partnerships, build local capacity, and screen for substance use among their patients. These activities provide a foundation upon which CAHs and their community partners can address identified local needs by selecting and implementing initiatives to minimize the onset of substance use and related harms (prevention), treat substance use disorders, and help individuals reclaim their lives (recovery). This brief makes the case for why CAHs should address substance use, provides a framework to support CAHs in doing so, describes examples of substance use activities undertaken by CAHs to substantiate the framework, and identifies resources that can be used by State Flex Programs to support CAHs in addressing this important public and population health problem

Closed genome and comparative phylogenetic analysis of the clinical multidrug resistant Shigella sonnei strain 866

Shigella sonneiis responsible for the majority of shigellosis infections in the US with over 500,000 cases reported annually. Here, wepresent the complete genome of the clinical multidrug resistant (MDR) strain 866, which is highly susceptible to bacteriophageinfections. The strain has a circular chromosome of 4.85 Mb and carries a 113 kb MDR plasmid. This IncB/O/K/Z-type plasmid, termedp866, confers resistance to five different classes of antibiotics including ß-lactamase, sulfonamide, tetracycline, aminoglycoside, andtrimethoprim. Comparative analysis of the plasmid architecture and gene inventory revealed that p866 shares its plasmid backbonewith previously described IncB/O/K/Z-typeShigellaspp. andEscherichiacoliplasmids, but is differentiated by the insertion of antibioticresistance cassettes, which we found associated with mobile genetic elements such as Tn3, Tn7, and Tn10. A whole genome-derivedphylogenetic reconstruction showed the evolutionary relationships ofS. sonneistrain 866 and the four establishedShigellaspecies,highlighting the clonal nature ofS. sonnei

A role for tumor necrosis factor-alpha in remodeling the splenic marginal zone during Leishmania donovani infection.

The development of secondary lymphoid organs is a highly regulated process, mediated by tumor necrosis factor (TNF) family cytokines. In contrast, the mechanisms controlling changes in lymphoid architecture that occur during infectious disease are poorly understood. Here we demonstrate that during infection with Leishmania donovani, the marginal zone of mice undergoes extensive remodeling, similar in extent to developmental abnormalities in mice lacking some TNF family cytokines. This process is selective, comprising a dramatic and rapid loss of marginal zone macrophages (MZMs). As a functional consequence, lymphocyte traffic into the white pulp is impaired during chronic leishmaniasis. Significantly, MZMs were preserved in L. donovani-infected B6.TNF-alpha(-/-) mice or mice that received anti-TNF-alpha antibodies, whereas studies in CD8(+) T-cell-deficient mice and in mice lacking functional CD95L, excluded a direct role for either cytotoxic T lymphocyte activity or CD95-mediated apoptosis in this process. Loss of MZMs was independent of parasite burden, yet could be partially prevented by chemotherapy, which in turn reduced endogenous TNF-alpha levels. This is the first report of an infectious agent causing selective and long-lasting changes to the marginal zone via TNF-alpha-mediated mechanisms, and illustrates that those cytokines involved in establishing lymphoid architecture during development, may also play a role in infection-induced lymphoid tissue remodeling

Oligonucleotide Based Magnetic Bead Capture of Onchocerca volvulus DNA for PCR Pool Screening of Vector Black Flies

The absence of infective larvae of Onchocerca volvulus in the black fly vector of this parasite is a major criterion used to certify that transmission has been eliminated in a focus. This process requires screening large numbers of flies. Currently, this is accomplished by screening pools of flies using a PCR-based assay. The number of flies that may be included in each pool is currently limited by the DNA purification process to 50 flies for Latin American vectors and 100 flies for African vectors. Here, we describe a new method for DNA purification that relies upon a specific oligonucleotide to capture and immobilize the parasite DNA on a magnetic bead. This method permits the reliable detection of a single infective larva of O. volvulus in pools containing up to 200 individual flies. The method described here will dramatically improve the efficiency of pool screening of vector black flies, making the process of elimination certification easier and less expensive to implement

De Broglie Wavelength of a Nonlocal Four-Photon

Superposition is one of the most distinct features of quantum theory and has been demonstrated in numerous realizations of Young's classical double-slit interference experiment and its analogues. However, quantum entanglement - a significant coherent superposition in multiparticle systems - yields phenomena that are much richer and more interesting than anything that can be seen in a one-particle system. Among them, one important type of multi-particle experiments uses path-entangled number-states, which exhibit pure higher-order interference and allow novel applications in metrology and imaging such as quantum interferometry and spectroscopy with phase sensitivity at the Heisenberg limit or quantum lithography beyond the classical diffraction limit. Up to now, in optical implementations of such schemes lower-order interference effects would always decrease the overall performance at higher particle numbers. They have thus been limited to two photons. We overcome this limitation and demonstrate a linear-optics-based four-photon interferometer. Observation of a four-particle mode-entangled state is confirmed by interference fringes with a periodicity of one quarter of the single-photon wavelength. This scheme can readily be extended to arbitrary photon numbers and thus represents an important step towards realizable applications with entanglement-enhanced performance.Comment: 19 pages, 4 figures, submitted on November 18, 200

Predicting progression of mild cognitive impairment to dementia using neuropsychological data: a supervised learning approach using time windows

Background: Predicting progression from a stage of Mild Cognitive Impairment to dementia is a major pursuit in current research. It is broadly accepted that cognition declines with a continuum between MCI and dementia. As such, cohorts of MCI patients are usually heterogeneous, containing patients at different stages of the neurodegenerative process. This hampers the prognostic task. Nevertheless, when learning prognostic models, most studies use the entire cohort of MCI patients regardless of their disease stages. In this paper, we propose a Time Windows approach to predict conversion to dementia, learning with patients stratified using time windows, thus fine-tuning the prognosis regarding the time to conversion. Methods: In the proposed Time Windows approach, we grouped patients based on the clinical information of whether they converted (converter MCI) or remained MCI (stable MCI) within a specific time window. We tested time windows of 2, 3, 4 and 5 years. We developed a prognostic model for each time window using clinical and neuropsychological data and compared this approach with the commonly used in the literature, where all patients are used to learn the models, named as First Last approach. This enables to move from the traditional question "Will a MCI patient convert to dementia somewhere in the future" to the question "Will a MCI patient convert to dementia in a specific time window". Results: The proposed Time Windows approach outperformed the First Last approach. The results showed that we can predict conversion to dementia as early as 5 years before the event with an AUC of 0.88 in the cross-validation set and 0.76 in an independent validation set. Conclusions: Prognostic models using time windows have higher performance when predicting progression from MCI to dementia, when compared to the prognostic approach commonly used in the literature. Furthermore, the proposed Time Windows approach is more relevant from a clinical point of view, predicting conversion within a temporal interval rather than sometime in the future and allowing clinicians to timely adjust treatments and clinical appointments.FCT under the Neuroclinomics2 project [PTDC/EEI-SII/1937/2014, SFRH/BD/95846/2013]; INESC-ID plurianual [UID/CEC/50021/2013]; LASIGE Research Unit [UID/CEC/00408/2013

Nrg4 promotes fuel oxidation and a healthy adipokine profile to ameliorate diet-induced metabolic disorders

OBJECTIVE: Brown and white adipose tissue exerts pleiotropic effects on systemic energy metabolism in part by releasing endocrine factors. Neuregulin 4 (Nrg4) was recently identified as a brown fat-enriched secreted factor that ameliorates diet-induced metabolic disorders, including insulin resistance and hepatic steatosis. However, the physiological mechanisms through which Nrg4 regulates energy balance and glucose and lipid metabolism remain incompletely understood. The aims of the current study were: i) to investigate the regulation of adipose Nrg4 expression during obesity and the physiological signals involved, ii) to elucidate the mechanisms underlying Nrg4 regulation of energy balance and glucose and lipid metabolism, and iii) to explore whether Nrg4 regulates adipose tissue secretome gene expression and adipokine secretion. METHODS: We examined the correlation of adipose Nrg4 expression with obesity in a cohort of diet-induced obese mice and investigated the upstream signals that regulate Nrg4 expression. We performed metabolic cage and hyperinsulinemic-euglycemic clamp studies in Nrg4 transgenic mice to dissect the metabolic pathways regulated by Nrg4. We investigated how Nrg4 regulates hepatic lipid metabolism in the fasting state and explored the effects of Nrg4 on adipose tissue gene expression, particularly those encoding secreted factors. RESULTS: Adipose Nrg4 expression is inversely correlated with adiposity and regulated by pro-inflammatory and anti-inflammatory signaling. Transgenic expression of Nrg4 increases energy expenditure and augments whole body glucose metabolism. Nrg4 protects mice from diet-induced hepatic steatosis in part through activation of hepatic fatty acid oxidation and ketogenesis. Finally, Nrg4 promotes a healthy adipokine profile during obesity. CONCLUSIONS: Nrg4 exerts pleiotropic beneficial effects on energy balance and glucose and lipid metabolism to ameliorate obesity-associated metabolic disorders. Biologic therapeutics based on Nrg4 may improve both type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in patients

Alcohol-related hypoglycemia in rural Uganda: socioeconomic and physiologic contrasts

Hypoglycemia is a rare but important complication seen in patients who present with alcohol intoxication. In a study by Marks and Teale, less than one percent of people with alcohol intoxication who presented to an American emergency department were hypoglycemic [1]. It is even more rare to see an intoxicated patient, who had been eating appropriately prior to or during the intoxication, present in a hypoglycemic coma. However, our analysis of the first 500 patients seen in a newly opened five-bed Emergency Department (ED) at Nyakibale Karoli Lwanga Hospital in rural southwestern Uganda, revealed multiple intoxicated patients who presented in hypoglycemic coma within hours of eating a full meal. Three of these cases are summarized and discussed below