Vascular Response to Spreading Depolarization Predicts Stroke Outcome

Background: Cortical spreading depolarization (CSD) is a massive neuro-glial depolarization wave, which propagates across the cerebral cortex. In stroke, CSD is a necessary and ubiquitous mechanism for the development of neuronal lesions that initiates in the ischemic core and propagates through the penumbra extending the tissue injury. Although CSD propagation induces dramatic changes in cerebral blood flow, the vascular responses in different ischemic regions and their consequences on reperfusion and recovery remain to be defined. Methods: Ischemia was performed using the thrombin model of stroke and reperfusion was induced by r-tPA (recombinant tissue-type plasminogen activator) administration in mice. We used in vivo electrophysiology and laser speckle contrast imaging simultaneously to assess both electrophysiological and hemodynamic characteristics of CSD after ischemia onset. Neurological deficits were assessed on day 1, 3, and 7. Furthermore, infarct sizes were quantified using 2,3,5-triphenyltetrazolium chloride on day 7. Results: After ischemia, CSDs were evidenced by the characteristic propagating DC shift extending far beyond the ischemic area. On the vascular level, we observed 2 types of responses: some mice showed spreading hyperemia confined to the penumbra area (penumbral spreading hyperemia) while other showed spreading hyperemia propagating in the full hemisphere (full hemisphere spreading hyperemia). Penumbral spreading hyperemia was associated with severe stroke-induced damage, while full hemisphere spreading hyperemia indicated beneficial infarct outcome and potential viability of the infarct core. In all animals, thrombolysis with r-tPA modified the shape of the vascular response to CSD and reduced lesion volume. Conclusions: Our results show that different types of spreading hyperemia occur spontaneously after the onset of ischemia. Depending on their shape and distribution, they predict severity of injury and outcome. Furthermore, our data show that modulating the hemodynamic response to CSD may be a promising therapeutic strategy to attenuate stroke outcome

Achieving the Millennium Development Goals: Does Mental Health Play a Role?

Miranda and Patel argue that mental disorders are among the most important causes of disability and premature mortality in developing countries

Guidance for Evidence-Informed Policies about Health Systems: Rationale for and Challenges of Guidance Development

In the first paper in a three-part series on health systems guidance, Xavier Bosch-Capblanch and colleagues examine how guidance is currently formulated in low- and middle-income countries, and the challenges to developing such guidance

Human resources for health planning and management in the Eastern Mediterranean region: facts, gaps and forward thinking for research and policy

BACKGROUND: The early decades of the 21(st )century are considered to be the era of human resources for health (HRH). The World Health Report (WHR) 2006 launched the Health Workforce Decade (2006–2015), with high priority given for countries to develop effective workforce policies and strategies. In many countries in the Eastern Mediterranean Region (EMR), particularly those classified as Low and Low-Middle Income Countries (LMICs), the limited knowledge about the nature, scope, composition and needs of HRH is hindering health sector reform. This highlights an urgent need to understand the current reality of HRH in several EMR countries. The objectives of this paper are to: (1) lay out the facts on what we know about the HRH for EMR countries; (2) generate and interpret evidence on the relationship between HRH and health status indicators for LMICs and middle and high income countries (MHICs) in the context of EMR; (3) identify and analyze the information gaps (i.e. what we do not know) and (4) provide forward thinking by identifying priorities for research and policy. METHODS: The variables used in the analysis were: nurse and physician density, gross national income, poverty, female literacy, health expenditure, Infant Mortality Rate (IMR), Under 5 Mortality Rate (U5MR), Maternal Mortality Rate (MMR) and Life Expectancy (LE). Univariate (charts), bivariate (Pearson correlation) and multivariate analysis (linear regression) was conducted using SPSS 14.0, besides a synthesis of HRH literature. RESULTS: Results demonstrate the significant disparities in physician and nurse densities within the EMR, particularly between LMICs and MHICs. Besides this, significant differences exist in health status indicators within the EMR. Results of the Pearson correlation revealed that physician and nurse density, as well as female literacy in EMR countries were significantly correlated with lower mortality rates and higher life expectancy. Results of the regression analysis for both LMICs and MHICs reveal that physician density is significantly associated with all health indicators for both income groups. Nurse density was found to be significantly associated with lower MMR for the two income groups. Female literacy is notably related to lower IMR and U5MR for both income groups; and only with MMR and LE in LMICs. Health expenditure is significantly associated with lower IMR and U5MR only for LMICs. Based on results, gap analysis and the literature synthesis, information gaps and priorities were identified. CONCLUSION: The implication of the results discussed in this paper will help EMR countries, particularly LMICs, determine priorities to improve health outcomes and achieve health-related Millenium Development Goals

Leptomeningeal collaterals regulate reperfusion in ischemic stroke

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet unknown functions. Utilizing a thrombin-based mouse model of stroke and the gold standard fibrinolytic treatment rt-PA, we here show that LMCs play a critical role in preserving vascular function in ischemic territories. We applied laser speckle contrast imaging, ultrafast ultrasound, and two-photon microscopy, to show that after thrombolysis, LMCs allow for gradual reperfusion resulting in small infarcts. On the contrary, in mice with poor LMCs, distal segments of recanalized arteries collapse and deleterious hyperemia causes hemorrhage and mortality. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for gradual reperfusion of ischemic tissues after stroke

Leptomeningeal collaterals regulate reperfusion in ischemic stroke and rescue the brain from futile recanalization.

Recanalization is the mainstay of ischemic stroke treatment. However, even with timely clot removal, many stroke patients recover poorly. Leptomeningeal collaterals (LMCs) are pial anastomotic vessels with yet-unknown functions. We applied laser speckle imaging, ultrafast ultrasound, and two-photon microscopy in a thrombin-based mouse model of stroke and fibrinolytic treatment to show that LMCs maintain cerebral autoregulation and allow for gradual reperfusion, resulting in small infarcts. In mice with poor LMCs, distal arterial segments collapse, and deleterious hyperemia causes hemorrhage and mortality after recanalization. In silico analyses confirm the relevance of LMCs for preserving perfusion in the ischemic region. Accordingly, in stroke patients with poor collaterals undergoing thrombectomy, rapid reperfusion resulted in hemorrhagic transformation and unfavorable recovery. Thus, we identify LMCs as key components regulating reperfusion and preventing futile recanalization after stroke. Future therapeutic interventions should aim to enhance collateral function, allowing for beneficial reperfusion after stroke

Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population

BackgroundTo better understand the associations between a history of tobacco use and survival outcomes, cigarette use was prospectively surveyed in 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24).MethodsKaplan–Meier and Cox models explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS).ResultsCigarette use duration, timing, and intensity were significant predictors for all outcomes in univariate analysis. Never smoking and pack‐years were not significantly associated with outcomes after adjustment for prognostic factors, such as stage, comorbidities, and human papillomavirus (HPV) status, which were strongly associated with clinical outcomes.ConclusionThe findings confirm the association between smoking history and survival and the importance of clinical variables in evaluating smoking as a prognostic factor. Timing, intensity, and duration of cigarette use should be considered with other prognostic factors when considering risk stratification for treatment planning. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1810–1820, 2016Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134806/1/hed24515.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134806/2/hed24515_am.pd

The health workforce crisis in TB control: a report from high-burden countries

BACKGROUND: Human resources (HR) constraints have been reported as one of the main barriers to achieving the 2005 global tuberculosis (TB) control targets in 18 of the 22 TB high-burden countries (HBCs); consequently we try to assess the current HR available for TB control in HBCs. METHODS: A standard questionnaire designed to collect information on staff numbers, skills, training activities and current staff shortages at different health service levels was sent to national TB control programme managers in all HBCs. RESULTS: Nineteen HBCs (86%) replied, and 17 (77%) followed the questionnaire format to provide data. Complete information on staff numbers at all service levels was available from nine countries and data on skill levels and training were complete in six countries. Data showed considerable variations in staff numbers, proportions of trained staff, length of courses and quality of training activities. Eleven HBCs had developed training materials, many used implementation guidelines for training and only three used participatory educational methods. Two countries reported shortages of staff at district health facility level, whereas 14 reported shortages at central level. There was no apparent association between reported staff numbers (and skills) and the country's TB burden or current case detection rates (CDR). CONCLUSION: There were few readily available data on HR for TB control in HBCs, particularly in the larger ones. The great variations in staff numbers and the poor association between information on workforce, proportion of trained staff, and length and quality of courses suggested a lack of valid information and/or poor data reliability. There is urgent need to support HBCs to develop a comprehensive HR strategy involving short-term and long-term HR development plans and strengthening their HR planning and management capabilities

Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD