Environmental enteric dysfunction is associated with carnitine deficiency and altered fatty acid oxidation

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. We measured serum metabolite...

Cancer-associated thrombosis: prevention and treatment

PubMed Central

Brose, K.M.J.; Lee, A.Y.Y.

2008-01-01

Patients with cancer are at high risk to develop venous thromboembolism, and they are also more likely to develop complications from anticoagulant treatment. Because little research has focused on the oncology population to date, the optimal methods of prophylaxis and treatment remain uncertain in some clinical situations. Currently, low molecular weight heparin and warfarin are the most frequently used pharmacologic agents; however, they have their limitations. Other therapeutic options, such as inferior caval filters, are poorly studied and remain controversial. A summary of the most recent evidence on the prevention and treatment of venous thromboembolism in cancer patients is presented here. PMID:18231650

Promoting Developmental Research: A Challenge for African Universities

ERIC Educational Resources Information Center

Mohamedbhai, Goolam

2014-01-01

There are two well-known and often-quoted facts about Sub-Saharan Africa. One is that, in spite of significant progress made in recent years, Africa remains the least developed region in the world and is unlikely to achieve all the Millennium Development Goals by 2015. The other is that Africa fares very poorly in terms of research and innovation;…

Development of an Automatic Judging System for Determining the Difficulty Levels of English Audio Materials

ERIC Educational Resources Information Center

Okazaki, Hironobu; Watanabe, Kanji; Hashimoto, Shinichi; Suzuki, Mitsuko; Fukuda, Eri; Kido, Kazuhiko

2014-01-01

Okazaki and Nitta (2005) developed an e-learning program called PLIMA (your Personal LIstening Manager) which focuses on improving poor phonological analysis such as the inability to hear liaison or unstressed sounds. However, the fact remains that there are certain types of liaison sounds that learners do not catch, and some types they do. This…

The Need for a Black Financial Infrastructure for Black Economic Development.

ERIC Educational Resources Information Center

Lloyd, R. Grann

1979-01-01

The underdevelopment of Blacks in the United States is due primarily to the lack of equal educational opportunities and to the denial of opportunity for on-the-job experience and training. If it is true that most capital formation must come from the savings of the developing group, the Black economy is likely to remain poor. (Author/RLV)

How much more exposed are the poor to natural disasters? Global and regional measurement.

PubMed

Kim, Namsuk

2012-04-01

This paper proposes a simple indicator to measure the exposure to natural disasters for the poor and non-poor population, in order to assess the global and regional trend of natural hazard and poverty. Globally, poor people are two times more exposed to natural disasters than the non-poor in the twenty-first century. The time trend varies across regions, with poor people in East Asia and Pacific being most exposed to natural disasters, followed by those in South Asia and Sub-Saharan Africa. The change of exposure measure over time is decomposed into two factors: a pure exposure change, which could be fuelled by climate change; and a concentration component. The result shows that the total net increase of exposure between the 1970s and the 2000s is driven significantly by the increased concentration of the poor (26 per cent) in disaster-prone areas, whereas the contribution of that factor remains very small for the non-poor (six per cent). © 2012 The Author(s). Disasters © Overseas Development Institute, 2012.

Poverty and access to health care in developing countries.

PubMed

Peters, David H; Garg, Anu; Bloom, Gerry; Walker, Damian G; Brieger, William R; Rahman, M Hafizur

2008-01-01

People in poor countries tend to have less access to health services than those in better-off countries, and within countries, the poor have less access to health services. This article documents disparities in access to health services in low- and middle-income countries (LMICs), using a framework incorporating quality, geographic accessibility, availability, financial accessibility, and acceptability of services. Whereas the poor in LMICs are consistently at a disadvantage in each of the dimensions of access and their determinants, this need not be the case. Many different approaches are shown to improve access to the poor, using targeted or universal approaches, engaging government, nongovernmental, or commercial organizations, and pursuing a wide variety of strategies to finance and organize services. Key ingredients of success include concerted efforts to reach the poor, engaging communities and disadvantaged people, encouraging local adaptation, and careful monitoring of effects on the poor. Yet governments in LMICs rarely focus on the poor in their policies or the implementation or monitoring of health service strategies. There are also new innovations in financing, delivery, and regulation of health services that hold promise for improving access to the poor, such as the use of health equity funds, conditional cash transfers, and coproduction and regulation of health services. The challenge remains to find ways to ensure that vulnerable populations have a say in how strategies are developed, implemented, and accounted for in ways that demonstrate improvements in access by the poor.

Dysarthria and Friedreich's Ataxia: What Can Intelligibility Assessment Tell Us?

ERIC Educational Resources Information Center

Blaney, Bronagh; Hewlett, Nigel

2007-01-01

Background: Friedreich's ataxia is one of the most common hereditary disorders of the nervous system. Dysarthria is a pervasive symptom of Friedreich's ataxia, yet the clinical presentation of speech symptoms remains poorly understood, leaving clinicians without the evidence required to develop therapy interventions. Aims: The research reported…

What's new in perioperative nutritional support?

PubMed

Awad, Sherif; Lobo, Dileep N

2011-06-01

To highlight recent developments in the field of perioperative nutritional support by reviewing clinically pertinent English language articles from October 2008 to December 2010, that examined the effects of malnutrition on surgical outcomes, optimizing metabolic function and nutritional status preoperatively and postoperatively. Recognition of patients with or at risk of malnutrition remains poor despite the availability of numerous clinical aids and clear evidence of the adverse effects of poor nutritional status on postoperative clinical outcomes. Unfortunately, poor design and significant heterogeneity remain amongst many studies of nutritional interventions in surgical patients. Patients undergoing elective surgery should be managed within a multimodal pathway that includes evidence-based interventions to optimize nutritional status perioperatively. The aforementioned should include screening patients to identify those at high nutritional risk, perioperative immuno-nutrition, minimizing 'metabolic stress' and insulin resistance by preoperative conditioning with carbohydrate-based drinks, glutamine supplementation, minimal access surgery and enhanced recovery protocols. Finally gut-specific nutrients and prokinetics should be utilized to improve enteral feed tolerance thereby permitting early enteral feeding. An evidence-based multimodal pathway that includes interventions to optimize nutritional status may improve outcomes following elective surgery.

Individualized controlled ovarian stimulation in expected poor-responders: an update.

PubMed

Haahr, Thor; Esteves, Sandro C; Humaidan, Peter

2018-03-09

Controlled ovarian stimulation with subsequent multi-follicular development continues to be a keystone in ART. Evidence supports an individualized approach to ovarian stimulation, usually involving combinations of ovarian reserve tests, body mass index and age to tailor the exogenous gonadotropin dose, and potentially adjuvant treatment aiming for high safety and a shortening of time to live birth. While stimulation and trigger concepts have been developed successfully in normo- and hyperresponder patients, the poor responder patient remains difficult to manage. However, recent advances in definition and classification of the expected poor ovarian responder patient might enable a more accurate and clinically useful interpretation of new treatment concepts in a more homogenous study population. In the present review, we discuss the classification of the expected poor ovarian responder patient as well as clinically useful measurements of efficacy for controlled ovarian stimulation, and finally, we discuss the evidence for clinical management of patients with expected poor ovarian response, including adjuvant treatments such as growth hormone, androgens, and LH activity.In conclusion, the best available evidence supports that the treatment of the expected poor ovarian response patient should be individualized in all steps of ART, including the choice of GnRH analogue, the gonadotropin type and dose, ovulation trigger, and the possible use of adjuvant therapies.

Poverty and behavior problems trajectories from 1.5 to 8 years of age: Is the gap widening between poor and non-poor children?

PubMed

Mazza, Julia Rachel S E; Boivin, Michel; Tremblay, Richard E; Michel, Gregory; Salla, Julie; Lambert, Jean; Zunzunegui, Maria Victoria; Côté, Sylvana M

2016-08-01

Poverty has been associated with high levels of behavior problems across childhood, yet patterns of associations over time remain understudied. This study aims: (a) to examine whether poverty predicts changes in behavior problems between 1.5 and 8 years of age; (b) to estimate potential selection bias for the observed associations. We used the 1998-2006 waves of the Quebec Longitudinal Study of Child Development (N = 2120). Main outcomes were maternal ratings of hyperactivity, opposition and physical aggression from 1.5 to 8 years of age. Linear mixed-effects models were used to assess the longitudinal association between poverty and behavior problems. Models were re-estimated adjusting for wave nonresponse and using multiple imputation to account for attrition. Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. Poverty predicted hyperactivity and opposition in a time dependent manner. Hyperactivity [Bpoverty*age = 0.052; CI 95 % (0.002; 0.101)] and opposition [Bpoverty*age = 0.049; CI 95 % (0.018; 0.079)] increased at a faster rate up to age 5 years, and then decreased at a slower rate for poor than non-poor children. Physical aggression decreased at a steady rate over time for all children [Bpoverty*age = -0.030; p = 0.064). Estimates remained similar when accounting for attrition. Poverty predicted higher levels of behavior problems between 1.5 and 8 years of age. The difference between poor and non-poor children was stable over time for physical aggression, but increased with age for hyperactivity and opposition. Attrition among poor children did not compromise the validity of results.

From the inside out: a new species of armoured catfish Corydoras with the description of poorly-explored character sources (Teleostei, Siluriformes, Callichthyidae).

PubMed

Espíndola, V C; Tencatt, L F C; Pupo, F M; Villa-Verde, L; Britto, M R

2018-05-01

A new species of the armoured catfish genus Corydoras is described from the Xingu-Tapajos ecoregion, Brazilian Amazon. The new species can be distinguished from its congeners by having the following combination of features: short mesethmoid, with anterior tip poorly developed, smaller than 50% of bone length; posterior margin of pectoral spine with serrations directed towards spine tip or perpendicularly oriented; infraorbital 2 only in contact with sphenotic; ventral laminar expansion of infraorbital 1 poorly or moderately developed; flank midline covered by small dark brown or black saddles with similar size to remaining markings on body; relatively larger, scarcer and more sparsely distributed dark brown or black spots on body; absence of stripe on flank midline; caudal fin with conspicuous dark brown or black spots along its entire surface; slender body; and strongly narrow frontals. A more comprehensive description of poorly-explored internal character sources, such as the gross morphology of the brain, Weberian apparatus and swimbladder capsule elements is presented. © 2018 The Fisheries Society of the British Isles.

Ocular melanoma: an overview of the current status

PubMed Central

Jovanovic, Predrag; Mihajlovic, Marija; Djordjevic-Jocic, Jasmina; Vlajkovic, Slobodan; Cekic, Sonja; Stefanovic, Vladisav

2013-01-01

Ocular melanoma is the second most common type of melanoma after cutaneous and the most common primary intraocular malignant tumor in adults. Large majority of ocular melanomas originate from uvea, while conjunctival melanomas are far less frequent. Incidence of uveal melanoma has remained stable over last three decades. Diagnosis is in most cases established by clinical examination with great accuracy. Local treatment of uveal melanoma has improved, with increased use of conservative methods and preservation of the eye, but survival rates have remained unchanged. Recent advances in cytogenetics and genetics enhanced prognostication and enabled to determine tumors with high metastatic potential. However, due to lack of effective systemic therapy, prognosis of patients with metastasis remains poor and metastatic disease remains the leading cause of death among patients with uveal melanoma. Conjunctival melanoma is rare, but its incidence is increasing. It mostly occurs among white adults. In majority of cases it originates from preceding primary acquired melanosis. Current standard treatment for conjunctival melanoma is wide local excision with adjuvant therapy, including brachytherapy, cryotherapy and topical application of chemotherapeutic agent. Rarity of this tumor limits conduction of controlled trials to define the best treatment modality. As well as for uveal melanoma, prognosis of patients with metastasis is poor because there is no effective systemic therapy. Better understanding of underlying genetic and molecular abnormalities implicated in development and progression of ocular melanomas provides a great opportunity for development of targeted therapy, which will hopefully improve prognosis of patients with metastatic disease. PMID:23826405

Probing crystallinity of never-dried wood cellulose with Raman spectroscopy

Treesearch

Umesh P. Agarwal; Sally A. Ralph; Richard S. Reiner; Carlos Baez

2016-01-01

The structure of wood cell wall cellulose in its native state remains poorly understood, limiting the progress of research and development in numerous areas, including plant science, biofuels, and nanocellulose based materials. It is generally believed that cellulose in cell wall microfibrils has both crystalline and amorphous regions. However, there is evidence that...

Seriously Considering Design in Educational Games

ERIC Educational Resources Information Center

Gaydos, Matthew

2015-01-01

Research suggests that well-designed games can be good for learning under the right conditions. How such games are designed remains poorly understood, as studies have focused more on "whether" games can produce learning than on how such games work or how they can be reliably developed. That is, though the design of a game is considered…

Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations

USDA-ARS?s Scientific Manuscript database

Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. Two independent studies were performed to...

Why are Formal Methods Not Used More Widely?

NASA Technical Reports Server (NTRS)

Knight, John C.; DeJong, Colleen L.; Gibble, Matthew S.; Nakano, Luis G.

1997-01-01

Despite extensive development over many years and significant demonstrated benefits, formal methods remain poorly accepted by industrial practitioners. Many reasons have been suggested for this situation such as a claim that they extent the development cycle, that they require difficult mathematics, that inadequate tools exist, and that they are incompatible with other software packages. There is little empirical evidence that any of these reasons is valid. The research presented here addresses the question of why formal methods are not used more widely. The approach used was to develop a formal specification for a safety-critical application using several specification notations and assess the results in a comprehensive evaluation framework. The results of the experiment suggests that there remain many impediments to the routine use of formal methods.

Predicting early spelling difficulties in children with specific language impairment: a clinical perspective.

PubMed

Cordewener, Kim A H; Bosman, Anna M T; Verhoeven, Ludo

2012-01-01

This study focused on the precursors of spelling difficulties in first grade for children with specific language impairment (SLI). A sample of 58 second-year kindergartners in The Netherlands was followed until the end of first grade. Linguistic, phonological, orthographic, letter knowledge, memory, and nonverbal-reasoning skills were considered as precursors, as was spelling level at an earlier point in time. Spelling difficulties at the end of first grade were most accurately identified by letter knowledge at the beginning of first grade and word spelling at the middle of first grade. It is concluded that spelling development in children with SLI can be seen as an autocatalytic process in which, without intervention, poor spellers generally remain poor spellers, and good spellers remain good spellers. A focus on early spelling intervention is thus emphasized. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of task shifting in community-based DOTS program as an effective control strategy for tuberculosis.

PubMed

Gabriel, André P; Mercado, Charles P

2011-01-01

Tuberculosis (TB) remains to be the most prevalent and debilitating pulmonary (PTB) infection in the world today, affecting about one-third of the world's population. TB is an endemic disease in many developing countries, and efforts at eliminating the disease remain futile. While the course of the disease is indolent with years of latency, the reactivation of the disease can pose serious pulmonary and systemic infections that compromise multiple organ functions which lead to respiratory failure or end-organ damage. Despite attempts to control and eradicate the mycobacterium, the prevalence of the disease remains high due to increasing population rate, persistence of poverty and poor health care, treatment failure, increasing multidrug resistance as a consequence of treatment failure and poor compliance, and existence of comorbid conditions that compromise immune response. Limited government resources to screen and monitor disease progression of TB in third world countries hamper the eradication of the disease. In response, we have evaluated the efficiency and effectivity of a Community-Based Directly Observed Treatment, Short-Course (CB-DOTS), which is an equally effective alternative strategy to health center DOTS.

Global notes: counting the world's poor--how do we define poverty?

PubMed

Vidyasagar, D

2006-06-01

Health professionals are in constant interaction with parents and infants who are victims of poverty and poor socioeconomic status. But an important question remains: do we know how to define poverty? Defining poverty accurately is important as the definition is the basis of policy development. The definition of poverty has changed during the last quarter century. In addition to economic considerations, it is broadened to include other dimensions of life such as literacy, health and longevity. This article attempts to provide national and international definitions of poverty, the magnitude and effects of poverty.

Growth, behavior, development and intelligence in rural children between 1-3 years of life.

PubMed

Agarwal, D K; Awasthy, A; Upadhyay, S K; Singh, P; Kumar, J; Agarwal, K N

1992-04-01

In a rural cohort of 625 children registered from 1981 to 1983 in 10 villages of K.V. Block, Varanasi, 196 children were assessed for physical growth, development, intelligence and concept development between 1 and 3 years of age. Home environment was also assessed using Caldwell Home inventory. These rural children remained below 3rd centile of NCHS standard for weight, height, skull and mid-arm circumferences throughout the study. Malnourished children scored poorly in all the areas of development, i.e., motor, adaptive, language and personal social, 9% in Grade I and 16.6% children in Grade II + III had IQ less than 79 (inferior). Concept for color shape and size was poorly developed in malnourished children. Maternal involvement and stimulation was strongly associated with better behavior development and intelligence. Multiple regression analysis showed that the effect of home environment on development and intelligence was of a higher magnitude as compared to status and family variables and nutritional status during 1-3 years of age.

The need for a standard approach to assessing the functionality of rural community water supplies

NASA Astrophysics Data System (ADS)

Bonsor, Helen; MacDonald, Alan; Casey, Vincent; Carter, Richard; Wilson, Paul

2018-03-01

The Sustainable Development Goals have set an agenda for transformational change in water access, aiming for secure household connections globally. Despite this goal, communal groundwater supplies are likely to remain the main source of improved water supplies for many rural areas in Africa and South Asia for decades to come. Understanding the poor functionality of existing communal supplies remains, therefore, a priority. A critical first step is to establish a sector-wide definition of borehole supply functionality and a standard method of its assessment.

Isotopic signals of summer denitrification in a northern hardwood forested catchment

Treesearch

Sarah K. Wexler; Christine L. Goodale; Kevin J. McGuire; Scott W. Bailey; Peter M. Groffman

2014-01-01

Despite decades of measurements, the nitrogen balance of temperate forest catchments remains poorly understood. Atmospheric nitrogen deposition often greatly exceeds streamwater nitrogen losses; the fate of the remaining nitrogen is highly uncertain. Gaseous losses of nitrogen to denitrification are especially poorly documented and are often ignored. Here, we provide...

Impact of water control projects on fisheries resources in Bangladesh

NASA Astrophysics Data System (ADS)

Mirza, Monirul Qader; Ericksen, Neil J.

1996-07-01

Bangladesh is a very flat delta built up by the Ganges—Brahmaputra—Meghna/Barak river systems. Because of its geographical location, floods cause huge destruction of lives and properties almost every year. Water control programs have been undertaken to enhance development through mitigating the threat of disasters. This structural approach to flood hazard has severely affected floodplain fisheries that supply the major share of protein to rural Bangladesh, as exemplified by the Chandpur Irrigation Project. Although the regulated environment of the Chandpur project has become favorable for closed-water cultured fish farming, the natural open-water fishery loss has been substantial. Results from research show that fish yields were better under preproject conditions. Under project conditions per capita fish consumption has dropped significantly, and the price of fish has risen beyond the means of the poor people, so that fish protein in the diet of poor people is gradually declining. Bangladesh is planning to expand water control facilities to the remaining flood-prone areas in the next 15 20 years. This will cause further loss of floodplain fisheries. If prices for closed-water fish remain beyond the buying power of the poor, alternative sources of cheap protein will be required.

Warranting Failure: The "System" that Breeds Poverty and Starves Public Schools

ERIC Educational Resources Information Center

Alexander, Kern; Salmon, Richard G.

2007-01-01

The inscription on the internal pedestal of the Statue of Liberty proclaiming "Give me your tired, your poor, your huddled masses" today is an ideal of another age. Compared with those of other developing countries, U.S. poverty rates are extraordinarily high, as are the odds of remaining in poverty intergenerationally. No longer do…

Thinning effects on tree mortality and snag recruitment in western Oregon

Treesearch

Erich Kyle Dodson; Klaus J. Puettmann; Adrian Ares

2013-01-01

Tree mortality shapes forest structural development and the resulting dead wood provides habitat for many species. However, the eff ects of thinning on mortality and large snag recruitment have been variable and remain poorly understood. We examined thinning eff ects on tree mortality at eleven Density Management Study (DMS) sites in western Oregon. Th inning reduced...

Mechanisms of plant survival and mortality during drought: Why do some plants survive while others succumb to drought?

Treesearch

Nate McDowell; William T. Pockman; Craig D. Allen; David D. Breshears; Neil Cobb; Thomas Kolb; Jennifer Plaut; John Sperry; Adam West; David G. Williams; Enrico A. Yepez

2008-01-01

Severe droughts have been associated with regional-scale forest mortality worldwide. Climate change is expected to exacerbate regional mortality events; however, prediction remains difficult because the physiological mechanisms underlying drought survival and mortality are poorly understood. We developed a hydraulically based theory considering carbon balance and...

Management of ganciclovir-resistant cytomegalovirus retinitis in HIV infection in the era of antiretroviral therapy.

PubMed

Adler, Hugh; De Gascun, Cillian F; McSweeney, Fionnuala; Acheson, Robert W; Brannigan, Eimear T; Duffy, Margaret; Keegan, David J; Lambert, John S

2014-10-01

The incidence of cytomegalovirus retinitis has decreased significantly since the advent of antiretroviral therapy. However, it remains an important problem in both the developed and developing worlds. Furthermore, long-term antiviral suppression is associated with a significant increase in viral resistance. We present the case of a 46-year-old man who developed cytomegalovirus retinitis one year after being diagnosed with HIV. While he initially demonstrated an excellent clinical response to ganciclovir, his cytomegalovirus viral load remained persistently elevated. Over the subsequent years, his virus developed ganciclovir resistance with a concomitant deterioration in his visual acuity. He responded poorly to salvage therapy with foscarnet and cidofovir. This case highlights the ongoing difficulty of managing cytomegalovirus disease nearly two decades into the era of antiretroviral therapy and underlines the need to develop new treatment strategies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Poverty, Disease, and the Ecology of Complex Systems

PubMed Central

Pluciński, Mateusz M.; Murray, Megan B.; Farmer, Paul E.; Barrett, Christopher B.; Keenan, Donald C.

2014-01-01

Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems—such as agriculture, fisheries, nutrition, and land use change—to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development. PMID:24690902

Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

PubMed

Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

2017-11-21

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

Poverty, disease, and the ecology of complex systems.

PubMed

Ngonghala, Calistus N; Pluciński, Mateusz M; Murray, Megan B; Farmer, Paul E; Barrett, Christopher B; Keenan, Donald C; Bonds, Matthew H

2014-04-01

Understanding why some human populations remain persistently poor remains a significant challenge for both the social and natural sciences. The extremely poor are generally reliant on their immediate natural resource base for subsistence and suffer high rates of mortality due to parasitic and infectious diseases. Economists have developed a range of models to explain persistent poverty, often characterized as poverty traps, but these rarely account for complex biophysical processes. In this Essay, we argue that by coupling insights from ecology and economics, we can begin to model and understand the complex dynamics that underlie the generation and maintenance of poverty traps, which can then be used to inform analyses and possible intervention policies. To illustrate the utility of this approach, we present a simple coupled model of infectious diseases and economic growth, where poverty traps emerge from nonlinear relationships determined by the number of pathogens in the system. These nonlinearities are comparable to those often incorporated into poverty trap models in the economics literature, but, importantly, here the mechanism is anchored in core ecological principles. Coupled models of this sort could be usefully developed in many economically important biophysical systems--such as agriculture, fisheries, nutrition, and land use change--to serve as foundations for deeper explorations of how fundamental ecological processes influence structural poverty and economic development.

Accounting for charity care on a systemwide basis.

PubMed

Peck, T

1988-06-01

The Daughters of Charity National Health System (DCNHS), St. Louis, has developed a systemwide model which formally sets a policy statement, goals, and procedures that enable the 42 DCNHS health-care ministries to effectively serve the poor in their communities on a daily basis, while addressing the long-term challenges of providing charity care for the sick poor. One of the first steps was forming a task force known as the Working Group on Care of the Poor. Its goal was to set the stage for the expansion and accountability of charity care at every level within the new national system. The group outlined these objectives: To identify and recommend several advocacy models. To recommend test models of healthcare delivery for the poor. To recommend strategies for involving the private sector. To develop a method of documenting charity care. To recommend linkage models to jointly provide charity care with related organizations. To gain a firm knowledge of charity care actually provided by the Daughters of Charity After hours of discussions and research, the task force developed a cohesive, workable set of goals and policies that today is helping individual health-care ministries nationwide meet local needs for care of the sick poor. By identifying specific programs and determining how to report charity care in terms of money and services, individual health-care institutions gain insights into their annual operational planning and reporting for the present and the future. This approach ensures that charity care remains in the forefront at every level of planning.

Predictive factors for poor prognosis febrile neutropenia.

PubMed

Ahn, Shin; Lee, Yoon-Seon

2012-07-01

Most patients with chemotherapy-induced febrile neutropenia recover rapidly without serious complications. However, it still remains a life-threatening treatment-related toxicity, and is associated with dose reductions and delays of chemotherapeutic agents that may compromise treatment outcomes. Recent developments of risk stratification enabled early discharge with oral antibiotics for low-risk patients. However, even in low-risk patients, medical complications including bacteremia could happen. The authors reviewed recent literature to provide an update on research regarding predictive factors for poor prognosis in patients with febrile neutropenia. Various prognostic factors have been suggested with controversies. Hematological parameters, prophylactic measurements and patient-specific risk factors showed inconsistent results. MASCC risk-index score, which was originally developed to identify low-risk patients, in turn showed that the lower the MASCC score, the poorer the prognosis of febrile neutropenia, with very low levels (<15), the rate of complications was high. Patients with severe sepsis and septic shock commonly had procalcitonin concentration above 2.0 ng/ml, and this level should be considered at high risk of poor prognosis. Lower MASCC score and higher procalcitonin concentration can predict poor outcomes in febrile neutropenia. More research is required with regard to the other factors showing controversies.

Is Adolescence a Critical Period for Learning Formal Thinking Skills? A Case Study Investigating the Development of Formal Thinking Skills in a Short-Term Inquiry-Based Intervention Program

ERIC Educational Resources Information Center

Towne, Forrest S.

2009-01-01

Current domestic and international comparative studies of student achievement in science are demonstrating that the U.S. needs to improve science education if it wants to remain competitive in the global economy. One of the causes of the poor performance of U.S. science education is the lack of students who have developed the formal thinking…

Move over, Douglas-fir: Oregon white oaks need room to grow.

Treesearch

J. Thompson

2007-01-01

Oregon white oak savanna and woodland habitat in the Pacific Northwest has declined to less than 10 percent of its former range, and much of what remains is of poor quality. In addition to urbanization and agricultural development, habitat is being lost to conifers that have invaded oak areas, which were once maintained through frequent burning by Native Americans. The...

Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming

USDA-ARS?s Scientific Manuscript database

Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. Here, we investigated whether earl...

Variation in logging debris cover influences competitor abundance, resource availability, and early growth of planted Douglas-fir

Treesearch

Timothy B. Harrington; Robert A. Slesak; Stephen H. Schoenholtz

2013-01-01

Logging debris remaining after timber harvest can modify the microclimate and growing conditions for forest regeneration. Debris also can influence tree seedlings indirectly through its effects on development of competing vegetation, although the mechanisms are poorly understood. At two sites in Washington and Oregon (USA) that differed in availability of soil water...

Body size and pubertal development explain ethnic differences in structural geometry at the femur in Asian, Hispanic and white early adolescent girls living in the US

USDA-ARS?s Scientific Manuscript database

Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification o...

Facial and bodily correlates of family background.

PubMed

Boothroyd, Lynda G; Perrett, David I

2006-09-22

It has been suggested that absence of the father during early childhood has long-reaching effects on reproductive strategy and development of offspring. This paper reports two studies designed to investigate the physical characteristics of daughters associated with father absence. Study 1 used a facial averaging method to produce composite images of faces of women whose parents separated during their childhood (who were 'father absent'), women whose parents remained together, but had poor quality relationships and women whose parents were together and had good quality relationships. Images were then rated by male and female judges. Father absence and poor parental relationships were associated with apparent facial masculinity and reduced attractiveness in daughters. Poor parental relationships were also associated with reduced apparent health. Study 2 compared family background with body measurements and found that father absence or a poor quality relationship between parents were associated with body masculinity (high waist-to-hip ratio) and increased weight-for-height and adiposity. These results highlight the possibility of physical masculinization being associated with purported father absence 'effects'.

Echinococcosis: Control and Prevention.

PubMed

Craig, P S; Hegglin, D; Lightowlers, M W; Torgerson, P R; Wang, Q

2017-01-01

Human cystic echinococcosis (CE) has been eliminated or significantly reduced as a public health problem in several previously highly endemic regions. This has been achieved by the long-term application of prevention and control measures primarily targeted to deworming dogs, health education, meat inspection, and effective surveillance in livestock and human populations. Human CE, however, remains a serious neglected zoonotic disease in many resource-poor pastoral regions. The incidence of human alveolar echinococcosis (AE) has increased in continental Europe and is a major public health problem in parts of Eurasia. Better understanding of wildlife ecology for fox and small mammal hosts has enabled targeted anthelmintic baiting of fox populations and development of spatially explicit models to predict population dynamics for key intermediate host species and human AE risk in endemic landscapes. Challenges that remain for echinococcosis control include effective intervention in resource-poor communities, better availability of surveillance tools, optimal application of livestock vaccination, and management and ecology of dog and wildlife host populations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developmental biology of gut-probiotic interaction

PubMed Central

Patel, Ravi Mangal

2010-01-01

While our current knowledge of probiotic interaction in the developing gut remains poorly understood, emerging science is providing greater biological insight into their mechanism of action and therapeutic potential for human disease. Given their beneficial effects, probiotics remain promising agents in neonatal gastrointestinal disorders. Probiotics may restore or supply essential bacterial strains needed for gut maturation and homeostasis, particularly in hosts where this process has been disrupted. Here we highlight the unique characteristics of developing intestinal epithelia with a focus on gut development and colonization as well as the inflammatory propensity of immature epithelia. Additionally, we review potential mechanisms of beneficial probiotic interaction with immature intestinal epithelia including immunomodulation, upregulation of cytoprotective genes, prevention and regulation of apoptosis and maintenance of barrier function. Improved knowledge of gut-probiotic interaction in developing epithelia will allow for a better understanding of how probiotics exert their beneficial effects and help guide their therapeutic use. PMID:21327024

Singing with yourself: evidence for an inverse modeling account of poor-pitch singing.

PubMed

Pfordresher, Peter Q; Mantell, James T

2014-05-01

Singing is a ubiquitous and culturally significant activity that humans engage in from an early age. Nevertheless, some individuals - termed poor-pitch singers - are unable to match target pitches within a musical semitone while singing. In the experiments reported here, we tested whether poor-pitch singing deficits would be reduced when individuals imitate recordings of themselves as opposed to recordings of other individuals. This prediction was based on the hypothesis that poor-pitch singers have not developed an abstract "inverse model" of the auditory-vocal system and instead must rely on sensorimotor associations that they have experienced directly, which is true for sequences an individual has already produced. In three experiments, participants, both accurate and poor-pitch singers, were better able to imitate sung recordings of themselves than sung recordings of other singers. However, this self-advantage was enhanced for poor-pitch singers. These effects were not a byproduct of self-recognition (Experiment 1), vocal timbre (Experiment 2), or the absolute pitch of target recordings (i.e., the advantage remains when recordings are transposed, Experiment 3). Results support the conceptualization of poor-pitch singing as an imitative deficit resulting from a deficient inverse model of the auditory-vocal system with respect to pitch. Copyright © 2014 Elsevier Inc. All rights reserved.

Supportive techniques and devices for endoscopic submucosal dissection of gastric cancer.

PubMed

Sakurazawa, Nobuyuki; Kato, Shunji; Fujita, Itsuo; Kanazawa, Yoshikazu; Onodera, Hiroyuki; Uchida, Eiji

2012-06-16

The indications for endoscopic treatment have expanded in recent years, and relatively intestinal-type mucosal stomach carcinomas with a low potential for metastasis are now often resected en bloc by endoscopic submucosal dissection (ESD), even if they measure over 20 mm in size. However, ESD requires complex maneuvers, which entails a long operation time, and is often accompanied by complications such as bleeding and perforation. Many technical developments have been implemented to overcome these complications. The scope, cutting device, hemostasis device, and other supportive devices have been improved. However, even with these innovations, ESD remains a potentially complex procedure. One of the major difficulties is poor visualization of the submucosal layer resulting from the poor countertraction afforded during submucosal dissection. Recently, countertraction devices have been developed. In this paper, we introduce countertraction techniques and devices mainly for gastric cancer.

Emerging roles for hemostatic dysfunction in malaria pathogenesis.

PubMed

O'Sullivan, Jamie M; Preston, Roger J S; O'Regan, Niamh; O'Donnell, James S

2016-05-12

Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum-infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance. © 2016 by The American Society of Hematology.

Health care seeking practices of caregivers of children under 5 with diarrhea in two informal settlements in Nairobi, Kenya.

PubMed

Mukiira, Carol; Ibisomi, Latifat

2015-06-01

In Kenya, as in other developing countries, diarrhea is among the leading causes of child mortality. Despite being easy to prevent and treat, care seeking for major child illnesses including diarrhea remains poor in the country. Mortality due to diarrhea is even worse in informal settlements that are characterized by poor sanitary conditions and largely unregulated health care system among other issues. The study aims to examine the health care seeking practices of caregivers of children under 5 with diarrhea in two informal settlements in Nairobi, Kenya. The article used data from a maternal and child health (MCH) prospective study conducted between 2006 and 2010. Results show that more than half (55%) of the caregivers sought inappropriate health care in the treatment of diarrhea of their child. Of the 55%, about 35% sought no care at all. Use of oral rehydration solution and zinc supplements, which are widely recommended for management of diarrhea, was very low. The critical predictors of health care seeking identified in the study are duration of illness, informal settlement of residence, and the child's age. The study showed that appropriate health care seeking practices for childhood diarrhea remain a great challenge among the urban poor in Kenya. © The Author(s) 2013.

The long-term dynamics of mortality benefits from improved water and sanitation in less developed countries.

PubMed

Jeuland, Marc A; Fuente, David E; Ozdemir, Semra; Allaire, Maura C; Whittington, Dale

2013-01-01

The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975-2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed.

The Long-Term Dynamics of Mortality Benefits from Improved Water and Sanitation in Less Developed Countries

PubMed Central

Jeuland, Marc A.; Fuente, David E.; Ozdemir, Semra; Allaire, Maura C.; Whittington, Dale

2013-01-01

The problem of inadequate access to water, sanitation and hygiene (WASH) in less-developed nations has received much attention over the last several decades (most recently in the Millennium Development Goals), largely because diseases associated with such conditions contribute substantially to mortality in poor countries. We present country-level projections for WASH coverage and for WASH-related mortality in developing regions over a long time horizon (1975–2050) and provide dynamic estimates of the economic value of potential reductions in this WASH-related mortality, which go beyond the static results found in previous work. Over the historical period leading up to the present, our analysis shows steady and substantial improvements in WASH coverage and declining mortality rates across many developing regions, namely East Asia and the Pacific, Latin America and the Caribbean, Eastern Europe and the Middle East. The economic value of potential health gains from eliminating mortality attributable to poor water and sanitation has decreased substantially, and in the future will therefore be modest in these regions. Where WASH-related deaths remain high (in parts of South Asia and much of Sub-Saharan Africa), if current trends continue, it will be several decades before economic development and investments in improved water and sanitation will result in the capture of these economic benefits. The fact that health losses will likely remain high in these two regions over the medium term suggests that accelerated efforts are needed to improve access to water and sanitation, though the costs and benefits of such efforts in specific locations should be carefully assessed. PMID:24116011

Inhomogeneous degradation in metal halide perovskites

NASA Astrophysics Data System (ADS)

Yang, Rong; Zhang, Li; Cao, Yu; Miao, Yanfeng; Ke, You; Wei, Yingqiang; Guo, Qiang; Wang, Ying; Rong, Zhaohua; Wang, Nana; Li, Renzhi; Wang, Jianpu; Huang, Wei; Gao, Feng

2017-08-01

Although the rapid development of organic-inorganic metal halide perovskite solar cells has led to certified power conversion efficiencies of above 20%, their poor stability remains a major challenge, preventing their practical commercialization. In this paper, we investigate the intrinsic origin of the poor stability in perovskite solar cells by using a confocal fluorescence microscope. We find that the degradation of perovskite films starts from grain boundaries and gradually extend to the center of the grains. Firmly based on our findings, we further demonstrate that the device stability can be significantly enhanced by increasing the grain size of perovskite crystals. Our results have important implications to further enhance the stability of optoelectronic devices based on metal halide perovskites.

[Insight into illness: an overview of the concept focusing on schizophrenia].

PubMed

Bottlender, Ronald; Hloucal, Teresa-Maria

2010-03-01

Insight into illness is key to successful treatment. Poor insight, especially in schizophrenia, is, however, quite a frequent phenomenon that is also associated with poor adherence to treatment and a variety of unfavorable outcome parameters. On that background, the concept of insight into illness has gained new reseach interest during the last 10 years. The present review aims to report new findings regarding conceptual changes of insight, findings on the etiology, contributing factors as well as the assessment and methods to develop insight. Based on a review of the literature, results from more recent studies on insight into illness will be presented. Insight into illness is a complex, multidimensional, strongly culturally embedded phenomenon that is influenced by a variety of factors. The etiology of insight still remains poorly understood but is likely to be multifactorial including psychological, neuropsychological and organic reasons. Further research is needed, in particularly regarding therapeutical techniques to improve insight into illness.

Laboratory challenges in the scaling up of HIV, TB, and malaria programs: The interaction of health and laboratory systems, clinical research, and service delivery.

PubMed

Birx, Deborah; de Souza, Mark; Nkengasong, John N

2009-06-01

Strengthening national health laboratory systems in resource-poor countries is critical to meeting the United Nations Millennium Development Goals. Despite strong commitment from the international community to fight major infectious diseases, weak laboratory infrastructure remains a huge rate-limiting step. Some major challenges facing laboratory systems in resource-poor settings include dilapidated infrastructure; lack of human capacity, laboratory policies, and strategic plans; and limited synergies between clinical and research laboratories. Together, these factors compromise the quality of test results and impact patient management. With increased funding, the target of laboratory strengthening efforts in resource-poor countries should be the integrating of laboratory services across major diseases to leverage resources with respect to physical infrastructure; types of assays; supply chain management of reagents and equipment; and maintenance of equipment.

Rich and poor states in the Middle East: Egypt and the New Arab Order

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herr, M.H.; Yassin, E.S.

1982-01-01

While oil wealth has enriched some Middle East Arab nations, those lacking oil resources have remained poor and are looking now to their oil-rich neighbors for development assistance. This collection of studies on the economic, social, and political relationships between the have and the have-nots focuses on Egypt, the largest state in the region, and on its prospects for change based on financial assistance from other Arab countries. The 13 authors disagree about the future of both rich and poor nations, and are skeptical about the possibility of transforming Egypt. They do agree that the future must be projected inmore » the framework of a new regional order in which oil wealth, labor migration, and a new regional order in which oil wealth, labor migration, and liberalized national economies are fundamental realities. 615 references, 5 figures, 67 tables.« less

Activism needed for vaccines to reach South.

PubMed

1998-06-30

An AIDS vaccine remains the only feasible strategy for curbing the spread of HIV infection in resource-poor developing countries because of its low cost and logistic simplicity. However, the pace of vaccine development has been slowed by difficulties persuading pharmaceutical companies to invest time and money in such research. These companies do not perceive a financial advantage to vaccine development. The International AIDS Vaccine Initiative is attempting to create a market for an AIDS vaccine. It is also urging developing countries to develop their own vaccines so they have intellectual property rights. Any advances in this area will require political pressure from community activists.

Use of modern contraception by the poor is falling behind.

PubMed

Gakidou, Emmanuela; Vayena, Effy

2007-02-01

The widespread increase in the use of contraception, due to multiple factors including improved access to modern contraception, is one of the most dramatic social transformations of the past fifty years. This study explores whether the global progress in the use of modern contraceptives has also benefited the poorest. Demographic and Health Surveys from 55 developing countries were analyzed using wealth indices that allow the identification of the absolute poor within each country. This article explores the macro level determinants of the differences in the use of modern contraceptives between the poor and the national averages of several countries. Despite increases in national averages, use of modern contraception by the absolute poor remains low. South and Southeast Asia have relatively high rates of modern contraception in the absolute poor, on average 17% higher than in Latin America. Over time the gaps in use persist and are increasing. Latin America exhibits significantly larger gaps in use between the poor and the averages, while gaps in sub-Saharan Africa are on average smaller by 15.8% and in Southeast Asia by 11.6%. The secular trend of increasing rates of modern contraceptive use has not resulted in a decrease of the gap in use for those living in absolute poverty. Countries with large economic inequalities also exhibit large inequalities in modern contraceptive use. In addition to macro level factors that influence contraceptive use, such as economic development and provision of reproductive health services, there are strong regional variations, with sub-Saharan Africa exhibiting the lowest national rates of use, South and Southeast Asia the highest use among the poor, and Latin America the largest inequalities in use.

Child Poverty and Its Lasting Consequence. Low-Income Working Families. Paper 21

ERIC Educational Resources Information Center

Ratcliffe, Caroline; McKernan, Signe-Mary

2012-01-01

One in six newborns were born poor over the past 40 years, and nearly half remained poor half their childhoods. These persistently poor children are nearly 90 percent more likely than never-poor children to enter their 20s without completing high school and are four times more likely to give birth outside of marriage during their teenage years.…

Biofilm community succession: a neutral perspective.

PubMed

Woodcock, Stephen; Sloan, William T

2017-05-22

Although biofilms represent one of the dominant forms of life in aqueous environments, our understanding of the assembly and development of their microbial communities remains relatively poor. In recent years, several studies have addressed this and have extended the concepts of succession theory in classical ecology into microbial systems. From these datasets, niche-based conceptual models have been developed explaining observed biodiversity patterns and their dynamics. These models have not, however, been formulated mathematically and so remain untested. Here, we further develop spatially resolved neutral community models and demonstrate that these can also explain these patterns and offer alternative explanations of microbial succession. The success of neutral models suggests that stochastic effects alone may have a much greater influence on microbial community succession than previously acknowledged. Furthermore, such models are much more readily parameterised and can be used as the foundation of more complex and realistic models of microbial community succession.

17-hydroxylase/17,20-lyase deficiency due to a R96Q mutation causing hypertension and poor breast development

PubMed Central

Al Suwaidi, Hana; Attia, Salima; Al Ameri, Ahlam

2015-01-01

Summary Combined17α-hydroxylase/17,20-lyase deficiency is a rare cause of congenital adrenal hyperplasia and hypogonadism. Hypertension and hypokalemia are essential presenting features. We report an Arab family with four affected XX siblings. The eldest presented with abdominal pain and was diagnosed with a retroperitoneal malignant mixed germ cell tumour. She was hypertensive and hypogonadal. One sibling presented with headache due to hypertension while the other two siblings were diagnosed with hypertension on a routine school check. A homozygous R96Q missense mutation in P450c17 was detected in the index case who had primary amenorrhea and lack of secondary sexual characters at 17 years. The middle two siblings were identical twins and had no secondary sexual characters at the age of 14. All siblings had hypokalemia, very low level of adrenal androgens, high ACTH and high levels of aldosterone substrates. Treatment was commenced with steroid replacement and puberty induction with estradiol. The index case had surgical tumor resection and chemotherapy. All siblings required antihypertensive treatment and the oldest remained on two antihypertensive medications 12 years after diagnosis. Her breast development remained poor despite adequate hormonal replacement. Combined 17α-hydroxylase/17,20-lyase deficiency is a rare condition but might be underdiagnosed. It should be considered in young patients presenting with hypertension, particularly if there is a family history of consanguinity and with more than one affected sibling. Antihypertensive medication might continue to be required despite adequate steroid replacement. Breast development may remain poor in mutations causing complete form of the disease. Learning points Endocrine hypertension due to rarer forms of CAH should be considered in children and adolescents, particularly if more than one sibling is affected and in the presence of consanguinity. 17α-hydroxylase/17,20-lyase deficiency is a rare form of CAH but might be underdiagnosed. Blood pressure measurement should be carried out in all females presenting with hypogonadism. Anti-hypertensive medications might be required despite adequate steroid replacement. Initial presenting features might vary within affected members of the same family. Adverse breast development might be seen in the complete enzyme deficiency forms of the disease. PMID:26543560

Working Poor Families in the Chicago Metropolitan Area. Statistical Profile and Proceedings of the Working Poor Policy Forum (Chicago, Illinois, December 8, 1993).

ERIC Educational Resources Information Center

Latino Inst., Chicago, IL.

A statistical profile of the working poor in Chicago (Illinois) and the proceedings of the Working Poor Policy Forum held to discuss the findings of the profile are presented. In America it is supposed to be impossible to work and remain chronically poor, but in fact this is not the case. There are many ways to define the income working families…

Prevalence and factors associated with poor sleep quality among secondary school teachers in a developing country.

PubMed

Musa, Nor Asma; Moy, Foong Ming; Wong, Li Ping

2018-05-31

This study aimed to determine the prevalence and factors associated with poor sleep quality among secondary school teachers in the state of Selangor, Malaysia. This was a cross sectional study, conducted in two phases. Phase I tested the reliability of the Pittsburgh Sleep Quality Index in the Malay language (M-PSQI), whereas Phase II determined the prevalence and factors associated with poor sleep quality where a total of 1871 secondary school teachers were studied. Participants were recruited using multistage sampling. Self-administered questionnaire was used to collect data on socio-demographic and teaching characteristics, comorbidities and characteristics of sleep. The M-PSQI was used to measure sleep quality. The Depression Anxiety Stress Scale-21 was used to measure mental health status. Results showed that the M-PSQI had a good internal consistency and moderate reliability. The prevalence of poor sleep quality was 61 (95% CI: 54-67) %. Total teaching hours/day, depression and stress were significantly associated with poor sleep quality in the univariate analysis, while only stress (OR 1.04; 95% CI 1.02-1.05%) remained significant in the multivariate analyses. In conclusion, stress level of the secondary school teachers should be reduced to improve sleep quality.

Promoting Access to Education for Disabled Children in Low-Income Countries: Do We Need to Know How Many Disabled Children There Are?

ERIC Educational Resources Information Center

Croft, Alison

2013-01-01

Poor people are most likely to be disabled, and the exclusion of disabled people from education means that they are also more likely to remain poor. Despite calls for better data to inform the extension of education for disabled children, data in this field remain weak. This paper asks whether a national survey of disability prevalence is the best…

Perceptions of Older Adults with Heart Failure on Playing an Interactive Digital e-Health Game (IDEG) for Learning About Heart Failure (HF): Prototype Development and Usability Testing.

PubMed

Radhakrishnan, Kavita; Toprac, Paul; O'Hair, Matt; Bias, Randolph; Mackert, Mike; Xie, Bo; Kim, Miyong; Bradley, Paul

2016-01-01

Effective self-management can decrease up to 50% of heart failure (HF) hospitalizations. However, self-management by patients with HF remains poor. We describe the development and usability testing of an interactive digital e-health game (IDEG) for older patients with HF in Central Texas, USA. Majority of the participants (5 out of 6) who participated in the usability testing found the game interesting, enjoyable and helpful to play. Developing an IDEG that is satisfying and acceptable to older adults with HF is feasible.

Scaling laws of passive-scalar diffusion in the interstellar medium

NASA Astrophysics Data System (ADS)

Colbrook, Matthew J.; Ma, Xiangcheng; Hopkins, Philip F.; Squire, Jonathan

2017-05-01

Passive-scalar mixing (metals, molecules, etc.) in the turbulent interstellar medium (ISM) is critical for abundance patterns of stars and clusters, galaxy and star formation, and cooling from the circumgalactic medium. However, the fundamental scaling laws remain poorly understood in the highly supersonic, magnetized, shearing regime relevant for the ISM. We therefore study the full scaling laws governing passive-scalar transport in idealized simulations of supersonic turbulence. Using simple phenomenological arguments for the variation of diffusivity with scale based on Richardson diffusion, we propose a simple fractional diffusion equation to describe the turbulent advection of an initial passive scalar distribution. These predictions agree well with the measurements from simulations, and vary with turbulent Mach number in the expected manner, remaining valid even in the presence of a large-scale shear flow (e.g. rotation in a galactic disc). The evolution of the scalar distribution is not the same as obtained using simple, constant 'effective diffusivity' as in Smagorinsky models, because the scale dependence of turbulent transport means an initially Gaussian distribution quickly develops highly non-Gaussian tails. We also emphasize that these are mean scalings that apply only to ensemble behaviours (assuming many different, random scalar injection sites): individual Lagrangian 'patches' remain coherent (poorly mixed) and simply advect for a large number of turbulent flow-crossing times.

A review of catalyst-enhanced magnesium hydride as a hydrogen storage material

NASA Astrophysics Data System (ADS)

Webb, C. J.

2015-09-01

Magnesium hydride remains an attractive hydrogen storage material due to the high hydrogen capacity and low cost of production. A high activation energy and poor kinetics at practical temperatures for the pure material have driven research into different additives to improve the sorption properties. This review details the development of catalytic additives and their effect on the activation energy, kinetics and thermodynamic properties of magnesium hydride.

Negotiating the labyrinth of modernity's promise a paradigm analysis of energy poverty in peri-urban Kumasi, Ghana

NASA Astrophysics Data System (ADS)

Odarno, Lily Ameley

Energy poverty in developing countries has been conventionally attributed to a lack of access to sufficient, sustainable and modern forms of energy (ESMAP 2001; Modi et al. 2006). Per this definition, Sub--Saharan Africa is the most energy poor region in the world today. In line with this, efforts at addressing energy poverty in the region have concentrated on the expansion of access to modern energy sources, particularly electricity. In spite of the implementation of diverse energy development interventions, access to modern energy services remains limited. That energy poverty remains one of the most pressing challenges in Sub--Saharan Africa today in spite of the many decades of energy development necessitates a candid and thorough re--evaluation of the questions that have been traditionally asked about this issue and the solutions that have been offered in response to it. Based on theoretical analyses and empirical studies in peri--urban Kumasi, Ghana, this study attempts to offer some of the much needed re--evaluations. Using Kuhn's paradigm approach as a conceptual tool, this dissertation identifies peri--urban energy poverty as a paradigm--scale conflict in the modern arrangement of energy--development relations. By emphasizing the importance of context and political economy in understanding energy poverty, the study proposes strategies for an alternative paradigm in which energy--development relations are fundamentally redefined; one which enlists appropriate knowledge, technologies, and institutions in addressing the needs of the energy poor in ways which promote environmental values, social equity and sustainable livelihoods.

The Social Development Summit and the developing countries.

PubMed

Barnabas, A P; Kulkarni, P D; Nanavatty, M C; Singh, R R

1996-01-01

This article discusses some concerns of the 1996 UN Summit on Social Development. Conference organizers identified the three key conference issues as poverty alleviation, social integration of the marginalized and disadvantaged, and expansion of productive employment. The goal of a "society for all" means dealing with the increasing differences between rich and poor countries, the survival of weaker economies in a competitive market system, wide variations in consumption patterns between countries, attainment of political stability while respecting ethnic identity, the rise in social problems among countries with a high human development index, and increasing joblessness. The Human Development Report for 1994 emphasizes human security. Social development is not the equivalent of human resource development nor a side issue of economic growth. The integration of ethnic groups poses social and political problems. There remains a question about what political system and culture would be best for social integration. Developed countries define poverty as the inability of people and government to provide resources and necessary services for people's productive activity. Poverty in developing countries is blamed on colonialism. Globally, developed countries control 71% of world trade. Sharing resources to meet basic needs throughout the world is not an operational ideal. The highest 20% of income earners receive 83% of the world income. The culture of poverty is the strategy used by the poor to survive. Welfare is not an end in itself but does enable the poor to improve their conditions. Development that focuses on productive employment is uncertain. Developed and developing countries do not share similar perceptions of human rights. There is a question as to who should set the priorities for social development. Sustainable social development is related to preservation of natural resources, control of population growth, and promotion of social security.

Bordetella pertussis pathogenesis: current and future challenges.

PubMed

Melvin, Jeffrey A; Scheller, Erich V; Miller, Jeff F; Cotter, Peggy A

2014-04-01

Pertussis, also known as whooping cough, has recently re-emerged as a major public health threat despite high levels of vaccination against the aetiological agent Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into B. pertussis virulence-factor function. We also discuss the changing epidemiology of pertussis and the challenges facing vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies.

Bordetella pertussis pathogenesis: current and future challenges

PubMed Central

Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

2014-01-01

Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

Tuberculosis in the tropics.

PubMed

Krause, V L; Britton, W J

1993-09-20

Until recently tuberculosis was considered a well controlled disease, at least in developed countries. In developing countries, more than seven million people are affected by active tuberculosis. This situation is exacerbated by poor infrastructure to support tuberculosis control measures and the interaction between tuberculosis and infection with the human immunodeficiency virus. The three major strategies for controlling tuberculosis remain BCG vaccination in children, appropriate preventive therapy and, most importantly, reducing the sources of infection through case finding and curative treatment. Research and resources to improve on these strategies should be given high priority by the international health community.

Nanostructured lipid carriers: versatile oral delivery vehicle

PubMed Central

Poonia, Neelam; Kharb, Rajeev; Lather, Viney; Pandita, Deepti

2016-01-01

Oral delivery is the most accepted and economical route for drug administration and leads to substantial reduction in dosing frequency. However, this route still remains a challenge for the pharmaceutical industry due to poorly soluble and permeable drugs leading to poor oral bioavailability. Incorporating bioactives into nanostructured lipid carriers (NLCs) has helped in boosting their therapeutic functionality and prolonged release from these carrier systems thus providing improved pharmacokinetic parameters. The present review provides an overview of noteworthy studies reporting impending benefits of NLCs in oral delivery and highlights recent advancements for developing engineered NLCs either by conjugating polymers over their surface or modifying their charge to overcome the mucosal barrier of GI tract for active transport across intestinal membrane. PMID:28031979

Telemedicine is the way forward for the management of cystic fibrosis- the case against.

PubMed

Lenney, Warren

2018-03-01

It is reasonable to suggest that Telemedicine could help in the management of chronic diseases by giving patients more flexibility to remain at home with opportunities to forward electronic data to healthcare professionals, reduce hospital emergency attendances and reduce overall costs. The reality, particularly in cystic fibrosis care, is this has not happened. There is concern that home-generated lung function data is of poor quality and virtually no studies show improved outcomes. The UK has a poor record in developing novel IT programmes and we need many more well designed clinical studies in Telemedicine before wading in with ill-conceived expensive plans just because the idea seems interesting. Copyright © 2017. Published by Elsevier Ltd.

'I'm a bad mum': pregnant presenteeism and poor health at work.

PubMed

Gatrell, Caroline Jane

2011-02-01

This paper contributes to research on women's health by challenging the 'common belief' that pregnant employees are prone to take sick leave. Conversely, it shows how some pregnant employees are so determined to appear 'well' that they remain at work when they are ill. The paper coins the phrase 'pregnant presenteeism' to describe pregnant employees who resist taking sick leave. The paper first acknowledges previous studies which show how employers associate pregnancy with incompetence and sickness absence. It then examines why (in contrast to employers' assumptions), some pregnant employees remain at work when they are ill. It does this through a qualitative study of 15 employed mothers in the UK, each of whom was working in a managerial/professional role at the time of her interview. Of these 15 women, three remained at work during pregnancy despite serious health problems. In order to understand the experiences of these 'pregnant presentees', the paper draws upon Annandale and Clark's (1996) concept of a 'binary opposition' which articulates the tendency within medicine to polarize women's and men's health as if at opposite ends of a scale, with women's health classified as 'poor' and men's health as 'good'. The paper argues that the conceptual principles of 'binary opposition' spill over into workplace contexts especially in relation to pregnancy. It then proposes that some employed pregnant women deny their own ill health due to fear of being identified with the female, 'poor health' end of the binary opposition scale. It articulates such denial as a potentially serious health issue for pregnant workers. The paper develops new and more explicit links between 'socio-cultural' feminist studies on the employed maternal body, and health research. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pre-operative Functional Cardiovascular Reserve Is Associated with Acute Kidney Injury after Intervention.

PubMed

Saratzis, A; Shakespeare, J; Jones, O; Bown, M J; Mahmood, A; Imray, C H E

2017-05-01

Acute kidney injury (AKI) is a common complication after endovascular intervention, associated with poor short and long-term outcomes. However, the mechanisms underlying AKI development remain poorly understood. The impact of pre-existing cardiovascular disease and low cardiovascular reserve (CVR) in AKI is unclear; it remains unknown whether AKI is primarily related to pre-existing comorbidity or to procedural parameters. The association between CVR and AKI after EVAR was therefore assessed. This is a case control study. From a database of 484 patients, 292 undergoing elective endovascular aneurysm repair (EVAR) of an infrarenal abdominal aortic aneurysm (AAA) in two tertiary centres were included. Of these, 73 patients who had developed AKI after EVAR were case matched, based on pre-operative estimated glomerular filtration rate (eGFR; within 5 mL/min/1.73 m 2 ) and age, with patients who had not developed AKI. Cardiopulmonary exercise testing (CPET) was used to assess CVR using the anaerobic threshold (AT). Development of AKI was defined using the Kidney Disease Improving Outcomes (KDIGO) guidance. Associations between CVR (based on AT levels) and AKI development were then analysed. Pre-operative AT levels were significantly different between those who did and did not develop AKI (12.1±2.9 SD vs. 14.8±3.0 mL/min/kg, p < .001). In multivariate analysis, a higher level of AT (per 1 mL/min/kg) was associated with a lower odds ratio (OR) of 0.72 (95% CI, 0.63-0.82, p < .001), relative to AKI development. A pre-operative AT level of < 11 mL/min/kg was associated with post-operative AKI development in adjusted analysis, with an OR of 7.8 (95% CI, 3.75-16.51, p < .001). The area under the curve (receiver operating characteristic) for AT as a predictor of post-operative AKI was 0.81 (standard error, 0.06, 95% CI, 0.69-0.93, p < .001). Poor CVR was strongly associated with the development of AKI. This provides pathophysiological insights into the mechanisms underlying AKI. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Occupational asthma in the developing and industrialised world: a review.

PubMed

Jeebhay, M F; Quirce, S

2007-02-01

Occupational asthma is the most common occupational lung disease in industrialised countries, and the second most common occupational lung disease reported after pneumoconioses in developing countries. The median proportion of adult cases of asthma attributable to occupational exposure is between 10% and 15%. The population attributable fraction appears to be similar in industrialised and developing countries characterised by rapid industrialisation (13-15%), but lower in less industrialised developing countries (6%). The high-risk occupations and industries associated with the development of occupational asthma vary depending on the dominant industrial sectors in a particular country. High-risk exposure to cleaning agents and pesticide exposure in developing countries appear to be as important as exposure to isocyanates, cereal flour/grain dust, welding fumes, wood dust and, more recently, hairdressing chemicals, commonly reported in industrialised countries. The reported mean annual incidence of occupational asthma in developing countries is less than 2 per 100 000 population, compared to very high rates of up to 18/100 000 in Scandinavian countries. While occupational asthma remains under-recognised, especially in developing countries, it remains poorly diagnosed and managed and inadequately compensated worldwide. Primary and secondary preventive strategies should be directed at controlling workplace exposures, accompanied by intense educational and managerial improvements. Appropriate treatment remains early removal from exposure to ensure that the worker has no further exposure to the causal agent, with preservation of income. However, up to one third of workers with occupational asthma continue to remain exposed to the causative agent or suffer prolonged work disruption, discrimination and risk of unemployment.

Advances in anesthesia technology are improving patient care, but many challenges remain.

PubMed

John Doyle, D; Dahaba, Ashraf; LeManach, Yannick

2018-04-13

Although significant advances in clinical monitoring technology and clinical practice development have taken place in the last several decades, in this editorial we argue that much more still needs to be done. We begin by identifying many of the improvements in perioperative technology that have become available in recent years; these include electroencephalographic depth of anesthesia monitoring, bedside ultrasonography, advanced neuromuscular transmission monitoring systems, and other developments. We then discuss some of the perioperative technical challenges that remain to be satisfactorily addressed, such as products that incorporate poor software design or offer a confusing user interface. Finally we suggest that the journal support initiatives to help remedy this problem by publishing reports on the evaluation of medical equipment as a means to restore the link between clinical research and clinical end-users.

The President's Veto of the Minimum Wage Bill: Impact on Poor and Minority Workers.

ERIC Educational Resources Information Center

Shapiro, Isaac

Restoration of an adequate minimum wage remains a critical ingredient in efforts to provide income security for poor and minority workers. The experience of recent years indicates that work does not provide economic security for many poor, Black, and Hispanic workers. National and minority unemployment rates have dropped during the economic…

Computer-Assisted Literacy Instruction in Phonics,

DTIC Science & Technology

1980-04-01

below 4.5, as measured on the Gates-MacGinitie reading test and poor word attack skills , as measured by the Wide Range Achievement Test (WRAT), Level...see and hear the words they were to pronouce, (2) to request that the synthesizer repronounce words, and (3) to sound out words in isolation and in...continued with the remaining 3 weeks of the ART Program, which covered vocabulary development, reading comprehension, and study skills . The RGLs of both

Associations of Military Divorce with Mental, Behavioral, and Physical Health Outcomes

DTIC Science & Technology

2015-06-19

recent divorce re - ported subsequent poor health and military outcomes compared to those who remained married during the same time frame. We...determined using DMDC re - cords and were backfilled with self-reported data to reduce missing values. Baseline functional health was eval- uated with the...4.8 %, 3.0 %, and 3.0 % developing each of these conditions, re - spectively, between baseline and follow-up. Smoking initi- ation and recidivism

Provider Compliance And Competence With Oral Cancer Screenings In The U.S. Army

DTIC Science & Technology

2016-05-01

irritation, poor dental hygiene, and marijuana use have been implicated in oral cancer development. Currently these causations remain unproven (9...assumed that, since oral cancer screening protocols were not required to be taught in dental school prior to 2010, 35 some providers would benefit ...felt that it would not, or had no opinion. It appears that Army providers and patients may benefit from increased oral cancer screening training. Of

Thermal evolution of a hyperextended rift basin, Mauléon Basin, western Pyrenees

NASA Astrophysics Data System (ADS)

Hart, Nicole R.; Stockli, Daniel F.; Lavier, Luc L.; Hayman, Nicholas W.

2017-06-01

Onshore and offshore geological and geophysical observations and numerical modeling have greatly improved the conceptual understanding of magma-poor rifted margins. However, critical questions remain concerning the thermal evolution of the prerift to synrift phases of thinning ending with the formation of hyperextended crust and mantle exhumation. In the western Pyrenees, the Mauléon Basin preserves the structural and stratigraphic record of Cretaceous extension, exhumation, and sedimentation of the proximal-to-distal margin development. Pyrenean shortening uplifted basement and overlying sedimentary basins without pervasive shortening or reheating, making the Mauléon Basin an ideal locality to study the temporal and thermal evolution of magma-poor hyperextended rift systems through coupling bedrock and detrital zircon (U-Th)/He thermochronometric data from transects characterizing different structural rifting domains. These new data indicate that the basin was heated during early rifting to >180°C with geothermal gradients of 80-100°C/km. The proximal margin recorded rift-related exhumation/cooling at circa 98 Ma, whereas the distal margin remained >180°C until the onset of Paleocene Pyrenean shortening. Lithospheric-scale numerical modeling shows that high geothermal gradients, >80°C/km, and synrift sediments >180°C, can be reached early in rift evolution via heat advection by lithospheric depth-dependent thinning and blanketing caused by the lower thermal conductivity of synrift sediments. Mauléon Basin thermochronometric data and numerical modeling illustrate that reheating of basement and synrift strata might play an important role and should be considered in the future development of conceptual and numerical models for hyperextended magma-poor continental rifted margins.

Nutritional and socioeconomic status in cognitive development of Santal children of Purulia district, India.

PubMed

Chowdhury, Sutanu Dutta; Ghosh, Tusharkanti

2011-03-01

Cognitive development of children depends on nutritional and socioeconomic factors. The objectives of the present study were to assess the cognitive development and to investigate the relationship of nutritional and socioeconomic status (SES) to cognitive development in 5-12 year old Santal children of Purulia district of West Bengal, India. The nutritional status of each child was assessed by z-score of height-for-age, weight-for-height and weight-for-age parameters. SES was measured using the updated Kuppusswami scale. Cognitive development was measured by Raven's Coloured Progressive Matrices (RCPM). The growth curve of RCPM scores of Santal children remained around the 5(th) percentile values of British children. The RCPM scores of the adequately nourished children and upper-lower SES were significantly higher (p < 0.05) than the children with lower SES and nutritional status. About 42.96% and 27.69% of Santal children were found to be in the intellectually deficient and below average groups, respectively. RCPM scores of Santal children were significantly correlated with nutritional status and socioeconomic factors (p < 0.01). The surveyed children showed poor cognitive functions. The vulnerable nutritional and socioeconomic statuses of Santal children are the major causes for their poor cognitive development.

Antidepressants and the adolescent brain.

PubMed

Cousins, Lesley; Goodyer, Ian M

2015-05-01

Major unipolar depression is a significant global health problem, with the highest incident risk being during adolescence. A depressive illness during this period is associated with negative long-term consequences including suicide, additional psychiatric comorbidity, interpersonal relationship problems, poor educational performance and poor employment attainment well into adult life. Despite previous safety concerns, selective serotonin reuptake inhibitors (SSRIs) remain a key component of the treatment of moderate to severe depression episodes in adolescents. The impact of SSRIs on the developing adolescent brain, however, remains unclear. In this review we first consider what is currently known about the developing brain during adolescence and how these development processes may be affected by a depressive illness. We then review our understanding of the action of SSRIs, their effects on the brain and how these may differ between adults and adolescents. We conclude that there is currently little evidence to indicate that the human adolescent brain is at developmental risk from SSRIs. Furthermore, there is no clear-cut evidence to support the concerns of marked suicidal adverse side effects accruing in depressed adolescents being treated with SSRIs. Neither, however, is there irrefutable evidence to dismiss all such concerns. This makes SSRI prescribing a matter of medical judgement, ensuring the benefits outweigh the risks for the individual patients, as with so much in therapeutics. Overall, SSRIs show clinical benefits that we judge to outweigh the risks to neurodevelopment and are an important therapeutic choice in the treatment of moderate to severe adolescent depression. © The Author(s) 2015.

Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

PubMed Central

Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena

2018-01-01

The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537

Speech Perception Deficits in Mandarin-Speaking School-Aged Children with Poor Reading Comprehension

PubMed Central

Liu, Huei-Mei; Tsao, Feng-Ming

2017-01-01

Previous studies have shown that children learning alphabetic writing systems who have language impairment or dyslexia exhibit speech perception deficits. However, whether such deficits exist in children learning logographic writing systems who have poor reading comprehension remains uncertain. To further explore this issue, the present study examined speech perception deficits in Mandarin-speaking children with poor reading comprehension. Two self-designed tasks, consonant categorical perception task and lexical tone discrimination task were used to compare speech perception performance in children (n = 31, age range = 7;4–10;2) with poor reading comprehension and an age-matched typically developing group (n = 31, age range = 7;7–9;10). Results showed that the children with poor reading comprehension were less accurate in consonant and lexical tone discrimination tasks and perceived speech contrasts less categorically than the matched group. The correlations between speech perception skills (i.e., consonant and lexical tone discrimination sensitivities and slope of consonant identification curve) and individuals’ oral language and reading comprehension were stronger than the correlations between speech perception ability and word recognition ability. In conclusion, the results revealed that Mandarin-speaking children with poor reading comprehension exhibit less-categorized speech perception, suggesting that imprecise speech perception, especially lexical tone perception, is essential to account for reading learning difficulties in Mandarin-speaking children. PMID:29312031

Epithelial-mesenchymal Transition---A Hallmark of Breast Cancer Metastasis.

PubMed

Wang, Yifan; Zhou, Binhua P

2013-03-01

Epithelial-mesenchymal transition (EMT) is a highly conserved cellular program that converts polarized, immotile epithelial cells to migratory mesenchymal cells. In addition, EMT was initially recognized as a key step for morphogenesis during embryonic development. Emerging evidences indicate that this important developmental program promotes metastasis, drug resistance, and tumor recurrence, features that are associated with a poor clinical outcome for patients with breast cancer. Therefore, better understanding of regulation and signaling pathways in EMT is essential to develop novel targeted therapeutics. In this review, we present updated developments underlying EMT in tumor progression and metastasis, and discuss the challenges remaining in breast cancer research.

STUDENTS IN BRUNEI DARUSSALAM.

PubMed

Lim, A G; Chong, V H; Salleh, S M; Poh, S H

2017-03-01

Sexually transmitted infections (STI) remain an important public health issue globally, particularly among the young population. Despite being preventable and curable, STI continue to spread. Lack of access to treatment is an important factor in many developing and underdeveloped nations. Lack of awareness and knowledge is another important factor. This study assessed the awareness, knowledge, and misconceptions among secondary school students on STI. Overall, awareness was poor but better among male students and those in the Pure Science academic streaming. Similarly, the knowledge level of STI was also poor: low level (63.0%), moderate level (34.4%), and high level (2.6%). Male students (p=0.014) and Pure Science academic streaming students (p<0.001) scored better. There were misconceptions, but poor knowledge was predominant. Common sources of information were teachers, health professionals, Internet, parents and TV programs. Based on our study, more needs to be done to improve the awareness and knowledge level of STI, and detailed inclusion into the educational curriculum may be a consideration.

Nitric oxide mediates local activity-dependent excitatory synapse development.

PubMed

Nikonenko, Irina; Nikonenko, Alexander; Mendez, Pablo; Michurina, Tatyana V; Enikolopov, Grigori; Muller, Dominique

2013-10-29

Learning related paradigms play an important role in shaping the development and specificity of synaptic networks, notably by regulating mechanisms of spine growth and pruning. The molecular events underlying these synaptic rearrangements remain poorly understood. Here we identify NO signaling as a key mediator of activity-dependent excitatory synapse development. We find that chronic blockade of NO production in vitro and in vivo interferes with the development of hippocampal and cortical excitatory spine synapses. The effect results from a selective loss of activity-mediated spine growth mechanisms and is associated with morphological and functional alterations of remaining synapses. These effects of NO are mediated by a cGMP cascade and can be reproduced or prevented by postsynaptic expression of vasodilator-stimulated phosphoprotein phospho-mimetic or phospho-resistant mutants. In vivo analyses show that absence of NO prevents the increase in excitatory synapse density induced by environmental enrichment and interferes with the formation of local clusters of excitatory synapses. We conclude that NO plays an important role in regulating the development of excitatory synapses by promoting local activity-dependent spine-growth mechanisms.

Opioid analgesics and P-glycoprotein efflux transporters: a potential systems-level contribution to analgesic tolerance.

PubMed

Mercer, Susan L; Coop, Andrew

2011-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationships to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation.

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Pharmacotherapy of Essential Tremor

PubMed Central

Hedera, Peter; Cibulčík, František; Davis, Thomas L.

2013-01-01

Essential tremor (ET) is a common movement disorder but its pathogenesis remains poorly understood. This has limited the development of effective pharmacotherapy. The current therapeutic armamentaria for ET represent the product of careful clinical observation rather than targeted molecular modeling. Here we review their pharmacokinetics, metabolism, dosing, and adverse effect profiles and propose a treatment algorithm. We also discuss the concept of medically refractory tremor, as therapeutic trials should be limited unless invasive therapy is contraindicated or not desired by patients. PMID:24385718

An aegialodontid upper molar and the evolution of mammal dentition.

PubMed

Lopatin, Alexey V; Averianov, Alexander O

2006-08-25

The most obvious key synapomorphy of the therian mammals is the tribosphenic pattern of their molars. Tribosphenic teeth are capable of both shearing and grinding, which substantially increase effectiveness of food processing and, in turn, permit evolution of a wide range of dietary specializations. Functional tribospheny developed repeatedly during mammalian evolution but was successful only in the Boreosphenida. The earliest stage in the development of boreosphenidan tribospheny has remained poorly understood, being documented only by lower molars of aegialodontids. Here, we report a known upper molar of an aegialodontid mammal, Kielantherium, from the Early Cretaceous of Mongolia.

Diastolic dysfunction in hypertension.

PubMed

Nazário Leão, R; Marques da Silva, P

Hypertension and coronary heart disease, often coexisting, are the most common risk factors for heart failure. The progression of hypertensive heart disease involves myocardial fibrosis and alterations in the left ventricular geometry that precede the functional change, initially asymptomatic. The left ventricular diastolic dysfunction is part of this continuum being defined by the presence of left ventricular diastolic dysfunction without signs or symptoms of heart failure or poor left ventricular systolic function. It is highly prevalent in hypertensive patients and is associated with increased cardiovascular morbidity and mortality. Despite its growing importance in clinical practice it remains poorly understood. This review aims to present the epidemiological fundamentals and the latest developments in the pathophysiology, diagnosis and treatment of left ventricular diastolic dysfunction. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Renal cell carcinoma in the allograft: what is the role of polyomavirus?

PubMed

Neirynck, Valerie; Claes, Kathleen; Naesens, Maarten; De Wever, Liesbeth; Pirenne, Jacques; Kuypers, Dirk; Vanrenterghem, Yves; Poppel, Hendrik Van; Kabanda, Andre; Lerut, Evelyne

2012-07-01

BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.

Effusive-constrictive pericarditis as the manifestation of an unexpected diagnosis.

PubMed

Marta, Liliana; Alves, Miguel; Peres, Marisa; Ferreira, Ricardo; Ferreira, Hugo; Leal, Margarida; Nobre, Ângelo

2015-01-01

Constrictive pericarditis is a clinical condition characterized by the appearance of signs and symptoms of right heart failure due to loss of pericardial compliance. Cardiac surgery is now one of the most frequent causes in developed countries, while tuberculosis remains the most prevalent cause in developing countries. Malignancy is a rare cause but usually has a poor prognosis. The diagnosis of constrictive pericarditis remains a clinical challenge and requires a combination of noninvasive diagnostic methods (echocardiography, cardiac magnetic resonance and computed tomography); in some cases, cardiac catheterization is needed to confirm the diagnosis. The authors present the case of a 51-year-old man, hospitalized due to cardiac tamponade. Diagnostic investigation was suggestive of tuberculous etiology. Despite directed medical therapy, the patient developed effusive-constrictive physiology. He underwent pericardiectomy and anatomopathologic study suggested a neoplastic etiology. The patient died in the postoperative period from biventricular failure. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Consideration of Environmental Factors in Planning and Development of Urban Areas

NASA Astrophysics Data System (ADS)

Kustysheva, I.

2017-11-01

Environmental factors, in varying degrees, always have a direct influence on the urban environment formation and the provision of favorable and safe conditions for the life of the population. Their role in the planning and development of urban areas remains an integral part of the management of such areas. Management should be aimed at improving the efficiency of use of the territories and ecological environment improvement. Planning must be done with the consideration of identified ecological processes in cities on the basis of the information about their occurrence in the past and present. Currently, cities face a multitude of problems that require urgent and immediate solutions. One of the most important issues is the poor state of the urban environment, so the environmental factors remain one of the most critical problems that should be considered by the authorities while implementing the urban areas’ development plans. The article discusses the role of environmental factors in the management and planning of urban territories by the example of the city of Tobolsk.

How do older employees with health problems remain productive at work?: a qualitative study.

PubMed

Leijten, Fenna; van den Heuvel, Swenneke; Geuskens, Goedele; Ybema, Jan Fekke; de Wind, Astrid; Burdorf, Alex; Robroek, Suzan

2013-03-01

The goal of this qualitative study was to gain insight into how older employees remain productive at work in spite of health problems. Twenty-six semi-structured telephone interviews were conducted with older employees, 46-63 years of age, who reported a poor health in the Study on Transitions in Employment, Ability, and Motivation. Demographic, health, and work information was gathered, followed by information on adjustments made in response to health problems. Inductive and deductive analyses were done independently by two researchers. Four pathways through which poor health could influence productivity were identified: (1) poor health did not influence productivity; (2) poor health created a temporary imbalance in demands and external and internal resources after which adjustments were made and productivity was maintained; (3) adjustments were made in response to an imbalance, but productivity remained reduced; and (4) no adjustments were made and productivity was reduced. Whether and which adjustments occurred was influenced by factors in various domains, such as: visibility of the problem (health), autonomy (work-related), support (relational), and the ability to ask for help (personal). Sustainable productivity was influenced by internal factors that enhanced or hindered the creation of a balance, and by whether appropriate adjustments were made. The influence that health can have on productivity depends on the individuals' unique imbalance and personal disposition. Helpful a priori work place characteristics and personal well-being should be promoted so that a balance between demands and resources can be found in times of poor health.

Operative management of penetrating carotid artery injuries.

PubMed

Reva, V A; Pronchenko, A A; Samokhvalov, I M

2011-07-01

To analyse management and outcomes of carotid artery (CA) injuries. Retrospective study of the patients in the combat operations in Chechnya (1999-2002) and in peacetime (2003-2009). A total of 46 patients with missile (27) and stab (19) wounds, who had common and internal CA injury, underwent an open surgery. Temporary shunts (TSs) were placed in eight patients with more severe injuries. Retrospective analysis of patients' data. CA ligation and CA repair were performed in 9 and 37 patients, respectively. Of the nine patients with CA ligation, five developed neurologic deficit; the remaining four patients died (100% of poor outcomes). Of the 37 patients with blood flow restoration, nine patients died and neurologic deficit persisted in two patients (30% of poor outcomes) (p < 0.05). Among patients with TS, three patients died and two had stable neurologic deficit (63% of poor results). Of the patients without TS, 10 patients died and five had neurologic disorders (56% of poor outcomes) (p = 0.53). CA repair is the method of choice in CA injury. TS use does not result in a decreased mortality rate or neurologic deficit reduction in patients with severe injuries. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Women and finance.

PubMed

Seaforth, W

1995-12-01

This article discusses women's rights to inherit land, the impact of flexible loan schemes for women, and the paucity of available loan schemes for women. The poor without land ownership have many problems obtaining credit for shelter from conventional finance markets. The poor must limit loans to small amounts that banks do not want to bother with. Eligibility criteria for loans usually require collateral, such as a high and regular income, savings, or land. The poor, and particularly poor women, cannot acquire credit or can do so only through a husband or male relative. Female heads of households are discriminated against when the man is assumed to be the major income source. Most housing purchases in developing countries are made through cash payments from family savings or informal loans. Even small loans may place a heavy burden on women. The author gives several examples of credit groups and their success in generating income and housing security. There remains a need to provide training and education for women and to improve women's access to credit and land. Information should be available to women on how to obtain credit. Governments and nongovernmental organizations have a responsibility to provide support for women's efforts to provide housing and support for their families.

Development process of an assessment tool for disruptive behavior problems in cross-cultural settings: the Disruptive Behavior International Scale – Nepal version (DBIS-N)

PubMed Central

Burkey, Matthew D.; Ghimire, Lajina; Adhikari, Ramesh P.; Kohrt, Brandon A.; Jordans, Mark J. D.; Haroz, Emily; Wissow, Lawrence

2017-01-01

Systematic processes are needed to develop valid measurement instruments for disruptive behavior disorders (DBDs) in cross-cultural settings. We employed a four-step process in Nepal to identify and select items for a culturally valid assessment instrument: 1) We extracted items from validated scales and local free-list interviews. 2) Parents, teachers, and peers (n=30) rated the perceived relevance and importance of behavior problems. 3) Highly rated items were piloted with children (n=60) in Nepal. 4) We evaluated internal consistency of the final scale. We identified 49 symptoms from 11 scales, and 39 behavior problems from free-list interviews (n=72). After dropping items for low ratings of relevance and severity and for poor item-test correlation, low frequency, and/or poor acceptability in pilot testing, 16 items remained for the Disruptive Behavior International Scale—Nepali version (DBIS-N). The final scale had good internal consistency (α=0.86). A 4-step systematic approach to scale development including local participation yielded an internally consistent scale that included culturally relevant behavior problems. PMID:28093575

Socioeconomic Determinants of Adult Mortality in Namibia Using an Event History Analysis.

PubMed

Kandjimbi, Alina; Nickanor, Ndeyapo; Kazembe, Lawrence N

2014-01-01

Adult mortality remains a neglected public health issue in sub-Saharan Africa, with most policy instruments concentrated on child and maternal health. In developed countries, adult mortality is negatively associated with socioeconomic factors. A similar pattern is expected in developing countries, but has not been extensively demonstrated, because of dearth of data. Understanding the hazard and factors associated with adult mortality is crucial for informing policies and for implementation of interventions aimed at improving adult survival. This paper applied a geo-additive survival model to elucidate effects of socioeconomic factors on adult mortality in Namibia, controlling for spatial frailties. Results show a clear disadvantage for adults in rural areas, for those not married and from poor households or in female-headed households. The hazard of adult mortality was highly variable with a 1.5-fold difference between areas, with highest hazard recorded in north eastern, central west and southern west parts of the country. The analysis emphasizes that, for Namibia to achieve its national development goals, targeted interventions should be aimed at poor-resourced adults, particularly in high-risk areas.

Psychosocial work environment and retirement age: a prospective study of 1876 senior employees.

PubMed

Thorsen, Sannie Vester; Jensen, Per H; Bjørner, Jakob Bue

2016-08-01

Retention of senior employees is a challenge for most developed countries. We aimed to identify psychosocial work environment factors of importance for the retention of older employees by evaluating the association between the psychosocial work environment and voluntary early retirement in a longitudinal study. Data about work environment, health, and background factors came from the DANES 2008 questionnaire survey. We followed members of the Danish early retirement scheme for up to 4 years in national registers-focusing on the age range, 60-64 years, where early retirement was possible. We used Cox proportional hazard regression to analyze the rate of early retirement. The study included 16 psychosocial work environment factors. The following 10 psychosocial factors were significant predictors of early retirement in covariate adjusted analyses: Low job satisfaction, low influence in job, low possibilities for development, low role clarity, perceived age discrimination, low recognition from management, low workplace justice, poor trust in management, poor leadership quality, and poor predictability. No significant association with early retirement was found for work pace, quantitative demands, emotional demands, role conflicts, social community between colleagues, and trust between colleagues. Older employees with high job satisfaction, influence, possibilities for development, positive management relations, and jobs with no age discrimination remained longer at the labor market. However, we found no evidence that low demands or good relations between colleagues could influence older employees' decision on early retirement.

A step toward development of printable dosage forms for poorly soluble drugs.

PubMed

Raijada, Dhara; Genina, Natalja; Fors, Daniela; Wisaeus, Erik; Peltonen, Jouko; Rantanen, Jukka; Sandler, Niklas

2013-10-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet printing (PIJ) and impression printing (flexography). The printed dosage forms were characterized using scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and the amount of drug was determined using high-performance liquid chromatography. Solutions of PRX in polyethylene glycol 400 (PEG-400):ethanol (40:60) and in PEG-400 were found to be optimal formulations for PIJ and flexography, respectively. SEM-EDX analysis revealed no visible solid particles on the printed dosage forms indicating the drug most likely remained in solution after printing. More accurate drug deposition was obtained by PIJ as compared with flexography. More than 90% drug release was achieved within 5 min regardless of printing method used. The solubility of drug in solvents/cosolvents, rheological properties of formulations, properties of substrate, feasibility and accuracy of the printing methods, and detection limit of analytical techniques for characterization of printed dosage forms are some of the concerns that need to be addressed for development of printable dosage forms of poorly soluble drugs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Opportunities and challenges in implementing community based skilled birth attendance strategy in Kenya.

PubMed

Mannah, Margaret Titty; Warren, Charlotte; Kuria, Shiphrah; Adegoke, Adetoro A

2014-08-15

Availability of skilled care at birth remains a major problem in most developing countries. In an effort to increase access to skilled birth attendance, the Kenyan government implemented the community midwifery programme in 2005. The aim of this programme was to increase women's access to skilled care during pregnancy, childbirth and post-partum within their communities. Qualitative research involving in-depth interviews with 20 community midwives and six key informants. The key informants were funder, managers, coordinators and supervisors of the programme. Interviews were conducted between June to July, 2011 in two districts in Western and Central provinces of Kenya. Findings showed major challenges and opportunities in implementing the community midwifery programme. Challenges of the programme were: socio-economic issues, unavailability of logistics, problems of transportation for referrals and insecurity. Participants also identified the advantages of having midwives in the community which were provision of individualised care; living in the same community with clients which made community midwives easily accessible; and flexible payment options. Although the community midwifery model is a culturally acceptable method to increase skilled birth attendance in Kenya, the use of skilled birth attendance however remains disproportionately lower among poor mothers. Despite several governmental efforts to increase access and coverage of delivery services to the poor, it is clear that the poor may still not access skilled care even with skilled birth attendants residing in the community due to several socio-economic barriers.

Human rights and the requirement for international medical aid.

PubMed

Tolchin, Benjamin

2008-08-01

Every year approximately 18 million people die prematurely from treatable medical conditions including infectious diseases and nutritional deficiencies. The deaths occur primarily amongst the poorest citizens of poor developing nations. Various groups and individuals have advanced plans for major international medical aid to avert many of these unnecessary deaths. For example, the World Health Organization's Commission on Macroeconomics and Health estimated that eight million premature deaths could be prevented annually by interventions costing roughly US$57 bn per year. This essay advances an argument that human rights require high-income nations to provide such aid. The essay briefly examines John Rawls' obligations of justice and the reasons that their applicability to cases of international medical aid remains controversial. Regardless, the essay argues that purely humanitarian obligations bind the governments and citizens of high-income liberal democracies at a minimum to provide major medical aid to avert premature deaths in poor nations. In refusing to undertake such medical relief efforts, developed nations fail to adequately protect a fundamental human right to life.

STUDIES ON RARE AND POORLY KNOWN LEECHES (ANNELIDA: HIRUDINEA: GLOSSIPHONIIDAE) IN EASTERN NORTH AMERICA

EPA Science Inventory

Three taxa within the leech family Glossiphoniidae, Actinobdella inequiannulata, Placobdella hollensis, and Theromyzon spp., though widespread in eastern North America, remain poorly known with respect to their biology and systematics. All three taxa have been collected in New E...

Poorly controlled postoperative pain: prevalence, consequences, and prevention

PubMed Central

Gan, Tong J

2017-01-01

This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine. PMID:29026331

Poorly controlled postoperative pain: prevalence, consequences, and prevention.

PubMed

Gan, Tong J

2017-01-01

This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine.

Pediatric anesthesia in developing countries.

PubMed

Bösenberg, Adrian T

2007-06-01

To highlight the problems faced in developing countries where healthcare resources are limited, with particular emphasis on pediatric anesthesia. The fact that very few publications address pediatric anesthesia in the developing world is not surprising given that most anesthetics are provided by nonphysicians, nurses or unqualified personnel. In compiling this article information is drawn from pediatric surgical, anesthetic and related texts. In a recent survey more than 80% of anesthesia providers in a poor country acknowledged that with the limited resources available they could not provide basic anesthesia for children less than 5 years. Although many publications could be regarded as anecdotal, the similarities to this survey suggest that the lack of facilities is more generalized than we would like to believe. The real risk of anesthesia in comparison to other major health risks such as human immunodeficiency virus, malaria, tuberculosis and trauma remains undetermined. The critical shortage of manpower remains a barrier to progress. Despite erratic electrical supplies, inconsistent oxygen delivery, paucity of drugs or equipment and on occasion even lack of running water, many provide life-saving anesthesia. Perioperative morbidity and mortality is, however, understandably high by developed world standards.

Current State of Animal (Mouse) Modeling in Melanoma Research.

PubMed

Kuzu, Omer F; Nguyen, Felix D; Noory, Mohammad A; Sharma, Arati

2015-01-01

Despite the considerable progress in understanding the biology of human cancer and technological advancement in drug discovery, treatment failure remains an inevitable outcome for most cancer patients with advanced diseases, including melanoma. Despite FDA-approved BRAF-targeted therapies for advanced stage melanoma showed a great deal of promise, development of rapid resistance limits the success. Hence, the overall success rate of melanoma therapy still remains to be one of the worst compared to other malignancies. Advancement of next-generation sequencing technology allowed better identification of alterations that trigger melanoma development. As development of successful therapies strongly depends on clinically relevant preclinical models, together with the new findings, more advanced melanoma models have been generated. In this article, besides traditional mouse models of melanoma, we will discuss recent ones, such as patient-derived tumor xenografts, topically inducible BRAF mouse model and RCAS/TVA-based model, and their advantages as well as limitations. Although mouse models of melanoma are often criticized as poor predictors of whether an experimental drug would be an effective treatment, development of new and more relevant models could circumvent this problem in the near future.

Retinitis and optic neuritis in a child with chickenpox: case report and review of literature.

PubMed

Tappeiner, Christoph; Aebi, Christoph; Garweg, Justus G

2010-12-01

In immunocompetent individuals, necrotizing retinopathy is a rare complication of chickenpox. Herein, we report on a 3-year-old immunocompetent boy who developed retinitis and optic neuritis 3 days after the onset of chickenpox and compare the findings to published cases. Since macula and optic nerve were affected, visual acuity remained poor. An early diagnosis and treatment of ocular manifestations in chickenpox is imperative for the preservation of a residual visual function and prevention of blinding secondary complications.

Mitral valve prolapse and Marfan syndrome.

PubMed

Thacoor, Amitabh

2017-07-01

Marfan syndrome is a multisystemic genetic condition affecting connective tissue. It carries a reduced life expectancy, largely dependent on cardiovascular complications. More common cardiac manifestations such as aortic dissection and aortic valve incompetence have been widely documented in the literature. Mitral valve prolapse (MVP), however, has remained poorly documented. This article aims at exploring the existing literature on the pathophysiology and diagnosis of MVP in patients with Marfan syndrome, defining its current management and outlining the future developments surrounding it. © 2017 Wiley Periodicals, Inc.

Poverty's threat.

PubMed

1988-03-01

In the debate on the Report of the World Commission on Environment and Development, chaired by Mrs. Gro Harlem Brundtland, Prime Minister of Norway, delegates to the UN General Assembly asserted that problems generated by the impact of poverty on the environment could not be solved by restricting aid to developing countries unless those countries promised to cease damaging their environment. Rather, most delegates agreed, aid should include the resources which would enable those countries to achieve "sustainable development," i.e., development that does not destroy the environment and deplete natural resources. The United States countered with the opinion that what is needed is not a UN organized "sustainable development program," but rather a grassroots "sustainable development movement" in all countries. Several delegates pointed out that it was the affluent countries which played a large part in the destruction of the environment. The Present of the Maldives, Maumoon Abdul Gayoom, pointed out, for example, that the greenhouse effect, generated by the burning of fossil fuels, would raise the sea level 2 meters, virtually submerging his country. Mrs. Brundtland pointed out that it was not morally acceptable to suggest that the poor remain poor to protect the environment. Governments at all levels, she said, must include environmental concerns in their decision making in all sectors of governmental functioning, e.g., finance, industry, energy, and agriculture.

Group 2 Pulmonary Hypertension: Pulmonary Venous Hypertension: Epidemiology and Pathophysiology.

PubMed

Clark, Craig B; Horn, Evelyn M

2016-08-01

Pulmonary hypertension from left heart disease (PH-LHD) is the most common form of PH, defined as mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure ≥15 mm Hg. PH-LHD development is associated with more severe left-sided disease and its presence portends a poor prognosis, particularly once right ventricular failure develops. Treatment remains focused on the underlying LHD and despite initial enthusiasm for PH-specific therapies, most studies have been disappointing and their routine clinical use cannot be recommended. More work is urgently needed to better understand the pathophysiology underlying this disease and to develop effective therapeutic strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

Microstructural and functional connectivity in the developing preterm brain

PubMed Central

Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Constable, R. Todd; Ment, Laura R.

2011-01-01

Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Since variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared to term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity. PMID:21255705

Psychosocial mechanisms linking the social environment to mental health in African Americans

USDA-ARS?s Scientific Manuscript database

Resource-poor social environments predict poor health, but the mechanisms and processes linking the social environment to psychological health and well-being remain unclear. This study explored psychosocial mediators of the association between the social environment and mental health in African Amer...

Opioid Analgesics and P-glycoprotein Efflux Transporters: A Potential Systems-Level Contribution to Analgesic Tolerance

PubMed Central

Mercer, Susan L.; Coop, Andrew

2012-01-01

Chronic clinical pain remains poorly treated. Despite attempts to develop novel analgesic agents, opioids remain the standard analgesics of choice in the clinical management of chronic and severe pain. However, mu opioid analgesics have undesired side effects including, but not limited to, respiratory depression, physical dependence and tolerance. A growing body of evidence suggests that P-glycoprotein (P-gp), an efflux transporter, may contribute a systems-level approach to the development of opioid tolerance. Herein, we describe current in vitro and in vivo methodology available to analyze interactions between opioids and P-gp and critically analyze P-gp data associated with six commonly used mu opioids to include morphine, methadone, loperamide, meperidine, oxycodone, and fentanyl. Recent studies focused on the development of opioids lacking P-gp substrate activity are explored, concentrating on structure-activity relationship development to develop an optimal opioid analgesic lacking this systems-level contribution to tolerance development. Continued work in this area will potentially allow for delineation of the mechanism responsible for opioid-related P-gp up-regulation and provide further support for evidence based medicine supporting clinical opioid rotation. PMID:21050174

The links between agriculture and health: an intersectoral opportunity to improve the health and livelihoods of the poor.

PubMed Central

Hawkes, Corinna; Ruel, Marie

2006-01-01

Agriculture and health are linked in many ways. First, agriculture is essential for good health: it produces the world's food, fibre and materials for shelter; in many countries it is also an important source of livelihood among the poor. At the same time, agriculture can be linked with poor health, including malnutrition, malaria, foodborne illnesses, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), livestock-related diseases, chronic diseases and occupational ill-health. Health also affects agriculture: people's health status influences the demand for agricultural outputs, and in agricultural communities, poor health reduces work performance, reducing income and productivity and perpetuating a downward spiral into ill-health. This paper presents an overview of the bidirectional links between agriculture and health with a focus on the developing world. It develops a conceptual framework that brings together the various links between agriculture and health into a single broad framework. The framework comprises the core components of the agricultural supply chain (producers, systems and outputs), key health concerns and the mechanisms of common interaction between the agricultural and health components: income, labour, environment and access -- all key social determinants of health. These links between agriculture and health present an opportunity for the two sectors to work together to find solutions to each other's problems. Yet the health and agricultural sectors remain poorly coordinated. Leadership from global health and agricultural institutions is needed to build policies and good governance to facilitate integration, while capacity building is needed at all levels to help translate the conceptual links into comprehensive action on the ground. Health and agricultural researchers likewise need to work more closely together to achieve common goals. PMID:17242835

Depression in obese patients with primary fibromyalgia: the mediating role of poor sleep and eating disorder features.

PubMed

Senna, Mohammed K; Ahmad, Hamada S; Fathi, Warda

2013-03-01

Depression is a prominent feature in fibromyalgia syndrome. Patients with fibromyalgia syndrome who are obese, with poor sleep quality, and those who have recurrent episodes of binge eating are at greater risk to develop depression. The aim of this cross-sectional study was to examine the hypothesis that the relationship between obesity and depression in patients with primary fibromyalgia syndrome is mediated by poor sleep, binge eating disorder (BED), and weight and shape concern. This study included 131 patients with primary fibromyalgia syndrome. Participants completed the following questionnaires: Pittsburgh Sleep Quality Index, Beck Depression Inventory-II, Eating Disorder questionnaire, and Fibromyalgia Impact Questionnaire. Body mass index (BMI) provided the primary indicator of obesity. Sobel test showed that the conditions for complete mediation were satisfied on the weight and shape concern as mediator between BMI and depression because the association between BMI and depression score became insignificant after controlling of weight and shape concern. However, since the association between BMI and depression remained significant after BED and poor sleep score were controlled, thus for both mediators, the conditions for partial mediation on the depression were satisfied. The findings suggest that in patients with primary fibromyalgia syndrome, weight and shape concern, BED, and poor sleep quality are important mediators of the relationship between obesity and depression. We suggest that a greater focus on these mediators in depression treatment may be indicated.

Re-employment, job quality, health and allostatic load biomarkers: prospective evidence from the UK Household Longitudinal Study

PubMed Central

Chandola, Tarani; Zhang, Nan

2018-01-01

Abstract Background There is little evidence on whether becoming re-employed in poor quality work is better for health and well-being than remaining unemployed. We examined associations of job transition with health and chronic stress-related biomarkers among a population-representative cohort of unemployed British adults. Methods A prospective cohort of 1116 eligible participants aged 35 to 75 years, who were unemployed at wave 1 (2009/10) of the UK Household Longitudinal Study, were followed up at waves 2 (2010/11) and 3 (2011/12) for allostatic load biomarkers and self-reported health. Negative binomial and multiple regression models estimated the association between job adversity and these outcomes. Results Compared with adults who remained unemployed, formerly unemployed adults who transitioned into poor quality jobs had higher levels of overall allostatic load (0.51, 0.32–0.71), log HbA1c (0.06, <0.001–0.12), log triglycerides (0.39, 0.22–0.56), log C-reactive protein (0.45, 0.16–0.75), log fibrinogen (0.09, 0.01–0.17) and total cholesterol to high-density lipoprotein (HDL) ratio (1.38, 0.88–1.88). Moreover, physically healthier respondents at wave 1 were more likely to transition into good quality and poor quality jobs after 1 year than those who remained unemployed. Conclusions Formerly unemployed adults who transitioned into poor quality work had greater adverse levels of biomarkers compared with their peers who remained unemployed. The selection of healthier unemployed adults into these poor quality or stressful jobs was unlikely to explain their elevated levels of chronic stress-related biomarkers. Job quality cannot be disregarded from the employment success of the unemployed, and may have important implications for their health and well-being. PMID:29024973

Twin Screw Extruder Production of MTTP Decoy Flares SERDP WP-1240

DTIC Science & Technology

2005-12-01

5 3. Carnauba Wax ( wax from palm tree exudate, a common ingredient in high quality car polish) Hazards of the remaining formulations were...1. Microsere 5866, a microcrystalline wax derived from refining petroleum 2. Elvax 250, poly(ethylene-co-vinyl acetate) (hot glue ingredient...5866 Poor performance when 1-gm sample ignited Elvax 250 Poor performance when 1-gm sample ignited Carnuba Wax Poor performance when 1-gm sample

Healthcare Access and Health Beliefs of the Indigenous Peoples in Remote Amazonian Peru

PubMed Central

Brierley, Charlotte K.; Suarez, Nicolas; Arora, Gitanjli; Graham, Devon

2014-01-01

Little is published about the health issues of traditional communities in the remote Peruvian Amazon. This study assessed healthcare access, health perceptions, and beliefs of the indigenous population along the Ampiyacu and Yaguasyacu rivers in north-eastern Peru. One hundred and seventy-nine adult inhabitants of 10 remote settlements attending health clinics were interviewed during a medical services trip in April 2012. Demographics, health status, access to healthcare, health education, sanitation, alcohol use, and smoke exposure were recorded. Our findings indicate that poverty, household overcrowding, and poor sanitation remain commonplace in this group. Furthermore, there are poor levels of health education and on-going barriers to accessing healthcare. Healthcare access and health education remain poor in the remote Peruvian Amazon. This combined with poverty and its sequelae render this population vulnerable to disease. PMID:24277789

Serving the world's poor, profitably.

PubMed

Prahalad, C K; Hammond, Allen

2002-09-01

By stimulating commerce and development at the bottom of the economic pyramid, multi-nationals could radically improve the lives of billions of people and help create a more stable, less dangerous world. Achieving this goal does not require MNCs to spearhead global social-development initiatives for charitable purposes. They need only act in their own self-interest. How? The authors lay out the business case for entering the world's poorest markets. Fully 65% of the world's population earns less than $2,000 per year--that's 4 billion people. But despite the vastness of this market, it remains largely untapped. The reluctance to invest is easy to understand, but it is, by and large, based on outdated assumptions of the developing world. While individual incomes may be low, the aggregate buying power of poor communities is actually quite large, representing a substantial market in many countries for what some might consider luxury goods like satellite television and phone services. Prices, and margins, are often much higher in poor neighborhoods than in their middle-class counterparts. And new technologies are already steadily reducing the effects of corruption, illiteracy, inadequate infrastructure, and other such barriers. Because these markets are in the earliest stages of economic development, revenue growth for multi-nationals entering them can be extremely rapid. MNCs can also lower costs, not only through low-cost labor but by transferring operating efficiencies and innovations developed to serve their existing operations. Certainly, succeeding in such markets requires MNCs to think creatively. The biggest change, though, has to come from executives: Unless business leaders confront their own preconceptions--particularly about the value of high-volume, low-margin businesses--companies are unlikely to master the challenges or reap the rewards of these developing markets.

The Other Poor: Rural Poverty and Education.

ERIC Educational Resources Information Center

Books, Sue

1997-01-01

This paper argues that rural poverty remains relatively invisible because, although shameful, it is profitable, and the rural poor pose little threat to their suburban neighbors. This is illustrated via interrogation concerning a rural poultry plant fire. The paper examines implications of this case for foundations scholars and educational…

Mathematics Anxiety in the Navajo Reservation School.

ERIC Educational Resources Information Center

Hadfield, Oakley D.; And Others

Of the many factors that have been proposed as a rationale for poor mathematics conceptualization by American Indians, cultural factors remain the most popular when explanations are submitted. Additionally, the accepted fault for poor achievement is focused upon mathematics anxiety. A study of American Indian school mathematics achievement and…

The association between dental health and nutritional status in chronic obstructive pulmonary disease.

PubMed

Terashima, Takeshi; Chubachi, Shotaro; Matsuzaki, Tatsu; Nakajima, Takahiro; Satoh, Minako; Iwami, Eri; Yoshida, Kyouko; Katakura, Akira; Betsuyaku, Tomoko

2017-11-01

Chronic obstructive pulmonary disease (COPD) and periodontitis are chronic inflammatory systemic diseases with common risk factors (smoking and aging). In COPD, poor periodontal health could result in inadequate nutrition, potentially causing loss of muscle volume. The purpose of this case-control study was to examine our hypothesis that COPD patients have poorer periodontal health and poorer nutritional status than non-COPD patients. Periodontal status was assessed using bleeding on probing (BOP), pocket depth (PD), and plaque-control ratio (PCR). Nutritional status was assessed using body mass index, lean body mass, and serum albumin levels. The COPD group ( n = 60) had fewer remaining teeth, greater BOP, greater PD, and lower serum albumin levels compared with smokers without COPD ( n = 41) and nonsmokers ( n = 35; p < 0.001). COPD was an independent risk factor for poor periodontal health, demonstrated by fewer remaining teeth (relative risk (RR), 5.48; p = 0.0024), BOP (RR, 12.8; p = 0.0009), and having >30% of remaining teeth with a PD ≥ 4 mm (RR, 4.82; p = 0.011). A significant negative correlation existed between the number of teeth with a PD ≥ 4 mm and serum albumin level ( r 2 = 0.127; p = 0.013). We demonstrated that poor periodontal health was associated with hypoalbuminemia, suggesting poor nutritional status and inflammation in COPD.

Age estimation of archaeological remains using amino acid racemization in dental enamel: a comparison of morphological, biochemical, and known ages-at-death.

PubMed

Griffin, R C; Chamberlain, A T; Hotz, G; Penkman, K E H; Collins, M J

2009-10-01

The poor accuracy of most current methods for estimating age-at-death in adult human skeletal remains is among the key problems facing palaeodemography. In forensic science, this problem has been solved for unburnt remains by the development of a chemical method for age estimation, using amino acid racemization in collagen extracted from dentine. Previous application of racemization methods to archaeological material has proven problematic. This study presents the application to archaeological human remains of a new age estimation method utilizing amino acid racemization in a potentially closed system-the dental enamel. The amino acid composition and extent of racemization in enamel from two Medieval cemeteries (Newcastle Blackgate and Grantham, England) and from a documented age-at-death sample from a 19th century cemetery (Spitalfriedhof St Johann, Switzerland) were determined. Alterations in the amino acid composition were detected in all populations, indicating that diagenetic change had taken place. However, in the Medieval populations, these changes did not appear to have substantially affected the relationship between racemization and age-at-death, with a strong relationship being retained between aspartic acid racemization and the morphological age estimates. In contrast, there was a poor relationship between racemization and age in the post-medieval documented age-at-death population from Switzerland. This appears to be due to leaching of amino acids post-mortem, indicating that enamel is not functioning as a perfectly closed system. Isolation of amino acids from a fraction of enamel which is less susceptible to leaching may improve the success of amino acid racemization for archaeological age estimation.

Health Changes in Low Income Men Transitioning from a State Funded Prostate Cancer Program to Comprehensive Insurance.

PubMed

Nabhani, Jamal A; Kuang, Ruby; Liu, Hui; Kwan, Lorna; Litwin, Mark S

2018-07-01

We evaluated the effect of transitioning from a prostate cancer specific treatment program to comprehensive insurance under the ACA (Patient Protection and Affordable Care Act) on the physical, mental and prostate cancer related health of poor, previously uninsured men. We assessed general and prostate cancer specific health related quality of life using the RAND SF-12v2™ (12-Item Short Form Survey, version 2) and the UCLA PCI (Prostate Cancer Index) at 3 time points in 24 men who transitioned to comprehensive insurance as the insured group relative to 39 who remained in the prostate cancer program as the control group. We used mixed effects models controlling for treatment and patient factors to measure health differences between the groups during the transition period. Demographics, prostate cancer treatment patterns, and mental, physical and general health were similar before transition in the control and insured groups. After transition men who gained insurance coverage reported significantly worse physical health than men who remained in the prostate cancer program (p = 0.0038). After adjustment in the mixed effects model physical health remained worse in men who gained insurance (p = 0.0036). Mental health and prostate cancer related quality of life did not differ with time between the groups. Compared to controls who remained in the state funded prostate cancer treatment program for poor, uninsured men, newly insured men reported worse physical health after transitioning to ACA coverage. Providers and policy makers may draw important lessons from understanding the mechanisms of this paradoxical worsening in physical health after gaining insurance. These results inform the development of disease specific models of care in the broader health insurance context. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Trends in Child Poverty in Sweden: Parental and Child Reports.

PubMed

Mood, Carina; Jonsson, Jan O

We use several family-based indicators of household poverty as well as child-reported economic resources and problems to unravel child poverty trends in Sweden. Our results show that absolute (bread-line) household income poverty, as well as economic deprivation, increased with the recession 1991-96, then reduced and has remained largely unchanged since 2006. Relative income poverty has however increased since the mid-1990s. When we measure child poverty by young people's own reports, we find few trends between 2000 and 2011. The material conditions appear to have improved and relative poverty has changed very little if at all, contrasting the development of household relative poverty. This contradictory pattern may be a consequence of poor parents distributing relatively more of the household income to their children in times of economic duress, but future studies should scrutinze potentially delayed negative consequences as poor children are lagging behind their non-poor peers. Our methodological conclusion is that although parental and child reports are partly substitutable, they are also complementary, and the simultaneous reporting of different measures is crucial to get a full understanding of trends in child poverty.

Using practice development methodology to develop children's centre teams: ideas for the future.

PubMed

Hemingway, Ann; Cowdell, Fiona

2009-09-01

The Children's Centre Programme is a recent development in the UK and brings together multi-agency teams to work with disadvantaged families. Practice development methods enable teams to work together in new ways. Although the term practice development remains relatively poorly defined, its key properties suggest that it embraces engagement, empowerment, evaluation and evolution. This paper introduces the Children's Centre Programme and practice development methods and aims to discuss the relevance of using this method to develop teams in children's centres through considering the findings from an evaluation of a two-year project to develop inter-agency public health teams. The evaluation showed that practice development methods can enable successful team development and showed that through effective facilitation, teams can change their practice to focus on areas of local need. The team came up with their own process to develop a strategy for their locality.

A mechanical model predicts morphological abnormalities in the developing human brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

Blocked, delayed, or obstructed: What causes poor white matter development in intrauterine growth restricted infants?

PubMed

Tolcos, Mary; Petratos, Steven; Hirst, Jonathan J; Wong, Flora; Spencer, Sarah J; Azhan, Aminath; Emery, Ben; Walker, David W

2017-07-01

Poor white matter development in intrauterine growth restricted (IUGR) babies remains a major, untreated problem in neonatology. New therapies, guided by an understanding of the mechanisms that underlie normal and abnormal oligodendrocyte development and myelin formation, are required. Much of our knowledge of the mechanisms that underlie impaired myelination come from studies in adult demyelinating disease, preterm brain injury, or experimental models of hypoxia-ischemia. However, relatively less is known for IUGR which is surprising because IUGR is a leading cause of perinatal mortality and morbidity, second only to premature birth. IUGR is also a significant risk factor for the later development of cerebral palsy, and is a greater risk compared to some of the more traditionally researched antecedents - asphyxia and inflammation. Recent evidence suggests that the white matter injury and reduced myelination in the brains of some preterm babies is due to impaired maturation of oligodendrocytes thereby resulting in the reduced capacity to synthesize myelin. Therefore, it is not surprising that the hypomyelination observable in the central nervous system of IUGR infants has similarly lead to investigations identifying a delay or blockade in the progress of maturation of oligodendrocytes in these infants. This review will discuss current ideas thought to account for the poor myelination often present in the neonate's brain following IUGR, and discuss novel interventions that are promising as treatments that promote oligodendrocyte maturation, and thereby repair the myelination deficits that otherwise persist into infancy and childhood and lead to neurodevelopmental abnormalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adoption and sustained use of cleaner cooking fuels in rural India: a case control study protocol to understand household, network, and organizational drivers.

PubMed

Kumar, Praveen; Dhand, Amar; Tabak, Rachel G; Brownson, Ross C; Yadama, Gautam N

2017-01-01

Implementing efficient stoves and clean fuels in low and middle-income countries are critical for improving health of poor women and children and improve the environment. Cleaner biomass stoves, however, perform poorly against the World Health Organization's indoor air quality guidelines. This has shifted the focus to systematic dissemination and implementation of cleaner cooking systems such as liquefied petroleum gas (LPG) among poor communities. Even when there is some uptake of LPG by poor communities, its sustained use has been low. Concurrent use of LPG with traditional biomass cookstoves compromises reductions in household air pollution and limits health and environmental dividends. Therefore understanding key drivers of adoption and sustained implementation of clean fuels among the poor is critical. There is a significant gap, however, in the research to understand determinants and sustained exclusive use of clean fuels in rural poor communities. Using a case control study design, this study will explore the impact of affordability, accessibility, and awareness on adoption and sustained use of LPG among rural poor communities of India. The study uses a multistage random sampling to collect primary data from 510 households. Case group or LPG adopters constitute 255 households while control group or non-LPG adopters constitute the remaining 255 households. The study will deploy sophisticated stove use monitoring sensors in each of the stoves in 100 case group households to monitor stove use and stacking behavior (using clean and traditional systems of cooking) of participants for 12 months. Moreover, this will be the first study to explore the impact of personal social networks striated by gender on LPG adoption. This study is guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation science evaluation framework. Lessons from this study will feed into a larger discussion on developing a pro-poor strategy to foster uptake and sustained use of cleaner cooking systems such as LPG. Understanding the determinants of adoption and sustained use of cleaner cooking systems through the RE-AIM framework will expand our insights on implementation of cleaner cooking systems among poor communities and will advance implementation science in the clean cooking sector. A thorough study of such implementation strategies is crucial to realize multiple UN Sustainable Development Goals on global health, climate change, and energy security.

The pathways from perceived discrimination to self-rated health: An investigation of the roles of distrust, social capital, and health behaviors

PubMed Central

Chen, Danhong; Yang, Tse-Chuan

2014-01-01

Although there has been extensive research on the adverse impacts of perceived discrimination on health, it remains unclear how perceived discrimination gets under the skin. This paper develops a comprehensive structural equation model (SEM) by incorporating both the direct effects of perceived discrimination on self-rated health (SRH), a powerful predictor for many health outcomes, and the indirect effects of perceived discrimination on SRH through health care system distrust, neighborhood social capital, and health behaviors and health conditions. Applying SEM to 9,880 adults (aged between 18 and 100) in the 2008 Southeastern Pennsylvania Household Health Survey, we not only confirmed the positive and direct association between discrimination and poor or fair SRH, but also verified two underlying mechanisms: 1) perceived discrimination is associated with lower neighborhood social capital, which further contributes to poor or fair SRH; and 2) perceived discrimination is related to risky behaviors (e.g., reduced physical activity and sleep quality, and intensified smoking) that lead to worse health conditions, and then result in poor or fair SRH. Moreover, we found that perceived discrimination is negatively associated with health care system distrust, but did not find a significant relationship between distrust and poor or fair SRH. PMID:24581063

Punishment and Welfare: Paternal Incarceration and Families' Receipt of Public Assistance

ERIC Educational Resources Information Center

Sugie, Naomi F.

2012-01-01

The United States criminal justice and welfare systems are two important government institutions in the lives of the poor. Despite many theoretical discussions about their relationship, their operation at the level of offenders and families remains poorly understood. This paper utilizes Fragile Families and Child Wellbeing data to examine how…

Developments in rabies vaccines.

PubMed

Hicks, D J; Fooks, A R; Johnson, N

2012-09-01

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.

Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes

PubMed Central

Rouanet, Marie; Lebrin, Marine; Gross, Fabian; Bournet, Barbara; Cordelier, Pierre; Buscail, Louis

2017-01-01

A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes). The latest developments in pancreatic carcinoma gene therapy are described including gene-based tumor cell sensitization to chemotherapy, vaccination and adoptive immunotherapy (chimeric antigen receptor T-cells strategy). Nowadays, there is a specific development of oncolytic virus therapies including oncolytic adenoviruses, herpes virus, parvovirus or reovirus. A summary of all published and on-going phase-1 trials is given. Most of them associate gene therapy and chemotherapy or radiochemotherapy. The first results are encouraging for most of the trials but remain to be confirmed in phase 2 trials. PMID:28594388

Executive Function Capacities, Negative Driving Behavior and Crashes in Young Drivers

PubMed Central

Winston, Flaura K.

2017-01-01

Motor vehicle crashes remain a leading cause of injury and death in adolescents, with teen drivers three times more likely to be in a fatal crash when compared to adults. One potential contributing risk factor is the ongoing development of executive functioning with maturation of the frontal lobe through adolescence and into early adulthood. Atypical development resulting in poor or impaired executive functioning (as in Attention-Deficit/Hyperactivity Disorder) has been associated with risky driving and crash outcomes. However, executive function broadly encompasses a number of capacities and domains (e.g., working memory, inhibition, set-shifting). In this review, we examine the role of various executive function sub-processes in adolescent driver behavior and crash rates. We summarize the state of methods for measuring executive control and driving outcomes and highlight the great heterogeneity in tools with seemingly contradictory findings. Lastly, we offer some suggestions for improved methods and practical ways to compensate for the effects of poor executive function (such as in-vehicle assisted driving devices). Given the key role that executive function plays in safe driving, this review points to an urgent need for systematic research to inform development of more effective training and interventions for safe driving among adolescents. PMID:29143762

Achieving Operability via the Mission System Paradigm

NASA Technical Reports Server (NTRS)

Hammer, Fred J.; Kahr, Joseph R.

2006-01-01

In the past, flight and ground systems have been developed largely-independently, with the flight system taking the lead, and dominating the development process. Operability issues have been addressed poorly in planning, requirements, design, I&T, and system-contracting activities. In many cases, as documented in lessons-learned, this has resulted in significant avoidable increases in cost and risk. With complex missions and systems, operability is being recognized as an important end-to-end design issue. Never-the-less, lessons-learned and operability concepts remain, in many cases, poorly understood and sporadically applied. A key to effective application of operability concepts is adopting a 'mission system' paradigm. In this paradigm, flight and ground systems are treated, from an engineering and management perspective, as inter-related elements of a larger mission system. The mission system consists of flight hardware, flight software, telecom services, ground data system, testbeds, flight teams, science teams, flight operations processes, procedures, and facilities. The system is designed in functional layers, which span flight and ground. It is designed in response to project-level requirements, mission design and an operations concept, and is developed incrementally, with early and frequent integration of flight and ground components.

Is there a role for higher education in preparing nurses?

PubMed

Watson, Roger

2006-12-01

Nurse education is now almost wholly situated within universities internationally. However, issues such as the necessity of higher education for what is seen as a practical occupation and the question of whether or not nursing is a profession arise. Newman viewed universities as places where training was given but character was also formed and self-awareness was developed through exposure to a wide range of disciplines and this type of education has helped to shape other professions. If nursing fulfills the criteria for a profession then it requires nurses to be properly educated in higher education. Poor media images of nursing, opposition from within and outside of the profession and poor funding for research, especially in the UK, where most nurses still do not enter the register with a degree, mean that the place of nursing in higher education remains on the periphery. Nurses must be competent to practice and higher education is not incompatible with the development of competent practitioners. However, higher education should take competent practitioners to a higher level whereby they become capable: able to respond appropriately in unfamiliar situations and to unfamiliar events. This paper argues for the role of higher education for nurses in terms of developing capability.

The discovery and development of analgesics: new mechanisms, new modalities

PubMed Central

Burgess, Gillian; Williams, Dic

2010-01-01

Despite intensive research into pain mechanisms and significant investment in research and development, the majority of analgesics available to prescribers and patients are based on mechanistic classes of compounds that have been known for many years. With considerable ingenuity and innovation, researchers continue to make the best of the mechanistic approaches available, with novel formulations, routes of administration, and combination products. Here we review some of the mechanisms and modalities of analgesics that have recently entered into clinical development, which, coupled with advances in the understanding of the pathophysiology of chronic pain, will hopefully bring the promise of new therapeutics that have the potential to provide improved pain relief for those many patients whose needs remain poorly met. PMID:21041957

Anammox-based technologies for nitrogen removal: Advances in process start-up and remaining issues.

PubMed

Ali, Muhammad; Okabe, Satoshi

2015-12-01

Nitrogen removal from wastewater via anaerobic ammonium oxidation (anammox)-based process has been recognized as efficient, cost-effective and low energy alternative to the conventional nitrification and denitrification processes. To date, more than one hundred full-scale anammox plants have been installed and operated for treatment of NH4(+)-rich wastewater streams around the world, and the number is increasing rapidly. Since the discovery of anammox process, extensive researches have been done to develop various anammox-based technologies. However, there are still some challenges in practical application of anammox-based treatment process at full-scale, e.g., longer start-up period, limited application to mainstream municipal wastewater and poor effluent water quality. This paper aimed to summarize recent status of application of anammox process and researches on technological development for solving these remaining problems. In addition, an integrated system of anammox-based process and microbial fuel cell is proposed for sustainable and energy-positive wastewater treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo.

PubMed

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis; Fre, Silvia

2013-10-14

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive "triple negative" human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

PubMed Central

Faria, Raquel; Gonçalves, João; Dias, Rita

2017-01-01

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient. PMID:28178431

Neuropsychiatric Systemic Lupus Erythematosus Involvement: Towards a Tailored Approach to Our Patients?

PubMed

Faria, Raquel; Gonçalves, João; Dias, Rita

2017-01-30

Neuropsychiatric involvement in systemic lupus erythematosus (NPSLE) is a complex condition that remains poorly understood, and includes heterogeneous manifestations involving both the central and peripheral nervous system, with disabling effects. There are several models to improve NPSLE diagnosis when a neurological syndrome is present. In the last couple of years, the growing knowledge of the role of cytokines and antibodies in NPSLE, as well as the development of new functional imaging techniques, has brought some insights into the physiopathology of the disease, but their validation for clinical use remains undetermined. Furthermore, besides the classic clinical approach, a new tool for screening the 19 NPSLE syndromes has also been developed. Regarding NPSLE therapeutics, there is still no evidence-based treatment approach, but some data support the safety of biological medication when classic treatment fails. Despite the tendency to reclassify SLE patients in clinical and immunological subsets, we hope that these data will inspire medical professionals to approach NPSLE in a manner more tailored to the individual patient.

Notch3 marks clonogenic mammary luminal progenitor cells in vivo

PubMed Central

Lafkas, Daniel; Rodilla, Veronica; Huyghe, Mathilde; Mourao, Larissa; Kiaris, Hippokratis

2013-01-01

The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells. PMID:24100291

Iron deposition and inflammation in multiple sclerosis. Which one comes first?

PubMed Central

2011-01-01

Whether iron deposition is an epiphenomenon of the multiple sclerosis (MS) disease process or may play a primary role in triggering inflammation and disease development remains unclear at this time, and should be studied at the early stages of disease pathogenesis. However, it is difficult to study the relationship between iron deposition and inflammation in early MS due to the delay between the onset of symptoms and diagnosis, and the poor availability of tissue specimens. In a recent article published in BMC Neuroscience, Williams et al. investigated the relationship between inflammation and iron deposition using an original animal model labeled as "cerebral experimental autoimmune encephalomyelitis", which develops CNS perivascular iron deposits. However, the relative contribution of iron deposition vs. inflammation in the pathogenesis and progression of MS remains unknown. Further studies should establish the association between inflammation, reduced blood flow, iron deposition, microglia activation and neurodegeneration. Creating a representative animal model that can study independently such relationship will be the key factor in this endeavor. PMID:21699686

The Status of Contemporary Image-Guided Modalities in Oncologic Surgery

PubMed Central

Rosenthal, Eben L; Warram, Jason M; Bland, Kirby I; Zinn, Kurt R

2014-01-01

Surgical resection remains the cornerstone of therapy for patients with early stage solid malignancies and more than half of all cancer patients undergo surgery each year. The technical ability of the surgeon to obtain clear surgical margins at the initial resection remains crucial to improve overall survival and long-term morbidity. Current resection techniques are largely based on subjective and subtle changes associated with tissue distortion by invasive cancer. As a result, positive surgical margins occur in a significant portion of tumor resections, which is directly correlated with a poor outcome. A variety of cancer imaging techniques have been adapted or developed for intraoperative surgical guidance that have been shown to improve functional and oncologic outcomes in randomized clinical trials. There are also a large number of novel, cancer-specific contrast agents that are in early stage clinical trials and preclinical development that demonstrate significant promise to improve real-time detection of subclinical cancer in the operative setting. PMID:25599326

Determining the efficacy of national strategies aimed at addressing the challenges facing health personnel working in rural areas in KwaZulu-Natal, South Africa

PubMed Central

2017-01-01

Background Shortages of Human Resources for Health (HRH) in rural areas are often driven by poor working and living conditions, inadequate salaries and benefits, lack of training and career development opportunities amongst others. The South African government has adopted a human resource strategy for the health sector in 2011 aimed at addressing these challenges. Aim This study reviews the challenges faced by health personnel against government strategies aimed at attracting and retaining health personnel in these underserved areas. Setting The study was conducted in six primary health care service sites in the Hlabisa sub-district of Umkhanyakude, located in northern KwaZulu-Natal, South Africa. Methods The study population comprised 25 health workers including 11 professional nurses, 4 staff nurses and 10 doctors (4 medical doctors, 3 foreign medical doctors and 3 doctors undertaking community service). Qualitative data were collected from semi-structured interviews and analysed using thematic analysis. Results Government initiatives including the rural allowance, deployment of foreign medical doctors and the presence of health personnel undertaking their community service in rural areas are positively viewed by health personnel working in rural health facilities. However, poor living and working conditions, together with inadequate personal development opportunities, remain unresolved challenges. It is these challenges that will continue to dissuade experienced health personnel from remaining in these underserved areas. Conclusion South Africa’s HRH strategy for the Health Sector 2012/13–2015/16 had highlighted the key challenges raised by respondents and identified strategies aimed at addressing these challenges. Implementation of these strategies is key to improving both living and working conditions, and providing health personnel with opportunities for further development will require inter-ministerial collaboration if the HRH 2030 objectives are to be realised. PMID:28828878

Mobilization for cervical cancer screening: lessons from a poor-urban Yoruba community in Nigeria.

PubMed

Thomas, J O; Babarinsa, I A; Ajayi, I O; Fawole, O; Ojemakinde, K O; Omigbodun, A O

2005-03-01

Cervical cancer is a major public health problem worldwide and it remains one of the commonest malignancies in Nigeria. Screening remains the most effective tool for the detection of pre-invasive stages of cervical cancer, giving the opportunity for prompt and effective treatment before the emergence of invasive disease. In Nigeria, as in most developing countries, the concept of screening for cancer and its pre-emptive treatment is underdeveloped. The fact that the facilities and logistics for cervical cancer screening are generally located in the hospital setting, a place where one goes when ill, according to local beliefs, makes acceptance more difficult. That Nigeria urgently needs to set up or develop cervical screening programmes that will reach women outside the hospital setting in a culturally acceptable milieu is not in doubt. A community cervical screening survey for the prevalence of cervical intraepithelial neoplasia and HPV infection was initiated in Idikan, a poor-urban inner core area of Ibadan. The challenges and experiences encountered in the execution of the project which could serve as useful knowledge to those undertaking similar exercises, requiring mass mobilization for cancer screening of an uninformed group, are highlighted. Our experience in the course of this study is important as it brought out the probable influences of community dynamics and social organization in illness decisions and prescriptions for health operative in this particular population group. Cervical cancer screening programmes should therefore make provisions to accommodate the occasional outcomes as we had encountered. In addition, screening programmes in developing societies would require sensitive designs that should address the cultural attitudes, personal conflicts, expectations of treatment and overall context of preventive care.

Determining the efficacy of national strategies aimed at addressing the challenges facing health personnel working in rural areas in KwaZulu-Natal, South Africa.

PubMed

Mburu, Grace; George, Gavin

2017-07-31

Shortages of Human Resources for Health (HRH) in rural areas are often driven by poor working and living conditions, inadequate salaries and benefits, lack of training and career development opportunities amongst others. The South African government has adopted a human resource strategy for the health sector in 2011 aimed at addressing these challenges. This study reviews the challenges faced by health personnel against government strategies aimed at attracting and retaining health personnel in these underserved areas. The study was conducted in six primary health care service sites in the Hlabisa sub-district of Umkhanyakude, located in northern KwaZulu-Natal, South Africa. The study population comprised 25 health workers including 11 professional nurses, 4 staff nurses and 10 doctors (4 medical doctors, 3 foreign medical doctors and 3 doctors undertaking community service). Qualitative data were collected from semi-structured interviews and analysed using thematic analysis. Government initiatives including the rural allowance, deployment of foreign medical doctors and the presence of health personnel undertaking their community service in rural areas are positively viewed by health personnel working in rural health facilities. However, poor living and working conditions, together with inadequate personal development opportunities, remain unresolved challenges. It is these challenges that will continue to dissuade experienced health personnel from remaining in these underserved areas. South Africa's HRH strategy for the Health Sector 2012/13-2015/16 had highlighted the key challenges raised by respondents and identified strategies aimed at addressing these challenges. Implementation of these strategies is key to improving both living and working conditions, and providing health personnel with opportunities for further development will require inter-ministerial collaboration if the HRH 2030 objectives are to be realised.

The Development of Body Structure Knowledge in Infancy

PubMed Central

Bhatt, Ramesh S.; Hock, Alyson; White, Hannah; Jubran, Rachel; Galati, Ashley

2016-01-01

Although we know much about the development of face processing, we know considerably less about the development of body knowledge—despite bodies also being significant sources of social information. One set of studies indicated that body structure knowledge is poor during the 1st year of life and spawned a model that posits that, unlike the development of face knowledge, which benefits from innate propensities and dedicated learning mechanisms, the development of body knowledge relies on general learning mechanisms and develops slowly. In this article, we review studies on infants’ knowledge about the structure of bodies and their processing of gender and emotion that paint a different picture. Although questions remain, a general social cognition system likely engenders similar trajectories of development of knowledge about faces and bodies, and may equip developing infants with the capacity to obtain socially critical information from many sources. PMID:28663770

Towards a Tool for Malaria Supply Chain Management Improvement in Rural Ghana.

PubMed

Carlo, Lorena; Bakken, Suzanne; Mamykina, Lena; Kodie, Richmond; Kanter, Andrew S

2015-01-01

The maintenance of adequate quantities of antimalarial medicines and rapid diagnostic tests (RDTs) at health facilities in rural areas of sub-Saharan Africa is a challenging task because of poor supply chain management. Antimalarial stock-outs in the communities could lead patients (that need to travel long distances to get medications) to remain untreated, develop severe malaria and die. A prototype to improve the management of health commodities in rural Ghana through the visualization of current stock levels and the forecasting of commodities is proposed.

Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

PubMed

Jin, Shu-Guang; Jiang, Xiao-Ping; Zhong, Lin

2016-10-01

Ewing's sarcoma (EWS) and peripheral primitive neuroectodermal tumor (pPNET) are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment. Copyright © 2014. Published by Elsevier B.V.

Hurricane and Monsoon Tracking with Driftsondes

NASA Astrophysics Data System (ADS)

Drobinski, Philippe; Cocquerez, Philippe; Doerenbecher, A.; Hock, Terrence; Lavaysse, C.; Parsons, D.; Redelsperger, J. L.

Tropical cyclones (TCs) are a typical weather threat. The threat can apply to humans, their properties, and activities. Their prediction, particularly their trajectory and intensity, remains difficult. In addition, TCs develop above the tropical oceans where the coverage by in situ observations is poor and within cloud clusters (mesoscale convective systems MCS) that limit the ability of numerical weather prediction (NWP) models to assimilate satellite data [18]. Improved forecast of TCs trajectories is a huge benefit in terms of material costs of evacuations and damage, not being able to quantify saved life.

Neuropsychiatric conditions associated with anesthesia exposure.

PubMed

Gross, Anne F; Stern, Theodore A

2014-01-01

Although anesthetics have been used for more than a century, their mechanisms of action remain poorly understood. Given that a number of intraoperative and postoperative neuropsychiatric syndromes have been linked to the use of anesthetics, practitioners should familiarize themselves with these conditions. Basic concepts about anesthesia are reviewed and neuropsychiatric syndromes associated with anesthesia exposure described. Emergence delirium, postoperative delirium, postoperative cognitive dysfunction, and intraoperative awareness can develop in association with use of inhalation anesthetics and intravenously administered anesthetics. Copyright © 2014 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Development of self-control in children aged 3 to 9 years: Perspective from a dual-systems model

PubMed Central

Tao, Ting; Wang, Ligang; Fan, Chunlei; Gao, Wenbin

2014-01-01

The current study tested a set of interrelated theoretical propositions based on a dual-systems model of self-control. Data were collected from 2135 children aged 3 to 9 years. The results suggest that (a) there was positive growth in good self-control, whereas poor control remained relatively stable; and (b) girls performed better than boys on tests of good self-control. The results are discussed in terms of their implications for a dual-systems model of self-control theory and future empirical work. PMID:25501669

Food insecurity in households in informal settlements in urban South Africa.

PubMed

Naicker, N; Mathee, A; Teare, J

2015-04-01

Food insecurity in the urban poor is a major public health challenge. The Health, Environment and Development study assessed trends in food insecurity and food consumption over a period of 7 years in an informal settlement in Johannesburg, South Africa (SA). Annual cross-sectional surveys were conducted in the informal settlement (Hospital Hill). The degree of household food insecurity decreased significantly from 2006 (85%) to 2012 (70%). There was a spike in 2009 (91%), possibly owing to global food price increases. Childhood food insecurity followed the same trend as household food insecurity. During the first 3 study years, consumption of protein, vegetables and fruit decreased by 10-20%, but had returned to previous levels by 2012. In this study, although declining, food insecurity remains unacceptably high. Hunger relief and poverty alleviation need to be more aggressively implemented in order to improve the quality of life in poor urban communities in SA.

USP7 is a SUMO deubiquitinase essential for DNA replication.

PubMed

Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar

2016-04-01

Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.

Social attribution processes and comorbid psychiatric symptoms in children with Asperger syndrome

PubMed Central

Meyer, Jessica A.; Mundy, Peter C.; Van Hecke, Amy Vaughan; Durocher, Jennifer Stella

2009-01-01

The factors that place children with Asperger syndrome at risk for comorbid psychiatric symptoms, such as anxiety and depression, remain poorly understood. We investigated the possibility that the children’s emotional and behavioral difficulties are associated with social information and attribution processing. Participants were children with either Asperger syndrome (n = 31) or typical development (n = 33).To assess social information and attribution processing, children responded to hypothetical social vignettes.They also completed self-report measures of social difficulties and psychological functioning. Their parents provided information on social competence and clinical presentation. Children with Asperger syndrome showed poor psychosocial adjustment, which was related to their social information and attribution processing patterns. Cognitive and social-cognitive abilities were associated with aspects of social information processing tendencies, but not with emotional and behavioral difficulties. Results suggest that the comorbid symptoms of children with Asperger syndrome may be associated with their social perception, understanding, and experience. PMID:16908481

Infectious and dietary risk factors of oral cancer.

PubMed

Meurman, Jukka H

2010-06-01

In addition to the classic risk factors of oral cancer, namely alcohol and tobacco, other factors both infectious and environmental are thought to be associated with the development of oral malignancy. Infections in the oral cavity may be an important preventable cause of cancer. Poor oral hygiene, periodontal disease, chronic candidiasis, human papilloma virus (HPV) and herpesvirus infections link statistically with cancer but the mechanisms involved are largely unknown. Infections may trigger cell proliferation, inhibit apoptosis, interfere with cellular signaling mechanisms and up-regulate tumor promoters. In addition, several oral micro-organisms metabolize alcohol to carcinogenic acetaldehyde thus explaining the association between poor oral hygiene, alcohol consumption and carcinogenesis. With regards to dietary factors the Mediterranean-type fruit and vegetable rich diet has been shown to reduce the risk of oral cancer but the evidence is weak, the effect of individual food components and trace elements on carcinogenesis remains unclear at present. Copyright 2010 Elsevier Ltd. All rights reserved.

Structural Equations and Causal Explanations: Some Challenges for Causal SEM

ERIC Educational Resources Information Center

Markus, Keith A.

2010-01-01

One common application of structural equation modeling (SEM) involves expressing and empirically investigating causal explanations. Nonetheless, several aspects of causal explanation that have an impact on behavioral science methodology remain poorly understood. It remains unclear whether applications of SEM should attempt to provide complete…

Verbal Understanding and Pavlovian Processes

ERIC Educational Resources Information Center

Tonneau, François

2004-01-01

The behavioral processes through which people react appropriately to verbal descriptions remain poorly understood. I argue here that these processes are Pavlovian. Common objections to a Pavlovian account of symbolic behavior evidence a lack of familiarity with the relevant data or misunderstandings of operant theory. Although much remains to be…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bilbao, Jose Ignacio; Quiroga, Jorge; Herrero, Jose Ignacio

Since the insertion of the first TIPS in 1989 much has been learned about this therapeutic procedure. It has an established role for the treatment of some complications of portal hypertension: prevention of recurrent variceal bleeding and rescue of patients with acute uncontrollable variceal bleeding. In addition TIPS is useful for Budd-Chiari syndrome, refractory ascites and hepatorenal syndrome, although its specific role in these indications remains to be definitively established. However, the decrease in sinusoidal blood flow induced by TIPS can lead to the patient developing hepatic encephalopathy and liver failure in some cases. Therefore, TIPS should be used withmore » caution in patients with very poor liver function. From a technical point of view, successful placement of TIPS is achieved in more than 98% of cases by experienced groups. At present, evaluation of TIPS dysfunction based on morphology probably leads to an overdiagnosis of this complication since most of these cases are not associated with clinical manifestations (recurrent bleeding or refractory ascites). The major disadvantage of TIPS remains its poor long-term patency requiring a mandatory surveillance program. The indicator for shunt function/malfunction should be the portosystemic pressure gradient, which is best assessed by intravascular measurements. Shunt obstructions may be prevented or reduced by the use of stent-grafts in the future.« less

Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

PubMed Central

Das, Subhamoy; Baker, Aaron B.

2016-01-01

Wound healing is an intricate process that requires complex coordination between many cell types and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care, the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds, including excessive inflammation, ischemia, scarring, and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or are currently used in clinical practice. PMID:27843895

Welfare, Work and Raising Children: Conversations with Twenty-One Maine Families.

ERIC Educational Resources Information Center

Hastedt, Christine B.; Smith, Rebekah J.

Five years after the massive overhaul of the nation's welfare system, 21 Maine families receiving public assistance spoke about their lives during welfare reform. The following were among the key themes that emerged throughout the conversations: (1) those leaving Temporary Assistance for Needy Families (TANF) often remain poor or very nearly poor;…

Parental "Choice": The Liberty Principle in Education Finance: New Scholar Section

ERIC Educational Resources Information Center

Ndimande, Bekisizwe

2006-01-01

Despite the promise of equal educational opportunities for all, most public schools in the townships of South Africa have remained poorly funded and thus have become dysfunctional. As a result most poor parents from townships have started to transfer their children to schools with better resources and education facilities in the suburban areas.…

Out of School: A Phenomenological Exploration of Extended Non-Attendance

ERIC Educational Resources Information Center

Baker, Matt; Bishop, Felicity L.

2015-01-01

The concept of "extended non-attendance" ("school phobia" or "school refusal") was distinguished from truancy early in the twentieth century, and refers to children who fear school and avoid attending. Despite much subsequent research, outcomes for those affected remain poor, and their voices remain largely absent…

The Effect of Empowerment and Self-Determination on Health Outcomes

ERIC Educational Resources Information Center

Garces-Ozanne, Arlene; Kalu, Edna Ikechi; Audas, Richard

2016-01-01

There remains a persistent gap in health outcomes between wealthy and poor countries. Basic measures such as life expectancy and infant and under-five mortality remain divergent, with preventable deaths being unacceptably high, despite significant efforts to reduce these disparities. We examine the impact of empowerment, measured by Freedom…

A systems view of health care for the poor.

PubMed Central

Prasad, N.

1989-01-01

A systems view is a synthesis of health policy, medical sociology, public health, and common clinical problems to describe the current crisis in health care for the poor. Medical sociology and public health are particularly relevant to understand the complexity of clinical issues. Although preventive medicine is in desuetude, it is crucial if we are to reduce the future liability of postponed medical care among the poor. Medicaid metamorphosed to Medicare, as half of its outlays are spent on care of the elderly in nursing homes. Health care for the poor will remain a moral challenge to the architects of health policy and the medical profession. PMID:2659807

Mapping risk of Nipah virus transmission across Asia and across Bangladesh.

PubMed

Peterson, A Townsend

2015-03-01

Nipah virus is a highly pathogenic but poorly known paramyxovirus from South and Southeast Asia. In spite of the risks that it poses to human health, the geography and ecology of its occurrence remain little understood-the virus is basically known from Bangladesh and peninsular Malaysia, and little in between. In this contribution, I use documented occurrences of the virus to develop ecological niche-based maps summarizing its likely broader occurrence-although rangewide maps could not be developed that had significant predictive abilities, reflecting minimal sample sizes available, maps within Bangladesh were quite successful in identifying areas in which the virus is predictably present and likely transmitted. © 2013 APJPH.

Outcomes in the management of esophageal cancer.

PubMed

Paul, Subroto; Altorki, Nasser

2014-10-01

Esophageal cancer rates have continued to rise in the Western World. Esophageal cancer will be responsible for an estimated 15,450 deaths in the United States in 2014 alone. Esophageal resection with or without preoperative therapy remains the mainstay of treatment. Advances in surgical technique and perioperative care have improved short-term outcomes considerably by decreasing operative mortality. Despite these advances though, esophagectomy remains a procedure associated with considerable morbidity from a wide range of complications. Prompt recognition and treatment of complications can lower overall morbidity and mortality. Unfortunately, long-term outcomes remain poor as the vast majority of patients present with loco-regionally advanced or metastatic disease. Surgery by itself provides poor loco-regional control and fails to address micrometastatic disease. Neoadjuvant chemotherapy or chemoradiation provides a modest survival advantage compared to surgical resection alone. Future gains in understanding the molecular biology of esophageal cancer will hopefully lead to improved therapeutics and resultant outcomes. © 2014 Wiley Periodicals, Inc.

Influence of collaterals on the left ventricular end-diastolic pressure and serum NT-proBNP levels in patients with coronary chronic total occlusion.

PubMed

Samadov, Fuad; Yesildag, Osman; Sari, Ibrahim; Atas, Halil; Akhundova, Aysel; Basaran, Yelda

2017-06-01

Although numerous studies have shown the protective effects of the well-developed coronary collaterals on left ventricular functions, the relationship between collateral grade and left ventricular end diastolic pressure has not been studied in chronic total occlusion patients. Also, there are conflicting data on the effect of collaterals on NT-proBNP levels. The aim of our study was to evaluate the relationship between coronary collateral circulation and left ventricular end diastolic pressure and NT-proBNP levels in chronic total occlusion patients. Study group was retrospectively selected from the patients who had undergone coronary angiography at our hospital between June 2011 and March 2013. Clinical, biochemical, angiographic and hemodynamic data of 199 consecutive patients having at least one totally occluded major epicardial coronary artery were evaluated. Coronary collateral circulation was graded according to Rentrop classification. While Rentrop grade 3 was defined as well-developed, all the remaining collateral grades were regarded as poor collaterals. Overall 87 patients were found to have good collaterals and 112 patients had poor collaterals. There was no significant difference between the patients with well- or poorly developed coronary collaterals with regard to left ventricular end diastolic pressure (16.84 ± 5.40 mmHg vs 16.10 ± 6.09, respectively, p  = 0,632) and log NT-proBNP (2.46 ± 0.58 vs 2.59 ± 0.76, respectively, p  = 0,335). In patients with coronary chronic total occlusion even well-developed coronary collaterals are not capable of protecting the rise of left ventricular end diastolic pressure and NT-proBNP levels which are reliable markers of the left ventricular dysfunction.

Elevated venous thromboembolism risk in preeclampsia: molecular mechanisms and clinical impact.

PubMed

Egan, Karl; Kevane, Barry; Ní Áinle, Fionnuala

2015-08-01

Venous thromboembolism (VTE) remains a leading cause of maternal death and morbidity in the developed world. Strategies for prevention of VTE in pregnancy have been the subject of recent guidelines and consensus statements. These guidelines recommend thrombosis prevention in women who have risk factors associated with an elevated VTE risk. Preeclampsia is characterized by maternal hypertension and proteinuria developing after 20 weeks gestation, complicating up to 7% of pregnancies and is associated with a massive annual morbidity and mortality burden. Women with preeclampsia have been shown to be at increased risk of VTE with studies to date suggesting that this risk may be up to 5-fold greater than the risk of pregnancy-associated VTE in the general population. Despite the fact that preeclampsia is so common and potentially devastating, our understanding of its pathogenesis and potential therapeutic strategies remain poor. In addition, the mechanisms underlying the prothrombotic phenotype in preeclampsia are also poorly characterized although a number of potential mechanisms have been postulated. Derangements of platelet and endothelial activation and impairment of endogenous anti-coagulant pathways have been reported and may contribute to the observed VTE risk. Recently, evidence for the role of neutrophil extracellular traps (NETs) and cell-free DNA in the pathogenesis of VTE has emerged and some evidence exists to suggest that this may be of relevance in preeclampsia. Future studies aimed at understanding the diagnostic and potential therapeutic relevance of this procoagulant state are likely to be of enormous clinical benefit for pregnant women affected with this potentially devastating condition. © 2015 Authors; published by Portland Press Limited.

Occupational exposure to municipal solid wastes and development of toxic neuropathies: possible role of nutrient supplementation, complementary and alternative medicines in chemoprevention.

PubMed

Ekor, Martins; Odewabi, Adesina O

2014-09-01

Achieving effective municipal solid waste (MSW) management remains a major challenge and waste generation and accumulation continue to constitute important environmental and public health concern, particularly in most developing countries. Although the general population is at risk of adverse health consequences and hazards associated with exposure to MSW, the waste management workers (WMWs) are the most vulnerable because of their direct involvement in the disposal of waste, with increasing evidence of work-related health and safety risks among these individuals. Among the numerous work-related health hazards prevalent in WMWs, development of toxic neuropathies following chronic occupational exposure remains poorly recognized. However, the risk or predisposition to toxic neuropathies is becoming evident considering the increasing recognition of large amount of neurotoxic heavy metals and hazardous industrial materials present in MSW in most parts of the world. The present review seeks to draw attention to the continuous vulnerability of the WMWs to developing toxic neuropathies. This is aimed at facilitating conscious efforts by relevant governmental and nongovernmental agencies towards promoting risk reduction and ensuring adequate protection against possible toxic polyneuropathies associated with occupational exposure to solid wastes. While continuous education of the WMWs on the need for adequate compliance to safety regulations and practice remains sacrosanct towards achieving significant reduction in toxic neuropathies and related adverse health consequences of waste handling, it is also our intention in this review to underscore the possible relevance of nutrient supplementation and alternative medicines in chemoprevention.

What does productivity really mean? Towards an integrative paradigm in the search for biodiversity-productivity relationships

Treesearch

Liangjun Hu; Qinfeng Guo

2013-01-01

How species diversity relates to productivity remains a major debate. To date, however, the underlying mechanisms that regulate the ecological processes involved are still poorly understood. Three major issues persist in early efforts at resolution. First, in the context that productivity drives species diversity, how the pathways operate is poorly-explained. Second,...

An Effective Programme Is Not Enough: A Review of Factors Associated with Poor Attendance and Engagement with Parenting Support Programmes

ERIC Educational Resources Information Center

Whittaker, Karen A.; Cowley, Sarah

2012-01-01

The provision of parenting support is a key feature of wealthier nations' health and social care services. However, attendance and engagement by the neediest parents remains poor. Barriers experienced by parents include personal life factors (beliefs, lifestyles and limited resources) and programme-specific factors (delivery, content and support…

Neurobehavioural methods, effects and prevention: workers' human rights are why the field matters for developing countries.

PubMed

London, L

2009-11-01

Little research into neurobehavioural methods and effects occurs in developing countries, where established neurotoxic chemicals continue to pose significant occupational and environmental burdens, and where agents newly identified as neurotoxic are also widespread. Much of the morbidity and mortality associated with neurotoxic agents remains hidden in developing countries as a result of poor case detection, lack of skilled personnel, facilities and equipment for diagnosis, inadequate information systems, limited resources for research and significant competing causes of ill-health, such as HIV/AIDS and malaria. Placing the problem in a human rights context enables researchers and scientists in developing countries to make a strong case for why the field of neurobehavioural methods and effects matters because there are numerous international human rights commitments that make occupational and environmental health and safety a human rights obligation.

Prediction of Poor Ovarian response by Biochemical and Biophysical Markers: A Logistic Regression Model.

PubMed

Jaiswar, S P; Natu, S M; Sujata; Sankhwar, P L; Manjari, Gupta

2015-12-01

To study correlation between ovarian reserve with biophysical markers (antral follicle count and ovarian volume) and biochemical markers (S. FSH, S. Inhibin B, and S. AMH) and use these markers to predict poor ovarian response to ovarian induction. This is a prospective observational study. One hundred infertile women attending the Obst & Gynae Dept, KGMU were recruited. Blood samples were collected on day 2/day 3 for assessment of S. FSH, S. Inhibin B, and S. AMH and TVS were done for antral follicle count and ovarian volume. Clomephene citrate 100 mg 1OD was given from day 2 to 6, and patients were followed up with serial USG measurements. The numbers of dominant follicles (> or = 14 mm) at the time of hCG administration were counted. Patients with <3 follicles in the 1st cycle were subjected to the 2nd cycle of clomephene 100 mg 1OD from day 2 to day 6 with Inj HMG 150 IU given i.m. starting from day 8 and every alternate day until at least one leading follicle attained ≥18 mm. Development of <3 follicles at end of the 2nd cycle was considered as poor response. Univariate analyses showed that s. inhibin B presented the highest (ROCAUC = 0.862) discriminating potential for predicting poor ovarian response, In multivariate logistic regression model, the variables age, FSH, AMH, INHIBIN B, and AFC remained significant, and the resulting model showed a predicted accuracy of 84.4 %. A derived multimarker computation by a logistic regression model for predicting poor ovarian response was obtained through this study. Thus, potential poor responders could be identified easily, and appropriate ovarian stimulation protocol could be devised for such pts.

Obesity: “Priming” the Lung for Injury

PubMed Central

Konter, Jason; Baez, Elizabeth; Summer, Ross S

2012-01-01

Acute lung injury (ALI) is a severe inflammatory condition that develops in response to local and systemic lung challenges. To date, specific risk factors for development of ALI remain poorly defined. Recent epidemiological studies have reported obesity as an important predisposing factor in the development of this condition. Although the pathogenic mechanisms linking obesity and ALI have not been well-elucidated, emerging scientific evidence has described factors secreted by adipose tissue that have important biological activities in lung and has suggested that altered secretion of these factors during obesity contributes to increased ALI susceptibility. The objective of this manuscript is to highlight recent clinical evidence supporting the association between obesity and ALI and to discuss the posited role for adipose tissue-derived factors in the pathogenesis of this condition. PMID:22449512

Accelerating Next Generation Vaccine Development for Global Disease Prevention

PubMed Central

Koff, Wayne C; Burton, Dennis R.; R.Johnson, Philip; Walker, Bruce D.; King, Charles R.; Nabel, Gary J.; Ahmed, Rafi; Bhan, Maharaj Kishan; Plotkin, Stanley A.

2014-01-01

Summary Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, TB, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances towards vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively inducing vaccine-induced protective immune responses. PMID:23723240

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer

PubMed Central

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Maria Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G.; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-01-01

Around, 30–40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer. PMID:27462779

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.

PubMed

Hergueta-Redondo, Marta; Sarrio, David; Molina-Crespo, Ángela; Vicario, Rocío; Bernadó-Morales, Cristina; Martínez, Lidia; Rojo-Sebastián, Alejandro; Serra-Musach, Jordi; Mota, Alba; Martínez-Ramírez, Ángel; Castilla, Mª Ángeles; González-Martin, Antonio; Pernas, Sonia; Cano, Amparo; Cortes, Javier; Nuciforo, Paolo G; Peg, Vicente; Palacios, José; Pujana, Miguel Ángel; Arribas, Joaquín; Moreno-Bueno, Gema

2016-08-30

Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.

Management of metastatic renal cell carcinoma patients with poor-risk features: current status and future perspectives.

PubMed

Santoni, Matteo; De Tursi, Michele; Felici, Alessandra; Lo Re, Giovanni; Ricotta, Riccardo; Ruggeri, Enzo Maria; Sabbatini, Roberto; Santini, Daniele; Vaccaro, Vanja; Milella, Michele

2013-06-01

With seven agents approved for renal cell carcinoma within the past few years, there has undoubtedly been progress in treating this disease. However, patients with poor-risk features remain a challenging and difficult-to-treat population, with the mTOR inhibitor, temsirolimus, the only agent approved in the first-line setting. Phase III trial data are still lacking VEGF-pathway inhibitors in patients with poor prognostic features. Poor-risk patients need to be considered as a heterogeneous population. Further understanding of biomarkers can lead to a better selection of patients who may benefit the most from treatment and improvements in prognosis. The presence of poor Karnofsky scores and liver or CNS disease may affect the outcome of these patients much more than other identified factors. This consideration may provide the rationale to further stratify poor-risk patients further subgroups destined to receive either cure or palliation.

Avoiding the Major Causes of Death: Does Childhood Misfortune Reduce the Likelihood of Being Disease Free in Later Life?

PubMed

Williams, Monica M; Kemp, Blakelee R; Ferraro, Kenneth F; Mustillo, Sarah A

2018-04-03

Although previous research reveals the detrimental effects of early misfortune on the development of chronic diseases in later life, few studies have investigated its effects on remaining disease free. This study draws on cumulative inequality theory to investigate whether experiencing childhood misfortune reduces the likelihood of remaining disease free over time. This study utilizes five waves of data from the Health and Retirement Study to test whether five domains of childhood misfortune predict being disease free at baseline (2004) and developing disease over time (2004-2012). Respondents reporting risky parental behaviors during childhood were less likely to be disease free at baseline and had an increased risk of disease onset over time, the latter driven by having a guardian who smoked in combination with more pack-years smoked in adulthood. Furthermore, we find that adult resources, i.e. wealth, help to mitigate the noxious effects of other misfortunes, notably poor socioeconomic conditions. Consistent with cumulative inequality theory, these findings reveal that experiencing multiple types of misfortune during childhood decreases the likelihood of remaining disease free in later life, but engaging in health behaviors, such as physical activity, can help to ameliorate some of the noxious effects of early misfortune.

Channelling urban modernity to sustainable pro-poor tourism development in Indonesia

NASA Astrophysics Data System (ADS)

Prasetyanti, R.

2017-06-01

Sustainable urban planning and development requires not only a fast-growing economic growth and modernity, but also social equity and environmental sustainability. Meanwhile, the global goals of sustainable development have fascinatingly set a promising urban development future by enhancing ecology based pro-poor policy program. Apparently, pro-poor development agenda has led to the notion of pro-poor tourism as part of urban development strategies on poverty alleviation. This research presents Jakarta Hidden Tour and Kampung Warna-warni as certain cases of pro-poor tourism in Indonesia. By the emergence of criticism on “pro-growth” paradigm, the critical analysis of this research focuses on the scenario of sustainable pro-poor tourism through eco-cultural based Kampung-Tour development. In accordance, debates and dilemma have been continuously arising as pros and cons regarding the ethical issues of poverty alleviation based Kampung-Tour development. Nevertheless, this paper tries to redefine Slum Kampung as potential; the writer wildly offers a concept of poverty alleviation by reinventing pro-poor tourism strategy; revitalizing slum site to eco-cultural based pro-poor tourism development as an embodiment of a sustainable urban development. By holding system thinking analysis as research method, sustainable pro-poor tourism highlights the urgency community based tourism and eco-tourism so that poverty alleviation based tourism can be tangibly perceived by the poor. In this sense, good local governance and public private partnership must be enhanced, it is due to, like any other development projects; sustainable pro-poor tourism needs a strong political commitment to alleviate urban poverty, as well as to pursue a better future of sustainable nation.

Acute myelopathy selectively involving lumbar anterior horns following intranasal insufflation of ecstasy and heroin

PubMed Central

Riva, Nilo; Riva, Nilo; Morana, Paolo; Cerri, Federica; Gerevini, Simonetta; Amadio, Stefano; Formaglio, Fabio; Comi, Giancarlo; Comola, Mauro; Del Carro, Ubaldo

2009-01-01

We report a patient who developed acute myelopathy after intranasal insufflation of amphetamines and heroin. The functional prognosis was very poor; after 4 months, she remained paraplegic. MRI imaging showed selective T2 hyperintensity and intense enhancement confined to the spinal anterior horns and lumbar nerve roots and plexus. This unique MRI pattern, together with neurophysiological data, suggests that the pathological process at the first primary affected spinal anterior horns (SAH), conditioning motoneuron cell death, and then nerve roots and lumbar plexus as a consequence of wallerian degeneration PMID:21686691

Seronegative rheumatoid arthritis: pathogenetic and therapeutic aspects.

PubMed

Pratt, Arthur G; Isaacs, John D

2014-08-01

Rheumatoid arthritis (RA) has long been recognised as a highly heterogeneous disease of immune dysregulation. Despite an ever-growing appreciation of the role of circulating autoantibodies in the development of 'seropositive' disease, the pathogenesis of seronegative RA remains poorly understood. Accumulating evidence suggests that RA 'serotypes', in fact, reflect distinct disease entities that, despite their clinical overlap, diverge in respect of genetic architecture, cellular pathology and even therapeutic responsiveness. Focussing on seronegative RA, this review considers these concepts and their implications for the management of patients with this challenging, though sometimes overlooked, condition. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Current available therapies and future directions in the treatment of malignant gliomas

PubMed Central

Desjardins, Annick; Reardon, David A; Vredenburgh, James J

2009-01-01

The prognosis of patients diagnosed with malignant glioma (MG) remains poor. However, recent advances in neuro-oncology allowing a better understanding of this particular disease have allowed the development of new therapeutics. Many molecular genetic and signal transduction pathway targets have been identified that are now being investigated. Novel locoregional treatments, as well as strategies to improve regional delivery, are being evaluated. Studies of combinations of these approaches are also underway. In this review, we will discuss the current and future therapies under evaluation for the treatment of malignant gliomas. PMID:19707392

Fire in the Earth system.

PubMed

Bowman, David M J S; Balch, Jennifer K; Artaxo, Paulo; Bond, William J; Carlson, Jean M; Cochrane, Mark A; D'Antonio, Carla M; Defries, Ruth S; Doyle, John C; Harrison, Sandy P; Johnston, Fay H; Keeley, Jon E; Krawchuk, Meg A; Kull, Christian A; Marston, J Brad; Moritz, Max A; Prentice, I Colin; Roos, Christopher I; Scott, Andrew C; Swetnam, Thomas W; van der Werf, Guido R; Pyne, Stephen J

2009-04-24

Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.

Update: Acute Heart Failure (VII): Nonpharmacological Management of Acute Heart Failure.

PubMed

Plácido, Rui; Mebazaa, Alexandre

2015-09-01

Acute heart failure is a major and growing public health problem worldwide with high morbidity, mortality, and cost. Despite recent advances in pharmacological management, the prognosis of patients with acute decompensated heart failure remains poor. Consequently, nonpharmacological approaches are being developed and increasingly used. Such techniques may include several modalities of ventilation, ultrafiltration, mechanical circulatory support, myocardial revascularization, and surgical treatment, among others. This document reviews the nonpharmacological approach in acute heart failure, indications, and prognostic implications. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Diversity of the human intestinal microbial flora.

PubMed

Eckburg, Paul B; Bik, Elisabeth M; Bernstein, Charles N; Purdom, Elizabeth; Dethlefsen, Les; Sargent, Michael; Gill, Steven R; Nelson, Karen E; Relman, David A

2005-06-10

The human endogenous intestinal microflora is an essential "organ" in providing nourishment, regulating epithelial development, and instructing innate immunity; yet, surprisingly, basic features remain poorly described. We examined 13,355 prokaryotic ribosomal RNA gene sequences from multiple colonic mucosal sites and feces of healthy subjects to improve our understanding of gut microbial diversity. A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms. We discovered significant intersubject variability and differences between stool and mucosa community composition. Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.

Fire in the Earth system

USGS Publications Warehouse

Bowman, David M.J.S.; Balch, Jennifer; Artaxo, Paulo; Bond, William J.; Carlson, Jean M.; Cochrane, Mark A.; D'Antonio, Carla M.; DeFries, Ruth S.; Doyle, John C.; Harrison, Sandy P.; Johnston, Fay H.; Keeley, Jon E.; Krawchuk, Meg A.; Kull, Christian A.; Marston, J. Brad; Moritz, Max A.; Prentice, I. Colin; Roos, Christopher I.; Scott, Andrew C.; Swetnam, Thomas W.; van der Werf, Guido R.; Pyne, Stephen

2009-01-01

Fire is a worldwide phenomenon that appears in the geological record soon after the appearance of terrestrial plants. Fire influences global ecosystem patterns and processes, including vegetation distribution and structure, the carbon cycle, and climate. Although humans and fire have always coexisted, our capacity to manage fire remains imperfect and may become more difficult in the future as climate change alters fire regimes. This risk is difficult to assess, however, because fires are still poorly represented in global models. Here, we discuss some of the most important issues involved in developing a better understanding of the role of fire in the Earth system.

Impaired decision-making under risk is associated with gaming-specific inhibition deficits among college students with Internet gaming disorder.

PubMed

Yao, Yuan-Wei; Wang, Ling-Jiao; Yip, Sarah W; Chen, Pin-Ru; Li, Song; Xu, Jiansong; Zhang, Jin-Tao; Deng, Lin-Yuan; Liu, Qin-Xue; Fang, Xiao-Yi

2015-09-30

A growing body of evidence indicates that both inhibition and decision-making deficits play essential roles in the development and maintenance of Internet gaming disorder (IGD). Clarifying whether impaired decision-making among individuals with IGD is related to poor inhibition will advance our understanding of IGD and contribute to intervention development. However, the relationship between these two functions remains unclear. In this study, we sought to systemically examine inhibitory processes, decision-making and the relationship between the two among individuals with IGD. Thirty-four individuals with IGD and 32 matched healthy controls (HCs) were recruited. In comparison to HCs, IGD subjects demonstrated inhibition deficits during performance of the gaming-related Go/No-Go task and impaired decision-making under risk. In addition, errors on No-Go trials during the gaming-related Go/No-Go task were positively associated with decision-making impairments under risk but not under ambiguity among IGD subjects. These results suggest individuals with IGD are impaired in some aspects of inhibition and decision-making functions, and that decision-making deficits under risk are linked to poor inhibition specifically related to gaming cues, which has implications for the development of novel intervention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The evolution of child health programmes in developing countries: from targeting diseases to targeting people.

PubMed Central

Claeson, M.; Waldman, R. J.

2000-01-01

Mortality rates among children and the absolute number of children dying annually in developing countries have declined considerably over the past few decades. However, the gains made have not been distributed evenly: childhood mortality remains higher among poorer people and the gap between rich and poor has grown. Several poor countries, and some poorer regions within countries, have experienced a levelling off of or even an increase in childhood mortality over the past few years. Until now, two types of programmes--short-term, disease-specific initiatives and more general programmes of primary health care--have contributed to the decline in mortality. Both types of programme can contribute substantially to the strengthening of health systems and in enabling households and communities to improve their health care. In order for them to do so, and in order to complete the unfinished agenda of improving child health globally, new strategies are needed. On the one hand, greater emphasis should be placed on promoting those household behaviours that are not dependent on the performance of health systems. On the other hand, more attention should be paid to interventions that affect health at other stages of the life cycle while efforts that have been made to develop interventions that can be used during childhood continue. PMID:11100618

Decision making, cognitive distortions and emotional distress: A comparison between pathological gamblers and healthy controls.

PubMed

Ciccarelli, Maria; Griffiths, Mark D; Nigro, Giovanna; Cosenza, Marina

2017-03-01

The etiology of problem gambling is multifaceted and complex. Among others factors, poor decision making, cognitive distortions (i.e., irrational beliefs about gambling), and emotional factors (e.g., negative mood states) appear to be among the most important factors in the development and maintenance of problem gambling. Although empirical evidence has suggested that cognitive distortions facilitate gambling and negative emotions are associated with gambling, the interplay between cognitive distortions, emotional states, and decision making in gambling remains unexplored. Pathological gamblers (N = 54) and healthy controls (N = 54) completed the South Oaks Gambling Screen (SOGS), the Iowa Gambling Task (IGT), the Gambling Related Cognitions Scale (GRCS), and the Depression Anxiety Stress Scale (DASS-21). Compared to healthy controls, pathological gamblers showed poorer decision making and reported higher scores on measures assessing cognitive distortions and emotional distress. All measures were positively associated with gambling severity. A significant negative correlation between decision making and cognitive distortions was also observed. No associations were found between poor decision making and emotional distress. Logistic regression analysis indicated that cognitive distortions, emotional distress, and poor decision making were significant predictors of problem gambling. The use of self-report measures and the absence of female participants limit the generalizability of the reported findings. The present study is the first to demonstrate the mutual influence between irrational beliefs and poor decision making, as well as the role of cognitive bias, emotional distress, and poor decision making in gambling disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Elaborated Environmental Stress Hypothesis as a Framework for Understanding the Association Between Motor Skills and Internalizing Problems: A Mini-Review

PubMed Central

Mancini, Vincent O.; Rigoli, Daniela; Cairney, John; Roberts, Lynne D.; Piek, Jan P.

2016-01-01

Poor motor skills have been shown to be associated with a range of psychosocial issues, including internalizing problems (anxiety and depression). While well-documented empirically, our understanding of why this relationship occurs remains theoretically underdeveloped. The Elaborated Environmental Stress Hypothesis by Cairney et al. (2013) provides a promising framework that seeks to explain the association between motor skills and internalizing problems, specifically in children with developmental coordination disorder (DCD). The framework posits that poor motor skills predispose the development of internalizing problems via interactions with intermediary environmental stressors. At the time the model was proposed, limited direct evidence was available to support or refute the framework. Several studies and developments related to the framework have since been published. This mini-review seeks to provide an up-to-date overview of recent developments related to the Elaborated Environmental Stress Hypothesis. We briefly discuss the past research that led to its development, before moving to studies that have investigated the framework since it was proposed. While originally developed within the context of DCD in childhood, recent developments have found support for the model in community samples. Through the reviewed literature, this article provides support for the Elaborated Environmental Stress Hypothesis as a promising theoretical framework that explains the psychosocial correlates across the broader spectrum of motor ability. However, given its recent conceptualization, ongoing evaluation of the Elaborated Environmental Stress Hypothesis is recommended. PMID:26941690

Renal Safety Pharmacology in Drug Discovery and Development.

PubMed

Benjamin, Amanda; Nogueira da Costa, Andre; Delaunois, Annie; Rosseels, Marie-Luce; Valentin, Jean-Pierre

2015-01-01

The kidney is a complex excretory organ playing a crucial role in various physiological processes such as fluid and electrolyte balance, control of blood pressure, removal of waste products, and drug disposition. Drug-induced kidney injury (DIKI) remains a significant cause of candidate drug attrition during drug development. However, the incidence of renal toxicities in preclinical studies is low, and the mechanisms by which drugs induce kidney injury are still poorly understood. Although some in vitro investigational tools have been developed, the in vivo assessment of renal function remains the most widely used methodology to identify DIKI. Stand-alone safety pharmacology studies usually include assessment of glomerular and hemodynamic function, coupled with urine and plasma analyses. However, as renal function is not part of the ICH S7A core battery, such studies are not routinely conducted by pharmaceutical companies. The most common approach consists in integrating renal/urinary measurements in repeat-dose toxicity studies. In addition to the standard analyses and histopathological examination of kidneys, novel promising urinary biomarkers have emerged over the last decade, offering greater sensitivity and specificity than traditional renal parameters. Seven of these biomarkers have been qualified by regulatory agencies for use in rat toxicity studies.

MULTIMODAL IMAGING OF SYPHILITIC MULTIFOCAL RETINITIS.

PubMed

Curi, Andre L; Sarraf, David; Cunningham, Emmett T

2015-01-01

To describe multimodal imaging of syphilitic multifocal retinitis. Observational case series. Two patients developed multifocal retinitis after treatment of unrecognized syphilitic uveitis with systemic corticosteroids in the absence of appropriate antibiotic therapy. Multimodal imaging localized the foci of retinitis within the retina in contrast to superficial retinal precipitates that accumulate on the surface of the retina in eyes with untreated syphilitic uveitis. Although the retinitis resolved after treatment with systemic penicillin in both cases, vision remained poor in the patient with multifocal retinitis involving the macula. Treatment of unrecognized syphilitic uveitis with corticosteroids in the absence of antitreponemal treatment can lead to the development of multifocal retinitis. Multimodal imaging, and optical coherence tomography in particular, can be used to distinguish multifocal retinitis from superficial retinal precipitates or accumulations.

Old and new adjuvants for hepatitis B vaccines.

PubMed

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Current developments in pharmacological therapeutics for chronic constipation

PubMed Central

Jiang, Chunhuan; Xu, Qinglong; Wen, Xiaoan; Sun, Hongbin

2015-01-01

Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field. PMID:26579459

Unmanned Vehicle Material Flammability Test

NASA Technical Reports Server (NTRS)

Urban, David L.; Ruff, Gary A.; Minster, Olivier; Toth, Balazs; Fernandez-Pello, A. Carlos; Tien, James S.; Torero, Jose L.; Cowlard, Adam J.; Legros, Guillaume; Eigenbrod, Christian;

Complementary Feeding: Review of Recommendations, Feeding Practices, and Adequacy of Homemade Complementary Food Preparations in Developing Countries – Lessons from Ethiopia

PubMed Central

Abeshu, Motuma Adimasu; Lelisa, Azeb; Geleta, Bekesho

2016-01-01

Breastfeeding provides the ideal food during the first 6 months of life. Complementary feeding starts when breast milk is no longer sufficient by itself, where the target age is for 6–23 months. The gap between nutritional requirement and amount obtained from breast milk increases with age. For energy, 200, 300, and 550 kcal per day is expected to be covered by complementary foods at 6–8, 9–11, and 12–23 months, respectively. In addition, the complementary foods must provide relatively large proportions of micronutrients such as iron, zinc, phosphorus, magnesium, calcium, and vitamin B6. In several parts of the developing world, complementary feeding continues as a challenge to good nutrition in children. In Ethiopia, only 4.2% of breastfed children of 6–23 months of age have a minimum acceptable diet. The gaps are mostly attributed to either poor dietary quality or poor feeding practices, if not both. Commercial fortified foods are often beyond the reach of the poor. Thus, homemade complementary foods remain commonly used. Even when based on an improved recipe, however, unfortified plant-based complementary foods provide insufficient key micronutrients (especially, iron, zinc, and calcium) during the age of 6–23 months. Thus, this review assessed complementary feeding practice and recommendation and reviewed the level of adequacy of homemade complementary foods. PMID:27800479

Impacts of crop insurance on water withdrawals for irrigation

NASA Astrophysics Data System (ADS)

Deryugina, Tatyana; Konar, Megan

2017-12-01

Agricultural production remains particularly vulnerable to weather fluctuations and extreme events, such as droughts, floods, and heat waves. Crop insurance is a risk management tool developed to mitigate some of this weather risk and protect farmer income in times of poor production. However, crop insurance may have unintended consequences for water resources sustainability, as the vast majority of freshwater withdrawals go to agriculture. The causal impact of crop insurance on water use in agriculture remains poorly understood. Here, we determine the empirical relationship between crop insurance and irrigation water withdrawals in the United States. Importantly, we use an instrumental variables approach to establish causality. Our methodology exploits a major policy change in the crop insurance system - the 1994 Federal Crop Insurance Reform Act - which imposed crop insurance requirements on farmers. We find that a 1% increase in insured crop acreage leads to a 0.223% increase in irrigation withdrawals, with most coming from groundwater aquifers. We identify farmers growing more groundwater-fed cotton as an important mechanism contributing to increased withdrawals. A 1% increase in insured crop acreage leads to a 0.624% increase in cotton acreage, or 95,602 acres. These results demonstrate that crop insurance causally leads to more irrigation withdrawals. More broadly, this work underscores the importance of determining causality in the water-food nexus as we endeavor to achieve global food security and water resources sustainability.

Current challenges in optimizing systemic therapy for patients with pancreatic cancer: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty.

PubMed

Segelov, Eva; Lordick, Florian; Goldstein, David; Chantrill, Lorraine A; Croagh, Daniel; Lawrence, Ben; Arnold, Dirk; Chau, Ian; Obermannova, Radka; Price, Timothy Jay

2017-10-01

Despite recent progress, the outlook for most patients with pancreatic cancer remains poor. There is variation in how patients are managed globally due to differing interpretations of the evidence, partly because studies in this disease are challenging to undertake. This article collates the evidence upon which current best practice is based and offers an expert opinion from an international faculty on how latest developments should influence current treatment paradigms. Areas covered: Optimal chemotherapy for first and subsequent lines of therapy; optimal management of locally advanced, non-metastatic cancer including the role of neoadjuvant chemo(radio)therapy, current evidence for adjuvant chemotherapy, major advances in pancreatic cancer genomics and challenges in supportive care particularly relevant to patients with pancreatic cancer. For each section, literature was reviewed by comprehensive search techniques, including clinical trial websites and abstracts from international cancer meetings. Expert commentary: For each section, a commentary is provided. Overall the challenges identified were: difficulties in diagnosing pancreatic cancer early, challenges for performing randomised clinical trials in all stages of the disease, some progress in systemic therapy with new agents and in identifying molecular subtypes that may be clinically relevant and move towards personalized therapy, but still, pancreatic cancer remains a very poor prognosis cancer with significant palliative care needs.

Ultrahigh-pressure polyamorphism in GeO2 glass with coordination number >6

NASA Astrophysics Data System (ADS)

Kono, Yoshio; Kenney-Benson, Curtis; Ikuta, Daijo; Shibazaki, Yuki; Wang, Yanbin; Shen, Guoyin

2016-03-01

Knowledge of pressure-induced structural changes in glasses is important in various scientific fields as well as in engineering and industry. However, polyamorphism in glasses under high pressure remains poorly understood because of experimental challenges. Here we report new experimental findings of ultrahigh-pressure polyamorphism in GeO2 glass, investigated using a newly developed double-stage large-volume cell. The Ge-O coordination number (CN) is found to remain constant at ∼6 between 22.6 and 37.9 GPa. At higher pressures, CN begins to increase rapidly and reaches 7.4 at 91.7 GPa. This transformation begins when the oxygen-packing fraction in GeO2 glass is close to the maximal dense-packing state (the Kepler conjecture = ∼0.74), which provides new insights into structural changes in network-forming glasses and liquids with CN higher than 6 at ultrahigh-pressure conditions.

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

PubMed

Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

2016-09-01

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

Unjamming and cell shape in the asthmatic airway epithelium

NASA Astrophysics Data System (ADS)

Park, Jin-Ah; Kim, Jae Hun; Bi, Dapeng; Mitchel, Jennifer A.; Qazvini, Nader Taheri; Tantisira, Kelan; Park, Chan Young; McGill, Maureen; Kim, Sae-Hoon; Gweon, Bomi; Notbohm, Jacob; Steward, Robert, Jr.; Burger, Stephanie; Randell, Scott H.; Kho, Alvin T.; Tambe, Dhananjay T.; Hardin, Corey; Shore, Stephanie A.; Israel, Elliot; Weitz, David A.; Tschumperlin, Daniel J.; Henske, Elizabeth P.; Weiss, Scott T.; Manning, M. Lisa; Butler, James P.; Drazen, Jeffrey M.; Fredberg, Jeffrey J.

2015-10-01

From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems--both inert and living--have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell-cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role.

Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation

PubMed Central

Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi

2010-01-01

Abdominal Aortic Aneurysm (AAA) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of AAA formation remains poorly understood. Currently, the treatment for AAA remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate AAA development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of AAA formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in AAA. PMID:18259804

Social Influence and Individual Risk Factors of HIV Unsafe Sex among Female Entertainment Workers in China

PubMed Central

Yang, Xiushi; Xia, Guomei; Li, Xiaoming; Latkin, Carl; Celentano, David

2010-01-01

Female entertainment workers in China are at increased sexual risk of HIV, but causes of their unprotected sex remain poorly understood. We develop a model that integrates information-motivation-behavioral skills (IMB) with social influences and test the model in a venue-based sample of 732 female entertainment workers in Shanghai. Most IMB and social influence measures are statistically significant in bivariate relationships to condom use; only HIV prevention motivation and behavioral self-efficacy remain significant in the multiple regressions. Self-efficacy in condom use is the most proximate correlate, mediating the relationship between information and motivation and condom use. Both peer and venue supports are important, but their influences over condom use are indirect and mediated through prevention motivation and/or self-efficacy. Behavioral intervention is urgently needed and should take a multi-level approach, emphasizing behavioral skills training and promoting a supportive social/working environment. PMID:20166789

A medical oncologist's approach to immunotherapy for advanced renal tumors: is nephrectomy indicated?

PubMed

Cooney, Matthew M; Remick, Scot C; Vogelzang, Nicholas J

2004-02-01

Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although interleukin-2 and interferon remain the most active agents for this disease, long-term survival rates remain poor. Two phase 3 trials, European Organization Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have demonstrated a survival benefit of nephrectomy followed by interferon versus interferon alone in patients having an excellent performance status (PS 0 and 1). Removal of the primary tumor followed by interferon is not recommended for patients with a moderate or poor PS (PS 2-4). Even with this aggressive approach, most patients eventually will die from their kidney cancer; therefore, every patient with metastatic disease should be considered for enrollment into clinical trials.

Expansion of Kes 73, a shell supernova remnant containing a magnetar

NASA Astrophysics Data System (ADS)

Borkowski, Kazimierz

2014-09-01

Formation and evolution of highly magnetized neutron stars (magnetars) remain poorly understood. We can learn about magnetars by studying their remnants. Kes 73 is a young supernova remnant containing a magnetar. But basic properties of Kes 73, including its age, remain poorly known. We propose a third-epoch observation of Kes 73 with Chandra. When combined with the 2000 and 2006 observations, this will allow for determination of the remnant's age through expansion rate measurements. We will also search for spatial variations in expansion rate that will help in understanding of the remnant's dynamics. New observations will also be used to determine abundances of heavy-element supernova ejecta, placing further constraints on the supernova that produced Kes 73.

Granuloma Transplantation: An Approach to Study Mycobacterium–Host Interactions

PubMed Central

Harding, Jeffrey S.; Schreiber, Heidi A.; Sandor, Matyas

2011-01-01

The host–pathogen biology during infection with Mycobacterium tuberculosis is incredibly complex and despite accelerating progress in research, remains poorly understood. Our limited understanding hinders the development of new drugs, next generation vaccines, and novel therapies. The granuloma is the site where mycobacteria are both controlled and allowed to persist, but it remains one of the least studied aspects of the host–pathogen relationship. Here, we review the development, application, potential uses, and limitations of a novel model of granuloma transplantation as a tool to study specific host–pathogen interactions that have been difficult to probe. Application of this new model has already contributed to our understanding of granuloma cell traffic, repopulation, and the relationship between systemic immunity and mycobacteria-containing granulomas. The data collected highlight the dynamic interaction between systemic and local immune processes and support a paradigm that defines the granuloma as a highly dynamic structure. Granuloma transplantation also has special potential as a novel latency model that can contribute to our understanding of host protection factors and bacterial mutants, and serve as a platform for drug testing. PMID:22180751

The prohibition of kidney sales and organ markets should remain.

PubMed

Danovitch, Gabriel M; Delmonico, Francis L

2008-08-01

There is an ongoing vigorous debate regarding the wisdom of the current prohibition of organ sales in the United States. We argue that this prohibition must remain in place. We discuss the current international realities regarding organ vending in order to show that even a so-called 'regulated' market brings with it danger to the welfare of transplant donors, their recipients, and potential recipients of nonrenal organs. We counter the specific arguments made in favor of organ sales while recommending multiple measures that can serve to remove disincentives to noncommercial organ donation. We encourage the investment in innovative healthy transplant practice for the benefit of all. In 'natural experiments' performed in developing countries the outcome for kidney vendors, in terms of both their medical and psychosocial health, has been shown to be poor. A high incidence of serious infections has been reported in recipients of vended organs. Commercialization of living kidney donation does not serve the interests of the donors, endangers the health of recipients, and undermines the healthy development of the international transplant endeavor.

X-ray Spectroscopy Uncovering the Effects of Cu Based Nanoparticle Concentration and Structure on Phaseolus vulgaris Germination and Seedling Development.

PubMed

Duran, Nádia M; Savassa, Susilaine M; Lima, Rafael Giovanini de; de Almeida, Eduardo; Linhares, Francisco S; van Gestel, Cornelis A M; Pereira de Carvalho, Hudson W

2017-09-13

Nanoparticles properties such as solubility, tunable surface charges, and singular reactivity might be explored to improve the performance of fertilizers. Nevertheless, these unique properties may also bring risks to the environment since the fate of nanoparticles is poorly understood. This study investigated the impact of a range of CuO nanoparticles sizes and concentrations on the germination and seedling development of Phaseolus vulgaris L. Nanoparticles did not affect seed germination, but seedling weight gain was promoted by 100 mg Cu L -1 and inhibited by 1 000 mg Cu L -1 of 25 nm CuO and CuSO 4 . Most of the Cu taken up remained in the seed coat with Cu hotspots in the hilum. X-ray absorption spectroscopy unraveled that most of the Cu remained in its pristine form. The higher surface reactivity of the 25 nm CuO nanoparticles might be responsible for its deleterious effects. The present study therefore highlights the importance of the nanoparticle structure for its physiological impacts.

Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer

PubMed Central

Katakai, Tomoya

2012-01-01

The architecture of secondary lymphoid organs (SLOs) is supported by several non-hematopoietic stromal cells. Currently it is established that two distinct stromal subsets, follicular dendritic cells and fibroblastic reticular cells, play crucial roles in the formation of tissue compartments within SLOs, i.e., the follicle and T zone, respectively. Although stromal cells in the anlagen are essential for SLO development, the relationship between these primordial cells and the subsets in adulthood remains poorly understood. In addition, the roles of stromal cells in the entry of antigens into the compartments through some tissue structures peculiar to SLOs remain unclear. A recently identified stromal subset, marginal reticular cells (MRCs), covers the margin of SLOs that are primarily located in the outer edge of follicles and construct a unique reticulum. MRCs are closely associated with specialized endothelial or epithelial structures for antigen transport. The similarities in marker expression profiles and successive localization during development suggest that MRCs directly descend from organizer stromal cells in the anlagen. Therefore, MRCs are thought to be a crucial stromal component for the organization and function of SLOs. PMID:22807928

Surgery for rheumatic mitral valve disease in sub-saharan African countries: why valve repair is still the best surgical option.

PubMed

Mvondo, Charles Mve; Pugliese, Marta; Giamberti, Alessandro; Chelo, David; Kuate, Liliane Mfeukeu; Boombhi, Jerome; Dailor, Ellen Marie

2016-01-01

Rheumatic valve disease, a consequence of acute rheumatic fever, remains endemic in developing countries in the sub-Saharan region where it is the leading cause of heart failure and cardiovascular death, involving predominantly a young population. The involvement of the mitral valve is pathognomonic and mitral surgery has become the lone therapeutic option for the majority of these patients. However, controversies exist on the choice between valve repair or prosthetic valve replacement. Although the advantages of mitral valve repair over prosthetic valve replacement in degenerative mitral disease are well established, this has not been the case for rheumatic lesions, where the use of prosthetic valves, specifically mechanical devices, even in poorly compliant populations remains very common. These patients deserve more accurate evaluation in the choice of the surgical strategy which strongly impacts the post-operative outcomes. This report discusses the factors supporting mitral repair surgery in rheumatic disease, according to the patients' characteristics and the effectiveness of the current repair techniques compared to prosthetic valve replacement in developing countries.

Impact of glycemic control on healthcare resource utilization and costs of type 2 diabetes: current and future pharmacologic approaches to improving outcomes.

PubMed

Banerji, Mary Ann; Dunn, Jeffrey D

2013-09-01

The incidence and prevalence of type 2 diabetes continue to grow in the United States and worldwide, along with the growing prevalence of obesity. Patients with type 2 diabetes are at greater risk for comorbid cardiovascular (CV) disease (CVD), which dramatically affects overall healthcare costs. To review the impact of glycemic control and medication adherence on morbidity, mortality, and healthcare costs of patients with type 2 diabetes, and to highlight the need for new drug therapies to improve outcomes in this patient population. This comprehensive literature search was conducted for the period between 2000 and 2013, using MEDLINE, to identify published articles that report the associations between glycemic control, medication adherence, CV morbidity and mortality, and healthcare utilization and costs. Search terms included "type 2 diabetes," "adherence," "compliance," "nonadherence," "drug therapy," "resource use," "cost," and "cost-effectiveness." Despite improvements in the management of CV risk factors in patients with type 2 diabetes, outcomes remain poor. The costs associated with the management of type 2 diabetes are increasing dramatically as the prevalence of the disease increases. Medication adherence to long-term drug therapy remains poor in patients with type 2 diabetes and contributes to poor glycemic control in this patient population, increased healthcare resource utilization and increased costs, as well as increased rates of comorbid CVD and mortality. Furthermore, poor adherence to established evidence-based guidelines for type 2 diabetes, including underdiagnosis and undertreatment, contributes to poor outcomes. New approaches to the treatment of patients with type 2 diabetes currently in development have the potential to improve medication adherence and consequently glycemic control, which in turn will help to reduce associated costs and healthcare utilization. As the prevalence of type 2 diabetes and its associated comorbidities grows, healthcare costs will continue to increase, indicating a need for better approaches to achieve glycemic control and manage comorbid conditions. Drug therapies are needed that enhance patient adherence and persistence levels far above levels reported with currently available drugs. Improvements in adherence to treatment guidelines and greater rates of lifestyle modifications also are needed. A serious unmet need exists for greatly improved patient outcomes, more effective and more tolerable drugs, as well as marked improvements in adherence to treatment guidelines and drug therapy to positively impact healthcare costs and resource use.

New perspectives on targeted therapy in ovarian cancer

PubMed Central

Coward, Jermaine IG; Middleton, Kathryn; Murphy, Felicity

2015-01-01

Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5 year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Although changes to the scheduling and administration of chemotherapy have improved outcomes to a degree, a therapeutic ceiling is being reached with this approach, resulting in a number of trials investigating the efficacy of targeted therapies alongside standard treatment algorithms. Furthermore, there is an urge to develop subtype-specific studies in an attempt to improve outcomes, which currently remain poor. This review summarizes the key studies with antiangiogenic agents, poly(adenosine diphosphate [ADP]-ribose) inhibitors, and epidermal growth factor receptor/human epidermal growth factor receptor family targeting, in addition to folate receptor antagonists and insulin growth factor receptor inhibitors. The efficacy of treatment paradigms used in non-ovarian malignancies for type I tumors is also highlighted, in addition to recent advances in appropriate patient stratification for targeted therapies in epithelial ovarian cancer. PMID:25678824

Genome-based vaccine design: the promise for malaria and other infectious diseases.

PubMed

Doolan, Denise L; Apte, Simon H; Proietti, Carla

2014-10-15

Vaccines are one of the most effective interventions to improve public health, however, the generation of highly effective vaccines for many diseases has remained difficult. Three chronic diseases that characterise these difficulties include malaria, tuberculosis and HIV, and they alone account for half of the global infectious disease burden. The whole organism vaccine approach pioneered by Jenner in 1796 and refined by Pasteur in 1857 with the "isolate, inactivate and inject" paradigm has proved highly successful for many viral and bacterial pathogens causing acute disease but has failed with respect to malaria, tuberculosis and HIV as well as many other diseases. A significant advance of the past decade has been the elucidation of the genomes, proteomes and transcriptomes of many pathogens. This information provides the foundation for new 21st Century approaches to identify target antigens for the development of vaccines, drugs and diagnostic tests. Innovative genome-based vaccine strategies have shown potential for a number of challenging pathogens, including malaria. We advocate that genome-based rational vaccine design will overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued vaccine developers for many years. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH).

PubMed

Gandaglia, Giorgio; Briganti, Alberto; Gontero, Paolo; Mondaini, Nicola; Novara, Giacomo; Salonia, Andrea; Sciarra, Alessandro; Montorsi, Francesco

2013-08-01

Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement. Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation. Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies. Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation. The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation. © 2013 BJU International.

Cushing disease as possible cause of persistent growth failure despite growth hormone therapy in a small for gestational age male.

PubMed

Heneghan, MaryKathleen; Alemzadeh, Ramin

2011-12-01

Growth hormone (GH) therapy in children with small for gestational age (SGA) has been shown to be of significant therapeutic benefit. We report the case of an 11-year-old Caucasian male who developed early adrenarche, hypertension and insulin resistance on GH therapy for SGA and profound short stature (ht -5 SD). This patient demonstrated a poor response to GH therapy and developed physical and biochemical findings of insulin resistance responsive to metformin therapy. He remained hypertensive, however, and continued to have elevated serum dehydroepiandrosterone sulfate levels. Urinary free cortisol excretion was subsequently found to be elevated. The diagnosis of Cushing's disease was confirmed with inferior petrosal sinus sampling and pituitary MRI. The patient underwent partial adenohypophysectomy with resulting normalization of plasma cortisol levels and associated symptoms. Our patient's diagnosis of Cushing's disease was complicated by his past history of poor growth since birth and history of SGA. The signs of Cushing's disease did not overtly appear until GH therapy was initiated to help treat severe short stature. It is possible that the metabolic effects of GH therapy unmasked the presence of underlying Cushing's disease.

Artificial neural network classifier predicts neuroblastoma patients' outcome.

PubMed

Cangelosi, Davide; Pelassa, Simone; Morini, Martina; Conte, Massimo; Bosco, Maria Carla; Eva, Alessandra; Sementa, Angela Rita; Varesio, Luigi

2016-11-08

More than fifty percent of neuroblastoma (NB) patients with adverse prognosis do not benefit from treatment making the identification of new potential targets mandatory. Hypoxia is a condition of low oxygen tension, occurring in poorly vascularized tissues, which activates specific genes and contributes to the acquisition of the tumor aggressive phenotype. We defined a gene expression signature (NB-hypo), which measures the hypoxic status of the neuroblastoma tumor. We aimed at developing a classifier predicting neuroblastoma patients' outcome based on the assessment of the adverse effects of tumor hypoxia on the progression of the disease. Multi-layer perceptron (MLP) was trained on the expression values of the 62 probe sets constituting NB-hypo signature to develop a predictive model for neuroblastoma patients' outcome. We utilized the expression data of 100 tumors in a leave-one-out analysis to select and construct the classifier and the expression data of the remaining 82 tumors to test the classifier performance in an external dataset. We utilized the Gene set enrichment analysis (GSEA) to evaluate the enrichment of hypoxia related gene sets in patients predicted with "Poor" or "Good" outcome. We utilized the expression of the 62 probe sets of the NB-Hypo signature in 182 neuroblastoma tumors to develop a MLP classifier predicting patients' outcome (NB-hypo classifier). We trained and validated the classifier in a leave-one-out cross-validation analysis on 100 tumor gene expression profiles. We externally tested the resulting NB-hypo classifier on an independent 82 tumors' set. The NB-hypo classifier predicted the patients' outcome with the remarkable accuracy of 87 %. NB-hypo classifier prediction resulted in 2 % classification error when applied to clinically defined low-intermediate risk neuroblastoma patients. The prediction was 100 % accurate in assessing the death of five low/intermediated risk patients. GSEA of tumor gene expression profile demonstrated the hypoxic status of the tumor in patients with poor prognosis. We developed a robust classifier predicting neuroblastoma patients' outcome with a very low error rate and we provided independent evidence that the poor outcome patients had hypoxic tumors, supporting the potential of using hypoxia as target for neuroblastoma treatment.

The impact of general anesthesia on child development and school performance: a population-based study.

PubMed

Schneuer, Francisco J; Bentley, Jason P; Davidson, Andrew J; Holland, Andrew Ja; Badawi, Nadia; Martin, Andrew J; Skowno, Justin; Lain, Samantha J; Nassar, Natasha

2018-04-27

There has been considerable interest in the possible adverse neurocognitive effects of exposure to general anesthesia and surgery in early childhood. The aim of this data linkage study was to investigate developmental and school performance outcomes of children undergoing procedures requiring general anesthesia in early childhood. We included children born in New South Wales, Australia of 37+ weeks' gestation without major congenital anomalies or neurodevelopmental disability with either a school entry developmental assessment in 2009, 2012, or Grade-3 school test results in 2008-2014. We compared children exposed to general anesthesia aged <48 months to those without any hospitalization. Children with only 1 hospitalization with general anesthesia and no other hospitalization were assessed separately. Outcomes included being classified developmentally high risk at school entry and scoring below national minimum standard in school numeracy and reading tests. Of 211 978 children included, 82 156 had developmental assessment and 153 025 had school test results, with 12 848 (15.7%) and 25 032 (16.4%) exposed to general anesthesia, respectively. Children exposed to general anesthesia had 17%, 34%, and 23% increased odds of being developmentally high risk (adjusted odds ratio [aOR]: 1.17; 95% CI: 1.07-1.29); or scoring below the national minimum standard in numeracy (aOR: 1.34; 95% CI: 1.21-1.48) and reading (aOR: 1.23; 95% CI: 1.12-1.36), respectively. Although the risk for being developmentally high risk and poor reading attenuated for children with only 1 hospitalization and exposure to general anesthesia, the association with poor numeracy results remained. Children exposed to general anesthesia before 4 years have poorer development at school entry and school performance. While the association among children with 1 hospitalization with 1 general anesthesia and no other hospitalization was attenuated, poor numeracy outcome remained. Further investigation of the specific effects of general anesthesia and the impact of the underlying health conditions that prompt the need for surgery or diagnostic procedures is required, particularly among children exposed to long duration of general anesthesia or with repeated hospitalizations. © 2018 John Wiley & Sons Ltd.

Interferon regulatory factor 4 attenuates Notch signaling to suppress the development of chronic lymphocytic leukemia

PubMed Central

Shukla, Vipul; Shukla, Ashima; Joshi, Shantaram S.

2016-01-01

Molecular pathogenesis of Chronic Lymphocytic Leukemia (CLL) is not fully elucidated. Genome wide association studies have linked Interferon Regulatory Factor 4 (IRF4) to the development of CLL. We recently established a causal relationship between low levels of IRF4 and development of CLL. However, the molecular mechanism through which IRF4 suppresses CLL development remains unclear. Deregulation of Notch signaling pathway has been identified as one of the most recurrent molecular anomalies in the pathogenesis of CLL. Yet, the role of Notch signaling as well as its regulation during CLL development remains poorly understood. Previously, we demonstrated that IRF4 deficient mice expressing immunoglobulin heavy chain Vh11 (IRF4−/−Vh11) developed spontaneous CLL with complete penetrance. In this study, we show that elevated Notch2 expression and the resulting hyperactivation of Notch signaling are common features of IRF4−/−Vh11 CLL cells. Our studies further reveal that Notch signaling is indispensable for CLL development in the IRF4−/−Vh11 mice. Moreover, we identify E3 ubiquitin ligase Nedd4, which targets Notch for degradation, as a direct target of IRF4 in CLL cells and their precursors. Collectively, our studies provide the first in vivo evidence for an essential role of Notch signaling in the development of CLL and establish IRF4 as a critical regulator of Notch signaling during CLL development. PMID:27232759

Comprehensive transcriptional map of primate brain development

PubMed Central

Bakken, Trygve E.; Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A.; Ng, Lydia; Szafer, Aaron; Dalley, Rachel A.; Royall, Joshua J.; Lemon, Tracy; Shapouri, Sheila; Aiona, Kaylynn; Arnold, James; Bennett, Jeffrey L.; Bertagnolli, Darren; Bickley, Kristopher; Boe, Andrew; Brouner, Krissy; Butler, Stephanie; Byrnes, Emi; Caldejon, Shiella; Carey, Anita; Cate, Shelby; Chapin, Mike; Chen, Jefferey; Dee, Nick; Desta, Tsega; Dolbeare, Tim A.; Dotson, Nadia; Ebbert, Amanda; Fulfs, Erich; Gee, Garrett; Gilbert, Terri L.; Goldy, Jeff; Gourley, Lindsey; Gregor, Ben; Gu, Guangyu; Hall, Jon; Haradon, Zeb; Haynor, David R.; Hejazinia, Nika; Hoerder-Suabedissen, Anna; Howard, Robert; Jochim, Jay; Kinnunen, Marty; Kriedberg, Ali; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Luong, Lon; Mastan, Naveed; May, Ryan; Melchor, Jose; Mosqueda, Nerick; Mott, Erika; Ngo, Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana; Pendergraft, Julie; Potekhina, Lydia; Reding, Melissa; Riley, Zackery L.; Roberts, Tyson; Rogers, Brandon; Roll, Kate; Rosen, David; Sandman, David; Sarreal, Melaine; Shapovalova, Nadiya; Shi, Shu; Sjoquist, Nathan; Sodt, Andy J.; Townsend, Robbie; Velasquez, Lissette; Wagley, Udi; Wakeman, Wayne B.; White, Cassandra; Bennett, Crissa; Wu, Jennifer; Young, Rob; Youngstrom, Brian L.; Wohnoutka, Paul; Gibbs, Richard A.; Rogers, Jeffrey; Hohmann, John G.; Hawrylycz, Michael J.; Hevner, Robert F.; Molnár, Zoltán; Phillips, John W.; Dang, Chinh; Jones, Allan R.; Amaral, David G.; Bernard, Amy; Lein, Ed S.

2017-01-01

The transcriptional underpinnings of brain development remain poorly understood, particularly in humans and closely related non-human primates. We describe a high resolution transcriptional atlas of rhesus monkey brain development that combines dense temporal sampling of prenatal and postnatal periods with fine anatomical parcellation of cortical and subcortical regions associated with human neuropsychiatric disease. Gene expression changes more rapidly before birth, both in progenitor cells and maturing neurons, and cortical layers and areas acquire adult-like molecular profiles surprisingly late postnatally. Disparate cell populations exhibit distinct developmental timing but also unexpected synchrony of processes underlying neural circuit construction including cell projection and adhesion. Candidate risk genes for neurodevelopmental disorders including primary microcephaly, autism spectrum disorder, intellectual disability, and schizophrenia show disease-specific spatiotemporal enrichment within developing neocortex. Human developmental expression trajectories are more similar to monkey than rodent, and approximately 9% of genes show human-specific regulation with evidence for prolonged maturation or neoteny. PMID:27409810

How Effective Have Thirty Years of Internationally Driven Conservation and Development Efforts Been in Madagascar?

PubMed

Waeber, Patrick O; Wilmé, Lucienne; Mercier, Jean-Roger; Camara, Christian; Lowry, Porter P

2016-01-01

Conservation and development are intricately linked. The international donor community has long provided aid to tropical countries in an effort to alleviate poverty and conserve biodiversity. While hundreds of millions of $ have been invested in over 500 environmental-based projects in Madagascar during the period covered by a series of National Environmental Action Plans (1993-2008) and the protected areas network has expanded threefold, deforestation remains unchecked and none of the eight Millennium Development Goals (MDGs) established for 2000-2015 were likely be met. Efforts to achieve sustainable development had failed to reduce poverty or deliver progress toward any of the MDGs. Cross-sectorial policy adjustments are needed that (i) enable and catalyze Madagascar's capacities rather than deepening dependency on external actors such as the World Bank, the International Monetary Fund and donor countries, and that (ii) deliver improvements to the livelihoods and wellbeing of the country's rural poor.

Relapsed or refractory pediatric acute lymphoblastic leukemia: current and emerging treatments.

PubMed

Martin, Alissa; Morgan, Elaine; Hijiya, Nobuko

2012-12-01

Relapsed acute lymphoblastic leukemia (ALL) represents a major cause of morbidity and mortality in pediatrics. With contemporary chemotherapy, >85% of patients with newly diagnosed ALL survive. Unfortunately, 20% of these patients will relapse and for these children, outcomes remain poor despite our best known chemotherapy protocols. Most of these children will achieve a second complete remission, but maintaining this remission remains difficult. Because relapsed ALL is such a significant cause of morbidity and mortality, it is the focus of much research interest. Efforts have been made and continue to focus on understanding the underlying biology that drives relapse. The role of hematopoietic stem cell transplantation in relapsed ALL remains unclear, but many clinicians still favor this for high-risk patients given the poor prognosis with current chemotherapy alone. It is important to use new drugs with little cross-resistance in the treatment of relapsed ALL. New classes of agents are currently being studied. We also discuss prognostic factors and the biology of relapsed ALL.

Does the risk of reprisal prevent nurses blowing the whistle on bad practice?

PubMed

Whitehead, Bill; Barker, Denise

Despite the introduction of legislation to protect people who report poor or unsafe practice, whistleblowing can still have serious consequences for nurses. To review the literature on whistleblowing in healthcare, and explore the barriers to reporting poor practice. Studies focusing on whistleblowing in healthcare were used to assess the safety of incident reporting, and to determine what prevented nurses from reporting poor practice. Four major themes were identified as the main barriers to whistleblowing in healthcare: experience of the nurse; confidentiality and reporting processes; incident severity; and personal beliefs. Reprisal for whistleblowing remains a major concern for nurses. Patient safety could be improved by prioritising confidentiality and creating an environment where nurses feel safe to report poor practice.

Residents of poor nations have a greater sense of meaning in life than residents of wealthy nations.

PubMed

Oishi, Shigehiro; Diener, Ed

2014-02-01

Using Gallup World Poll data, we examined the role of societal wealth for meaning in life across 132 nations. Although life satisfaction was substantially higher in wealthy nations than in poor nations, meaning in life was higher in poor nations than in wealthy nations. In part, meaning in life was higher in poor nations because people in those nations were more religious. The mediating role of religiosity remained significant after we controlled for potential third variables, such as education, fertility rate, and individualism. As Frankl (1963) stated in Man's Search for Meaning, it appears that meaning can be attained even under objectively dire living conditions, and religiosity plays an important role in this search.

Improving outcome in schizophrenia: the potential importance of EPS and neuroleptic dysphoria.

PubMed

Gerlach, Jes

2002-03-01

Despite half a century of antipsychotic drug treatment, the outcome of therapy in schizophrenia remains disappointing. Relapse, rehospitalization, limited fulfilment of social roles, and suicide remain frequent, and the economic costs are high. Current relapse rates may be two to three times higher than those that could be achieved with optimal use of therapy. Poor compliance with treatment is considered to be a significant preventable cause of poor outcome and is in turn likely to be influenced by the patient's experience of drug treatment. There is some evidence that extrapyramidal symptoms (EPS), particularly akathisia and neuroleptic dysphoria, are associated with poor compliance and poor treatment outcome. Atypical antipsychotics have a lower risk of EPS than do standard antipsychotics. Some (risperidone, olanzapine, and ziprasidone) show evidence of a dose-related increase in EPS, but clozapine and quetiapine have demonstrated a placebo-level incidence of EPS across the dose range. Quetiapine does not require the regular blood monitoring mandated for clozapine, and results from a patient survey indicate a high degree of patient satisfaction with treatment. While further research is needed, it is possible that wider use of medications with low EPS and high patient acceptability could promote better compliance and improve the outcome of schizophrenia treatment.

A current perspective on stereotactic body radiation therapy for pancreatic cancer

PubMed Central

Hong, Julian C; Czito, Brian G; Willett, Christopher G; Palta, Manisha

2016-01-01

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies. PMID:27826200

A current perspective on stereotactic body radiation therapy for pancreatic cancer.

PubMed

Hong, Julian C; Czito, Brian G; Willett, Christopher G; Palta, Manisha

2016-01-01

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.

Health Seeking in Men: A Concept Analysis.

PubMed

Hooper, Gwendolyn L; Quallich, Susanne A

2016-01-01

This article describes the analysis of the concept of health seeking in men. Men have shorter life expectancies and utilize health services less often than women, leading to poor health outcomes, but a gendered basis for health seeking remains poorly defined. Walker and Avant’s framework was used to guide this concept analysis. Literature published in English from 1990-2015 was reviewed. Thematic analysis identified attributes, antecedents, and consequences of the concept. Based on the analysis, a contemporary definition for health seeking in men was constructed, rooted in the concept of health. The definition is based on the concept analysis and the defining attributes that were identified. This analysis provides a definition specifically for health seeking in American men, making it more specific and gender-based than the parent concept of “health.” This concept analysis provides conceptual clarity that can guide development of a conceptual framework that may be uniquely relevant to providers in urology. Further exploration will uncover specific cultural, social, sexual, and geographic perspectives.

Neuroblastoma arginase activity creates an immunosuppressive microenvironment that impairs autologous and engineered immunity

PubMed Central

Mussai, Francis; Egan, Sharon; Hunter, Stuart; Webber, Hannah; Fisher, Jonathan; Wheat, Rachel; McConville, Carmel; Sbirkov, Yordan; Wheeler, Kate; Bendle, Gavin; Petrie, Kevin; Anderson, John; Chesler, Louis; De Santo, Carmela

2015-01-01

Neuroblastoma is the most common extra cranial solid tumour of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumour cells suppress T cell proliferation, through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34+ progenitor proliferation. Finally we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1 specific TCR and GD2-specific CAR engineered T cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for neuroblastoma patients. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumour and blood that leads to impaired immune surveillance and sub-optimal efficacy of immunotherapeutic approaches. PMID:26054597

Winners and losers in the competition for space in tropical forest canopies.

PubMed

Kellner, James R; Asner, Gregory P

2014-05-01

Trees compete for space in the canopy, but where and how individuals or their component parts win or lose is poorly understood. We developed a stochastic model of three-dimensional dynamics in canopies using a hierarchical Bayesian framework, and analysed 267,533 positive height changes from 1.25 m pixels using data from airborne LiDAR within 43 ha on the windward flank of Mauna Kea. Model selection indicates a strong resident's advantage, with 97.9% of positions in the canopy retained by their occupants over 2 years. The remaining 2.1% were lost to a neighbouring contender. Absolute height was a poor predictor of success, but short stature greatly raised the risk of being overtopped. Growth in the canopy was exponentially distributed with a scaling parameter of 0.518. These findings show how size and spatial proximity influence the outcome of competition for space, and provide a general framework for the analysis of canopy dynamics. © 2014 John Wiley & Sons Ltd/CNRS.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

PubMed

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

2016-02-25

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

Linking research to global health equity: the contribution of product development partnerships to access to medicines and research capacity building.

PubMed

Pratt, Bridget; Loff, Bebe

2013-11-01

Certain product development partnerships (PDPs) recognize that to promote the reduction of global health disparities they must create access to their products and strengthen research capacity in developing countries. We evaluated the contribution of 3 PDPs--Medicines for Malaria Venture, Drugs for Neglected Diseases Initiative, and Institute for One World Health--according to Frost and Reich's access framework. We also evaluated PDPs' capacity building in low- and middle-income countries at the individual, institutional, and system levels. We found that these PDPs advance public health by ensuring their products' registration, distribution, and adoption into national treatment policies in disease-endemic countries. Nonetheless, ensuring broad, equitable access for these populations--high distribution coverage; affordability, particularly for the poor; and adoption at provider and end-user levels--remains a challenge.

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

PubMed Central

Karshikoff, Bianka; Sundelin, Tina; Lasselin, Julie

2017-01-01

Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions. PMID:28163706

Mesoporous carbon incorporated metal oxide nanomaterials as supercapacitor electrodes.

PubMed

Jiang, Hao; Ma, Jan; Li, Chunzhong

2012-08-08

Supercapacitors have attracted huge attention in recent years as they have the potential to satisfy the demand of both huge energy and power density in many advanced technologies. However, poor conductivity and cycling stability remains to be the major challenge for its widespread application. Various strategies have been developed for meeting the ever-increasing energy and power demands in supercapacitors. This Research News article aims to review recent progress in the development of mesoporous carbon incorporated metal oxide nanomaterials, especially metal oxide nanoparticles confined in ordered mesoporous carbon and 1D metal oxides coated with a layer of mesoporous carbon for high-performance supercapacitor applications. In addition, a recent trend in supercapacitor development - hierarchical porous graphitic carbons (HPGC) combining macroporous cores, mesoporous walls, and micropores as an excellent support for metal oxides - is also discussed.

Anatomy of the Spinal Meninges.

PubMed

Sakka, Laurent; Gabrillargues, Jean; Coll, Guillaume

2016-06-01

The spinal meninges have received less attention than the cranial meninges in the literature, although several points remain debatable and poorly understood, like their phylogenesis, their development, and their interactions with the spinal cord. Their constancy among the chordates shows their crucial importance in central nervous system homeostasis and suggests a role far beyond mechanical protection of the neuraxis. This work provides an extensive study of the spinal meninges, from an overview of their phylogenesis and embryology to a descriptive and topographic anatomy with clinical implications. It examines their involvement in spinal cord development, functioning, and repair. This work is a review of the literature using PubMed as a search engine on Medline. The stages followed by the meninges along the phylogenesis could not be easily compared with their development in vertebrates for methodological aspects and convergence processes throughout evolution. The distinction between arachnoid and pia mater appeared controversial. Several points of descriptive anatomy remain debatable: the functional organization of the arterial network, and the venous and lymphatic drainages, considered differently by classical anatomic and neuroradiological approaches. Spinal meninges are involved in neurodevelopment and neurorepair producing neural stem cells and morphogens, in cerebrospinal fluid dynamics and neuraxis functioning by the synthesis of active molecules, and the elimination of waste products of central nervous system metabolism. The spinal meninges should be considered as dynamic functional formations evolving over a lifetime, with ultrastructural features and functional interactions with the neuraxis remaining not fully understood.

A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

PubMed

Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

2017-07-01

To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count <5% at diagnosis, previous haematological disorder, lower risk IPSS-R and a normal karyotype. Four out of five patients who received intensive therapy/transplant remain alive with median OS of 14 months. Median OS of Azacitidine-treated group was 11 months. t-MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

Towards the implementation of malaria elimination policy in South Africa: the stakeholders' perspectives.

PubMed

Hlongwana, Khumbulani Welcome; Tsoka-Gwegweni, Joyce

2017-01-01

The past decade has seen substantial global reduction in malaria morbidity and mortality due to increased international funding and decisive steps by the international malaria community to fight malaria. South Africa has been declared ready to institute malaria elimination. However, research on the factors that would affect this policy implementation is inadequate. To investigate the stakeholders' understanding of the malaria elimination policy in South Africa, including their perceived barriers and facilitators to effective policy implementation. The study followed a constructivist epistemological approach which manifests in phenomenological study design. Twelve purposively selected key informants from malaria researchers, provincial and national malaria programmes were interviewed using semi-structured interviews. Interview questions elicited interviewees' knowledge of the policy and its achievability, including any perceived barriers and facilitating factors to effective implementation. The hybrid approach was used to perform thematic data analysis. The dominant view was that malaria remains a problem in South Africa, exacerbated by staff attitudes and poor capacity, lack of resources, lack of new effective intervention tools, lack of intra- and inter-departmental collaboration, poor cross-border collaboration and weak stakeholder collaboration. Informants were concerned about the target year (2018) for elimination, and about the process followed in developing the policy, including the perceived malaria epidemiology shortfalls, regulatory issues and political context of the policy. Achievability of malaria elimination remains a subject of intense debate for a variety of reasons. These include the sporadic nature of malaria resurgence, raising questions about the contributions of malaria control interventions and climate to the transmission trends in South Africa. The shortage of resources, inadequate staff capacity, lack of any new effective intervention tools, and gaps in malaria epidemiology were key concerns, as was the superficially participative nature of the consultation process followed in developing the policy.

Effects of postnatal growth restriction and subsequent catch-up growth on neurodevelopment and glucose homeostasis in rats.

PubMed

Alexeev, Erica E; Lönnerdal, Bo; Griffin, Ian J

2015-06-05

There is increasing evidence that poor growth of preterm infants is a risk factor for poor long-term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine the consequences of different patterns of postnatal growth and hypothesized that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11, R pups were re-randomized into litters of 6 (R-6), 10 (R-10) or 16 (R-16) pups/dam. N pups remained in litters of 10 pups/dam (N-10). Memory and learning were examined through T-maze test. Insulin sensitivity was measured by i.p. insulin tolerance test and glucose tolerance test. By d10, N pups weighed 20% more than R pups (p < 0.001). By d15, the R-6 group caught up to the N-10 group in weight, the R-10 group showed partial catch-up growth and the R-16 group showed no catch-up growth. All R groups showed poorer scores in developmental testing when compared with the N-10 group during T-Maze test (p < 0.05). Although R-16 were more insulin sensitive than R-6 and R-10, all R groups were more glucose tolerant than N-10. In rats, differences in postnatal growth restriction leads to changes in development and in insulin sensitivity. These results may contribute to better elucidating the causes of poor developmental outcomes in human preterm infants.

The treatment of psychogenic polydipsia with risperidone in two children diagnosed with schizophrenia.

PubMed

Dogangün, Burak; Hergüner, Sabri; Atar, Murat; Kara, Bülent; Aksoy, M Umut; Kayaalp, Levent; Tüzün, Umran

2006-08-01

Polydipsia is a well-known phenomenon in adult psychiatry, but the literature regarding children is very limited. Just as the pathogenesis remains poorly understood, so does its management remain a clinical challenge. Data regarding the effect of risperidone on polydipsia are contradictory. We present case studies of remission of severe polydipsia with risperidone in two children.

When you reach a fork in the road, take it: science and product development as linked paths.

PubMed

Keusch, Gerald T

2008-01-01

There is a simple underlying message in this discussion, which has three parts. First, science has the capacity to generate new knowledge and harness that knowledge in the cause of developing products and technology that can reduce disease burdens among developing nation populations. Second, intellectual property is a tool to use in order to insure that new knowledge is not expropriated and exploited in a manner that threatens the ability to provide products and technology to poor people at an affordable price. Third, and finally, academic scientists need to understand that they can stride both pathways of the R&D road, remaining involved in generating basic knowledge while participating in the application of that knowledge towards product development and, through the use of best practice IP management, making it available in resource-poor environments. In order for this to happen, academia needs to maintain bridges to the private sector, while assiduously avoiding financial conflicts of interest, a topic not discussed in this paper. Academic scientists, whether already established or still completing their education, need access to training modules that allows them to define the challenges of the high disease burdens in the third world in human, and not just in consumption or dollar, terms. They also need education regarding the problems they work on, in order to engage them in the technology transfer from academia to the private sector; promote collaboration with scientists in the developing world; provide them with enough insights into the process and how it operates so that they know about the terms of any agreements with the private sector that would prevent poor people from accessing the ultimate product; and finally "reward" them in the academic system by advancement based on applied and field-based international translational and operational applied research. If these education programs develop and expand to increasing numbers of people in the research sector of academia, the number of people taking both paths described here will substantially increase. With that, the amount of research relevant to improving the health status--and indirectly, development--of developing countries will have been substantially increased.

Adverse Childhood Experiences Related to Poor Adult Health Among Lesbian, Gay, and Bisexual Individuals

PubMed Central

Herrick, Harry; Proescholdbell, Scott

2016-01-01

Objectives. We explored the association of sexual orientation with poor adult health outcomes before and after adjustment for exposure to adverse childhood experiences (ACEs). Methods. Data were from the 2012 North Carolina, 2011 Washington, and 2011 and 2012 Wisconsin Behavioral Risk Factor Surveillance System (BRFSS) surveys regarding health risks, perceived poor health, and chronic conditions by sexual orientation and 8 categories of ACEs. There were 711 lesbian, gay, and bisexual (LGB) respondents and 29 690 heterosexual respondents. Results. LGB individuals had a higher prevalence of all ACEs than heterosexuals, with odds ratios ranging from 1.4 to 3.1. After adjustment for cumulative exposure to ACEs, sexual orientation was no longer associated with poor physical health, current smoking, and binge drinking. Associations with poor mental health, activity limitation, HIV risk behaviors, current asthma, depression, and disability remained, but were attenuated. Conclusions. The higher prevalence of ACEs among LGB individuals may account for some of their excess risk for poor adult health outcomes. PMID:26691127

Influences of early child nutritional status and home learning environment on child development in Vietnam.

PubMed

Nguyen, Phuong H; DiGirolamo, Ann M; Gonzalez-Casanova, Ines; Young, Melissa; Kim, Nicole; Nguyen, Son; Martorell, Reynaldo; Ramakrishnan, Usha

2018-01-01

Early childhood development plays a key role in a child's future health, educational success, and economic status. However, suboptimal early development remains a global challenge. This study examines the influences of quality of the home learning environment (HOME) and child stunting in the first year of life on child development. We used data collected from a randomized controlled trial of preconceptional micronutrient supplementation in Vietnam (n = 1,458). The Bayley Scales of Infant Development-III were used to assess cognition, language, and motor development domains at 2 years. At 1 year, 14% of children were stunted, and 15%, 58%, and 28% of children lived in poor, medium, and high HOME environments, respectively. In multivariate generalized linear regression models, living in a high HOME environment was significantly associated with higher scores (0.10 to 0.13 SD) in each of the developmental domains. Stunted children scored significantly lower for cognitive, language, and motor development (-0.11 to -0.18), compared to nonstunted children. The negative associations between stunting on development were modified by HOME; the associations were strong among children living in homes with a poor learning environment whereas they were nonsignificant for those living in high-quality learning environments. In conclusion, child stunting the first year of life was negatively associated with child development at 2 years among children in Vietnam, but a high-quality HOME appeared to attenuate these associations. Early interventions aimed at improving early child growth as well as providing a stimulating home environment are critical to ensure optimal child development. © 2017 John Wiley & Sons Ltd.

The Rotator Cuff Organ: Integrating Developmental Biology, Tissue Engineering, and Surgical Considerations to Treat Chronic Massive Rotator Cuff Tears.

PubMed

Rothrauff, Benjamin B; Pauyo, Thierry; Debski, Richard E; Rodosky, Mark W; Tuan, Rocky S; Musahl, Volker

2017-08-01

The torn rotator cuff remains a persistent orthopedic challenge, with poor outcomes disproportionately associated with chronic, massive tears. Degenerative changes in the tissues that comprise the rotator cuff organ, including muscle, tendon, and bone, contribute to the poor healing capacity of chronic tears, resulting in poor function and an increased risk for repair failure. Tissue engineering strategies to augment rotator cuff repair have been developed in an effort to improve rotator cuff healing and have focused on three principal aims: (1) immediate mechanical augmentation of the surgical repair, (2) restoration of muscle quality and contractility, and (3) regeneration of native enthesis structure. Work in these areas will be reviewed in sequence, highlighting the relevant pathophysiology, developmental biology, and biomechanics, which must be considered when designing therapeutic applications. While the independent use of these strategies has shown promise, synergistic benefits may emerge from their combined application given the interdependence of the tissues that constitute the rotator cuff organ. Furthermore, controlled mobilization of augmented rotator cuff repairs during postoperative rehabilitation may provide mechanotransductive cues capable of guiding tissue regeneration and restoration of rotator cuff function. Present challenges and future possibilities will be identified, which if realized, may provide solutions to the vexing condition of chronic massive rotator cuff tears.

Strategies to Reduce Exclusion among Populations Living in Urban Slum Settlements in Bangladesh

PubMed Central

2009-01-01

The health and rights of populations living in informal or slum settlements are key development issues of the twenty-first century. As of 2007, the majority of the world's population lives in urban areas. More than one billion of these people, or one in three city-dwellers, live in inadequate housing with no or a few basic resources. In Bangladesh, urban slum settlements tend to be located in low-lying, flood-prone, poorly-drained areas, having limited formal garbage disposal and minimal access to safe water and sanitation. These areas are severely crowded, with 4–5 people living in houses of just over 100 sq feet. These conditions of high density of population and poor sanitation exacerbate the spread of diseases. People living in these areas experience social, economic and political exclusion, which bars them from society's basic resources. This paper overviews policies and actions that impact the level of exclusion of people living in urban slum settlements in Bangladesh, with a focus on improving the health and rights of the urban poor. Despite some strategies adopted to ensure better access to water and health, overall, the country does not have a comprehensive policy for urban slum residents, and the situation remains bleak. PMID:19761090

Strategies to reduce exclusion among populations living in urban slum settlements in Bangladesh.

PubMed

Rashid, Sabina Faiz

2009-08-01

The health and rights of populations living in informal or slum settlements are key development issues of the twenty-first century. As of 2007, the majority of the world's population lives in urban areas. More than one billion of these people, or one in three city-dwellers, live in inadequate housing with no or a few basic resources. In Bangladesh, urban slum settlements tend to be located in low-lying, flood-prone, poorly-drained areas, having limited formal garbage disposal and minimal access to safe water and sanitation. These areas are severely crowded, with 4-5 people living in houses of just over 100 sq feet. These conditions of high density of population and poor sanitation exacerbate the spread of diseases. People living in these areas experience social, economic and political exclusion, which bars them from society's basic resources. This paper overviews policies and actions that impact the level of exclusion of people living in urban slum settlements in Bangladesh, with a focus on improving the health and rights of the urban poor. Despite some strategies adopted to ensure better access to water and health, overall, the country does not have a comprehensive policy for urban slum residents, and the situation remains bleak.

Health and the 2008 Economic Recession: Evidence from the United Kingdom

PubMed Central

Astell-Burt, Thomas; Feng, Xiaoqi

2013-01-01

Introduction The economic recession which began in 2008 has resulted in a substantial increase in unemployment across many countries, including the United Kingdom. Strong association between unemployment and poor health status among individuals is widely recognised. We investigated whether the prevalence of poor health at a population level increased concurrent to the rise in unemployment during the economic recession, and whether the impact on health varied by geographical and socioeconomic circumstances. Method Health, demographic and socioeconomic measures on 1.36 million survey responses aged 16–64 were extracted from the Quarterly Labour Force Survey of the United Kingdom, collected every three months, from January 2006 to December 2010. The likelihood of self-reporting poor health status and specific types of health problems (depression, mental illness, cardiovascular and respiratory) across time were estimated separately using logistic regression. Explanatory variables included economic status (International Labour Organization definition), occupational class, age, gender, country of birth, ethnicity, educational qualifications, couple status, household tenure, number of dependents, and geographical region. Results Unemployment (age-gender adjusted) rose from 4.5% in January 2008 to 7.1% by September 2009. The reporting of poor health status increased from 25.7% in July 2009 to 29.5% by December 2010. Similar increases were found for cardiovascular and respiratory health problems; not depression or mental illness. The prevalence of poor health status among the unemployed decreased from 28.8% in July 2008, to 24.9% by March 2009; but this was followed by an increase in poor health experienced across all regions and by all socioeconomic groups, including those who remained employed, regardless of their occupational class. Interpretation Although our study found no exacerbation of pre-recession health inequalities, the rise in poor health status not only for the unemployed, but also among people who remained employed, regardless of their occupational class, justifies concern voiced among many public health commentators. PMID:23437208

A quantitative analysis of the state of knowledge of turtles of the United States and Canada

USGS Publications Warehouse

Lovich, Jeffrey E.; Ennen, Joshua R.

2013-01-01

The “information age” ushered in an explosion of knowledge and access to knowledge that continues to revolutionize society. Knowledge about turtles, as measured by number of published papers, has been growing at an exponential rate since the early 1970s, a phenomenon mirrored in all scientific disciplines. Although knowledge about turtles, as measured by number of citations for papers in scientific journals, has been growing rapidly, this taxonomic group remains highly imperiled suggesting that knowledge is not always successfully translated into effective conservation of turtles. We reviewed the body of literature on turtles of the United States and Canada and found that: 1) the number of citations is biased toward large-bodied species, 2) the number of citations is biased toward wide-ranging species, and 3) conservation status has little effect on the accumulation of knowledge for a species, especially after removing the effects of body size or range size. The dispersion of knowledge, measured by Shannon Weiner diversity and evenness indices across species, was identical from 1994 to 2009 suggesting that poorly studied species remained poorly-studied species while well-studied species remained well studied. Several species listed as threatened or endangered under the U.S. Endangered Species Act (e.g., Pseudemys alabamensis, Sternotherus depressus, and Graptemys oculifera) remain poorly studied with the estimated number of citations for each ranging from only 13-24. The low number of citations for these species could best be explained by their restricted distribution and/or their smaller size. Despite the exponential increase in knowledge of turtles in the United States and Canada, no species of turtle listed under the Endangered Species Act has ever been delisted for reason of recovery. Therefore, increased knowledge does not necessarily contribute appreciably to recovery of threatened turtles.

Changes in insulin and insulin signaling in Alzheimer’s disease: cause or consequence?

PubMed Central

Stanley, Molly; Macauley, Shannon L.

2016-01-01

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD. PMID:27432942

[Approaches to therapy for pulmonary hypertension: Role of the endothelin receptor antagonist bosentan].

PubMed

Avdeev, S N

2015-01-01

Pulmonary hypertension (PH) is a specific clinical group of severe and rare diseases with similar morphological, hemodynamic, and therapeutic characteristics. Despite the fact that there have been international conciliative documents and advances in drug therapy for PH, the long-term prognosis of the.disease in these patients remains rather poor. Clinical trials have demonstrated that bosentan therapy in patients with PH improves pulmonary hemodynamics and exercise endurance and delays the development of the disease. According to the data of long-term studies, as compared to the historical control, bosentan used as a first-line drug can improve survival in PH patients.

How infrastructure and financial institutions affect rural income and poverty: evidence from Bangladesh.

PubMed

Khandker, Shahidur R; Koolwal, Gayatri B

2010-01-01

The mechanisms by which the poor benefit from economic growth remain a topic of debate in development literature. We address this issue in the context of rural Bangladesh, using a pooled dataset of three household panels between 1991-2001. Expansion of irrigation, paved roads, electricity, and access to formal and informal credit have (through different veins) led to higher rural farm and non-farm incomes, accounting for exogenous local agroclimatic endowments that explain a large part of the variation in the growth of infrastructure and credit programmes. However, this has not translated into substantial reductions in poverty for the poorest households.

No allergic reaction after TKA in a chrome-cobalt-nickel-sensitive patient: case report and review of the literature.

PubMed

Thienpont, Emmanuel; Berger, Yorick

2013-03-01

Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. Although 20-25 % of total joint arthroplasty patients develop metal sensitivity, only a few highly susceptible persons (<1 %) exhibit symptoms. We present a case report of a fifty-two-year-old woman with a preoperatively documented metal allergy who underwent bilateral total knee arthroplasty using a titanium-niobium-coated implant on one side and a chrome-cobalt implant on the other side because of a logistics problem. At 2-year follow-up, no clinical symptoms of allergy or loosening of the implant were observed. Level of evidence IV.

Global vision of druggability issues: applications and perspectives.

PubMed

Abi Hussein, Hiba; Geneix, Colette; Petitjean, Michel; Borrel, Alexandre; Flatters, Delphine; Camproux, Anne-Claude

2017-02-01

During the preliminary stage of a drug discovery project, the lack of druggability information and poor target selection are the main causes of frequent failures. Elaborating on accurate computational druggability prediction methods is a requirement for prioritizing target selection, designing new drugs and avoiding side effects. In this review, we describe a survey of recently reported druggability prediction methods mainly based on networks, statistical pocket druggability predictions and virtual screening. An application for a frequent mutation of p53 tumor suppressor is presented, illustrating the complementarity of druggability prediction approaches, the remaining challenges and potential new drug development perspectives. Copyright © 2016 Elsevier Ltd. All rights reserved.

Environmental impact of engineered carbon nanoparticles: from releases to effects on the aquatic biota.

PubMed

Mottier, Antoine; Mouchet, Florence; Pinelli, Éric; Gauthier, Laury; Flahaut, Emmanuel

2017-08-01

Nano-ecotoxicology is an emerging science which aims to assess the environmental effect of nanotechnologies. The development of this particular aspect of ecotoxicology was made necessary in order to evaluate the potential impact of recently produced and used materials: nanoparticles (NPs). Among all the types of NPs, carbon nanoparticles (CNPs) especially draw attention giving the increasing number of applications and integration into consumer products. However the potential impacts of CNPs in the environment remain poorly known. This review aims to point out the critical issues and aspects that will govern the toxicity of CNPs in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Macrophage heterogeneity in tissues: phenotypic diversity and functions

PubMed Central

Gordon, Siamon; Plüddemann, Annette; Martinez Estrada, Fernando

2014-01-01

During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation. PMID:25319326

Management of patients with pulmonary arterial hypertension due to congenital heart disease: recent advances and future directions.

PubMed

Blok, Ilja M; van Riel, Annelieke C M J; Mulder, Barbara J M; Bouma, Berto J

2015-12-01

Pulmonary arterial hypertension is a serious complication of adult congenital heart disease associated with systemic-to-pulmonary shunts. Although early shunt closure restricts development of pulmonary arterial hypertension, patients remain at risk even after repair. The development of pulmonary arterial hypertension is associated with a markedly increased morbidity and mortality. It is important to identify patients with a poor prognosis using disease specific markers. Echocardiography and biomarkers arise as practical tools to determine the risk of mortality. Although pulmonary arterial hypertension cannot be cured, four classes of disease-targeting therapies are currently available and several promising therapies are being studied. There is a shift in drug studies towards more clinically relevant endpoints such as time to clinical worsening and morbidity and mortality events.

The contribution of health to the economy in the European Union.

PubMed

Suhrcke, Marc; McKee, Martin; Stuckler, David; Sauto Arce, Regina; Tsolova, Svetla; Mortensen, Jørgen

2006-11-01

Despite increasing recognition of the link between health and economic development in low-income countries, the relationship has to date received scant attention in rich countries. We argue that this lack of attention is not justifiable. While the economic argument for investing in health in rich countries may differ in detail from that in low-income countries, there is considerable and convincing evidence that significant economic benefits can be achieved by improving health not only in poor, but also in rich countries. Better health increases labour supply and productivity and historically, health has been a major contributor to economic growth. In spite of remaining evidence gaps economic policy-makers also in developed countries should consider investing in health as one (of few) ways by which to achieve their economic objectives.

Febuxostat hypersensitivity: another cause of DRESS syndrome in chronic kidney disease?

PubMed

Paschou, E; Gavriilaki, E; Papaioannou, G; Tsompanakou, A; Kalaitzoglou, A; Sabanis, N

2016-11-01

Febuxostat is a xanthine oxidase inhibitor that during the last years has successfully replaced allopurinol treatment in patients with chronic kidney disease (CKD) and hyperuricemia. Several adverse events have been observed during therapy with febuxostat. DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) syndrome induced by febuxostat has been poorly described, mainly in patient with CKD who previously developed allopurinol hypersensitivity syndrome. DRESS syndrome is characterized by manifold cutaneous reactions and systemic disorders with potential devastating consequences. The underlying pathogenetic mechanisms remain unidentified, though immune responses are often complicated. P-i concept can partially explain the phenomenon. The role of renal insufficiency appears to be crucial and further investigation is required. The present article describes the case of a CKD patient that developed febuxostat-related DRESS syndrome.

Malnutrition and vaccination in developing countries

PubMed Central

Prendergast, Andrew J.

2015-01-01

Malnutrition contributes to an estimated 45% of deaths among children under 5 years of age in developing countries, predominantly due to infections. Malnourished children therefore stand to benefit hugely from vaccination, but malnutrition has been described as the most common immunodeficiency globally, suggesting that they may not be able to respond effectively to vaccines. The immunology of malnutrition remains poorly characterized, but is associated with impairments in mucosal barrier integrity, and innate and adaptive immune dysfunction. Despite this, the majority of malnourished children can mount a protective immune response following vaccination, although the timing, quality and duration of responses may be impaired. This paper reviews the evidence for vaccine immunogenicity in malnourished children, discusses the importance of vaccination in prevention of malnutrition and highlights evidence gaps in our current knowledge. PMID:25964453

Prevention and control of rheumatic heart disease: Overcoming core challenges in resource-poor environments.

PubMed

Dougherty, Scott; Beaton, Andrea; Nascimento, Bruno R; Zühlke, Liesl J; Khorsandi, Maziar; Wilson, Nigel

2018-01-01

Rheumatic heart disease (RHD) has long receded as a significant threat to public health in high-income countries. In low-resource settings, however, the specter of RHD remains unabated, as exemplified by recent data from the Global Burden of Diseases Study. There are many complex reasons for this ongoing global disparity, including inadequate data on disease burden, challenges in effective advocacy, ongoing poverty and inequality, and weak health systems, most of which predominantly affect developing nations. In this review, we discuss how each of these acts as a core challenge in RHD prevention and control. We then examine key lessons learnt from successful control programs in the past and highlight resources that have been developed to help create strong national RHD control programs.

Neural Changes Developed during the Extinction of Cocaine Self-Administration Behavior

PubMed Central

Higuera-Matas, Alejandro; Miguens, Miguel; del Olmo, Nuria; García-Lecumberri, Carmen; Ambrosio, Emilio

2011-01-01

The high rate of recidivism in cocaine addiction after prolonged periods of abstinence poses a significant problem for the effective treatment of this condition. Moreover, the neurobiological basis of this relapse phenomenon remains poorly understood. In this review, we will discuss the evidence currently available regarding the neurobiological changes during the extinction of cocaine self-administration. Specifically, we will focus on alterations in the dopaminergic, opioidergic, glutamatergic, cholinergic, serotoninergic and CRF systems described in self-administration experiments and extinction studies after chronic cocaine administration. We will also discuss the differences related to contingent versus non-contingent cocaine administration, which highlights the importance of environmental cues on drug effects and extinction. The findings discussed in this review may aid the development of more effective therapeutic approaches to treat cocaine relapse. PMID:26791639

The spleen in liver cirrhosis: revisiting an old enemy with novel targets.

PubMed

Li, Liang; Duan, Mubing; Chen, Weisan; Jiang, An; Li, Xiaoming; Yang, Jun; Li, Zongfang

2017-05-23

The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.

Endocrine therapy toxicity: management options.

PubMed

Henry, N Lynn

2014-01-01

Treatment with adjuvant endocrine therapy, including tamoxifen and the aromatase inhibitors, has resulted in notable improvements in disease-free and overall survival for patients with hormone receptor-positive breast cancer. Despite their proven benefit, however, adherence to and persistence with the medications is poor in part because of bothersome side effects that can negatively affect quality of life. Retrospective analyses have identified possible predictors of development of toxicity. Reports have also suggested that development of toxicity may be a biomarker of better response to therapy. In addition, there has been considerable research investment into the management of these side effects, which may lead to improved adherence and persistence with therapy. However, although notable advances have been made, much more remains to be done to provide patients with truly personalized therapy for hormone receptor-positive breast cancer.

Prevention and control of rheumatic heart disease: Overcoming core challenges in resource-poor environments

PubMed Central

Dougherty, Scott; Beaton, Andrea; Nascimento, Bruno R; Zühlke, Liesl J; Khorsandi, Maziar; Wilson, Nigel

2018-01-01

Rheumatic heart disease (RHD) has long receded as a significant threat to public health in high-income countries. In low-resource settings, however, the specter of RHD remains unabated, as exemplified by recent data from the Global Burden of Diseases Study. There are many complex reasons for this ongoing global disparity, including inadequate data on disease burden, challenges in effective advocacy, ongoing poverty and inequality, and weak health systems, most of which predominantly affect developing nations. In this review, we discuss how each of these acts as a core challenge in RHD prevention and control. We then examine key lessons learnt from successful control programs in the past and highlight resources that have been developed to help create strong national RHD control programs. PMID:29440834

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

PubMed Central

Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

The pillars of land plants: new insights into stem development.

PubMed

Serrano-Mislata, Antonio; Sablowski, Robert

2018-05-12

In spite of its central importance in evolution, plant architecture and crop improvement, stem development remains poorly understood relative to other plant organs. Here, we summarise current knowledge of stem ontogenesis and its regulation, including insights from new image analysis and biophysical approaches. The stem initiates in the rib zone (RZ) of the shoot apical meristem, under transcriptional control by DELLA and BLH proteins. Links have emerged between these regulators and cell proliferation, patterning and oriented growth in the RZ. During subsequent internode elongation, cell wall properties and mechanics have been analysed in detail, revealing pectin modification as a prominent control point. Recent work has also highlighted signalling to coordinate growth of stem tissues with different mechanical properties. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Compensating Losses in Bridge Employment? Examining Relations between Compensation Strategies, Health Problems, and Intention to Remain at Work

ERIC Educational Resources Information Center

Muller, Andreas; De Lange, Annet; Weigl, Matthias; Oxfart, Caroline; Van der Heijden, Beatrice

2013-01-01

In order to better understand the precursors of bridge employment, this study aimed to investigate whether individual action strategies in terms of selection, optimization, and compensation (SOC; Baltes & Baltes, 1990) are able to buffer the well-known negative impact of poor health on the intention to remain in the workforce. 784 employees (60-85…

Determination of Appropriate Service Delivery Level for Quantitative Attributes of Household Toilets in Rural Settlements of India from Users' Perspective

NASA Astrophysics Data System (ADS)

Rashid, Mohammad; Pandit, Debapratim

2018-04-01

Improvement of quality of sanitation services in rural settlements is an important development goal in developing countries including India and accordingly several strategies are adopted which promote the demand and use of household toilets through creating awareness and providing subsidies to poor people for construction of household toilets with service-level standards specified from experts' perspective. In many cases, users are unsatisfied with the quality of toilets constructed using subsidies and the same remain unused. Users' satisfaction depends on their perceptions of service quality of individual attributes and overall service quality of the household toilets, which is an important determinant of sustainability and sustained use of toilets. This study aims to assess and benchmark the appropriate service delivery level for quantitative attributes of rural household toilets based on user perception. The service quality is determined with the help of level of service (LOS) scales developed using successive interval scaling technique, the zone of tolerance (ZOT), and users satisfaction level (USL) which relates service delivery levels with user satisfaction directly. The study finds that the service quality of most of the attributes of household toilets constructed using subsidies is perceived as poor. The results also suggest that most of the users expect to have a toilet with the service level of attributes ranging between LOS A and LOS B.

The eICU research institute - a collaboration between industry, health-care providers, and academia.

PubMed

McShea, Michael; Holl, Randy; Badawi, Omar; Riker, Richard R; Silfen, Eric

2010-01-01

As the volume of data that is electronically available promliferates, the health-care industry is identifying better ways to use this data for patient care. Ideally, these data are collected in real time, can support point-of-care clinical decisions, and, by providing instantaneous quality metrics, can create the opportunities to improve clinical practice as the patient is being cared for. The business-world technology supporting these activities is referred to as business intelligence, which offers competitive advantage, increased quality, and operational efficiencies. The health-care industry is plagued by many challenges that have made it a latecomer to business intelligence and data-mining technology, including delayed adoption of electronic medical records, poor integration between information systems, a lack of uniform technical standards, poor interoperability between complex devices, and the mandate to rigorously protect patient privacy. Efforts at developing a health care equivalent of business intelligence (which we will refer to as clinical intelligence) remains in its infancy. Until basic technology infrastructure and mature clinical applications are developed and implemented throughout the health-care system, data aggregation and interpretation cannot effectively progress. The need for this approach in health care is undisputed. As regional and national health information networks emerge, we need to develop cost-effective systems that reduce time and effort spent documenting health-care data while increasing the application of knowledge derived from that data.

Determination of Appropriate Service Delivery Level for Quantitative Attributes of Household Toilets in Rural Settlements of India from Users' Perspective.

PubMed

Rashid, Mohammad; Pandit, Debapratim

2018-04-01

Improvement of quality of sanitation services in rural settlements is an important development goal in developing countries including India and accordingly several strategies are adopted which promote the demand and use of household toilets through creating awareness and providing subsidies to poor people for construction of household toilets with service-level standards specified from experts' perspective. In many cases, users are unsatisfied with the quality of toilets constructed using subsidies and the same remain unused. Users' satisfaction depends on their perceptions of service quality of individual attributes and overall service quality of the household toilets, which is an important determinant of sustainability and sustained use of toilets. This study aims to assess and benchmark the appropriate service delivery level for quantitative attributes of rural household toilets based on user perception. The service quality is determined with the help of level of service (LOS) scales developed using successive interval scaling technique, the zone of tolerance (ZOT), and users satisfaction level (USL) which relates service delivery levels with user satisfaction directly. The study finds that the service quality of most of the attributes of household toilets constructed using subsidies is perceived as poor. The results also suggest that most of the users expect to have a toilet with the service level of attributes ranging between LOS A and LOS B.

An investigation of the relationship between subjective sleep quality, loneliness and mood in an Australian sample: can daily routine explain the links?

PubMed

Smith, Simon Squire; Kozak, Nahum; Sullivan, Karen Anne

2012-03-01

Loneliness and low mood are associated with significant negative health outcomes including poor sleep, but the strength of the evidence underlying these associations varies. There is strong evidence that poor sleep quality and low mood are linked, but only emerging evidence that loneliness and poor sleep are associated. To independently replicate the finding that loneliness and poor subjective sleep quality are associated and to extend past research by investigating lifestyle regularity as a possible mediator of relationships, since lifestyle regularity has been linked to loneliness and poor sleep. Using a cross-sectional design, 97 adults completed standardized measures of loneliness, lifestyle regularity, subjective sleep quality and mood. Loneliness was a significant predictor of sleep quality. Lifestyle regularity was not a predictor of, nor associated with, mood, sleep quality or loneliness. This study provides an important independent replication of the association between poor sleep and loneliness. However, the mechanism underlying this link remains unclear. A theoretically plausible mechanism for this link, lifestyle regularity, does not explain the relationship between loneliness and poor sleep. The nexus between loneliness and poor sleep is unlikely to be broken by altering the social rhythm of patients who present with poor sleep and loneliness.

Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications.

PubMed

Kawabata, Yohei; Wada, Koichi; Nakatani, Manabu; Yamada, Shizuo; Onoue, Satomi

2011-11-25

The poor oral bioavailability arising from poor aqueous solubility should make drug research and development more difficult. Various approaches have been developed with a focus on enhancement of the solubility, dissolution rate, and oral bioavailability of poorly water-soluble drugs. To complete development works within a limited amount of time, the establishment of a suitable formulation strategy should be a key consideration for the pharmaceutical development of poorly water-soluble drugs. In this article, viable formulation options are reviewed on the basis of the biopharmaceutics classification system of drug substances. The article describes the basic approaches for poorly water-soluble drugs, such as crystal modification, micronization, amorphization, self-emulsification, cyclodextrin complexation, and pH modification. Literature-based examples of the formulation options for poorly water-soluble compounds and their practical application to marketed products are also provided. Classification of drug candidates based on their biopharmaceutical properties can provide an indication of the difficulty of drug development works. A better understanding of the physicochemical and biopharmaceutical properties of drug substances and the limitations of each delivery option should lead to efficient formulation development for poorly water-soluble drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

Addressing the Complexity of Tourette's Syndrome through the Use of Animal Models

PubMed Central

Nespoli, Ester; Rizzo, Francesca; Boeckers, Tobias M.; Hengerer, Bastian; Ludolph, Andrea G.

2016-01-01

Tourette's syndrome (TS) is a neurodevelopmental disorder characterized by fluctuating motor and vocal tics, usually preceded by sensory premonitions, called premonitory urges. Besides tics, the vast majority—up to 90%—of TS patients suffer from psychiatric comorbidities, mainly attention deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The etiology of TS remains elusive. Genetics is believed to play an important role, but it is clear that other factors contribute to TS, possibly altering brain functioning and architecture during a sensitive phase of neural development. Clinical brain imaging and genetic studies have contributed to elucidate TS pathophysiology and disease mechanisms; however, TS disease etiology still is poorly understood. Findings from genetic studies led to the development of genetic animal models, but they poorly reflect the pathophysiology of TS. Addressing the role of neurotransmission, brain regions, and brain circuits in TS disease pathomechanisms is another focus area for preclinical TS model development. We are now in an interesting moment in time when numerous innovative animal models are continuously brought to the attention of the public. Due to the diverse and largely unknown etiology of TS, there is no single preclinical model featuring all different aspects of TS symptomatology. TS has been dissected into its key symptomst hat have been investigated separately, in line with the Research Domain Criteria concept. The different rationales used to develop the respective animal models are critically reviewed, to discuss the potential of the contribution of animal models to elucidate TS disease mechanisms. PMID:27092043

The Use of Radiation Response (RR) in Selecting the Method of Treatment of Carcinoma Cervicis Uteri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chesterman, John N.

1963-03-01

Attempts were made to determine the choice treatment of cervical squamous carcinoma (surgery, radiation, or surgery with radiation) in Stages I and II. A study of 50 patients showed good results from surgery in patients with poor radiation response (RR) and that the RR, estimated by a precise and uniform technique, will identify those patients who will not respond well to complete radiation therapy. Moreover, it will do this after a first radium application of moderate dosage, at a time when it is still possible to interrupt this therapy. A radiation dose of at least 1000 r at the cervixmore » will be followed by the maximum RR, in a good response, between the 8th and 14th (especially 10th to 12th) days. A poor RR will reach its maximum earlier than a good one, on about the 10th day after radium implantation. When deciding the definition of good RR, it was found that the radiation changes present in a count of 100 cells were seen in more than 70 cells. There is evidence that age, menopause, and hormonal status influence the radiation reaction. If poor RR is more frequently found with high estrogenic activity, young patients treated by radiation should be expected to have a worse survival rate than old. The survival rate is about 1/3) in the young patient as against 1/2 in the postmenopausal. A good sensitization response (SR) was, in most cases, followed by good RR after radiation. Of 39 patients with good SR, 34 had good RR after one application of radium. However, this correlation was absent when the SR was poor. Of 41 patients with poor SR, 18 remained poor after radiation and 23 developed good RR. Finally, this SR should not be taken alone as a guide to treatment, but all patients should be given the first radium application and the RR assessed.« less

Dpp signaling inhibits proliferation in the Drosophila wing by Omb-dependent regional control of bantam.

PubMed

Zhang, Xubo; Luo, Dan; Pflugfelder, Gert O; Shen, Jie

2013-07-01

The control of organ growth is a fundamental aspect of animal development but remains poorly understood. The morphogen Dpp has long been considered as a general promoter of cell proliferation during Drosophila wing development. It is an ongoing debate whether the Dpp gradient is required for the uniform cell proliferation observed in the wing imaginal disc. Here, we investigated how the Dpp signaling pathway regulates proliferation during wing development. By systematic manipulation of Dpp signaling we observed that it controls proliferation in a region-specific manner: Dpp, via omb, promoted proliferation in the lateral and repressed proliferation in the medial wing disc. Omb controlled the regional proliferation rate by oppositely regulating transcription of the microRNA gene bantam in medial versus lateral wing disc. However, neither the Dpp nor Omb gradient was essential for uniform proliferation along the anteroposterior axis.

Intercellular and systemic spread of RNA and RNAi in plants.

PubMed

Nazim Uddin, Mohammad; Kim, Jae-Yean

2013-01-01

Plants possess dynamic networks of intercellular communication that are crucial for plant development and physiology. In plants, intercellular communication involves a combination of ligand-receptor-based apoplasmic signaling, and plasmodesmata and phloem-mediated symplasmic signaling. The intercellular trafficking of macromolecules, including RNAs and proteins, has emerged as a novel mechanism of intercellular communication in plants. Various forms of regulatory RNAs move over distinct cellular boundaries through plasmodesmata and phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also involved in development, nutrient homeostasis, gene silencing, pathogen defense, and many other physiological processes. However, the mechanism underlying macromolecular trafficking in plants remains poorly understood. Current progress made in RNA trafficking research and its biological relevance to plant development will be summarized. Diverse plant regulatory mechanisms of cell-to-cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs, and small RNAs, will also be discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment.

PubMed

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas.

Molecular Biology in Pediatric High-Grade Glioma: Impact on Prognosis and Treatment

PubMed Central

Rizzo, Daniela; Ruggiero, Antonio; Martini, Maurizio; Rizzo, Valentina; Maurizi, Palma; Riccardi, Riccardo

2015-01-01

High-grade gliomas are the main cause of death in children with brain tumours. Despite recent advances in cancer therapy, their prognosis remains poor and the treatment is still challenging. To date, surgery followed by radiotherapy and temozolomide is the standard therapy. However, increasing knowledge of glioma biology is starting to impact drug development towards targeted therapies. The identification of agents directed against molecular targets aims at going beyond the traditional therapeutic approach in order to develop a personalized therapy and improve the outcome of pediatric high-grade gliomas. In this paper, we critically review the literature regarding the genetic abnormalities implicated in the pathogenesis of pediatric malignant gliomas and the current development of molecularly targeted therapies. In particular, we analyse the impact of molecular biology on the prognosis and treatment of pediatric high-grade glioma, comparing it to that of adult gliomas. PMID:26448930

Early but not late blindness leads to enhanced arithmetic and working memory abilities.

PubMed

Dormal, Valérie; Crollen, Virginie; Baumans, Christine; Lepore, Franco; Collignon, Olivier

2016-10-01

Behavioural and neurophysiological evidence suggest that vision plays an important role in the emergence and development of arithmetic abilities. However, how visual deprivation impacts on the development of arithmetic processing remains poorly understood. We compared the performances of early (EB), late blind (LB) and sighted control (SC) individuals during various arithmetic tasks involving addition, subtraction and multiplication of various complexities. We also assessed working memory (WM) performances to determine if they relate to a blind person's arithmetic capacities. Results showed that EB participants performed better than LB and SC in arithmetic tasks, especially in conditions in which verbal routines and WM abilities are needed. Moreover, EB participants also showed higher WM abilities. Together, our findings demonstrate that the absence of developmental vision does not prevent the development of refined arithmetic skills and can even trigger the refinement of these abilities in specific tasks. Copyright © 2016 Elsevier Ltd. All rights reserved.

Vaccines Against Malaria

PubMed Central

Ouattara, Amed; Laurens, Matthew B.

2015-01-01

Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

Autonomic nerve development contributes to prostate cancer progression.

PubMed

Magnon, Claire; Hall, Simon J; Lin, Juan; Xue, Xiaonan; Gerber, Leah; Freedland, Stephen J; Frenette, Paul S

2013-07-12

Nerves are a common feature of the microenvironment, but their role in tumor growth and progression remains unclear. We found that the formation of autonomic nerve fibers in the prostate gland regulates prostate cancer development and dissemination in mouse models. The early phases of tumor development were prevented by chemical or surgical sympathectomy and by genetic deletion of stromal β2- and β3-adrenergic receptors. Tumors were also infiltrated by parasympathetic cholinergic fibers that promoted cancer dissemination. Cholinergic-induced tumor invasion and metastasis were inhibited by pharmacological blockade or genetic disruption of the stromal type 1 muscarinic receptor, leading to improved survival of the mice. A retrospective blinded analysis of prostate adenocarcinoma specimens from 43 patients revealed that the densities of sympathetic and parasympathetic nerve fibers in tumor and surrounding normal tissue, respectively, were associated with poor clinical outcomes. These findings may lead to novel therapeutic approaches for prostate cancer.

Antimalarial Drug: From its Development to Deface.

PubMed

Barik, Tapan Kumar

2015-01-01

Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.

Emerging technologies in point-of-care molecular diagnostics for resource-limited settings.

PubMed

Peeling, Rosanna W; McNerney, Ruth

2014-06-01

Emerging molecular technologies to diagnose infectious diseases at the point at which care is delivered have the potential to save many lives in developing countries where access to laboratories is poor. Molecular tests are needed to improve the specificity of syndromic management, monitor progress towards disease elimination and screen for asymptomatic infections with the goal of interrupting disease transmission and preventing long-term sequelae. In simplifying laboratory-based molecular assays for use at point-of-care, there are inevitable compromises between cost, ease of use and test performance. Despite significant technological advances, many challenges remain for the development of molecular diagnostics for resource-limited settings. There needs to be more advocacy for these technologies to be applied to infectious diseases, increased efforts to lower the barriers to market entry through streamlined and harmonized regulatory approaches, faster policy development for adoption of new technologies and novel financing mechanisms to enable countries to scale up implementation.

Purtscher's retinopathy that occurred 6 months before acute pancreatitis.

PubMed

Sharma, Ashish G; Kazim, Nadia A; Eliott, Dean; Houghton, Odette; Abrams, Gary W

2006-01-01

To report Purtscher's retinopathy in a patient with chronic pancreatitis 6 months before the development of fulminant acute pancreatitis. Observational case report. Review of clinical chart, photographs, fluorescein angiography, and optical coherence tomography. A 45-year-old man with a history of alcohol abuse with a 3-day history of decreased vision in both eyes was examined. Diffuse retinal whitening and intraretinal hemorrhages that were consistent with Purtscher's retinopathy were present in both eyes. Serum amylase and lipase levels were normal. Six months later, he experienced intractable abdominal pain. Serum amylase and lipase levels were elevated markedly. Abdominal computed tomography and endoscopic retrograde cholangiopancreatography confirmed acute pancreatitis, with evidence of coexisting chronic pancreatitis. His funduscopic examination after the development of acute pancreatitis was improved, with almost complete resolution of retinal whitening and hemorrhages. Visual acuity remained poor because of retinal ischemia. Purtscher's retinopathy can be associated with chronic pancreatitis and can precede the development of fulminant acute pancreatitis.

Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

PubMed

Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

2017-09-01

The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

Collective arrangements and social networks: Coping strategies for the poor households in the Great Ruaha Catchment in Tanzania

NASA Astrophysics Data System (ADS)

Kadigi, Reuben M. J.; Mdoe, N. S. Y.; Ashimogo, G. C.

Access to water and land resources underpins the socio-economic fabric of many societies in the Southern Africa region, which is characterized broadly as underdeveloped with widespread food insecurity, exacerbated by persistent droughts, erratic rainfalls and increasing human populations. The availability of land and water resources is increasingly diminishing and becoming a stumbling block to the development of the agrarian societies in the region. The poor households have in turn adopted new livelihood coping mechanisms but little research has been done to assess the effectiveness of these ‘instruments’. Consequently, the concepts of sustainable water resources management and agricultural development have remained elusive and poorly understood by policy makers as well as by water resources planners and managers. Recognizing this, a study was conducted between 2002 and 2005 under the RIPARWIN (Raising Irrigation Productivity and Releasing Water for Intersectoral Needs) project to assess the spatial dynamics of livelihood capital, vulnerability and coping strategies for the poor agrarian households in the Upper Great Ruaha River Catchment (GRRC) in Tanzania. The results of analysis showed an array of livelihood platforms and institutional contexts that act to shape the existing livelihood typologies in the GRRC. In addition, the results showed a gradual increase in household vulnerability from upstream to downstream, particularly in terms of access to physical and natural assets. Vulnerability was found to be directly associated with the number of dependants. The female-headed households were relatively more likely to be vulnerable than the male-headed households (cf. probabilities of 27% and 21%, respectively). The value of collective arrangements and drawing on social networks crosscut all social strata and ranked as the most common livelihood strategy. This suggests that the scope for reducing vulnerability among the poor households in the GRRC critically depends on the existing institutional arrangements and mechanisms. Of paramount importance is perhaps the need to facilitate the establishment and empowerment of water use associations and apex bodies. In the study area, this appears to be promising enough to build ‘strong’ institutional platforms through which water and land resources would be managed sustainably.

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

PubMed

Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

2010-04-29

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Enhancing Leadership and Governance Competencies to Strengthen Health Systems in Nigeria: Assessment of Organizational Human Resources Development

PubMed Central

Uneke, Chigozie J.; Ezeoha, Abel E.; Ndukwe, Chinwendu D.; Oyibo, Patrick G.; Onwe, Fri Day

2012-01-01

The lack of effective leadership and governance in the health sector has remained a major challenge in Nigeria and contributes to the failure of health systems and poor development of human resources. In this cross-sectional intervention study, leadership and governance competencies of policy makers were enhanced through a training workshop, and an assessment was conducted of organizational activities designed to promote evidence-informed leadership and governance to improve human resources for health (HRH). The training workshop increased the understanding of policy makers with regard to leadership and governance factors that ensure the functionality of health systems and improve human resources development, including policy guidance, intelligence and oversight, collaboration and coalition building, regulation, system design and accountability. Findings indicated that systems for human resources development exist in all participants' organizations, but the functionality of these systems was suboptimal. More systematic and standardized processes are required to improve competencies of leadership and governance for better human resources development in low-income settings. PMID:23372582

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dirix, Piet; Nuyts, Sandra; Geussens, Yasmyne

Purpose: To evaluate the long-term clinical outcome and toxicity of conventional and three-dimensional conformal radiotherapy for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between January 1976 and February 2003, 127 patients with histologically proven cancer of the paranasal sinuses (n = 119) or nasal cavity (n = 8) were treated with preoperative (n = 61), postoperative (n = 51), or primary (n = 15) radiotherapy, using conventional (n = 74) or three-dimensional conformal (n = 53) techniques. No elective neck irradiation of the cervical lymph nodes was performed in N0 patients. Results: Median follow-up was 5.6more » years (range, 3-307 months) for all patients, and 7.3 years (range, 47-307 months) for patients still alive at the close-out date. The actuarial 5-year local control, overall survival, and disease-free survival rates were 53%, 54%, and 37%, respectively. Only 6 (5%) of all 127 patients and 4 (3%) of 122 originally N0 patients developed a regional failure in the neck. Distant metastasis occurred in 20% of patients. Both primary tumor extent and lymph node involvement were the most important prognostic factors, together with squamous cell carcinoma histology. Conclusion: Local failure remains the dominant cause of poor outcome for patients with sinonasal cancer, despite aggressive local treatment with combined surgery and radiotherapy in operable patients. Distant metastasis and certainly regional relapse were much less common sites of failure. Overall survival remains poor, suggesting the need for more efficacious local and possibly systemic therapy.« less

Milk: the new white gold? Milk production options for smallholder farmers in Southern Mali.

PubMed

de Ridder, N; Sanogo, O M; Rufino, M C; van Keulen, H; Giller, K E

2015-07-01

Until the turn of the century, farmers in West Africa considered cotton to be the 'white gold' for their livelihoods. Large fluctuations in cotton prices have led farmers to innovate into other business including dairy. Yet the productivity of cows fed traditional diets is very poor, especially during the long dry season. This study combines earlier published results of farmer participatory experiments with simulation modelling to evaluate the lifetime productivity of cows under varying feeding strategies and the resulting economic performance at farm level. We compared the profitability of cotton production to the innovation of dairy. The results show that milk production of the West African Méré breed could be expanded if cows are supplemented and kept stall-fed during the dry season. This option seems to be profitable for better-off farmers, but whether dairy will replace (some of) the role of cotton as the white gold for these smallholder farmers will depend on the cross price elasticity of cotton and milk. Farmers may (partly) replace cotton production for fodder production to produce milk if the price of cotton remains poor (below US$0.35/kg) and the milk price relatively strong (higher than US$0.38/kg). Price ratios need to remain stable over several seasons given the investments required for a change in production strategy. Furthermore, farmers will only seize the opportunity to engage in dairy if marketing infrastructure and milk markets are further developed.

Graft failure after allogeneic hematopoietic stem cell transplantation.

PubMed

Ozdemir, Zehra Narli; Civriz Bozdağ, Sinem

2018-04-18

Graft failure is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Successful transplantation depends on the formation of engrafment, in which donor cells are integrated into the recipient's cell population. In this paper, we distinguish two different entities, graft failure (GF) and poor graft function (PGF), and review the current comprehensions of the interactions between the immune and hematopoietic compartments in these conditions. Factors associated with graft failure include histocompatibility locus antigen (HLA)-mismatched grafts, underlying disease, type of conditioning regimen and stem cell source employed, low stem cell dose, ex vivo T-cell depletion, major ABO incompatibility, female donor grafts for male recipients, disease status at transplantation. Although several approaches have been developed which aimed to prevent graft rejection, establish successful engraftment and treat graft failure, GF remains a major obstacle to the success of allo-HSCT. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) still remains to be the curative treatment option for various non-malignant and malignant hematopoietic diseases. The outcome of allo-HSCT primarily depends on the engraftment of the graft. Graft failure (GF), is a life-threatening complication which needs the preferential therapeutic manipulation. In this paper, we focused on the definitions of graft failure / poor graft function and also we reviewed the current understanding of the pathophysiology, risk factors and treatment approaches for these entities. Copyright © 2018. Published by Elsevier Ltd.

Self-rated health and standard risk factors for myocardial infarction: a cohort study.

PubMed

Waller, Göran; Janlert, Urban; Norberg, Margareta; Lundqvist, Robert; Forssén, Annika

2015-02-13

To investigate the relationship between self-rated health, adjusted for standard risk factors, and myocardial infarction. Population-based prospective cohort study. Enrolment took place between 1990 and 2004 in Västerbotten County, Sweden Every year, persons in the total population, aged 40, 50 or 60 were invited. Participation rate was 60%. The cohort consisted of 75 386 men and women. After exclusion for stroke or myocardial infarction before, or within 12 months after enrolment or death within 12 months after enrolment, 72 530 persons remained for analysis. Mean follow-up time was 13.2 years. Cox regression analysis was used to estimate HRs for the end point of first non-fatal or fatal myocardial infarction. HR were adjusted for age, sex, systolic blood pressure, total cholesterol, smoking, diabetes, body mass index, education, physical activity and self-rated health in the categories very good; pretty good; somewhat good; pretty poor or poor. In the cohort, 2062 persons were diagnosed with fatal or non-fatal myocardial infarction. Poor self-rated health adjusted for sex and age was associated with the outcome with HR 2.03 (95% CI 1.45 to 2.84). All categories of self-rated health worse than very good were statistically significant and showed a dose-response relationship. In a multivariable analysis with standard risk factors (not including physical activity and education) HR was attenuated to 1.61 (95% CI 1.13 to 2.31) for poor self-rated health. All categories of self-rated health remained statistically significant. We found no interaction between self-rated health and standard risk factors except for poor self-rated health and diabetes. This study supports the use of self-rated health as a standard risk factor among others for myocardial infarction. It remains to demonstrate whether self-rated health adds predictive value for myocardial infarction in combined algorithms with standard risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Is demand-side financing equity enhancing? Lessons from a maternal health voucher scheme in Bangladesh.

PubMed

Ahmed, Shakil; Khan, M Mahmud

2011-05-01

Demand-side financing (DSF) is used in the less-developed countries of the world to improve access to healthcare and to encourage market supply. Under DSF, households receive vouchers that can be used to pay for healthcare services. This study evaluated the effects of a universal DSF on maternal healthcare service utilization in Bangladesh. A household survey was conducted in and around the voucher scheme area one year after the initiation of the project. Women who gave birth within a year prior to the survey were interviewed. The utilization rates of maternal health services were found to be higher for all socioeconomic groups in the project area than in the comparison areas. Voucher recipients in the project area were 3.6 times more likely to be assisted by skilled health personnel during delivery, 2.5 times more likely to deliver the baby in a health facility, 2.8 times more likely to receive postnatal care (PNC), 2.0 times more likely to get antenatal care (ANC) services and 1.5 times more likely to seek treatment for obstetric complications than pregnant women not in the program. The degree of socioeconomic inequality in maternal health service utilization was also lower in the project area than in the comparison area. The use of vouchers evidenced much stronger demand-increasing effects on the poor. Poor voucher recipients were 4.3 times more likely to deliver in a health facility and two times more likely to use skilled health personnel at delivery than the non-poor recipients. Contrary to the inverse equity hypothesis, the voucher scheme reduced inequality even in the short run. Despite these improvements, socioeconomic disparity in the use of maternal health services has remained pro-rich, implying that demand-side financing alone will be insufficient to achieve the Millennium Development Goal for maternal health. A comprehensive system-wide approach, including supply-side strengthening, will be needed to adequately address maternal health concerns in poor developing countries. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ethical issues in funding research and development of drugs for neglected tropical diseases.

PubMed

Oprea, L; Braunack-Mayer, A; Gericke, C A

2009-05-01

Neglected and tropical diseases, pervasive in developing countries, are important contributors to global health inequalities. They remain largely untreated due to lack of effective and affordable treatments. Resource-poor countries cannot afford to develop the public health interventions needed to control neglected diseases. In addition, neglected diseases do not represent an attractive market for pharmaceutical industry. Although a number of international commitments, stated in the Millennium Development Goals, have been made to avert the risk of communicable diseases, tropical diseases still remain neglected due to delays in international assistance. This delay can be explained by the form international cooperation has generally taken, which is limited to promoting countries' national interests, rather than social justice at a global level. This restricts the international responsibility for global inequalities in health to a humanitarian assistance. We propose an alternative view, arguing that expanding the scope of international cooperation by promoting shared health and economic value at a global level will create new opportunities for innovative, effective and affordable interventions worldwide. It will also promote neglected diseases as a global research priority. We build our argument on a proposal to replace the patenting system that currently regulates pharmaceutical research with a global fund to reward this research based on actual decreases in morbidity and mortality at a global level. We argue that this approach is beneficent because it will decrease global health inequalities and promote social justice worldwide.

Longitudinal patterns of poverty and health in early childhood: exploring the influence of concurrent, previous, and cumulative poverty on child health outcomes

PubMed Central

2012-01-01

Background Although the links between poverty and health have often been studied , the dynamics of poverty and physical health in early childhood remain under-investigated. In particular, it is not known whether the health of young children is affected differently from that of adults by patterns of poverty unique to them. Methods We examined patterns of health from 5 to 41 months of age as a function of concurrent, lagged, and chronic exposure to insufficient income. Using data from the first four rounds of the Quebec Longitudinal Study of Child Development, we performed multilevel logistic and multilevel Poisson regressions and latent growth curve analyses to explore associations between exposure to poverty and mother-reported asthma-like attacks, and maternal perception of health status controlling for neonatal, maternal, and environmental characteristics. Results The mean number of mother-reported asthma-like attacks significantly decreased as children aged. The likelihood of being perceived in a poorer health status also decreased across time. Concurrent poverty was associated with more mother-reported asthma-like attacks and with a higher risk of being perceived in poorer health status. One-period-lagged poverty was associated with more mother-reported asthma-like attacks and this remained significant after controlling for concurrent poverty. The number of mother-reported asthma-like attacks was significantly higher among children in the chronic poverty class compared to those in the never-poor class, particularly at 17 and 29 months. Perceived health status at 5-months was significantly poorer among chronically poor children compared to never-poor children. Conclusion Exposure to poverty negatively affects two major health indicators in early childhood – maternal perception of child health and mother-reported asthma-like attacks. Patterns of the effects vary according to timing and duration of poverty exposure. Further longitudinal research is warranted to disentangle time-specific from cumulative effects of poverty on child health. PMID:22947499

Longitudinal patterns of poverty and health in early childhood: exploring the influence of concurrent, previous, and cumulative poverty on child health outcomes.

PubMed

Béatrice, Nikiéma; Lise, Gauvin; Victoria, Zunzunegui Maria; Louise, Séguin

2012-09-04

Although the links between poverty and health have often been studied , the dynamics of poverty and physical health in early childhood remain under-investigated. In particular, it is not known whether the health of young children is affected differently from that of adults by patterns of poverty unique to them. We examined patterns of health from 5 to 41 months of age as a function of concurrent, lagged, and chronic exposure to insufficient income. Using data from the first four rounds of the Quebec Longitudinal Study of Child Development, we performed multilevel logistic and multilevel Poisson regressions and latent growth curve analyses to explore associations between exposure to poverty and mother-reported asthma-like attacks, and maternal perception of health status controlling for neonatal, maternal, and environmental characteristics. The mean number of mother-reported asthma-like attacks significantly decreased as children aged. The likelihood of being perceived in a poorer health status also decreased across time. Concurrent poverty was associated with more mother-reported asthma-like attacks and with a higher risk of being perceived in poorer health status. One-period-lagged poverty was associated with more mother-reported asthma-like attacks and this remained significant after controlling for concurrent poverty. The number of mother-reported asthma-like attacks was significantly higher among children in the chronic poverty class compared to those in the never-poor class, particularly at 17 and 29 months. Perceived health status at 5-months was significantly poorer among chronically poor children compared to never-poor children. Exposure to poverty negatively affects two major health indicators in early childhood - maternal perception of child health and mother-reported asthma-like attacks. Patterns of the effects vary according to timing and duration of poverty exposure. Further longitudinal research is warranted to disentangle time-specific from cumulative effects of poverty on child health.

Vector competence of Aedes aegypti mosquitoes for filarial nematodes is affected by age and nutrient limitation.

PubMed

Ariani, Cristina V; Juneja, Punita; Smith, Sophia; Tinsley, Matthew C; Jiggins, Francis M

2015-01-01

Mosquitoes are one of the most important vectors of human disease. The ability of mosquitoes to transmit disease is dependent on the age structure of the population, as mosquitoes must survive long enough for the parasites to complete their development and infect another human. Age could have additional effects due to mortality rates and vector competence changing as mosquitoes senesce, but these are comparatively poorly understood. We have investigated these factors using the mosquito Aedes aegypti and the filarial nematode Brugia malayi. Rather than observing any effects of immune senescence, we found that older mosquitoes were more resistant, but this only occurred if they had previously been maintained on a nutrient-poor diet of fructose. Constant blood feeding reversed this decline in vector competence, meaning that the number of parasites remained relatively unchanged as mosquitoes aged. Old females that had been maintained on fructose also experienced a sharp spike in mortality after an infected blood meal ("refeeding syndrome") and few survived long enough for the parasite to develop. Again, this effect was prevented by frequent blood meals. Our results indicate that old mosquitoes may be inefficient vectors due to low vector competence and high mortality, but that frequent blood meals can prevent these effects of age. Copyright © 2014 Elsevier Inc. All rights reserved.

Fine motor skill proficiency in typically developing children: On or off the maturation track?

PubMed

Gaul, David; Issartel, Johann

2016-04-01

Fine motor skill proficiency is an essential component of numerous daily living activities such as dressing, feeding or playing. Poor fine motor skills can lead to difficulties in academic achievement, increased anxiety and poor self-esteem. Recent findings have shown that children's gross motor skill proficiency tends to fall below established developmental norms. A question remains: do fine motor skill proficiency levels also fall below developmental norms? The aim of this study was to examine the current level of fine motor skill in Irish children. Children (N=253) from 2nd, 4th and 6th grades (mean age=7.12, 9.11 and 11.02 respectively) completed the Fine Motor Composite of the Bruininks Oseretsky Test of Motor Proficiency 2nd Edition (BOT-2). Analysis revealed that only 2nd grade children met the expected level of fine motor skill proficiency. It was also found that despite children's raw scores improving with age, children's fine motor skill proficiency was not progressing at the expected rate given by normative data. This leads us to question the role and impact of modern society on fine motor skills development over the past number of decades. Copyright © 2015 Elsevier B.V. All rights reserved.

Legal risk management and injury in the fitness industry: the outcomes of focus group research and a national survey of fitness professionals.

PubMed

Keyzer, Patrick; Coyle, Ian R; Dietrich, Joachim; Norton, Kevin; Sekendiz, Betul; Jones, Veronica; Finch, Caroline F

2014-06-01

The Australian Fitness Industry Risk Management (AFIRM) Project was set up to explore the operation of rules and regulations for the delivery of safe fitness services. This article summarises the results of recent focus group research and a national survey of risk management practices by the AFIRM Project. Our focus group research in four States identified the following most important concerns: (1) the competency of fitness professionals; (2) the effectiveness of pre-exercise screening and the management of de-conditioned clients; (3) poor supervision of fitness service users and incorrect use of equipment; (4) fitness trainers failing to remain within their scope of practice; (5) equipment misuse (as distinct from incorrect use); and (6) poor fitness training environments. This information was then used to develop 45 specific items for a questionnaire that was disseminated throughout the fitness industry. The survey, which is the largest ever conducted in the Australian fitness industry (n = 1,178), identified similar concerns. Our research indicates that efforts to improve risk management in the fitness industry should focus, first and foremost, on the development and monitoring of safety policy, and improvements in the education and training of fitness instructors to ensure that they can incorporate risk management practices.

DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease

PubMed Central

Jeziorska, Danuta M.; Murray, Robert J. S.; De Gobbi, Marco; Gaentzsch, Ricarda; Garrick, David; Ayyub, Helena; Chen, Taiping; Li, En; Telenius, Jelena; Lynch, Magnus; Graham, Bryony; Smith, Andrew J. H.; Lund, Jonathan N.; Hughes, Jim R.; Higgs, Douglas R.

2017-01-01

The human genome contains ∼30,000 CpG islands (CGIs). While CGIs associated with promoters nearly always remain unmethylated, many of the ∼9,000 CGIs lying within gene bodies become methylated during development and differentiation. Both promoter and intragenic CGIs may also become abnormally methylated as a result of genome rearrangements and in malignancy. The epigenetic mechanisms by which some CGIs become methylated but others, in the same cell, remain unmethylated in these situations are poorly understood. Analyzing specific loci and using a genome-wide analysis, we show that transcription running across CGIs, associated with specific chromatin modifications, is required for DNA methyltransferase 3B (DNMT3B)-mediated DNA methylation of many naturally occurring intragenic CGIs. Importantly, we also show that a subgroup of intragenic CGIs is not sensitive to this process of transcription-mediated methylation and that this correlates with their individual intrinsic capacity to initiate transcription in vivo. We propose a general model of how transcription could act as a primary determinant of the patterns of CGI methylation in normal development and differentiation, and in human disease. PMID:28827334

Antiviral agents and HIV prevention: controversies, conflicts, and consensus

PubMed Central

Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.

2013-01-01

Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927

5 CFR 9701.408 - Developing performance and addressing poor performance.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Developing performance and addressing poor performance. (a) Subject to budgetary and other organizational... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Developing performance and addressing poor performance. 9701.408 Section 9701.408 Administrative Personnel DEPARTMENT OF HOMELAND SECURITY...

Challenges in the management of rheumatoid arthritis in developing countries.

PubMed

Mody, Girish M; Cardiel, Mario H

2008-08-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by chronic inflammation of the joints. Patients experience chronic pain and suffering, and increasing disability; without treatment, life expectancy is reduced. It is imperative to identify patients early so that control of inflammation can prevent joint destruction and disability. Although great advances have been made in the developed nations, early diagnosis remains a great challenge for developing countries during the Bone and Joint Decade (2000-2010) and beyond. Developing countries face important and competitive social, economic, health- and poverty-related issues, and this frequently results in chronic diseases such as RA being forgotten in health priorities when urgent health needs are considered in an environment with poor education and scarce resources. Epidemiological studies in developing countries show a lower but still important prevalence in different regions when compared to that in Caucasians. It seems that the severity of RA varies among different ethnic groups, and probably starts at a younger age in developing countries. Practising rheumatologists in these regions need to take into account several important problems that include suboptimal undergraduate education, inadequate diagnosis, late referrals, lack of human and technical resources, poor access to rheumatologists, and some deficiencies in drug availability. Infections are very important in RA, and special care is needed in developing countries as some endemic infections include tuberculosis, human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. These infections should be carefully taken into account when medications are prescribed and monitored. This chapter presents published information covering the main challenges faced in these environments, and suggests strategies to overcome these important problems in RA management.

Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility

PubMed Central

Zhao, Lu; Yuan, Shiaulou; Cao, Ying; Kallakuri, Sowjanya; Li, Yuanyuan; Kishimoto, Norihito; DiBella, Linda; Sun, Zhaoxia

2013-01-01

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by defective cilia motility. The identified PCD genes account for about half of PCD incidences and the underlying mechanisms remain poorly understood. We demonstrate that Reptin/Ruvbl2, a protein known to be involved in epigenetic and transcriptional regulation, is essential for cilia motility in zebrafish. We further show that Reptin directly interacts with the PCD protein Lrrc6/Seahorse and this interaction is critical for the in vivo function of Lrrc6/Seahorse in zebrafish. Moreover, whereas the expression levels of multiple dynein arm components remain unchanged or become elevated, the density of axonemal dynein arms is reduced in reptinhi2394 mutants. Furthermore, Reptin is highly enriched in the cytosol and colocalizes with Lrrc6/Seahorse. Combined, these results suggest that the Reptin-Lrrc6/Seahorse complex is involved in dynein arm formation. We also show that although the DNA damage response is induced in reptinhi2394 mutants, it remains unchanged in cilia biogenesis mutants and lrrc6/seahorse mutants, suggesting that increased DNA damage response is not intrinsic to ciliary defects and that in vertebrate development, Reptin functions in multiple processes, both cilia specific and cilia independent. PMID:23858445

Reptin/Ruvbl2 is a Lrrc6/Seahorse interactor essential for cilia motility.

PubMed

Zhao, Lu; Yuan, Shiaulou; Cao, Ying; Kallakuri, Sowjanya; Li, Yuanyuan; Kishimoto, Norihito; DiBella, Linda; Sun, Zhaoxia

2013-07-30

Primary ciliary dyskinesia (PCD) is an autosomal recessive disease caused by defective cilia motility. The identified PCD genes account for about half of PCD incidences and the underlying mechanisms remain poorly understood. We demonstrate that Reptin/Ruvbl2, a protein known to be involved in epigenetic and transcriptional regulation, is essential for cilia motility in zebrafish. We further show that Reptin directly interacts with the PCD protein Lrrc6/Seahorse and this interaction is critical for the in vivo function of Lrrc6/Seahorse in zebrafish. Moreover, whereas the expression levels of multiple dynein arm components remain unchanged or become elevated, the density of axonemal dynein arms is reduced in reptin(hi2394) mutants. Furthermore, Reptin is highly enriched in the cytosol and colocalizes with Lrrc6/Seahorse. Combined, these results suggest that the Reptin-Lrrc6/Seahorse complex is involved in dynein arm formation. We also show that although the DNA damage response is induced in reptin(hi2394) mutants, it remains unchanged in cilia biogenesis mutants and lrrc6/seahorse mutants, suggesting that increased DNA damage response is not intrinsic to ciliary defects and that in vertebrate development, Reptin functions in multiple processes, both cilia specific and cilia independent.

The Double Burden of Undernutrition and Overnutrition in Developing Countries: an Update.

PubMed

Abdullah, Asnawi

2015-09-01

Many developing countries have achieved a remarkable improvement in nutrition status in the past decades. However, the prevalence of undernutrition remains a serious problem. At the same time, the prevalence of obesity is increasing substantially, and in some countries, it has approached that of developed countries. This article provides an update on this double burden of malnutrition (DBMN) in developing nations. One hundred countries (lower, middle-lower, and upper-middle income countries) were selected and analysed, and to support the analysis, a systematic review of current published studies was performed. The results show that DBMN already exists in almost all developing countries and that the DBMN ratio (i.e., overweight/underweight) has increased as income per capita has increased. DBMN may manifest within the community, household, or individual. In addition to common factors, poor nutrition in early childhood is suggested as another important driving factor behind the rising obesity rate in most developing countries. A life-course approach has been proposed to prevent undernutrition and overnutrition and should be integrated into the development of health systems to control double burden in developing countries.

Impact of Glycemic Control on Healthcare Resource Utilization and Costs of Type 2 Diabetes: Current and Future Pharmacologic Approaches to Improving Outcomes

PubMed Central

Banerji, Mary Ann; Dunn, Jeffrey D.

2013-01-01

Background The incidence and prevalence of type 2 diabetes continue to grow in the United States and worldwide, along with the growing prevalence of obesity. Patients with type 2 diabetes are at greater risk for comorbid cardiovascular (CV) disease (CVD), which dramatically affects overall healthcare costs. Objectives To review the impact of glycemic control and medication adherence on morbidity, mortality, and healthcare costs of patients with type 2 diabetes, and to highlight the need for new drug therapies to improve outcomes in this patient population. Methods This comprehensive literature search was conducted for the period between 2000 and 2013, using MEDLINE, to identify published articles that report the associations between glycemic control, medication adherence, CV morbidity and mortality, and healthcare utilization and costs. Search terms included “type 2 diabetes,” “adherence,” “compliance,” “nonadherence,” “drug therapy,” “resource use,” “cost,” and “cost-effectiveness.” Discussion Despite improvements in the management of CV risk factors in patients with type 2 diabetes, outcomes remain poor. The costs associated with the management of type 2 diabetes are increasing dramatically as the prevalence of the disease increases. Medication adherence to long-term drug therapy remains poor in patients with type 2 diabetes and contributes to poor glycemic control in this patient population, increased healthcare resource utilization and increased costs, as well as increased rates of comorbid CVD and mortality. Furthermore, poor adherence to established evidence-based guidelines for type 2 diabetes, including underdiagnosis and undertreatment, contributes to poor outcomes. New approaches to the treatment of patients with type 2 diabetes currently in development have the potential to improve medication adherence and consequently glycemic control, which in turn will help to reduce associated costs and healthcare utilization. Conclusions As the prevalence of type 2 diabetes and its associated comorbidities grows, healthcare costs will continue to increase, indicating a need for better approaches to achieve glycemic control and manage comorbid conditions. Drug therapies are needed that enhance patient adherence and persistence levels far above levels reported with currently available drugs. Improvements in adherence to treatment guidelines and greater rates of lifestyle modifications also are needed. A serious unmet need exists for greatly improved patient outcomes, more effective and more tolerable drugs, as well as marked improvements in adherence to treatment guidelines and drug therapy to positively impact healthcare costs and resource use. PMID:24991370

Decomposing the gap in missed opportunities for vaccination between poor and non-poor in sub-Saharan Africa: A Multicountry Analyses.

PubMed

Ndwandwe, Duduzile; Uthman, Olalekan A; Adamu, Abdu A; Sambala, Evanson Z; Wiyeh, Alison B; Olukade, Tawa; Bishwajit, Ghose; Yaya, Sanni; Okwo-Bele, Jean-Marie; Wiysonge, Charles S

2018-04-24

Understanding the gaps in missed opportunities for vaccination (MOV) in sub-Saharan Africa would inform interventions for improving immunisation coverage to achieving universal childhood immunisation. We aimed to conduct a multicountry analyses to decompose the gap in MOV between poor and non-poor in SSA. We used cross-sectional data from 35 Demographic and Health Surveys in SSA conducted between 2007 and 2016. Descriptive statistics used to understand the gap in MOV between the urban poor and non-poor, and across the selected covariates. Out of the 35 countries included in this analysis, 19 countries showed pro-poor inequality, 5 showed pro-non-poor inequality and remaining 11 countries showed no statistically significant inequality. Among the countries with statistically significant pro-illiterate inequality, the risk difference ranged from 4.2% in DR Congo to 20.1% in Kenya. Important factors responsible for the inequality varied across countries. In Madagascar, the largest contributors to inequality in MOV were media access, number of under-five children, and maternal education. However, in Liberia media access narrowed inequality in MOV between poor and non-poor households. The findings indicate that in most SSA countries, children belonging to poor households are most likely to have MOV and that socio-economic inequality in is determined not only by health system functions, but also by factors beyond the scope of health authorities and care delivery system. The findings suggest the need for addressing social determinants of health.

Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein.

PubMed

Tan, Jintong; Kan, Juan; Qiu, Gang; Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

2015-01-01

Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1-4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis.

Self-assessment and goal-setting is associated with an improvement in interviewing skills.

PubMed

Hanley, Kathleen; Zabar, Sondra; Charap, Joseph; Nicholson, Joseph; Disney, Lindsey; Kalet, Adina; Gillespie, Colleen

2014-01-01

Purpose Describe the relationship between medical students' self-assessment and goal-setting (SAGS) skills and development of interviewing skills during the first-year doctoring course. Method 157 first-year medical students completed three two-case standardized patient (SP) interviews. After each of the first two, students viewed videotapes of their interview, completed a SAGS worksheet, and reviewed a selected tape segment in a seminar. SAGS was categorized into good and poor quality and interviewing skills were rated by trained raters. Results SAGS improved over time (37% good week 1 vs. 61% good week 10). Baseline SAGS and interviewing skills were not associated. Initial SAGS quality was associated with change in interviewing skills - those with poor-quality SAGS demonstrated a decrease and those with good-quality SAGS demonstrated an increase in scores by 17 weeks (ANOVA F=4.16, p=0.024). For students whose SAGS skills were good at both week 1 and 10, interviewing skills declined in weeks 1-10 and then increased significantly at week 17. For those whose SAGS remained 'poor' in weeks 1-10, interviewing skills declined in weeks 10-17. Conclusions In general, the quality of students' SAGS improved over time. Poor baseline SAGS skills and failure to improve were associated with a decrease in interviewing skills at 17 weeks. For students with better SAGS, interviewing skills increased at week 17. Improvement in SAGS skills was not associated with improved interviewing skills. Understanding structured self-assessment skills helps identify student characteristics that influence progressive mastery of communication skills and therefore may inform curriculum and remediation tailoring.

Decision-making deficits in normal elderly persons associated with executive personality disturbances.

PubMed

Nguyen, Christopher M; Barrash, Joseph; Koenigs, Anna L; Bechara, Antoine; Tranel, Daniel; Denburg, Natalie L

2013-11-01

The problems that some community-dwelling elderly persons develop in real-world decision-making may have disastrous consequences for their health and financial well-being. Investigations across the adult life span have identified personality as an important individual differences variable that is related to decision-making ability. The aim of this study was to investigate the relationship between personality characteristics, as rated by an informant, and complex decision-making performance among elderly persons. It was hypothesized that deficits in decision-making would be associated with personality characteristics reflecting weak executive functioning (Lack of Planning, Poor Judgment, Lack of Persistence, Perseveration, Lack of Initiative, Impulsivity, and Indecisiveness). Fifty-eight elderly persons participated. Their health and cognitive status were deemed intact via comprehensive neuropsychological evaluation. The Iowa Scales of Personality, completed by an informant, was used to assess personality characteristics, and the Iowa Gambling Task, completed by the participant, was used to assess complex decision-making abilities. Longstanding disturbances in executive personality characteristics were found to be associated with poor decision-making, and these disturbances remained predictive of poor decision-making even after taking into consideration demographic, neuropsychological, and mood factors. Acquired personality disturbances did not add significantly to prediction after longstanding disturbances were taken into account. Disturbances in other dimensions of personality were not significantly associated with poor decision-making. Our study suggests that attentiveness to the personality correlates of difficulties with aspects of executive functioning over the adult years could enhance the ability to identify older individuals at risk for problems with real-world decision-making.

Magnocellular-dorsal pathway and sub-lexical route in developmental dyslexia

PubMed Central

Gori, Simone; Cecchini, Paolo; Bigoni, Anna; Molteni, Massimo; Facoetti, Andrea

2014-01-01

Although developmental dyslexia (DD) is frequently associate with a phonological deficit, the underlying neurobiological cause remains undetermined. Recently, a new model, called “temporal sampling framework” (TSF), provided an innovative prospect in the DD study. TSF suggests that deficits in syllabic perception at a specific temporal frequencies are the critical basis for the poor reading performance in DD. This approach was presented as a possible neurobiological substrate of the phonological deficit of DD but the TSF can also easily be applied to the visual modality deficits. The deficit in the magnocellular-dorsal (M-D) pathway - often found in individuals with DD - fits well with a temporal oscillatory deficit specifically related to this visual pathway. This study investigated the visual M-D and parvocellular-ventral (P-V) pathways in dyslexic and in chronological age and IQ-matched normally reading children by measuring temporal (frequency doubling illusion) and static stimuli sensitivity, respectively. A specific deficit in M-D temporal oscillation was found. Importantly, the M-D deficit was selectively shown in poor phonological decoders. M-D deficit appears to be frequent because 75% of poor pseudo-word readers were at least 1 SD below the mean of the controls. Finally, a replication study by using a new group of poor phonological decoders and reading level controls suggested a crucial role of M-D deficit in DD. These results showed that a M-D deficit might impair the sub-lexical mechanisms that are critical for reading development. The possible link between these findings and TSF is discussed. PMID:25009484

Decision-Making Deficits in Normal Elderly Persons Associated with Executive Personality Disturbances

PubMed Central

Nguyen, Christopher M.; Barrash, Joseph; Koenigs, Anna L.; Bechara, Antoine; Tranel, Daniel; Denburg, Natalie L.

2014-01-01

Background The problems that some community-dwelling elderly develop in real-world decision-making may have disastrous consequences for their health and financial well-being. Investigations across the adult life span have identified personality as an important individual differences variable that is related to decision-making ability. The aim of this study was to investigate the relationship between personality characteristics, as rated by an informant, and complex decision-making performance among elders. It was hypothesized that deficits in decision-making would be associated with personality characteristics reflecting weak executive functioning (Lack of Planning, Poor Judgment, Lack of Persistence, Perseveration, Lack of Initiative, Impulsivity, and Indecisiveness). Methods Fifty-eight elderly persons participated. Their health and cognitive status were deemed intact via comprehensive neuropsychological evaluation. The Iowa Scales of Personality, completed by an informant, was used to assess personality characteristics, and the Iowa Gambling Task, completed by the participant, was used to assess complex decision-making abilities. Results Longstanding disturbances in executive personality characteristics were found to be associated with poor decision-making, and these disturbances remained predictive of poor decision-making even after taking into consideration demographic, neuropsychological, and mood factors. Acquired personality disturbances did not add significantly to prediction after longstanding disturbances were taken into account. Disturbances in other dimensions of personality were not significantly associated with poor decision-making. Conclusions Our study suggests that attentiveness to the personality correlates of difficulties with aspects of executive functioning over the adult years could enhance the ability to identify older individuals at risk for problems with real-world decision-making. PMID:23906413

Self-assessment and goal-setting is associated with an improvement in interviewing skills.

PubMed

Hanley, Kathleen; Zabar, Sondra; Charap, Joseph; Nicholson, Joseph; Disney, Lindsey; Kalet, Adina; Gillespie, Colleen

2014-01-01

Describe the relationship between medical students' self-assessment and goal-setting (SAGS) skills and development of interviewing skills during the first-year doctoring course. 157 first-year medical students completed three two-case standardized patient (SP) interviews. After each of the first two, students viewed videotapes of their interview, completed a SAGS worksheet, and reviewed a selected tape segment in a seminar. SAGS was categorized into good and poor quality and interviewing skills were rated by trained raters. SAGS improved over time (37% good week 1 vs. 61% good week 10). Baseline SAGS and interviewing skills were not associated. Initial SAGS quality was associated with change in interviewing skills - those with poor-quality SAGS demonstrated a decrease and those with good-quality SAGS demonstrated an increase in scores by 17 weeks (ANOVA F=4.16, p=0.024). For students whose SAGS skills were good at both week 1 and 10, interviewing skills declined in weeks 1-10 and then increased significantly at week 17. For those whose SAGS remained 'poor' in weeks 1-10, interviewing skills declined in weeks 10-17. In general, the quality of students' SAGS improved over time. Poor baseline SAGS skills and failure to improve were associated with a decrease in interviewing skills at 17 weeks. For students with better SAGS, interviewing skills increased at week 17. Improvement in SAGS skills was not associated with improved interviewing skills. Understanding structured self-assessment skills helps identify student characteristics that influence progressive mastery of communication skills and therefore may inform curriculum and remediation tailoring.

Early-life conditions and older adult health in low- and middle-income countries: a review

PubMed Central

McEniry, M.

2012-01-01

Population aging and subsequent projected large increases in chronic conditions will be important health concerns in low- and middle-income countries. Although evidence is accumulating, little is known regarding the impact of poor early-life conditions on older adult (50 years and older) health in these settings. A systematic review of 1141 empirical studies was conducted to identify population-based and community studies in low- and middle-income countries, which examined associations between early-life conditions and older adult health. The resulting review of 20 studies revealed strong associations between (1) in utero/early infancy exposures (independent of other early life and adult conditions) and adult heart disease and diabetes; (2) poor nutrition during childhood and difficulties in adult cognition and diabetes; (3) specific childhood illnesses such as rheumatic fever and malaria and adult heart disease and mortality; (4) poor childhood health and adult functionality/disability and chronic diseases; (5) poor childhood socioeconomic status (SES) and adult mortality, functionality/disability and cognition; and (6) parental survival during childhood and adult functionality/disability and cognition. In several instances, associations remained strong even after controlling for adult SES and lifestyle. Although exact mechanisms cannot be identified, these studies reinforce to some extent the importance of early-life environment on health at older ages. Given the paucity of cohort data from the developing world to examine hypotheses of early-life conditions and older adult health, population-based studies are relevant in providing a broad perspective on the origins of adult health. PMID:23316272

Using targeted vouchers and health equity funds to improve access to skilled birth attendants for poor women: a case study in three rural health districts in Cambodia.

PubMed

Ir, Por; Horemans, Dirk; Souk, Narin; Van Damme, Wim

2010-01-07

In many developing countries, the maternal mortality ratio remains high with huge poor-rich inequalities. Programmes aimed at improving maternal health and preventing maternal mortality often fail to reach poor women. Vouchers in health and Health Equity Funds (HEFs) constitute a financial mechanism to improve access to priority health services for the poor. We assess their effectiveness in improving access to skilled birth attendants for poor women in three rural health districts in Cambodia and draw lessons for further improvement and scaling-up. Data on utilisation of voucher and HEF schemes and on deliveries in public health facilities between 2006 and 2008 were extracted from the available database, reports and the routine health information system. Qualitative data were collected through focus group discussions and key informant interviews. We examined the trend of facility deliveries between 2006 and 2008 in the three health districts and compared this with the situation in other rural districts without voucher and HEF schemes. An operational analysis of the voucher scheme was carried out to assess its effectiveness at different stages of operation. Facility deliveries increased sharply from 16.3% of the expected number of births in 2006 to 44.9% in 2008 after the introduction of voucher and HEF schemes, not only for voucher and HEF beneficiaries, but also for self-paid deliveries. The increase was much more substantial than in comparable districts lacking voucher and HEF schemes. In 2008, voucher and HEF beneficiaries accounted for 40.6% of the expected number of births among the poor. We also outline several limitations of the voucher scheme. Vouchers plus HEFs, if carefully designed and implemented, have a strong potential for reducing financial barriers and hence improving access to skilled birth attendants for poor women. To achieve their full potential, vouchers and HEFs require other interventions to ensure the supply of sufficient quality maternity services and to address other non-financial barriers to demand. If these conditions are met, voucher and HEF schemes can be further scaled up under close monitoring and evaluation.

Where Do the Poorest Go to Seek Outpatient Care in Bangladesh: Hospitals Run by Government or Microfinance Institutions?

PubMed Central

Tseng, Yu-hwei; Khan, Mujibul Alam

2015-01-01

Introduction Health programs implemented by microfinance institutions (MFIs) aim to benefit the poor, but whether these services reach the poorest remains uncertain. This study intended to investigate the socioeconomic distribution of patients in hospitals operated by microfinance institutions (i.e. MFI hospitals) in Bangladesh and compare the differences with public hospitals to determine if the programs were consistent with their pro-poor mandate. Methods In this cross-sectional study, we used the convenience sampling method to conduct an interviewer-assisted questionnaire survey among 347 female outpatients, with 170 in public hospitals and 177 in MFI hospitals. Independent variables were patient characteristics categorized into predisposing factors (age, education, marital status, family size), enabling factors (microcredit membership, household income) and need factors (self-rated health, perceived needs for care). We employed Generalized Estimating Equations (GEE) to evaluate how these factors contributed to MFI hospital use. Results Use of MFI hospitals was associated with microcredit membership over 5 years (OR=2.9, p<.01), moderately poor household (OR=4.09, p<.001), non-poor household (OR=7.34, p<.01) and need for preventive care (OR=3.4, p<.01), compared with public hospitals. Combining membership and income, we found microcredit members had a higher tendency towards utilization but membership effect pertained to the non- and moderately-poor. Compared with the group who were non-members and the poorest, microcredit members who were non-poor had the highest likelihood (OR=7.46, p<.001) to visit MFI hospitals, followed by members with moderate income (OR=6.91, p<.001) and then non-members in non-poor households (OR=4.48, p<.01). Those who were members but the poorest had a negative association (OR=0.42), though not significant. Despite a higher utilization of preventive services in MFI hospitals, expenditure there was significantly higher. Conclusion Inequity was more pronounced in MFI hospitals than public ones. MFI hospitals appeared to miss their target population. We suggest that MFIs reorganize health programs toward primary health care to make care equitable and universally accessible. This study holds practical implications for governments, development agencies and microfinance practitioners working at the grassroots level. PMID:25807500

Where do the poorest go to seek outpatient care in Bangladesh: hospitals run by government or microfinance institutions?

PubMed

Tseng, Yu-hwei; Khan, Mujibul Alam

2015-01-01

Health programs implemented by microfinance institutions (MFIs) aim to benefit the poor, but whether these services reach the poorest remains uncertain. This study intended to investigate the socioeconomic distribution of patients in hospitals operated by microfinance institutions (i.e. MFI hospitals) in Bangladesh and compare the differences with public hospitals to determine if the programs were consistent with their pro-poor mandate. In this cross-sectional study, we used the convenience sampling method to conduct an interviewer-assisted questionnaire survey among 347 female outpatients, with 170 in public hospitals and 177 in MFI hospitals. Independent variables were patient characteristics categorized into predisposing factors (age, education, marital status, family size), enabling factors (microcredit membership, household income) and need factors (self-rated health, perceived needs for care). We employed Generalized Estimating Equations (GEE) to evaluate how these factors contributed to MFI hospital use. Use of MFI hospitals was associated with microcredit membership over 5 years (OR=2.9, p<.01), moderately poor household (OR=4.09, p<.001), non-poor household (OR=7.34, p<.01) and need for preventive care (OR=3.4, p<.01), compared with public hospitals. Combining membership and income, we found microcredit members had a higher tendency towards utilization but membership effect pertained to the non- and moderately-poor. Compared with the group who were non-members and the poorest, microcredit members who were non-poor had the highest likelihood (OR=7.46, p<.001) to visit MFI hospitals, followed by members with moderate income (OR=6.91, p<.001) and then non-members in non-poor households (OR=4.48, p<.01). Those who were members but the poorest had a negative association (OR=0.42), though not significant. Despite a higher utilization of preventive services in MFI hospitals, expenditure there was significantly higher. Inequity was more pronounced in MFI hospitals than public ones. MFI hospitals appeared to miss their target population. We suggest that MFIs reorganize health programs toward primary health care to make care equitable and universally accessible. This study holds practical implications for governments, development agencies and microfinance practitioners working at the grassroots level.

Using targeted vouchers and health equity funds to improve access to skilled birth attendants for poor women: a case study in three rural health districts in Cambodia

PubMed Central

2010-01-01

Background In many developing countries, the maternal mortality ratio remains high with huge poor-rich inequalities. Programmes aimed at improving maternal health and preventing maternal mortality often fail to reach poor women. Vouchers in health and Health Equity Funds (HEFs) constitute a financial mechanism to improve access to priority health services for the poor. We assess their effectiveness in improving access to skilled birth attendants for poor women in three rural health districts in Cambodia and draw lessons for further improvement and scaling-up. Methods Data on utilisation of voucher and HEF schemes and on deliveries in public health facilities between 2006 and 2008 were extracted from the available database, reports and the routine health information system. Qualitative data were collected through focus group discussions and key informant interviews. We examined the trend of facility deliveries between 2006 and 2008 in the three health districts and compared this with the situation in other rural districts without voucher and HEF schemes. An operational analysis of the voucher scheme was carried out to assess its effectiveness at different stages of operation. Results Facility deliveries increased sharply from 16.3% of the expected number of births in 2006 to 44.9% in 2008 after the introduction of voucher and HEF schemes, not only for voucher and HEF beneficiaries, but also for self-paid deliveries. The increase was much more substantial than in comparable districts lacking voucher and HEF schemes. In 2008, voucher and HEF beneficiaries accounted for 40.6% of the expected number of births among the poor. We also outline several limitations of the voucher scheme. Conclusions Vouchers plus HEFs, if carefully designed and implemented, have a strong potential for reducing financial barriers and hence improving access to skilled birth attendants for poor women. To achieve their full potential, vouchers and HEFs require other interventions to ensure the supply of sufficient quality maternity services and to address other non-financial barriers to demand. If these conditions are met, voucher and HEF schemes can be further scaled up under close monitoring and evaluation. PMID:20059767

Prevent and cure disuse bone loss

NASA Technical Reports Server (NTRS)

Jee, Webster S. S.

1994-01-01

Anabolic agents like parathyroid hormone and postagladin E-like substances were studied in dogs and rats to determine their effectiveness in the prevention and cure of bone loss due to immobilization. It was determined that postagladin E2 administration prevented immobilization while at the same time it added extra bone in a dose responsive manner. Although bone mass returns, poor trabecular architecture remains after normal ambulation recovery from immobilization. Disuse related bone loss and poor trabecular architecture were cured by post-immobilization postagladin E2 treatment.

Estrogen Receptors in Breast and Bone: from Virtue of Remodeling to Vileness of Metastasis

PubMed Central

Bado, Igor; Gugala, Zbigniew; Fuqua, Suzanne A. W.; Zhang, Xiang H.-F.

2017-01-01

Bone metastasis is a prominent cause of morbidity and mortality in cancer. High rates of bone colonization in breast cancer, especially in the subtype expressing estrogen receptors (ERs), suggests tissue-specific proclivities for metastatic tumor formation. The mechanisms behind this subtype-specific organ-tropism remains largely elusive. Interestingly, as the major driver of ER+ breast cancer, ERs also play important roles in bone development and homeostasis. Thus, any agents targeting ER will also inevitably affect the microenvironment, i.e., the osteoblasts and osteoclasts. Yet, how such microenvironmental effects are integrated with direct therapeutic responses of cancer cells remain poorly understood. Recent findings on ER mutations, especially their enrichment in bone metastasis, raised even more provocative questions on the role of ER in cancer-bone interaction. In this review, we evaluate the importance of estrogen receptors (ERs) in bone metastasis and discuss new avenues of investigation for bone metastasis treatment based on current knowledge. PMID:28368409

The role of the oncogenic Rab35 in cancer invasion, metastasis, and immune evasion, especially in leukemia.

PubMed

Villagomez, Fabian R; Medina-Contreras, Oscar; Cerna-Cortes, Jorge Francisco; Patino-Lopez, Genaro

2018-05-28

The study of cancer has allowed researchers to describe some biological characteristics that tumor cells acquire during their development, known as the "hallmarks of cancer" but more research is needed to expand our knowledge about cancer biology and to generate new strategies of treatment. The role that RabGTPases might play in some hallmarks of cancer represents interesting areas of study since these proteins are frequently altered in cancer. However, their participation is not well known. Recently, Rab35was recognized as an oncogenic RabGTPase and and because of its association with different cellular functions, distinctly important in immune cells, a possible role of Rab35 in leukemia can be suggested. Nevertheless, the involvement of Rab35 in cancer remains poorly understood and its possible specific role in leukemia remains unknown. In this review, we analyze general aspects of the participation of RabGTPases in cancer, and especially, the plausible role of Rab35 in leukemia.

Cohesin Can Remain Associated with Chromosomes during DNA Replication.

PubMed

Rhodes, James D P; Haarhuis, Judith H I; Grimm, Jonathan B; Rowland, Benjamin D; Lavis, Luke D; Nasmyth, Kim A

2017-09-19

To ensure disjunction to opposite poles during anaphase, sister chromatids must be held together following DNA replication. This is mediated by cohesin, which is thought to entrap sister DNAs inside a tripartite ring composed of its Smc and kleisin (Scc1) subunits. How such structures are created during S phase is poorly understood, in particular whether they are derived from complexes that had entrapped DNAs prior to replication. To address this, we used selective photobleaching to determine whether cohesin associated with chromatin in G1 persists in situ after replication. We developed a non-fluorescent HaloTag ligand to discriminate the fluorescence recovery signal from labeling of newly synthesized Halo-tagged Scc1 protein (pulse-chase or pcFRAP). In cells where cohesin turnover is inactivated by deletion of WAPL, Scc1 can remain associated with chromatin throughout S phase. These findings suggest that cohesion might be generated by cohesin that is already bound to un-replicated DNA. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Fine needle aspiration cytology of radiation-induced changes in nonneoplastic breast lesions. Possible pitfalls in cytodiagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterse, J.L.; Thunnissen, F.B.; van Heerde, P.

1989-03-01

The range of radiation-induced changes in fine needle aspiration (FNA) smears of the breast is described. In 41 of more than 800 patients who underwent breast-conserving treatment, a palpable breast lesion developed, and FNA was performed. In six cases, a recurrent carcinoma was present. In the remaining cases, three patterns of nonneoplastic lesions could be discerned: epithelial atypia (14 cases), fat necrosis (10 cases) and poorly cellular smears without epithelial atypia or fat necrosis (13 cases). It is important to be familiar with the patterns of radiation-induced epithelial atypia, since such atypia may lead to a misdiagnosis of recurrent carcinoma.more » These atypical cells may show impressive anisocytosis and anisonucleosis; however, the nuclear/cytoplasmic ratio remains normal and an admixture of bipolar cells is present. Cell dissociation and necrotic cell debris, as often seen in breast cancer smears, were never encountered in FNA smears from radiated nonneoplastic breasts.« less

Solutal Marangoni flows of miscible liquids drive transport without surface contamination

NASA Astrophysics Data System (ADS)

Kim, Hyoungsoo; Muller, Koen; Shardt, Orest; Afkhami, Shahriar; Stone, Howard A.

2017-11-01

Mixing and spreading of different liquids are omnipresent in nature, life and technology, such as oil pollution on the sea, estuaries, food processing, cosmetic and beverage industries, lab-on-a-chip devices, and polymer processing. However, the mixing and spreading mechanisms for miscible liquids remain poorly characterized. Here, we show that a fully soluble liquid drop deposited on a liquid surface remains as a static lens without immediately spreading and mixing, and simultaneously a Marangoni-driven convective flow is generated, which are counterintuitive results when two liquids have different surface tensions. To understand the dynamics, we develop a theoretical model to predict the finite spreading time and length scales, the Marangoni-driven convection flow speed, and the finite timescale to establish the quasi-steady state for the Marangoni flow. The fundamental understanding of this solutal Marangoni flow may enable driving bulk flows and constructing an effective drug delivery and surface cleaning approach without causing surface contamination by immiscible chemical species.

Identification and treatment of intra-abdominal fetal skeletal remains: A consequence of illicit and unsafe abortion.

PubMed

Rohilla, Minakshi; Kalpdev, Arun; Jain, Vanita

2015-06-01

The safety of abortions has always been a matter of concern for women's health. Unsafe abortion is one of the most neglected health-care problems in developing countries due to lack of awareness of the legal issues and limited access to authorised services often leading the women to poor quality of abortion in unsafe settings through untrained health personnel. Two rare cases of second trimester unsafe abortions are reported here in which women presented after several weeks with well-preserved remains of fetal skeleton in their abdomen along with complicated multiple visceral injuries. Both these second trimester abortions were performed by untrained village abortionists for sex selection and unwanted pregnancy in an unmarried adolescent girl. The management in the unmarried girl was further complicated due to undisclosed history of abortion. These reports of unsafe abortion highlight the need for clinicians to have a high index of suspicion for an undisclosed abortion when treating any morbid woman of reproductive age with a bizarre abdominal clinical picture.

The market for precedent: shifting visions of the role of clinical negligence claims and trials.

PubMed

Mulcahy, Linda

2014-01-01

This article considers the interface between the standard setting activity of the NHS Litigation Authority, and the courts and uses the clinical negligence action as a prism through which to examine it. It is suggested that despite its many disadvantages, the clinical negligence action remains an important safety valve when internal regulatory systems fail or are insufficiently transparent to gain full legitimacy. More specifically, it explores the ways in which attitudes about the usefulness of the data contained in claims against the NHS have changed in the aftermath of a number of high profile inquiries which have focused on issues of poor performance. The article concludes that while much greater use is now been made of the data contained in claims when setting standards, strategies for prompting judicial precedent as an alternative way of mobilising standard setting behaviour remain under developed. © The Author 2014. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevention and management of post-instability glenohumeral arthropathy

PubMed Central

Waterman, Brian R; Kilcoyne, Kelly G; Parada, Stephen A; Eichinger, Josef K

2017-01-01

Post-instability arthropathy may commonly develop in high-risk patients with a history of recurrent glenohumeral instability, both with and without surgical stabilization. Classically related to anterior shoulder instability, the incidence and rates of arthritic progression may vary widely. Radiographic arthritic changes may be present in up to two-thirds of patients after primary Bankart repair and 30% after Latarjet procedure, with increasing rates associated with recurrent dislocation history, prominent implant position, non-anatomic reconstruction, and/or lateralized bone graft placement. However, the presence radiographic arthrosis does not predict poor patient-reported function. After exhausting conservative measures, both joint-preserving and arthroplasty surgical options may be considered depending on a combination of patient-specific and anatomic factors. Arthroscopic procedures are optimally indicated for individuals with focal disease and may yield superior symptomatic relief when combined with treatment of combined shoulder pathology. For more advanced secondary arthropathy, total shoulder arthroplasty remains the most reliable option, although the clinical outcomes, wear characteristics, and implant survivorship remains a concern among active, young patients. PMID:28361016

[AA amyloidosis].

PubMed

Stojanovic, Katia Stankovic; Georgin-Lavialle, Sophie; Grateau, Gilles

2017-06-01

AA amyloidosis remains one of the three main types of systemic amyloidosis with AL and ATTR. Its incidence has been however decreasing recently in Western countries. Chronic inflammatory diseases are currently the first cause of AA amyloidosis, including rheumatoid arthritis, spondyloarthritis and autoinflammatory diseases. Castleman's disease is a specific cause of AA amyloidosis that can be cured by surgery. A chronic inflammatory response is required to develop amyloidosis. Other genetic and environmental factors are also involved. The first clinical manifestation is a chronic glomerular nephropathy, which can be detected by urine examination and serum creatinine measure. Immunohistochemistry is mandatory to confirm the clinical diagnosis of AA amyloidosis and to avoid misdiagnosis. Long-term prognosis remains poor on chronic dialysis in case of clinical gut involvement. Current treatment is based on the control of the inflammatory response. Specific treatment aimed at inhibiting amyloid formation targeting serum amyloid P component and heparan sulphate are currently evaluated. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Shear thinning in soft particle suspensions

NASA Astrophysics Data System (ADS)

Voudouris, Panayiotis; van der Zanden, Berco; Florea, Daniel; Fahimi, Zahra; Wyss, Hans

2012-02-01

Suspensions of soft deformable particles are encountered in a wide range of food and biological materials. Examples are biological cells, micelles, vesicles or microgel particles. While the behavior of suspenions of hard spheres - the classical model system of colloid science - is reasonably well understood, a full understanding of these soft particle suspensions remains elusive. The relation between single particle properties and macroscopic mechanical behavior still remains poorly understood in these materials. Here we examine the surprising shear thinning behavior that is observed in soft particle suspensions as a function of particle softness. We use poly-N-isopropylacrylamide (p-NIPAM) microgel particles as a model system to study this effect in detail. These soft spheres show significant shear thinning even at very large Peclet numbers, where this would not be observed for hard particles. The degree of shear thinning is directly related to the single particle elastic properties, which we characterize by the recently developed Capillary Micromechanics technique. We present a simple model that qualitatively accounts for the observed behavior.

30 CFR 256.57 - Using a third-party guarantee instead of a bond.

Code of Federal Regulations, 2010 CFR

2010-07-01

... are beyond your guarantor's control and that do not affect your guarantor's likelihood of remaining in... either Moody's Investor Service or Standard and Poor's Corporation; (ii) Your guarantor's net worth...

The role of atherectomy in the treatment of lower extremity peripheral artery disease

PubMed Central

2012-01-01

Background The incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons. Method Typical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis. Conclusions This review summarizes the features and the current applications of new debulking devices. PMID:23173800

Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

PubMed

Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida T G; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

2015-08-01

Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. © 2015 The Authors.

Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection

PubMed Central

Inácio, Patricia; Zuzarte-Luís, Vanessa; Ruivo, Margarida TG; Falkard, Brie; Nagaraj, Nagarjuna; Rooijers, Koos; Mann, Matthias; Mair, Gunnar; Fidock, David A; Mota, Maria M

2015-01-01

Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s—the active form of the UPR mediator XBP1—and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection. PMID:26113366

Associative fear learning and perceptual discrimination: a perceptual pathway in the development of chronic pain.

PubMed

Zaman, Jonas; Vlaeyen, Johan W S; Van Oudenhove, Lukas; Wiech, Katja; Van Diest, Ilse

2015-04-01

Recent neuropsychological theories emphasize the influence of maladaptive learning and memory processes on pain perception. However, the precise relationship between these processes as well as the underlying mechanisms remain poorly understood; especially the role of perceptual discrimination and its modulation by associative fear learning has received little attention so far. Experimental work with exteroceptive stimuli consistently points to effects of fear learning on perceptual discrimination acuity. In addition, clinical observations have revealed that in individuals with chronic pain perceptual discrimination is impaired, and that tactile discrimination training reduces pain. Based on these findings, we present a theoretical model of which the central tenet is that associative fear learning contributes to the development of chronic pain through impaired interoceptive and proprioceptive discrimination acuity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-thermal plasma technologies: new tools for bio-decontamination.

PubMed

Moreau, M; Orange, N; Feuilloley, M G J

2008-01-01

Bacterial control and decontamination are crucial to industrial safety assessments. However, most recently developed materials are not compatible with standard heat sterilization treatments. Advanced oxidation processes, and particularly non-thermal plasmas, are emerging and promising technologies for sanitation because they are both efficient and cheap. The applications of non-thermal plasma to bacterial control remain poorly known for several reasons: this technique was not developed for biological applications and most of the literature is in the fields of physics and chemistry. Moreover, the diversity of the devices and complexity of the plasmas made any general evaluation of the potential of the technique difficult. Finally, no experimental equipment for non-thermal plasma sterilization is commercially available and reference articles for microbiologists are rare. The present review aims to give an overview of the principles of action and applications of plasma technologies in biodecontamination.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

PubMed

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

Evolution of Endovascular Therapy in Acute Stroke: Implications of Device Development

PubMed Central

Balasubramaian, Adithya; Mitchell, Peter; Dowling, Richard

2015-01-01

Intravenous thrombolysis is an effective treatment for acute ischaemic stroke. However, vascular recanalization rates remain poor especially in the setting of large artery occlusion. On the other hand, endovascular intra-arterial therapy addresses this issue with superior recanalization rates compared with intravenous thrombolysis. Although previous randomized controlled studies of intra-arterial therapy failed to demonstrate superiority, the failings may be attributed to a combination of inferior intra-arterial devices and suboptimal selection criteria. The recent results of several randomized controlled trials have demonstrated significantly improved outcomes, underpinning the advantage of newer intra-arterial devices and superior recanalization rates, leading to renewed interest in establishing intra-arterial therapy as the gold standard for acute ischaemic stroke. The aim of this review is to outline the history and development of different intra-arterial devices and future directions in research. PMID:26060800

A new definition of maternal depletion syndrome.

PubMed Central

Winkvist, A; Rasmussen, K M; Habicht, J P

1992-01-01

BACKGROUND. Although the term "maternal depletion syndrome" has been commonly used to explain poor maternal and infant health, whether such a syndrome actually exists remains unclear. This uncertainty may be due to the lack of a clear definition of the syndrome and the absence of theoretical frameworks that account for the many factors related to reproductive nutrition. METHODS. We propose a new definition of maternal depletion syndrome within a framework that accounts for potential confounding factors. RESULTS. Our conceptual framework distinguishes between childbearing pattern and inadequate diet as causes of poor maternal health; hence, our definition of maternal depletion syndrome has both biological and practical meaning. The new definition is based on overall change in maternal nutritional status over one reproductive cycle in relation to possible depletion and repletion phases and in relation to initial nutritional status. CONCLUSIONS. The empirical application of this approach should permit the testing of the existence of maternal depletion syndrome in the developing world, and the distinction between populations where family planning will alleviate maternal depletion and those in which an improved diet is also necessary. PMID:1566948

Limnology of Taylor Creek impoundment : with reference to other bodies in Upper St Johns River Basin, Florida

USGS Publications Warehouse

Goolsby, D.A.; McPherson, Benjamin F.

1978-01-01

Taylor Creek Impoundment, on the western part of the upper St. Johns basin, Fla., provides flood control and flow regulation. The 4,000-acre impoundment was first filled in 1969. The water was of relatively poor quality during the first three years of its existence, 1970-72. The impoundment is deep enough for thermal stratification, and a thermocline usually develops at 8 to 10 feet. During 1970-72 the hypolimnion remained anaerobic for more than six months. The poor water quality is attributed to the decomposition of flooded vegetation, of soil organic matter, and to heavy growths of phytoplankton and duckweed stimulated by an abundant supply of nutrients. Since 1972, the quality of the water has improved because of flushing of the impoundment and depletion of leachable nutrients and soil organic matter. The water is now similar in quality to that of nearby Wolf and Jane Green Creeks. Large releases of water may produce velocities great enough to resuspend bottom sediments several miles downstream where Taylor Creek flows into Lake Poinsett. (Woodard-USGS)

Current perspectives on the etiology and manifestation of the “silent” component of the Female Athlete Triad

PubMed Central

Mallinson, Rebecca J; De Souza, Mary Jane

2014-01-01

The Female Athlete Triad (Triad) represents a syndrome of three interrelated conditions that originate from chronically inadequate energy intake to compensate for energy expenditure; this environment results in insufficient stored energy to maintain physiological processes, a condition known as low energy availability. The physiological adaptations associated with low energy availability, in turn, contribute to menstrual cycle disturbances. The downstream effects of both low energy availability and suppressed estrogen concentrations synergistically impair bone health, leading to low bone mineral density, compromised bone structure and microarchitecture, and ultimately, a decrease in bone strength. Unlike the other components of the Triad, poor bone health often does not have overt symptoms, and therefore develops silently, unbeknownst to the athlete. Compromised bone health among female athletes increases the risk of fracture throughout the lifespan, highlighting the long-term health consequences of the Triad. The purpose of this review is to examine the current state of Triad research related to the third component of the Triad, ie, poor bone health, in an effort to summarize what we know, what we are learning, and what remains unknown. PMID:24833922

Restructuring opens new doors. Business ventures redirect deflected revenue.

PubMed

Moore, R F

1989-01-01

To fulfill its mission of caring for the sick and the poor while remaining competitive, St. Vincent's Medical Center, Jacksonville, FL, underwent corporate restructuring in 1983. Three existing entities--the medical center, a skilled nursing facility, and a fund-raising foundation--incorporated under St. Vincent dePaul Community Stewardship Services, Inc. One of the goals was to make optimal use of existing facilities and expertise while also creating channels to redirect deflected revenue to the corporate mission of service to the poor. Among its projects St. Vincent's established 12 ambulatory care facilities; offered use of its laboratory to physicians' offices, nursing homes, and other entities needing fast, high-quality service; developed a mobile magnetic resonance imaging service; created a nurse staffing business; and entered into services-oriented, price-competitive, for-profit operations. By assuming some of the broad-based responsibilities for planning, financing, marketing, and providing administrative and legal support, the parent company has freed the entities under it to concentrate on the jobs they do best: the delivery of healthcare products and services and the generation of referrals to the medical staff and, in turn, to the medical center.

Nurse managers' experiences in continuous quality improvement in resource-poor healthcare settings.

PubMed

Kakyo, Tracy Alexis; Xiao, Lily Dongxia

2017-06-01

Ensuring safe and quality care for patients in hospitals is an important part of a nurse manager's role. Continuous quality improvement has been identified as one approach that leads to the delivery of quality care services to patients and is widely used by nurse managers to improve patient care. Nurse managers' experiences in initiating continuous quality improvement activities in resource-poor healthcare settings remain largely unknown. Research evidence is highly demanded in these settings to address disease burden and evidence-based practice. This interpretive qualitative study was conducted to gain an understanding of nurse managers' Continuous Quality Improvement experiences in rural hospitals in Uganda. Nurse managers in rural healthcare settings used their role to prioritize quality improvement activities, monitor the Continuous Quality Improvement process, and utilize in-service education to support continuous quality improvement. The nurse managers in our sample encountered a number of barriers during the implementation of Continuous Quality Improvement, including: limited patient participation, lack of materials, and limited human resources. Efforts to address the challenges faced through good governance and leadership development require more attention. © 2017 John Wiley & Sons Australia, Ltd.

Predictive modeling and mapping of Malayan Sun Bear (Helarctos malayanus) distribution using maximum entropy.

PubMed

Nazeri, Mona; Jusoff, Kamaruzaman; Madani, Nima; Mahmud, Ahmad Rodzi; Bahman, Abdul Rani; Kumar, Lalit

2012-01-01

One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt) is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify the key factors shaping the potential distribution of the vulnerable Malayan Sun Bear (Helarctos malayanus) in one of the main remaining habitats in Peninsular Malaysia. MaxEnt results showed that even though Malaysian sun bear habitat is tied with tropical evergreen forests, it lives in a marginal threshold of bio-climatic variables. On the other hand, current protected area networks within Peninsular Malaysia do not cover most of the sun bears potential suitable habitats. Assuming that the predicted suitability map covers sun bears actual distribution, future climate change, forest degradation and illegal hunting could potentially severely affect the sun bear's population.

Heterogeneity of Clonal Expansion and Maturation-Linked Mutation Acquisition in Hematopoietic Progenitors in Human Acute Myeloid Leukemia

PubMed Central

Walter, Roland B.; Laszlo, George S.; Lionberger, Jack M.; Pollard, Jessica A.; Harrington, Kimberly H.; Gudgeon, Chelsea J.; Othus, Megan; Rafii, Shahin; Meshinchi, Soheil; Appelbaum, Frederick R.; Bernstein, Irwin D.

2014-01-01

Recent technological advances led to an appreciation of the genetic complexity of human acute myeloid leukemia (AML) but underlying progenitor cells remain poorly understood because their rarity precludes direct study. We developed a co-culture method integrating hypoxia, aryl hydrocarbon receptor inhibition, and micro-environmental support via human endothelial cells to isolate these cells. X-chromosome inactivation studies of the least mature precursors derived following prolonged culture of CD34+/CD33− cells revealed polyclonal growth in highly curable AMLs, suggesting mutations necessary for clonal expansion were acquired in more mature progenitors. Consistently, in core-binding factor (CBF) leukemias with known complementing mutations, immature precursors derived following prolonged culture of CD34+/CD33− cells harbored neither mutation or the CBF mutation alone, whereas more mature precursors often carried both mutations. These results were in contrast to those with leukemias with poor prognosis that showed clonal dominance in the least mature precursors. These data indicate heterogeneity among progenitors in human AML that may have prognostic and therapeutic implications. PMID:24721792

Predictive Modeling and Mapping of Malayan Sun Bear (Helarctos malayanus) Distribution Using Maximum Entropy

PubMed Central

Nazeri, Mona; Jusoff, Kamaruzaman; Madani, Nima; Mahmud, Ahmad Rodzi; Bahman, Abdul Rani; Kumar, Lalit

2012-01-01

One of the available tools for mapping the geographical distribution and potential suitable habitats is species distribution models. These techniques are very helpful for finding poorly known distributions of species in poorly sampled areas, such as the tropics. Maximum Entropy (MaxEnt) is a recently developed modeling method that can be successfully calibrated using a relatively small number of records. In this research, the MaxEnt model was applied to describe the distribution and identify the key factors shaping the potential distribution of the vulnerable Malayan Sun Bear (Helarctos malayanus) in one of the main remaining habitats in Peninsular Malaysia. MaxEnt results showed that even though Malaysian sun bear habitat is tied with tropical evergreen forests, it lives in a marginal threshold of bio-climatic variables. On the other hand, current protected area networks within Peninsular Malaysia do not cover most of the sun bears potential suitable habitats. Assuming that the predicted suitability map covers sun bears actual distribution, future climate change, forest degradation and illegal hunting could potentially severely affect the sun bear’s population. PMID:23110182

2015 Oman Heart Association guidelines for the management of hypertension : practical recommendations from the Oman Heart Association (OHA).

PubMed

El-Deeb, Mohammed H; Sulaiman, Kadhim J; Al-Riyami, Abdullah A; Mohsin, Nabil; Al-Mukhaini, Mohamed; Al-Lamki, Mohamed; Al-Busaidi, Noor; Al-Salmi, Issa; Al-Lawati, Jawad; Al-Rawahi, Najib; Al-Riyami, Mohamed B; Abdul-Rahman, Said; Al-Hinai, Said; Jaffer, Batool; Al-Wahaebi, Ahmed; Al-Khalili, Hanan; Al-Zadjali, Matllooba

2015-03-01

Hypertension (HTN) is a major independent risk factor for the development of stroke, coronary artery disease (CAD), peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD). HTN is a growing public health problem in Oman, almost certainly the most prevalent modifiable risk factor for cardiovascular disease (CVD). The risk of CVD in patients with HTN can be greatly reduced with lifestyle modifications and effective antihypertensive therapy. Randomized trials have shown that blood pressure (BP) lowering produces rapid reductions in CV risk. Several studies have shown that the majority of the hypertensive patients remain uncontrolled. It is well established that the observed poor control of the disease is not only related to poor adherence to medications, but also to limited awareness and adherence to evidence-based management of hypertension among physicians. Several guidelines for the management of patients with hypertension have been published. However, the aim of this document is to provide the busy physicians in Oman with more concise and direct approach towards implementing these guidelines into clinical practice.

Clinical characteristics and prognostic factors of prostate cancer with liver metastases.

PubMed

Wang, HaiTao; Li, BaoGuo; Zhang, PengYu; Yao, YanHong; Chang, JiWu

2014-01-01

Liver metastasis from prostate cancer is uncommon and remains poorly understood. We computer searched the clinical records of all our patients registered into a database to identify patients that presented or developed liver metastases. A total of 27 prostate cancer patients with ultrasound or CT/MR imaging evidence of liver metastases were included in our analysis. The liver metastasis rate from metastatic prostate cancer was 4.29%. Eight (29.63%) patients had previously untreated, hormone-naive prostate cancer (synchronous liver metastases at diagnosis of prostate cancer), whereas 19 (70.37%) patients had already been diagnosed as having hormone-refractory prostate cancer. In the hormone-naive group, the median overall survival after liver metastases diagnosis was 38 months and half of the patients were still alive at the latest follow-up, whereas only 6 months in the hormone-refractory group (p = 0.003). High concentration of serum neuron-specific enolase and previous chemotherapy were associated with a significantly poor overall survival after liver metastases in the hormone-refractory group using Kaplan–Meier curves and logrank tests for univariate analysis.

How Effective Have Thirty Years of Internationally Driven Conservation and Development Efforts Been in Madagascar?

PubMed Central

Wilmé, Lucienne; Mercier, Jean-Roger; Camara, Christian; Lowry, Porter P.

2016-01-01

Conservation and development are intricately linked. The international donor community has long provided aid to tropical countries in an effort to alleviate poverty and conserve biodiversity. While hundreds of millions of $ have been invested in over 500 environmental-based projects in Madagascar during the period covered by a series of National Environmental Action Plans (1993–2008) and the protected areas network has expanded threefold, deforestation remains unchecked and none of the eight Millennium Development Goals (MDGs) established for 2000–2015 were likely be met. Efforts to achieve sustainable development had failed to reduce poverty or deliver progress toward any of the MDGs. Cross-sectorial policy adjustments are needed that (i) enable and catalyze Madagascar’s capacities rather than deepening dependency on external actors such as the World Bank, the International Monetary Fund and donor countries, and that (ii) deliver improvements to the livelihoods and wellbeing of the country’s rural poor. PMID:27532499

A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.

PubMed

Vidaki, Marina; Drees, Frauke; Saxena, Tanvi; Lanslots, Erwin; Taliaferro, Matthew J; Tatarakis, Antonios; Burge, Christopher B; Wang, Eric T; Gertler, Frank B

2017-08-02

During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons. We find that translation of dyrk1a, a Down syndrome- and autism spectrum disorders-related gene, is dependent on Mena, both in steady-state conditions and upon BDNF stimulation. We identify hundreds of additional mRNAs that associate with the Mena complex, suggesting that it plays broader role(s) in post-transcriptional gene regulation. Our work establishes a dual role for Mena in neurons, providing a potential link between regulation of actin dynamics and local translation. Copyright © 2017 Elsevier Inc. All rights reserved.

Developmental Trajectories for Children With Dyslexia and Low IQ Poor Readers

PubMed Central

2016-01-01

Reading difficulties are found in children with both high and low IQ and it is now clear that both groups exhibit difficulties in phonological processing. Here, we apply the developmental trajectories approach, a new methodology developed for studying language and cognitive impairments in developmental disorders, to both poor reader groups. The trajectory methodology enables identification of atypical versus delayed development in datasets gathered using group matching designs. Regarding the cognitive predictors of reading, which here are phonological awareness, phonological short-term memory (PSTM) and rapid automatized naming (RAN), the method showed that trajectories for the two groups diverged markedly. Children with dyslexia showed atypical development in phonological awareness, while low IQ poor readers showed developmental delay. Low IQ poor readers showed atypical PSTM and RAN development, but children with dyslexia showed developmental delay. These divergent trajectories may have important ramifications for supporting each type of poor reader, although all poor readers showed weakness in all areas. Regarding auditory processing, the developmental trajectories were very similar for the two poor reader groups. However, children with dyslexia demonstrated developmental delay for auditory discrimination of Duration, while the low IQ children showed atypical development on this measure. The data show that, regardless of IQ, poor readers have developmental trajectories that differ from typically developing children. The trajectories approach enables differences in trajectory classification to be identified across poor reader group, as well as specifying the individual nature of these trajectories. PMID:27110928

"SINCE I MUST PLEASE THOSE BELOW": HUMAN SKELETAL REMAINS RESEARCH AND THE LAW.

PubMed

Holland, Thomas D

2015-01-01

The ethics of non-invasive scientific research on human skeletal remains are poorly articulated and lack a single, definitive analogue in western law. Laws governing invasive research on human fleshed remains, as well as bio-ethical principles established for research on living subjects, provide effective models for the establishment of ethical guidelines for non-invasive research on human skeletal remains. Specifically, non-invasive analysis of human remains is permissible provided that the analysis and collection of resulting data (1) are accomplished with respect for the dignity of the individual, (2) do not violate the last-known desire of the deceased, (3) do not adversely impact the right of the next of kin to perform a ceremonious and decent disposal of the remains, and (4) do not unduly or maliciously violate the privacy interests of the next of kin.

Fluid Overload is Associated with Late Poor Outcomes in Neonates Following Cardiac Surgery

PubMed Central

Wilder, Nicole S; Yu, Sunkyung; Donohue, Janet E; Goldberg, Caren S; Blatt, Neal B

2016-01-01

Objective Acute kidney injury (AKI) is a severe complication of cardiac surgery associated with increased morbidity and mortality, yet AKI classification for neonates remains challenging. We characterized patterns of post-operative fluid overload (FO) as a surrogate marker for AKI and as a risk factor of poor post-operative outcomes in neonates undergoing cardiac surgery. Design Retrospective cohort study. Setting Single, congenital heart center destination program. Patients 435 neonates undergoing cardiac surgery with cardiopulmonary bypass from January 2006 through December 2010. Interventions None Measurements and Main Results Demographics, diagnosis, and perioperative clinical variables were collected, including daily weights and serum creatinine (SCr) levels. A composite poor clinical outcome (death, need for renal replacement therapy (RRT), or extracorporeal life support (ECLS) within 30 post-operative days) was considered the primary outcome measure. Twenty-one neonates (5%) had a composite poor outcome with 7 (2%) requiring RRT, 8 (2%) requiring ECLS, and 14 (3%) dying between 3 and 30 days post-surgery. Neonates with a composite poor outcome had significantly higher maximum FO (>20%) and were slower to diurese. A receiver-operating characteristic curve determined that FO ≥ 16% and SCr ≥ 0.9 on post-operative day 3 were the optimal cutoffs for significant discrimination on the primary outcome (area under the curve = 0.71 and 0.76, respectively). In multivariable analysis, FO ≥ 16% (adjusted odds ratio [AOR] = 3.7) and SCr ≥ 0.9 (AOR = 6.6) on post-operative day 3 remained an independent risk factor for poor outcome. FO ≥ 16% was also significantly associated with cardiac arrest requiring cardiopulmonary resuscitation, prolonged intensive care unit stay, and chest re-exploration. Conclusions This study highlights the importance of monitoring fluid balance in the neonatal cardiac surgical population, and suggests that daily FO, a readily-available, non-invasive marker of renal function, may be a sensitive and specific predictor of adverse outcomes. PMID:27028790

Breast cancer statistics, 2011.

PubMed

DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

2011-01-01

In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population. Copyright © 2011 American Cancer Society, Inc.

Epigenetic Modifications of Major Depressive Disorder

PubMed Central

Saavedra, Kathleen; Molina-Márquez, Ana María; Saavedra, Nicolás; Zambrano, Tomás; Salazar, Luis A.

2016-01-01

Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders. PMID:27527165

Nutritional management and growth in children with chronic kidney disease.

PubMed

Rees, Lesley; Jones, Helen

2013-04-01

Despite continuing improvements in our understanding of the causes of poor growth in chronic kidney disease, many unanswered questions remain: why do some patients maintain a good appetite whereas others have profound anorexia at a similar level of renal function? Why do some, but not all, patients respond to increased nutritional intake? Is feed delivery by gastrostomy superior to oral and nasogastric routes? Do children who are no longer in the 'infancy' stage of growth benefit from enteral feeding? Do patients with protein energy wasting benefit from increased nutritional input? How do we prevent obesity, which is becoming so prevalent in the developed world? This review will address these issues.

The upper atmospheres of extrasolar planets

NASA Astrophysics Data System (ADS)

Lellouch, E.

2003-04-01

Over 100 extrasolar planets have been already detected, the vast majority of which by radial velocity measurements. While numerous models have been developed to describe their thermal structure, composition, spectrum, dynamics and evolution, the physical characterization of these objects remains remarkably poor, since in most cases only an estimate of the object's mass is available. Most observational efforts have so far been focused on close, short-period exoplanets ("hot Jupiters"), in particular on HD 209458B which appears to transit across its parent star and was confirmed to be as a genuine hydrogen-rich exoplanet . A highlight of these observations was the detection of sodium in its atmosphere (Charbonneau et al. 2002). Observational results and prospects will be briefly reviewed.

Evolutionary traps as keys to understanding behavioral maladaptation

USGS Publications Warehouse

Robertson, Bruce A.; Chalfoun, Anna

2016-01-01

Evolutionary traps are severe cases of behavioral maladaptation that occur when, due to human activity, the cues animals use to guide their behavior become uncoupled from their fitness consequences. The result is that animals can prefer the most dangerous resources or behaviors, even when better options are available. Traps are increasingly common and represent a significant wildlife conservation problem. Understanding of the more proximate sensory-cognitive mechanisms underpinning traps remains poor, which highlights the need for interdisciplinary and collaborative approaches to investigating traps. Key to advancing basic trap theory and its conservation applications will be the development of appropriate and tractable model systems to investigate the mechanisms that cause traps within species, and how mechanisms vary across species.

A challenging case of ocular melanoma.

PubMed

Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

2015-01-01

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Diagnosis and management of hemangiomas and vascular malformations of the head and neck.

PubMed

Buckmiller, L M; Richter, G T; Suen, J Y

2010-07-01

Vascular anomalies are congenital errors in vascular development. They frequently involve the head, neck, and oral cavity. Subdivided into vascular tumors (hemangiomas) and vascular malformations, vascular anomalies remain poorly understood. However, growing interest and recent advances in the diagnosis, management, and molecular characterization of these lesions are improving treatment strategies. The role of the multidisciplinary team cannot be overstated. This review provides both basic and up-to-date knowledge on the most common vascular anomalies encountered by physicians and practitioners. Because treatment options for vascular anomalies are widely variable and often debated, this report aims to provide a comprehensive approach to these lesions based upon current concepts and practical clinical experience.

Zebrafish models in neuropsychopharmacology and CNS drug discovery.

PubMed

Khan, Kanza M; Collier, Adam D; Meshalkina, Darya A; Kysil, Elana V; Khatsko, Sergey L; Kolesnikova, Tatyana; Morzherin, Yury Yu; Warnick, Jason E; Kalueff, Allan V; Echevarria, David J

2017-07-01

Despite the high prevalence of neuropsychiatric disorders, their aetiology and molecular mechanisms remain poorly understood. The zebrafish (Danio rerio) is increasingly utilized as a powerful animal model in neuropharmacology research and in vivo drug screening. Collectively, this makes zebrafish a useful tool for drug discovery and the identification of disordered molecular pathways. Here, we discuss zebrafish models of selected human neuropsychiatric disorders and drug-induced phenotypes. As well as covering a broad range of brain disorders (from anxiety and psychoses to neurodegeneration), we also summarize recent developments in zebrafish genetics and small molecule screening, which markedly enhance the disease modelling and the discovery of novel drug targets. © 2017 The British Pharmacological Society.

Fear of crime and its relationship to self-reported health and stress among men.

PubMed

Macassa, Gloria; Winersjö, Rocio; Wijk, Katarina; McGrath, Cormac; Ahmadi, Nader; Soares, Joaquim

2017-12-13

Fear of crime is a growing social and public health problem globally, including in developed countries such as Sweden. This study investigated the impact of fear of crime on self-reported health and stress among men living in Gävleborg County. The study used data collected from 2993 men through a cross sectional survey in the 2014 Health in Equal Terms survey. Descriptive and logistic regression analyses were carried out to study the relationship between fear of crime and self-reported health and stress. There was a statistically significant association between fear of crime and self-reported poor health and stress among men residing in Gävleborg County. In the bivariate analysis, men who reported fear of crime had odds of 1.98 (CI 1.47-2.66) and 2.23 (CI 1.45-3.41) respectively. Adjusting for demographic, social and economic variables in the multivariate analysis only reduced the odds ratio for self-reported poor health to 1.52 (CI 1.05-2.21) but not for self-reported stress with odds of 2.22 (1.27-3.86). Fear of crime among men was statistically significantly associated with self-reported poor health and stress in Gävleborg County. However, the statistically significant relationship remained even after accounting for demographic, social and economic factors, which warrants further research to better understand the role played by other variables.

Audit to assess the quality of communication between operators and technicians in a fixed prosthodontic laboratory: educational and training implications.

PubMed

Dickie, J; Shearer, A C; Ricketts, D N J

2014-02-01

This audit aimed to assess the quality of communication between dental students/qualified dentists and dental technicians, increase the percentage of satisfactorily completed laboratory prescriptions and reduce the number of errors that can result from poor communication. A subsidiary aim was to educate students and staff in this respect. An audit of laboratory prescription completion was conducted within Dundee Dental Hospital. Four hundred and eighteen prescriptions for indirect fixed restorations completed by dental undergraduates and qualified staff were audited over a three month period (first audit cycle). Educational reminders on laboratory prescriptions were then provided to undergraduates and qualified staff, a further three hundred and twenty-two prescriptions were audited (second audit cycle) and compared with the first cycle. Satisfactorily completed prescriptions increased from 28% to 43% following basic educational intervention. However, this percentage still signifies a poor level of completion and the need for improvement. Some aspects of the prescription were completed better than others, but overall the standard remained poor with a significant number failing to comply with guidelines set by the UK General Dental Council, the European Union's Medical Devices Directive and the British Society for Restorative Dentistry (BSRD). Further undergraduate and staff training on laboratory prescription writing will be necessary through staff training events and developments in the undergraduate curriculum. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Description of interventions is under-reported in physical therapy clinical trials.

PubMed

Hariohm, K; Jeyanthi, S; Kumar, J Saravan; Prakash, V

Amongst several barriers to the application of quality clinical evidence and clinical guidelines into routine daily practice, poor description of interventions reported in clinical trials has received less attention. Although some studies have investigated the completeness of descriptions of non-pharmacological interventions in randomized trials, studies that exclusively analyzed physical therapy interventions reported in published trials are scarce. To evaluate the quality of descriptions of interventions in both experimental and control groups in randomized controlled trials published in four core physical therapy journals. We included all randomized controlled trials published from the Physical Therapy Journal, Journal of Physiotherapy, Clinical Rehabilitation, and Archives of Physical Medicine and Rehabilitation between June 2012 and December 2013. Each randomized controlled trial (RCT) was analyzed and coded for description of interventions using the checklist developed by Schroter et al. Out of 100 RCTs selected, only 35 RCTs (35%) fully described the interventions in both the intervention and control groups. Control group interventions were poorly described in the remaining RCTs (65%). Interventions, especially in the control group, are poorly described in the clinical trials published in leading physical therapy journals. A complete description of the intervention in a published report is crucial for physical therapists to be able to use the intervention in clinical practice. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Mapping cortical haemodynamics during neonatal seizures using diffuse optical tomography: A case study

PubMed Central

Singh, Harsimrat; Cooper, Robert J.; Wai Lee, Chuen; Dempsey, Laura; Edwards, Andrea; Brigadoi, Sabrina; Airantzis, Dimitrios; Everdell, Nick; Michell, Andrew; Holder, David; Hebden, Jeremy C.; Austin, Topun

2014-01-01

Seizures in the newborn brain represent a major challenge to neonatal medicine. Neonatal seizures are poorly classified, under-diagnosed, difficult to treat and are associated with poor neurodevelopmental outcome. Video-EEG is the current gold-standard approach for seizure detection and monitoring. Interpreting neonatal EEG requires expertise and the impact of seizures on the developing brain remains poorly understood. In this case study we present the first ever images of the haemodynamic impact of seizures on the human infant brain, obtained using simultaneous diffuse optical tomography (DOT) and video-EEG with whole-scalp coverage. Seven discrete periods of ictal electrographic activity were observed during a 60 minute recording of an infant with hypoxic–ischaemic encephalopathy. The resulting DOT images show a remarkably consistent, high-amplitude, biphasic pattern of changes in cortical blood volume and oxygenation in response to each electrographic event. While there is spatial variation across the cortex, the dominant haemodynamic response to seizure activity consists of an initial increase in cortical blood volume prior to a large and extended decrease typically lasting several minutes. This case study demonstrates the wealth of physiologically and clinically relevant information that DOT–EEG techniques can yield. The consistency and scale of the haemodynamic responses observed here also suggest that DOT–EEG has the potential to provide improved detection of neonatal seizures. PMID:25161892

Integrating geographically isolated wetlands into land management decisions

EPA Science Inventory

Wetlands across the globe provide extensive ecosystem services. However, many wetlands – especially those surrounded by uplands, often referred to as geographically isolated wetlands (GIWs) – remain poorly protected. Protection and restoration of wetlands frequently r...

What Can Plasticity Contribute to Insect Responses to Climate Change?

PubMed

Sgrò, Carla M; Terblanche, John S; Hoffmann, Ary A

2016-01-01

Plastic responses figure prominently in discussions on insect adaptation to climate change. Here we review the different types of plastic responses and whether they contribute much to adaptation. Under climate change, plastic responses involving diapause are often critical for population persistence, but key diapause responses under dry and hot conditions remain poorly understood. Climate variability can impose large fitness costs on insects showing diapause and other life cycle responses, threatening population persistence. In response to stressful climatic conditions, insects also undergo ontogenetic changes including hardening and acclimation. Environmental conditions experienced across developmental stages or by prior generations can influence hardening and acclimation, although evidence for the latter remains weak. Costs and constraints influence patterns of plasticity across insect clades, but they are poorly understood within field contexts. Plastic responses and their evolution should be considered when predicting vulnerability to climate change-but meaningful empirical data lag behind theory.

Examining the Academic Achievement-Delinquency Relationship Among Southeast Asian Americans.

PubMed

Bui, Laura

2018-05-01

The extent to which poor academic achievement is strongly related to delinquency among Southeast Asian Americans (SEAA) remains unclear; reasons are methodological limitations and aggregated findings for Asian Americans, which mask evidence that SEAA have a higher prevalence of criminality and poor academic performance than other Asian American groups. The present study examines the academic achievement-delinquency relationship in a diverse group of 1,214 SEAA using data from the Children of Immigrants Longitudinal Study (CILS). Propensity score matching (PSM) was used to make causal inferences and assess whether poor academic achieving SEAA, after being matched with higher academic achieving SEAA, displayed a higher prevalence of delinquency. Findings showed that, even after matching, poor academic achieving SEAA were still more likely to exhibit delinquent behavior than those who performed academically better. Interventions targeting SEAA communities will need to focus more on improving academic achievement to directly prevent and decrease delinquent behavior.

Achieving the same for less: improving mood depletes blood glucose for people with poor (but not good) emotion control.

PubMed

Niven, Karen; Totterdell, Peter; Miles, Eleanor; Webb, Thomas L; Sheeran, Paschal

2013-01-01

Previous studies have found that acts of self-control like emotion regulation deplete blood glucose levels. The present experiment investigated the hypothesis that the extent to which people's blood glucose levels decline during emotion regulation attempts is influenced by whether they believe themselves to be good or poor at emotion control. We found that although good and poor emotion regulators were equally able to achieve positive and negative moods, the blood glucose of poor emotion regulators was reduced after performing an affect-improving task, whereas the blood glucose of good emotion regulators remained unchanged. As evidence suggests that glucose is a limited energy resource upon which self-control relies, the implication is that good emotion regulators are able to achieve the same positive mood with less cost to their self-regulatory resource. Thus, depletion may not be an inevitable consequence of engaging in emotion regulation.

A Culture in Transition: Poor Reading and Writing Ability among Children in South African Townships.

ERIC Educational Resources Information Center

Pretorius, E.; Naude, H.

2002-01-01

This study examined factors contributing to poor literacy and numeracy development among black South African children ages 5.5 to 7 years. Findings pointed to a conglomerate of factors, namely inadequate visual-motor integration, poor visual analysis and synthesis, poor fine motor development, and inadequate exposure to mediated reading and…

Social determinants that lead to poor knowledge about, and inappropriate precautionary practices towards, avian influenza among butchers in Kathmandu, Nepal

PubMed Central

2013-01-01

Background Avian influenza (AI) is a global public health threat. Understanding the knowledge that butchers have about it and the precautionary practices they take against it is crucial for designing future preparedness programs. This study aimed to identify the social determinants of knowledge and precautionary measures of AI among butchers in the Kathmandu district in Nepal. Methods The study was based on a cross-sectional study design using structured interview questionnaires and checklists to observe social determinants and the precautionary measures of 120 butchers aged 15 years and above from the Kathmandu district. Results The majority of the respondents were male (69.2%) and more than half (53.3%) were from the age group of 25–39 years (mean: 31.08, SD: ±9.82). Nearly two-thirds (61.3%) of the respondents had a ‘poor knowledge’, and the remaining had ‘some knowledge’, about AI. More than half (55.4%) of the respondents were in the category of displaying ‘poor practice’ towards AI and the remaining half were in the ‘satisfactory practice’ category. None of the respondents had ‘adequate knowledge’ or displayed ‘good practice’. The respondents in the >25 years of age group were less likely [OR 0.169; 95% CI (0.056-0.512)] compared to those in the <25 years age group to have a poor knowledge about AI; and the respondents with ‘primary education’ were more likely [OR 3.265; 95% CI (1.326-8.189)] to have a poor knowledge about AI as compared to those who had a secondary or above level of education. Respondents who did not know the correct definition of AI were more likely to follow poor practices [OR 4.265; 95% CI (1.193-15.242)]; and the respondents who did not know the risk groups associated with AI were also more likely to follow poor practices [OR 3.103; 95% CI (1.191-8.083)]. Conclusion This study points out the need to address butchers to improve their knowledge of, and more importantly their compliance with, the precautionary measures to prevent avian influenza. PMID:23849460

Elevated Fasting Blood Glucose Is Predictive of Poor Outcome in Non-Diabetic Stroke Patients: A Sub-Group Analysis of SMART.

PubMed

Yao, Ming; Ni, Jun; Zhou, Lixin; Peng, Bin; Zhu, Yicheng; Cui, Liying

2016-01-01

Although increasing evidence suggests that hyperglycemia following acute stroke adversely affects clinical outcome, whether the association between glycaemia and functional outcome varies between stroke patients with\\without pre-diagnosed diabetes remains controversial. We aimed to investigate the relationship between the fasting blood glucose (FBG) and the 6-month functional outcome in a subgroup of SMART cohort and further to assess whether this association varied based on the status of pre-diagnosed diabetes. Data of 2862 patients with acute ischemic stroke (629 with pre-diagnosed diabetics) enrolled from SMART cohort were analyzed. Functional outcome at 6-month post-stroke was measured by modified Rankin Scale (mRS) and categorized as favorable (mRS:0-2) or poor (mRS:3-5). Binary logistic regression model, adjusting for age, gender, educational level, history of hypertension and stroke, baseline NIHSS and treatment group, was used in the whole cohort to evaluate the association between admission FBG and functional outcome. Stratified logistic regression analyses were further performed based on the presence/absence of pre-diabetes history. In the whole cohort, multivariable logistical regression showed that poor functional outcome was associated with elevated FBG (OR1.21 (95%CI 1.07-1.37), p = 0.002), older age (OR1.64 (95% CI1.38-1.94), p<0.001), higher NIHSS (OR2.90 (95%CI 2.52-3.33), p<0.001) and hypertension (OR1.42 (95%CI 1.13-1.98), p = 0.04). Stratified logistical regression analysis showed that the association between FBG and functional outcome remained significant only in patients without pre-diagnosed diabetes (OR1.26 (95%CI 1.03-1.55), p = 0.023), but not in those with premorbid diagnosis of diabetes (p = 0.885). The present results demonstrate a significant association between elevated FBG after stroke and poor functional outcome in patients without pre-diagnosed diabetes, but not in diabetics. This finding confirms the importance of glycemic control during acute phase of ischemic stroke especially in patients without pre-diagnosed diabetes. Further investigation for developing optimal strategies to control blood glucose level in hyperglycemic setting is therefore of great importance. ClinicalTrials.gov NCT00664846.

Do client fees help or hurt?

PubMed

Barnett, B

1998-01-01

This article discusses the impact of client fees for family planning (FP) services on cost recovery and level of user services in developing countries. The UN Population Fund reports that developing country governments currently pay 75% of the costs of FP programs. Donors contribute 15%, and clients pay 10%. Current pressures are on FP services to broaden and improve their scope, while user demand is increasing. Program managers should consider the program's need for funds and the clients' willingness to pay. Clients are willing to pay about 1% of their income for contraception. A study of sterilization acceptance in Mexico finds that the average monthly case load declined by 10% after the 1st price increase from $43 to $55 and declined by 58% after the 2nd price increase to $60. Fewer low-income clients requested sterilization. A CEMOPLAF study in Ecuador finds that in three price increase situations the number of clients seeking services declined, but the economic mix of clients remained about the same. The decline was 20% in the group with a 20% price increase and 26% in the 40% increase group. In setting fees, the first need is to determine unit costs. The Futures Group International recommends considering political, regulatory, and institutional constraints for charging fees; priorities for revenue use; protection for poor clients; and monitoring of money collection and expenditure. Management Sciences for Health emphasizes consideration of the reasons for collection of fees, client affordability, and client perception of quality issues. Sliding scales can be used to protect poor clients. Charging fees for laboratory services can subsidize poor clients. A Bangladesh program operated a restaurant and catering service in order to subsidize FP services. Colombia's PROFAMILIA sells medical and surgical services and a social marketing program in order to expand clinics.

Posttraumatic Stress Disorder Is Associated With Worse Endothelial Function Among Veterans.

PubMed

Grenon, S Marlene; Owens, Christopher D; Alley, Hugh; Perez, Sandra; Whooley, Mary A; Neylan, Thomas C; Aschbacher, Kirstin; Gasper, Warren J; Hilton, Joan F; Cohen, Beth E

2016-03-23

Current research in behavioral cardiology reveals a significant association between posttraumatic stress disorder (PTSD) and increased risk for cardiovascular disease and mortality; however, the underlying mechanisms remain poorly understood. We hypothesized that patients with PTSD would exhibit endothelial dysfunction, a potential mechanism involved in the development and progression of cardiovascular disease. A total of 214 outpatients treated at the San Francisco Veterans Affairs Medical Center underwent tests of endothelial function and evaluation for PTSD. Flow-mediated vasodilation of the brachial artery was performed to assess endothelial function, and current PTSD status was defined by the PTSD Checklist, based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition), with a score ≥40. Multivariable linear regression models were used to estimate the association between PTSD status and endothelial function. Patients with PTSD (n=67) were more likely to be male (99% versus 91%, P=0.04) and to have depression (58% versus 8%, P<0.0001) and were less likely to be on an angiotensin-converting enzyme inhibitor (17% versus 36%, P=0.007) or β-blocker treatment (25% versus 41%, P=0.03). Univariate analysis demonstrated that patients with PTSD had significantly lower flow-mediated vasodilation (5.8±3.4% versus 7.5±3.7%; P=0.003); furthermore, lower flow-mediated vasodilation was associated with increasing age (P=0.008), decreasing estimated glomerular filtration rate (P=0.003), hypertension (P=0.002), aspirin (P=0.03), and β-blocker treatments (P=0.01). In multivariable analysis, PTSD remained independently associated with lower flow-mediated vasodilation (P=0.0005). After adjusting for demographic, comorbidity, and treatment characteristics, PTSD remained associated with worse endothelial function in an outpatient population. Whether poor endothelial function contributes to the higher risk of cardiovascular disease in patients with PTSD deserves further study. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

MYCN Promotes the Expansion of Phox2B-Positive Neuronal Progenitors to Drive Neuroblastoma Development

PubMed Central

Alam, Goleeta; Cui, Hongjuan; Shi, Huilin; Yang, Liqun; Ding, Jane; Mao, Ling; Maltese, William A.; Ding, Han-Fei

2009-01-01

Amplification of the oncogene MYCN is a tumorigenic event in the development of a subset of neuroblastomas that commonly consist of undifferentiated or poorly differentiated neuroblasts with unfavorable clinical outcome. The cellular origin of these neuroblasts is unknown. Additionally, the cellular functions and target cells of MYCN in neuroblastoma development remain undefined. Here we examine the cell types that drive neuroblastoma development in TH-MYCN transgenic mice, an animal model of the human disease. Neuroblastoma development in these mice begins with hyperplastic lesions in early postnatal sympathetic ganglia. We show that both hyperplasia and primary tumors are composed predominantly of highly proliferative Phox2B+ neuronal progenitors. MYCN induces the expansion of these progenitors by both promoting their proliferation and preventing their differentiation. We further identify a minor population of undifferentiated nestin+ cells in both hyperplastic lesions and primary tumors that may serve as precursors of Phox2B+ neuronal progenitors. These findings establish the identity of neuroblasts that characterize the tumor phenotype and suggest a cellular pathway by which MYCN can promote neuroblastoma development. PMID:19608868

Designing Targeted Educational Voucher Schemes for the Poor in Developing Countries

ERIC Educational Resources Information Center

Shafiq, M. Najeeb

2010-01-01

A targeted educational voucher scheme (TEVS) is often proposed for the poor in developing countries. Essentially, TEVS involves issuing vouchers to poor households, thus enabling them to pay tuition and fees for their children's schooling at participating non-public schools. However, little is known about TEVS' design in developing countries. This…

Impact of lifestyle and technology developments on sleep

PubMed Central

Shochat, Tamar

2012-01-01

Although the physiological and psychological mechanisms involved in the development of sleep disorders remain similar throughout history, factors that potentiate these mechanisms are closely related to the “zeitgeist”, ie, the sociocultural, technological and lifestyle trends which characterize an era. Technological advancements have afforded modern society with 24-hour work operations, transmeridian travel and exposure to a myriad of electronic devices such as televisions, computers and cellular phones. Growing evidence suggests that these advancements take their toll on human functioning and health via their damaging effects on sleep quality, quantity and timing. Additional behavioral lifestyle factors associated with poor sleep include weight gain, insufficient physical exercise and consumption of substances such as caffeine, alcohol and nicotine. Some of these factors have been implicated as self-help aids used to combat daytime sleepiness and impaired daytime functioning. This review aims to highlight current lifestyle trends that have been shown in scientific investigations to be associated with sleep patterns, sleep duration and sleep quality. Current understanding of the underlying mechanisms of these associations will be presented, as well as some of the reported consequences. Available therapies used to treat some lifestyle related sleep disorders will be discussed. Perspectives will be provided for further investigation of lifestyle factors that are associated with poor sleep, including developing theoretical frameworks, identifying underlying mechanisms, and establishing appropriate therapies and public health interventions aimed to improve sleep behaviors in order to enhance functioning and health in modern society. PMID:23616726

Poverty, development, and women: why should we care?

PubMed

Thompson, Joyce E Beebe

2007-01-01

Healthy, prosperous nations require healthy women and newborns. Young girls and women in resource-poor nations suffer the greatest ill-health consequences from low status, denial of basic human rights, and poverty. Poverty and poor health result in poor economic development. The Millennium Development Goals call for immediate efforts to reduce poverty, improve health, especially of girls and women, and foster development in the world's poorest nations.

Leptospirosis in the Asia Pacific region

PubMed Central

2009-01-01

Background Leptospirosis is a worldwide zoonotic infection that has been recognized for decades, but the problem of the disease has not been fully addressed, particularly in resource-poor, developing countries, where the major burden of the disease occurs. This paper presents an overview of the current situation of leptospirosis in the region. It describes the current trends in the epidemiology of leptospirosis, the existing surveillance systems, and presents the existing prevention and control programs in the Asia Pacific region. Methods Data on leptospirosis in each member country were sought from official national organizations, international public health organizations, online articles and the scientific literature. Papers were reviewed and relevant data were extracted. Results Leptospirosis is highly prevalent in the Asia Pacific region. Infections in developed countries arise mainly from occupational exposure, travel to endemic areas, recreational activities, or importation of domestic and wild animals, whereas outbreaks in developing countries are most frequently related to normal daily activities, over-crowding, poor sanitation and climatic conditions. Conclusion In the Asia Pacific region, predominantly in developing countries, leptospirosis is largely a water-borne disease. Unless interventions to minimize exposure are aggressively implemented, the current global climate change will further aggravate the extent of the disease problem. Although trends indicate successful control of leptospirosis in some areas, there is no clear evidence that the disease has decreased in the last decade. The efficiency of surveillance systems and data collection varies significantly among the countries and areas within the region, leading to incomplete information in some instances. Thus, an accurate reflection of the true burden of the disease remains unknown. PMID:19732423

Honey Bee Workers That Are Pollen Stressed as Larvae Become Poor Foragers and Waggle Dancers as Adults

PubMed Central

Scofield, Hailey N.; Mattila, Heather R.

2015-01-01

The negative effects on adult behavior of juvenile undernourishment are well documented in vertebrates, but relatively poorly understood in invertebrates. We examined the effects of larval nutritional stress on the foraging and recruitment behavior of an economically important model invertebrate, the honey bee (Apis mellifera). Pollen, which supplies essential nutrients to developing workers, can become limited in colonies because of seasonal dearths, loss of foraging habitat, or intensive management. However, the functional consequences of being reared by pollen-stressed nestmates remain unclear, despite growing concern that poor nutrition interacts with other stressors to exacerbate colony decline. We manipulated nurse bees’ access to pollen and then assessed differences in weight, longevity, foraging activity, and waggle-dance behavior of the workers that they reared (who were co-fostered as adults). Pollen stress during larval development had far-reaching physical and behavioral effects on adult workers. Workers reared in pollen-stressed colonies were lighter and shorter lived than nestmates reared with adequate access to pollen. Proportionally fewer stressed workers were observed foraging and those who did forage started foraging sooner, foraged for fewer days, and were more likely to die after only a single day of foraging. Pollen-stressed workers were also less likely to waggle dance than their unstressed counterparts and, if they danced, the information they conveyed about the location of food was less precise. These performance deficits may escalate if long-term pollen limitation prevents stressed foragers from providing sufficiently for developing workers. Furthermore, the effects of brief pollen shortages reported here mirror the effects of other environmental stressors that limit worker access to nutrients, suggesting the likelihood of their synergistic interaction. Honey bees often experience the level of stress that we created, thus our findings underscore the importance of adequate nutrition for supporting worker performance and their potential contribution to colony productivity and quality pollination services. PMID:25853902

Honey bee workers that are pollen stressed as larvae become poor foragers and waggle dancers as adults.

PubMed

Scofield, Hailey N; Mattila, Heather R

2015-01-01

The negative effects on adult behavior of juvenile undernourishment are well documented in vertebrates, but relatively poorly understood in invertebrates. We examined the effects of larval nutritional stress on the foraging and recruitment behavior of an economically important model invertebrate, the honey bee (Apis mellifera). Pollen, which supplies essential nutrients to developing workers, can become limited in colonies because of seasonal dearths, loss of foraging habitat, or intensive management. However, the functional consequences of being reared by pollen-stressed nestmates remain unclear, despite growing concern that poor nutrition interacts with other stressors to exacerbate colony decline. We manipulated nurse bees' access to pollen and then assessed differences in weight, longevity, foraging activity, and waggle-dance behavior of the workers that they reared (who were co-fostered as adults). Pollen stress during larval development had far-reaching physical and behavioral effects on adult workers. Workers reared in pollen-stressed colonies were lighter and shorter lived than nestmates reared with adequate access to pollen. Proportionally fewer stressed workers were observed foraging and those who did forage started foraging sooner, foraged for fewer days, and were more likely to die after only a single day of foraging. Pollen-stressed workers were also less likely to waggle dance than their unstressed counterparts and, if they danced, the information they conveyed about the location of food was less precise. These performance deficits may escalate if long-term pollen limitation prevents stressed foragers from providing sufficiently for developing workers. Furthermore, the effects of brief pollen shortages reported here mirror the effects of other environmental stressors that limit worker access to nutrients, suggesting the likelihood of their synergistic interaction. Honey bees often experience the level of stress that we created, thus our findings underscore the importance of adequate nutrition for supporting worker performance and their potential contribution to colony productivity and quality pollination services.

A translational study of resistance emergence using sequential direct-acting antiviral agents for hepatitis C using ultra-deep sequencing.

PubMed

Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki

2013-09-01

Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.

Understanding and Improving the Health of People Who Experience Incarceration: An Overview and Synthesis.

PubMed

Kinner, Stuart A; Young, Jesse T

2018-06-01

The world prison population is growing at a rate that exceeds the rate of population growth. This issue of Epidemiologic Reviews comprises articles in which researchers summarize what is known about some of the key health issues facing people in prison, particularly in relation to human immunodeficiency virus and other blood-borne viral infections. A key recurring theme is that addressing the health needs of people in prison is important to reducing health inequalities at the population level-that prisoner health is public health. The reviews also highlight some critical evidence gaps, notably the lack of evidence from low- and middle-income countries, and the limited number of longitudinal studies in which health behaviors, health outcomes, or health service experiences after release from prison are documented. Despite growing evidence of the poor health of detained adolescents, none of the included reviews considered this population. Further research on the health of young people who cycle through juvenile detention should be a priority. Despite a rapidly growing literature on the health of people who experience incarceration, some critical health issues remain poorly understood, and there has been insufficient attention devoted to co-occurring health conditions and the consequent need for coordinated care. Key populations in custodial settings remain understudied, limiting capacity to develop targeted, evidence-based responses to their health needs. The quality of many studies is suboptimal, and although rigorous, independent research in correctional settings can be challenging, it is not impossible and is critical to laying the groundwork for evidence-based reform.

Migration of scientists and the International Centre for Theoretical Physics -- a Personal and Professional Perspective

NASA Astrophysics Data System (ADS)

Sreenivasan, Katepalli R.

2011-03-01

Scientists migrate for a variety of reasons: political problems with their governments, lack of professional opportunities in their countries, the lure of better lives, financial security for them and their families, better education for their off-springs, and so forth. Migration usually occurs from poor and oppressed countries--the two categories are not one and the same--to the rich and the open. It has created, over time, a dilemma for the poor countries: in the midst of all their other problems, how to justify spending on higher education and research when that investment often results in the most enterprising of its citizens to leave their countries behind? (When migration has reversed direction occasionally, it is because of certain necessities of the scientists to be back in their countries or for opportunities that some individuals see for wielding greater scientific power.) The ideal of keeping the best scientists in their own countries, still ensuring that they remain scientifically productive and inspiring to the youth, is what provided the motivation for the creation of the International Centre for Theoretical Physics in Trieste, Italy, where I served as Director for some seven years. In this talk, I will present the story behind the formation of the Centre in 1964, explain its rationale, and analyze its evolution over time to accommodate the changing scene in world; I will discuss how some things have remained the same even as more of them have changed over time. Finally, I will remark on the broad needs of developing countries even though such needs are often very specific to a country.

Handheld echocardiography versus auscultation for detection of rheumatic heart disease.

PubMed

Godown, Justin; Lu, Jimmy C; Beaton, Andrea; Sable, Craig; Mirembe, Grace; Sanya, Richard; Aliku, Twalib; Yu, Sunkyung; Lwabi, Peter; Webb, Catherine L; Ensing, Gregory J

2015-04-01

Rheumatic heart disease (RHD) remains a major public health concern in developing countries, and routine screening has the potential to improve outcomes. Standard portable echocardiography (STAND) is far more sensitive than auscultation for the detection of RHD but remains cost-prohibitive in resource-limited settings. Handheld echocardiography (HAND) is a lower-cost alternative. The purpose of this study was to assess the incremental value of HAND over auscultation to identify RHD. RHD screening was completed for schoolchildren in Gulu, Uganda, by using STAND performed by experienced echocardiographers. Any child with mitral or aortic regurgitation or stenosis plus a randomly selected group of children with normal STAND findings underwent HAND and auscultation. STAND and HAND studies were interpreted by 6 experienced cardiologists using the 2012 World Heart Federation criteria. Sensitivity and specificity of HAND and auscultation for the detection of RHD and pathologic mitral or aortic regurgitation were calculated by using STAND as the gold standard. Of 4773 children who underwent screening with STAND, a subgroup of 1317 children underwent HAND and auscultation. Auscultation had uniformly poor sensitivity for the detection of RHD or valve disease. Sensitivity was significantly improved by using HAND compared with auscultation for the detection of definite RHD (97.8% vs 22.2%), borderline or definite RHD (78.4% vs 16.4%), and pathologic aortic insufficiency (81.8% vs 13.6%). Auscultation alone is a poor screening test for RHD. HAND significantly improves detection of RHD and may be a cost-effective screening strategy for RHD in resource-limited settings. Copyright © 2015 by the American Academy of Pediatrics.

Household exposure and animal-bite surveillance following human rabies detection in Southern Ghana.

PubMed

Afakye, Kofi; Kenu, Ernest; Nyarko, Kofi Mensah; Johnson, Sherry Ama Mawuko; Wongnaah, Florence; Bonsu, George Kwame

2016-01-01

Rabies remains a neglected tropical zoonotic disease with 100% case fatality rate and estimated 6,000 global mortality annually, and yet vaccine preventable. In Ghana, rabies outbreaks receive poor response. We investigated rabies in a 5-year old boy to find the source of infection, identify exposed persons for post-exposure prophylaxis and describe animal-bite surveillance in Manya-Krobo District of Ghana. We actively searched for cases and exposures by interviewing household members of the victim, schoolmates, and health professionals using WHO case definition, interview guide and checklist. We reviewed health and veterinary records and reports, and interviewed stakeholders. Descriptive data analyses were carried out and presented using tables and charts. Recorded responses were transcribed into thematic areas and analysed. Child had dog-bite at the wrist, and developed hyperactivity, hydrophobia and hyperventilation 2 months post bite. He was hospitalised and died from respiratory failure day 3 after admission. Thirty-three persons were exposed to rabies infectious material. Females were 66%, age-groups 5-15yrs and 30-59 yrs were 33.3% and 39.4% respectively. A third (11/33) were category II exposure by WHO classification and were recommended for post-exposure prophylaxis. Surveillance records showed ninety-two animal-bite cases were reported for past 12 months. Half were females, and 18-59yrs age-group was 43%. Surveillance data quality was poor. Rabies remains a public health burden inGhana with domestic dog as reservoir of the virus and females more vulnerable to secondary exposures. Health education on rabies should be intensified, and robust animal-bite surveillance system put in place.

Factors associated with numbers of remaining teeth among type 2 diabetes: a cross-sectional study.

PubMed

Huang, Jui-Chu; Peng, Yun-Shing; Fan, Jun-Yu; Jane, Sui-Whi; Tu, Liang-Tse; Chang, Chang-Cheng; Chen, Mei-Yen

2013-07-01

To explore the factors associated with the numbers of remaining teeth among type 2 diabetes community residents. Promoting oral health is an important nursing role for patients with diabetes, especially in disadvantaged areas. However, limited research has been carried out on the relationship between numbers of remaining teeth, diabetes-related biomarkers and personal oral hygiene among diabetic rural residents. A cross-sectional, descriptive design with a simple random sample was used. This study was part of a longitudinal cohort study of health promotion for preventing diabetic foot among rural community diabetic residents. It was carried out in 18 western coastal and inland districts of Chiayi County in central Taiwan. In total, 703 participants were enrolled in this study. The findings indicated that a high percentage of the participants (26%) had no remaining natural teeth. Nearly three quarters (74%) had fewer than 20 natural teeth. After controlling for the potential confounding factors, multivariate analysis demonstrated that the factors determining numbers of remaining teeth were age (p < 0.001), education (p < 0.001), using dental floss (p = 0.003), ankle brachial pressure index (p = 0.028), waist circumference (p = 0.024) and HbA1C (p = 0.033). Except for some unmodifiable factors, the factors most significantly associated with numbers of remaining teeth were less tooth-brushing with dental floss, abnormal ankle brachial pressure and poor glycemic control. This study highlights the importance of nursing intervention in oral hygiene for patients with type 2 diabetes. It is necessary to initiate oral health promotion activities when diabetes is first diagnosed, especially for older diabetic residents of rural or coastal areas who are poorly educated. © 2013 John Wiley & Sons Ltd.

Cellular mechanism of oral absorption of solidified polymer micelles.

PubMed

Abramov, Eva; Cassiola, Flavia; Schwob, Ouri; Karsh-Bluman, Adi; Shapero, Mara; Ellis, James; Luyindula, Dema; Adini, Irit; D'Amato, Robert J; Benny, Ofra

2015-11-01

Oral delivery of poorly soluble and permeable drugs represents a significant challenge in drug development. The oral delivery of drugs remains to be the ultimate route of any drugs. However, in many cases, drugs are not absorbed well in the gastrointestinal tract, or they lose their activity. Polymer micelles were recognized as an effective carrier system for drug encapsulation, and are now studied as a vehicle for oral delivery of insoluble compounds. We characterized the properties of monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles, and visualized their internalization in mouse small intestine. Using Caco-2 cells as a cellular model, we studied the kinetics of particle uptake, their transport, and the molecular mechanism of their intestinal absorption. Moreover, by inhibiting specific endocytosis pathways, pharmacologically and genetically, we found that mPEG-PLA nanoparticle endocytosis is mediated by clathrin in an energy-dependent manner, and that the low-density lipoprotein receptor is involved. Many current drugs used are non-water soluble and indeed, the ability to deliver these drugs via the gastrointestinal tract remains the holy grail for many researchers. The authors in this paper developed monomethoxy polyethylene glycol-poly lactic acid (mPEG-PLA) micelles as a drug nanocarrier, and studied the mechanism of uptake across intestinal cells. The findings should improve our current understanding and point to the development of more nanocarriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Impact of hygiene of housing conditions on performance and health of two pig genetic lines divergent for residual feed intake.

PubMed

Chatelet, A; Gondret, F; Merlot, E; Gilbert, H; Friggens, N C; Le Floc'h, N

2018-02-01

Pigs selected for high performance may be more at risk of developing diseases. This study aimed to assess the health and performance of two pig lines divergently selected for residual feed intake (RFI) (low RFI (LRFI) v. high RFI (HRFI)) and housed in two contrasted hygiene conditions (poor v. good) using a 2×2 factorial design (n=40/group). The challenge period (Period 1), started on week zero (W0) when 12-week-old pigs were transferred to good or poor housing conditions. At week 6 (W6), half of the pigs in each group were slaughtered. During a recovery period (Period 2) from W6 to W13 to W14, the remaining pigs (n=20/group) were transferred in good hygiene conditions before being slaughtered. Blood was collected every three (Period 1) or 2 weeks (Period 2) to assess blood indicators of immune and inflammatory responses. Pulmonary lesions at slaughter and performance traits were evaluated. At W6, pneumonia prevalence was greater for pigs housed in poor than in good conditions (51% v. 8%, respectively, P<0.001). Irrespective of hygiene conditions, lung lesion scores were lower for LRFI pigs than for HRFI pigs (P=0.03). At W3, LRFI in poor conditions had the highest number of blood granulocytes (hygiene×line, P=0.03) and at W6, HRFI pigs in poor conditions had the greatest plasma haptoglobin concentrations (hygiene×line, P=0.02). During Period 1, growth rate and growth-to-feed ratio were less affected by poor hygiene in LRFI pigs than in HRFI pigs (hygiene×line, P=0.001 and P=0.02, respectively). Low residual feed intake pigs in poor conditions ate more than the other groups (hygiene×line, P=0.002). Irrespective of the line, fasting plasma glucose concentrations were higher in poor conditions, whereas fasting free fatty acids concentrations were lower than in good conditions. At the end of Period 2, pneumonia prevalence was similar for both housing conditions (39% v. 38%, respectively). During Period 2, plasma protein concentrations were greater for pigs previously housed in poor than in good conditions during Period 1. Immune traits, gain-to-feed ratio, BW gain and feed consumption did not differ during Period 2. Nevertheless, at W12, BW of HRFI previously housed in poor conditions was 13.4 kg lower than BW of HRFI pigs (P<0.001) previously housed in good conditions. In conclusion, health of the most feed efficient LRFI pigs was less impaired by poor hygiene conditions. This line was able to preserve its health, growth performance and its feed ingestion to a greater extent than the less efficient HRFI line.

Poor embryo development in post-ovulatory in vivo-aged mouse oocytes is associated with mitochondrial dysfunction, but mitochondrial transfer from somatic cells is not sufficient for rejuvenation.

PubMed

Igarashi, Hideki; Takahashi, Toshifumi; Abe, Hiroyuki; Nakano, Hiroshi; Nakajima, Osamu; Nagase, Satoru

2016-10-01

Does in vivo aging of mouse oocytes affect mitochondrial function? Mitochondrial function was impaired in post-ovulatory in vivo-aged mouse oocytes and microinjection of somatic cell mitochondria did not rescue poor fertilization and embryonic development rates. The mechanisms underlying the decline in oocyte quality associated with oocyte aging remain unknown, although studies have suggested that the decline is regulated by mitochondrial dysfunction. However, only a limited number of studies have provided direct evidence implicating mitochondrial dysfunction in oocyte quality during the aging of oocytes. We used post-ovulatory, in vivo-aged mouse oocytes as a model for studying low-quality oocytes in oocyte aging. Superovulated oocytes released from the oviduct at 14 h and 20-24 h post-hCG injection were designated as 'fresh' and 'aged' oocytes, respectively. Membrane potentials and oxygen consumption in single oocytes were evaluated as measures of mitochondrial function in fresh and aged oocytes. Mitochondrial transcriptional factor A (TFAM) expression levels were examined by western blotting, and colocalization of mitochondria and TFAM was analyzed by measuring immunofluorescence in fresh and aged oocytes. IVF and blastocyst formation rates were calculated after oocyte microinjection with mitochondria derived from liver cells. The average mitochondrial membrane potential in fresh oocytes was significantly higher than that in aged oocytes (P < 0.05). The average oxygen consumption rate in aged oocytes was significantly lower than that in fresh oocytes (P < 0.05). Although total TFAM expression was unchanged, its colocalization with mitochondria decreased in aged oocytes. IVF and blastocyst formation rates for mitochondrion-injected aged oocytes were not significantly different from those for buffer-injected aged oocytes. Not applicable. A limitation of this study is that we did not examine the effects of microinjecting mitochondria from other somatic cell types into aged oocytes on their fertilization and embryonic development rates. The results from the present study showed that poor embryonic development was associated with impairment of mitochondrial functions in in vivo-aged oocytes. However, the microinjection of mitochondria from liver cells did not improve the low fertilization and embryonic development rates of aged oocytes. It remains to be demonstrated whether oocyte quality can be rescued by the transfer of cytosolic factors or cellular organelles, such as the endoplasmic reticulum or mitochondria, from specific cell types. This study was supported by Grants-in-Aid for General Science Research to Toshifumi Takahashi (No. 25462550) and Hideki Igarashi (No. 26462474). The funding source played no role in study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The authors have no conflict of interest to disclose. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of larvicides in developing management guidelines for long-term control of pest blackflies (Diptera: Simuliidae) along the Orange River, South Africa.

PubMed

Palmer, R W; Rivers-Moore, N A

2008-12-01

In 2000 and 2001 Orange River levels were higher than normal: associated serious outbreaks of blackfly had a substantial detrimental impact on the local economy. The poor control was attributed to the suspected development of larval resistance to temephos. A long-term solution to blackfly control, through the identification of a suitable replacement to temephos for use during high flow conditions, was proposed. This study, however, failed to identify or register a suitable larvicide for use during high flow conditions. Although permethrin was highly effective against blackfly larvae, it was rejected because of its detrimental impacts on non-target fauna. Various formulations of locally produced dry Bacillus thuringiensis var. israelensis (B.t.i.) were tested, but these were ineffective against blackflies. The study also confirmed that resistance to temephos has developed among Simulium chutteri in the middle and lower Orange River. The feasibility of "reversing" the resistance to temephos through the use of the synergist piperonyl butoxide (PBO) was investigated, but the results were not favourable. Furthermore, PBO was highly toxic to blackflies and non-target organisms, and was not recommended for further testing. This means that B.t.i. currently remains the only symptomatic measure of treatment currently applied. Although resistance to B.t.i. has not been reported for blackflies elsewhere in South Africa, there is a need to remain vigilant and to implement an operational strategy that minimizes the risks of resistance developing.

Fear of moving outdoors and development of outdoor walking difficulty in older people.

PubMed

Rantakokko, Merja; Mänty, Minna; Iwarsson, Susanne; Törmäkangas, Timo; Leinonen, Raija; Heikkinen, Eino; Rantanen, Taina

2009-04-01

To study which individual characteristics and environmental factors correlate with fear of moving outdoors and whether fear of moving outdoors predicts development of mobility limitation. Observational prospective cohort study and cross-sectional analyses. Community and research center. Seven hundred twenty-seven community-living people aged 75 to 81 were interviewed at baseline, of whom 314 took part in a 3.5-year follow-up. Fear of moving outdoors and its potential individual and environmental correlates were assessed at baseline. Perceived difficulties in walking 0.5 km and 2 km were assessed twice a year over a 3.5-year period. At baseline, 65% of the women and 29% of the men reported fear of moving outdoors. Poor socioeconomic status; musculoskeletal diseases; slow walking speed; and the presence of poor street conditions, hills in the nearby environment, and noisy traffic correlated with fear of moving outdoors. At the first 6-month follow-up, participants with fear of moving outdoors had more than four times the adjusted risk (odds ratio (OR)=4.6, 95% confidence interval (CI)=1.92-11.00) of developing difficulties in walking 0.5 km and a three times greater adjusted risk (OR=3.10, 95% CI=1.49-6.46) for developing difficulty in walking 2 km compared with those without fear. The difference in the prevalence of walking difficulties remained statistically significant over the 3.5-year follow-up (P=.02 and P=.009, respectively). Fear of moving outdoors is common in older adults and increases the risk of developing self-reported difficulties in walking 0.5 km and 2 km. Knowledge about individual and environmental factors underlying fear of moving outdoors and finding ways to alleviate fear of moving outdoors are important for community planning and prevention of disability.

Trade, development, and regulatory issues in food.

PubMed

Ramaswamy, Sunder; Viswanathan, Brinda

2007-03-01

Trade in food and animal products has increased several-fold in the past decade, and simultaneously regulations governing the movement of such products across national boundaries have also increased. The present study reviews harmonization in food trade regulation by focusing on nutritional aspects to understand its role in enhancing world trade on the one hand and consumer interest and welfare on the other. Harmonization to a large extent brings in more regulation from the developed world acting through their governments, consumer organizations, and multinational companies; it does not seem to address, in general, the concerns of the large segments of the poor population for whom agriculture and food trade are the main sources of livelihood. There is a lack of quantifiable estimates of the loss in well-being of the disadvantaged. However, there is substantial research focused on the potential harm to developed nations as a result of nonadherence to the rules. Clearly, lack of adequate infrastructure, resource constraints, and weak institutions not only result in poor food safety regulation within developing countries but also remain barriers to realizing the greater potential benefits from increased trade. Harmonization of standards would have some losers and some winners, but to make it more inclusive, scientific knowledge alone may not be adequate; social and cultural aspects also need to be considered, since food systems differ among regions, with varying preferences, local resource availability, and levels of economic development. Improvement in governance in many countries not only would ensure better participation in international rule-making and the negotiation process for fairer trade but also would result in effective domestic legislation to ensure safer health for citizens, resulting in higher overall well-being.

Deep sequencing of foot-and-mouth disease virus reveals RNA sequences involved in genome packaging.

PubMed

Logan, Grace; Newman, Joseph; Wright, Caroline F; Lasecka-Dykes, Lidia; Haydon, Daniel T; Cottam, Eleanor M; Tuthill, Tobias J

2017-10-18

Non-enveloped viruses protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. Packaging and capsid assembly in RNA viruses can involve interactions between capsid proteins and secondary structures in the viral genome as exemplified by the RNA bacteriophage MS2 and as proposed for other RNA viruses of plants, animals and human. In the picornavirus family of non-enveloped RNA viruses, the requirements for genome packaging remain poorly understood. Here we show a novel and simple approach to identify predicted RNA secondary structures involved in genome packaging in the picornavirus foot-and-mouth disease virus (FMDV). By interrogating deep sequencing data generated from both packaged and unpackaged populations of RNA we have determined multiple regions of the genome with constrained variation in the packaged population. Predicted secondary structures of these regions revealed stem loops with conservation of structure and a common motif at the loop. Disruption of these features resulted in attenuation of virus growth in cell culture due to a reduction in assembly of mature virions. This study provides evidence for the involvement of predicted RNA structures in picornavirus packaging and offers a readily transferable methodology for identifying packaging requirements in many other viruses. Importance In order to transmit their genetic material to a new host, non-enveloped viruses must protect their genomes by packaging them into an outer shell or capsid of virus-encoded proteins. For many non-enveloped RNA viruses the requirements for this critical part of the viral life cycle remain poorly understood. We have identified RNA sequences involved in genome packaging of the picornavirus foot-and-mouth disease virus. This virus causes an economically devastating disease of livestock affecting both the developed and developing world. The experimental methods developed to carry out this work are novel, simple and transferable to the study of packaging signals in other RNA viruses. Improved understanding of RNA packaging may lead to novel vaccine approaches or targets for antiviral drugs with broad spectrum activity. Copyright © 2017 Logan et al.

Assessment of physical and mental health in male university students with varying sleep habits.

PubMed

Matsumoto, Yuuki; Toyomasu, Kouji; Uchimura, Naohisa

2011-01-01

Healthy sleep habits entail not only sleeping for a sufficient period (quantity) but also regularity of the sleep cycle and getting sound sleep (quality). University students often have erratic schedules that cause irregular sleep patterns even though sleep durations remain relatively constant. This study compared the physical and mental health of 90 male university students with different sleep habits. We created sleep habit scales using the Tokyo Metropolitan Institute for Neuroscience life habits inventory (TMIN-LHI; Miyashita, 1994) by performing a factor analysis and classifying sleeping habits based on regularity, quality, and quantity. Four types of sleep habits were identified by cluster analysis; good sleep was characterized by regular and high quality sleep but of relatively short sleep duration; long sleep was regular and relatively long but of low quality; short sleep was of high quality but short and irregular, while poor sleep was irregular, of low quality, and relatively long. The good sleep group had a significantly lower average waist circumference, and lower systolic and diastolic blood pressure. The long and poor sleep groups, which both had low quality sleep, scored lower than the national standard on the mental component summary (MCS) calculated from the Social Functioning-36 (SF-36) short-form health survey. Furthermore, the average MCS score of the poor sleep group was significantly lower than that of any other sleep habit group. Subjects with poor sleep also scored lowest on the Self-rating Depression Scale (SDS). In addition, the short and poor sleep groups were prone to glucose or lipid metabolism disorders. Maintaining good physical and mental health without sound sleep and a regular sleep cycle is difficult, even if sleeping hours are kept constant. Therefore, we included the assessment of regularity and quality in addition to hours of sleep in order to develop appropriate sleep guidelines for improved physical and mental health.

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

PubMed

Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

Mechanisms of increased lifespan in hypoxia

USDA-ARS?s Scientific Manuscript database

Genetic variation accounts for a relatively small amount of the variation in lifespan (generally 15-30%), while environmental stressors are very strong predictors (Finch and Kirkwood 2000). Hypoxia is an environmental stress that increases longevity in some contexts, but the mechanisms remain poorly...

INVESTIGATION OF TRANSFER OF FLUORESCENT TRACERS FROM SURFACES TO SKIN

EPA Science Inventory

Under the provisions of the Food Quality Protection Act (FQPA), aggregate exposure assessments must be conducted for pesticides proposed for registration. Many aspects of dermal exposure assessment remain poorly quantified. For purposes of assessing surface-to-skin transfers ...

Maternal stress, well-being, and impaired sleep in mothers of children with developmental disabilities: a literature review.

PubMed

Lee, Jiwon

2013-11-01

Having children with developmental disabilities (DDs) requires a high level of caregiving responsibilities, and existing studies support that mothers of children with DDs experience high levels of maternal stress as well as poor sleep and well-being. Given the fact that the number of children with DDs has increased, an up-to-date literature review is necessary to identify factors associated with maternal stress, sleep, and well-being. In addition, understanding these factors and their relationships may provide better strategies in designing effective interventions that can reduce the burden in mothers of children with DDs. This review summarized 28 scientific research papers that examined maternal stress, sleep, and well-being in mothers of children with DDs in past 12 years. The study findings indicate that mothers of children with DDs experience higher levels of stress than mothers of typically developing children, and it remains high over time. In addition, these mothers often encounter depressive symptoms as well as poor sleep quality. The study results also reveal that there is a bidirectional relationship between maternal stress and depressive symptoms as well as between poor sleep quality and depressive symptoms. For example, higher stress mothers experienced more depressive symptoms. Mothers of children with DDs with poor sleep quality are significantly associated with more depressive symptoms. Child behavior problems were significantly associated with both maternal stress and depressive symptoms, but cautious interpretation is warranted due to the shared variance between child behavior problems, maternal stress, and depressive symptoms. Methodological guidelines for future research involve the use of reliable and valid instruments for the measurement of child behavior problems, maternal stress, and sleep. Recommendations for future research are included. Copyright © 2013 Elsevier Ltd. All rights reserved.

Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting.

PubMed

Belsches, Theodore C; Tilly, Alyssa E; Miller, Tonya R; Kambeyanda, Rohan H; Leadford, Alicia; Manasyan, Albert; Chomba, Elwyn; Ramani, Manimaran; Ambalavanan, Namasivayam; Carlo, Waldemar A

2013-09-01

Term infants in resource-poor settings frequently develop hypothermia during the first hours after birth. Plastic bags or wraps are a low-cost intervention for the prevention of hypothermia in preterm and low birth weight infants that may also be effective in term infants. Our objective was to test the hypothesis that placement of term neonates in plastic bags at birth reduces hypothermia at 1 hour after birth in a resource-poor hospital. This parallel-group randomized controlled trial was conducted at University Teaching Hospital, the tertiary referral center in Zambia. Inborn neonates with both a gestational age ≥37 weeks and a birth weight ≥2500 g were randomized 1:1 to either a standard thermoregulation protocol or to a standard thermoregulation protocol with placement of the torso and lower extremities inside a plastic bag within 10 minutes after birth. The primary outcome was hypothermia (<36.5°C axillary temperature) at 1 hour after birth. Neonates randomized to plastic bag (n = 135) or to standard thermoregulation care (n = 136) had similar baseline characteristics (birth weight, gestational age, gender, and baseline temperature). Neonates in the plastic bag group had a lower rate of hypothermia (60% vs 73%, risk ratio 0.76, confidence interval 0.60-0.96, P = .026) and a higher axillary temperature (36.4 ± 0.5°C vs 36.2 ± 0.7°C, P < .001) at 1 hour after birth compared with infants receiving standard care. Placement in a plastic bag at birth reduced the incidence of hypothermia at 1 hour after birth in term neonates born in a resource-poor setting, but most neonates remained hypothermic.

Refining the Association of Fever with Functional Outcome in Aneurysmal Subarachnoid Hemorrhage.

PubMed

Kramer, Christopher L; Pegoli, Marianna; Mandrekar, Jay; Lanzino, Giuseppe; Rabinstein, Alejandro A

2017-02-01

We analyzed the impact of cause, severity, and duration of fever on functional outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Fever characteristics were analyzed in 584 consecutive patients with aSAH. Fever was defined as core body temperature ≥38.3 °C on ≥2 consecutive days. Subfebrile measurements were those between 37 and 38.2 °C. Febrile and subfebrile loads were the number of hours with fever or subfebrile measurements, respectively. Univariate and multivariate logistic regression models were developed to define predictors of outcome using various categorizations of fever cause, severity, and duration. Febrile measurements were observed in 281/584 (48.1 %) patients, recurring over a mean duration of 2.1 ± 3.0 days. Early fever within 24 and 72 h was encountered in 69 (11.9 %) and 110 (18.9 %) of patients, respectively. An infectious source was discovered in 126 (44.8 %) febrile patients. On univariate analysis, days of fever, febrile load, and fever onset within 24 and 72 h were associated with poor outcome (all p < 0.001); but subfebrile load was not (p = 0.56). On multivariate model constructed with all variables associated with outcome on univariate analyses, days of fever remained independently associated with poor outcome (OR 1.14 of poor outcome per day of fever, 95 % CI 1.06-1.22; p = 0.0006) displacing all other fever measures from the final model. Early onset of fever, number of hours with fever, and especially days of fever are associated with poor functional outcome. Conversely, subfebrile load does not influence clinical outcome. These data suggest prolonged fever should be avoided, but subfebrile temperatures may not justify intervention.

Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.

PubMed

Solé, Francesc; Luño, Elisa; Sanzo, Carmen; Espinet, Blanca; Sanz, Guillermo F; Cervera, José; Calasanz, María José; Cigudosa, Juan Cruz; Millà, Fuensanta; Ribera, Josep Maria; Bureo, Encarna; Marquez, Maria Luisa; Arranz, Eva; Florensa, Lourdes

2005-09-01

The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.

The association between income and life expectancy revisited: deindustrialization, incarceration and the widening health gap.

PubMed

Nosrati, Elias; Ash, Michael; Marmot, Michael; McKee, Martin; King, Lawrence P

2017-11-22

The health gap between the top and the bottom of the income distribution is widening rapidly in the USA, but the lifespan of America's poor depends substantially on where they live. We ask whether two major developments in American society, deindustrialization and incarceration, can explain variation among states in life expectancy of those in the lowest income quartile. Life expectancy estimates at age 40 of those in the bottom income quartile were used to fit panel data models examining the relationship with deindustrialization and incarceration between 2001 and 2014 for all US states. A one standard deviation (s.d.) increase in deindustrialization (mean = 11.2, s.d. = 3.5) reduces life expectancy for the poor by 0.255 years [95% confidence interval (CI): 0.090-0.419] and each additional prisoner per 1000 residents (mean = 4.0, s.d. = 1.5) is associated with a loss of 0.468 years (95% CI: 0.213-0.723). Our predictors explain over 20% of the state-level variation in life expectancy among the poor and virtually the entire increase in the life expectancy gap between the top and the bottom income quartiles since the turn of the century. In the USA between 2001 and 2014, deindustrialization and incarceration subtracted roughly 2.5 years from the lifespan of the poor, pointing to their role as major health determinants. Future research must remain conscious of the upstream determinants and the political economy of public health. If public policy responses to growing health inequalities are to be effective, they must consider strengthening industrial policy and ending hyper-incarceration. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Poverty, development, and Himalayan ecosystems.

PubMed

Sandhu, Harpinder; Sandhu, Sukhbir

2015-05-01

The Himalayas are rich in biodiversity but vulnerable to anthropogenic pressures. They are also host to growing number of rural poor who are dependent on forest and ecosystem services for their livelihood. Local and global efforts to integrate poverty alleviation and biodiversity conservation in the Himalayas remain elusive so far. In this work, we highlight two key impediments in achieving sustainable development in the Himalayas. On the positive side, we also highlight the work of Ashoka Trust for Research in Ecology and the Environment (ATREE), a research organization based in India that seeks to integrate biodiversity concerns with livelihood security. For impediments, we draw on two examples from the Darjeeling district, India, in Eastern Himalayan region to illustrate how development organizations are failing to simultaneously address poverty and environmental issues. Based on the success of ATREE, we then propose a conceptual framework to integrate livelihood generating activities with sustainable and equitable development agenda. We recommend developing a Hindu-Kush Himalayan Ecosystem Services Network in the region to formulate a strategy for further action. We conclude by offering measures to address the challenge of integrating livelihood and environment issues through this network.

Sustainability Assessment Model in Product Development

NASA Astrophysics Data System (ADS)

Turan, Faiz Mohd; Johan, Kartina; Nor, Nik Hisyamudin Muhd; Omar, Badrul

2017-08-01

Faster and more efficient development of innovative and sustainable products has become the focus for manufacturing companies in order to remain competitive in today’s technologically driven world. Design concept evaluation which is the end of conceptual design is one of the most critical decision points. It relates to the final success of product development, because poor criteria assessment in design concept evaluation can rarely compensated at the later stages. Furthermore, consumers, investors, shareholders and even competitors are basing their decisions on what to buy or invest in, from whom, and also on what company report, and sustainability is one of a critical component. In this research, a new methodology of sustainability assessment in product development for Malaysian industry has been developed using integration of green project management, new scale of “Weighting criteria” and Rough-Grey Analysis. This method will help design engineers to improve the effectiveness and objectivity of the sustainable design concept evaluation, enable them to make better-informed decisions before finalising their choice and consequently create value to the company or industry. The new framework is expected to provide an alternative to existing methods.

Social Consequences of Alcohol Use among Urban Poor: A Cross-sectional Study in Kathmandu Valley.

PubMed

Thapa, P; Mishra, S R; Bista, B; Dhungana, R R; Adhikari, N; Soti, L; Puri, S; Aryal, K K

2015-01-01

Nepal is not an exception to alcohol use; urban poor are more prone than the general population. The question of social consequences of alcohol use among urban poor remains largely unanswered in Nepal. Study explored the alcohol linked social consequences among the urban poor of Kathmandu Valley. Taking 422 urban poor from four squatter settlements of Kathmandu Valley, a cross-sectional study was carried out. A series of univariate and bivariate analysis were performed in R version 3.1.2. Four out of 10 current drinkers (42.86%, 95% CI: 31.4-54.3) encountered various social consequences. The number one consequence hitting 23.19% drinkers was money loss. Male drinkers were 4.43 times (95% CI: 1.810.8) more likely to face social consequences than their female counterparts. Being male frequent drinker increased the odds of social consequence 3.80 times (95% CI:1.3-11.0) than that of female frequent drinker. A behaviour change communication campaign needs initiation; male populace and frequent drinkers being the target.

Advanced EUS Guided Tissue Acquisition Methods for Pancreatic Cancer

PubMed Central

Kandel, Pujan; Wallace, Michael B.

2018-01-01

Pancreas cancer is a lethal cancer as the majority patients are diagnosed at an advanced incurable stage. Despite improvements in diagnostic modalities and management strategies, including surgery and chemotherapies, the outcome of pancreas cancer remains poor. Endoscopic ultrasound (EUS) is an important imaging tool for pancreas cancer. For decades, resected pancreas cancer and other cancer specimens have been used to identify tissue biomarkers or genomics for precision therapy; however, only 20% of patients undergo surgery, and thus, this framework is not useful for unresectable pancreas cancer. With advancements in needle technologies, tumor specimens can be obtained at the time of tissue diagnosis. Tumor tissue can be used for development of personalized cancer treatment, such as performing whole exome sequencing and global genomic profiling of pancreas cancer, development of tissue biomarkers, and targeted mutational assays for precise chemotherapy treatment. In this review, we discuss the recent advances in tissue acquisition of pancreas cancer. PMID:29463004

Use of Animal Models in Understanding Cancer-induced Bone Pain

PubMed Central

Slosky, Lauren M; Largent-Milnes, Tally M; Vanderah, Todd W

2015-01-01

Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP’s unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP. PMID:26339191

Articular cartilage tissue engineering: the role of signaling molecules

PubMed Central

Kwon, Heenam; Paschos, Nikolaos K.; Hu, Jerry C.; Athanasiou, Kyriacos

2017-01-01

Effective early disease modifying options for osteoarthritis remain lacking. Tissue engineering approach to generate cartilage in vitro has emerged as a promising option for articular cartilage repair and regeneration. Signaling molecules and matrix modifying agents, derived from knowledge of cartilage development and homeostasis, have been used as biochemical stimuli toward cartilage tissue engineering and have led to improvements in the functionality of engineered cartilage. Clinical translation of neocartilage faces challenges, such as phenotypic instability of the engineered cartilage, poor integration, inflammation, and catabolic factors in the arthritic environment; these can all contribute to failure of implanted neocartilage. A comprehensive understanding of signaling molecules involved in osteoarthritis pathogenesis and their actions on engineered cartilage will be crucial. Thus, while it is important to continue deriving inspiration from cartilage development and homeostasis, it has become increasing necessary to incorporate knowledge from osteoarthritis pathogenesis into cartilage tissue engineering. PMID:26811234

Bone marrow-resident NK cells prime monocytes for regulatory function during infection

PubMed Central

Askenase, Michael H.; Han, Seong-Ji; Byrd, Allyson L.; da Fonseca, Denise Morais; Bouladoux, Nicolas; Wilhelm, Christoph; Konkel, Joanne E.; Hand, Timothy W.; Lacerda-Queiroz, Norinne; Su, Xin-Zhuan; Trinchieri, Giorgio; Grainger, John R.; Belkaid, Yasmine

2015-01-01

SUMMARY Tissue-infiltrating Ly6Chi monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. How and where this diversity of function is imposed remains poorly understood. Here we show that during acute gastrointestinal infection, priming of monocytes for regulatory function preceded systemic inflammation and was initiated prior to bone marrow egress. Notably, natural killer (NK) cell-derived IFN-γ promoted a regulatory program in monocyte progenitors during development. Early bone marrow NK cell activation was controlled by systemic interleukin-12 (IL-12) produced by Batf3-dependent dendritic cells (DC) in the mucosal-associated lymphoid tissue (MALT). This work challenges the paradigm that monocyte function is dominantly imposed by local signals following tissue recruitment, and instead proposes a sequential model of differentiation in which monocytes are pre-emptively educated during development in the bone marrow to promote their tissue-specific function. PMID:26070484

New perspectives on dandruff and seborrheic dermatitis: lessons we learned from bacterial and fungal skin microbiota.

PubMed

Paulino, Luciana Campos

2017-06-01

The human body is inhabited by complex microbial communities, which positively impact different aspects of our health, and might also be related to the development of diseases. Progress in technologies, particularly sequencing methods and bioinformatics tools, has been crucial for the advances in this field. Microbial communities from skin can modulate immune response and protect the host against pathogens, and there are also data supporting their association with several skin conditions; including dandruff and seborrheic dermatitis. For decades, they have been thought to be related to Malassezia yeasts; however, the microbial role has not been elucidated, and their etiology remains poorly understood. This review discusses the recent findings in dandruff and seborrheic dermatitis and their relation to the skin microbiota. Data provided new perceptions to aid in the understanding of these skin disorders, broadening our view of their etiology and the possible roles of microbial communities in symptom development.

Pseudomonas aeruginosa dose response and bathing water infection.

PubMed

Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

2014-03-01

Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.

Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.

PubMed

Howard, Rebecca J; Trudell, James R; Harris, R Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy.

Maternal Obesity, Inflammation, and Developmental Programming

PubMed Central

Segovia, Stephanie A.; Vickers, Mark H.; Reynolds, Clare M.

2014-01-01

The prevalence of obesity, especially in women of child-bearing age, is a global health concern. In addition to increasing the immediate risk of gestational complications, there is accumulating evidence that maternal obesity also has long-term consequences for the offspring. The concept of developmental programming describes the process in which an environmental stimulus, including altered nutrition, during critical periods of development can program alterations in organogenesis, tissue development, and metabolism, predisposing offspring to obesity and metabolic and cardiovascular disorders in later life. Although the mechanisms underpinning programming of metabolic disorders remain poorly defined, it has become increasingly clear that low-grade inflammation is associated with obesity and its comorbidities. This review will discuss maternal metainflammation as a mediator of programming in insulin sensitive tissues in offspring. Use of nutritional anti-inflammatories in pregnancy including omega 3 fatty acids, resveratrol, curcumin, and taurine may provide beneficial intervention strategies to ameliorate maternal obesity-induced programming. PMID:24967364

Normative brain size variation and brain shape diversity in humans.

PubMed

Reardon, P K; Seidlitz, Jakob; Vandekar, Simon; Liu, Siyuan; Patel, Raihaan; Park, Min Tae M; Alexander-Bloch, Aaron; Clasen, Liv S; Blumenthal, Jonathan D; Lalonde, Francois M; Giedd, Jay N; Gur, Ruben C; Gur, Raquel E; Lerch, Jason P; Chakravarty, M Mallar; Satterthwaite, Theodore D; Shinohara, Russell T; Raznahan, Armin

2018-06-15

Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

From Embryonic Development to Human Diseases: The Functional Role of Caveolae/Caveolin

PubMed Central

Sohn, Jihee; Brick, Rachel M.; Tuan, Rocky S.

2017-01-01

Caveolae, an almost ubiquitous, structural component of the plasma membrane, play a critical role in many functions essential for proper cell function, including membrane trafficking, signal transduction, extracellular matrix remodeling, and tissue regeneration. Three main types of caveolin proteins have been identified from caveolae since the discovery of caveolin-1 in the early 1990s. All three (Cav-1, Cav-2, and Cav-3) play crucial roles in mammalian physiology, and can effect pathogenesis in a wide range of human diseases. While many biological activities of caveolins have been uncovered since its discovery, their role and regulation in embryonic develop remain largely poorly understood, although there is increasing evidence that caveolins may be linked to lung and brain birth defects. Further investigations are clearly needed to decipher how caveolae/caveolins mediate cellular functions and activities of normal embryogenesis and how their perturbations contribute to developmental disorders. PMID:26991990

Epidemic cholera spreads like wildfire

NASA Astrophysics Data System (ADS)

Roy, Manojit; Zinck, Richard D.; Bouma, Menno J.; Pascual, Mercedes

2014-01-01

Cholera is on the rise globally, especially epidemic cholera which is characterized by intermittent and unpredictable outbreaks that punctuate periods of regional disease fade-out. These epidemic dynamics remain however poorly understood. Here we examine records for epidemic cholera over both contemporary and historical timelines, from Africa (1990-2006) and former British India (1882-1939). We find that the frequency distribution of outbreak size is fat-tailed, scaling approximately as a power-law. This pattern which shows strong parallels with wildfires is incompatible with existing cholera models developed for endemic regions, as it implies a fundamental role for stochastic transmission and local depletion of susceptible hosts. Application of a recently developed forest-fire model indicates that epidemic cholera dynamics are located above a critical phase transition and propagate in similar ways to aggressive wildfires. These findings have implications for the effectiveness of control measures and the mechanisms that ultimately limit the size of outbreaks.

Multiple Sclerosis: Immunopathology and Treatment Update

PubMed Central

Dargahi, Narges; Katsara, Maria; Tselios, Theodore; Androutsou, Maria-Eleni; Matsoukas, John

2017-01-01

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. PMID:28686222

Notch1 acts via Foxc2 to promote definitive hematopoiesis via effects on hemogenic endothelium

PubMed Central

Jang, Il Ho; Lu, Yi-Fen; Zhao, Long; Wenzel, Pamela L.; Kume, Tsutomu; Datta, Sumon M.; Arora, Natasha; Guiu, Jordi; Lagha, Mounia; Kim, Peter G.; Do, Eun Kyoung; Kim, Jae Ho; Schlaeger, Thorsten M.; Zon, Leonard I.; Bigas, Anna; Burns, Caroline E.

2015-01-01

Hematopoietic and vascular development share many common features, including cell surface markers and sites of origin. Recent lineage-tracing studies have established that definitive hematopoietic stem and progenitor cells arise from vascular endothelial–cadherin+ hemogenic endothelial cells of the aorta-gonad-mesonephros region, but the genetic programs underlying the specification of hemogenic endothelial cells remain poorly defined. Here, we discovered that Notch induction enhances hematopoietic potential and promotes the specification of hemogenic endothelium in differentiating cultures of mouse embryonic stem cells, and we identified Foxc2 as a highly upregulated transcript in the hemogenic endothelial population. Studies in zebrafish and mouse embryos revealed that Foxc2 and its orthologs are required for the proper development of definitive hematopoiesis and function downstream of Notch signaling in the hemogenic endothelium. These data establish a pathway linking Notch signaling to Foxc2 in hemogenic endothelial cells to promote definitive hematopoiesis. PMID:25587036

Malignant Melanoma of the Anus Found during Routine Colonoscopy in Ulcerative Colitis.

PubMed

Seo, Kwang Il; Moon, Won; Kim, Sung Eun; Park, Moo In; Park, Seun Ja

2017-06-25

Inflammatory bowel disease (IBD) is characterized by recurrent or chronic inflammation of the gastrointestinal tract, which results in increased risk of developing cancer. Anorectal malignant melanoma is often misdiagnosed as either hemorrhoids or benign anorectal conditions in inflammatory bowel disease. Therefore, the overall prognosis and survival of IBD are poor. To date, the best treatment strategy remains controversial. Only early diagnosis and complete excision yield survival benefit. Here, we report a 64-year-old woman with ulcerative colitis, who was found to have anal malignant melanoma on routine colonoscopy. The lesion was confined to the mucosa with no distant metastasis. She underwent complete trans-anal excision. There was no recurrence at the four-year follow-up. Physicians should be aware of increased risk of cancer development in IBD patients and remember the importance of meticulous inspection of the anal canal.

Methods for genetic modification of megakaryocytes and platelets.

PubMed

Pendaries, Caroline; Watson, Stephen P; Spalton, Jennifer C

2007-09-01

During recent decades there have been major advances in the fields of thrombosis and haemostasis, in part through development of powerful molecular and genetic technologies. Nevertheless, genetic modification of megakaryocytes and generation of mutant platelets in vitro remains a highly specialized area of research. Developments are hampered by the low frequency of megakaryocytes and their progenitors, a poor efficiency of transfection and a lack of understanding with regard to the mechanism by which megakaryocytes release platelets. Current methods used in the generation of genetically modified megakaryocytes and platelets include mutant mouse models, cell line studies and use of viruses to transform primary megakaryocytes or haematopoietic precursor cells. This review summarizes the advantages, limitations and technical challenges of such methods, with a particular focus on recent successes and advances in this rapidly progressing field including the potential for use in gene therapy for treatment of patients with platelet disorders.

High School Dropout in Proximal Context: The Triggering Role of Stressful Life Events.

PubMed

Dupéré, Véronique; Dion, Eric; Leventhal, Tama; Archambault, Isabelle; Crosnoe, Robert; Janosz, Michel

2018-03-01

Adolescents who drop out of high school experience enduring negative consequences across many domains. Yet, the circumstances triggering their departure are poorly understood. This study examined the precipitating role of recent psychosocial stressors by comparing three groups of Canadian high school students (52% boys; M age  = 16.3 years; N = 545): recent dropouts, matched at-risk students who remain in school, and average students. Results indicate that in comparison with the two other groups, dropouts were over three times more likely to have experienced recent acute stressors rated as severe by independent coders. These stressors occurred across a variety of domains. Considering the circumstances in which youth decide to drop out has implications for future research and for policy and practice. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Aspects of sleep disorders in children and adolescents

PubMed Central

Stores, Gregory

2009-01-01

Sleep disorders in children and adolescents is a topic that has been, and remains, neglected in both public health education and professional training. Although much knowledge has been accumulated in recent times, it has been poorly disseminated and, therefore, relatively little is put into practice. Only some general issues can be discussed in this article. The aspects chosen relate mainly to clinical practice, but they also have relevance for research. They concern various differences between sleep disorders in children and those in adults, the occurrence of such disorders in young people, their effects on psychological and physical development, the essential (but often ignored) distinction between sleep problems and their underlying causes (ie, sleep disorders), types of sleep disturbance encountered at different ages during development, and the differential diagnosis of certain parasomnias that are at particular risk of being confused with each other. PMID:19432390

Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration

PubMed Central

Wertheimer, Tobias; Velardi, Enrico; Tsai, Jennifer; Cooper, Kirsten; Xiao, Shiyun; Kloss, Christopher C.; Ottmüller, Katja J.; Mokhtari, Zeinab; Brede, Christian; deRoos, Paul; Kinsella, Sinéad; Palikuqi, Brisa; Ginsberg, Michael; Young, Lauren F.; Kreines, Fabiana; Lieberman, Sophia R.; Lazrak, Amina; Guo, Peipei; Malard, Florent; Smith, Odette M.; Shono, Yusuke; Jenq, Robert R.; Hanash, Alan M.; Nolan, Daniel J.; Butler, Jason M.; Beilhack, Andreas; Manley, Nancy R.; Rafii, Shahin; Dudakov, Jarrod A; van den Brink, Marcel RM

2018-01-01

The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. Here we show that thymic endothelial cells (ECs) comprise a critical pathway of regeneration, via their production of BMP4. ECs increased their production of BMP4 after thymic damage, and abrogating BMP4 signalling or production by either pharmacologic or genetic inhibition impaired thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to increase their expression of Foxn1, a key transcription factor involved in TEC development, maintenance and regeneration; and its downstream targets such as Dll4, itself a key mediator of thymocyte development and regeneration. These studies demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration and offer a potential clinical approach to enhance T cell immunity. PMID:29330161

A new simplex chemometric approach to identify olive oil blends with potentially high traceability.

PubMed

Semmar, N; Laroussi-Mezghani, S; Grati-Kamoun, N; Hammami, M; Artaud, J

2016-10-01

Olive oil blends (OOBs) are complex matrices combining different cultivars at variable proportions. Although qualitative determinations of OOBs have been subjected to several chemometric works, quantitative evaluations of their contents remain poorly developed because of traceability difficulties concerning co-occurring cultivars. Around this question, we recently published an original simplex approach helping to develop predictive models of the proportions of co-occurring cultivars from chemical profiles of resulting blends (Semmar & Artaud, 2015). Beyond predictive model construction and validation, this paper presents an extension based on prediction errors' analysis to statistically define the blends with the highest predictability among all the possible ones that can be made by mixing cultivars at different proportions. This provides an interesting way to identify a priori labeled commercial products with potentially high traceability taking into account the natural chemical variability of different constitutive cultivars. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seeking Structural Specificity: Direct Modulation of Pentameric Ligand-Gated Ion Channels by Alcohols and General Anesthetics

PubMed Central

Trudell, James R.; Harris, R. Adron

2014-01-01

Alcohols and other anesthetic agents dramatically alter neurologic function in a wide range of organisms, yet their molecular sites of action remain poorly characterized. Pentameric ligand-gated ion channels, long implicated in important direct effects of alcohol and anesthetic binding, have recently been illuminated in renewed detail thanks to the determination of atomic-resolution structures of several family members from lower organisms. These structures provide valuable models for understanding and developing anesthetic agents and for allosteric modulation in general. This review surveys progress in this field from function to structure and back again, outlining early evidence for relevant modulation of pentameric ligand-gated ion channels and the development of early structural models for ion channel function and modulation. We highlight insights and challenges provided by recent crystal structures and resulting simulations, as well as opportunities for translation of these newly detailed models back to behavior and therapy. PMID:24515646

Epidemic cholera spreads like wildfire

PubMed Central

Roy, Manojit; Zinck, Richard D.; Bouma, Menno J.; Pascual, Mercedes

2014-01-01

Cholera is on the rise globally, especially epidemic cholera which is characterized by intermittent and unpredictable outbreaks that punctuate periods of regional disease fade-out. These epidemic dynamics remain however poorly understood. Here we examine records for epidemic cholera over both contemporary and historical timelines, from Africa (1990–2006) and former British India (1882–1939). We find that the frequency distribution of outbreak size is fat-tailed, scaling approximately as a power-law. This pattern which shows strong parallels with wildfires is incompatible with existing cholera models developed for endemic regions, as it implies a fundamental role for stochastic transmission and local depletion of susceptible hosts. Application of a recently developed forest-fire model indicates that epidemic cholera dynamics are located above a critical phase transition and propagate in similar ways to aggressive wildfires. These findings have implications for the effectiveness of control measures and the mechanisms that ultimately limit the size of outbreaks. PMID:24424273

Epidemic cholera spreads like wildfire.

PubMed

Roy, Manojit; Zinck, Richard D; Bouma, Menno J; Pascual, Mercedes

2014-01-15

Cholera is on the rise globally, especially epidemic cholera which is characterized by intermittent and unpredictable outbreaks that punctuate periods of regional disease fade-out. These epidemic dynamics remain however poorly understood. Here we examine records for epidemic cholera over both contemporary and historical timelines, from Africa (1990-2006) and former British India (1882-1939). We find that the frequency distribution of outbreak size is fat-tailed, scaling approximately as a power-law. This pattern which shows strong parallels with wildfires is incompatible with existing cholera models developed for endemic regions, as it implies a fundamental role for stochastic transmission and local depletion of susceptible hosts. Application of a recently developed forest-fire model indicates that epidemic cholera dynamics are located above a critical phase transition and propagate in similar ways to aggressive wildfires. These findings have implications for the effectiveness of control measures and the mechanisms that ultimately limit the size of outbreaks.

SCFSlmb E3 ligase-mediated degradation of Expanded is inhibited by the Hippo pathway in Drosophila

PubMed Central

Zhang, Hongtao; Li, Changqing; Chen, Hanqing; Wei, Chuanxian; Dai, Fei; Wu, Honggang; Dui, Wen; Deng, Wu-Min; Jiao, Renjie

2015-01-01

Deregulation of the evolutionarily conserved Hippo pathway has been implicated in abnormal development of animals and in several types of cancer. One mechanism of Hippo pathway regulation is achieved by controlling the stability of its regulatory components. However, the executive E3 ligases that are involved in this process, and how the process is regulated, remain poorly defined. In this study, we identify, through a genetic candidate screen, the SCFSlmb E3 ligase as a novel negative regulator of the Hippo pathway in Drosophila imaginal tissues via mediation of the degradation of Expanded (Ex). Mechanistic study shows that Slmb-mediated degradation of Ex is inhibited by the Hippo signaling. Considering the fact that Hippo signaling suppresses the transcription of ex, we propose that the Hippo pathway employs a double security mechanism to ensure fine-tuned homeostasis during development. PMID:25522691

Community-based technology transfer in rural aquaculture: the case of mudcrab Scylla serrata nursery in ponds in Northern Samar, Central Philippines.

PubMed

Baticados, Didi B; Agbayani, Renato F; Quinitio, Emilia T

2014-12-01

Finding aquaculture development approaches to open up livelihood opportunities for the rural poor and in mainstreaming smallholder fish farmers to reduce poverty remain a challenge. This paper examines the community-based technology transfer mechanism of mudcrab nursery in ponds and its socioeconomic impacts on smallholder mudcrab growers in Northern Samar, Philippines. Results indicated that the technology is a viable enterprise done by a straight culture system method, which is the rearing of crablets from <1.0 to 4.0 cm for 42 days, or by-phases. However, technology adoption hinges on many factors like area ownership, farm distance from household, and market including the type of strategy needed to enhance technology uptake. Collaboration among research and development institutions and local partners is critical in training and empowering rural communities to adopt aquaculture technologies.

Risk analysis and bovine tuberculosis, a re-emerging zoonosis.

PubMed

Etter, Eric; Donado, Pilar; Jori, Ferran; Caron, Alexandre; Goutard, Flavie; Roger, François

2006-10-01

The widespread of immunodeficiency with AIDS, the consequence of poverty on sanitary protection and information at both individual and state levels lead control of tuberculosis (TB) to be one of the priorities of World Health Organization programs. The impact of bovine tuberculosis (BTB) on humans is poorly documented. However, BTB remains a major problem for livestock in developing countries particularly in Africa and wildlife is responsible for the failure of TB eradication programs. In Africa, the consumption of raw milk and raw meat, and the development of bushmeat consumption as a cheap source of proteins, represent one of the principal routes for human contaminations with BTB. The exploration of these different pathways using tools as participatory epidemiology allows the risk analysis of the impact of BTB on human health in Africa. This analysis represents a management support and decision tool in the study and the control of zoonotic BTB.

Developmental potential in the first 5 years for children in developing countries

PubMed Central

Grantham-McGregor, Sally; Cheung, Yin Bun; Cueto, Santiago; Glewwe, Paul; Richter, Linda; Strupp, Barbara

2007-01-01

Summary Many children younger than 5 years in developing countries are exposed to multiple risks, including poverty, malnutrition, poor health, and unstimulating home environments, which detrimentally affect their cognitive, motor, and social-emotional development. There are few national statistics on the development of young children in developing countries. We therefore identified two factors with available worldwide data—the prevalence of early childhood stunting and the number of people living in absolute poverty—to use as indicators of poor development. We show that both indicators are closely associated with poor cognitive and educational performance in children and use them to estimate that over 200 million children under 5 years are not fulfilling their developmental potential. Most of these children live in south Asia and sub-Saharan Africa. These disadvantaged children are likely to do poorly in school and subsequently have low incomes, high fertility, and provide poor care for their children, thus contributing to the intergenerational transmission of poverty. PMID:17208643

Eggs: the uncracked potential for improving maternal and young child nutrition among the world's poor.

PubMed

Iannotti, Lora L; Lutter, Chessa K; Bunn, David A; Stewart, Christine P

2014-06-01

Eggs have been consumed throughout human history, though the full potential of this nutritionally complete food has yet to be realized in many resource-poor settings around the world. Eggs provide essential fatty acids, proteins, choline, vitamins A and B12 , selenium, and other critical nutrients at levels above or comparable to those found in other animal-source foods, but they are relatively more affordable. Cultural beliefs about the digestibility and cleanliness of eggs, as well as environmental concerns arising from hygiene practices and toxin exposures, remain as barriers to widespread egg consumption. There is also regional variability in egg intake levels. In Latin American countries, on average, greater proportions of young children consume eggs than in Asian or African countries. In China and Indonesia, nutrition education and social marketing have been associated with greater amounts of eggs in the diets of young children, though generally, evidence from interventions is minimal. Homestead chicken-and-egg production with appropriate vaccination, extension service, and other supports can simultaneously address poverty and nutrition in very poor rural households. With undernutrition remaining a significant problem in many parts of the world, eggs may be an uncracked part of the solution. © 2014 International Life Sciences Institute.

The Long-Term Effects of the Periconceptional Period on Embryo Epigenetic Profile and Phenotype; The Paternal Role and His Contribution, and How Males Can Affect Offspring's Phenotype/Epigenetic Profile.

PubMed

Lucas, Emma S; Watkins, Adam J

2017-01-01

The number of adults afflicted with heart disease, obesity and diabetes, central components of metabolic disorder, has grown rapidly in recent decades, affecting up to one quarter of the world's population. Typically, these diseases are attributed to lifestyle factors such as poor diet, lack of exercise and smoking. However, studies have now identified strong associations between patterns of growth during foetal and neonatal life and an increase predisposition towards developing heart disease, obesity and diabetes in adult life. While the connection between a mother's diet and the long-term health of her offspring has been studied in great detail, our understanding of whether offspring health might be affected by a father's diet remains limited. Greater insight into the impact that paternal nutrition has on sperm quality, epigenetic status and potential offspring programming mechanisms is needed to redress this parental-programming knowledge imbalance. Disturbances in paternal reproductive epigenetic status represents one key mechanism linking paternal diet with the programing of offspring development and adult health, as many enzymatic processes involved in epigenetic regulation use metabolic intermediates to modify DNA and histones. Here, poor paternal nutrition could result in perturbed sperm and testicular epigenetic status, impacting on post-fertilisation gene transcriptional regulation and protein expression in offspring tissues, resulting in increased incidences of metabolic disorder in adult life.

Priorities for the poor: a conceptual framework for policy analysis.

PubMed

Pleskovic, B; Sivitanides, P

1993-04-01

A number of poverty alleviation strategies have been developed over the last 2 decades. While these varies approaches have helped stimulate and guide policymaker consideration of the issue, poverty nonetheless remains an enormous problem in most developing countries. Budgetary and administrative constraints demand that the comprehensive basic needs of the poor not be addressed concurrently. Poverty policy and practice will instead be most effective if needs and expenditures identified by evaluating social indicators and social expenditure programs are prioritized. Applied to the case of Morocco, a conceptual framework is presented for identifying priority poverty problems and social expenditure policies. The methodology allows one to sort out critical poverty problems and analyze their causes by using aggregate, territorial, and references indicators; provides a framework for understanding and evaluating the interlinked effects of investments in social sectors; and introduces a tool for selecting cost-effective policy packages for poverty alleviation. The methodology could, however, be refined by improving the derivation of reference indicators by accounting for predetermined government objectives. The estimation of direct and indirect effects of investments in the critical poverty sectors could also be improved. Additional research is called for to determine how econometric models should be structured to aid in quantifying Morocco's SIO tables and how the estimated linkages may be used to extend and improve the cost-benefit analysis of antipoverty policies.

Monitoring water quality in a hypereutrophic reservoir using Landsat ETM+ and OLI sensors: how transferable are the water quality algorithms?

PubMed

Deutsch, Eliza S; Alameddine, Ibrahim; El-Fadel, Mutasem

2018-02-15

The launch of the Landsat 8 in February 2013 extended the life of the Landsat program to over 40 years, increasing the value of using Landsat to monitor long-term changes in the water quality of small lakes and reservoirs, particularly in poorly monitored freshwater systems. Landsat-based water quality hindcasting often incorporate several Landsat sensors in an effort to increase the temporal range of observations; yet the transferability of water quality algorithms across sensors remains poorly examined. In this study, several empirical algorithms were developed to quantify chlorophyll-a, total suspended matter (TSM), and Secchi disk depth (SDD) from surface reflectance measured by Landsat 7 ETM+ and Landsat 8 OLI sensors. Sensor-specific multiple linear regression models were developed by correlating in situ water quality measurements collected from a semi-arid eutrophic reservoir with band ratios from Landsat ETM+ and OLI sensors, along with ancillary data (water temperature and seasonality) representing ecological patterns in algae growth. Overall, ETM+-based models outperformed (adjusted R 2 chlorophyll-a = 0.70, TSM = 0.81, SDD = 0.81) their OLI counterparts (adjusted R 2 chlorophyll-a = 0.50, TSM = 0.58, SDD = 0.63). Inter-sensor differences were most apparent for algorithms utilizing the Blue spectral band. The inclusion of water temperature and seasonality improved the power of TSM and SDD models.

Classical Galactosaemia in Ireland: incidence, complications and outcomes of treatment.

PubMed

Coss, K P; Doran, P P; Owoeye, C; Codd, M B; Hamid, N; Mayne, P D; Crushell, E; Knerr, I; Monavari, A A; Treacy, E P

2013-01-01

Newborn screening for the inborn error of metabolism, classical galactosaemia prevents life-threatening complications in the neonatal period. It does not however influence the development of long-term complications and the complex pathophysiology of this rare disease remains poorly understood. The objective of this study was to report the development of a healthcare database (using Distiller Version 2.1) to review the epidemiology of classical galactosaemia in Ireland since initiation of newborn screening in 1972 and the long-term clinical outcomes of all patients attending the National Centre for Inherited Metabolic Disorders (NCIMD). Since 1982, the average live birth incidence rate of classical galactosaemia in the total Irish population was approximately 1:16,476 births. This reflects a high incidence in the Irish 'Traveller' population, with an estimated birth incidence of 1:33,917 in the non-Traveller Irish population. Despite early initiation of treatment (dietary galactose restriction), the long-term outcomes of classical galactosaemia in the Irish patient population are poor; 30.6 % of patients ≥ 6 yrs have IQs <70, 49.6 % of patients ≥ 2.5 yrs have speech or language impairments and 91.2 % of females ≥ 13 yrs suffer from hypergonadotrophic hypogonadism (HH) possibly leading to decreased fertility. These findings are consistent with the international experience. This emphasizes the requirement for continued clinical research in this complex disorder.

Urbanization and health in developing countries.

PubMed

Harpham, T; Stephens, C

1991-01-01

In developing countries the level of urbanization is expected to increase to 39.5% by the end of this century and to 56.9% by 2025. The number of people living in slums and shanty towns represent about one-third of the people living in cities in developing countries. This article focuses upon these poor urban populations and comments upon their lifestyle and their exposure to hazardous environmental conditions which are associated with particular patterns of morbidity and mortality. The concept of marginality has been used to describe the lifestyle of the urban poor in developing countries. This concept is critically examined and it is argued that any concept of the urban poor in developing countries being socially, economically or politically marginal is a myth. However, it can certainly be claimed that in health terms the urban poor are marginal as demonstrated by some of the studies reviewed in this article. Most studies of the health of the urban poor in developing countries concentrate on the environmental conditions in which they live. The environmental conditions of the urban poor are one of the main hazards of the lifestyle of poor urban residents. However, other aspects of their way of life, or lifestyle, have implications for their health. Issues such as smoking, diet, alcohol and drug abuse, and exposure to occupational hazards, have received much less attention in the literature and there is an urgent need for more research in these areas.

Life history linked to immune investment in developing amphibians.

PubMed

Woodhams, Douglas C; Bell, Sara C; Bigler, Laurent; Caprioli, Richard M; Chaurand, Pierre; Lam, Brianna A; Reinert, Laura K; Stalder, Urs; Vazquez, Victoria M; Schliep, Klaus; Hertz, Andreas; Rollins-Smith, Louise A

2016-01-01

The broad diversity of amphibian developmental strategies has been shaped, in part, by pathogen pressure, yet trade-offs between the rate of larval development and immune investment remain poorly understood. The expression of antimicrobial peptides (AMPs) in skin secretions is a crucial defense against emerging amphibian pathogens and can also indirectly affect host defense by influencing the composition of skin microbiota. We examined the constitutive or induced expression of AMPs in 17 species at multiple life-history stages. We found that AMP defenses in tadpoles of species with short larval periods (fast pace of life) were reduced in comparison with species that overwinter as tadpoles and grow to a large size. A complete set of defensive peptides emerged soon after metamorphosis. These findings support the hypothesis that species with a slow pace of life invest energy in AMP production to resist potential pathogens encountered during the long larval period, whereas species with a fast pace of life trade this investment in defense for more rapid growth and development.

Preclinical and clinical development of siRNA-based therapeutics

PubMed Central

Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L.; Sood, Anil K.; Lopez-Berestein, Gabriel

2015-01-01

Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. PMID:25666164

Fluid pressure and shear zone development over the locked to slow slip region in Cascadia.

PubMed

Audet, Pascal; Schaeffer, Andrew J

2018-03-01

At subduction zones, the deep seismogenic transition from a frictionally locked to steady sliding interface is thought to primarily reflect changes in rheology and fluid pressure and is generally located offshore. The development of fluid pressures within a seismic low-velocity layer (LVL) remains poorly constrained due to the scarcity of dense, continuous onshore-offshore broadband seismic arrays. We image the subducting Juan de Fuca oceanic plate in northern Cascadia using onshore-offshore teleseismic data and find that the signature of the LVL does not extend into the locked zone. Thickening of the LVL down dip where viscous creep dominates suggests that it represents the development of an increasingly thick and fluid-rich shear zone, enabled by fluid production in subducting oceanic crust. Further down dip, episodic tremor, and slip events occur in a region inferred to have locally increased fluid pressures, in agreement with electrical resistivity structure and numerical models of fault slip.

Fluid pressure and shear zone development over the locked to slow slip region in Cascadia

PubMed Central

Audet, Pascal; Schaeffer, Andrew J.

2018-01-01

At subduction zones, the deep seismogenic transition from a frictionally locked to steady sliding interface is thought to primarily reflect changes in rheology and fluid pressure and is generally located offshore. The development of fluid pressures within a seismic low-velocity layer (LVL) remains poorly constrained due to the scarcity of dense, continuous onshore-offshore broadband seismic arrays. We image the subducting Juan de Fuca oceanic plate in northern Cascadia using onshore-offshore teleseismic data and find that the signature of the LVL does not extend into the locked zone. Thickening of the LVL down dip where viscous creep dominates suggests that it represents the development of an increasingly thick and fluid-rich shear zone, enabled by fluid production in subducting oceanic crust. Further down dip, episodic tremor, and slip events occur in a region inferred to have locally increased fluid pressures, in agreement with electrical resistivity structure and numerical models of fault slip. PMID:29536046

Neural correlates of socioeconomic status in the developing human brain.

PubMed

Noble, Kimberly G; Houston, Suzanne M; Kan, Eric; Sowell, Elizabeth R

2012-07-01

Socioeconomic disparities in childhood are associated with remarkable differences in cognitive and socio-emotional development during a time when dramatic changes are occurring in the brain. Yet, the neurobiological pathways through which socioeconomic status (SES) shapes development remain poorly understood. Behavioral evidence suggests that language, memory, social-emotional processing, and cognitive control exhibit relatively large differences across SES. Here we investigated whether volumetric differences could be observed across SES in several neural regions that support these skills. In a sample of 60 socioeconomically diverse children, highly significant SES differences in regional brain volume were observed in the hippocampus and the amygdala. In addition, SES × age interactions were observed in the left superior temporal gyrus and left inferior frontal gyrus, suggesting increasing SES differences with age in these regions. These results were not explained by differences in gender, race or IQ. Likely mechanisms include differences in the home linguistic environment and exposure to stress, which may serve as targets for intervention at a time of high neural plasticity. © 2012 Blackwell Publishing Ltd.

A chemical screen in zebrafish embryonic cells establishes that Akt activation is required for neural crest development

PubMed Central

Ciarlo, Christie; Kaufman, Charles K; Kinikoglu, Beste; Michael, Jonathan; Yang, Song; D′Amato, Christopher; Blokzijl-Franke, Sasja; den Hertog, Jeroen; Schlaeger, Thorsten M; Zhou, Yi; Liao, Eric

2017-01-01

The neural crest is a dynamic progenitor cell population that arises at the border of neural and non-neural ectoderm. The inductive roles of FGF, Wnt, and BMP at the neural plate border are well established, but the signals required for subsequent neural crest development remain poorly characterized. Here, we conducted a screen in primary zebrafish embryo cultures for chemicals that disrupt neural crest development, as read out by crestin:EGFP expression. We found that the natural product caffeic acid phenethyl ester (CAPE) disrupts neural crest gene expression, migration, and melanocytic differentiation by reducing Sox10 activity. CAPE inhibits FGF-stimulated PI3K/Akt signaling, and neural crest defects in CAPE-treated embryos are suppressed by constitutively active Akt1. Inhibition of Akt activity by constitutively active PTEN similarly decreases crestin expression and Sox10 activity. Our study has identified Akt as a novel intracellular pathway required for neural crest differentiation. PMID:28832322

Enhanced laboratory capacity development: a boost for effective tuberculosis control in resource-limited settings.

PubMed

Alabi, Abraham Sunday; Traoré, Afsatou Ndama; Loembe, Marguerite Massinga; Ateba-Ngoa, Ulysse; Frank, Matthias; Adegnika, Ayola Akim; Lell, Bertrand; Mahoumbou, Jocelyn; Köhler, Carsten; Kremsner, Peter Gottfried; Grobusch, Martin Peter

2017-03-01

Both routine and research tuberculosis (TB) laboratory capacity urgently need to be expanded in large parts of Sub-Saharan Africa. In 2009, the Centre de Recherches Médicales de Lambaréné (CERMEL) took a strategic decision to expand its activities by building TB laboratory capacity to address research questions and to improve routine diagnostic and treatment capacity. Over the past 7 years, a standard laboratory has been developed that is contributing significantly to TB diagnosis, treatment, and control in Gabon; training has also been provided for TB research staff in Central Africa. CERMEL has a cordial relationship with the Gabon National TB Control Programme (PNLT), which has culminated in a successful Global Fund joint application. This endeavour is considered a model for similar developments needed in areas of high TB prevalence and where TB control remains poor to date. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Family- and Neighborhood-Level Factors as Predictors of Conduct Problems in School among Young, Urban, Minority Children

PubMed Central

Palamar, Joseph J.; Calzada, Esther J.; Theise, Rachelle; Huang, Keng-Yen; Petkova, Eva; Brotman, Laurie Miller

2017-01-01

Minority children attending schools in urban socioeconomically disadvantaged neighborhoods are at high risk for conduct problems. Although a number of family and neighborhood characteristics have been implicated in the onset and progression of conduct problems, there remains incomplete understanding of the unique contributions of poverty-related factors early in development. This prospective study of 298 black public school children considered family- and neighborhood-level predictors of teacher-reported conduct problems from pre-kindergarten through first grade. Results from multi-level analyses indicate that percentage of poor residents in a student’s neighborhood made a robust independent contribution to the prediction of development of conduct problems, over and above family- and other neighborhood-level demographic factors. For children of single parents, the percentage of black residents in the neighborhood also predicted the development of conduct problems. School-based interventions to prevent conduct problems should consider impact for children at highest risk based on neighborhood poverty. PMID:24673380

Family- and Neighborhood-Level Factors as Predictors of Conduct Problems in School among Young, Urban, Minority Children.

PubMed

Palamar, Joseph J; Calzada, Esther J; Theise, Rachelle; Huang, Keng-Yen; Petkova, Eva; Brotman, Laurie Miller

2015-01-01

Minority children attending schools in urban socioeconomically disadvantaged neighborhoods are at high risk for conduct problems. Although a number of family and neighborhood characteristics have been implicated in the onset and progression of conduct problems, there remains incomplete understanding of the unique contributions of poverty-related factors early in development. This prospective study of 298 black public school children considered family- and neighborhood-level predictors of teacher-reported conduct problems from pre-kindergarten through first grade. Results from multi-level analyses indicate that percentage of poor residents in a student's neighborhood made a robust independent contribution to the prediction of development of conduct problems, over and above family- and other neighborhood-level demographic factors. For children of single parents, the percentage of black residents in the neighborhood also predicted the development of conduct problems. School-based interventions to prevent conduct problems should consider impact for children at highest risk based on neighborhood poverty.

Transcriptional regulation of intermediate progenitor cell generation during hippocampal development

PubMed Central

Harris, Lachlan; Zalucki, Oressia; Gobius, Ilan; McDonald, Hannah; Osinki, Jason; Harvey, Tracey J.; Essebier, Alexandra; Vidovic, Diana; Gladwyn-Ng, Ivan; Burne, Thomas H.; Heng, Julian I.; Richards, Linda J.; Gronostajski, Richard M.

2016-01-01

During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development. PMID:27965439

Preclinical and clinical development of siRNA-based therapeutics.

PubMed

Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L; Sood, Anil K; Lopez-Berestein, Gabriel

2015-06-29

The discovery of RNA interference, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

The complexities of malaria disease manifestations with a focus on asymptomatic malaria

PubMed Central

2012-01-01

Malaria is a serious parasitic disease in the developing world, causing high morbidity and mortality. The pathogenesis of malaria is complex, and the clinical presentation of disease ranges from severe and complicated, to mild and uncomplicated, to asymptomatic malaria. Despite a wealth of studies on the clinical severity of disease, asymptomatic malaria infections are still poorly understood. Asymptomatic malaria remains a challenge for malaria control programs as it significantly influences transmission dynamics. A thorough understanding of the interaction between hosts and parasites in the development of different clinical outcomes is required. In this review, the problems and obstacles to the study and control of asymptomatic malaria are discussed. The human and parasite factors associated with differential clinical outcomes are described and the management and treatment strategies for the control of the disease are outlined. Further, the crucial gaps in the knowledge of asymptomatic malaria that should be the focus of future research towards development of more effective malaria control strategies are highlighted. PMID:22289302

The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus.

PubMed

Martin, E Anne; Muralidhar, Shruti; Wang, Zhirong; Cervantes, Diégo Cordero; Basu, Raunak; Taylor, Matthew R; Hunter, Jennifer; Cutforth, Tyler; Wilke, Scott A; Ghosh, Anirvan; Williams, Megan E

2015-11-17

Synaptic target specificity, whereby neurons make distinct types of synapses with different target cells, is critical for brain function, yet the mechanisms driving it are poorly understood. In this study, we demonstrate Kirrel3 regulates target-specific synapse formation at hippocampal mossy fiber (MF) synapses, which connect dentate granule (DG) neurons to both CA3 and GABAergic neurons. Here, we show Kirrel3 is required for formation of MF filopodia; the structures that give rise to DG-GABA synapses and that regulate feed-forward inhibition of CA3 neurons. Consequently, loss of Kirrel3 robustly increases CA3 neuron activity in developing mice. Alterations in the Kirrel3 gene are repeatedly associated with intellectual disabilities, but the role of Kirrel3 at synapses remained largely unknown. Our findings demonstrate that subtle synaptic changes during development impact circuit function and provide the first insight toward understanding the cellular basis of Kirrel3-dependent neurodevelopmental disorders.

Macrophage sphingolipids are essential for the entry of mycobacteria.

PubMed

Viswanathan, Gopinath; Jafurulla, Md; Kumar, G Aditya; Raghunand, Tirumalai R; Chattopadhyay, Amitabha

2018-07-01

Mycobacteria are intracellular pathogens that can invade and survive within host macrophages. Mycobacterial infections remain a major cause of mortality and morbidity worldwide, with serious concerns of emergence of multi and extensively drug-resistant tuberculosis. While significant advances have been made in identifying mycobacterial virulence determinants, the detailed molecular mechanism of internalization of mycobacteria into host cells remains poorly understood. Although several studies have highlighted the crucial role of sphingolipids in mycobacterial growth, persistence and establishment of infection, the role of sphingolipids in the entry of mycobacteria into host cells is not known. In this work, we explored the role of host membrane sphingolipids in the entry of Mycobacterium smegmatis into J774A.1 macrophages. Our results show that metabolic depletion of sphingolipids in host macrophages results in a significant reduction in the entry of M. smegmatis. Importantly, the entry of Escherichia coli into host macrophages under similar conditions remained invariant, implying the specificity of the requirement of sphingolipids in mycobacterial entry. To the best of our knowledge, our results constitute the first report demonstrating the role of host macrophage sphingolipids in the entry of mycobacteria. Our results could help in the development of novel therapeutic strategies targeting sphingolipid-mediated entry of mycobacteria into host cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Comments on the article 'Defining hormesis', by EJ Calabrese and LA Baldwin.

PubMed

Upton, A C

2002-02-01

In view of the diversity of biological responses and the extent to which many of them remain poorly elucidated, there is merit in the suggestion by Calabrese and Baldwin that the term 'hormesis' should be applicable to those adaptive responses that are characterized by biphasic dose-response relationships, without reference to any associated beneficial or harmful effects. Whether the dose-response relationships for radiation-induced mutations and chromosome aberrations are biphasic in nature is an important question that remains to be resolved.

Bending Genders: The Biology of Natural Sex Change in Fish.

PubMed

Todd, Erica V; Liu, Hui; Muncaster, Simon; Gemmell, Neil J

2016-01-01

Sexual fate is no longer seen as an irreversible deterministic switch set during early embryonic development but as an ongoing battle for primacy between male and female developmental trajectories. That sexual fate is not final and must be actively maintained via continuous suppression of the opposing sexual network creates the potential for flexibility into adulthood. In many fishes, sexuality is not only extremely plastic, but sex change is a usual and adaptive part of the life cycle. Sequential hermaphrodites begin life as one sex, changing sometime later to the other, and include species capable of protandrous (male-to-female), protogynous (female-to-male), or serial (bidirectional) sex change. Natural sex change involves coordinated transformations across multiple biological systems, including behavioural, anatomical, neuroendocrine, and molecular axes. We here review the biological processes underlying this amazing transformation, focussing particularly on its molecular basis, which remains poorly understood, but where new genomic technologies are significantly advancing our understanding of how sex change is initiated and progressed at the molecular level. Knowledge of how a usually committed developmental process remains plastic in sequentially hermaphroditic fishes is relevant to understanding the evolution and functioning of sexual developmental systems in vertebrates generally, as well as pathologies of sexual development in humans. © 2016 S. Karger AG, Basel.

Characterization of a Weak Allele of Zebrafish cloche Mutant

PubMed Central

Ma, Ning; Huang, Zhibin; Chen, Xiaohui; He, Fei; Wang, Kun; Liu, Wei; Zhao, Linfeng; Xu, Xiangmin; Liao, Wangjun; Ruan, Hua; Luo, Shenqiu; Zhang, Wenqing

2011-01-01

Hematopoiesis is a complicated and dynamic process about which the molecular mechanisms remain poorly understood. Danio rerio (zebrafish) is an excellent vertebrate system for studying hematopoiesis and developmental mechanisms. In the previous study, we isolated and identified a cloche 172 (clo 172) mutant, a novel allele compared to the original cloche (clo) mutant, through using complementation test and initial mapping. Here, according to whole mount in-situ hybridization, we report that the endothelial cells in clo 172 mutant embryos, although initially developed, failed to form the functional vascular system eventually. In addition, further characterization indicates that the clo 172 mutant exhibited weaker defects instead of completely lost in primitive erythroid cells and definitive hematopoietic cells compared with the clo s5 mutant. In contrast, primitive myeloid cells were totally lost in clo 172 mutant. Furthermore, these reappeared definitive myeloid cells were demonstrated to initiate from the remaining hematopoietic stem cells (HSCs) in clo 172 mutant, confirmed by the dramatic decrease of lyc in clo 172 runx1w84x double mutant. Collectively, the clo 172 mutant is a weak allele compared to the clo s5 mutant, therefore providing a model for studying the early development of hematopoietic and vascular system, as well as an opportunity to further understand the function of the cloche gene. PMID:22132109

Passage of American shad: paradigms and realities

USGS Publications Warehouse

Haro, Alex; Castro-Santos, Theodore

2012-01-01

Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

Management of colonic diverticular disease with poorly absorbed antibiotics and other therapies

PubMed Central

Sopeña, Federico; Lanas, Angel

2011-01-01

Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80–85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications. About 1–2% will require hospitalization and 0.5% will require surgery. Factors predicting the development of symptoms remain to be identified. However, it is generally recognized that diverticular disease is probably related to complex interactions between colon structure, intestinal motility, diet, and genetic features. Epidemiologic studies have demonstrated an association between diverticulosis and diets that are low in fiber and high in refined carbohydrates. Although the causes of symptom development are still unclear, it is thought that previous episodes of intestinal inflammation may play a role. Changes in intestinal microflora could be one of the putative mechanisms responsible for low-grade inflammation. In patients with uncomplicated diverticulosis, a diet abundant in fruit and vegetables is recommended. The current therapeutic approaches in preventing recurrence of symptoms are based on nonabsorbable antibiotics, mesalazine, and/or probiotics. Cyclic rifaximin administration seems to be an adequate approach to relieving symptoms and preventing acute diverticulitis in patients with symptomatic diverticulosis. PMID:22043229

Refugee camps, fire disasters and burn injuries.

PubMed

Atiyeh, B S; Gunn, S W A

2017-09-30

In the past five years, no fewer than 15 conflicts have brought unspeakable tragedy and misery to millions across the world. At present, nearly 20 people are forcibly displaced every minute as a result of conflict or persecution, representing a crisis of historic proportions. Many displaced persons end up in camps generally developing in an impromptu fashion, and are totally dependent on humanitarian aid. The precarious condition of temporary installations puts the nearly 700 refugee camps worldwide at high risk of disease, child soldier and terrorist recruitment, and physical and sexual violence. Poorly planned, densely packed refugee settlements are also one of the most pathogenic environments possible, representing high risk for fires with potential for uncontrolled fire spread and development over sometimes quite large areas. Moreover, providing healthcare to refugees comes with its own unique challenges. Internationally recognized guidelines for minimum standards in shelters and settlements have been set, however they remain largely inapplicable. As for fire risk reduction, and despite the high number of fire incidents, it is not evident that fire safety can justify a higher priority. In that regard, a number of often conflicting influences will need to be considered. The greatest challenge remains in balancing the various risks, such as the need/cost of shelter against the fire risk/cost of fire protection.

NFIX Regulates Neural Progenitor Cell Differentiation During Hippocampal Morphogenesis

PubMed Central

Heng, Yee Hsieh Evelyn; McLeay, Robert C.; Harvey, Tracey J.; Smith, Aaron G.; Barry, Guy; Cato, Kathleen; Plachez, Céline; Little, Erica; Mason, Sharon; Dixon, Chantelle; Gronostajski, Richard M.; Bailey, Timothy L.; Richards, Linda J.; Piper, Michael

2014-01-01

Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix−/− mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix−/− mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix−/− mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure. PMID:23042739

Refugee camps, fire disasters and burn injuries

PubMed Central

Atiyeh, B.S.; Gunn, S.W.A.

2017-01-01

Summary In the past five years, no fewer than 15 conflicts have brought unspeakable tragedy and misery to millions across the world. At present, nearly 20 people are forcibly displaced every minute as a result of conflict or persecution, representing a crisis of historic proportions. Many displaced persons end up in camps generally developing in an impromptu fashion, and are totally dependent on humanitarian aid. The precarious condition of temporary installations puts the nearly 700 refugee camps worldwide at high risk of disease, child soldier and terrorist recruitment, and physical and sexual violence. Poorly planned, densely packed refugee settlements are also one of the most pathogenic environments possible, representing high risk for fires with potential for uncontrolled fire spread and development over sometimes quite large areas. Moreover, providing healthcare to refugees comes with its own unique challenges. Internationally recognized guidelines for minimum standards in shelters and settlements have been set, however they remain largely inapplicable. As for fire risk reduction, and despite the high number of fire incidents, it is not evident that fire safety can justify a higher priority. In that regard, a number of often conflicting influences will need to be considered. The greatest challenge remains in balancing the various risks, such as the need/cost of shelter against the fire risk/cost of fire protection. PMID:29849526

Brainstem encephalitis: etiologies, treatment, and predictors of outcome

PubMed Central

Tan, Ik Lin; Mowry, Ellen M.; Steele, Sonya U.; Pardo, Carlos A.; McArthur, Justin C.; Nath, Avindra

2016-01-01

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy. PMID:23749332

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

A Multilevel Investigation of Neighborhood Effects on Parental Warmth

ERIC Educational Resources Information Center

Tendulkar, Shalini A.; Buka, Stephen; Dunn, Erin C.; Subramanian, S. V.; Koenen, Karestan C.

2010-01-01

Although researchers recognize that social contexts shape parenting behaviors, the relationship between neighborhood environment and parenting remains poorly understood. To address this gap, we investigated the associations between compositional and contextual (structural, social, and safety) characteristics of neighborhoods and parental warmth.…

REVIEW OF QUANTITATIVE STANDARDS AND GUIDELINES FOR FUNGI IN INDOOR AIR

EPA Science Inventory

Exposure to fungal aerosols clearly causes human disease. However, methods for assessing exposure remain poorly understood, and guidelines for interpreting data are often contradictory. The purposes of this paper are to review and compare existing guidelines for indoor airborne...

Punishment and Welfare: Paternal Incarceration and Families' Receipt of Public Assistance.

PubMed

Sugie, Naomi F

2012-01-01

The United States criminal justice and welfare systems are two important government institutions in the lives of the poor. Despite many theoretical discussions about their relationship, their operation at the level of offenders and families remains poorly understood. This paper utilizes Fragile Families and Child Wellbeing data to examine how recent paternal incarceration is associated with families' receipt of TANF, food stamps, and Medicaid/SCHIP. Results robust to multiple tests find that incarceration is not related to subsequent TANF receipt but is significantly associated with increased receipt of food stamps and Medicaid/SCHIP. The findings suggest that greater government involvement among poor families is an unexpected consequence of mass imprisonment; however, increased participation does not include TANF-the cash assistance program of most concern to theorists.

The upside down world of diabetes care medical economics and what we might do to improve it.

PubMed

Harlan, David M; Hirsch, Irl B

2017-04-01

Increasingly over the past generation, the American healthcare delivery system has received consistently poor marks with regard to public health outcomes and costs. This review by two seasoned diabetes care providers is intended to shed light on the fundamental flaws we believe to underlie that poor performance, and suggest options for better outcomes and cost efficiencies. Despite major advances in diabetes management medications and tools, overall public health with regard to diabetes outcomes remains poor. Efforts focused on controlling costs appear to be exacerbating the problem. For chronic diseases like diabetes, fee-for-service care models are fundamentally flawed and predictably fail. We suggest that a major overhaul of the medical economics underlying diabetes care can improve patient outcomes and decrease costs.

C-GRApH: A Validated Scoring System for Early Stratification of Neurologic Outcome After Out-of-Hospital Cardiac Arrest Treated With Targeted Temperature Management.

PubMed

Kiehl, Erich L; Parker, Alex M; Matar, Ralph M; Gottbrecht, Matthew F; Johansen, Michelle C; Adams, Mark P; Griffiths, Lori A; Dunn, Steven P; Bidwell, Katherine L; Menon, Venu; Enfield, Kyle B; Gimple, Lawrence W

2017-05-20

Out-of-hospital cardiac arrest (OHCA) results in significant morbidity and mortality, primarily from neurologic injury. Predicting neurologic outcome early post-OHCA remains difficult in patients receiving targeted temperature management. Retrospective analysis was performed on consecutive OHCA patients receiving targeted temperature management (32-34°C) for 24 hours at a tertiary-care center from 2008 to 2012 (development cohort, n=122). The primary outcome was favorable neurologic outcome at hospital discharge, defined as cerebral performance category 1 to 2 (poor 3-5). Patient demographics, pre-OHCA diagnoses, and initial laboratory studies post-resuscitation were compared between favorable and poor neurologic outcomes with multivariable logistic regression used to develop a simple scoring system ( C-GRApH ). The C-GRApH score ranges 0 to 5 using equally weighted variables: ( C ): coronary artery disease, known pre-OHCA; ( G ): glucose ≥200 mg/dL; ( R ): rhythm of arrest not ventricular tachycardia/fibrillation; ( A ): age >45; ( pH ): arterial pH ≤7.0. A validation cohort (n=344) included subsequent patients from the initial site (n=72) and an external quaternary-care health system (n=272) from 2012 to 2014. The c-statistic for predicting neurologic outcome was 0.82 (0.74-0.90, P <0.001) in the development cohort and 0.81 (0.76-0.87, P <0.001) in the validation cohort. When subdivided by C-GRApH score, similar rates of favorable neurologic outcome were seen in both cohorts, 70% each for low (0-1, n=60), 22% versus 19% for medium (2-3, n=307), and 0% versus 2% for high (4-5, n=99) C-GRApH scores in the development and validation cohorts, respectively. C-GRApH stratifies neurologic outcomes following OHCA in patients receiving targeted temperature management (32-34°C) using objective data available at hospital presentation, identifying patient subsets with disproportionally favorable ( C-GRApH ≤1) and poor ( C-GRApH ≥4) prognoses. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

The Belgian commitment to pharmaceutical quality: a model policy to improve quality assurance of medicines available through humanitarian and development programs.

PubMed

Ravinetto, Raffaella; Roosen, Tim; Dujardin, Catherine

2018-01-01

Today, a combination of globalization of pharmaceutical production, lack of regulatory harmonization, and weakness of Medicines Regulatory Authorities, creates the "perfect conditions" for poor-quality medicine to circulate in the global market and to penetrate the less-regulated countries. Medicines regulation is the responsibility of the national regulatory authorities in the recipient country, but in the poorer countries, in practice, the responsibility of supply of quality-assured medicines is often taken by Non-Governmental Organizations and other implementers. But with some notable exceptions, many donors lack a pharmaceutical procurement policy with adequate quality requirements; and many implementers lack the skills and expertise needed to orient themselves in the complex web of global pharmaceutical supply. Thus, patients served by humanitarian or development programs may remain exposed to the risk of poor-quality medicines. When public money is used to purchase medicines for medical programs to be carried out overseas, adequate policies should be in place to assure that the same quality requirements are set that would be required for medicines marketed in the "donor" country. We will describe here a policy recently adopted in Belgium, i.e. the "Commitment to Quality Assurance for Pharmaceutical Products", signed in October 2017 by the Vice Prime Minister and Minister for Development Cooperation and 19 Belgian implementing agencies. By signing the new policy, the counterparts committed to ensure quality of medicines in the programs funded by Belgium's Official Development Assistance, and to build quality-assurance capacity in the recipient countries. Implementers are requested to integrate in their financing applications a section for pharmaceutical quality assurance, with a justified budget. They are also invited to consider how costs could be rationalized and mutualized by aligning the strengths of the various implementers. This model policy has the potential to be considered for adoption by other donors, to help to reduce the current multiple standards in pharmaceutical quality, and to contribute to protect vulnerable communities from the plague of poor-quality medicines. The online version of this article (10.1186/s40545-018-0136-z) contains an additional file, which is available to authorized users.

Mapping Proteome-Wide Interactions of Reactive Chemicals Using Chemoproteomic Platforms

PubMed Central

Counihan, Jessica L.; Ford, Breanna; Nomura, Daniel K.

2015-01-01

A large number of pharmaceuticals, endogenous metabolites, and environmental chemicals act through covalent mechanisms with protein targets. Yet, their specific interactions with the proteome still remain poorly defined for most of these reactive chemicals. Deciphering direct protein targets of reactive small-molecules is critical in understanding their biological action, off-target effects, potential toxicological liabilities, and development of safer and more selective agents. Chemoproteomic technologies have arisen as a powerful strategy that enable the assessment of proteome-wide interactions of these irreversible agents directly in complex biological systems. We review here several chemoproteomic strategies that have facilitated our understanding of specific protein interactions of irreversibly-acting pharmaceuticals, endogenous metabolites, and environmental electrophiles to reveal novel pharmacological, biological, and toxicological mechanisms. PMID:26647369

EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.

PubMed

Dong, Yixin; Isono, Kyo-Ichi; Ohbo, Kazuyuki; Endo, Takaho A; Ohara, Osamu; Maekawa, Mamiko; Toyama, Yoshiro; Ito, Chizuru; Toshimori, Kiyotaka; Helin, Kristian; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Yamagata, Kazutsune; Kitabayashi, Issay; Koseki, Haruhiko

2017-10-01

Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome. Copyright © 2017 American Society for Microbiology.

Roles for Hedgehog signaling in adult organ homeostasis and repair

PubMed Central

Petrova, Ralitsa; Joyner, Alexandra L.

2014-01-01

The hedgehog (HH) pathway is well known for its mitogenic and morphogenic functions during development, and HH signaling continues in discrete populations of cells within many adult mammalian tissues. Growing evidence indicates that HH regulates diverse quiescent stem cell populations, but the exact roles that HH signaling plays in adult organ homeostasis and regeneration remain poorly understood. Here, we review recently identified functions of HH in modulating the behavior of tissue-specific adult stem and progenitor cells during homeostasis, regeneration and disease. We conclude that HH signaling is a key factor in the regulation of adult tissue homeostasis and repair, acting via multiple different routes to regulate distinct cellular outcomes, including maintenance of plasticity, in a context-dependent manner. PMID:25183867

An analytical model of prominence dynamics

NASA Astrophysics Data System (ADS)

Routh, Swati; Saha, Snehanshu; Bhat, Atul; Sundar, M. N.

2018-01-01

Solar prominences are magnetic structures incarcerating cool and dense gas in an otherwise hot solar corona. Prominences can be categorized as quiescent and active. Their origin and the presence of cool gas (∼104 K) within the hot (∼106K) solar corona remains poorly understood. The structure and dynamics of solar prominences was investigated in a large number of observational and theoretical (both analytical and numerical) studies. In this paper, an analytic model of quiescent solar prominence is developed and used to demonstrate that the prominence velocity increases exponentially, which means that some gas falls downward towards the solar surface, and that Alfvén waves are naturally present in the solar prominences. These theoretical predictions are consistent with the current observational data of solar quiescent prominences.

Prostatic carcinosarcoma with lung metastases.

PubMed

Furlan, Stefanie R; Kang, David J; Armas, Armando

2013-01-01

Carcinosarcoma of the prostate is an uncommon malignancy with poor long-term prognosis. The cancer is typically discovered at an advanced stage, and with less than 100 reported cases, there is limited literature concerning treatment options. Our patient presented with a history of benign prostatic hypertrophy, erectile dysfunction, and nocturia. Biopsy of his prostate indicated that the patient had prostatic adenocarcinoma, but histopathology after prostatectomy revealed carcinosarcoma. It has been over six years since this patient's diagnosis of carcinosarcoma. Over this span of time, he has received a radical prostatectomy, radiotherapy, and androgen ablative therapy. The patient also developed multiple lung metastases that have been treated with video-assisted thoracic surgery and stereotactic body radiosurgery. Overall, he has remained unimpaired and in good condition despite his aggressive form of cancer.

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

PubMed

Paddock, Silvia; Goodman, Clifford; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel

2017-10-01

Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates.

Contaminated water as a source of Helicobacter pylori infection: A review

PubMed Central

Aziz, Ramy K.; Khalifa, Mohammed M.; Sharaf, Radwa R.

2013-01-01

Over the preceding years and to date, the definitive mode of human infection by Helicobacter pylori has remained largely unknown and has thus gained the interest of researchers around the world. Numerous studies investigated possible sources of transmission of this emerging carcinogenic pathogen that colonizes >50% of humans, in many of which contaminated water is mentioned as a major cause. The infection rate is especially higher in developing countries, where contaminated water, combined with social hardships and poor sanitary conditions, plays a key role. Judging from the growing global population and the changing climate, the rate is expected to rise. Here, we sum up the current views of the water transmission hypothesis, and we discuss its implications. PMID:26199743

Cocoa Bioactive Compounds: Significance and Potential for the Maintenance of Skin Health

PubMed Central

Scapagnini, Giovanni; Davinelli, Sergio; Di Renzo, Laura; De Lorenzo, Antonino; Olarte, Hector Hugo; Micali, Giuseppe; Cicero, Arrigo F.; Gonzalez, Salvador

2014-01-01

Cocoa has a rich history in human use. Skin is prone to the development of several diseases, and the mechanisms in the pathogenesis of aged skin are still poorly understood. However, a growing body of evidence from clinical and bench research has begun to provide scientific validation for the use of cocoa-derived phytochemicals as an effective approach for skin protection. Although the specific molecular and cellular mechanisms of the beneficial actions of cocoa phytochemicals remain to be elucidated, this review will provide an overview of the current literature emphasizing potential cytoprotective pathways modulated by cocoa and its polyphenolic components. Moreover, we will summarize in vivo studies showing that bioactive compounds of cocoa may have a positive impact on skin health. PMID:25116848

Mechanism of action of rapalogues: the antiangiogenic hypothesis.

PubMed

Faivre, Sandrine; Raymond, Eric

2008-11-01

mTOR interacts with multiple proteins involved in major signal transduction pathways controlling cell growth, proliferation, and apoptosis. mTOR is acknowledged to play major roles in cellular interplays between cancer and stroma cells, including endothelial cells. Rapalogues demonstrated antitumour activity in several hypervascularized tumours in clinical trials. Whether rapalogues directly affect cancer cells or other stroma cells in tumours remains poorly understood. Knowing whether rapalogues act directly against cancer cells and/or could be considered as antiangiogenic agents has major implications in terms of medical indications and may help to further improve their drug development. Herein, we hypothesize that current rapalogues demonstrating activity in hypervascularized tumours may primarily act through antiangiogenic effects in patients, a hypothesis that certainly requires further translational investigations.