Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.

PubMed

Isojima, Tsuyoshi; Yokoya, Susumu

2017-12-01

Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.

Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

PubMed Central

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

2016-01-01

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

Emotion Risk-Factor in Patients with Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study).

PubMed

Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghei, Abbas

2015-05-17

Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) Was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases.

Alport Syndrome in Women and Girls.

PubMed

Savige, Judy; Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

2016-09-07

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%-30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The "Expert guidelines for the diagnosis and management of Alport syndrome" recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling, informed of their reproductive options, and monitored closely during pregnancy for the development of hypertension. Copyright © 2016 by the American Society of Nephrology.

Alport Syndrome in Women and Girls

PubMed Central

Colville, Deb; Rheault, Michelle; Gear, Susie; Lennon, Rachel; Lagas, Sharon; Finlay, Moira; Flinter, Frances

2016-01-01

Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Inheritance is X-linked (85%) or autosomal recessive (15%). Many renal physicians think of Alport syndrome as primarily affecting men. However, twice as many women are affected by the X-linked diseases. Affected women are commonly undiagnosed, but 15%–30% develop renal failure by 60 years and often hearing loss by middle age. Half of their sons and daughters are also affected. Autosomal recessive Alport syndrome is less common, but is often mistaken for X-linked disease. Recessive inheritance is suspected where women develop early-onset renal failure or lenticonus. Their family may be consanguineous. The prognosis for other family members is very different from X-linked disease. Other generations, including parents and offspring, are not affected, and on average only one in four of their siblings inherit the disease. All women with Alport syndrome should have their diagnosis confirmed with genetic testing, even if their renal function is normal, because of their own risk of renal failure and the risk to their offspring. Their mutations indicate the mode of inheritance and the likelihood of disease transmission to their children, and the mutation type suggests the renal prognosis for both X-linked and recessive disease. Women with X-linked Alport syndrome should be tested at least annually for albuminuria and hypertension. The “Expert guidelines for the diagnosis and management of Alport syndrome” recommend treating those with albuminuria with renin-angiotensin-aldosterone system (RAAS) blockade (and adequate birth control because of the teratogenic risks of angiotensin converting enzyme inhibitors), believing that this will delay renal failure. Current recommendations are that women with autosomal recessive Alport syndrome should be treated with RAAS blockade from the time of diagnosis. In addition, women should be offered genetic counseling, informed of their reproductive options, and monitored closely during pregnancy for the development of hypertension. PMID:27287265

21 CFR 510.3 - Definitions and interpretations.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., mitigating, treating, or preventing a disease, or to affect a structure or function of the animal body, even though such drug is not a new animal drug when used in another disease or to affect another structure or... drug as defined in part 516 of this chapter, who must be the real party in interest of the development...

21 CFR 510.3 - Definitions and interpretations.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., mitigating, treating, or preventing a disease, or to affect a structure or function of the animal body, even though such drug is not a new animal drug when used in another disease or to affect another structure or... drug as defined in part 516 of this chapter, who must be the real party in interest of the development...

Development of the parental needs scale for rare diseases: a tool for measuring the supportive care needs of parents caring for a child with a rare disease.

PubMed

Pelentsov, Lemuel J; Fielder, Andrea L; Laws, Thomas A; Esterman, Adrian J

2016-01-01

Children and families affected by rare diseases have received scant consideration from the medical, scientific, and political communities, with parents' needs especially having received little attention. Affected parents often have limited access to information and support and appropriate health care services. While scales to measure the needs of parents of children with chronic illnesses have been developed, there have been no previous attempts to develop a scale to assess the needs of parents of children with rare diseases. To develop a scale for measuring the supportive care needs of parents of children with rare diseases. A total of 301 responses to our Parental Needs Survey were randomly divided into two halves, one for exploratory factor analysis and the other for confirmatory factor analysis (CFA). After removing unsuitable items, exploratory factor analysis was undertaken to determine the factor structure of the data. CFA using structural equation modeling was then undertaken to confirm the factor structure. Seventy-two items were entered into the CFA, with a scree plot showing a likely four-factor solution. The results provided four independent subscales of parental needs: Understanding the disease (four items); Working with health professionals (four items); Emotional issues (three items); and Financial needs (three items). The structural equation modeling confirmed the suitability of the four-factor solution and demonstrated that the four subscales could be added to provide an overall scale of parental need. This is the first scale developed to measure the supportive care needs of parents of children with rare diseases. The scale is suitable for use in surveys to develop policy, in individual clinical assessments, and, potentially, for evaluating new programs. Measuring the supportive care needs of parents caring for a child with a rare disease will hopefully lead to better physical and psychological health outcomes for parents and their affected children.

The impact of globalization on vaccine development and availability.

PubMed

Milstien, Julie B; Kaddar, Miloud; Kieny, Marie Paule

2006-01-01

Globalization is likely to affect many aspects of public health, one of which is vaccine-preventable communicable diseases. Important forces include increased funding initiatives supporting immunization at the global level; regulatory harmonization; widespread intellectual property rights provisions through the World Trade Organization agreements; the emergence of developing-country manufacturers as major players in vaccine supply; and the appearance of new communicable disease threats, including those potentially linked to bioterrorism. All of these forces can affect, either positively and negatively, the development and availability of vaccines. Harnessing these will be a challenge for policymakers and immunization stakeholders.

Children, Sports, and Chronic Disease.

ERIC Educational Resources Information Center

Goldberg, Barry

1990-01-01

Discusses four chronic diseases (cystic fibrosis, congenital heart disease, rheumatoid arthritis, and asthma) that affect American children. Many have their physical activities unnecessarily restricted, though sports and exercise can actually alleviate symptoms and improve their psychosocial development. Physicians are encouraged to prescribe…

How glyphosate affects plant disease development: it is more than enhanced susceptibility.

PubMed

Hammerschmidt, Ray

2018-05-01

Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Taxonomy of rare genetic metabolic bone disorders.

PubMed

Masi, L; Agnusdei, D; Bilezikian, J; Chappard, D; Chapurlat, R; Cianferotti, L; Devolgelaer, J-P; El Maghraoui, A; Ferrari, S; Javaid, M K; Kaufman, J-M; Liberman, U A; Lyritis, G; Miller, P; Napoli, N; Roldan, E; Papapoulos, S; Watts, N B; Brandi, M L

2015-10-01

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes. Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients. IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis. This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity. This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

The impact of the Orphan Drug Act on drug discovery.

PubMed

Haffner, Marlene E; Maher, Paul D

2006-11-01

For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

Care assessment platform: an ICT-enabled home care model for secondary prevention of cardiovascular diseases.

PubMed

Karunanithi, Mohanraj; Varnfield, Marlien; Ding, Hang; Garcia, Elsa; Whittaker, Frank; Sarela, Antti

2010-01-01

Cardiovascular disease (CVD) is the leading chronic diseases affecting developed countries. Traditional approach to secondary prevention of CVD through hospital-based cardiac rehabilitation (CR) is hampered by the lack of uptake and adherence.

[New therapies for children affected by bone diseases].

PubMed

Ballhausen, Diana; Dépraz, Nuria Garcia; Kern, Ilse; Unger, Sheila; Bonafé, Luisa

2012-02-22

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

Characterizing Myeloid Cell Activation in NF1 Vasculopathy

DTIC Science & Technology

2016-07-01

mechanistic insight and develop therapeutic targets for the prevention/treatment of neurofibromatosis type 1 (NF1) related cardiovascular disease ...therapeutic targets for the prevention/treatment of neurofibromatosis type 1 (NF1) related cardiovascular diseases . Cardiovascular disease affects upwards...superoxide; macrophages; monocytes; arteries; cardiovascular disease Major Goals and Accomplishments: Significant progress toward accomplishing

[Hand osteoarthritis].

PubMed

Šenolt, Ladislav

Hand osteoarthritis (OA) is a common chronic disorder causing pain and limitation of mobility of affected joints. The prevalence of hand OA increases with age and more often affects females. Clinical signs obviously do not correlate with radiographic findings - symptomatic hand OA affects approximately 26 % of adult subjects, but radiographic changes can be found in up to two thirds of females and half of males older than 55 years.Disease course differ among individual patients. Hand OA is a heterogeneous disease. Nodal hand OA is the most common subtype affecting interphalangeal joints, thumb base OA affects first carpometacarpal joint. Erosive OA represents a specific subtype of hand OA, which is associated with joint inflammation, more pain, functional limitation and erosive findings on radiographs.Treatment of OA is limited. Analgesics and nonsteroidal anti-inflammatory drugs are the only agents reducing symptoms. New insights into the pathogenesis of disease should contribute to the development of novel effective treatment of hand OA.

MITOCHONDRIAL DISEASES PART II: MOUSE MODELS OF OXPHOS DEFICIENCIES CAUSED BY DEFECTS IN REGULATORY FACTORS AND OTHER COMPONENTS REQUIRED FOR MITOCHONDRIAL FUNCTION

PubMed Central

Iommarini, Luisa; Peralta, Susana; Torraco, Alessandra; Diaz, Francisca

2015-01-01

Mitochondrial disorders are defined as defects that affect the oxidative phosphorylation system (OXPHOS). They are characterized by a heterogeneous array of clinical presentations due in part to a wide variety of factors required for proper function of the components of the OXPHOS system. There is no cure for these disorders owing our poor knowledge of the pathogenic mechanisms of disease. To understand the mechanisms of human disease numerous mouse models have been developed in recent years. Here we summarize the features of several mouse models of mitochondrial diseases directly related to those factors affecting mtDNA maintenance, replication, transcription, translation as well to other proteins that are involved in mitochondrial dynamics and quality control which affect mitochondrial OXPHOS function without been intrinsic components of the system. We discuss how these models have contributed to our understanding of mitochondrial diseases and their pathogenic mechanisms. PMID:25640959

Wnt and the Wnt signaling pathway in bone development and disease

PubMed Central

Wang, Yiping; Li, Yi-Ping; Paulson, Christie; Shao, Jian-Zhong; Zhang, Xiaoling; Wu, Mengrui; Chen, Wei

2014-01-01

Wnt signaling affects both bone modeling, which occurs during development, and bone remodeling, which is a lifelong process involving tissue renewal. Wnt signals are especially known to affect the differentiation of osteoblasts. In this review, we summarize recent advances in understanding the mechanisms of Wnt signaling, which is divided into two major branches: the canonical pathway and the noncanonical pathway. The canonical pathway is also called the Wnt/β-catenin pathway. There are two major noncanonical pathways: the Wnt-planar cell polarity pathway (Wnt-PCP pathway) and the Wnt-calcium pathway (Wnt-Ca2+ pathway). This review also discusses how Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists affect both the bone modeling and bone remodeling processes. We also review the role of Wnt ligands, receptors, intracellular effectors, transcription factors, and antagonists in bone as demonstrated in mouse models. Disrupted Wnt signaling is linked to several bone diseases, including osteoporosis, van Buchem disease, and sclerosteosis. Studying the mechanism of Wnt signaling and its interactions with other signaling pathways in bone will provide potential therapeutic targets to treat these bone diseases. PMID:24389191

Environmental determinants of allergy and asthma in early life.

PubMed

Burbank, Allison J; Sood, Amika K; Kesic, Matthew J; Peden, David B; Hernandez, Michelle L

2017-07-01

Allergic disease prevalence has increased significantly in recent decades. Primary prevention efforts are being guided by study of the exposome (or collective environmental exposures beginning during the prenatal period) to identify modifiable factors that affect allergic disease risk. In this review we explore the evidence supporting a relationship between key components of the external exposome in the prenatal and early-life periods and their effect on atopy development focused on microbial, allergen, and air pollution exposures. The abundance and diversity of microbial exposures during the first months and years of life have been linked with risk of allergic sensitization and disease. Indoor environmental allergen exposure during early life can also affect disease development, depending on the allergen type, dose, and timing of exposure. Recent evidence supports the role of ambient air pollution in allergic disease inception. The lack of clarity in the literature surrounding the relationship between environment and atopy reflects the complex interplay between cumulative environmental factors and genetic susceptibility, such that no one factor dictates disease development in all subjects. Understanding the effect of the summation of environmental exposures throughout a child's development is needed to identify cost-effective interventions that reduce atopy risk in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

PubMed

Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

2014-11-01

Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.

Precision medicine and drug development in Alzheimer's disease: The importance of sexual dimorphism and patient stratification.

PubMed

Hampel, Harald; Vergallo, Andrea; Giorgi, Filippo Sean; Kim, Seung Hyun; Depypere, Herman; Graziani, Manuela; Saidi, Amira; Nisticò, Robert; Lista, Simone

2018-06-12

Neurodegenerative diseases (ND) are among the leading causes of disability and mortality. Considerable sex differences exist in the occurrence of the various manifestations leading to cognitive decline. Alzheimer's disease (AD) exhibits substantial sexual dimorphisms and disproportionately affects women. Women have a higher life expectancy compared to men and, consequently, have more lifespan to develop AD. The emerging precision medicine and pharmacology concepts - taking into account the individual genetic and biological variability relevant for disease risk, prevention, detection, diagnosis, and treatment - are expected to substantially enhance our knowledge and management of AD. Stratifying the affected individuals by sex and gender is an important basic step towards personalization of scientific research, drug development, and care. We hypothesize that sex and gender differences, extending from genetic to psychosocial domains, are highly relevant for the understanding of AD pathophysiology, and for the conceptualization of basic/translational research and for clinical therapy trial design. Copyright © 2018 Elsevier Inc. All rights reserved.

Microbiome/microbiota and allergies.

PubMed

Inoue, Yuzaburo; Shimojo, Naoki

2015-01-01

Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the frequency of allergic diseases is thought to be primarily due to environmental changes related to a westernized lifestyle, which affects the commensal microbes in the human body. The human gut is the largest organ colonized by bacteria and contains more than 1000 bacterial species, called the "gut microbiota." The recent development of sequencing technology has enabled researchers to genetically investigate and clarify the diversity of all species of commensal microbes. The collective genomes of commensal microbes are together called the "microbiome." Although the detailed mechanisms remain unclear, it has been proposed that the microbiota/microbiome, especially that in the gut, impacts the systemic immunity and metabolism, thus affecting the development of various immunological diseases, including allergies. In this review, we summarize the recent findings regarding the importance of the microbiome/microbiota in the development of allergic diseases and also the results of interventional studies using probiotics or prebiotics to prevent allergies.

Substantia nigra and Parkinson disease (image)

MedlinePlus

... is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as ...

Male fertility potential alteration in rheumatic diseases: a systematic review.

PubMed

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfa, Eloisa; Srougi, Miguel; Silva, Clovis A

2016-01-01

Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy.

Emerging viral diseases from a vaccinology perspective: preparing for the next pandemic.

PubMed

Graham, Barney S; Sullivan, Nancy J

2018-01-01

Emerging infectious diseases will continue to threaten public health and are sustained by global commerce, travel and disruption of ecological systems. Most pandemic threats are caused by viruses from either zoonotic sources or vector-borne sources. Developing better ways to anticipate and manage the ongoing microbial challenge will be critical for achieving the United Nations Sustainable Development Goals and, conversely, each such goal will affect the ability to control infectious diseases. Here we discuss how technology can be applied effectively to better prepare for and respond to new viral diseases with a focus on new paradigms for vaccine development.

Crohn's disease in adolescence: presentation and treatment.

PubMed

Cullen, Mick; Barnes, Claire

2015-05-13

Crohn's disease is a chronic inflammatory bowel condition that affects more than 115,000 people in the UK. This article focuses on Crohn's disease in adolescents. Management of the condition in this group should address adolescent-specific characteristics and treatment goals. Key elements include optimising growth, pubertal development and social functioning, including education. The condition can affect an individual's mental and emotional wellbeing significantly, as well as their physical health. As adolescence is a time of great change, the additional burden of a chronic illness can prove difficult to manage. The authors provide information on the presentation of Crohn's disease in adolescence and insights into the particular issues encountered by this group.

Pediatric inflammatory bowel disease and bone health.

PubMed

Mascarenhas, Maria R; Thayu, Meena

2010-08-01

Childhood and adolescence are important periods for bone development. Any disease that affects bone health has the potential to affect the bones not only in the short term but also later in life. Bone health abnormalities in patients with inflammatory bowel disease are being increasingly recognized. Screening the at-risk patient is important so that appropriate treatments can be instituted. Treatment options are limited to vitamin D and calcium supplementation, control of underlying disease activity, and appropriate physical activity. The role of bisphosphonates in these patients needs to be better studied, and treatment with bisphosphonates may be considered for some patients in consultation with a bone health expert.

Phylloquinone and vitamin D status: associations with incident chronic kidney disease in the Framingham Offspring Cohort

USDA-ARS?s Scientific Manuscript database

Cardiovascular risk factors are associated with the development of chronic kidney disease (CKD), and CKD and vascular disease are etiologically linked. Evidence suggests deficiencies of vitamins D and K may adversely affect the cardiovascular system, but data from longitudinal studies are lacking. W...

Alzheimer disease: diagnosis, costs, and dimensions of treatment.

PubMed

DeKosky, S T; Orgogozo, J M

2001-08-01

Alzheimer disease (AD) is the most frequent cause of dementia in developed Western countries. Over time, affected patients invariably develop cognitive and functional decline, and most develop early or later behavioral disturbances. Declining cognitive and functional abilities contribute to loss of independent living and feelings of denial, confusion, fear and guilt until, finally, the patient loses most abilities to think, move, speak, or perceive. As patients' dependency on assistance increases, the level of caregiver strain rises. The caregiver may develop feelings of anger, grief, loneliness and resentment, and the health and well-being of most caregivers are often affected. Approximately 3-4 million people currently have AD in the USA, at an annual cost of up to US$100 billion, and the disease is expected to reach epidemic proportions by 2020. To achieve a clinically relevant, long-term outcome, pharmacotherapy must have sustained favorable effects on cognitive, functional and behavioral symptoms of AD. Slowing the development of these features of the disease will mean a long-term improvement in quality of life for patients and caregivers. Postponing the emergence of behavioral symptoms would bring about direct beneficial effects on patients with AD and their families, help delay long-term care placement and lower costs.

Interview with Dr Bernard Pécoul, Executive Director of the Drugs for Neglected Diseases Initiative.

PubMed

Pécoul, Bernard

2009-05-01

A significant number of product-development partnerships have arisen in the past 10 years to tackle diseases that mainly affect developing countries. With their coherent research and development leadership, they have become key players in identifying gaps and overcoming bottlenecks in order to deliver medicines to those who need them most in the developing world. Dr Bernard Pécoul is the Executive Director of one such partnership, the Drugs for Neglected Diseases Initiative (DNDi). Under his leadership, the DNDi has built the largest and most robust R&D portfolio for three of the most neglected diseases. He speaks to Future Medicinal Chemistry about challenges facing neglected disease R&D and the DNDi's ongoing work.

Heart Disease and Depression: Is Culture a Factor?

PubMed

Gholizadeh, Leila; Davidson, Patricia M; Heydari, Mehrdad; Salamonson, Yenna

2014-07-01

This article seeks to review and discuss the evidence linking depression, coronary heart disease (CHD), and culture. PsychInfo, CINAHL, PubMed, and Google were searched for pertinent evidence linking depression, culture, and CHD, and retrieved articles were analyzed using thematic content analysis. Identified themes were the followings: depression is a factor in development and prognosis of CHD and affects the capacity to self-manage and adhere to treatment recommendations; culture mediates mental health/illness representations and treatment-seeking behaviors; screening and assessment of depression can be affected by cultural factors; and there is a need for culturally appropriate screening and therapeutic strategies. As depression is a predictor and moderating variable in the genesis and progression of CHD, understanding how factors such as culture affect screening and management of the disease is important to inform the development of culturally and linguistically competent strategies that ensure accurate screening, detection, and treatment of depression in cardiac patients in clinical practice. © The Author(s) 2014.

A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

PubMed

Park, Seonmi; Gianotti-Sommer, Andreia; Molina-Estevez, Francisco Javier; Vanuytsel, Kim; Skvir, Nick; Leung, Amy; Rozelle, Sarah S; Shaikho, Elmutaz Mohammed; Weir, Isabelle; Jiang, Zhihua; Luo, Hong-Yuan; Chui, David H K; Figueiredo, Maria Stella; Alsultan, Abdulraham; Al-Ali, Amein; Sebastiani, Paola; Steinberg, Martin H; Mostoslavsky, Gustavo; Murphy, George J

2017-04-11

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

EPA Science Inventory

Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et...

Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

ERIC Educational Resources Information Center

Wright, Robin; Boggs, James

2002-01-01

To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…

Annosus Root Disease Hazard Rating, Detection, and Management Strategies in the Southeastern United States

Treesearch

S. A. Alexander

1989-01-01

Annosus root disease (ARD), is the major root disease of pines in the southeastern United States where severely affected trees exhibit growth loss. Assessing the potential damage of ARD is essential for making effective disease control and management decisions. A soil hazard rating system developed to identify potential for tree mortality is described. The Annosus...

Plants used to treat skin diseases

PubMed Central

Tabassum, Nahida; Hamdani, Mariya

2014-01-01

Skin diseases are numerous and a frequently occurring health problem affecting all ages from the neonates to the elderly and cause harm in number of ways. Maintaining healthy skin is important for a healthy body. Many people may develop skin diseases that affect the skin, including cancer, herpes and cellulitis. Some wild plants and their parts are frequently used to treat these diseases. The use of plants is as old as the mankind. Natural treatment is cheap and claimed to be safe. It is also suitable raw material for production of new synthetic agents. A review of some plants for the treatment of skin diseases is provided that summarizes the recent technical advancements that have taken place in this area during the past 17 years. PMID:24600196

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

PubMed Central

Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

2013-01-01

The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results. PMID:24324827

Assessing Quality of Life in Older Adult Patients with Skin Disorders

PubMed Central

Farage, Miranda A.; Miller, Kenneth W.; Sherman, Susan N.; Tsevat, Joel

2012-01-01

Significance for Public Health The global population is aging. In the industrial world, adults over 65 outnumber children and comprise almost 20% of the population in some countries. Older adults experience a number of skin diseases and disorders that substantially affect their quality of life. Opportunity exists for developing and validating health-related quality of life (HRQoL) measures specifically for dermatological conditions most pertinent to older patients. Older adults experience a number of skin diseases and disorders that substantially affect quality of life. In the last two decades, a number of instruments have been developed for use among general dermatology patients to assess the effects of treatment and disease progression, perceptions of well-being, and the value that patients place on their dermatologic state of health. This chapter reviews some health-related quality of life (HRQoL) (HRQoL) measures developed and validated specifically for dermatological conditions. However, opportunity exists for developing and validating HRQoL measures specifically for dermatological conditions most pertinent to older patients. PMID:22980159

Advances in disease-resistant varieties

USDA-ARS?s Scientific Manuscript database

Soybean yields worldwide are reduced by a variety of diseases that affect plant stands, seed development, and/or seed quality, but soybean breeders, pathologists, and genomicists have made considerable progress in the identification, characterization and utilization of sources of resistance genes. M...

Recognizing and managing sapstreak disease of sugar maple

Treesearch

David R. Houston; David R. Houston

1993-01-01

Sapstreak disease, a potentially serious problem of sugarbushes and forest stands, occurs when the causal fungus, Ceratocystis virescens, invades the sapwood of roots and bases of stems through wounds inflicted during logging, saphauling, or other activities. Describes how to recognize the disease, the factors that affect its occurrence and development, and management...

Sycamore diseases

Treesearch

F. I. McCracken

1989-01-01

The canker stain disease, one of several fungi that cause cankers of sycamore, can cause serious loss of sycamores in natural stands, plantations, and urban areas. As many as 35 percent of the trees in some stands may be diseased. Affected trees develop thin crowns, twig dieback, small leaves and epicormic branches. The narrow, elongate, bark covered, flat, spiraling...

Nanomedicine in GI

PubMed Central

Laroui, Hamed; Wilson, David S.; Dalmasso, Guillaume; Salaita, Khalid; Murthy, Niren; Sitaraman, Shanthi V.

2011-01-01

Recent advances in nanotechnology offer new hope for disease detection, prevention, and treatment. Nanomedicine is a rapidly evolving field wherein targeted therapeutic approaches using nanotechnology based on the pathophysiology of gastrointestinal diseases are being developed. Nanoparticle vectors capable of delivering drugs specifically and exclusively to regions of the gastrointestinal tract affected by disease for a prolonged period of time are likely to significantly reduce the side effects of existing otherwise effective treatments. This review aims at integrating various applications of the most recently developed nanomaterials that have tremendous potential for the detection and treatment of gastrointestinal diseases. PMID:21148398

Male fertility potential alteration in rheumatic diseases: a systematic review

PubMed Central

Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A

2016-01-01

ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778

Transcutaneous photodynamic therapy delays the onset of paralysis in a murine multiple sclerosis model

NASA Astrophysics Data System (ADS)

Hunt, David W. C.; Leong, Simon; Levy, Julia G.; Chan, Agnes H.

1995-03-01

Photodynamic therapy (PDT) using benzoporphyrin derivative (BPD, Verteporfin) and whole body irradiation, can affect the course of adoptively transferred experimental allergic (autoimmune) encephalomyelitis (EAE) in PL mice. Murine EAE is a T cell-mediated autoimmune disease which serves as a model for human multiple sclerosis. Using a novel disease induction protocol, we found that mice characteristically developed EAE within 3 weeks of receipt of myelin basic protein (MBP)-sensitized, in vitro-cultured spleen or lymph node cells. However, if animals were treated with PDT (1 mg BPD/kg bodyweight and exposed to whole body 15 Joules cm2 of LED light) 24 hours after receiving these cells, disease onset time was significantly delayed. PDT-treated mice developed disease symptoms 45 +/- 3 days following cell administration whereas untreated controls were affected within 23 +/- 2 days. In contrast, application of PDT 48 or 120 hours following injection of the pathogenic cells had no significant effect upon the development of EAE. Experiments are in progress to account for the protective effect of PDT in this animal model. These studies should provide evidence on the feasibility of PDT as a treatment for human autoimmune disease.

Preterm Birth Affects the Risk of Developing Immune-Mediated Diseases

PubMed Central

Goedicke-Fritz, Sybelle; Härtel, Christoph; Krasteva-Christ, Gabriela; Kopp, Matthias V.; Meyer, Sascha; Zemlin, Michael

2017-01-01

Prematurity affects approximately 10% of all children, resulting in drastically altered antigen exposure due to premature confrontation with microbes, nutritional antigens, and other environmental factors. During the last trimester of pregnancy, the fetal immune system adapts to tolerate maternal and self-antigens, while also preparing for postnatal immune defense by acquiring passive immunity from the mother. Since the perinatal period is regarded as the most important “window of opportunity” for imprinting metabolism and immunity, preterm birth may have long-term consequences for the development of immune-mediated diseases. Intriguingly, preterm neonates appear to develop bronchial asthma more frequently, but atopic dermatitis less frequently in comparison to term neonates. The longitudinal study of preterm neonates could offer important insights into the process of imprinting for immune-mediated diseases. On the one hand, preterm birth may interrupt influences of the intrauterine environment on the fetus that increase or decrease the risk of later immune disease (e.g., maternal antibodies and placenta-derived factors), whereas on the other hand, it may lead to the premature exposure to protective or harmful extrauterine factors such as microbiota and nutritional antigen. Solving this puzzle may help unravel new preventive and therapeutic approaches for immune diseases. PMID:29062316

Management of Sickle Cell Disease: A Review for Physician Education in Nigeria (Sub-Saharan Africa)

PubMed Central

Adewoyin, Ademola Samson

2015-01-01

Sickle cell disease (SCD) predominates in sub-Saharan Africa, East Mediterranean areas, Middle East, and India. Nigeria, being the most populous black nation in the world, bears its greatest burden in sub-Saharan Africa. The last few decades have witnessed remarkable scientific progress in the understanding of the complex pathophysiology of the disease. Improved clinical insights have heralded development and establishment of disease modifying interventions such as chronic blood transfusions, hydroxyurea therapy, and haemopoietic stem cell transplantation. Coupled with parallel improvements in general supportive, symptomatic, and preventive measures, current evidence reveals remarkable appreciation in quality of life among affected individuals in developed nations. Currently, in Nigeria and other West African states, treatment and control of SCD are largely suboptimal. Improved knowledge regarding SCD phenotypes and its comprehensive care among Nigerian physicians will enhance quality of care for affected persons. This paper therefore provides a review on the aetiopathogenesis, clinical manifestations, and management of SCD in Nigeria, with a focus on its local patterns and peculiarities. Established treatment guidelines as appropriate in the Nigerian setting are proffered, as well as recommendations for improving care of affected persons. PMID:25667774

Advances in the microbial etiology and pathogenesis of early childhood caries

PubMed Central

Hajishengallis, Evlambia; Parsaei, Yassmin; Klein, Marlise I.; Koo, Hyun

2016-01-01

Early childhood caries (ECC) is one of the most prevalent infectious diseases affecting children worldwide. ECC is an aggressive form of dental caries, which left untreated, can result in rapid and extensive cavitation in teeth (rampant caries) that is painful and costly to treat. Furthermore, it affects mostly children from impoverished background, and thus constitutes a major challenge in public health. The disease is a prime example of the consequences arising from complex, dynamic interactions between microorganisms, host and diet, leading to the establishment of highly pathogenic (cariogenic) biofilms. To date, there are no effective methods to identify those at risk of developing ECC or control the disease in affected children. Recent advances in deep-sequencing technologies, novel imaging methods and (meta)proteomics-metabolomics approaches provide an unparalleled potential to reveal new insights to illuminate our current understanding about the etiology and pathogenesis of the disease. In this concise review, we provide a broader perspective about the etiology and pathogenesis of ECC based on previous and current knowledge on biofilm matrix, microbial diversity and host-microbe interactions which could have direct implications for developing new approaches for improved risk assessment and prevention of this devastating and costly childhood health condition. PMID:26714612

[Periodonta disease in smokers, and the parameters of oxidative stress].

PubMed

Golusińska-Kardach, Ewelina; Napierała, Marta; Sokalski, Jerzy; Kardachi, Hubert; Florek, Ewa

2015-01-01

Periodontal disease, periodontitis, and caries disease, are the two most common disease occurring in the mouth. They affect a large proportion of the world's population. The causes of periodontitis are varied, but the largest group are those caused by infections. The characteristic long asymptomatic period of development of periodontitis, make that patients are not aware of their condition. In-addition, it was observed that tobacco abuse affects the growth of disease and advancing disease state for periodontal diseases. Free radicals and other reactive particles are capable of destroying many cellular structures. They are produced mostly during the breathing process and the immune response or come from the environment. The evolution of living organisms ensure the proper tools to fight against reactive oxygen species after enzymatic and non-enzymatic by antioxidants. Sometimes this protection is not sufficient and the balance between antioxidants and oxidants is compromised. This condition is called oxidative stress. A number of studies looking for a link between oxidative stress, and diseases affecting human and determined that it is an important risk factor in many diseases. Evaluating the parameters of oxidative stress in the saliva allows for effective monitoring of disease progression, evaluation of the therapy and taking preventive measures in a timely manner.

Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association.

PubMed

Lui, George K; Saidi, Arwa; Bhatt, Ami B; Burchill, Luke J; Deen, Jason F; Earing, Michael G; Gewitz, Michael; Ginns, Jonathan; Kay, Joseph D; Kim, Yuli Y; Kovacs, Adrienne H; Krieger, Eric V; Wu, Fred M; Yoo, Shi-Joon

2017-11-14

Life expectancy and quality of life for those born with congenital heart disease (CHD) have greatly improved over the past 3 decades. While representing a great advance for these patients, who have been able to move from childhood to successful adult lives in increasing numbers, this development has resulted in an epidemiological shift and a generation of patients who are at risk of developing chronic multisystem disease in adulthood. Noncardiac complications significantly contribute to the morbidity and mortality of adults with CHD. Reduced survival has been documented in patients with CHD with renal dysfunction, restrictive lung disease, anemia, and cirrhosis. Furthermore, as this population ages, atherosclerotic cardiovascular disease and its risk factors are becoming increasingly prevalent. Disorders of psychosocial and cognitive development are key factors affecting the quality of life of these individuals. It is incumbent on physicians who care for patients with CHD to be mindful of the effects that disease of organs other than the heart may have on the well-being of adults with CHD. Further research is needed to understand how these noncardiac complications may affect the long-term outcome in these patients and what modifiable factors can be targeted for preventive intervention. © 2017 American Heart Association, Inc.

Automatic Detection of Diseased Tomato Plants Using Thermal and Stereo Visible Light Images

PubMed Central

Raza, Shan-e-Ahmed; Prince, Gillian; Clarkson, John P.; Rajpoot, Nasir M.

2015-01-01

Accurate and timely detection of plant diseases can help mitigate the worldwide losses experienced by the horticulture and agriculture industries each year. Thermal imaging provides a fast and non-destructive way of scanning plants for diseased regions and has been used by various researchers to study the effect of disease on the thermal profile of a plant. However, thermal image of a plant affected by disease has been known to be affected by environmental conditions which include leaf angles and depth of the canopy areas accessible to the thermal imaging camera. In this paper, we combine thermal and visible light image data with depth information and develop a machine learning system to remotely detect plants infected with the tomato powdery mildew fungus Oidium neolycopersici. We extract a novel feature set from the image data using local and global statistics and show that by combining these with the depth information, we can considerably improve the accuracy of detection of the diseased plants. In addition, we show that our novel feature set is capable of identifying plants which were not originally inoculated with the fungus at the start of the experiment but which subsequently developed disease through natural transmission. PMID:25861025

Collaborative Development of 2-Hydroxypropyl-β-Cyclodextrin for the Treatment of Niemann-Pick Type C1 Disease

PubMed Central

Ottinger, Elizabeth A.; Kao, Mark L.; Carrillo-Carrasco, Nuria; Yanjanin, Nicole; Shankar, Roopa Kanakatti; Janssen, Marjo; Brewster, Marcus; Scott, Ilona; Xu, Xin; Cradock, Jim; Terse, Pramod; Dehdashti, Seameen; Marugan, Juan; Zheng, Wei; Portilla, Lili; Hubbs, Alan; Pavan, William J.; Heiss, John; Vite, Charles H.; Walkley, Steven U.; Ory, Daniel S.; Silber, Steven A.; Porter, Forbes D.; Austin, Christopher P.; McKew, John C.

2014-01-01

In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Science (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collaborative model between the NIH, academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies. This paper describes one of the first TRND programs, the development of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of Niemann-Pick disease type C1 (NPC1). NPC is a neurodegenerative, autosomal recessive rare disease caused by a mutation in either the NPC1 (about 95% of cases) or the NPC2 gene (about 5% of cases). These mutations affect the intracellular trafficking of cholesterol and other lipids, which leads to a progressive accumulation of unesterified cholesterol and glycosphingolipids in the CNS and visceral organs. Affected individuals typically exhibit ataxia, swallowing problems, seizures, and progressive impairment of motor and intellectual function in early childhood, and usually die in adolescence. There is no disease modifying therapy currently approved for NPC1 in the US. A collaborative drug development program has been established between TRND, public and private partners that has completed the pre-clinical development of HP-β-CD through IND filing for the current Phase I clinical trial that is underway. Here we discuss how this collaborative effort helped to overcome scientific, clinical and financial challenges facing the development of new drug treatments for rare and neglected diseases, and how it will incentivize the commercialization of HP-β-CD for the benefit of the NPC patient community. PMID:24283970

Early Postnatal Protein-Calorie Malnutrition and Cognition: A Review of Human and Animal Studies

PubMed Central

Laus, Maria Fernanda; Vales, Lucas Duarte Manhas Ferreira; Costa, Telma Maria Braga; Almeida, Sebastião Sousa

2011-01-01

Malnutrition continues to be recognized as the most common and serious form of children’s dietary disease in the developing countries and is one of the principal factors affecting brain development. The purpose of this paper is to review human and animal studies relating malnutrition to cognitive development, focusing in correlational and interventional data, and to provide a discussion of possible mechanisms by which malnutrition affects cognition. PMID:21556206

Hand in glove: brain and skull in development and dysmorphogenesis

PubMed Central

Flaherty, Kevin

2013-01-01

The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease. PMID:23525521

The importance of appropriate initial bacterial colonization of the intestine in newborn, child and adult health

PubMed Central

Walker, W. Allan

2017-01-01

The fetus does not reside in a sterile intrauterine environment and is exposed to commensal bacteria from the maternal gut/blood stream which crosses the placenta and enters the amniotic fluid. This intestinal exposure to colonizing bacteria continues at birth and during the first year of life and has a profound influence on lifelong health. Why is this important? Intestinal crosstalk with colonizing bacteria in the developing intestine affects the infant’s adaptation to extrauterine life (immune homeostasis) and provides protection against disease expression (allergy, autoimmune disease, obesity, etc.) later in life. Colonizing intestinal bacteria are critical to the normal development of host defense. Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section delivery, use of perinatal antibiotics or premature delivery may adversely affect gut development of host defense and predispose to inflammation rather than homeostasis leading to increased susceptibility to disease later in life. Babies born by cesarean section have a higher incidence of allergy, type 1 diabetes and obesity. Infants given repeated antibiotic regimens during the first year of life are more likely to have asthma as adolescents. This research breakthrough helps to explain the shift in disease paradigms from infections to immune mediated in children from developed countries. This review will develop this research breakthrough. PMID:28426649

Interview with Solomon Nwaka.

PubMed

Nwaka, Solomon

2011-09-01

Solomon Nwaka was born in Nigeria and grew up seeing at first hand the impact of neglected diseases. His research efforts have taken him across the globe, in both the developed and developing world. Following posts in academia, industry and at the Medicines for Malaria Venture, he is now at the WHO where he is engaged in initiating schemes to support research into neglected diseases in developing countries, notably the African Network for Drugs and Diagnostics Innovation, which is now an organization under the United Nations Economic Commission for Africa. He speaks to Future Medicinal Chemistry about what inspired him to take up a career in neglected disease research and how the developing world should lead the effort to tackle some of the diseases that most affect them.

Gender differences in the relationship between built environment and non-communicable diseases: A systematic review.

PubMed

Valson, Joanna Sara; Kutty, V Raman

2018-02-05

Non-communicable diseases are on the rise globally. Risk factors of non-communicable diseases continue to be a growing concern in both developed and developing countries. With significant rise in population and establishment of buildings, rapid changes have taken place in the built environment. Relationship between health and place, particularly with non-communicable diseases has been established in previous literature. This systematic review assesses the current evidence on influence of gender in the relationship between built environment and non-communicable diseases. A systematic literature search using PubMed was done to identify all studies that reported relationship between gender and built environment. All titles and abstracts were scrutinised to include only articles based on risk factors, prevention, treatment and outcome of non-communicable diseases. The Gender Analysis Matrix developed by the World Health Organization was used to describe the findings of gender differences. Sex differences, biological susceptibility, gender norms/ values, roles and activities related to gender and access to/control over resources were themes for the differences in the relationship. A total of 15 out of 214 articles met the inclusion criteria. Majority of the studies were on risk factors of non-communicable diseases, particularly cardiovascular diseases. Gender differences in physical access to recreational facilities, neighbourhood perceptions of safety and walkability have been documented. Men and women showed differential preferences to walking, engaging in physical activity and in perceiving safety of the neighbourhood. Girls and boys showed differences in play activities at school and in their own neighbourhood environment. Safety from crime and safety from traffic were also perceived important to engage in physical activity. Gender norms and gender roles and activities have shown basis for the differences in the prevalence of non-communicable diseases. Sparse evidence was found on how built environment affects health seeking behaviour, preventive options or experience with health providers. Though yet unexplored in the developing or low/middle income countries, there seems to be a major role in the gendered perception of how men and women are affected by noncommunicable diseases. Large gaps still exist in the research evidence on gender-based differences in non-communicable diseases and built environment relationship. Future research directions could bring out underpinnings of how perceived and objective built environment could largely affect the health behaviour of men and women across the globe.

New strategies for innovation in global health: a pharmaceutical industry perspective.

PubMed

Witty, Andrew

2011-01-01

Diseases that disproportionately affect developing countries play a large role in stalling economic and social development. Pharmaceutical companies are driving crucial research into new vaccines and medicines; however, although there is an imperative for industry to research new therapies for diseases of the poor, the financial returns are often seen as limited. This is beginning to change. The pharmaceutical industry and the public sector are thinking differently than before about how to improve access to medicines and advance research and development for neglected diseases. The public and private sectors must work together to develop a wide range of innovative tools, partnerships, and approaches.

GUIDELINES OF CARE FOR THE MANAGEMENT OF ATOPIC DERMATITIS

PubMed Central

Eichenfield, Lawrence F.; Tom, Wynnis L.; Chamlin, Sarah L.; Feldman, Steven R.; Hanifin, Jon M.; Simpson, Eric L.; Berger, Timothy G.; Bergman, James N.; Cohen, David E.; Cooper, Kevin D.; Cordoro, Kelly M.; Davis, Dawn M.; Krol, Alfons; Margolis, David J.; Paller, Amy S.; Schwarzenberger, Kathryn; Silverman, Robert A.; Williams, Hywel C.; Elmets, Craig A.; Block, Julie; Harrod, Christopher G.; Begolka, Wendy Smith; Sidbury, Robert

2014-01-01

Atopic dermatitis (AD) is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2–3% of adults. This guideline addresses important clinical questions that arise in AD management and care, providing updated and expanded recommendations based on the available evidence. In this first of four sections, methods for diagnosis and monitoring of disease, outcomes measures for assessment and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. PMID:24290431

Nutritional epigenomics: a portal to disease prevention.

PubMed

Choi, Sang-Woon; Claycombe, Kate J; Martinez, J Alfredo; Friso, Simonetta; Schalinske, Kevin L

2013-09-01

Epigenetics can be defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence. Epigenomics is the study of genome-wide epigenetic modifications. Because gene expression changes are critical in both normal development and disease progression, epigenetics is widely applicable to many aspects of biological research. The influences of nutrients and bioactive food components on epigenetic phenomena such as DNA methylation and various types of histone modifications have been extensively investigated. Because an individual's epigenetic patterns are established during early gestation and are changed and personalized by environmental factors during our lifetime, epigenetic mechanisms are quite important in the development of transgenerational and adult obesity as well as in the development of diabetes mellitus. Aging and cancer demonstrate profound genome-wide DNA methylation changes, suggesting that nutrition may affect the aging process and cancer development through epigenetic mechanisms.

Development and testing of an artificial arterial and venous pulse oximeter.

PubMed

Cloete, G; Fourie, P R; Scheffer, C

2013-01-01

The monitoring of patients healthcare is of a prime importance to ensure their efficient and effective treatment. Monitoring blood oxygen saturation is a field which has grown significantly in recent times and more specifically in tissues affected by diseases or conditions that may negatively affect the function of the tissue. This study involved the development and testing of a highly sensitive non-invasive blood oxygen saturation monitoring device. A device that can be used to continuously monitor the condition of tissue affected by diseases which affect the blood flow through the tissue, and the oxygen usage in tissue. The device's system was designed to specifically monitor occluded tissue which has low oxygen saturations and low perfusion. Although with limitted validation the system was unable to accurately measure the venous oxygenation specifically, but it was able to measure the mixed oxygen saturation. With further research it would be possible to validate the system for measuring both the arterial and venous oxygen saturations.

New Insights into Gastrointestinal Anthrax Infection

PubMed Central

Owen, Jennifer L.; Yang, Tao; Mohamadzadeh, Mansour

2014-01-01

Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the “archetype zoonotic” pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target establishment of infection. PMID:25577136

Epstein-Barr virus-positive mucocutaneous ulcer in Crohn's disease. A condition to consider in immunosuppressed IBD patients.

PubMed

Juan, Alba; Lobatón, Triana; Tapia, Gustavo; Mañosa, Míriam; Cabré, Eduard; Domènech, Eugeni

2017-08-01

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a little known entity that can affect the oropharyngeal mucosa, the gastrointestinal tract and the skin. The main risk factor for the development of this lesion is immunosuppression. Because its features are similar to other Epstein-Barr virus-associated lymphoproliferative disorders, a differential diagnosis can sometimes prove challenging. Here, we report the case of a man diagnosed with Crohn's disease and treated with azathioprine and infliximab who developed ulceration at the rectum that was refractory to conventional medical treatment. Although the histological characteristics were suggestive of an EBVMCU, lymphoproliferative disease could not be ruled out. The patient did not improve after discontinuation of the treatment, a proctectomy was performed and the diagnosis of this disease was confirmed. Although very few cases of EBVMCU affecting the colon have been reported, its diagnosis should be always considered in refractory cases of inflammatory bowel disease with patients undergoing immunosuppressive treatment. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Chronic obstructive pulmonary disease in women: exploring gender differences.

PubMed

Varkey, Anita B

2004-03-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. This major public health threat is ranked twelfth as a worldwide burden of disease and is projected to rank fifth by the year 2020 as a cause of lost quantity and quality of life. The impact of this disease in women is significantly understudied but the evidence that does exist reveals potentially substantial gender differences in the susceptibility to, severity of, and response to management of COPD. The best known risk factor for the development of COPD is tobacco smoking. While smoking rates in women have largely stabilized in developed countries, the rates are continuing to climb in developing countries. While it is not clear whether women are more susceptible to the toxic effects of cigarette smoke than men, it is known that the incidence and prevalence of COPD will continue to climb as more women smoke. Other known risk factors for the development of COPD include air pollution, infections, occupational exposures, and genetic factors. Air pollution, particularly fine particulate indoor air pollution from biomass fuels disproportionately affects women. Infections such as human immunodeficiency virus (HIV) and tuberculosis (TB) disproportionately affect vulnerable populations such as poor women and occupational exposures to various dusts and toxins are often gender specific. Genetic factors are still being explored but there seems a preponderance of women who are affected by early-onset and non-smoking related COPD. Women with COPD also seem to be underdiagnosed by physicians and may have different responses to medical treatment, smoking cessation interventions, and pulmonary rehabilitation programs. Chronic obstructive pulmonary disease in women is an understudied subject but is gaining attention as a significant public health threat. In developed countries, efforts at preventing the initiation of tobacco smoking and targeting smoking cessation programs in women are needed. In developing countries, efforts to promote cleaner fuels, improved stoves, better home ventilation, reduce toxic dust and fume exposures, combat infectious diseases such as TB and HIV, and improve nutrition are all ways in which the lung health of women can be improved.

[Indications and approaches in rehabilitation with children].

PubMed

Petermann, F; Bauer, C-P

2011-04-01

Against the background of rising prevalence of chronic diseases in childhood and adolescence, the rehabilitation of children and adolescents plays a major role in medical treatment. Early diagnosis and multimodal intervention are necessary to prevent a chronic course of disease and disease consequences for those affected and their families. In recent years, significant content and structural improvement of child and youth rehabilitation has been observed; currently some trends that affect not only the access to rehabilitation but also the quality of outcomes are becoming apparent. These include salutogenetic approaches, the development of specific diagnostic and treatment guidelines, the establishment of networks, integrated care, modularization, and flexibility of rehabilitation measures.

[Risk factors negatively affecting on the formation of musculoskeletal system in children and adolescents in the present conditions].

PubMed

Mirskaya, N B

2013-01-01

Identifying risk factors affecting the formation of the musculoskeletal system (MSS) in children and adolescents is considered by the author as a necessary condition for the implementation of prevention, timely diagnosis and adequate correction of the MSS disorders and diseases. Introduction in the educational process developed by the author for the first time a conceptual model of prevention and correction of the MSS disorders and diseases in schoolchildren allowed significantly reduce the prevalence of functional disorders and early forms of the MSS diseases in students of a number of comprehensive schools in Moscow by 50%.

How health affects small business in South Africa.

PubMed

Chao, Li-Wei; Pauly, Mark V

2007-03-01

Preventable and treatable diseases have taken a devastating human and economic toll on many developing countries. That economic toll is likely to be underestimated because most studies focus on productivity losses in the formal, or large-firm, sector; yet, a large portion of the population of developing countries works in the informal sector in very small businesses, either as an owner-worker or as an employee. It is plausible that ill health might affect small businesses most severely, possibly putting the entire business at risk. This Issue Brief summarizes a three-year study that tracks small businesses in Durban, South Africa, and investigates the connection between the owner's health and business growth, survival, or closure. The results bolster the economic case for investing resources in the prevention and treatment of disease in developing countries.

Resources, challenges and way forward in rare mitochondrial diseases research.

PubMed

Rajput, Neeraj Kumar; Singh, Vipin; Bhardwaj, Anshu

2015-01-01

Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases.

Epigenetic modifications: basic mechanisms and role in cardiovascular disease (2013 Grover Conference series).

PubMed

Loscalzo, Joseph; Handy, Diane E

2014-06-01

Epigenetics refers to heritable traits that are not a consequence of DNA sequence. Three classes of epigenetic regulation exist: DNA methylation, histone modification, and noncoding RNA action. In the cardiovascular system, epigenetic regulation affects development, differentiation, and disease propensity or expression. Defining the determinants of epigenetic regulation offers opportunities for novel strategies for disease prevention and treatment.

The molecular biology of inflammatory bowel diseases.

PubMed

Corfield, Anthony P; Wallace, Heather M; Probert, Chris S J

2011-08-01

IBDs (inflammatory bowel diseases) are a group of diseases affecting the gastrointestinal tract. The diseases are multifactorial and cover genetic aspects: susceptibility genes, innate and adaptive responses to inflammation, and structure and efficacy of the mucosal protective barrier. Animal models of IBD have been developed to gain further knowledge of the disease mechanisms. These topics form an overlapping background to enable an improved understanding of the molecular features of these diseases. A series of articles is presented based on the topics covered at the Biochemical Society Focused Meeting The Molecular Biology of Inflammatory Bowel Diseases.

Concentration of carp edema virus (CEV) DNA in koi tissues affected by koi sleepy disease (KSD).

PubMed

Adamek, Mikolaj; Jung-Schroers, Verena; Hellmann, John; Teitge, Felix; Bergmann, Sven Michael; Runge, Martin; Kleingeld, Dirk Willem; Way, Keith; Stone, David Michael; Steinhagen, Dieter

2016-05-26

Carp edema virus (CEV), the causative agent of 'koi sleepy disease' (KSD), appears to be spreading worldwide and to be responsible for losses in koi, ornamental varieties of the common carp Cyprinus carpio. Clinical signs of KSD include lethargic behaviour, swollen gills, sunken eyes and skin alterations and can easily be mistaken for other diseases, such as infection with cyprinid herpesvirus 3 (CyHV-3). To improve the future diagnosis of CEV infection and to provide a tool to better explore the relationship between viral load and clinical disease, we developed a specific quantitative PCR (qPCR) for strains of the virus known to infect koi carp. In samples from several clinically affected koi, CEV-specific DNA was present in a range from 1 to 2,046,000 copies, with a mean of 129,982 copies and a median of 45 copies per 250 ng of isolated DNA, but virus DNA could not be detected in all clinically affected koi. A comparison of the newly developed qPCR, which is based on a dual-labelled probe, to an existing end-point PCR procedure revealed higher specificity and sensitivity of the qPCR and demonstrated that the new protocol could improve CEV detection in koi. In addition to improved diagnosis, the newly developed qPCR test would be a useful research tool. For example, studies on the pathobiology of CEV could employ controlled infection experiments in which the development of clinical signs could be examined in parallel with a quantitative determination of virus load.

Lay understanding of familial risk of common chronic diseases: a systematic review and synthesis of qualitative research.

PubMed

Walter, Fiona M; Emery, Jon; Braithwaite, Dejana; Marteau, Theresa M

2004-01-01

Although the family history is increasingly used for genetic risk assessment of common chronic diseases in primary care, evidence suggests that lay understanding about inheritance may conflict with medical models. This study systematically reviewed and synthesized the qualitative literature exploring understanding about familial risk held by persons with a family history of cancer, coronary artery disease, and diabetes mellitus. Twenty-two qualitative articles were found after a comprehensive literature search and were critically appraised; 11 were included. A meta-ethnographic approach was used to translate the studies across each other, synthesize the translation, and express the synthesis. A dynamic process emerged by which a personal sense of vulnerability included some features that mirror the medical factors used to assess risk, such as the number of affected relatives. Other features are more personal, such as experience of a relative's disease, sudden or premature death, perceived patterns of illness relating to gender or age at death, and comparisons between a person and an affected relative. The developing vulnerability is interpreted using personal mental models, including models of disease causation, inheritance, and fatalism. A person's sense of vulnerability affects how that person copes with, and attempts to control, any perceived familial risk. Persons with a family history of a common chronic disease develop a personal sense of vulnerability that is informed by the salience of their family history and interpreted within their personal models of disease causation and inheritance. Features that give meaning to familial risk may be perceived differently by patients and professionals. This review identifies key areas for health professionals to explore with patients that may improve the effectiveness of communication about disease risk and management.

Perinatal risk factors increase the risk of being affected by both type 1 diabetes and coeliac disease.

PubMed

Adlercreutz, Emma H; Wingren, Carl Johan; Vincente, Raquel P; Merlo, Juan; Agardh, Daniel

2015-02-01

This study investigated whether perinatal factors influenced the risk of a double diagnosis of type 1 diabetes and coeliac disease. We used multinomial logistic regression models to study the associations between perinatal factors, gender, mode of delivery, season of birth and the risk of type 1 diabetes, coeliac disease or both, in Swedish-born singleton children. We found that 4327 of the 768 395 children (0.6%) had been diagnosed with type 1 diabetes, 3817 (0.5%) had been diagnosed with coeliac disease and 191 (0.02%) were affected by both diseases. If the children already had type 1 diabetes (n = 4518), the absolute risk of being affected by coeliac disease increased to 4.2% (n = 191). Children with both type 1 diabetes and coeliac disease were more likely to be female (OR = 1.48, 95% CI = 1.01-1.97), delivered by Caesarean section (OR = 1.60, 95% CI = 1.07-2.39), have native-born Swedish mothers (OR = 4.84, 95% CI = 1.96-11.97) or be born during the summer months (OR = 1.43, 95% CI = 1.07-1.92). The increased risk of being affected by a double diagnosis of type 1 diabetes and coeliac disease was modulated by perinatal risk factors. This suggests that early life events are important when it comes to children with type 1 diabetes also developing coeliac disease. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Preterm piglets are a clinically relevant model of pediatric GI disease

USDA-ARS?s Scientific Manuscript database

The goal of our research is to establish how nutritional support, enteral versus parenteral, affects gut function and susceptibility to disease in early development. We and others have used the neonatal pig to establish unique models of clinically relevant problems in pediatric gastroenterology, esp...

Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis.

PubMed

Pancaldi, Fabrizio; Sebastiani, Marco; Cassone, Giulia; Luppi, Fabrizio; Cerri, Stefania; Della Casa, Giovanni; Manfredi, Andreina

2018-05-01

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis. Copyright © 2018 Elsevier Ltd. All rights reserved.

[The development of verrucous pastern dermatitis syndrome in heavy draught horses. Part I: Review of the literature].

PubMed

Geburek, F; Deegen, E; Hewicker-Trautwein, M; Ohnesorge, B

2005-06-01

Verrucous pastern dermatitis is a chronic hyperplastic dermatopathy of the feet of horses which is characterized by a greasy, odorous coating of the skin and, in advanced stages, by clearly demarcated calluses and wart-like proliferations. The disease occurs almost exclusively in cold-blooded and other heavy horses, with certain breeds affected most frequently. It is considered a distinct disease entity within the framework of pastern dermatitis syndrome. There is no consensus in the literature about relationship of the disease to the sex and age of the horse. Horses with a high cannon circumference and pronounced fetlock tufts of hair seem to be affected most severely. In chiefly anecdotal reports the cause of the disease or its aggravation has been ascribed to housing conditions and environmental influences, chemicals, mechanical insults, feeding, or infections with Chorioptes skin mites. It thus seems likely that the disease is affected by a variety of factors. Although verrucous pastern dermatitis has been known for hundreds of years, its etiology and pathogenesis remain unclear.

Twenty years of audiology in a patient with Norrie disease.

PubMed

Halpin, Chris; Sims, Katherine

2008-11-01

To describe disease progression and treatment outcomes over a 20-year period (ages 5-25) in a young man with Norrie disease (occuloacousticocerebral dysplasia), ND; OMIM #310600. Affected individuals are born blind and develop progressive sensory loss with onset in adolescence. This disease is X-linked and has been associated with mutations of the NDP gene (Xp11.4). The patient was followed using repeated audiograms, as well as reports of educational progress and hearing aid use. The specific mutation was found by molecular analysis. The patient demonstrated progressive sensory loss with good preservation of word recognition. The loss was initially high frequency and asymmetric in adolescence and became more severe, more symmetric and affected practically all frequencies by the end of childhood. Educational progress was affected by the cognitive effects of the syndrome, and hearing aid use was very effective. A bilateral progressive sensory loss with good preservation of word recognition was documented in detail. The residual word recognition supported good use of hearing aids in this case.

Affected parent sex and severity of autosomal dominant polycystic kidney disease: a retrospective cohort study
.

PubMed

Nowak, Kristen L; Chonchol, Michel; You, Zhiying; Gupta, Malika; Gitomer, Berenice

2018-03-01

Parental inheritance may differentially affect autosomal dominant polycystic kidney disease (-ADPKD) severity via genetic imprinting or in utero epigenetic modifications; however, evidence is inconsistent. We conducted a longitudinal retrospective cohort study to assess the association between sex of the affected parent and time to hypertension diagnosis, end-stage renal disease (ESRD), and death in patients with the PKD1 genotype. 814 individuals who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was parental sex, and outcomes were diagnosis of hypertension, progression to ESRD, and death. We also examined associations in four strata according to affected parent and participant sex, as previous studies have reported earlier onset of ESRD in males compared to females. The median follow-up for each outcome was as follows: hypertension, 30 (interquartile range (IQR): 18, 37); ESRD, 43 (IQR: 31, 52), death 39 (IQR: 25, 52) years of age. Among affected offspring in the entire cohort, there was no difference in hypertension diagnosis (p = 0.97) or progression to ESRD (p = 0.79) according to affected parent sex; however, participants with an affected mother were more likely to die than participants with an affected father (p < 0.05). In stratified analyses, males were more likely than females to develop hypertension and reach ESRD when the affected parent was the father (p < 0.01) but not when the affected parent was the mother (p ≥ 0.11). Our results are largely in contrast to the hypothesis that severity of ADPKD is worse with maternal inheritance of disease.
.

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476

Persistent impacts of West Nile virus on North American bird populations

PubMed Central

George, T. Luke; Harrigan, Ryan J.; LaManna, Joseph A.; DeSante, David F.; Saracco, James F.; Smith, Thomas B.

2015-01-01

Since its introduction to North America in 1999, West Nile virus (WNV) has had devastating impacts on native host populations, but to date these impacts have been difficult to measure. Using a continental-scale dataset comprised of a quarter-million birds captured over nearly two decades and a recently developed model of WNV risk, we estimated the impact of this emergent disease on the survival of avian populations. We find that populations were negatively affected by WNV in 23 of the 49 species studied (47%). We distinguished two groups of species: those for which WNV negatively impacted survival only during initial spread of the disease (n = 11), and those that show no signs of recovery since disease introduction (n = 12). Results provide a novel example of the taxonomic breadth and persistent impacts of this wildlife disease on a continental scale. Phylogenetic analyses further identify groups (New World sparrows, finches, and vireos) disproportionally affected by temporary or persistent WNV effects, suggesting an evolutionary dimension of disease risk. Identifying the factors affecting the persistence of a disease across host species is critical to mitigating its effects, particularly in a world marked by rapid anthropogenic change. PMID:26578774

Nutritional Epigenomics: A Portal to Disease Prevention12

PubMed Central

Choi, Sang-Woon; Claycombe, Kate J.; Martinez, J. Alfredo; Friso, Simonetta; Schalinske, Kevin L.

2013-01-01

Epigenetics can be defined as inheritable and reversible phenomena that affect gene expression without altering the underlying base pair sequence. Epigenomics is the study of genome-wide epigenetic modifications. Because gene expression changes are critical in both normal development and disease progression, epigenetics is widely applicable to many aspects of biological research. The influences of nutrients and bioactive food components on epigenetic phenomena such as DNA methylation and various types of histone modifications have been extensively investigated. Because an individual’s epigenetic patterns are established during early gestation and are changed and personalized by environmental factors during our lifetime, epigenetic mechanisms are quite important in the development of transgenerational and adult obesity as well as in the development of diabetes mellitus. Aging and cancer demonstrate profound genome-wide DNA methylation changes, suggesting that nutrition may affect the aging process and cancer development through epigenetic mechanisms. PMID:24038247

[Psychopathology and clinical features of oneiroid-catatonic conditions during endogenous diseases].

PubMed

Alekseeva, A G

2011-01-01

Psychopathology and clinical features of oneiroid-catatonic conditions during endogenous diseases remain a topical problem in modem psychiatry. The author describes psychopathologcal features of oneiroid depending on the form of the affect and presents new data on its relation to peculiarities of the development of attacks.

Emerging Therapeutic Approaches to Mitochondrial Diseases

ERIC Educational Resources Information Center

Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

2010-01-01

Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

Transcriptional and microscopic analyses of citrus stem and root responses to Candidatus Liberibacter asiaticus infection.

PubMed

Aritua, Valente; Achor, Diann; Gmitter, Frederick G; Albrigo, Gene; Wang, Nian

2013-01-01

Huanglongbing (HLB) is the most destructive disease that affects citrus worldwide. The disease has been associated with Candidatus Liberibacter. HLB diseased citrus plants develop a multitude of symptoms including zinc and copper deficiencies, blotchy mottle, corky veins, stunting, and twig dieback. Ca. L. asiaticus infection also seriously affects the roots. Previous study focused on gene expression of leaves and fruit to Ca. L. asiaticus infection. In this study, we compared the gene expression levels of stems and roots of healthy plants with those in Ca. L. asiaticus infected plants using microarrays. Affymetrix microarray analysis showed a total of 988 genes were significantly altered in expression, of which 885 were in the stems, and 111 in the roots. Of these, 551 and 56 were up-regulated, while 334 and 55 were down-regulated in the stem and root samples of HLB diseased trees compared to healthy plants, respectively. Dramatic differences in the transcriptional responses were observed between citrus stems and roots to Ca. L. asiaticus infection, with only 8 genes affected in both the roots and stems. The affected genes are involved in diverse cellular functions, including carbohydrate metabolism, cell wall biogenesis, biotic and abiotic stress responses, signaling and transcriptional factors, transportation, cell organization, protein modification and degradation, development, hormone signaling, metal handling, and redox. Microscopy analysis showed the depletion of starch in the roots of the infected plants but not in healthy plants. Collapse and thickening of cell walls were observed in HLB affected roots, but not as severe as in the stems. This study provides insight into the host response of the stems and roots to Ca. L. asiaticus infection.

Transcriptional and Microscopic Analyses of Citrus Stem and Root Responses to Candidatus Liberibacter asiaticus Infection

PubMed Central

Aritua, Valente; Achor, Diann; Gmitter, Frederick G.; Albrigo, Gene; Wang, Nian

2013-01-01

Huanglongbing (HLB) is the most destructive disease that affects citrus worldwide. The disease has been associated with Candidatus Liberibacter. HLB diseased citrus plants develop a multitude of symptoms including zinc and copper deficiencies, blotchy mottle, corky veins, stunting, and twig dieback. Ca. L. asiaticus infection also seriously affects the roots. Previous study focused on gene expression of leaves and fruit to Ca. L. asiaticus infection. In this study, we compared the gene expression levels of stems and roots of healthy plants with those in Ca. L. asiaticus infected plants using microarrays. Affymetrix microarray analysis showed a total of 988 genes were significantly altered in expression, of which 885 were in the stems, and 111 in the roots. Of these, 551 and 56 were up-regulated, while 334 and 55 were down-regulated in the stem and root samples of HLB diseased trees compared to healthy plants, respectively. Dramatic differences in the transcriptional responses were observed between citrus stems and roots to Ca. L. asiaticus infection, with only 8 genes affected in both the roots and stems. The affected genes are involved in diverse cellular functions, including carbohydrate metabolism, cell wall biogenesis, biotic and abiotic stress responses, signaling and transcriptional factors, transportation, cell organization, protein modification and degradation, development, hormone signaling, metal handling, and redox. Microscopy analysis showed the depletion of starch in the roots of the infected plants but not in healthy plants. Collapse and thickening of cell walls were observed in HLB affected roots, but not as severe as in the stems. This study provides insight into the host response of the stems and roots to Ca. L. asiaticus infection. PMID:24058486

The role of plant disease in the development of controlled ecological life support systems

NASA Technical Reports Server (NTRS)

Nelson, B.

1986-01-01

Plant diseases could be important factors affecting growth of higher plants in Closed Ecological Life Support Systems (CELSS). Disease control, therefore, will be needed to maintain healthy plants. The most important controls should be aimed at preventing the introduction, reproduction and spread of pathogens and preventing plant infection. An integrared ease control program will maximize that approach. In the design and operation of CELSS, plant disease should be considered an important aspect of plant growth. The effects of plant diseases are reviewed and several disease control measures are discussed.

New insights into gastrointestinal anthrax infection.

PubMed

Owen, Jennifer L; Yang, Tao; Mohamadzadeh, Mansour

2015-03-01

Bacterial infections are the primary cause of gastrointestinal (GI) disorders in both developing and developed countries, and are particularly dangerous for infants and children. Bacillus anthracis is the 'archetype zoonotic' pathogen; no other infectious disease affects such a broad range of species, including humans. Importantly, there are more case reports of GI anthrax infection in children than inhalational disease. Early diagnosis is difficult and widespread systemic disease develops rapidly. This review highlights new findings concerning the roles of the gut epithelia, commensal microbiota, and innate lymphoid cells (ILCs) in initiation of disease and systemic dissemination in animal models of GI anthrax, the understanding of which is crucial to designing alternative therapies that target the establishment of infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Globalization, inequality, and transmission of tropical diseases in the Venezuelan Amazon].

PubMed

Botto-Abella, Carlos; Graterol-Mendoza, Beatriz

2007-01-01

Economic globalization appears to be causing greater inequalities and increased vulnerability to tropical diseases around the world. The Venezuelan Amazon population, especially the rural indigenous population, displays among the worst health indicators in the Americas. High infant mortality rates in remote indigenous populations indicate that such communities have been affected by the globalization of disease, rather than favored by globalization of health. Globalization has also influenced public policies in the country, affecting the efficiency of control programs targeting tropical diseases. A new global pact for the sustainable development of the planet is needed, supported by the globalization of human values and rights. In Venezuela, new policies for the indigenous health sector, more resources, and greater autonomy could help reduce the inequities described here in the Venezuelan Amazon.

Resources, challenges and way forward in rare mitochondrial diseases research

PubMed Central

Rajput, Neeraj Kumar; Singh, Vipin; Bhardwaj, Anshu

2015-01-01

Over 300 million people are affected by about 7000 rare diseases globally. There are tremendous resource limitations and challenges in driving research and drug development for rare diseases. Hence, innovative approaches are needed to identify potential solutions. This review focuses on the resources developed over the past years for analysis of genome data towards understanding disease biology especially in the context of mitochondrial diseases, given that mitochondria are central to major cellular pathways and their dysfunction leads to a broad spectrum of diseases. Platforms for collaboration of research groups, clinicians and patients and the advantages of community collaborative efforts in addressing rare diseases are also discussed. The review also describes crowdsourcing and crowdfunding efforts in rare diseases research and how the upcoming initiatives for understanding disease biology including analyses of large number of genomes are also applicable to rare diseases. PMID:26180633

Tissue-specific insulin signaling, metabolic syndrome and cardiovascular disease

PubMed Central

Rask-Madsen, Christian; Kahn, C. Ronald

2012-01-01

Summary Impaired insulin signaling is central to the development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension and a proinflammatory state. However, insulin action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes. Recent advances in our understanding of the complex pathophysiology of insulin’s effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders. PMID:22895666

Women's Health and Lung Development and Disease.

PubMed

Kocurek, Emily G; Hemnes, Anna R

2016-06-01

Although the lung is not traditionally thought of as an organ affected by sex-based differences, emerging literature elucidates major differences between men and women in the development, physiology, and predilection to and outcomes in lung diseases. These differences are driven by both differences in sex hormones and differences in environmental exposures. However, in many cases the underlying etiology of these sex- and gender-based differences is unknown. This article outlines the state-of-the-art knowledge on the etiology of sex differences in lung disease, including differences in lung development and physiology, and reviews therapy recommendations that are sex based. Copyright © 2016 Elsevier Inc. All rights reserved.

BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

PubMed

Nowacka, Marta; Obuchowicz, Ewa

2013-01-01

Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

Case report of Aspergillus osteomyelitis of the ribs in an immunocompetent patient.

PubMed

D'sa, Shilpa Reynal; Singh, Suvir; Satyendra, Sowmya; Mathews, Prasad

2013-07-01

Aspergillus is a saprophytic fungus which is universally found in the environment. Most people breathe in the spores of Aspergillus every day without development of disease. It commonly affects immunocompromised hosts. There are only few reported cases in an immunocompetent host. It most commonly affects the respiratory system, causing superficial or invasive disease. It also affects the skin, brain and eye in severely immunocompromised patients. Aspergillosis of the bone is extremely rare. Amongst all the reported cases of invasive aspergillosis the incidence of osteomyelitis is less than three percent. In these cases commonly of the spine is reported. We present a case of Aspergillus osteomyelitis of the ribs in an immunocompetent host.

Case Report of Aspergillus Osteomyelitis of the Ribs in an Immunocompetent Patient

PubMed Central

D’sa, Shilpa Reynal; Singh, Suvir; Satyendra, Sowmya; Mathews, Prasad

2013-01-01

Aspergillus is a saprophytic fungus which is universally found in the environment. Most people breathe in the spores of Aspergillus every day without development of disease. It commonly affects immunocompromised hosts. There are only few reported cases in an immunocompetent host. It most commonly affects the respiratory system, causing superficial or invasive disease. It also affects the skin, brain and eye in severely immunocompromised patients. Aspergillosis of the bone is extremely rare. Amongst all the reported cases of invasive aspergillosis the incidence of osteomyelitis is less than three percent. In these cases commonly of the spine is reported. We present a case of Aspergillus osteomyelitis of the ribs in an immunocompetent host. PMID:24049367

Differential accumulation of proteins in oil palms affected by fatal yellowing disease

PubMed Central

do Nascimento, Sidney Vasconcelos; Magalhães, Marcelo Murad; Cunha, Roberto Lisboa; Costa, Paulo Henrique de Oliveira; Alves, Ronnie Cley de Oliveira; de Oliveira, Guilherme Corrêa

2018-01-01

There is still no consensus on the true origin of fatal yellowing, one of the most important diseases affecting oil palm (Elaeis guineensis Jacq.) plantations. This study involved two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-UPLC-MSE) analyses to identify changes in protein profiles of oil palms affected by FY disease. Oil palm roots were sampled from two growing areas. Differential accumulation of proteins was assessed by comparing plants with and without symptoms and between plants at different stages of FY development. Most of the proteins identified with differential accumulation were those related to stress response and energy metabolism. The latter proteins include the enzymes alcohol dehydrogenase and aldehyde dehydrogenase, related to alcohol fermentation, which were identified in plants with and without symptoms. The presence of these enzymes suggests an anaerobic condition before or during FY. Transketolase, isoflavone reductase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, S-adenosylmethionine synthase, aldehyde dehydrogenase and ferritin, among others, were identified as potential marker proteins and could be used to guide selection of FY-tolerant oil palm genotypes or to understand the source of this anomaly. When comparing different stages of FY, we observed high accumulation of alcohol dehydrogenase and other abiotic stress related-proteins at all disease stages. On the other hand, biological stress-related proteins were more accumulated at later stages of the disease. These results suggest that changes in abiotic factors can trigger FY development, creating conditions for the establishment of opportunistic pathogens. PMID:29621343

Multidisciplinary approach to R&D in vitiligo, a neglected skin disease.

PubMed

Valle, Yan; Lotti, Torello M; Hercogova, Jana; Schwartz, Robert A; Korobko, Igor V

2012-01-01

A global interest in therapies for neglected diseases is rising, but traditional biopharma research and development (R&D) process is prohibitively expensive to justify cost of their development. Vitiligo is a multifactorial orphan disease that affects at minimum 35 million people worldwide, yet no therapeutic solutions exist. The present authors describe a budget-minded pursuit of the new therapy development for vitiligo, which includes a multidiscipline collaboration and effective bridging between academic research, biobanking, and bioinformatics. The present authors anticipate that the present authors' "theoretically induced and empirically guided" discovery process will enable development of more leads, with a much greater probability of success and under tighter budgets compared with those of the biopharma company. Ultimately, the multidisciplinary approach described below facilitates the collaborative development of personalized treatments for different patient subpopulations in vitiligo and other neglected diseases. © 2012 Wiley Periodicals, Inc.

Highlights of the 11th International Bordetella Symposium: from Basic Biology to Vaccine Development

PubMed Central

Wirsing von König, Carl Heinz; Lan, Ruiting; Cotter, Peggy A.; Deora, Rajendar; Merkel, Tod J.; van Els, Cécile A.; Locht, Camille; Hozbor, Daniela; Rodriguez, Maria E.

2016-01-01

Pertussis is a severe respiratory disease caused by infection with the bacterial pathogen Bordetella pertussis. The disease affects individuals of all ages but is particularly severe and sometimes fatal in unvaccinated young infants. Other Bordetella species cause diseases in humans, animals, and birds. Scientific, clinical, public health, vaccine company, and regulatory agency experts on these pathogens and diseases gathered in Buenos Aires, Argentina from 5 to 8 April 2016 for the 11th International Bordetella Symposium to discuss recent advances in our understanding of the biology of these organisms, the diseases they cause, and the development of new vaccines and other strategies to prevent these diseases. Highlights of the meeting included pertussis epidemiology in developing nations, genomic analysis of Bordetella biology and evolution, regulation of virulence factor expression, new model systems to study Bordetella biology and disease, effects of different vaccines on immune responses, maternal immunization as a strategy to prevent newborn disease, and novel vaccine development for pertussis. In addition, the group approved the formation of an International Bordetella Society to promote research and information exchange on bordetellae and to organize future meetings. A new Bordetella.org website will also be developed to facilitate these goals. PMID:27655886

Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.

PubMed

Kido, Tatsuo; Sun, Zhaoyu; Lau, Yun-Fai Chris

2017-06-23

Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY ON ) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRY ON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

Bibliometric study of research and development for neglected diseases in the BRICS.

PubMed

Bai, Jing; Li, Wei; Huang, Yang-Mu; Guo, Yan

2016-09-06

Large numbers of people are suffering from a group of diseases that mainly affect developing countries, as there are no available or affordable products for prevention or treatment. Research and development (R&D) for these diseases is still a low priority on the health agenda. Brazil, Russia, India, China and South Africa (BRICS) are quickly growing economies and having more and more positive impact on global health. Additionally, their R&D capacity is believed to be enhanced through decades of investment in education and life science research. The BRICS, as a group of emerging and developing countries, are expected to make greater contributions to solving the problem that mainly affects the entire developing countries community. However, there has been little research to provide a macroscopic overview of BRICS' effort in R&D for neglected diseases. The aim of this study is to investigate scientific production in BRICS countries in this area and their main research hotspots. Global relevant literature was searched without time limits through PubMed and high yield countries were identified using GoPubMed. Literature up to the end of 2013 from the BRICS was obtained and high frequency words were extracted and clustered using Bibliography Item Co-occurrence Mining System 2.0 (BICOMS) and Graphical Clustering Toolkit 1.0 (gCLUTO). In total, 32, 47, 51, 31 and 44 high frequency words from Brazil, Russia, India, China and South Africa respectively were extracted for clustering analysis. The clustering indicated that eight diseases were research hotspots in BRICS countries. India had the most extensive hotspots and Brazil came in second. The other three countries shared common research foci: helminthiasis, Human Immunodeficiency Virus infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) and tuberculosis. Developed countries still make the majority of contributions to R&D on neglected diseases, but BRICS countries are playing a growing role. Instead of the "big three diseases" (HIV/AIDS, malaria and tuberculosis) recognized by WHO, the BRICS focus more on major causes of disease burden in their own countries. Disease burden and domestic policy, especially patent law, exert primary influence on the research focus.

Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

PubMed

D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

2015-07-29

Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how the immune system signals the brain to alter brain function. These findings broaden our understanding of how probiotics may beneficially affect brain function in the context of inflammation occurring within the body and may open potential new therapeutic alternatives for the treatment of these alterations in behavior that can greatly affect patient quality of life. Copyright © 2015 the authors 0270-6474/15/3510822-10$15.00/0.

Self-Management Education for Rehabilitation Inpatients Suffering from Inflammatory Bowel Disease: A Cluster-Randomized Controlled Trial

ERIC Educational Resources Information Center

Reusch, A.; Weiland, R.; Gerlich, C.; Dreger, K.; Derra, C.; Mainos, D.; Tuschhoff, T.; Berding, A.; Witte, C.; Kaltz, B.; Faller, H.

2016-01-01

Although inflammatory bowel disease (IBD) affects patients' psychological well-being, previous educational programs have failed to demonstrate effects on psychosocial outcomes and quality of life. Therefore, we developed a group-based psychoeducational program that combined provision of both medical information and psychological self-management…

Landscape Risk Factors for Lyme Disease in the Eastern Broadleaf Forest Province of the Hudson River Valley and the Effect of Explanatory Data Classification Resolution

EPA Science Inventory

This study assessed how landcover classification affects associations between landscape characteristics and Lyme disease rate. Landscape variables were derived from the National Land Cover Database (NLCD), including native classes (e.g., deciduous forest, developed low intensity)...

A Cardiovascular Health Program for Latinos Supplemented with Pedometers

ERIC Educational Resources Information Center

Trudnak, Tara; Lloyd, Angela; Westhoff, Wayne W.; Corvin, Jaime

2011-01-01

Background: Physical inactivity is an important modifiable risk factor for many chronic diseases which disproportionately affect Latinos in the U.S. Targeting at-risk Latinos for prevention and intervention programs to increase physical activity can help decrease their risk for developing these diseases. Purpose: The purpose of this study was to…

Using comparative genomics to develop a new model of understanding Verticillium wilt resistance in potato

USDA-ARS?s Scientific Manuscript database

Verticillium wilt (VW) is a persistent and costly disease affecting potato production. VW is caused by the soilborne fungi Verticillium dahliae and V. albo-atrum. Because of the difficulty in dealing with this disease, host resistance offers a low input, effective method of control. Most potato cult...

Lifestyle Factors in Late Adolescence Associate With Later Development of Diverticular Disease Requiring Hospitalization.

PubMed

Järbrink-Sehgal, M Ellionore; Schmidt, Peter T; Sköldberg, Filip; Hemmingsson, Tomas; Hagström, Hannes; Andreasson, Anna

2018-04-12

The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life. We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease. Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007). In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Analysis of Nucleotide Variations in Genes of Iron Management in Patients of Parkinson's Disease and Other Movement Disorders

PubMed Central

Castiglioni, Emanuela; Finazzi, Dario; Goldwurm, Stefano; Pezzoli, Gianni; Forni, Gianluca; Girelli, Domenico; Maccarinelli, Federica; Poli, Maura; Ferrari, Maurizio; Cremonesi, Laura; Arosio, Paolo

2011-01-01

The capacity to act as an electron donor and acceptor makes iron an essential cofactor of many vital processes. Its balance in the body has to be tightly regulated since its excess can be harmful by favouring oxidative damage, while its deficiency can impair fundamental activities like erythropoiesis. In the brain, an accumulation of iron or an increase in its availability has been associated with the development and/or progression of different degenerative processes, including Parkinson's disease, while iron paucity seems to be associated with cognitive deficits, motor dysfunction, and restless legs syndrome. In the search of DNA sequence variations affecting the individual predisposition to develop movement disorders, we scanned by DHPLC the exons and intronic boundary regions of ceruloplasmin, iron regulatory protein 2, hemopexin, hepcidin and hemojuvelin genes in cohorts of subjects affected by Parkinson's disease and idiopathic neurodegeneration with brain iron accumulation (NBIA). Both novel and known sequence variations were identified in most of the genes, but none of them seemed to be significantly associated to the movement diseases of interest. PMID:20981230

Patient-specific induced pluripotent stem cells (iPSCs) for the study and treatment of retinal degenerative diseases.

PubMed

Wiley, Luke A; Burnight, Erin R; Songstad, Allison E; Drack, Arlene V; Mullins, Robert F; Stone, Edwin M; Tucker, Budd A

2015-01-01

Vision is the sense that we use to navigate the world around us. Thus it is not surprising that blindness is one of people's most feared maladies. Heritable diseases of the retina, such as age-related macular degeneration and retinitis pigmentosa, are the leading cause of blindness in the developed world, collectively affecting as many as one-third of all people over the age of 75, to some degree. For decades, scientists have dreamed of preventing vision loss or of restoring the vision of patients affected with retinal degeneration through drug therapy, gene augmentation or a cell-based transplantation approach. In this review we will discuss the use of the induced pluripotent stem cell technology to model and develop various treatment modalities for the treatment of inherited retinal degenerative disease. We will focus on the use of iPSCs for interrogation of disease pathophysiology, analysis of drug and gene therapeutics and as a source of autologous cells for cell transplantation and replacement. Copyright © 2014. Published by Elsevier Ltd.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Tc-99m pyrophosphate myocardial scanning in Chagas' disease

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

Goncalves da Rocha, A.F.; Meguerian, B.A.; Harbert, J.C.

1981-04-01

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas's disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Ecology and management of grapevine leafroll disease.

PubMed

Almeida, Rodrigo P P; Daane, Kent M; Bell, Vaughn A; Blaisdell, G Kai; Cooper, Monica L; Herrbach, Etienne; Pietersen, Gerhard

2013-01-01

Grapevine leafroll disease (GLD) is caused by a complex of vector-borne virus species in the family Closteroviridae. GLD is present in all grape-growing regions of the world, primarily affecting wine grape varieties. The disease has emerged in the last two decades as one of the major factors affecting grape fruit quality, leading to research efforts aimed at reducing its economic impact. Most research has focused on the pathogens themselves, such as improved detection protocols, with limited work directed toward disease ecology and the development of management practices. Here we discuss the ecology and management of GLD, focusing primarily on Grapevine leafroll-associated virus 3, the most important virus species within the complex. We contextualize research done on this system within an ecological framework that forms the backbone of the discussion regarding current and potential GLD management strategies. To reach this goal, we introduce various aspects of GLD biology and ecology, followed by disease management case studies from four different countries and continents (South Africa, New Zealand, California-USA, and France). We review ongoing regional efforts that serve as models for improved strategies to control this economically important and worldwide disease, highlighting scientific gaps that must be filled for the development of knowledge-based sustainable GLD management practices.

Ecology and management of grapevine leafroll disease

PubMed Central

Almeida, Rodrigo P. P.; Daane, Kent M.; Bell, Vaughn A.; Blaisdell, G. Kai; Cooper, Monica L.; Herrbach, Etienne; Pietersen, Gerhard

2013-01-01

Grapevine leafroll disease (GLD) is caused by a complex of vector-borne virus species in the family Closteroviridae. GLD is present in all grape-growing regions of the world, primarily affecting wine grape varieties. The disease has emerged in the last two decades as one of the major factors affecting grape fruit quality, leading to research efforts aimed at reducing its economic impact. Most research has focused on the pathogens themselves, such as improved detection protocols, with limited work directed toward disease ecology and the development of management practices. Here we discuss the ecology and management of GLD, focusing primarily on Grapevine leafroll-associated virus 3, the most important virus species within the complex. We contextualize research done on this system within an ecological framework that forms the backbone of the discussion regarding current and potential GLD management strategies. To reach this goal, we introduce various aspects of GLD biology and ecology, followed by disease management case studies from four different countries and continents (South Africa, New Zealand, California-USA, and France). We review ongoing regional efforts that serve as models for improved strategies to control this economically important and worldwide disease, highlighting scientific gaps that must be filled for the development of knowledge-based sustainable GLD management practices. PMID:23630520

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

NASA Astrophysics Data System (ADS)

Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

2016-05-01

The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

Cow milk induced allergies (CMA) and asthma in new born.

PubMed

Wang, W; Wu, H-W; Liu, J-F

2016-01-01

The prevalence of asthma and allergic diseases in childhood has increased in several industrialized countries since the second half of the twentieth century. In some countries, the prevalence is still rising, although in others it seems to have plateaued or even decreased. It has been suggested that environmental factors operating prenatally and in early life affect the development of asthma and allergic diseases. Particularly changes in microbial exposure are proposed to play an important role in the development and maturation of the immune system. Thus, the factors that affect microbial exposure, such as mode of delivery and the use of antibiotics, may influence the development of asthma and allergic diseases. Several studies have explored the associations between perinatal factors and children's use of antibiotics and the risk of asthma, with inconsistent findings. The present review article will be focused on the important findings related with factors responsible for above allergic reactions along with asthma in young infants. Also, the influence of cow milk intake will also be taken in account to cover the aspect of cow milk induced allergies and asthma in infants.

Emerging topical onychomycosis therapies - quo vadis?

PubMed

Elkeeb, Rania; Hui, Xiaoying; Murthy, Narasimha; Maibach, Howard I

2014-12-01

Onychomycosis, a common chronic fungal infection affecting fingernails and toenails, globally may affect 10 - 30% of the population. This chronic disease is difficult to eradicate. The goal of developing a highly effective and safe topical treatment has not yet been reached as it depends on the type of onychomycosis and the variety of invaders. Topical drug delivery to the nail is highly desirable in treating nail disorders. However, efficacy of topical therapies is low due to their limited permeability across the nail plate. Advances have especially been made by the development of new therapeutic options including new drug entities, new formulations and reformulations. This overview updates emerging topical treatments for onychomycosis, research progress and future perspectives. Development of novel effective noninvasive topical therapy for treating onychomycosis and other nail diseases such as psoriasis is long overdue. Previously there was a lack of basic knowledge about nail and its barrier properties, but with the recent increased interest in this field both from industry and academia, we hope extensive research will continue in this field to bring about successful and safe treatments for such chronic diseases.

A theoretical flaw in the advance market commitment idea.

PubMed

Sonderholm, Jorn

2010-06-01

Infectious and parasitic diseases cause massive health problems in the developing world. Research and development of drugs for diseases that mainly affect poor people in developing countries is limited. The advance market commitment (AMC) idea is an incentivising mechanism for research and development of drugs for neglected diseases. Discussion of the AMC idea is of renewed interest given the launch in June 2009 of the first AMC. This pilot AMC is designed to, among other things, test the idea for potential future applications. This paper is a critique of the AMC idea. It seeks to show that the idea has a hitherto unrecognised theoretical flaw that should make policy-makers and donors hesitant to embrace future applications of the idea.

Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

PubMed

Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

2016-03-01

Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant. © The Author(s) 2015.

Advances on Fungal Phytotoxins and Their Role in Grapevine Trunk Diseases.

PubMed

Masi, Marco; Cimmino, Alessio; Reveglia, Pierluigi; Mugnai, Laura; Surico, Giuseppe; Evidente, Antonio

2018-06-20

Grapevines are produced worldwide with important impact on local economies. Several biotic stresses induce serious diseases of grapevine, which severely affect the quantity and quality of production. One of the most important problems of vineyards worldwide is the high incidence of grapevine trunk diseases (GTD) induced by fungi belonging to several genera. Environmentally friendly methods for GTD control are being studied. This perspective offers an advanced overview on the fungal phytotoxins involved in GTD and their eventual role in the development of disease symptoms.

Diverticular disease: A therapeutic overview

PubMed Central

Tursi, Antonio

2010-01-01

Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment efficacy by shortening the course of the disease and preventing recurrences. PMID:21577292

Impact of yellow fever on the developing world.

PubMed

Tomori, O

1999-01-01

Yellow fever (YF) has remained a disease of public health importance since it was first described in the fifteenth century. At different periods in human history, YF has caused untold hardship and indescribable misery among populations in the Americas, Europe, and Africa. It brought economic disaster in its wake, constituting a stumbling block to development. Yellow fever is an arboviral infection with three epidemiological transmission cycles between monkeys, mosquitoes, and humans. It is an acute infectious disease characterized by sudden onset, with two phases of development separated by a short period of remission. The clinical spectrum of YF varies from a very mild, nonspecific, febrile illness to a fulminating, sometimes fatal disease with pathognomonic features. In severe cases, jaundice and bleeding diathesis with hepatorenal involvement are common. The fatality rate of severe YF is 50% or higher. Despite landmark achievements in the understanding of the epidemiology of YF and the availability of a safe, efficacious vaccine, YF remains a major public health problem in both Africa and South America, where annually the disease affects an estimated 200,000 persons, causing an estimated 30,000 deaths. Since the 1980s epidemics of YF in Africa have affected predominantly children under the age of 15 years. The failure to control YF arises from a misapplication of public health strategies and insufficient political commitment by governments in YF endemic areas, especially in Africa, to control the disease.

Roles of O-GlcNAc in chronic diseases of aging.

PubMed

Banerjee, Partha S; Lagerlöf, Olof; Hart, Gerald W

2016-10-01

O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diverticular Disease-associated Colitis: What Do We Know? A Review of Literature.

PubMed

Haddad, Fady G; El Bitar, Sandy; Al Moussawi, Hassan; Chang, Qing; Deeb, Liliane

2018-02-24

Diverticular disease (DD) is a leading cause of hospitalizations in developed countries affecting 30-50% of individuals older than 60 years. Identified as a distinct entity since 1980, diverticular disease-associated colitis (DAC) describes the occurrence of mucosal inflammation in a colon segment affected with DD with relative sparing of the rectum and proximal colon. Its prevalence is suggested around 1.3-3.8%. Pathogenesis is multifactorial with multiple reports noting clinicopathological overlap between DAC and inflammatory bowel disease (IBD) especially in patients with granulomatous colitis. In this setting, caution should be exercised to avoid an inappropriate diagnosis of IBD. Recurrence rates and long-term outcomes of DAC are not well defined and could range from a benign course to an overt IBD. More studies are needed in order to further characterize this entity.

Intravital multiphoton tomography as an appropriate tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

NASA Astrophysics Data System (ADS)

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Mess, Christian; Dimitrova, Valentina; Schwarz, Martin; Riemann, Iris; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

2011-03-01

Increasing incidence of inflammatory skin diseases such as Atopic Dermatitis (AD) has been noted in the past years. According to recent estimations around 15% of newborn subjects are affected with a disease severity that requires medical treatment. Although its pathogenesis is multifactorial, recent reports indicate that an impaired physical skin barrier predispose for the development of AD. The major part of this barrier is formed by the stratum corneum (SC) wherein corneocytes are embedded in a complex matrix of proteins and lipids. Its components were synthesized in the stratum granulosum (SG) and secreted via lamellar bodies at the SC/SG interface. Within a clinical in vivo study we focused on the skin metabolism at the SC/SG interface in AD affected patients in comparison to healthy subjects. Measurement of fluorescence life-time of NADH provides access to the metabolic state of skin. Due to the application of a 5D intravital tomographic skin analysis we facilitate the non-invasive investigation of human epidermis in the longitudinal course of AD therapy. We could ascertain by blinded analysis of 40 skin areas of 20 patients in a three month follow-up that the metabolic status at the SC/SG interface was altered in AD compromised skin even in non-lesional, apparent healthy skin regions. This illustrates an impaired skin barrier formation even at non-affected skin of AD subjects appearing promotive for the development of acute skin inflammation. Therefore, our findings allow a deeper understanding of the individual disease development and the improved management of the therapeutic intervention in clinical application.

Drug discovery and development for rare genetic disorders.

PubMed

Sun, Wei; Zheng, Wei; Simeonov, Anton

2017-09-01

Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.

The role of gut microbiota in the pathogenesis of rheumatic diseases.

PubMed

Zhong, Danli; Wu, Chanyuan; Zeng, Xiaofeng; Wang, Qian

2018-01-01

Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses. In this article, we discussed the role of gut microbiota in the pathogenesis of rheumatic diseases based on a large number of experimental and clinical materials, thereby providing a new insight for microbiota-targeted therapies to prevent or cure rheumatic diseases.

The Neurotrophins and Their Role in Alzheimer’s Disease

PubMed Central

Allen, Shelley J; Watson, Judy J; Dawbarn, David

2011-01-01

Besides being essential for correct development of the vertebrate nervous system the neurotrophins also play a vital role in adult neuron survival, maintenance and regeneration. In addition they are implicated in the pathogenesis of certain neurodegenerative diseases, and may even provide a therapeutic solution for some. In particular there have been a number of studies on the involvement of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in the development of Alzheimer’s disease. This disease is of growing concern as longevity increases worldwide, with little treatment available at the moment to alleviate the condition. Memory loss is one of the earliest symptoms associated with Alzheimer’s disease. The brain regions first affected by pathology include the hippocampus, and also the entorhinal cortex and basal cholinergic nuclei which project to the hippocampus; importantly, all these areas are required for memory formation. Both NGF and BDNF are affected early in the disease and this is thought to initiate a cascade of events which exacerbates pathology and leads to the symptoms of dementia. This review briefly describes the pathology, symptoms and molecular processes associated with Alzheimer’s disease; it discusses the involvement of the neurotrophins, particularly NGF and BDNF, and their receptors, with changes in BDNF considered particularly in the light of its importance in synaptic plasticity. In addition, the possibilities of neurotrophin-based therapeutics are evaluated. PMID:22654716

Malignant melanoma and Charcot-Marie-Tooth disease: A further case

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

Manoukian, S.; Briscioli, V.; Lalatta, F.

1997-01-20

In a previous issue of this journal, Greene et al. described 2 patients with Charcot-Marie-Tooth (CMT) disease who later developed cutaneous malignant melanoma. Although the development of the two diseases in the same patient may have occurred by chance, the authors raised the possibility of a shared neural crest defect or a genetic linkage. Among the patients reported by Greene et al., one had a dominant form of CMT. The patient`s mother and brother were similarly affected. A paternal aunt died of melanoma. The second patient had a neuronal type of CMT. His brother showed the same disease, but themore » parents were not examined. 7 refs.« less

Optical Diagnostics for Classifying Stages of Dental Erythema

NASA Astrophysics Data System (ADS)

Davis, Matthew J.; Splinter, Robert; Lockhart, Peter; Brennan, Michael; Fox, Philip C.

2003-02-01

Periodontal disease is a term used to describe an inflammatory disease affecting the tissues surrounding and supporting the teeth. Periodontal diseases are some of the most common chronic disorders, which affect humans in all parts of the world. Treatment usually involves the removal of plaque and calculus by scaling and polishing the tooth. In some cases a surgical reduction of hyperplastic tissue, may also be required. In addition, periodontitis is a risk factor for systemic disorders such as cardiovascular disease and diabetes. Current detection methods are qualitative, inaccurate, and often do not detect the periodontal disease in its early, reversible stages. Therefore, an early detection method should be implemented identifying the relationship of periodontal disease with erythema. In order to achieve this purpose we are developing an optical erythema meter to diagnose the periodontal disease in its reversible, gingival stage. The discrimination between healthy and diseased gum tissue was made by using the reflection of two illuminating wavelengths provided by light emitting diodes operating at wavelengths that target the absorption and reflection spectra of the highlights of each particular tissue type (healthy or diseased, and what kind of disease). Three different color gels could successfully be distinguished with a statistical significance of P < 0.05.

Shortening the decade-long gap between adult and paediatric drug formulations: a new framework based on the HIV experience in low- and middle-income countries.

PubMed

Penazzato, Martina; Lewis, Linda; Watkins, Melynda; Prabhu, Vineet; Pascual, Fernando; Auton, Martin; Kreft, Wesley; Morin, Sébastien; Vicari, Marissa; Lee, Janice; Jamieson, David; Siberry, George K

2018-02-01

Despite the coordinated efforts by several stakeholders to speed up access to HIV treatment for children, development of optimal paediatric formulations still lags 8 to 10 years behind that of adults, due mainly to lack of market incentives and technical complexities in manufacturing. The small and fragmented paediatric market also hinders launch and uptake of new formulations. Moreover, the problems affecting HIV similarly affect other disease areas where development and introduction of optimal paediatric formulations is even slower. Therefore, accelerating processes for developing and commercializing optimal paediatric drug formulations for HIV and other disease areas is urgently needed. The Global Accelerator for Paediatric Formulations (GAP-f) is an innovative collaborative model that will accelerate availability of optimized treatment options for infectious diseases, such as HIV, tuberculosis and viral hepatitis, affecting children in low- and middle-income countries (LMICs). It builds on the HIV experience and existing efforts in paediatric drug development, formalizing collaboration between normative bodies, research networks, regulatory agencies, industry, supply and procurement organizations and funding bodies. Upstream, the GAP-f will coordinate technical support to companies to design and study optimal paediatric formulations, harmonize efforts with regulators and incentivize manufacturers to conduct formulation development. Downstream, the GAP-f will reinforce coordinated procurement and communication with suppliers. The GAP-f will be implemented in a three-stage process: (1) development of a strategic framework and promotion of key regulatory efficiencies; (2) testing of feasibility and results, building on the work of existing platforms such as the Paediatric HIV Treatment Initiative (PHTI) including innovative approaches to incentivize generic development and (3) launch as a fully functioning structure. GAP-f is a key partnership example enhancing North-South and international cooperation on and access to science and technology and capacity building, responding to Sustainable Development Goal (SDG) 17.6 (technology) and 17.9. (capacity-building). By promoting access to the most needed paediatric formulations for HIV and high-burden infectious diseases in low-and middle-income countries, GAP-f will support achievement of SDG 3.2 (infant mortality), 3.3 (end of AIDS and combat other communicable diseases) and 3.8 (access to essential medicines), and be an essential component of meeting the global Start Free, Stay Free, AIDS Free super-fast-track targets. © 2018 World Health Organization; licensee IAS.

Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies.

PubMed

Joshi, Lok R; Mohr, Kristin A; Clement, Travis; Hain, Kyle S; Myers, Bryan; Yaros, Joseph; Nelson, Eric A; Christopher-Hennings, Jane; Gava, Danielle; Schaefer, Rejane; Caron, Luizinho; Dee, Scott; Diel, Diego G

2016-06-01

Senecavirus A (SVA) is an emerging picornavirus that has been recently associated with an increased number of outbreaks of vesicular disease and neonatal mortality in swine. Many aspects of SVA infection biology and epidemiology remain unknown. Here, we present a diagnostic investigation conducted in swine herds affected by vesicular disease and increased neonatal mortality. Clinical and environmental samples were collected from affected and unaffected herds and were screened for the presence of SVA by real-time reverse transcriptase PCR and virus isolation. Notably, SVA was detected and isolated from vesicular lesions and tissues of affected pigs, environmental samples, mouse feces, and mouse small intestine. SVA nucleic acid was also detected in houseflies collected from affected farms and from a farm with no history of vesicular disease. Detection of SVA in mice and housefly samples and recovery of viable virus from mouse feces and small intestine suggest that these pests may play a role on the epidemiology of SVA. These results provide important information that may allow the development of improved prevention and control strategies for SVA. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Detection of the Emerging Picornavirus Senecavirus A in Pigs, Mice, and Houseflies

PubMed Central

Joshi, Lok R.; Mohr, Kristin A.; Clement, Travis; Hain, Kyle S.; Myers, Bryan; Yaros, Joseph; Nelson, Eric A.; Christopher-Hennings, Jane; Gava, Danielle; Schaefer, Rejane; Caron, Luizinho; Dee, Scott

2016-01-01

Senecavirus A (SVA) is an emerging picornavirus that has been recently associated with an increased number of outbreaks of vesicular disease and neonatal mortality in swine. Many aspects of SVA infection biology and epidemiology remain unknown. Here, we present a diagnostic investigation conducted in swine herds affected by vesicular disease and increased neonatal mortality. Clinical and environmental samples were collected from affected and unaffected herds and were screened for the presence of SVA by real-time reverse transcriptase PCR and virus isolation. Notably, SVA was detected and isolated from vesicular lesions and tissues of affected pigs, environmental samples, mouse feces, and mouse small intestine. SVA nucleic acid was also detected in houseflies collected from affected farms and from a farm with no history of vesicular disease. Detection of SVA in mice and housefly samples and recovery of viable virus from mouse feces and small intestine suggest that these pests may play a role on the epidemiology of SVA. These results provide important information that may allow the development of improved prevention and control strategies for SVA. PMID:27030489

Iron Deficiency Anemia: Focus on Infectious Diseases in Lesser Developed Countries

PubMed Central

Shaw, Julia G.; Friedman, Jennifer F.

2011-01-01

Iron deficiency anemia is thought to affect the health of more than one billion people worldwide, with the greatest burden of disease experienced in lesser developed countries, particularly women of reproductive age and children. This greater disease burden is due to both nutritional and infectious etiologies. Individuals in lesser developed countries have diets that are much lower in iron, less access to multivitamins for young children and pregnant women, and increased rates of fertility which increase demands for iron through the life course. Infectious diseases, particularly parasitic diseases, also lead to both extracorporeal iron loss and anemia of inflammation, which decreases bioavailability of iron to host tissues. This paper will address the unique etiologies and consequences of both iron deficiency anemia and the alterations in iron absorption and distribution seen in the context of anemia of inflammation. Implications for diagnosis and treatment in this unique context will also be discussed. PMID:21738863

Parasitic diseases and urban development.

PubMed Central

Mott, K. E.; Desjeux, P.; Moncayo, A.; Ranque, P.; de Raadt, P.

1990-01-01

The distribution and epidemiology of parasitic diseases in both urban and periurban areas of endemic countries have been changing as development progresses. The following different scenarios involving Chagas disease, lymphatic filariasis, leishmaniasis and schistosomiasis are discussed: (1) infected persons entering nonendemic urban areas without vectors; (2) infected persons entering nonendemic urban areas with vectors; (3) infected persons entering endemic urban areas; (4) non-infected persons entering endemic urban areas; (5) urbanization or domestication of natural zoonotic foci; and (6) vectors entering nonendemic urban areas. Cultural and social habits from the rural areas, such as type of house construction and domestic water usage, are adopted by migrants to urban areas and increase the risk of disease transmission which adversely affects employment in urban populations. As the urban health services must deal with the rise in parasitic diseases, appropriate control strategies for the urban setting must be developed and implemented. PMID:2127380

Global food security: the impact of veterinary parasites and parasitologists.

PubMed

Fitzpatrick, J L

2013-08-01

Global food security will require the production of more food using resources including land more efficiently, and with less waste. This goal must be achieved within the context of climate change and while ensuring minimal adverse environmental impact from both crop and livestock production. Disease, especially infectious disease, is a main constraint of biologically efficient livestock production and both endemic and exotic disease results in mortality and morbidity and hence less food than should ideally be available in current farming systems. A significant proportion of diseases affect the safety of food supplies, in addition to or instead of, their effect on volume and quality of food products. Parasitological diseases including those caused by nematodes, trematodes, protozoa and ectoparasites, have widely differing effects on meat, milk and fibre production and many new technologies have been developed in order to prevent or treat them. Approaches to developing better control of parasites have included livestock breeding strategies, improved nutrition and management, and the development of new drugs, diagnostic tests and vaccines. Some of the most important examples include both the development of new anthelmintic products, and better means of using existing drugs in order to maximise their effectiveness in the face of rapidly increasing parasite resistance; diagnostic tests which are able to detect low levels of nucleic acids or proteins from infectious agents rapidly; and vaccines derived from either native or recombinant proteins and designed to stimulate the most appropriate protective response from livestock species. Some of the parasitic diseases affect restricted regions around the world, however most affect very large global populations. The development of technologies of suitable and affordable livestock products for use in developing countries where most pressure on increased production for food will occur, provides a particular challenge. Most if not all new technologies form part of integrated management schemes on farms and these vary hugely in differing systems and geographical regions of the world. If the benefit of improved technologies for optimal health, welfare and biological efficiency of livestock is to be realised, then the veterinary, farming, commercial animal health and public service communities need to learn lessons from past successes and failures in the delivery of newly developed technologies to the farmer. The combination of technology and rural development in the veterinary parasitological field has played a key role in current food production and is well placed to continue this trend to help in ensuring future food requirements for the world. Copyright © 2013. Published by Elsevier B.V.

Recent Mitochondrial DNA Mutations Increase the Risk of Developing Common Late-Onset Human Diseases

PubMed Central

Hudson, Gavin; Gomez-Duran, Aurora; Wilson, Ian J.; Chinnery, Patrick F.

2014-01-01

Mitochondrial DNA (mtDNA) is highly polymorphic at the population level, and specific mtDNA variants affect mitochondrial function. With emerging evidence that mitochondrial mechanisms are central to common human diseases, it is plausible that mtDNA variants contribute to the “missing heritability” of several complex traits. Given the central role of mtDNA genes in oxidative phosphorylation, the same genetic variants would be expected to alter the risk of developing several different disorders, but this has not been shown to date. Here we studied 38,638 individuals with 11 major diseases, and 17,483 healthy controls. Imputing missing variants from 7,729 complete mitochondrial genomes, we captured 40.41% of European mtDNA variation. We show that mtDNA variants modifying the risk of developing one disease also modify the risk of developing other diseases, thus providing independent replication of a disease association in different case and control cohorts. High-risk alleles were more common than protective alleles, indicating that mtDNA is not at equilibrium in the human population, and that recent mutations interact with nuclear loci to modify the risk of developing multiple common diseases. PMID:24852434

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

PubMed Central

Vidal-Brime, Laia; Lynn, K. Sabrina

2018-01-01

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease. PMID:29701678

Market Dynamics and Optimal Timber Salvage After a Natural Catastrophe

Treesearch

Jeffrey P. Prestemon; Thomas P. Holmes

2004-01-01

Forest-based natural catastrophes are regular features of timber production in the United States, especially from hurricanes, fires, and insect and disease outbreaks. These catastrophes affect timber prices and result in economic transfers. We develop a model of timber market dynamics after such a catastrophe that shows how timber salvage affects the welfare of...

How Wearable Sensors Can Support Parkinson's Disease Diagnosis and Treatment: A Systematic Review

PubMed Central

Rovini, Erika; Maremmani, Carlo; Cavallo, Filippo

2017-01-01

Background: Parkinson's disease (PD) is a common and disabling pathology that is characterized by both motor and non-motor symptoms and affects millions of people worldwide. The disease significantly affects quality of life of those affected. Many works in literature discuss the effects of the disease. The most promising trends involve sensor devices, which are low cost, low power, unobtrusive, and accurate in the measurements, for monitoring and managing the pathology. Objectives: This review focuses on wearable devices for PD applications and identifies five main fields: early diagnosis, tremor, body motion analysis, motor fluctuations (ON–OFF phases), and home and long-term monitoring. The concept is to obtain an overview of the pathology at each stage of development, from the beginning of the disease to consider early symptoms, during disease progression with analysis of the most common disorders, and including management of the most complicated situations (i.e., motor fluctuations and long-term remote monitoring). Data sources: The research was conducted within three databases: IEEE Xplore®, Science Direct®, and PubMed Central®, between January 2006 and December 2016. Study eligibility criteria: Since 1,429 articles were found, accurate definition of the exclusion criteria and selection strategy allowed identification of the most relevant papers. Results: Finally, 136 papers were fully evaluated and included in this review, allowing a wide overview of wearable devices for the management of Parkinson's disease. PMID:29056899

How Wearable Sensors Can Support Parkinson's Disease Diagnosis and Treatment: A Systematic Review.

PubMed

Rovini, Erika; Maremmani, Carlo; Cavallo, Filippo

2017-01-01

Background: Parkinson's disease (PD) is a common and disabling pathology that is characterized by both motor and non-motor symptoms and affects millions of people worldwide. The disease significantly affects quality of life of those affected. Many works in literature discuss the effects of the disease. The most promising trends involve sensor devices, which are low cost, low power, unobtrusive, and accurate in the measurements, for monitoring and managing the pathology. This review focuses on wearable devices for PD applications and identifies five main fields: early diagnosis, tremor, body motion analysis, motor fluctuations (ON-OFF phases), and home and long-term monitoring. The concept is to obtain an overview of the pathology at each stage of development, from the beginning of the disease to consider early symptoms, during disease progression with analysis of the most common disorders, and including management of the most complicated situations (i.e., motor fluctuations and long-term remote monitoring). The research was conducted within three databases: IEEE Xplore®, Science Direct®, and PubMed Central®, between January 2006 and December 2016. Since 1,429 articles were found, accurate definition of the exclusion criteria and selection strategy allowed identification of the most relevant papers. Finally, 136 papers were fully evaluated and included in this review, allowing a wide overview of wearable devices for the management of Parkinson's disease.

Ecosystem screening approach for pathogen-associated microorganisms affecting host disease.

PubMed

Galiana, Eric; Marais, Antoine; Mura, Catherine; Industri, Benoît; Arbiol, Gilles; Ponchet, Michel

2011-09-01

The microbial community in which a pathogen evolves is fundamental to disease outcome. Species interacting with a pathogen on the host surface shape the distribution, density, and genetic diversity of the inoculum, but the role of these species is rarely determined. The screening method developed here can be used to characterize pathogen-associated species affecting disease. This strategy involves three steps: (i) constitution of the microbial community, using the pathogen as a trap; (ii) community selection, using extracts from the pathogen as the sole nutrient source; and (iii) molecular identification and the screening of isolates focusing on their effects on the growth of the pathogen in vitro and host disease. This approach was applied to a soilborne plant pathogen, Phytophthora parasitica, structured in a biofilm, for screening the microbial community from the rhizosphere of Nicotiana tabacum (the host). Two of the characterized eukaryotes interfered with the oomycete cycle and may affect the host disease. A Vorticella species acted through a mutualistic interaction with P. parasitica, disseminating pathogenic material by leaving the biofilm. A Phoma species established an amensal interaction with P. parasitica, strongly suppressing disease by inhibiting P. parasitica germination. This screening method is appropriate for all nonobligate pathogens. It allows the definition of microbial species as promoters or suppressors of a disease for a given biotope. It should also help to identify important microbial relationships for ecology and evolution of pathogens.

Environmental Conditions Affect Botrytis cinerea Infection of Mature Grape Berries More Than the Strain or Transposon Genotype.

PubMed

Ciliberti, Nicola; Fermaud, Marc; Roudet, Jean; Rossi, Vittorio

2015-08-01

Effects of environment, Botrytis cinerea strain, and their interaction on the infection of mature grape berries were investigated. The combined effect of temperature (T) of 15, 20, 25, and 30°C and relative humidity (RH) of 65, 80, 90, and 100% was studied by inoculating berries with mycelium plugs. Regardless of the T, no disease occurred at 65% RH, and both disease incidence and severity increased with increasing RH. The combined effect of T (5 to 30°C) and wetness duration (WD) of 3, 6, 12, 24, and 36 h was studied by inoculating berries with conidia. At WD of 36 h, disease incidence was approximately 75% of affected berries at 20 or 25°C, 50% at 15°C, and 30 to 20% at 30 and 10°C; no infection occurred at 5°C. Under favorable conditions (100% RH or 36 h of WD) and unfavorable conditions (65% RH or 3 h of WD), berry wounding did not significantly affect disease incidence; under moderately favorable conditions (80% RH or 6 to 12 h of WD), disease incidence was approximately 1.5 to 5 times higher in wounded than in intact berries. Our data collectively showed that (i) T and RH or WD were more important than strain for mature berry infection by either mycelium or conidia and (ii) the effect of the environment on the different strains was similar. Two equations were developed describing the combined effect of T and RH, or T and WD, on disease incidence following inoculation by mycelium (R2=0.99) or conidia (R2=0.96), respectively. These equations may be useful in the development of models used to predict and control Botrytis bunch rot during berry ripening.

A conceptual disease model for adult Pompe disease.

PubMed

Kanters, Tim A; Redekop, W Ken; Rutten-Van Mölken, Maureen P M H; Kruijshaar, Michelle E; Güngör, Deniz; van der Ploeg, Ans T; Hakkaart, Leona

2015-09-15

Studies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life. The structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses. Enzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions. We conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making.

Caplan syndrome

MedlinePlus

... not clear how RP develops. There are two theories: When people breathe in inorganic dust, it affects ... than treating any lung and joint disease. Support Groups Attending a support group with people who have ...

Development of a marker assisted selection program for cacao.

PubMed

Schnell, R J; Kuhn, D N; Brown, J S; Olano, C T; Phillips-Mora, W; Amores, F M; Motamayor, J C

2007-12-01

ABSTRACT Production of cacao in tropical America has been severely affected by fungal pathogens causing diseases known as witches' broom (WB, caused by Moniliophthora perniciosa), frosty pod (FP, caused by M. roreri) and black pod (BP, caused by Phytophthora spp.). BP is pan-tropical and causes losses in all producing areas. WB is found in South America and parts of the Caribbean, while FP is found in Central America and parts of South America. Together, these diseases were responsible for over 700 million US dollars in losses in 2001 (4). Commercial cacao production in West Africa and South Asia are not yet affected by WB and FP, but cacao grown in these regions is susceptible to both. With the goal of providing new disease resistant cultivars the USDA-ARS and Mars, Inc. have developed a marker assisted selection (MAS) program. Quantitative trait loci have been identified for resistance to WB, FP, and BP. The potential usefulness of these markers in identifying resistant individuals has been confirmed in an experimental F(1) family in Ecuador.

Assessment of reportable disease incidence after Hurricane Sandy, New York City, 2012.

PubMed

Greene, Sharon K; Wilson, Elisha L; Konty, Kevin J; Fine, Annie D

2013-10-01

Hurricane Sandy's October 29, 2012 arrival in New York City caused flooding, power disruption, and population displacement. Infectious disease risk may have been affected by floodwater exposure, residence in emergency shelters, overcrowding, and lack of refrigeration or heating. For 42 reportable diseases that could have been affected by hurricane-related exposures, we developed methods to assess whether hurricane-affected areas had higher disease incidence than other areas of NYC. We identified post-hurricane cases as confirmed, probable, or suspected cases with onset or diagnosis between October 30 and November 26 that were reported via routine passive surveillance. Pre-hurricane cases for the same 4-week period were identified in 5 prior years, 2007-2011. Cases were geocoded to the census tract of residence. Using data compiled by the NYC Office of Emergency Management, we determined (1) the proportion of the population in each census tract living in a flooded block and (2) the subset of flooded tracts severely "impacted", e.g., by prolonged service outages or physical damage. A separate multivariable regression model was constructed for each disease, modeling the outcome of case counts using a negative binomial distribution. Independent variables were: neighborhood poverty; whether cases were pre- or post-hurricane (time); the proportion of the population flooded in impacted and not impacted tracts; and interaction terms between the flood/impact variables and time. Models used repeated measures to adjust for correlated observations from the same tract and an offset term of the log of the population size. Sensitivity analyses assessed the effects of case count fluctuations and accounted for variations in reporting volume by using an offset term of the log of total cases. Only legionellosis was statistically significantly associated with increased occurrence in flooded/impacted areas post-hurricane, adjusting for baseline differences (P = .04). However, there was only 1 legionellosis case post-hurricane in a flooded/impacted area. Hurricane Sandy did not appear to elevate reportable disease incidence in NYC. Defining and acquiring reliable data and meta-data regarding hurricane-affected areas was a challenge in the weeks post-storm. Relevant metrics could be developed during disaster preparedness planning. These methods to detect excess disease can be adapted for future emergencies.

Dietary phytonutrients as alternatives-to-antibiotics in agricultural animals: Mode of action in modulating cross-talks amonh immunity, disease resistance and gut microbiota

USDA-ARS?s Scientific Manuscript database

New antibiotic regulatory policies affecting agricultural animal production now challenge animal scientists to think outside of the box to develop alternative strategies for sustainable animal agriculture. For those animal infectious diseases for which effective vaccines are lacking, there is a cri...

Intellectual Development of Infants, Children and Adolescents with Congenital Heart Disease

ERIC Educational Resources Information Center

Wray, Jo

2006-01-01

Cardiac disease is the most common congenital defect in children, affecting between 3 and 10 in every 1000 live births. While significant advances in medical and surgical management have resulted in increasing numbers of survivors, it is also recognized that there is a growing population of children living with neurological impairment and lowered…

Neato Mosquito: An Elementary Curriculum Guide. 2nd Edition.

ERIC Educational Resources Information Center

Nasci, Roger S.; Herrington, James E.

This curriculum guide was designed with the purpose of developing public awareness of LaCrosse (LAC) encephalitis, which is a mosquito transmitted disease. LAC cases have been increasing in large numbers in the Upper Midwest and Great Lakes regions during recent years. This disease primarily affects children under the age of 15, and this guide…

Tick-Pathogen Interactions and Vector Competence: Identification of Molecular Drivers for Tick-Borne Diseases

PubMed Central

de la Fuente, José; Antunes, Sandra; Bonnet, Sarah; Cabezas-Cruz, Alejandro; Domingos, Ana G.; Estrada-Peña, Agustín; Johnson, Nicholas; Kocan, Katherine M.; Mansfield, Karen L.; Nijhof, Ard M.; Papa, Anna; Rudenko, Nataliia; Villar, Margarita; Alberdi, Pilar; Torina, Alessandra; Ayllón, Nieves; Vancova, Marie; Golovchenko, Maryna; Grubhoffer, Libor; Caracappa, Santo; Fooks, Anthony R.; Gortazar, Christian; Rego, Ryan O. M.

2017-01-01

Ticks and the pathogens they transmit constitute a growing burden for human and animal health worldwide. Vector competence is a component of vectorial capacity and depends on genetic determinants affecting the ability of a vector to transmit a pathogen. These determinants affect traits such as tick-host-pathogen and susceptibility to pathogen infection. Therefore, the elucidation of the mechanisms involved in tick-pathogen interactions that affect vector competence is essential for the identification of molecular drivers for tick-borne diseases. In this review, we provide a comprehensive overview of tick-pathogen molecular interactions for bacteria, viruses, and protozoa affecting human and animal health. Additionally, the impact of tick microbiome on these interactions was considered. Results show that different pathogens evolved similar strategies such as manipulation of the immune response to infect vectors and facilitate multiplication and transmission. Furthermore, some of these strategies may be used by pathogens to infect both tick and mammalian hosts. Identification of interactions that promote tick survival, spread, and pathogen transmission provides the opportunity to disrupt these interactions and lead to a reduction in tick burden and the prevalence of tick-borne diseases. Targeting some of the similar mechanisms used by the pathogens for infection and transmission by ticks may assist in development of preventative strategies against multiple tick-borne diseases. PMID:28439499

Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

PubMed Central

Ayo, Christiane Maria; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Reis, Pâmela Guimarães; Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Sell, Ana Maria

2013-01-01

Chagas disease, which is caused by the flagellate parasite Trypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during human T. cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC, KIR, and cytokine host genetic factors on the infection by T. cruzi and the clinical course of Chagas disease. PMID:24069594

A prospective birth cohort study of different risk factors for development of allergic diseases in offspring of non-atopic parents

PubMed Central

Lee, Ming-Tsung; Wu, Chih-Chiang; Ou, Chia-Yu; Chang, Jen-Chieh; Liu, Chieh-An; Wang, Chih-Lu; Chuang, Hau; Kuo, Ho-Chang; Hsu, Te-Yao; Chen, Chie-Pein; Yang, Kuender D.

2017-01-01

Background: Allergic diseases are thought to be inherited. Prevalence of allergic diseases has, however, increased dramatically in last decades, suggesting environmental causes for the development of allergic diseases. Objective: We studied risk factors associated with the development of atopic dermatitis (AD), allergic rhinitis (AR) and asthma (AS) in children of non-atopic parents in a subtropical country. Methods: In a birth cohort of 1,497 newborns, parents were prenatally enrolled and validated for allergic diseases by questionnaire, physician-verified and total or specific Immunoglobulin E (IgE) levels; 1,236 and 756 children, respectively, completed their 3-year and 6-year follow-up. Clinical examination, questionnaire, and blood samples for total and specific IgE of the children were collected at each follow-up visit. Results: Prevalence of AD, AR and AS was, respectively, 8.2%, 30.8% and 12.4% in children of non-atopic parents. Prevalence of AR (p<.001) and AS (p=.018) was significantly higher in children of parents who were both atopic. A combination of Cesarean section (C/S) and breastfeeding for more than 1 month showed the highest risk for AD (OR=3.111, p=.006). Infants living in homes with curtains and no air filters had the highest risk for AR (OR=2.647, p<.001), and male infants of non-atopic parents living in homes without air filters had the highest risk for AS (OR=1.930, p=.039). Conclusions: Breastfeeding and C/S affect development of AD. Gender, use of curtains and/or air filters affect AR and AS, suggesting that control of the perinatal environment is necessary for the prevention of atopic diseases in children of non-atopic parents. PMID:28086237

A prospective birth cohort study of different risk factors for development of allergic diseases in offspring of non-atopic parents.

PubMed

Lee, Ming-Tsung; Wu, Chih-Chiang; Ou, Chia-Yu; Chang, Jen-Chieh; Liu, Chieh-An; Wang, Chih-Lu; Chuang, Hau; Kuo, Ho-Chang; Hsu, Te-Yao; Chen, Chie-Pein; Yang, Kuender D

2017-02-14

Allergic diseases are thought to be inherited. Prevalence of allergic diseases has, however, increased dramatically in last decades, suggesting environmental causes for the development of allergic diseases. We studied risk factors associated with the development of atopic dermatitis (AD), allergic rhinitis (AR) and asthma (AS) in children of non-atopic parents in a subtropical country. In a birth cohort of 1,497 newborns, parents were prenatally enrolled and validated for allergic diseases by questionnaire, physician-verified and total or specific Immunoglobulin E (IgE) levels; 1,236 and 756 children, respectively, completed their 3-year and 6-year follow-up. Clinical examination, questionnaire, and blood samples for total and specific IgE of the children were collected at each follow-up visit. Prevalence of AD, AR and AS was, respectively, 8.2%, 30.8% and 12.4% in children of non-atopic parents. Prevalence of AR (p<.001) and AS (p=.018) was significantly higher in children of parents who were both atopic. A combination of Cesarean section (C/S) and breastfeeding for more than 1 month showed the highest risk for AD (OR=3.111, p=.006). Infants living in homes with curtains and no air filters had the highest risk for AR (OR=2.647, p<.001), and male infants of non-atopic parents living in homes without air filters had the highest risk for AS (OR=1.930, p=.039). Breastfeeding and C/S affect development of AD. Gender, use of curtains and/or air filters affect AR and AS, suggesting that control of the perinatal environment is necessary for the prevention of atopic diseases in children of non-atopic parents.

Prevention of Rheumatic Diseases: Strategies, Caveats and Future Directions

PubMed Central

Finckh, Axel

2014-01-01

Rheumatic diseases affect a significant portion of the population and lead to increased health care costs, disability and even premature mortality; as such, effective preventive measures for these diseases could lead to substantial improvements in public health. Importantly, established and emerging data from natural history studies show that for most rheumatic diseases there is a period of ‘preclinical’ disease development during which abnormal biomarkers or other processes can be detected. These changes are useful to understand mechanisms of disease pathogenesis; in addition, they may be applied to estimate a personal risk of future disease, while individuals are still relatively asymptomatic. Based on this, a hope is to implement effective screening and preventive approaches for some rheumatic diseases, perhaps in the near future. However, a key part of such approaches is a deep understanding of the mechanisms of disease development as well as evidence-based and effective screening and preventive interventions that incorporate disease biology as well as ethical and public health concerns. PMID:25437291

76 FR 59399 - Statement of Organization, Functions and Delegations of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-26

... needs; assessing the design and effectiveness of health promotion/disease prevention endeavors... mechanisms to support data infrastructure development to support outcomes research as well as developing and... officials and employees of affected organizational components will continue in them or their successors...

Global gene expression and Ingenuity biological functions analysis on PCBs 153 and 138 induced human PBMC in vitro reveals differential mode(s) of action in developing toxicities.

PubMed

Ghosh, Somiranjan; Zang, Shizhu; Mitra, Partha S; Ghimbovschi, Svetlana; Hoffman, Eric P; Dutta, Sisir K

2011-07-01

Several reports have indicated that low level of polychlorinated biphenyl (PCB) exposure can adversely affect a multitude of physiological disorders and diseases in in vitro, in vivo, and as reported in epidemiological studies. This investigation is focused on the possible contribution of two most prevalent PCB congeners in vitro in developing toxicities. We used PCBs 138 and 153 at the human equivalence level as model agents to test their specificity in developing toxicities. We chose a global approach using oligonucleotide microarray technology to investigate modulated gene expression for biological effects, upon exposure of PCBs, followed by Ingenuity Pathway Analysis (IPA), to understand the underlying consequence in developing disease and disorders. We performed in vitro studies with human peripheral blood mononuclear cells (PBMC), where PBMC cells were exposed to respective PCBs for 48 h. Overall, our observation on gene expression indicated that PCB produces a unique signature affecting different pathways, specific for each congener. While analyzing these data through IPA, the prominent and interesting disease and disorders were neurological disease, cancer, cardiovascular disease, respiratory disease, as well as endocrine system disorders, genetic disorders, and reproductive system disease. They showed strong resemblances with in vitro, in vivo, and in the epidemiological studies. A distinct difference was observed in renal and urological diseases, organisimal injury and abnormalities, dental disease, ophthalmic disease, and psychological disorders, which are only revealed by PCB 138 exposure, but not in PCB 153. The present study emphasizes the challenges of global gene expression in vitro and was correlated with the results of exposed human population. The microarray results give a molecular mechanistic insight and functional effects, following PCB exposure. The extent of changes in genes related to several possible mode(s) of action highlights the changes in cellular functions and signaling pathways that play major roles. In addition to understanding the pathways related to mode of action for chemicals, these data could lead to the identification of genomic signatures that could be used for screening of chemicals for their potential to cause disease and developmental disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Primary biliary cirrhosis associated with Graves' disease in a male patient.

PubMed

Suzuki, Yuji; Ishida, Kazuyuki; Takahashi, Hiroshi; Koeda, Norihiko; Kakisaka, Keisuke; Miyamoto, Yasuhiro; Suzuki, Akiko; Takikawa, Yasuhiro

2016-04-01

Primary biliary cirrhosis (PBC), which predominantly affects women, has been associated with various autoimmune diseases. Although hypothyroidism accompanying PBC is well documented, the concomitance of PBC and hyperthyroidism is rare. Herein, we report the case of a 62-year-old man who was diagnosed with PBC several years after the development of Graves' disease. This is the first case of a male patient developing PBC with Graves' disease. Both serum alanine aminotransferase levels and serum thyroid hormone levels were normalized after the administration of thiamazole for Graves' disease. However, the cholestatic liver enzyme abnormalities continued, indicating that the PBC was actualized by the administration of thiamazole. After starting ursodeoxycholic acid treatment, cholestatic liver enzyme abnormalities improved. Taken together, when a cholestatic pattern of liver enzymes is observed during follow-up for Graves' disease, an association between Graves' disease and PBC should be considered as a differential diagnosis.

The life cycle of chondrocytes in the developing skeleton

PubMed Central

Shum, Lillian; Nuckolls, Glen

2002-01-01

Cartilage serves multiple functions in the developing embryo and in postnatal life. Genetic mutations affecting cartilage development are relatively common and lead to skeletal malformations, dysfunction or increased susceptibility to disease or injury. Characterization of these mutations and investigation of the molecular pathways in which these genes function have contributed to an understanding of the mechanisms regulating skeletal patterning, chondrogenesis, endochondral ossification and joint formation. Extracellular growth and differentiation factors including bone morphogenetic proteins, fibroblast growth factors, parathyroid hormone-related peptide, extracellular matrix components, and members of the hedgehog and Wnt families provide important signals for the regulation of cell proliferation, differentiation and apoptosis. Transduction of these signals within the developing mesenchymal cells and chondrocytes results in changes in gene expression mediated by transcription factors including Smads, Msx2, Sox9, signal transducer and activator of transcription (STAT), and core-binding factor alpha 1. Further investigation of the interactions of these signaling pathways will contribute to an understanding of cartilage growth and development, and will allow for the development of strategies for the early detection, prevention and treatment of diseases and disorders affecting the skeleton. PMID:11879545

Simultaneous acquisition of corrugator electromyography and functional magnetic resonance imaging: A new method for objectively measuring affect and neural activity concurrently

PubMed Central

Heller, Aaron S.; Greischar, Lawrence L; Honor, Ann; Anderle, Michael J; Davidson, Richard J.

2011-01-01

The development of functional neuroimaging of emotion holds the promise to enhance our understanding of the biological bases of affect and improve our knowledge of psychiatric diseases. However, up to this point, researchers have been unable to objectively, continuously and unobtrusively measure the intensity and dynamics of affect concurrently with functional magnetic resonance imaging (fMRI). This has hindered the development and generalizability of our field. Facial electromyography (EMG) is an objective, reliable, valid, sensitive, and unobtrusive measure of emotion. Here, we report the successful development of a method for simultaneously acquiring fMRI and facial EMG. The ability to simultaneously acquire brain activity and facial physiology will allow affective neuroscientists to address theoretical, psychiatric, and individual difference questions in a more rigorous and generalizable way. PMID:21742043

Therapeutic antibodies: A new era in the treatment of respiratory diseases?

PubMed

Sécher, T; Guilleminault, L; Reckamp, K; Amanam, I; Plantier, L; Heuzé-Vourc'h, N

2018-05-04

Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease - one of the most common non-communicable causes of death - and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends. Copyright © 2018 Elsevier Inc. All rights reserved.

Hit and lead criteria in drug discovery for infectious diseases of the developing world.

PubMed

Katsuno, Kei; Burrows, Jeremy N; Duncan, Ken; Hooft van Huijsduijnen, Rob; Kaneko, Takushi; Kita, Kiyoshi; Mowbray, Charles E; Schmatz, Dennis; Warner, Peter; Slingsby, B T

2015-11-01

Reducing the burden of infectious diseases that affect people in the developing world requires sustained collaborative drug discovery efforts. The quality of the chemical starting points for such projects is a key factor in improving the likelihood of clinical success, and so it is important to set clear go/no-go criteria for the progression of hit and lead compounds. With this in mind, the Japanese Global Health Innovative Technology (GHIT) Fund convened with experts from the Medicines for Malaria Venture, the Drugs for Neglected Diseases initiative and the TB Alliance, together with representatives from the Bill &Melinda Gates Foundation, to set disease-specific criteria for hits and leads for malaria, tuberculosis, visceral leishmaniasis and Chagas disease. Here, we present the agreed criteria and discuss the underlying rationale.

Deleterious role of trace elements - Silica and lead in the development of chronic kidney disease.

PubMed

Mascarenhas, Starlaine; Mutnuri, Srikanth; Ganguly, Anasuya

2017-06-01

Chronic-Kidney-Disease of Unknown-etiology (CKDu) has been reported in developing-countries like Sri-Lanka, India and Central-America without sparing the Indian sub-district (namely Canacona) located in south-Goa. The disease etiology is unlinked to common causes of diabetes and hypertension and assumed to be environmentally induced due to its asymptomatic-nature and occurrence in groundwater relying communities. This study aimed to understand environmental risk-factors underlying CKDu-etiology using Indian sub-district (Canacona) as case-study. Biochemical-analysis of CKDu-affected and non-affected individual's blood and detailed hydro-geochemical analyses of CKDu-affected and non-affected region's groundwater (drinking-water)were conducted. Trace geogenic-element-silica was highly dominant in affected-region's groundwater, thus its nephrotoxic-potential was analysed via in-vitro cytotoxicity-assays on human-kidney-cell-lines. All CKDu-affected-subjects showed increased-levels of serum-urea (52.85 mM),creatinine (941.5 μM),uric-acid (1384.5 μM), normal blood-glucose (4.65 mM), being distinct biomarkers of environmentally-induced CKD-'chronic-tubulo-interstitial-nephritis'. Affected-subjects reported high blood-lead levels (1.48 μM)suggesting direct-nephrotoxicity resulting in impaired blood-clearance and also exhibits indirect-nephrotoxicity by disrupting calcium-homeostasis causing skeletal-disorders and prolonged-consumption of NSAID's (pain-alleviation), indirectly causing renal-damage. Affected-region's groundwater was acidic (pH-5.6), resulting in borderline-lead (9.98 μgL -1 ) and high-silica (115.5 mgL -1 )contamination. Silica's bio-availability (determining its nephrotoxicity) was enhanced at groundwater's acidic-pH and Ca-Mg-deficient-composition (since these cations complex with silica reducing bioavailability). Silica exhibited renal-proximal-tubular-cytotoxicity on long-term exposure comparable with affected-region's groundwater silica-levels, by apoptosis-mediated-cell-death resulting in tubular-atrophy, interstitial-fibrosis and irreversible renal-damage (CKD). Thus this study provides novel-insights into nephrotoxic-potential of trace-geogenic-element-silica in CKDu causation. It highlights direct-indirect nephrotoxicity exhibited by lead at low-levels due to its bio-accumulative-capacity. Silica's nephrotoxic-potential can be considered when deciphering etiology of CKDu-problem in developing-countries (relying on groundwater). Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear DNA replication and repair in parasites of the genus Leishmania: Exploiting differences to develop innovative therapeutic approaches.

PubMed

Uzcanga, Graciela; Lara, Eliana; Gutiérrez, Fernanda; Beaty, Doyle; Beske, Timo; Teran, Rommy; Navarro, Juan-Carlos; Pasero, Philippe; Benítez, Washington; Poveda, Ana

2017-03-01

Leishmaniasis is a common tropical disease that affects mainly poor people in underdeveloped and developing countries. This largely neglected infection is caused by Leishmania spp, a parasite from the Trypanosomatidae family. This parasitic disease has different clinical manifestations, ranging from localized cutaneous to more harmful visceral forms. The main limitations of the current treatments are their high cost, toxicity, lack of specificity, and long duration. Efforts to improve treatments are necessary to deal with this infectious disease. Many approved drugs to combat diseases as diverse as cancer, bacterial, or viral infections take advantage of specific features of the causing agent or of the disease. Recent evidence indicates that the specific characteristics of the Trypanosomatidae replication and repair machineries could be used as possible targets for the development of new treatments. Here, we review in detail the molecular mechanisms of DNA replication and repair regulation in trypanosomatids of the genus Leishmania and the drugs that could be useful against this disease.

World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

PubMed Central

Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

2014-01-01

According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries. PMID:25332915

World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients.

PubMed

Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

2014-09-26

According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.

Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

PubMed Central

DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

2014-01-01

Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

Understanding Parkinson Disease: A Complex and Multifaceted Illness.

PubMed

Gopalakrishna, Apoorva; Alexander, Sheila A

2015-12-01

Parkinson disease is an incredibly complex and multifaceted illness affecting millions of people in the United States. Parkinson disease is characterized by progressive dopaminergic neuronal dysfunction and loss, leading to debilitating motor, cognitive, and behavioral symptoms. Parkinson disease is an enigmatic illness that is still extensively researched today to search for a better understanding of the disease, develop therapeutic interventions to halt or slow progression of the disease, and optimize patient outcomes. This article aims to examine in detail the normal function of the basal ganglia and dopaminergic neurons in the central nervous system, the etiology and pathophysiology of Parkinson disease, related signs and symptoms, current treatment, and finally, the profound impact of understanding the disease on nursing care.

Origins and consequences of congenital heart defects affecting the right ventricle.

PubMed

Woudstra, Odilia I; Ahuja, Suchit; Bokma, Jouke P; Bouma, Berto J; Mulder, Barbara J M; Christoffels, Vincent M

2017-10-01

Congenital heart disease is a major health issue, accounting for a third of all congenital defects. Improved early surgical management has led to a growing population of adults with congenital heart disease, including patients with defects affecting the right ventricle, which are often classified as severe. Defects affecting the right ventricle often cause right ventricular volume or pressure overload and affected patients are at high risk for complications such as heart failure and sudden death. Recent insights into the developmental mechanisms and distinct developmental origins of the left ventricle, right ventricle, and the outflow tract have shed light on the common features and distinct problems arising in specific defects. Here, we provide a comprehensive overview of the current knowledge on the development into the normal and congenitally malformed right heart and the clinical consequences of several congenital heart defects affecting the right ventricle. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

21 CFR 516.13 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Species Animal Drug Development of the FDA Center for Veterinary Medicine. Intended use means the intended treatment, control or prevention of a disease or condition, or the intention to affect the structure or...

Environmental temperature affects prevalence of blood parasites of birds on an elevation gradient: implications for disease in a warming climate.

PubMed

Zamora-Vilchis, Itzel; Williams, Stephen E; Johnson, Christopher N

2012-01-01

The rising global temperature is predicted to expand the distribution of vector-borne diseases both in latitude and altitude. Many host communities could be affected by increased prevalence of disease, heightening the risk of extinction for many already threatened species. To understand how host communities could be affected by changing parasite distributions, we need information on the distribution of parasites in relation to variables like temperature and rainfall that are predicted to be affected by climate change. We determined relations between prevalence of blood parasites, temperature, and seasonal rainfall in a bird community of the Australian Wet Tropics along an elevation gradient. We used PCR screening to investigate the prevalence and lineage diversity of four genera of blood parasites (Plasmodium, Haemoproteus, Leucocytozoon and Trypanosoma) in 403 birds. The overall prevalence of the four genera of blood parasites was 32.3%, with Haemoproteus the predominant genus. A total of 48 unique lineages were detected. Independent of elevation, parasite prevalence was positively and strongly associated with annual temperature. Parasite prevalence was elevated during the dry season. Low temperatures of the higher elevations can help to reduce both the development of avian haematozoa and the abundance of parasite vectors, and hence parasite prevalence. In contrast, high temperatures of the lowland areas provide an excellent environment for the development and transmission of haematozoa. We showed that rising temperatures are likely to lead to increased prevalence of parasites in birds, and may force shifts of bird distribution to higher elevations. We found that upland tropical areas are currently a low-disease habitat and their conservation should be given high priority in management plans under climate change.

Environmental Temperature Affects Prevalence of Blood Parasites of Birds on an Elevation Gradient: Implications for Disease in a Warming Climate

PubMed Central

Zamora-Vilchis, Itzel; Williams, Stephen E.; Johnson, Christopher N.

2012-01-01

Background The rising global temperature is predicted to expand the distribution of vector-borne diseases both in latitude and altitude. Many host communities could be affected by increased prevalence of disease, heightening the risk of extinction for many already threatened species. To understand how host communities could be affected by changing parasite distributions, we need information on the distribution of parasites in relation to variables like temperature and rainfall that are predicted to be affected by climate change. Methodology/Principal Findings We determined relations between prevalence of blood parasites, temperature, and seasonal rainfall in a bird community of the Australian Wet Tropics along an elevation gradient. We used PCR screening to investigate the prevalence and lineage diversity of four genera of blood parasites (Plasmodium, Haemoproteus, Leucocytozoon and Trypanosoma) in 403 birds. The overall prevalence of the four genera of blood parasites was 32.3%, with Haemoproteus the predominant genus. A total of 48 unique lineages were detected. Independent of elevation, parasite prevalence was positively and strongly associated with annual temperature. Parasite prevalence was elevated during the dry season. Conclusions/Significance Low temperatures of the higher elevations can help to reduce both the development of avian haematozoa and the abundance of parasite vectors, and hence parasite prevalence. In contrast, high temperatures of the lowland areas provide an excellent environment for the development and transmission of haematozoa. We showed that rising temperatures are likely to lead to increased prevalence of parasites in birds, and may force shifts of bird distribution to higher elevations. We found that upland tropical areas are currently a low-disease habitat and their conservation should be given high priority in management plans under climate change. PMID:22723966

Disease management positively affects patient quality of life.

PubMed

Walker, David R; Landis, Darryl L; Stern, Patricia M; Vance, Richard P

2003-04-01

Health care costs are spiraling upward. The population of the United States is aging, and many baby boomers will develop multiple chronic health conditions. Disease management is one method for reducing costs associated with chronic health conditions. Although these programs have been proven effective in improving patient health, detailed information about their effect on patient quality of life has been scarce. This article provides preliminary evidence that disease management programs for coronary artery disease, chronic obstructive pulmonary disease, diabetes, and heart failure lead to improved quality of life, which correlates with a healthier, more satisfied, and less costly patient.

Molecular detection of infectious bronchitis and Newcastle disease viruses in broiler chickens with respiratory signs using Duplex RT-PCR.

PubMed

Saba Shirvan, Aylar; Mardani, Karim

2014-01-01

Infectious bronchitis (IB) and Newcastle disease (ND) are highly contagious and the most economically important diseases of the poultry affecting respiratory tract and causing economic losses in poultry industry throughout the world. In the present study, the simultaneous detection and differentiation of causative agents of these diseases were investigated using duplex-RT-PCR. RNA was extracted from vaccinal and reference strains of infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) and then cDNA was synthesized. Using two universal primer sets for detection of IBV and NDV, the duplex-RT-PCR was developed. In order to assess the efficiency of the developed duplex RT-PCR, a number of 12 broiler farms with the symptoms of respiratory tract infection was sampled (trachea, lung and kidney were sampled from affected birds suspicious for IBV and NDV infections). After RNA extraction from tissues and cDNA synthesis, the presence of IBV and NDV genome were investigated using duplex-PCR. The results showed that three of twelve examined broiler farms were positive for IBV and two farms were positive for NDV and IBV. The results revealed that the duplex-RT-PCR is a quick and sensitive procedure for simultaneously detecting IBV and NDV in birds with respiratory infections.

[The road to elimination: an overview of neglected infectious diseases in Latin America and the Caribbean].

PubMed

Ault, Steven Kenyon; Catalá Pascual, Laura; Grados-Zavala, Maria Elena; Gonzálvez García, Guillermo; Castellanos, Luis Gerardo

2014-04-01

Neglected infectious diseases (NID) affect mainly isolated populations living in isolation and in poor socioeconomic conditions. These diseases, by their chronic and silent nature, often affect communities with a weak political voice. This translates into very little attention or political priority; which is reflected in minimal and insufficient preventive measures, monitoring and control. However, there is evidence this situation is changing favorably in some countries of the Americas. In recent years, several resolutions (official agreement of the member countries of the Pan American Health Organization / World Health Organization-PAHO / WHO), regional and global agreements on public health; with a greater commitment from the pharmaceutical industry, and other donors and international partners in combination with the development and use of integrated action plans have allowed countries to intensify public interventions to control these diseases and thus achieve target elimination of NID. Onchocerciasis, lymphatic filariasis, Chagas disease, leprosy and trachoma blindness, among others, have been eliminated in several countries and endemic areas, regardless of the level of development of the country or geographical area where they are located. The political decision reflected in adequate financial resources in the next decade will be crucial to achieving the goals of elimination of NID (regional and national).

Mouse models of mitochondrial DNA defects and their relevance for human disease

PubMed Central

Tyynismaa, Henna; Suomalainen, Anu

2009-01-01

Qualitative and quantitative changes in mitochondrial DNA (mtDNA) have been shown to be common causes of inherited neurodegenerative and muscular diseases, and have also been implicated in ageing. These diseases can be caused by primary mtDNA mutations, or by defects in nuclear-encoded mtDNA maintenance proteins that cause secondary mtDNA mutagenesis or instability. Furthermore, it has been proposed that mtDNA copy number affects cellular tolerance to environmental stress. However, the mechanisms that regulate mtDNA copy number and the tissue-specific consequences of mtDNA mutations are largely unknown. As post-mitotic tissues differ greatly from proliferating cultured cells in their need for mtDNA maintenance, and as most mitochondrial diseases affect post-mitotic cell types, the mouse is an important model in which to study mtDNA defects. Here, we review recently developed mouse models, and their contribution to our knowledge of mtDNA maintenance and its role in disease. PMID:19148224

Appearance of Abnormal Cardiothoracic Ratio of Fetuses with Hemoglobin Bart's Disease: Life Table Analysis.

PubMed

Wanapirak, Chanane; Sirichotiyakul, Supatra; Luewan, Suchaya; Srisupundit, Kasemsri; Tongprasert, Fuanglada; Tongsong, Theera

2017-10-01

Objective  To determine the timeline of the first appearance of an increased CT ratio of fetuses with hemoglobin (Hb) Bart's disease. Materials and Methods  A prospective longitudinal study was conducted on pregnancies at risk for fetal Hb Bart's disease. Sonographic markers including cardiothoracic (CT) ratio and middle cerebral artery peak systolic velocity (MCA-PSV) were serially assessed and recorded from the first trimester. The definite diagnosis of fetal Hb Bart's disease based on DNA analysis (CVS), or fetal Hb typing (HPLC; cordocentesis) was performed at the first appearance of an increased CT ratio. Results  Of 275 pregnancies at risk, 64 fetuses were finally proven to be affected and life table analysis was performed. Most affected fetuses showed an increased CT ratio in late first trimester and early second trimester, with median time of the first appearance at 13 weeks and all affected fetuses were detected at 23 weeks or less. The CT ratio yielded a sensitivity of 100 % at a gestational age of 23 weeks with a false-positive rate of 8 %. MCA-PSV appeared later than CT ratio. Only 9.4 % of affected cases developed abnormal MCA-PSV before an increased CT ratio. Conclusion  The timeline of the first appearance of an increased CT ratio of fetuses with Hb Bart's disease was established. This may help us identify Hb Bart's disease among fetuses at risk in earlier gestation and proper schedules for serial ultrasound could be made more effectively. © Georg Thieme Verlag KG Stuttgart · New York.

Community perceptions of health and chronic disease in South Indian rural transitional communities: a qualitative study.

PubMed

Hayter, Arabella K M; Jeffery, Roger; Sharma, Chitra; Prost, Audrey; Kinra, Sanjay

2015-01-01

Chronic diseases are now the leading cause of death and disability worldwide; this epidemic has been linked to rapid economic growth and urbanisation in developing countries. Understanding how characteristics of the physical, social, and economic environment affect behaviour in the light of these changes is key to identifying successful interventions to mitigate chronic disease risk. We undertook a qualitative study consisting of nine focus group discussions (FGDs) (n=57) in five villages in rural Andhra Pradesh, South India, to understand people's perceptions of community development and urbanisation in relation to chronic disease in rural transitional communities. Specifically, we sought to understand perceptions of change linked to diet, physical activity, and pollution (because these exposures are most relevant to chronic diseases), with the aim of defining future interventions. The transcripts were analysed thematically. Participants believed their communities were currently less healthy, more polluted, less physically active, and had poorer access to nutritious food and shorter life expectancies than previously. There were contradictory perceptions of the effects of urbanisation on health within and between individuals; several of the participants felt their quality of life had been reduced. In the present study, residents viewed change and development within their villages as an inevitable and largely positive process but with some negative health consequences. Understanding how these changes are affecting populations in transitional rural areas and how people relate to their environment may be useful to guide community planning for health. Measures to educate and empower people to make healthy choices within their community may help reduce the spread of chronic disease risk factors in future years.

Bone-Immune Cell Crosstalk: Bone Diseases

PubMed Central

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma. PMID:26000310

Bone-immune cell crosstalk: bone diseases.

PubMed

Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

2015-01-01

Bone diseases are associated with great morbidity; thus, the understanding of the mechanisms leading to their development represents a great challenge to improve bone health. Recent reports suggest that a large number of molecules produced by immune cells affect bone cell activity. However, the mechanisms are incompletely understood. This review aims to shed new lights into the mechanisms of bone diseases involving immune cells. In particular, we focused our attention on the major pathogenic mechanism underlying periodontal disease, psoriatic arthritis, postmenopausal osteoporosis, glucocorticoid-induced osteoporosis, metastatic solid tumors, and multiple myeloma.

Congenital Minamata disease: warnings from Japan's experience.

PubMed

Kondo, K

2000-07-01

Minamata disease is alkylmercury poisoning causing Hunter-Russell syndrome due to ingestion of seafood polluted by industrial waste. Two epidemics occurred in Minamata (1956) and Niigata (1965), Japan. Many infants with "cerebral palsy" in villages where adult cases occurred were established as having congenital Minamata disease. Developing brains were affected by alkylmercury through transplacental exposure and even by breastfeeding. This report reviews the history, clinical features, pathology, epidemiology, metal analysis, experiments, and sociolegal aspects of congenital Minamata disease. Many victims are still alive and their present conditions are reviewed.

Adipose tissue as an endocrine organ.

PubMed

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

Animal leptospirosis.

PubMed

Ellis, William A

2015-01-01

Leptospirosis is a global disease of animals, which can have a major economic impact on livestock industries and is an important zoonosis. The current knowledge base is heavily biased towards the developed agricultural economies. The disease situation in the developing economies presents a major challenge as humans and animals frequently live in close association. The severity of disease varies with the infecting serovar and the affected species, but there are many common aspects across the species; for example, the acute phase of infection is mostly sub-clinical and the greatest economic losses arise from chronic infection causing reproductive wastage. The principles of, and tests for, diagnosis, treatment, control and surveillance are applicable across the species.

Empowering Local Organizations and Decision-makers in a Changing Climate: EO-guided Environmental Surveillance of Cholera and Rotavirus for South Asia

NASA Astrophysics Data System (ADS)

Akanda, A. S.; Hasan, M. A.; Jutla, A.; Aziz, S.; Alam, M.; Ahsan, G. U.; Huq, A.; Colwell, R. R.

2017-12-01

Despite significant advancements in scientific research, diarrheal diseases remain a leading cause of mortality and morbidity in the developing world. Although under-5 child mortality due to such diseases is dropping, prevalence of most diarrheal diseases has increased over past decades, exerting a terrible toll on global public health. Providing safe water and sanitation access, and a safe and clean environment in a sustainable manner remains a critical challenge in the face of rapid population growth, urbanization and increasing threats of natural hazards in a changing climate. We focus on the Bengal Delta region of South Asia, where Cholera and Rotavirus diarrhea continue to have a devastating impact on the public health burden. Climatic change and anthropogenic forcings have greatly affected available water quantity and quality, while the lack of effective institutions and capacity have greatly affected the water-sanitation and public health sectors. The region suffers from recurring dry season freshwater scarcity and temperature extremes, salinity intrusion in coastal areas, inland flooding during monsoons, and resulting water contamination across the delta region. We use earth observation (EO) datasets and techniques to develop a series of tools for surveillance, analysis and decision support to empower government, academic, and non-government stakeholder organizations in South Asia to monitor changes in environmental conditions related to the two most devastating diarrheal diseases, cholera and rotavirus. The developed tools will enable decision makers and stakeholders to significantly increase their understanding of the threats to public health and environmental and climatic conditions related to these diseases, ways to monitor future projections of disease risk, and help identify required policy interventions and strategies to strengthen prevention efforts and limit disease burden in near- (tactical) and long- (strategic) terms.

Predictors of Cardiovascular Events After Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2017-05-01

Indications for liver transplant have been extended, and older and sicker patients are undergoing transplantation. Infectious, malignant, and cardiovascular diseases account for the most posttransplant deaths. Cirrhotic patients can develop heart disease through systemic diseases affecting the heart and the liver, cirrhosis-specific heart disease, or common cardiovascular. No single factor can predict posttransplant cardiovascular complications. Patients with history of cardiovascular disease, and specific abnormalities on echocardiography, electrocardiography, or serum markers of heart disease seem to be at increased risk of complications. Pretransplant cardiovascular evaluation is essential to detecting these risk factors so their effects can be mitigated through appropriate intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Familial Renal Cancer: Molecular Genetics and Surgical Management

PubMed Central

Barrisford, Glen W.; Singer, Eric A.; Rosner, Inger L.; Linehan, W. Marston; Bratslavsky, Gennady

2011-01-01

Familial renal cancer (FRC) is a heterogeneous disorder comprised of a variety of subtypes. Each subtype is known to have unique histologic features, genetic alterations, and response to therapy. Through the study of families affected by hereditary forms of kidney cancer, insights into the genetic basis of this disease have been identified. This has resulted in the elucidation of a number of kidney cancer gene pathways. Study of these pathways has led to the development of novel targeted molecular treatments for patients affected by systemic disease. As a result, the treatments for families affected by von Hippel-Lindau (VHL), hereditary papillary renal carcinoma (HPRC), hereditary leiomyomatosis renal cell carcinoma (HLRCC), and Birt-Hogg-Dubé (BHD) are rapidly changing. We review the genetics and contemporary surgical management of familial forms of kidney cancer. PMID:22312516

[Homeostasis and Disorder of Musculoskeletal System.Diagnosis and Treatment of Congenital Musculoskeletal Diseases.

PubMed

Michigami, Toshimi

Congenital skeletal dysplasias have been considered to be fundamentally untreatable diseases. However, molecular diagnosis by genetic testing has become more prevalent, and efforts are being made to develop novel therapies based on the pathogenesis. As treatments for osteogenesis imperfecta, in addition to anti-resorptive agents, neutralizing antibodies against sclerostin and transforming growth factor(TGF)-β and chemical chaperones can be beneficial. Enzyme replacement therapy using bone-targeting recombinant alkaline phosphatase has been recently developed to treat hypophosphatasia and has much improved the prognosis of the patients affected with severe forms of the disease. To treat the severe short stature in achondroplasia, drugs targeting the fibroblast growth factor receptor 3(FGFR3)-mediated signal are in development for clinical use.

Myotonic Dystrophies: State of the Art of New Therapeutic Developments for the CNS

PubMed Central

Gourdon, Genevieve; Meola, Giovanni

2017-01-01

Myotonic dystrophies are multisystemic diseases characterized not only by muscle and heart dysfunction but also by CNS alteration. They are now recognized as brain diseases affecting newborns and children for myotonic dystrophy type 1 and adults for both myotonic dystrophy type 1 and type 2. In the past two decades, much progress has been made in understanding the mechanisms underlying the DM symptoms allowing development of new molecular therapeutic tools with the ultimate aim of curing the disease. This review describes the state of the art for the characterization of CNS related symptoms, the development of molecular strategies to target the CNS as well as the available tools for screening and testing new possible treatments. PMID:28473756

Alzheimer's Disease Assessment: A Review and Illustrations Focusing on Item Response Theory Techniques.

PubMed

Balsis, Steve; Choudhury, Tabina K; Geraci, Lisa; Benge, Jared F; Patrick, Christopher J

2018-04-01

Alzheimer's disease (AD) affects neurological, cognitive, and behavioral processes. Thus, to accurately assess this disease, researchers and clinicians need to combine and incorporate data across these domains. This presents not only distinct methodological and statistical challenges but also unique opportunities for the development and advancement of psychometric techniques. In this article, we describe relatively recent research using item response theory (IRT) that has been used to make progress in assessing the disease across its various symptomatic and pathological manifestations. We focus on applications of IRT to improve scoring, test development (including cross-validation and adaptation), and linking and calibration. We conclude by describing potential future multidimensional applications of IRT techniques that may improve the precision with which AD is measured.

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region.

PubMed

Nwanodi, Oroma

2017-09-08

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness.

Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

PubMed Central

Llorens-Martín, María; Hernández, Félix; Avila, Jesús

2013-01-01

Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field. PMID:23690659

Spotlight on ixekizumab for the treatment of moderate-to-severe plaque psoriasis: design, development, and use in therapy.

PubMed

Giunta, Alessandro; Ventura, Alessandra; Chimenti, Maria Sole; Bianchi, Luca; Esposito, Maria

2017-01-01

Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population, associated with discomfort and impaired quality of life. In recent years, the pathogenic cytokine network of psoriasis has been extensively studied leading to the development of new treatments that provide greater efficacy. Interleukin 17A (IL-17A) has been recognized as a crucial cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab - indicated for the treatment of adults with moderate-to-severe plaque psoriasis - is a subcutaneously administered humanized monoclonal antibody that targets IL-17A. A large percentage of patients affected by psoriasis achieved consistent benefits in terms of disease control and rapid onset of action during clinical trials. Overall, ixekizumab brought clinical improvement and a favorable safety profile in phase III trials. Ixekizumab is characterized by consistent efficacy and rapid onset of response; it is not influenced by previous exposure to biologics and has shown good results in areas that are difficult to treat and in severe clinical variants of psoriasis. Ixekizumab has shown significant improvements in the activity of the disease and in those physical functions that inhibit radiographic progression in patients with concomitant involvement of joints. Our data support ixekizumab as a successful therapeutic option for patients affected by moderate-to-severe plaque-type psoriasis.

Disruption of Serinc1, which facilitates serine-derived lipid synthesis, fails to alter macrophage function, lymphocyte proliferation or autoimmune disease susceptibility.

PubMed

Chu, Edward P F; Elso, Colleen M; Pollock, Abigail H; Alsayb, May A; Mackin, Leanne; Thomas, Helen E; Kay, Thomas W H; Silveira, Pablo A; Mansell, Ashley S; Gaus, Katharina; Brodnicki, Thomas C

2017-02-01

During immune cell activation, serine-derived lipids such as phosphatidylserine and sphingolipids contribute to the formation of protein signaling complexes within the plasma membrane. Altering lipid composition in the cell membrane can subsequently affect immune cell function and the development of autoimmune disease. Serine incorporator 1 (SERINC1) is a putative carrier protein that facilitates synthesis of serine-derived lipids. To determine if SERINC1 has a role in immune cell function and the development of autoimmunity, we characterized a mouse strain in which a retroviral insertion abolishes expression of the Serinc1 transcript. Expression analyses indicated that the Serinc1 transcript is readily detectable and expressed at relatively high levels in wildtype macrophages and lymphocytes. The ablation of Serinc1 expression in these immune cells, however, did not significantly alter serine-derived lipid composition or affect macrophage function and lymphocyte proliferation. Analyses of Serinc1-deficient mice also indicated that systemic ablation of Serinc1 expression did not affect viability, fertility or autoimmune disease susceptibility. These results suggest that Serinc1 is dispensable for certain immune cell functions and does not contribute to previously reported links between lipid composition in immune cells and autoimmunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Very Young Children Affected and Infected by HIV/AIDS: How are they Living?: A Case Study from Namibia

ERIC Educational Resources Information Center

Hayden, Jacqueline; Otaala, Barnabas

2005-01-01

This paper describes a recent study conducted jointly by the authors in the Khomas Region of Namibia. The study developed and trialled research and documentation methods regarding very young children who had been infected or affected by the HIV/AIDS pandemic. Because of the stigma attached to the disease, effective methods for assessing…

Sub-Saharan Africa Report No. 2807.

DTIC Science & Technology

1983-06-08

USSR Journalists’ Agreement Afghan Revolution Supported GDR Farmers’ Agreement GABON Observers Reportedly Consider Bongo Firmly in...is the position of white workers in South Africa? To what extent have pri- vileges affected their attitudes?" "What is your definition of the...reconversion of huge military expenditure into sound develop- ment programmes to alleviate poverty, illiteracy, disease and hunger which affect millions of

Perspectives in Genetics and Sickle Cell Disease Prevention in Africa: Beyond the Preliminary Data from Cameroon.

PubMed

Wonkam, Ambroise; Ngo Bitoungui, Valentina Josiane; Ngogang, Jeanne

2015-01-01

Management of sickle cell disease (SCD) in Africa needs to be accompanied by various preventive strategies, including early detection via prenatal genetic diagnosis (PND). Contrary to Cameroonian doctors who considered termination of an affected pregnancy (TAP) for SCD in 36.1%, the majority of parents (62.5%) with affected children accepted TAP in principle. In practice, most women opted for TAP (90%), justified by a huge psycho-social burden. The ethical and legal challenges of PND prompted the need to explore the use of genetics for secondary prevention of SCD. In 610 Cameroonian SCD patients, the genomic variations in two principal foetal haemoglobin-promoting loci were significantly associated with foetal haemoglobin levels. In addition, the co-inheritance of a 3.7-kb α-globin gene deletion and SCD was associated with a late disease onset and possibly improved survival: there was a much higher allele frequency of the 3.7-kb α-globin gene deletion in SCD patients (∼ 40%) than in haemoglobin AA controls (∼ 10%). The data indicate the urgent need to develop and implement policy actions in sub-Saharan Africa on at least four levels: (1) the implementation of SCD screening practices and early neonatal follow-up; (2) the development and incorporating of socio-economic support to alleviate the burden of SCD on affected families; (3) the exploration of the appropriateness of the medical abortion laws for SCD, and (4) the development of national plans for genetic medicine, including research on genomic variants that affect the phenotypes of SCD, in order to potentially use them for anticipatory guidance. © 2015 S. Karger AG, Basel.

Cyprinid herpesvirus-3 (CyHV-3) disturbs osmotic balance in carp (Cyprinus carpio L.)--A potential cause of mortality.

PubMed

Negenborn, J; van der Marel, M C; Ganter, M; Steinhagen, D

2015-06-12

Cyprinid herpesvirus-3 (CyHV-3) causes a fatal disease in carp (Cyprinus carpio) and its ornamental koi varieties which seriously affects production and trade of this fish species globally. Up to now, the pathophysiology of this disease remains unclear. Affected individuals develop most prominent lesions in gills, skin and kidney, in tissues which are involved in the osmotic regulation of freshwater teleosts. Therefore, here serum and urine electrolyte levels were examined during the course of an experimental infection of carp with CyHV-3. In infected carp an interstitial nephritis with a progressive deterioration of nephric tubules developed, which was paralleled by elevated electrolyte losses, mainly Na(+) in the urine. The urine/plasma ratio for Na(+) increased from 0.03 in uninfected carp to 0.43-0.83 in carp under CyHV-3 infection, while concentration of divalent ions were not significantly changed. These electrolyte losses could not be compensated since plasma osmolality and Na(+) concentration dropped significantly in CyHV-3 infected carp. This was most probably caused by the progressive deterioration of the branchial epithelium, which in teleosts plays a prominent role in osmoregulation, and which was seen concomitantly with decreasing electrolyte levels in the serum of carp under CyHV-3 infection. Immediately after infection with CyHV-3, by day 2 post exposure, affected carp showed severe anaemia and prominent leucocytosis indicating the development of an acute inflammation, which could intensify the observed hydro-mineral imbalances. The data presented here show that an infection with CyHV-3 induces an acute inflammation and a severe dysfunction of osmoregulation in affected carp or koi, which may lead to death in particular in the case of acute disease progression. Copyright © 2015 Elsevier B.V. All rights reserved.

Prenatal Tests

MedlinePlus

... disease (STD) or cervical cancer In a developing child, prenatal tests can: identify treatable health problems that can affect the baby show characteristics of the baby, including size, sex, age, and position in the uterus help determine ...

[(Over-)flowing bone: the rare disease of melorheostosis: clinical presentation and therapeutic concepts demonstrated by three cases].

PubMed

Hesse, E; Brand, J; Bastian, L; Krettek, C; Meller, R

2008-07-01

Melorheostosis is a rare, benign, and sporadically occurring osteosclerosis of unknown cause. The onset of the disease is usually in early adulthood. Melorheostosis affects both genders, develops progressively, and is usually limited to one side of the human body. The sclerosis originates predominantly from the cortices of the long bones of the lower limbs and rarely the upper limbs. Frequently, the sclerosis involves the soft tissue surrounding the affected bones which may cause limitations in the range of motion, contractures, deformities, and pain. Melorheostosis is usually diagnosed by radiograms. Pain relief and restoration of the full range of motion are the primary goals of the therapeutic approach. A good outcome cannot always be achieved and a recurrence of the disease happens very often.

[Gastroparesis and other gastrointestinal symptoms in Parkinson's disease].

PubMed

Santos-Garcia, D; de Deus, T; Tejera-Perez, C; Exposito-Ruiz, I; Suarez-Castro, E; Carpintero, P; Macias-Arribi, M

2015-09-16

Different gastrointestinal symptoms, such as excessive salivation, deterioration and other disorders affecting the teeth, dysphagia, gastroparesis, gastroesophageal reflux, constipation, difficult defecation or loss of weight are frequent events in all the stages of the development of Parkinson's disease and affect at least a third of the patients. These symptoms reflect the dysfunction of the enteric nervous system, and the stomach is one of the organs where alpha-synuclein is first deposited. Other factors, such as the dysfunction of structures in the central nervous system like the dorsal motor nucleus of the vagal nerve, hormonal factors or secondary effects deriving from the consumption of antiparkinsonian drugs, are involved in its origin. The present article offers a detailed review of the epidemiological, pathophysiological, clinical and therapeutic management aspects of the different gastrointestinal symptoms in Parkinson's disease.

[Mental disorders in digestive system diseases - internist's and psychiatrist's insight].

PubMed

Kukla, Urszula; Łabuzek, Krzysztof; Chronowska, Justyna; Krzystanek, Marek; Okopień, BogusŁaw

2015-05-01

Mental disorders accompanying digestive system diseases constitute interdisciplinary yet scarcely acknowledged both diagnostic and therapeutic problem. One of the mostly recognized examples is coeliac disease where patients endure the large spectrum of psychopathological symptoms, starting with attention deficit all the way down to the intellectual disability in extreme cases. It has not been fully explained how the pathomechanism of digestive system diseases affects patient's mental health, however one of the hypothesis suggests that it is due to serotonergic or opioid neurotransmission imbalance caused by gluten and gluten metabolites effect on central nervous system. Behavioral changes can also be invoked by liver or pancreatic diseases, which causes life-threatening abnormalities within a brain. It occurs that these abnormalities reflexively exacerbate the symptoms of primary somatic disease and aggravate its course, which worsens prognosis. The dominant mental disease mentioned in this article is depression which because of its effect on a hypothalamuspituitary- adrenal axis and on an autonomic nervous system, not only aggravates the symptoms of inflammatory bowel diseases but may accelerate their onset in genetically predisposed patients. Depression is known to negatively affects patients' ability to function in a society and a quality of their lives. Moreover, as far as children are concerned, the occurrence of digestive system diseases accompanied by mental disorders, may adversely affect their further physical and psychological development, which merely results in worse school performance. All those aspects of mental disorders indicate the desirability of the psychological care for patients with recognized digestive system disease. The psychological assistance should be provided immediately after diagnosis of a primary disease and be continued throughout the whole course of treatment. © 2015 MEDPRESS.

Thematic analysis of blog narratives written by people with Alzheimer's disease and other dementias and care partners.

PubMed

Kannaley, Kristie; Mehta, Shreya; Yelton, Brooks; Friedman, Daniela B

2018-01-01

Limited research takes a socio-biographical approach to study the experiences and perspectives of individuals affected by Alzheimer's disease and related dementias. The purpose of this study was to thematically analyze blog narratives written by people with Alzheimer's disease and related dementia and care partners in order to increase understanding of their experiences. Nineteen blogs written by people with Alzheimer's disease and related dementia and 44 blogs written by care partners were analyzed. The first two authors utilized line-by-line open coding to analyze five posts from each group for the development of a codebook. Using NVivo software, the first author proceeded to code the remaining blogs for emergent themes and subcategories. Emergent themes included (1) effects of Alzheimer's disease and related dementia on the person with Alzheimer's disease and related dementia and/or the care partner; (2) seeing the positives; (3) feeling out of control; (4) advocacy and empowerment; (5) coping mechanisms and compensatory strategies; and (6) candid descriptions of experiences with Alzheimer's disease and related dementia. These themes also encompassed numerous subcategories that are discussed in this paper. Results from this study provide insights into the experiences of individuals affected by Alzheimer's disease and related dementia. Writers discussed several topics that are consistent with research on illness narratives of individuals with chronic diseases, including loss of identity, strategies for coping, and poignant descriptions of life with the disease. This study provides information in the form of overlapping themes from first-person perspectives of numerous individuals affected by Alzheimer's disease and related dementia. This type of data is crucial to understand the experiences of people who live with ADRD.

Ageing and muscular dystrophy differentially affect murine pharyngeal muscles in a region-dependent manner

PubMed Central

Randolph, Matthew E; Luo, Qingwei; Ho, Justin; Vest, Katherine E; Sokoloff, Alan J; Pavlath, Grace K

2014-01-01

The inability to swallow, or dysphagia, is a debilitating and life-threatening condition that arises with ageing or disease. Dysphagia results from neurological or muscular impairment of one or more pharyngeal muscles, which function together to ensure proper swallowing and prevent the aspiration of food or liquid into the lungs. Little is known about the effects of age or disease on pharyngeal muscles as a group. Here we show ageing affected pharyngeal muscle growth and atrophy in wild-type mice depending on the particular muscle analysed. Furthermore, wild-type mice also developed dysphagia with ageing. Additionally, we studied pharyngeal muscles in a mouse model for oculopharyngeal muscular dystrophy, a dysphagic disease caused by a polyalanine expansion in the RNA binding protein, PABPN1. We examined pharyngeal muscles of mice overexpressing either wild-type A10 or mutant A17 PABPN1. Overexpression of mutant A17 PABPN1 differentially affected growth of the palatopharyngeus muscle dependent on its location within the pharynx. Interestingly, overexpression of wild-type A10 PABPN1 was protective against age-related muscle atrophy in the laryngopharynx and prevented the development of age-related dysphagia. These results demonstrate that pharyngeal muscles are differentially affected by both ageing and muscular dystrophy in a region-dependent manner. These studies lay important groundwork for understanding the molecular and cellular mechanisms that regulate pharyngeal muscle growth and atrophy, which may lead to novel therapies for individuals with dysphagia. PMID:25326455

Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream

PubMed Central

López-Bueno, Alberto; Mavian, Carla; Labella, Alejandro M.; Castro, Dolores; Borrego, Juan J.; Alcami, Antonio

2016-01-01

ABSTRACT Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought. IMPORTANCE Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae. In the Mediterranean area, the gilthead sea bream (Sparus aurata), an important farmed fish, is frequently affected. Using next-generation sequencing, we have identified within S. aurata lymphocystis lesions the concurrent presence of an additional LCDV species (LCDV-Sa) as well as two novel viruses. These are members of polyomavirus and papillomavirus families, and here we report them to be frequently associated with the presence of lymphocysts in affected fish. Because papillomaviruses have not been described in fish before, these findings support a more ancient origin of this virus family than previously thought and evolutionary implications are discussed. PMID:27440877

Concurrence of Iridovirus, Polyomavirus, and a Unique Member of a New Group of Fish Papillomaviruses in Lymphocystis Disease-Affected Gilthead Sea Bream.

PubMed

López-Bueno, Alberto; Mavian, Carla; Labella, Alejandro M; Castro, Dolores; Borrego, Juan J; Alcami, Antonio; Alejo, Alí

2016-10-01

Lymphocystis disease is a geographically widespread disease affecting more than 150 different species of marine and freshwater fish. The disease, provoked by the iridovirus lymphocystis disease virus (LCDV), is characterized by the appearance of papillomalike lesions on the skin of affected animals that usually self-resolve over time. Development of the disease is usually associated with several environmental factors and, more frequently, with stress conditions provoked by the intensive culture conditions present in fish farms. In gilthead sea bream (Sparus aurata), an economically important cultured fish species in the Mediterranean area, a distinct LCDV has been identified but not yet completely characterized. We have used direct sequencing of the virome of lymphocystis lesions from affected S. aurata fish to obtain the complete genome of a new LCDV-Sa species that is the largest vertebrate iridovirus sequenced to date. Importantly, this approach allowed us to assemble the full-length circular genome sequence of two previously unknown viruses belonging to the papillomaviruses and polyomaviruses, termed Sparus aurata papillomavirus 1 (SaPV1) and Sparus aurata polyomavirus 1 (SaPyV1), respectively. Epidemiological surveys showed that lymphocystis disease was frequently associated with the concurrent appearance of one or both of the new viruses. SaPV1 has unique characteristics, such as an intron within the L1 gene, and as the first member of the Papillomaviridae family described in fish, provides evidence for a more ancient origin of this family than previously thought. Lymphocystis disease affects marine and freshwater fish species worldwide. It is characterized by the appearance of papillomalike lesions on the skin that contain heavily enlarged cells (lymphocysts). The causative agent is the lymphocystis disease virus (LCDV), a large icosahedral virus of the family Iridoviridae In the Mediterranean area, the gilthead sea bream (Sparus aurata), an important farmed fish, is frequently affected. Using next-generation sequencing, we have identified within S. aurata lymphocystis lesions the concurrent presence of an additional LCDV species (LCDV-Sa) as well as two novel viruses. These are members of polyomavirus and papillomavirus families, and here we report them to be frequently associated with the presence of lymphocysts in affected fish. Because papillomaviruses have not been described in fish before, these findings support a more ancient origin of this virus family than previously thought and evolutionary implications are discussed. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Disease risk factors and disease progress in coast live oak and tanoak affected by Phytophthora ramorum canker (sudden oak death)

Treesearch

Tedmund J. Swiecki; Elizabeth Bernhardt

2006-01-01

This paper reports on five years of observations in a case-control study examining the role of tree and site factors on the development of Phytophthora ramorum stem canker (sudden oak death) in coast live oak (Quercus agrifolia) and tanoak (Lithocarpus densiflorus). In September of each year from 2000 through...

A Follow-up of a National Cohort of Breast Disease Factors Affecting the Development of Breast Cancer.

DTIC Science & Technology

1996-09-01

The study is based on a twelve-year follow-up of the cohort of 3500 women histologically diagnosed nationwide for benign and malignant breast lesions...between US whites and Africans. This study offers a unique opportunity to evaluate the progression of benign and malignant breast disease on a whole community base population.

New Perspectives on Oxidized Genome Damage and Repair Inhibition by Pro-Oxidant Metals in Neurological Diseases

PubMed Central

Mitra, Joy; Guerrero, Erika N.; Hegde, Pavana M.; Wang, Haibo; Boldogh, Istvan; Rao, Kosagi Sharaf; Mitra, Sankar; Hegde, Muralidhar L.

2014-01-01

The primary cause(s) of neuronal death in most cases of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are still unknown. However, the association of certain etiological factors, e.g., oxidative stress, protein misfolding/aggregation, redox metal accumulation and various types of damage to the genome, to pathological changes in the affected brain region(s) have been consistently observed. While redox metal toxicity received major attention in the last decade, its potential as a therapeutic target is still at a cross-roads, mostly because of the lack of mechanistic understanding of metal dyshomeostasis in affected neurons. Furthermore, previous studies have established the role of metals in causing genome damage, both directly and via the generation of reactive oxygen species (ROS), but little was known about their impact on genome repair. Our recent studies demonstrated that excess levels of iron and copper observed in neurodegenerative disease-affected brain neurons could not only induce genome damage in neurons, but also affect their repair by oxidatively inhibiting NEIL DNA glycosylases, which initiate the repair of oxidized DNA bases. The inhibitory effect was reversed by a combination of metal chelators and reducing agents, which underscore the need for elucidating the molecular basis for the neuronal toxicity of metals in order to develop effective therapeutic approaches. In this review, we have focused on the oxidative genome damage repair pathway as a potential target for reducing pro-oxidant metal toxicity in neurological diseases. PMID:25036887

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

PubMed

Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

2008-12-01

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

Including the Group Quarters Population in the US Synthesized Population Database

PubMed Central

Chasteen, Bernadette M.; Wheaton, William D.; Cooley, Philip C.; Ganapathi, Laxminarayana; Wagener, Diane K.

2011-01-01

In 2005, RTI International researchers developed methods to generate synthesized population data on US households for the US Synthesized Population Database. These data are used in agent-based modeling, which simulates large-scale social networks to test how changes in the behaviors of individuals affect the overall network. Group quarters are residences where individuals live in close proximity and interact frequently. Although the Synthesized Population Database represents the population living in households, data for the nation’s group quarters residents are not easily quantified because of US Census Bureau reporting methods designed to protect individuals’ privacy. Including group quarters population data can be an important factor in agent-based modeling because the number of residents and the frequency of their interactions are variables that directly affect modeling results. Particularly with infectious disease modeling, the increased frequency of agent interaction may increase the probability of infectious disease transmission between individuals and the probability of disease outbreaks. This report reviews our methods to synthesize data on group quarters residents to match US Census Bureau data. Our goal in developing the Group Quarters Population Database was to enable its use with RTI’s US Synthesized Population Database in the Modeling of Infectious Diseases Agent Study. PMID:21841972

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals.

PubMed

Dunn, Caitlin; Callahan, Kelly; Katabarwa, Moses; Richards, Frank; Hopkins, Donald; Withers, P Craig; Buyon, Lucas E; McFarland, Deborah

2015-05-01

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the "big three" diseases--namely HIV, tuberculosis (TB), and malaria--has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda.

[Physical activity and respiratory tract diseases asthma and allergy].

PubMed

Carlsen, K H

2000-11-10

This article presents a review of the relationship between physical training and airways diseases: the relationship between physical activity and the development of airways diseases, and the effect of physical training in rehabilitation after airways diseases. The article is a systematic review of exercise-induced asthma (EIA), the effect of physical training upon bronchial hyperresponsiveness and the development of asthma; how chronic lung diseases affect the ability to participate in physical activity; and the use of physical training in rehabilitation after airways diseases. Physical training may provoke EIA in asthmatic patients. Furthermore, heavy regular training over long periods of time may contribute to the development of asthma. Mastering EIA is an important goal in the management of asthma, especially in children and adolescents, in order to foster normal physical and mental development. Physical training improves fitness and the mastering of asthma, but not of bronchial hyperresponsiveness and asthma activity. In other airways disorders like cystic fibrosis or chronic obstructive lung disease, a reduced lung function may limit the ability to participate in physical activity. Training is an important tool in the rehabilitation of patients with pulmonary disorders as it improves physical fitness and quality of life.

A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early Developed Pulmonary Hypertension.

PubMed

Vaidya, Gaurang; Sarwar, Muhammad; Sun, Zongxia; Wei, Tiemin; Liu, Kan

2015-01-01

Pulmonary hypertension (PH) worsens the mortality of the patients with sickle cell disease (SCD). The exact mechanism of PH development/progression in SCD, including the role of tricuspid regurgitation (TR), remains unclear. We herein report an unusual SCD case, complicated by chronic thromboembolic disorder, who developed severe TR and an accelerated progression of PH. Tricuspid valve surgery significantly ameliorated the patient's symptoms and reduced hospital readmission. The early detection and management of the reversible disorder accelerating the PH development in SCD patients may alter the clinical course, improve the quality of life, and potentially affect the long-term outcome.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.

PubMed

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases.

A Type A and Type D Combined Personality Typology in Essential Hypertension and Acute Coronary Syndrome Patients: Associations with Demographic, Psychological, Clinical, and Lifestyle Indicators

PubMed Central

Steca, Patrizia; D’Addario, Marco; Magrin, Maria Elena; Miglioretti, Massimo; Monzani, Dario; Pancani, Luca; Sarini, Marcello; Scrignaro, Marta; Vecchio, Luca; Fattirolli, Francesco; Giannattasio, Cristina; Cesana, Francesca; Riccobono, Salvatore Pio

2016-01-01

Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed. PMID:27589065

Helminths and the IBD hygiene hypothesis.

PubMed

Weinstock, Joel V; Elliott, David E

2009-01-01

Helminths are parasitic animals that have evolved over 100,000,000 years to live in the intestinal track or other locations of their hosts. Colonization of humans with these organisms was nearly universal until the early 20th century. More than 1,000,000,000 people in less developed countries carry helminths even today. Helminths must quell their host's immune system to successfully colonize. It is likely that helminths sense hostile changes in the local host environment and take action to control such responses. Inflammatory bowel disease (IBD) probably results from an inappropriately vigorous immune response to contents of the intestinal lumen. Environmental factors strongly affect the risk for IBD. People living in less developed countries are protected from IBD. The "IBD hygiene hypothesis" states that raising children in extremely hygienic environments negatively affects immune development, which predisposes them to immunological diseases like IBD later in life. Modern day absence of exposure to intestinal helminths appears to be an important environmental factor contributing to development of these illnesses. Helminths interact with both host innate and adoptive immunity to stimulate immune regulatory circuitry and to dampen effector pathways that drive aberrant inflammation. The first prototype worm therapies directed against immunological diseases are now under study in the United States and various countries around the world. Additional studies are in the advanced planning stage.

Redox Regulation of Cell Survival

PubMed Central

Trachootham, Dunyaporn; Lu, Weiqin; Ogasawara, Marcia A.; Valle, Nilsa Rivera-Del

2008-01-01

Abstract Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to promote cell proliferation and survival, whereas severe increase of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. This review focuses on the roles of key transcription factors, signal-transduction pathways, and cell-death regulators in affecting cell survival, and how the redox systems regulate the functions of these molecules. The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed. We also discuss how the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases. Antioxid. Redox Signal. 10, 1343–1374. PMID:18522489

[Cryptococcal meningitis as a diagnostic problem in a patient with SLE--case report].

PubMed

Bosnić, Dubravka; Cerovec, Mislav; Anić, Branimir; Mayer, Miroslav; Sentić, Mirna; Baresić, Marko; Markeljević, Jasenka; Cikes, Nada

2008-01-01

Systemic erythematosus lupus (SLE) is a disease with wide range of clinical manifestations, signs and symptoms. Disease outcome depends mostly on the affection of kidneys and central nervous system by the disease. Very important cause of death in patients with SLE is infection. Infections are very common among these patients due to aggressive immunosuppressive treatment that is needed for the disease inflammatory activity control. In this case report we have presented a patient with SLE who initially had severe renal affection, but also complications of immunosuppressive therapy that was administered. Even though the disease was accidentally diagnosed, it had a severe clinical progress. Because of lupus nephropathy, in the early phase of the disease we administered aggressive immunosuppressive therapy (combined parenteral therapy of glucocorticoides and cyclophosphamide). As an outcome of the combined effect of disease and immunosuppressive agents used in the treatment of the disease, the patient had increased infective diathesis (repeated infections caused by S. enteritidis--urinary infections and sepsis). During one of the disease flares the patient was hospitalized an opportunistic infection developed. It was meningitis caused by C. neoformans. This opportunistic mycosis infection presented with clinically totally nonspecific signs and symptoms of CNS affection. Therefore, we suspected affection of CNS with SLE. Even though all diagnostic procedures were made on time and that adequate antifungal and supportive agents were applied very early after the infection onset, the outcome was fatal. Because of infective diathesis in patients with SLE, which present with common and opportunistic infections, and due to high mortality rates caused by these infections, we have tried to emphasise the importance of taking adequate specimens early after infection outcome for these rare infective agents like C. neophormans. In recent medical literature are dominant cases reported in Asia. Reports from Europe are very rare, and this case is the one of that kind in Croatia.

Effectiveness of knowledge translation tools addressing multiple high-burden chronic diseases affecting older adults: protocol for a systematic review alongside a realist review

PubMed Central

Kastner, Monika; Perrier, Laure; Hamid, Jemila; Tricco, Andrea C; Cardoso, Roberta; Ivers, Noah M; Liu, Barbara; Marr, Sharon; Holroyd-Leduc, Jayna; Wong, Geoff; Graves, Lisa; Straus, Sharon E

2015-01-01

Introduction The burden of chronic disease is a global phenomenon, particularly among people aged 65 years and older. More than half of older adults have more than one chronic disease and their care is not optimal. Chronic disease management (CDM) tools have the potential to meet this challenge but they are primarily focused on a single disease, which fails to address the growing number of seniors with multiple chronic conditions. Methods and analysis We will conduct a systematic review alongside a realist review to identify effective CDM tools that integrate one or more high-burden chronic diseases affecting older adults and to better understand for whom, under what circumstances, how and why they produce their outcomes. We will search MEDLINE, EMBASE, CINAHL, AgeLine and the Cochrane Library for experimental, quasi-experimental, observational and qualitative studies in any language investigating CDM tools that facilitate optimal disease management in one or more high-burden chronic diseases affecting adults aged ≥65 years. Study selection will involve calibration of reviewers to ensure reliability of screening and duplicate assessment of articles. Data abstraction and risk of bias assessment will also be performed independently. Analysis will include descriptive summaries of study and appraisal characteristics, effectiveness of each CDM tool (meta-analysis if appropriate); and a realist programme theory will be developed and refined to explain the outcome patterns within the included studies. Ethics and dissemination Ethics approval is not required for this study. We anticipate that our findings, pertaining to gaps in care across high-burden chronic diseases affecting seniors and highlighting specific areas that may require more research, will be of interest to a wide range of knowledge users and stakeholders. We will publish and present our findings widely, and also plan more active dissemination strategies such as workshops with our key stakeholders. Trial registration number Our protocol is registered with PROSPERO (registration number CRD42014014489). PMID:25649215

Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents.

PubMed

Krzewska, Aleksandra; Ben-Skowronek, Iwona

2016-01-01

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.

The role of irrational thought in medicine adherence: people with diabetic kidney disease.

PubMed

Williams, Allison F; Manias, Elizabeth; Walker, Rowan

2009-10-01

This paper is a report of a study conducted to examine how irrational thinking affects people's adherence to multiple medicines prescribed to manage their diabetic kidney disease. Approximately 50% of people are non-adherent to their prescribed medicines and the risk of non-adherence escalates as the number of prescribed medicines increases. Adherence to prescribed medicines can slow disease progression in diabetic kidney disease. A descriptive exploratory design was used. In-depth interviews were conducted with 23 participants recruited from a nephrology outpatient clinic in Australia in 2007. Data were analysed using a 'framework' method. Participants' mean age was 59 years, they had approximately six chronic conditions in addition to their diabetic kidney disease and were prescribed a median of ten medicines daily. Two major themes of irrational thinking--heuristics and denial--and subthemes were identified. Heuristics contributed to inaccurate risk assessment and biases affecting rational judgement concerning medicines, whereas denial was used to enhance coping necessary to manage this complex health condition. Participants underestimated their health risks because they had been taking medicines for many years and preferred not to dwell on their ill health. A large amount of irrational thinking was related to maintaining the emotional strength necessary to manage their comorbid conditions as best they could. Regular assessment and support of medicine adherence throughout the disease course is necessary to avert the development of counterproductive heuristics and denial affecting medicine adherence.

Rethinking Nuclear Receptors as Potential Therapeutic Targets for Retinal Diseases.

PubMed

Choudhary, Mayur; Malek, Goldis

2016-12-01

Collectively, retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, result in severe vision impairment worldwide. The absence and/or limited availability of successful drug therapies for these blinding disorders necessitates further understanding their pathobiology and identifying new targetable signaling pathways. Nuclear receptors are transcription regulators of many key aspects of human physiology, as well as pathophysiology, with reported roles in development, aging, and disease. Some of the pathways regulated by nuclear receptors include, but are not limited to, angiogenesis, inflammation, and lipid metabolic dysregulation, mechanisms also important in the initiation and development of several retinal diseases. Herein, we present an overview of the biology of three diseases affecting the posterior eye, summarize a growing body of evidence that suggests direct or indirect involvement of nuclear receptors in disease progression, and discuss the therapeutic potential of targeting nuclear receptors for treatment.

Rethinking Nuclear Receptors as Potential Therapeutic Targets for Retinal Diseases

PubMed Central

Choudhary, Mayur; Malek, Goldis

2017-01-01

Collectively, retinal diseases, including age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy, result in severe vision impairment worldwide. The absence and/or limited availability of successful drug therapies for these blinding disorders necessitates further understanding their pathobiology and identifying new targetable signaling pathways. Nuclear receptors are transcription regulators of many key aspects of human physiology, as well as pathophysiology, with reported roles in development, aging, and disease. Some of the pathways regulated by nuclear receptors include, but are not limited to, angiogenesis, inflammation, and lipid metabolic dysregulation, mechanisms also important in the initiation and development of several retinal diseases. Herein, we present an overview of the biology of three diseases affecting the posterior eye, summarize a growing body of evidence that suggests direct or indirect involvement of nuclear receptors in disease progression, and discuss the therapeutic potential of targeting nuclear receptors for treatment. PMID:27455994

Pathology of Minamata disease.

PubMed

Eto, K

1997-01-01

Minamata disease, or methylmercury poisoning, was first discovered in 1956 around Minamata Bay, Kumamoto Prefecture, Japan. A similar epidemic occurred in 1965 along the Agano River, Niigata Prefecture, Japan. The neuropathology of Minamata disease has been well studied; this review focuses on human cases of Minamata disease in Kumamoto Prefecture. Nervous system lesions associated with Minamata disease have a characteristic distribution. In the cerebral cortex, the calcarine cortex was found to be involved in all cases of Minamata disease, particularly along the calcarine fissure. The destruction of nerve tissue was prominent in the anterior portions of the calcarine cortex. Occasionally, the centrifugal route from the visual and visual association areas (internal sagittal stratum) showed secondary degeneration in prolonged cases after acute onset. Postcentral, precentral, and temporal transverse cortices showed similar changes, though they were less severe. Intense lesions in the precentral cortex caused the development of secondary bilateral degeneration of the pyramidal tracts. In the cerebellum, the lesions occurred deeper in the hemisphere. The granule cell population was most affected. In the peripheral nerves, sensory nerves were more affected than motor nerves. Secondary degeneration of Goll's tracts was occasionally seen in prolonged or chronic cases.

A model to evaluate quality and effectiveness of disease management.

PubMed

Lemmens, K M M; Nieboer, A P; van Schayck, C P; Asin, J D; Huijsman, R

2008-12-01

Disease management has emerged as a new strategy to enhance quality of care for patients suffering from chronic conditions, and to control healthcare costs. So far, however, the effects of this strategy remain unclear. Although current models define the concept of disease management, they do not provide a systematic development or an explanatory theory of how disease management affects the outcomes of care. The objective of this paper is to present a framework for valid evaluation of disease-management initiatives. The evaluation model is built on two pillars of disease management: patient-related and professional-directed interventions. The effectiveness of these interventions is thought to be affected by the organisational design of the healthcare system. Disease management requires a multifaceted approach; hence disease-management programme evaluations should focus on the effects of multiple interventions, namely patient-related, professional-directed and organisational interventions. The framework has been built upon the conceptualisation of these disease-management interventions. Analysis of the underlying mechanisms of these interventions revealed that learning and behavioural theories support the core assumptions of disease management. The evaluation model can be used to identify the components of disease-management programmes and the mechanisms behind them, making valid comparison feasible. In addition, this model links the programme interventions to indicators that can be used to evaluate the disease-management programme. Consistent use of this framework will enable comparisons among disease-management programmes and outcomes in evaluation research.

A Risk Analysis Approach to Prioritizing Epidemics: Ebola Virus Disease in West Africa as a Case Study

PubMed Central

Chughtai, Abrar Ahmad; MacIntyre, C. Raina

2017-01-01

Abstract The 2014 Ebola virus disease (EVD) outbreak affected several countries worldwide, including six West African countries. It was the largest Ebola epidemic in the history and the first to affect multiple countries simultaneously. Significant national and international delay in response to the epidemic resulted in 28,652 cases and 11,325 deaths. The aim of this study was to develop a risk analysis framework to prioritize rapid response for situations of high risk. Based on findings from the literature, sociodemographic features of the affected countries, and documented epidemic data, a risk scoring framework using 18 criteria was developed. The framework includes measures of socioeconomics, health systems, geographical factors, cultural beliefs, and traditional practices. The three worst affected West African countries (Guinea, Sierra Leone, and Liberia) had the highest risk scores. The scores were much lower in developed countries that experienced Ebola compared to West African countries. A more complex risk analysis framework using 18 measures was compared with a simpler one with 10 measures, and both predicted risk equally well. A simple risk scoring system can incorporate measures of hazard and impact that may otherwise be neglected in prioritizing outbreak response. This framework can be used by public health personnel as a tool to prioritize outbreak investigation and flag outbreaks with potentially catastrophic outcomes for urgent response. Such a tool could mitigate costly delays in epidemic response. PMID:28810081

[Hypotonic syndrome in the newborn infant].

PubMed

Gaona, Víctor Alejandro

2013-09-06

Hypotonia is understood to refer to a pronounced decrease in muscle tone that affects normal motor development and that may affect the axial muscles as well as those of the limbs and, sometimes, the face. It is a very challenging clinical picture because it consists in a fairly wide range of conditions that affect different areas of the central and peripheral nervous system and may be the expression of pathologies that can be either benign or of an uncertain prognosis. These cover myopathies, metabolic disorders, diseases based on genetic causes, pathologies affecting the endocrine glands and progressive or chronic diseases, among other aetiologies. The important development of medicine today has made a number of tools available to the examiner with which to refine or pronounce a diagnosis. Such instruments include the developments achieved in genetic research, together with studies conducted in imaging and optical and electronic microscopy. However, in spite of having all this material available for use, it is still the clinical features that allow a rational use to be made of these advances to be able to point towards the possible causation, topographic location and developmental control. It is useful, for the diagnostic approach and the use of auxiliary methods, to know the topographic location of the disorder, whether it is situated in the brain, the cerebellum, the stem, the spinal cord, the peripheral nerves, the myoneural junction or the muscle.

Incidence and prevalence of pregnancy-related heart disease.

PubMed

Sliwa, Karen; Böhm, Michael

2014-03-15

Worldwide, the numbers of women who have a pre-existing cardiovascular disease or develop cardiac problems during pregnancy are increasing and, due to the lack of evidenced-based data, this provides challenges for the treating physician. Cardiovascular disease in pregnancy is a complex topic as women can present either pre- or post-partum, due to a pre-existing heart disease such as operated on or unoperated on congenital heart disease, valvular heart disease, chronic hypertension, or familial dilated cardiomyopathy. Women often present with symptoms and signs of acute heart failure. On the other hand, there are diseases which are directly related to pregnancy, such as hypertensive disorders of pregnancy and peripartum cardiomyopathy, or where pregnancy increases risk of a disease as, for example, the risk of myocardial infarction. These diseases can have long-term implications to the life of the affected women and their families. There is, in particular, a paucity of data from developing countries of this unique disease pattern and its presentations. This review summarizes the current knowledge of the incidence and prevalence of pregnancy-related cardiovascular disease in women presenting pre- or post-partum.

Primary Follicular Dystrophy with Scarring Dermatitis in C57BL/6 Mouse Substrains Resembles Central Centrifugal Cicatricial Alopecia in Humans

PubMed Central

Sundberg, John P.; Taylor, Douglas; Lorch, Gwendolen; Miller, Jim; Silva, Kathleen A.; Sundberg, Beth A.; Roopenian, Derry; Sperling, Leonard; Ong, David; King, Lloyd E.; Everts, Helen

2011-01-01

A number of C57BL/6 (B6) substrains are commonly used by scientists for basic biomedical research. One of several B6 strain specific background diseases is focal alopecia that may resolve or progress to severe, ulcerative dermatitis. Clinical and progressive histologic changes of skin disease commonly observed in C57BL/6J and preliminary studies in other closely related substrains are presented. Lesions develop due to a primary follicular dystrophy with rupture of severely affected follicles leading to formation of secondary foreign body granulomas (trichogranulomas) in affected B6 substrains of mice. Histologically these changes resemble the human disease called central centrifugal cicatrical alopecia (CCCA). Four B6 substrains tested have a polymorphism in alcohol dehydrogenase 4 (Adh4) that reduces its activity and potentially affects removal of excess retinol. Using immunohistochemistry, differential expression of epithelial retinol dehydrogenase (DHRS9) was detected which may partially explain anecdotal reports of frequency differences between B6 substrains. The combination of these two defects have the potential to make high dietary vitamin A levels toxic in some B6 substrains while not affecting most other commonly used inbred strains. PMID:20861494

Progress towards genetic and pharmacological therapies for keratin genodermatoses: current perspective and future promise

PubMed Central

Chamcheu, Jean Christopher; Wood, Gary S.; Siddiqui, Imtiaz A.; Syed, Deeba N.; Adhami, Vaqar M.; Teng, Joyce M.; Mukhtar, Hasan

2012-01-01

Hereditary keratin disorders of the skin and its appendages comprise a large group of clinically heterogeneous disfiguring blistering and ichthyotic diseases, primarily characterized by the loss of tissue integrity, blistering and hyperkeratosis in severely affected tissues. Pathogenic mutations in keratins cause these afflictions. Typically, these mutations in concert with characteristic features have formed the basis for improved disease diagnosis, prognosis and most recently therapy development. Examples include epidermolysis bullosa simplex, keratinopathic ichthyosis, pachyonychia congenita and several other tissue-specific hereditary keratinopathies. Understanding the molecular and genetic events underlying skin dysfunction has initiated alternative treatment approaches that may provide novel therapeutic opportunities for affected patients. Animal and in vitro disease modelling studies have shed more light on molecular pathogenesis, further defining the role of keratins in disease processes and promoting the translational development of new gene and pharmacological therapeutic strategies. Given that the molecular basis for these monogenic disorders is well established, gene therapy and drug discovery targeting pharmacological compounds with the ability to reinforce the compromised cytoskeleton may lead to promising new therapeutic strategies for treating hereditary keratinopathies. In this review, we will summarize and discuss recent advances in the preclinical and clinical modelling and development of gene, natural product, pharmacological and protein-based therapies for these disorders, highlighting the feasibility of new approaches for translational clinical therapy. PMID:22716242

Progress towards genetic and pharmacological therapies for keratin genodermatoses: current perspective and future promise.

PubMed

Chamcheu, Jean Christopher; Wood, Gary S; Siddiqui, Imtiaz A; Syed, Deeba N; Adhami, Vaqar M; Teng, Joyce M; Mukhtar, Hasan

2012-07-01

Hereditary keratin disorders of the skin and its appendages comprise a large group of clinically heterogeneous disfiguring blistering and ichthyotic diseases, primarily characterized by the loss of tissue integrity, blistering and hyperkeratosis in severely affected tissues. Pathogenic mutations in keratins cause these afflictions. Typically, these mutations in concert with characteristic features have formed the basis for improved disease diagnosis, prognosis and most recently therapy development. Examples include epidermolysis bullosa simplex, keratinopathic ichthyosis, pachyonychia congenita and several other tissue-specific hereditary keratinopathies. Understanding the molecular and genetic events underlying skin dysfunction has initiated alternative treatment approaches that may provide novel therapeutic opportunities for affected patients. Animal and in vitro disease modelling studies have shed more light on molecular pathogenesis, further defining the role of keratins in disease processes and promoting the translational development of new gene and pharmacological therapeutic strategies. Given that the molecular basis for these monogenic disorders is well established, gene therapy and drug discovery targeting pharmacological compounds with the ability to reinforce the compromised cytoskeleton may lead to promising new therapeutic strategies for treating hereditary keratinopathies. In this review, we will summarize and discuss recent advances in the preclinical and clinical modelling and development of gene, natural product, pharmacological and protein-based therapies for these disorders, highlighting the feasibility of new approaches for translational clinical therapy. © 2012 John Wiley & Sons A/S.

Kidney disease and obesity: epidemiology, mechanisms and treatment.

PubMed

Câmara, Niels Olsen Saraiva; Iseki, Kunitoshi; Kramer, Holly; Liu, Zhi-Hong; Sharma, Kumar

2017-03-01

The theme of World Kidney Day 2017 is 'kidney disease and obesity: healthy lifestyle for healthy kidneys'. To mark this event, Nature Reviews Nephrology invited five leading researchers to describe changes in the epidemiology of obesity-related kidney disease, advances in current understanding of the mechanisms and current approaches to the management of affected patients. The researchers also highlight new advances that could lead to the development of novel treatments and identify areas in which further basic and clinical studies are needed.

Communicable Disease Research

NASA Technical Reports Server (NTRS)

1982-01-01

The COSMIC program FITLOS is used regularly by the Centers for Disease Control (CDC), for analyzing data from radioimmunoassays, which involve testing human body substances to provide information on how deficits or excesses of those substances affect a body's ability to ward off disease. A liquid scintillation counter's data is analyzed by the FITLOS program. FITLOS data, then aids in establishing reference methods for hospitals and other health laboratories in their radioimmunoassays. CDC's use of this program enabled them to avoid the cost of designing and developing a new program.

ENPP1 Mutation Causes Recessive Cole Disease by Altering Melanogenesis.

PubMed

Chourabi, Marwa; Liew, Mei Shan; Lim, Shawn; H'mida-Ben Brahim, Dorra; Boussofara, Lobna; Dai, Liang; Wong, Pui Mun; Foo, Jia Nee; Sriha, Badreddine; Robinson, Kim Samirah; Denil, Simon; Common, John Ea; Mamaï, Ons; Ben Khalifa, Youcef; Bollen, Mathieu; Liu, Jianjun; Denguezli, Mohamed; Bonnard, Carine; Saad, Ali; Reversade, Bruno

2018-02-01

Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Learning cell biology as a team: a project-based approach to upper-division cell biology.

PubMed

Wright, Robin; Boggs, James

2002-01-01

To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular and molecular biology of the disease, and recent research focused on understanding the cellular mechanisms of the disease process. To support effective teamwork and to help students develop collaboration skills useful for their future careers, we provide training in working in small groups. A final poster presentation, held in a public forum, summarizes what students have learned throughout the quarter. Although student satisfaction with the course is similar to that of standard lecture-based classes, a project-based class offers unique benefits to both the student and the instructor.

Garlic Organosulfur Compounds Reduce Inflammation and Oxidative Stress during Dengue Virus Infection

PubMed Central

Hall, Alex; Troupin, Andrea; Londono-Renteria, Berlin; Colpitts, Tonya M.

2017-01-01

Dengue virus (DENV) is a mosquito-borne flavivirus that causes significant global human disease and mortality. One approach to develop treatments for DENV infection and the prevention of severe disease is through investigation of natural medicines. Inflammation plays both beneficial and harmful roles during DENV infection. Studies have proposed that the oxidative stress response may be one mechanism responsible for triggering inflammation during DENV infection. Thus, blocking the oxidative stress response could reduce inflammation and the development of severe disease. Garlic has been shown to both reduce inflammation and affect the oxidative stress response. Here, we show that the garlic active compounds diallyl disulfide (DADS), diallyl sulfide (DAS) and alliin reduced inflammation during DENV infection and show that this reduction is due to the effects on the oxidative stress response. These results suggest that garlic could be used as an alternative treatment for DENV infection and for the prevention of severe disease development. PMID:28644404

Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network.

PubMed

Cordes, Kristina M; Cookson, Susan T; Boyd, Andrew T; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad; Husain, Farah

2017-11-01

Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security.

Real-Time Surveillance in Emergencies Using the Early Warning Alert and Response Network

PubMed Central

Cordes, Kristina M.; Cookson, Susan T.; Boyd, Andrew T.; Hardy, Colleen; Malik, Mamunur Rahman; Mala, Peter; El Tahir, Khalid; Everard, Marthe; Jasiem, Mohamad

2017-01-01

Humanitarian emergencies often result in population displacement and increase the risk for transmission of communicable diseases. To address the increased risk for outbreaks during humanitarian emergencies, the World Health Organization developed the Early Warning Alert and Response Network (EWARN) for early detection of epidemic-prone diseases. The US Centers for Disease Control and Prevention has worked with the World Health Organization, ministries of health, and other partners to support EWARN through the implementation and evaluation of these systems and the development of standardized guidance. Although protocols have been developed for the implementation and evaluation of EWARN, a need persists for standardized training and additional guidance on supporting these systems remotely when access to affected areas is restricted. Continued collaboration between partners and the Centers for Disease Control and Prevention for surveillance during emergencies is necessary to strengthen capacity and support global health security. PMID:29155660

Selective primary health care: an interim strategy for disease control in developing countries.

PubMed

Walsh, J A; Warren, K S

1979-11-01

Priorities among the infectious diseases affecting the three billion people in the less developed world have been based on prevalence, morbidity, mortality and feasibility of control. With these priorities in mind a program of selective primary health care is compared with other approaches and suggested as the most cost-effective form of medical intervention in the least developed countries. A flexible program delivered by either fixed or mobile units might include measles and diphtheria-pertussis-tetanus vaccination, treatment for febrile malaria and oral rehydration for diarrhea in children, and tetanus toxoid and encouragement of breast feeding in mothers. Other interventions might be added on the basis of regional needs and new developments. For major diseases for which control measures are inadequate, research is an inexpensive approach on the basis of cost per infected person per year.

Rapid Assessment Tool for Haemophilus influenzae type b Disease in Developing Countries1

PubMed Central

Nelson, Christopher B.; Watt, James P.; Mohsni, Ezzeddine; Wenger, Jay D.; Levine, Orin S.

2004-01-01

Haemophilus influenzae type b (Hib) still causes a substantial number of deaths among children in developing countries, despite the availability of effective conjugate vaccines. A major obstacle in developing a Hib vaccine has been limited awareness about the impact of Hib disease. A tool was developed to estimate the national rates of Hib meningitis and pneumonia by assessing retrospective local data over 7 to 10 days. Data from 11 countries in Africa, the Middle East, and Asia were studied and showed rates of Hib meningitis from >50 cases per 100,000 children >5 years in Ghana and Uganda to <15 per 100,000 in Iran, Jordan, and Uzbekistan. Results were affected by the quality of available data. The Hib rapid assessment tool can be useful to countries that desire a timely assessment of Hib disease rates. PMID:15324548

De novo development of artistic creativity in Alzheimer's disease.

PubMed

Chakravarty, Ambar

2011-10-01

The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed.

De novo development of artistic creativity in Alzheimer's disease

PubMed Central

Chakravarty, Ambar

2011-01-01

The case of an 82-year-old female with probable Alzheimer's disease (AD), who developed unusual artistic creativity after development of her disease, is described. The possible pathogenetic mechanism is discussed. The patient showed no inclination toward visual arts during her premorbid years. However, 4 years after development of AD suggestive symptoms she started painting beautiful pictures rather impulsively. Some such paintings have been appreciated even by a qualified art expert. Such de novo development of artistic creativity had been described earlier in subjects with the semantic form of fronto-temporal dementia (FTD), but not in AD. The prevailing concept of lateralized compromise and paradoxical functional facilitation, proposed in connection with FTD subjects, may not be applicable in AD subjects where the affection is more diffuse and more posterior in the brain. Hence, the likely pathogenetic mechanism involved in the case described may remain uncertain. Possibilities are discussed. PMID:22346020

Disease models for the development of therapies for lysosomal storage diseases.

PubMed

Xu, Miao; Motabar, Omid; Ferrer, Marc; Marugan, Juan J; Zheng, Wei; Ottinger, Elizabeth A

2016-05-01

Lysosomal storage diseases (LSDs) are a group of rare diseases in which the function of the lysosome is disrupted by the accumulation of macromolecules. The complexity underlying the pathogenesis of LSDs and the small, often pediatric, population of patients make the development of therapies for these diseases challenging. Current treatments are only available for a small subset of LSDs and have not been effective at treating neurological symptoms. Disease-relevant cellular and animal models with high clinical predictability are critical for the discovery and development of new treatments for LSDs. In this paper, we review how LSD patient primary cells and induced pluripotent stem cell-derived cellular models are providing novel assay systems in which phenotypes are more similar to those of the human LSD physiology. Furthermore, larger animal disease models are providing additional tools for evaluation of the efficacy of drug candidates. Early predictors of efficacy and better understanding of disease biology can significantly affect the translational process by focusing efforts on those therapies with the higher probability of success, thus decreasing overall time and cost spent in clinical development and increasing the overall positive outcomes in clinical trials. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation[S

PubMed Central

Allende, Maria L.; Cook, Emily K.; Larman, Bridget C.; Nugent, Adrienne; Brady, Jacqueline M.; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J.

2018-01-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses. PMID:29358305

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

PubMed

Allende, Maria L; Cook, Emily K; Larman, Bridget C; Nugent, Adrienne; Brady, Jacqueline M; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J; Proia, Richard L

2018-03-01

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of β-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB -corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB -corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB -corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

Increased risks of coronary heart disease and stroke among spousal caregivers of cancer patients.

PubMed

Ji, Jianguang; Zöller, Bengt; Sundquist, Kristina; Sundquist, Jan

2012-04-10

Spousal caregivers of cancer patients suffer psychological and physical burdens that may affect their risk of subsequently developing coronary heart disease and stroke. Cancer patients were identified in the Swedish Cancer Registry, and information on their spouses was retrieved from the Swedish Multi-Generation Register. Follow-up of caregivers was performed from the date of the first diagnosis of cancer in their spouses through 2008. Standardized incidence ratios were calculated for spousal caregivers of cancer patients compared with those without an affected spouse. After the cancer diagnosis in wives, the risks of coronary heart disease, ischemic stroke, and hemorrhagic stroke in husbands were 1.13 (95% confidence interval [CI], 1.10-1.16), 1.24 (95% CI, 1.21-1.27), and 1.25 (95% CI, 1.18-1.32), respectively. The corresponding risks in wives with an affected husband were 1.13 (95% CI, 1.10-1.16), 1.29 (95% CI, 1.26-1.32), and 1.27 (95% CI, 1.19-1.34). The increases were consistent over time and were more pronounced if the spouse was affected by a cancer with a high mortality rate, such as pancreatic and lung cancers. Spousal caregivers of cancer patients have increased risks of coronary heart disease and stroke that persist over time. Clinical attention should be paid to spousal caregivers, especially those caring for cancer patients with high mortality rates.

Impact of early life exposures to geohelminth infections on the development of vaccine immunity, allergic sensitization, and allergic inflammatory diseases in children living in tropical Ecuador: the ECUAVIDA birth cohort study

PubMed Central

2011-01-01

Background Geohelminth infections are highly prevalent infectious diseases of childhood in many regions of the Tropics, and are associated with significant morbidity especially among pre-school and school-age children. There is growing concern that geohelminth infections, particularly exposures occurring during early life in utero through maternal infections or during infancy, may affect vaccine immunogenicity in populations among whom these infections are endemic. Further, the low prevalence of allergic disease in the rural Tropics has been attributed to the immune modulatory effects of these infections and there is concern that widespread use of anthelmintic treatment in high-risk groups may be associated with an increase in the prevalence of allergic diseases. Because the most widely used vaccines are administered during the first year of life and the antecedents of allergic disease are considered to occur in early childhood, the present study has been designed to investigate the impact of early exposures to geohelminths on the development of protective immunity to vaccines, allergic sensitization, and allergic disease. Methods/Design A cohort of 2,403 neonates followed up to 8 years of age. Primary exposures are infections with geohelminth parasites during the last trimester of pregnancy and the first 2 years of life. Primary study outcomes are the development of protective immunity to common childhood vaccines (i.e. rotavirus, Haemophilus influenzae type B, Hepatitis B, tetanus toxoid, and oral poliovirus type 3) during the first 5 years of life, the development of eczema by 3 years of age, the development of allergen skin test reactivity at 5 years of age, and the development of asthma at 5 and 8 years of age. Potential immunological mechanisms by which geohelminth infections may affect the study outcomes will be investigated also. Discussion The study will provide information on the potential effects of early exposures to geohelminths (during pregnancy and the first 2 years of life) on the development of vaccine immunity and allergy. The data will inform an ongoing debate of potential effects of geohelminths on child health and will contribute to policy decisions on new interventions designed to improve vaccine immunogenicity and protect against the development of allergic diseases. Trial registration Current Controlled Trials ISRCTN41239086. PMID:21714922

Interaction between periodontitis and liver diseases

PubMed Central

Han, Pengyu; Sun, Dianxing; Yang, Jie

2016-01-01

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

AMP-Activated Protein Kinase as a Reprogramming Strategy for Hypertension and Kidney Disease of Developmental Origin.

PubMed

Tain, You-Lin; Hsu, Chien-Ning

2018-06-12

Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.

Telomere-driven diseases and telomere-targeting therapies

PubMed Central

2017-01-01

Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is proposed to be a primary molecular cause of aging. Short telomeres block the proliferative capacity of stem cells, affecting their potential to regenerate tissues, and trigger the development of age-associated diseases. Mutations in telomere maintenance genes are associated with pathologies referred to as telomere syndromes, including Hoyeraal-Hreidarsson syndrome, dyskeratosis congenita, pulmonary fibrosis, aplastic anemia, and liver fibrosis. Telomere shortening induces chromosomal instability that, in the absence of functional tumor suppressor genes, can contribute to tumorigenesis. In addition, mutations in telomere length maintenance genes and in shelterin components, the protein complex that protects telomeres, have been found to be associated with different types of cancer. These observations have encouraged the development of therapeutic strategies to treat and prevent telomere-associated diseases, namely aging-related diseases, including cancer. Here we review the molecular mechanisms underlying telomere-driven diseases and highlight recent advances in the preclinical development of telomere-targeted therapies using mouse models. PMID:28254828

Genetics Home Reference: Ménière disease

MedlinePlus

... dizziness (vertigo), a roaring sound in the ears (tinnitus), a feeling of pressure or fullness in the ... many affected individuals develop ongoing problems with unsteadiness, tinnitus, and a feeling of fullness in the ears. ...

Research to Develop Biomedical Applications of Free Electron Laser Technology

DTIC Science & Technology

2011-03-31

Wellman Center for Photomedicine/Massachusetts General Hospital ,55 Fruit St,Boston,MA,02114-2621 8. PERFORMING ORGANIZATION REPORT NUMBER ; AFRL-OSR... affect soldiers. To achieve this broad goal, we have undertaken projects focused on novel treatments of infectious diseases and physical trauma...death. Burns destroy the cutaneous barrier, rendering the affected tissue non- perfused, and bacteria find the burn wound a highly nutritional environment

An individual-based model of rabbit viral haemorrhagic disease on European wild rabbits (Oryctolagus cuniculus)

USGS Publications Warehouse

Fa, John E.; Sharples, Colin M.; Bell, Diana J.; DeAngelis, Donald L.

2001-01-01

We developed an individual-based model of Rabbit Viral Hemorrhagic Disease (RVHD) for European wild rabbits (Oryctolagus cuniculus L.), representing up to 1000 rabbits in four hectares. Model output for productivity and recruitment matched published values. The disease was density-dependent and virulence affected outcome. Strains that caused death after several days produced greater overall mortality than strains in which rabbits either died or recovered very quickly. Disease effect also depended on time of year. We also elaborated a larger scale model representing 25 km2 and 100,000+ rabbits, split into a number of grid-squares. This was a more traditional model that did not represent individual rabbits, but employed a system of dynamic equations for each grid-square. Disease spread depended on probability of transmission between neighboring grid-squares. Potential recovery from a major population crash caused by the disease relied on disease virulence and frequency of recurrence. The model's dependence on probability of disease transmission between grid-squares suggests the way that the model represents the spatial distribution of the population affects simulation. Although data on RVHD in Europe are lacking, our models provide a basis for describing the disease in realistic detail and for assessing influence of various social and spatial factors on spread.

A model to estimate effects of SNPs on host susceptibility and infectivity for an endemic infectious disease.

PubMed

Biemans, Floor; de Jong, Mart C M; Bijma, Piter

2017-06-30

Infectious diseases in farm animals affect animal health, decrease animal welfare and can affect human health. Selection and breeding of host individuals with desirable traits regarding infectious diseases can help to fight disease transmission, which is affected by two types of (genetic) traits: host susceptibility and host infectivity. Quantitative genetic studies on infectious diseases generally connect an individual's disease status to its own genotype, and therefore capture genetic effects on susceptibility only. However, they usually ignore variation in exposure to infectious herd mates, which may limit the accuracy of estimates of genetic effects on susceptibility. Moreover, genetic effects on infectivity will exist as well. Thus, to design optimal breeding strategies, it is essential that genetic effects on infectivity are quantified. Given the potential importance of genetic effects on infectivity, we set out to develop a model to estimate the effect of single nucleotide polymorphisms (SNPs) on both host susceptibility and host infectivity. To evaluate the quality of the resulting SNP effect estimates, we simulated an endemic disease in 10 groups of 100 individuals, and recorded time-series data on individual disease status. We quantified bias and precision of the estimates for different sizes of SNP effects, and identified the optimum recording interval when the number of records is limited. We present a generalized linear mixed model to estimate the effect of SNPs on both host susceptibility and host infectivity. SNP effects were on average slightly underestimated, i.e. estimates were conservative. Estimates were less precise for infectivity than for susceptibility. Given our sample size, the power to estimate SNP effects for susceptibility was 100% for differences between genotypes of a factor 1.56 or more, and was higher than 60% for infectivity for differences between genotypes of a factor 4 or more. When disease status was recorded 11 times on each animal, the optimal recording interval was 25 to 50% of the average infectious period. Our model was able to estimate genetic effects on susceptibility and infectivity. In future genome-wide association studies, it may serve as a starting point to identify genes that affect disease transmission and disease prevalence.

Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: A Systematic Review.

PubMed

Alvarez, Carolina; Gotuzzo, Eduardo; Vandamme, Anne-Mieke; Verdonck, Kristien

2016-01-01

Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse) favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when, and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan ( n = 30) and Brazil ( n = 10). These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease ( n = 223). The diseases most frequently reported were ATLL (115 families) and HAM/TSP (102 families). Most families ( n = 144) included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2 to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1 to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an affected parent with one or more affected children. The evidence in the literature, although weak, does suggest that HTLV-1-associated diseases sometimes cluster in families. Whether familial transmission of HTLV-1 is the only determining factor, or whether other factors are also involved, needs further research.

Overcoming research barriers in Chagas disease-designing effective implementation science.

PubMed

Henao-Martínez, Andrés F; Colborn, Kathryn; Parra-Henao, Gabriel

2017-01-01

Chagas disease is a complex tropical parasitic infection. It affects a significant portion of the population in Latin America, especially in areas of poverty and poor access to health care. It also affects immigrants in high-income countries who lack access to health care due to their legal status. Millions of people are at risk of contracting the disease, and approximately 30 % of chronically infected patients will develop cardiomyopathy. The cost of caring for patients that have been infected is substantial. Basic science research has introduced new concepts and knowledge for the parasite and vector biology as well as better understanding of the pathophysiology of the disease. These research findings nevertheless require effective and timely translation into clinical practice. Likewise, the design of new research projects should account for the multiple system-based barriers. Implementation science facilitates the applicability of research findings and identifies barriers to its execution. Creation of implementation science measures to reach and sustain research programs with greater potential to impact Chagas disease are lacking. This point of view proposes opportunities for implementation science in Chagas disease and strategies for researching effective interventions for preventing and treating the disease.

Topography and crop management are key factors for the development of american leaf spot epidemics on coffee in costa rica.

PubMed

Avelino, Jacques; Cabut, Sandrine; Barboza, Bernardo; Barquero, Miguel; Alfaro, Ronny; Esquivel, César; Durand, Jean-François; Cilas, Christian

2007-12-01

ABSTRACT We monitored the development of American leaf spot of coffee, a disease caused by the gemmiferous fungus Mycena citricolor, in 57 plots in Costa Rica for 1 or 2 years in order to gain a clearer understanding of conditions conducive to the disease and improve its control. During the investigation, characteristics of the coffee trees, crop management, and the environment were recorded. For the analyses, we used partial least-squares regression via the spline functions (PLSS), which is a nonlinear extension to partial least-squares regression (PLS). The fungus developed well in areas located between approximately 1,100 and 1,550 m above sea level. Slopes were conducive to its development, but eastern-facing slopes were less affected than the others, probably because they were more exposed to sunlight, especially in the rainy season. The distance between planting rows, the shade percentage, coffee tree height, the type of shade, and the pruning system explained disease intensity due to their effects on coffee tree shading and, possibly, on the humidity conditions in the plot. Forest trees and fruit trees intercropped with coffee provided particularly propitious conditions. Apparently, fertilization was unfavorable for the disease, probably due to dilution phenomena associated with faster coffee tree growth. Finally, series of wet spells interspersed with dry spells, which were frequent in the middle of the rainy season, were critical for the disease, probably because they affected the production and release of gemmae and their viability. These results could be used to draw up a map of epidemic risks taking topographical factors into account. To reduce those risks and improve chemical control, our results suggested that farmers should space planting rows further apart, maintain light shading in the plantation, and prune their coffee trees.

[Globalization and infectious diseases].

PubMed

Mirski, Tomasz; Bartoszcze, Michał; Bielawska-Drózd, Agata

2011-01-01

Globalization is a phenomenon characteristic of present times. It can be considered in various aspects: economic, environmental changes, demographic changes, as well as the development of new technologies. All these aspects of globalization have a definite influence on the emergence and spread of infectious diseases. Economic aspects ofglobalization are mainly the trade development, including food trade, which has an impact on the spread of food-borne diseases. The environmental changes caused by intensive development of industry, as a result of globalization, which in turn affects human health. The demographic changes are mainly people migration between countries and rural and urban areas, which essentially favors the global spread of many infectious diseases. While technological advances prevents the spread of infections, for example through better access to information, it may also increase the risk, for example through to create opportunities to travel into more world regions, including the endemic regions for various diseases. The phenomenon ofglobalization is also closely associated with the threat of terrorism, including bioterrorism. It forces the governments of many countries to develop effective programs to protect and fight against this threat.

Chronic kidney disease after hematopoietic stem cell transplantation

PubMed Central

Cohen, Eric P; Pais, Priya; Moulder, John E

2010-01-01

Acute and chronic kidney diseases occur after hematopoietic stem cell transplantation. These are caused by the transplant itself, and the complications of transplant. Recent estimates show that near 15% of subjects undergoing HSCT will develop CKD, which is a complication rate that can affect outcome and reduce survival. Investigation of the causes of CKD is needed, as are ways to prevent, mitigate and treat it. PMID:21146127

[Challenge and strategy of prevention and control of important parasitic diseases under the Belt and Road Initiative].

PubMed

Chun-Li, Cao; Jia-Gang, Guo

2018-04-17

China was once a country with the heaviest burden of parasitic diseases. Under the leadership of the Communist Party and national authority, after more than 60 years' efforts of prevention and control, the remarkable results have been achieved in China. However, affected by the social and economic development and environmental changes, the prevention and control of parasitic diseases, especially imported parasitic diseases, are facing new challenges, and the parasitic diseases, such as malaria, schistosomiasis, leishmaniasis, filariasis and trypanosomiasis, appear increasingly. With the development of the Belt and Road Initiative, the transmission risks of these diseases are more increased. The purpose of this paper is to describe the experience and results of parasitic disease prevention and control in China, understand the present parasitic disease epidemic situation of the Belt and Road Initiative related countries, analyze the transmission risks of important parasitic diseases, and present some relevant suggestions, so as to provide the evidence for the health administrative department formulating the prevention and control strategies of such parasitic diseases timely and effectively.

Acute and chronic psychological stress as risk factors for cardiovascular disease: Insights gained from epidemiological, clinical and experimental studies.

PubMed

Lagraauw, H Maxime; Kuiper, Johan; Bot, Ilze

2015-11-01

Cardiovascular disease (CVD) remains a leading cause of death worldwide and identification and therapeutic modulation of all its risk factors is necessary to ensure a lower burden on the patient and on society. The physiological response to acute and chronic stress exposure has long been recognized as a potent modulator of immune, endocrine and metabolic pathways, however its direct implications for cardiovascular disease development, progression and as a therapeutic target are not completely understood. More and more attention is given to the bidirectional interaction between psychological and physical health in relation to cardiovascular disease. With atherosclerosis being a chronic disease starting already at an early age the contribution of adverse early life events in affecting adult health risk behavior, health status and disease development is receiving increased attention. In addition, experimental research into the biological pathways involved in stress-induced cardiovascular complications show important roles for metabolic and immunologic maladaptation, resulting in increased disease development and progression. Here we provide a concise overview of human and experimental animal data linking chronic and acute stress to CVD risk and increased progression of the underlying disease atherosclerosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Fungal disease and the developing story of bat white-nose syndrome

USGS Publications Warehouse

Blehert, David S.

2012-01-01

Two recently emerged cutaneous fungal diseases of wildlife, bat white-nose syndrome (WNS) and amphibian chytridiomycosis, have devastated affected populations. Fungal diseases are gaining recognition as significant causes of morbidity and mortality to plants, animals, and humans, yet fewer than 10% of fungal species are known. Furthermore, limited antifungal therapeutic drugs are available, antifungal therapeutics often have associated toxicity, and there are no approved antifungal vaccines. The unexpected emergence of WNS, the rapidity with which it has spread, and its unprecedented severity demonstrate both the impacts of novel fungal disease upon naïve host populations and challenges to effective management of such diseases.

Linking the microbiota, chronic disease and the immune system

PubMed Central

Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

2016-01-01

Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults

PubMed Central

Gallaway, Patrick J.; Miyake, Hiroji; Buchowski, Maciej S.; Shimada, Mieko; Yoshitake, Yutaka; Kim, Angela S.; Hongu, Nobuko

2017-01-01

A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. PMID:28230730

Health-related biotechnologies for infectious disease control in Africa: Ethical, Legal and Social Implications (ELSI) of transfer and development.

PubMed

Sommerfeld, J; Oduola, A M J

2007-01-01

The African continent is disproportionately affected by infectious diseases. Malaria, HIV/AIDS, tuberculosis, and more "neglected" diseases including African trypanosomiasis, Buruli ulcer, leishmaniasis, onchocerciasis and trachoma continue to dramatically impact social and economic development on the continent. Health biotechnologies provide potential to develop effective strategies for the fight against the vicious circle of poverty and infections by helping in the development and improvement of novel affordable drugs, diagnostics and vaccines against these diseases. As the prospects of this emerging biotechnology research and deployment of its products become a reality in Africa, there is a need to consider the ethical, legal and social implications of both the scientific and technological advances and their use in the communities. The article provides a short overview of the potential values of biotechnology, issues involved in its transfer and presents the rationale, design and recommendations of the international workshop/symposium held in April 2005 at the International Institute for Tropical Agriculture (IITA) in Ibadan, Nigeria.

Is Beta-Amyloid Accumulation a Cause or Consequence of Alzheimer’s Disease?

PubMed Central

Wang, Shaoxun; Mims, Paige N.; Roman, Richard J.; Fan, Fan

2017-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by the pathological hallmarks of extracellular beta-amyloid (Aβ) plaques and intraneuronal tau-containing neurofibrillary tangles in the brain. Intraneuronal accumulation of Aβ also plays a role to accelerate AD progression by promoting neurodegeneration. Additionally, AD is associated with the development of amyloid angiopathy (CAA), in which Aβ builds up on the walls of the cerebral arteries, which augments the development of cerebral vascular disease (CVD). Conversely, CVD promotes Aβ deposition and the development of AD by affecting the balance of Aβ production and clearance. However, it remains to be determined whether the accumulation of Aβ is a cause or consequence of AD. The interaction between AD and CVD is a topic of considerable current interest. Here, we discuss the role of CVD in Aβ accumulation and the development of AD to provide a new point of view that combination therapies that address the accompanying cerebral microvascular disease may potentiate the efficacy of emerging treatment for AD. PMID:28815226

Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience.

PubMed

Ward, Natalie C; Pang, Jing; Ryan, Jacqueline D M; Watts, Gerald F

2018-01-01

There is considerable evidence for the role of low-density lipoprotein cholesterol (LDL-C) in the development of atherosclerotic cardiovascular disease. Although statin therapy remains the most frequency prescribed medication to reduce LDL-C and lower risk of cardiovascular disease, a considerable number of patients develop muscle-related side affects. This review summarizes recent literature supporting the role of nutraceuticals as LDL-C-lowering therapy in statin-intolerant patients, with evidence from our own clinical practices. © 2018 Wiley Periodicals, Inc.

Global Breast Cancer: The Lessons to Bring Home

PubMed Central

Formenti, Silvia C.; Arslan, Alan A.; Love, Susan M.

2012-01-01

Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries. PMID:22295243

Attitudes towards Human Papilloma Virus Vaccination in the Latin American Andean Region

PubMed Central

2017-01-01

This commentary explores the distribution of human papilloma virus (HPV) and HPV-related diseases, and factors affecting attitudes towards HPV, HPV-related diseases, and HPV vaccination in the Latin American Andean region. Lack of knowledge of HPV, known negative attitudes or incorrect assumptions about HPV, HPV-related diseases, and HPV vaccination provide a basis upon which to develop targeted HPV awareness and preventive health media campaigns. For maximal effect, media campaigns should use the internet, radio, and television to address health care providers, parents, and students. Additional programming can be developed for clinics to use in-house with their clients. Ministries of Education, Finance, and Health all have roles to play to increase national HPV, HPV-related diseases, and HPV vaccination awareness. PMID:28885601

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.

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

Temperature and population density: interactional effects of environmental factors on phenotypic plasticity, immune defenses, and disease resistance in an insect pest.

PubMed

Silva, Farley W S; Elliot, Simon L

2016-06-01

Temperature and crowding are key environmental factors mediating the transmission and epizooty of infectious disease in ectotherm animals. The host physiology may be altered in a temperature-dependent manner and thus affects the pathogen development and course of diseases within an individual and host population, or the transmission rates (or infectivity) of pathogens shift linearly with the host population density. To our understanding, the knowledge of interactive and synergistic effects of temperature and population density on the host-pathogen system is limited. Here, we tested the interactional effects of these environmental factors on phenotypic plasticity, immune defenses, and disease resistance in the velvetbean caterpillar Anticarsia gemmatalis . Upon egg hatching, caterpillars were reared in thermostat-controlled chambers in a 2 × 4 factorial design: density (1 or 8 caterpillars/pot) and temperature (20, 24, 28, or 32°C). Of the immune defenses assessed, encapsulation response was directly affected by none of the environmental factors; capsule melanization increased with temperature in both lone- and group-reared caterpillars, although the lone-reared ones presented the most evident response, and hemocyte numbers decreased with temperature regardless of the population density. Temperature, but not population density, affected considerably the time from inoculation to death of velvetbean caterpillar. Thus, velvetbean caterpillars succumbed to Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) more quickly at higher temperatures than at lower temperatures. As hypothesized, temperature likely affected caterpillars' movement rates, and thus the contact between conspecifics, which in turn affected the phenotypic expression of group-reared caterpillars. Our results suggest that environmental factors, mainly temperature, strongly affect both the course of disease in velvetbean caterpillar population and its defenses against pathogens. As a soybean pest, velvetbean caterpillar may increase its damage on soybean fields under a scenario of global warming as caterpillars may reach the developmental resistance faster, and thus decrease their susceptibility to biological control by AgMNPV.

An Update on Inflamm-Aging: Mechanisms, Prevention, and Treatment

PubMed Central

Wu, Junzhen

2016-01-01

Inflamm-aging is a challenging and promising new branch of aging-related research fields that includes areas such as immunosenescence. Increasing evidence indicates that inflamm-aging is intensively associated with many aging diseases, such as Alzheimer's disease, atherosclerosis, heart disease, type II diabetes, and cancer. Mounting studies have focused on the role of inflamm-aging in disease progression and many advances have been made in the last decade. However, the underlying mechanisms by which inflamm-aging affects pathological changes and disease development are still unclear. Here, we review studies of inflamm-aging that explore the concept, pathological features, mechanisms, intervention, and the therapeutic strategies of inflamm-aging in disease progression. PMID:27493973

How the microbiota shapes rheumatic diseases.

PubMed

Van de Wiele, Tom; Van Praet, Jens T; Marzorati, Massimo; Drennan, Michael B; Elewaut, Dirk

2016-07-01

The human gut harbours a tremendously diverse and abundant microbial community that correlates with, and even modulates, many health-related processes. The mucosal interfaces are particularly active sites of microorganism-host interplay. Growing insight into the characteristic composition and functionality of the mucosal microbiota has revealed that the microbiota is involved in mucosal barrier integrity and immune function. This involvement affects proinflammatory and anti-inflammatory processes not only at the epithelial level, but also at remote sites such as the joints. Here, we review the role of the gut microbiota in shaping local and systemic immune responses and how disturbances in the host-microorganism interplay can potentially affect the development and progression of rheumatic diseases. Increasing our understanding of how to promote host-microorganism homeostasis could therefore reveal novel strategies for the prevention or alleviation of rheumatic disease.

Interleukins and interleukin receptors in rheumatoid arthritis: Research, diagnostics and clinical implications

PubMed Central

Magyari, Lili; Varszegi, Dalma; Kovesdi, Erzsebet; Sarlos, Patricia; Farago, Bernadett; Javorhazy, Andras; Sumegi, Katalin; Banfai, Zsolt; Melegh, Bela

2014-01-01

Rheumatoid arthritis (RA) is an autoimmune disease, resulting in a chronic, systemic inflammatory disorder. It may affect many tissues and organs, but it primarily affects the flexible joints. In clinical practice patient care generates many questions about diagnosis, prognosis, and treatment. It is challenging for health care specialists to keep up to date with the medical literature. This review summarizes the pathogenesis, the polymorphisms of interleukin and interleukin genes and the standard available and possible future immunologic targets for RA treatment. The identification of disease-associated interleukin and interleukin receptor genes can provide precious insight into the genetic variations prior to disease onset in order to identify the pathways important for RA pathogenesis. The knowledge of the complex genetic background may prove useful for developing novel therapies and making personalized medicine based on the individual’s genetics. PMID:25232528

Oral Myiasis Caused by Cochliomyia hominivorax in a Disabled Person.

PubMed

Novo-Neto, José Pereira; Dos Santos, Fabiano de Sant'Ana; Pontes, Ana Emília Farias; Ribeiro, Fernando Salimon; Scannavino, Fábio Luiz Ferreira; Martins, Alex Tadeu

2015-01-01

Myiasis is a parasitic disease caused by developing maggots of fly species, which can infect humans. Patients with special needs, especially those with severe neuropsychomotor limitations, may have oral manifestations of this disease. Here, we present a clinical case in which a disabled person was affected by oral myiasis caused by Cochliomyia hominivorax. Maggots were found in two ulcerated lesions, a 2 cm diameter lesion in the maxilla and a 6 cm diameter lesion in the mandible. Forty-five maggots were removed during inspection, whereas 75 maggots were surgically removed under general anesthesia with nasotracheal intubation. Dipyrone, ivermectin, and clindamycin were prescribed, and the patient remained hospitalized for 3 days. Seven days after surgical intervention, no maggots were observed. Our study emphasizes that dentists must recognize the symptoms and behaviors of parasitic diseases that affect the oral cavity.

A history of the development of Brucella vaccines.

PubMed

Avila-Calderón, Eric Daniel; Lopez-Merino, Ahidé; Sriranganathan, Nammalwar; Boyle, Stephen M; Contreras-Rodríguez, Araceli

2013-01-01

Brucellosis is a worldwide zoonosis affecting animal and human health. In the last several decades, much research has been performed to develop safer Brucella vaccines to control the disease mainly in animals. Till now, no effective human vaccine is available. The aim of this paper is to review and discuss the importance of methodologies used to develop Brucella vaccines in pursuing this challenge.

Fabry disease: Review and experience during newborn screening.

PubMed

Hsu, Ting-Rong; Niu, Dau-Ming

2018-05-01

Fabry disease (FD) is an X-linked lysosomal storage disease and is the result of mutation in the α-Galactosidase A gene; such mutations cause a deficiency in α-Galactosidase A enzyme and an accumulation of glycosphingolipid in tissue. Affected males with classic FD have little or no enzyme activity and have an early onset of symptoms and signs, including acroparesthesias, hypohidrosis, angiokeratomas, gastrointestinal dysfunction and/or a characteristic corneal dystrophy during childhood/adolescence. Males with late-onset FD who have residual enzyme activity develop progressive multi-systemic involvement that leads to renal failure and hypertrophic cardiomyopathy, as well as cerebrovascular disease; these events mostly occur during the fourth to seventh decades of life. Heterozygous females can develop vital organ damage that in turn causes severe morbidity and mortality; these symptoms may be as severe as those in affected males. For the treatable disease, this review aims to raise awareness of early recognition and further management of FD based on newborn screening. As newborn screening for FD has been implemented worldwide, it allows the early detection of individuals with Fabry mutations. Based on screening studies, the prevalence of the later-onset type FD is much higher than that of classical type FD. Newborn screening studies have also revealed that patients with FD may develop insidious but ongoing irreversible organ damage. The timing of enzyme replacement therapy, which is able to stabilize the progression of disease, is important in order to prevent irreversible organ damage. Therapies that may become available in the future include pharmacological chaperones and substrate reduction therapy, both of which are still under investigation as ways of improving the health of individuals with FD. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac and Respiratory Disease in Aged Horses.

PubMed

Marr, Celia M

2016-08-01

Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids. Copyright © 2016 Elsevier Inc. All rights reserved.

The complexity of epigenetic diseases.

PubMed

Brazel, Ailbhe Jane; Vernimmen, Douglas

2016-01-01

Over the past 30 years, a plethora of pathogenic mutations affecting enhancer regions and epigenetic regulators have been identified. Coupled with more recent genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) implicating major roles for regulatory mutations in disease, it is clear that epigenetic mechanisms represent important biomarkers for disease development and perhaps even therapeutic targets. Here, we discuss the diversity of disease-causing mutations in enhancers and epigenetic regulators, with a particular focus on cancer. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Carcinoid heart disease: Diagnosis and management.

PubMed

Luis, Sushil A; Pellikka, Patricia A

2016-01-01

Hedinger syndrome refers to carcinoid valvular heart disease. The disease is believed to be triggered by vasoactive substances that result in valvular fibrosis. It classically occurs in patients with metastatic carcinoid and preferentially involves the right sided cardiac valves. Affected valves become thickened and retracted, exhibiting regurgitation and sometimes, stenosis. Echocardiography is recommended in patients with carcinoid syndrome and a follow up study is advisable in those who develop a murmur or other symptoms or signs of valvular heart disease. For appropriately selected patients, valve replacement surgery appears to improve outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

REACTIVE OXYGEN AND NITROGEN SPECIES IN PULMONARY HYPERTENSION

PubMed Central

Tabima, Diana M.; Frizzell, Sheila; Gladwin, Mark T.

2013-01-01

Pulmonary vascular disease can be defined as either a disease affecting the pulmonary capillaries and pulmonary arterioles, termed pulmonary arterial hypertension, or as a disease affecting the left ventricle, called pulmonary venous hypertension. Pulmonary arterial hypertension (PAH) is a disorder of the pulmonary circulation characterized by endothelial dysfunction, as well as intimal and smooth muscle proliferation. Progressive increases in pulmonary vascular resistance and pressure impair the performance of the right ventricle, resulting in declining cardiac output, reduced exercise capacity, right heart failure, and ultimately death. While the primary and heritable forms of the disease are thought to affect over 5,000 patients in the U.S., the disease can occur secondary to congenital heart disease, most advanced lung diseases, and many systemic diseases. Multiple studies implicate oxidative stress in the development of PAH. Further, this oxidative stress has been shown to be associated with alterations in reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO) signaling pathways, whereby bioavailable NO is decreased and ROS and RNS production are increased. Many canonical ROS and NO signaling pathways are simultaneously disrupted in PAH, with increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and xanthine oxidoreductase, uncoupling of endothelial NO synthase (eNOS), and reduction in mitochondrial number, as well as impaired mitochondrial function. Upstream dysregulation of ROS/NO redox homeostasis impairs vascular tone and contributes to the pathological activation of anti-apoptotic and mitogenic pathways, leading to cell proliferation and obliteration of the vasculature. This manuscript will review the available data regarding the role of oxidative and nitrosative stress and endothelial dysfunction in the pathophysiology of pulmonary hypertension, and provide a description of targeted therapies for this disease. PMID:22401856

Climate change impacts on coffee rust disease

NASA Astrophysics Data System (ADS)

Alfonsi, W. M. V.; Koga-Vicente, A.; Pinto, H. S.; Alfonsi, E. L., Sr.; Coltri, P. P.; Zullo, J., Jr.; Patricio, F. R.; Avila, A. M. H. D.; Gonçalves, R. R. D. V.

2016-12-01

Changes in climate conditions and in extreme weather events may affect the food security due to impacts in agricultural production. Despite several researches have been assessed the impacts of extremes in yield crops in climate change scenarios, there is the need to consider the effects in pests and diseases which increase losses in the sector. Coffee Arabica is an important commodity in world and plays a key role in Brazilian agricultural exports. Although the coffee crop has a world highlight, its yield is affected by several factors abiotic or biotic. The weather as well pests and diseases directly influence the development and coffee crop yield. These problems may cause serious damage with significant economic impacts. The coffee rust, caused by the fungus Hemileia vastarix,is among the diseases of greatest impact for the crop. The disease emerged in Brazil in the 70s and is widely spread in all producing regions of coffee in Brazil, and in the world. Regions with favorable weather conditions for the pathogen may exhibit losses ranging from 30% to 50% of the total grain production. The evaluation of extreme weather events of coffee rust disease in futures scenarios was carried out using the climatic data from CMIP5 models, data field of coffee rust disease incidence and, incubation period simulation data for Brazilian municipalities. Two Regional Climate Models were selected, Eta-HadGEM2-ES and Eta-MIROC5, and the Representative Concentration Pathways 8.5 w/m2 was adopted. The outcomes pointed out that in these scenarios the period of incubation tends to decrease affecting the coffee rust disease incidence, which tends to increase. Nevertheless, the changing in average trends tends to benefit the reproduction of the pathogen. Once the temperature threshold for the disease reaches the adverse conditions it may be unfavorable for the incidence.

Building a Beneficial Microbiome from Birth12

PubMed Central

Castanys-Muñoz, Esther; Martin, Maria J; Vazquez, Enrique

2016-01-01

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota. PMID:26980815

Building a Beneficial Microbiome from Birth.

PubMed

Castanys-Muñoz, Esther; Martin, Maria J; Vazquez, Enrique

2016-03-01

The microbiota has recently been recognized as a driver of health that affects the immune, nervous, and metabolic systems. This influence is partially exerted through the metabolites produced, which may be relevant for optimal infant development and health. The gut microbiota begins developing early in life, and this initial colonization is remarkably important because it may influence long-term microbiota composition and activity. Considering that the microbiome may play a key role in health and disease, maintaining a protective microbiota could be critical in preventing dysbiosis-related diseases such as allergies, autoimmunity disorders, and metabolic syndrome. Breast milk and milk glycans in particular are thought to play a major role in shaping the early-life microbiota and promoting its development, thus affecting health. This review describes some of the effects the microbiota has on the host and discusses the role microbial metabolites play in shaping newborn health and development. We describe the gut microbiota structure and function during early life and the factors that determine its composition and hypothesize about the effects of human milk oligosaccharides and other prebiotic fibers on the neonatal microbiota. © 2016 American Society for Nutrition.

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

Contrasting nutrient-disease relationships: Potassium gradients in barley leaves have opposite effects on two fungal pathogens with different sensitivities to jasmonic acid.

PubMed

Davis, Jayne L; Armengaud, Patrick; Larson, Tony R; Graham, Ian A; White, Philip J; Newton, Adrian C; Amtmann, Anna

2018-05-31

Understanding the interactions between mineral nutrition and disease is essential for crop management. Our previous studies with Arabidopsis thaliana demonstrated that potassium (K) deprivation induced the biosynthesis of jasmonate (JA) and increased the plant's resistance to herbivorous insects. Here we addressed the question how tissue K affects the development of fungal pathogens and whether sensitivity of the pathogens to JA could play a role for the K-disease relationship in barley (Hordeum vulgare cv. Optic). We report that K-deprived barley plants showed increased leaf concentrations of JA and other oxylipins. Furthermore, a natural tip-to base K-concentrations gradient within leaves of K-sufficient plants was quantitatively mirrored by the transcript levels of JA-responsive genes. The local leaf tissue K concentrations affected the development of two economically important fungi in opposite ways, showing a positive correlation with powdery mildew (Blumeria graminis) and a negative correlation with leaf scald (Rhynchosporium commune) disease symptoms. B. graminis induced a JA-response in the plant and was sensitive to methyl-JA treatment while R. commune initiated no JA-response and was JA-insensitive. Our study challenges the view that high K generally improves plant health and suggests that JA-sensitivity of pathogens could be an important factor determining the exact K-disease relationship. This article is protected by copyright. All rights reserved.

[Immunologic aspects of allergic diseases development in female workers of contemporary poultry factory].

PubMed

Rybakov, I D; Bakirov, A B; Masiagutova, L M

2009-01-01

The article presents results of immunologic parameters study in female workers of contemporary poultry factories. Occupational factors were proved to affect all immunity sections. The authors suggested coefficient to diagnose latent sensibilization.

Traffic fatalities and economic growth

DOT National Transportation Integrated Search

2003-04-01

As countries develop death rates usually fall, especially for diseases that affect the young and result in substantial life-years lost. Deaths due to traffic accidents are a notable exception: the growth in motor vehicles that accompanies economic gr...

LONG-TERM EFFECTS OF THE DEVELOPMENTAL ENVIRONMENT

EPA Science Inventory

Clinical and epidemiological studies have shown significant correlations between conditions during development and various diseases later in life. In humans, low birth weight has been used as a surrogate for adverse developmental conditions, but the specific conditions affecting...

Transcriptomic analysis of molecular responses in Malus domestica 'M26' roots affected by apple replant disease.

PubMed

Weiß, Stefan; Bartsch, Melanie; Winkelmann, Traud

2017-06-01

Gene expression studies in roots of apple replant disease affected plants suggested defense reactions towards biotic stress to occur which did not lead to adequate responses to the biotic stressors. Apple replant disease (ARD) leads to growth inhibition and fruit yield reduction in replanted populations and results in economic losses for tree nurseries and fruit producers. The etiology is not well understood on a molecular level and causal agents show a great diversity indicating that no definitive cause, which applies to the majority of cases, has been found out yet. Hence, it is pivotal to gain a better understanding of the molecular and physiological reactions of the plant when affected by ARD and later to overcome the disease, for example by developing tolerant rootstocks. For the first time, gene expression was investigated in roots of ARD affected plants employing massive analysis of cDNA ends (MACE) and RT-qPCR. In reaction to ARD, genes in secondary metabolite production as well as plant defense, regulatory and signaling genes were upregulated whereas for several genes involved in primary metabolism lower expression was detected. For internal verification of MACE data, candidate genes were tested via RT-qPCR and a strong positive correlation between both datasets was observed. Comparison of apple 'M26' roots cultivated in ARD soil or γ-irradiated ARD soil suggests that typical defense reactions towards biotic stress take place in ARD affected plants but they did not allow responding to the biotic stressors attack adequately, leading to the observed growth depressions in ARD variants.

Physical activity and metabolic disease among people with affective disorders: Prevention, management and implementation.

PubMed

Vancampfort, Davy; Stubbs, Brendon

2017-12-15

One in ten and one in three of people with affective disorders experience diabetes and metabolic syndrome respectively. Physical activity (PA) and sedentary behaviour (SB) are key risk factors that can ameliorate the risk of metabolic disease among this population. However, PA is often seen as luxury and/or a secondary component within the management of people with affective disorders. The current article provides a non-systematic best-evidence synthesis of the available literature, detailing a number of suggestions for the implementation of PA into clinical practice. Whilst the evidence is unequivocal for the efficacy of PA to prevent and manage metabolic disease in the general population, it is in its infancy in this patient group. Nonetheless, action must be taken now to ensure that PA and reducing SB are given a priority to prevent and manage metabolic diseases and improve wider health outcomes. PA should be treated as a vital sign and all people with affective disorders asked about their activity levels and if appropriate advised to increase this. There is a need for investment in qualified exercise specialists in clinical practice such as physiotherapists to undertake and oversee PA in practice. Behavioural strategies such as the self-determined theory should be employed to encourage adherence. Funding is required to develop the evidence base and elucidate the optimal intervention characteristics. PA interventions should form an integral part of the multidisciplinary management of people with affective disorders and our article outlines the evidence and strategies to implement this in practice. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical ecology of animal and human pathogen vectors in a changing global climate.

PubMed

Pickett, John A; Birkett, Michael A; Dewhirst, Sarah Y; Logan, James G; Omolo, Maurice O; Torto, Baldwyn; Pelletier, Julien; Syed, Zainulabeuddin; Leal, Walter S

2010-01-01

Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on "The Chemical Ecology of Disease Vectors" at the 25th Annual ISCE meeting in Neuchatel, Switzerland. The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.

Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association.

PubMed

Cannas, A; Spissu, A; Floris, G L; Congia, S; Saddi, M V; Melis, M; Mascia, M M; Pinna, F; Tuveri, A; Solla, P; Milia, A; Giagheddu, M; Tacconi, P

2002-09-01

Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).

Food Allergies: The Basics

PubMed Central

Valenta, Rudolf; Hochwallner, Heidrun; Linhart, Birgit; Pahr, Sandra

2015-01-01

IgE-associated food allergy affects approximately 3% of the population and has severe effects on the daily life of patients—manifestations occur not only in the gastrointestinal tract but also affect other organ systems. Birth cohort studies have shown that allergic sensitization to food allergens develops early in childhood. Mechanisms of pathogenesis include cross-linking of mast cell– and basophil-bound IgE and immediate release of inflammatory mediators, as well as late-phase and chronic allergic inflammation, resulting from T-cell, basophil, and eosinophil activation. Researchers have begun to characterize the molecular features of food allergens and have developed chip-based assays for multiple allergens. These have provided information about cross-reactivity among different sources of food allergens, identified disease-causing food allergens, and helped us to estimate the severity and types of allergic reactions in patients. Importantly, learning about the structure of disease-causing food allergens has allowed researchers to engineer synthetic and recombinant vaccines. PMID:25680669

Exome sequencing identifies SUCO mutations in mesial temporal lobe epilepsy.

PubMed

Sha, Zhiqiang; Sha, Longze; Li, Wenting; Dou, Wanchen; Shen, Yan; Wu, Liwen; Xu, Qi

2015-03-30

Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Antibiotic Types and Handling Practices in Disease Management among Pig Farms in Ashanti Region, Ghana

PubMed Central

Osei Sekyere, John

2014-01-01

Antibiotic resistance in bacteria is affected by the type of antibiotics used and how they are handled. The types of antibiotics used by 110 pig farms in the Ashanti region and the handling practices of the farmers during disease management were assessed. Injectable tetracycline, sulphadimidine, benzylpenicillin, and dihydrostreptomycin containing antibiotics were overly used by the farmers especially in the management of diarrhea, rashes, and coughs. Unsafe storage and disposal practices observed among the farms reflected the abysmal knowledge on appropriate use of antibiotics. Misdiagnosis and inadequate protection during antibiotic handling in the farms increased the risk of antibiotic resistance development and spread. The factors affecting antibiotic resistance development and spread are rife in pig farms in Ashanti region and appropriate education and veterinary interventions are needed to prevent resistant bacteria from becoming endemic in pork and pig farm communities. PMID:26464936

Space-time models for a panzootic in bats, with a focus on the endangered Indiana bat

USGS Publications Warehouse

Thogmartin, Wayne E.; King, R. Andrew; Szymanski, Jennifer A.; Pruitt, Lori

2012-01-01

Knowledge of current trends of quickly spreading infectious wildlife diseases is vital to efficient and effective management. We developed space-time mixed-effects logistic regressions to characterize a disease, white-nose syndrome (WNS), quickly spreading among endangered Indiana bats (Myotis sodalis) in eastern North America. Our goal was to calculate and map the risk probability faced by uninfected colonies of hibernating Indiana bats. Model covariates included annual distance from and direction to nearest sources of infection, geolocational information, size of the Indiana bat populations within each wintering population, and total annual size of populations known or suspected to be affected by WNS. We considered temporal, spatial, and spatiotemporal formulae through the use of random effects for year, complex (a collection of interacting hibernacula), and yearxcomplex. Since first documented in 2006, WNS has spread across much of the range of the Indiana bat. No sizeable wintering population now occurs outside of the migrational distance of an infected source. Annual rates of newly affected wintering Indiana bat populations between winter 2007 to 2008 and 2010 to 2011 were 4, 6, 8, and 12%; this rate increased each year at a rate of 3%. If this increasing rate of newly affected populations continues, all wintering populations may be affected by 2016. Our models indicated the probability of a wintering population exhibiting infection was a linear function of proximity to affected Indiana bat populations and size of the at-risk population. Geographic location was also important, suggesting broad-scale influences. For every 50-km increase in distance from a WNS-affected population, risk of disease declined by 6% (95% CI=5.2-5.7%); for every increase of 1,000 Indiana bats, there was an 8% (95% CI = 1-21%) increase in disease risk. The increasing rate of infection seems to be associated with the movement of this disease into the core of the Indiana bat range. Our spatially explicit estimates of disease risk may aid managers in prioritizing surveillance and management for wintering populations of Indiana bats and help understand the risk faced by other hibernating bat species.

Toward developmental models of psychiatric disorders in zebrafish

PubMed Central

Norton, William H. J.

2013-01-01

Psychiatric disorders are a diverse set of diseases that affect all aspects of mental function including social interaction, thinking, feeling, and mood. Although psychiatric disorders place a large economic burden on society, the drugs available to treat them are often palliative with variable efficacy and intolerable side-effects. The development of novel drugs has been hindered by a lack of knowledge about the etiology of these diseases. It is thus necessary to further investigate psychiatric disorders using a combination of human molecular genetics, gene-by-environment studies, in vitro pharmacological and biochemistry experiments, animal models, and investigation of the non-biological basis of these diseases, such as environmental effects. Many psychiatric disorders, including autism spectrum disorder, attention-deficit/hyperactivity disorder, mental retardation, and schizophrenia can be triggered by alterations to neural development. The zebrafish is a popular model for developmental biology that is increasingly used to study human disease. Recent work has extended this approach to examine psychiatric disorders as well. However, since psychiatric disorders affect complex mental functions that might be human specific, it is not possible to fully model them in fish. In this review, I will propose that the suitability of zebrafish for developmental studies, and the genetic tools available to manipulate them, provide a powerful model to study the roles of genes that are linked to psychiatric disorders during neural development. The relative speed and ease of conducting experiments in zebrafish can be used to address two areas of future research: the contribution of environmental factors to disease onset, and screening for novel therapeutic compounds. PMID:23637652

Comprehensive analyses of tissue-specific networks with implications to psychiatric diseases

PubMed Central

Lin, Guan Ning; Corominas, Roser; Nam, Hyun-Jun; Urresti, Jorge; Iakoucheva, Lilia M.

2017-01-01

Recent advances in genome sequencing and “omics” technologies are opening new opportunities for improving diagnosis and treatment of human diseases. The precision medicine initiative in particular aims at developing individualized treatment options that take into account individual variability in genes and environment of each person. Systems biology approaches that group genes, transcripts and proteins into functionally meaningful networks will play crucial role in the future of personalized medicine. They will allow comparison of healthy and disease-affected tissues and organs from the same individual, as well as between healthy and disease-afflicted individuals. However, the field faces a multitude of challenges ranging from data integration to statistical and combinatorial issues in data analyses. This chapter describes computational approaches developed by us and the others to tackle challenges in tissue-specific network analyses, with the main focus on psychiatric diseases. PMID:28849569

[Liver diseases: The pathogenetic role of the gut microbiome and the potential of treatment for its modulation].

PubMed

Aitbaev, K A; Murkamilov, I T; Fomin, V V

The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.

Definition of the mutation responsible for maple syrup urine disease in Poll Shorthorns and genotyping Poll Shorthorns and Poll Herefords for maple syrup urine disease alleles.

PubMed

Dennis, J A; Healy, P J

1999-08-01

The organisation of the E1alpha subunit of bovine branched-chain alpha-keto acid dehydrogenase gene was established. c DNA was cloned from Poll Shorthorn x Poll Hereford calves affected with Maple Syrup Urine Disease to identify the mutation responsible for the disease in Poll Shorthorns. Clones containing the c DNA sequences inherited from the Poll Shorthorn sire of the affected calves were identified. Paternal clones were sequenced and a cytidine to thymidine transition was found at nucleotide 1380. The mutation is predicted to substitute leucine in place of a highly conserved proline at codon 372. A polymerase chain reaction procedure was developed for detection of the 1380C-->T mutation in genomic DNA. Three Poll Shorthorn parents of affected calves and three affected Poll Shorthorn x Poll Hereford calves were heterozygous and an affected Poll Shorthorn calf was homozygous for this mutation. An improved polymerase chain reaction procedure was also devised to genotype Poll Herefords for the 248C-->T mutation. The procedures will facilitate disease prevention programs and assist in differential diagnosis of conditions in new-born calves that present with a rapid onset of progressive neurological disease and are characterised histologically by 'status spongiosus'. Maple Syrup Urine Disease (MSUD) is an autosomal recessive defect reported in humans (Danner and Elsas 1989), and in Poll Hereford (PH) and Poll Shorthorn (PS) calves (Harper et al 1986, Healy et al 1992). The clinical, biochemical and pathological manifestations of the disease are identical in the two breeds of cattle, and are characterised by the rapid onset of progressive neurological disease, leading to death within a few days of birth. The disease is caused by a deficiency of activity of the mitochondrial enzyme branched-chain alpha-keto acid dehydrogenase (BCKADH). This deficiency leads to elevated concentrations, in blood and tissues, of branched chain alpha-keto acids and their precursors, the branched chain amino acids, valine, leucine and isoleucine. BCKADH consists of four subunits E1alpha, E1beta, E2 and E3 that are encoded by separate genes, and MSUD may result from deficiency of any of the subunits. In PH s, the disease in caused by premature termination of translation, of the E1alpha subunit, that is induced by a cytidine to thymidine transition exon 2 (248C-->T), that converts the glutamine codon -6 to a stop codon (Q-6ST; Zhang et al 1990). We have shown that MSUD -affected PSxPH calves are heterozygous at the PH locus, illustrating molecular heterogeneity exists for bovine MSUD (Healy and Dennis 1994a). The fact that these crossbred calves are affected, indicates the PS, like the PH mutation, resides in the E1alpha subunit. Copyright 1999 Harcourt Publishers Ltd.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT

PubMed Central

Mussawy, Haider; Schmidt, Tobias; Rolvien, Tim; Rüther, Wolfgang; Amling, Michael

2017-01-01

Summary Introduction Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. Methods Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. Results Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. Discussion CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases. PMID:28740526

BRIDGING SCALES IN THE EVOLUTION OF INFECTIOUS DISEASE LIFE HISTORIES: APPLICATION

PubMed Central

Mideo, Nicole; Nelson, William A.; Reece, Sarah E.; Bell, Andrew S.; Read, Andrew F.; Day, Troy

2014-01-01

Within- and between-host disease processes occur on the same timescales, therefore changes in the within-host dynamics of parasites, resources, and immunity can interact with changes in the epidemiological dynamics to affect evolutionary outcomes. Consequently, studies of the evolution of disease life histories, that is, infection-age-specific patterns of transmission and virulence, have been constrained by the need for a mechanistic understanding of within-host disease dynamics. In a companion paper (Day et al. 2011), we develop a novel approach that quantifies the relevant within-host aspects of disease through genetic covariance functions. Here, we demonstrate how to apply this theory to data. Using two previously published datasets from rodent malaria infections, we show how to translate experimental measures into disease life-history traits, and how to quantify the covariance in these traits. Our results show how patterns of covariance can interact with epidemiological dynamics to affect evolutionary predictions for disease life history. We also find that the selective constraints on disease life-history evolution can vary qualitatively, and that “simple” virulence-transmission trade-offs that are often the subject of experimental investigation can be obscured by trade-offs within one trait alone. Finally, we highlight the type and quality of data required for future applications. PMID:22023593

Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

PubMed

Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

2017-10-25

The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

A Spirochaete is suggested as the causative agent of Akoya oyster disease by metagenomic analysis

PubMed Central

Yasuike, Motoshige; Fujiwara, Atushi; Nakamura, Yoji; Takano, Tomokazu; Takeuchi, Takeshi; Satoh, Noriyuki; Adachi, Yoshikazu; Tsuchihashi, Yasushi; Aoki, Hideo; Odawara, Kazushi; Iwanaga, Shunsuke; Kurita, Jun; Kamaishi, Takashi; Nakayasu, Chihaya

2017-01-01

Mass mortality that is acompanied by reddish browning of the soft tissues has been occurring in cultured pearl oyster, Pinctada fucata martensii. The disease is called Akoya oyster disease (AOD). Although spreading pattern of the disease and transmission experiments suggest that the disease is infectious, the causative agent has not yet been identified. We used shotgun and 16S rRNA-based metagenomic analysis to identify genes that are present specifically in affected oysters. The genes found only in diseased oysters were mostly bacterial origin, suggesting that the causative agent was a bacterial pathogen. This hypothesis was supported by the inhibition of AOD development in naïve oysters injected with the hemolymph of diseased animals followed immediately with penicillin bath-administration. Further analyses of the hemolymph and mantle specifically and universally detected genes of bacteria that belong to phylum Spirochaetes in diseased pearl oysters but not in healthy oysters. By in situ hybridization or immunostaining, a Brachyspira-like bacterium was observed in the smears of hemolymph from affected oysters, but not from healthy oysters. Phylogenetic analysis using 16S rRNA sequences showed that the presumptive causative bacterium was outside of but most closely related to family Brachyspiraceae. We propose ‘Candidatus Maribrachyspira akoyae’ gen. nov, sp nov., for this bacterium. PMID:28771537

The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

PubMed

Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

2016-08-01

Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

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.

Normalization of white matter intensity on T1-weighted images of patients with acquired central nervous system demyelination.

PubMed

Ghassemi, Rezwan; Brown, Robert; Narayanan, Sridar; Banwell, Brenda; Nakamura, Kunio; Arnold, Douglas L

2015-01-01

Intensity variation between magnetic resonance images (MRI) hinders comparison of tissue intensity distributions in multicenter MRI studies of brain diseases. The available intensity normalization techniques generally work well in healthy subjects but not in the presence of pathologies that affect tissue intensity. One such disease is multiple sclerosis (MS), which is associated with lesions that prominently affect white matter (WM). To develop a T1-weighted (T1w) image intensity normalization method that is independent of WM intensity, and to quantitatively evaluate its performance. We calculated median intensity of grey matter and intraconal orbital fat on T1w images. Using these two reference tissue intensities we calculated a linear normalization function and applied this to the T1w images to produce normalized T1w (NT1) images. We assessed performance of our normalization method for interscanner, interprotocol, and longitudinal normalization variability, and calculated the utility of the normalization method for lesion analyses in clinical trials. Statistical modeling showed marked decreases in T1w intensity differences after normalization (P < .0001). We developed a WM-independent T1w MRI normalization method and tested its performance. This method is suitable for longitudinal multicenter clinical studies for the assessment of the recovery or progression of disease affecting WM. Copyright © 2014 by the American Society of Neuroimaging.

Analysis of the contribution of HLA genes to genetic predisposition in inflammatory bowel disease

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

Naom, I.; Haris, I.; Hodgson, S.V.

1996-07-01

Crohn disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBDs) of unknown etiology. First-degree relatives of IBD patients have a 10-fold increase in risk of developing the same disease, and distinct associations between specific HLA types and both CD and UC have been reported. We have evaluated the contribution of genes at the HLA locus to susceptibility in IBD by linkage analysis of highly informative microsatellite polymorphisms in 43 families with multiple affected cases. No evidence for linkage of HLA to IBD was obtained under any of the four models tested. Analysis of HLA haplotype sharing inmore » affected relatives indicated that the relative risk to a sibling conferred by the HLA locus was 1.11 in UC and 0.75 in CD, with upper (95%) confidence limits of 2.41 and 1.37, respectively. This suggests that other genetic or environmental factors are responsible for most of the familial aggregation in IBD. 31 refs., 1 fig., 2 tabs.« less

Diverse structures, functions and uses of FK506 binding proteins.

PubMed

Bonner, Julia Maeve; Boulianne, Gabrielle L

2017-10-01

FK506 (Tacrolimus), isolated from Streptomyces tsukubaenis is a powerful immunosuppressant shown to inhibit T cell activation. FK506 mediated immunosuppression requires the formation of a complex between FK506, a FK506 binding protein (FKBP) and calcineurin. Numerous FKBPs have been identified in a wide range of species, from single celled organisms to humans. FKBPs show peptidylprolyl cis/trans isomerase (PPIase) activity and have been shown to affect a wide range of cellular processes including protein folding, receptor signaling and apoptosis. FKBPs also affect numerous biological functions in addition to immunosuppression including regulation of cardiac function, neuronal function and development and have been implicated in several diseases including cardiac disease, cancer and neurodegenerative diseases such as Alzheimer's disease. More recently, FKBPs have proven useful as molecular tools for studying protein interactions, localization and functions. This review provides an overview of the current state of knowledge of FKBPs and their numerous biological functions and uses. Copyright © 2017 Elsevier Inc. All rights reserved.

Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways

PubMed Central

Sturgeon, John A.; Finan, Patrick H.; Zautra, Alex J.

2017-01-01

In addition to recurrent pain, fatigue, and increased rates of physical disability, individuals with rheumatoid arthritis (RA) show an increased prevalence of some mental health disorders, particularly those involving mood disturbances. This narrative Review provides an overview of mental health comorbidities in RA, and discusses how these comorbidities interact with disease processes, including dysregulation of inflammatory responses, prolonged difficulties with pain and fatigue, and the development of cognitive and behavioural responses that could exacerbate the physical and psychological difficulties associated with RA. This article describes how the social context of individuals with RA affects both their coping strategies and psychological responses to the disease, and can also impair responses to treatment through disruption of therapeutic alliance and treatment adherence. Evidence from the literature on chronic pain suggests that the resulting alterations in neural pathways of reward processing could yield new insights into the connections between disease processes in RA and psychological distress. Finally, the role of psychological interventions in the effective and comprehensive treatment of RA is discussed. PMID:27411910

Ongoing Oxidative Stress Causes Subclinical Neuronal Dysfunction in the Recovery Phase of EAE

PubMed Central

Radbruch, Helena; Bremer, Daniel; Guenther, Robert; Cseresnyes, Zoltan; Lindquist, Randall; Hauser, Anja E.; Niesner, Raluca

2016-01-01

Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET–FLIM, providing a possible mechanism of disease progression in MS. PMID:27014271

Imaging epigenetics in Alzheimer's disease.

PubMed

Lista, Simone; Garaci, Francesco G; Toschi, Nicola; Hampel, Harald

2013-01-01

Sporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging methods with epigenetic markers in humans appears promising. This evolving development may lead to a new research discipline - imaging epigenetics - that will provide deeper insight into the causative pathogenetic and pathophysiological pathways through which genes and environment interrelate during life and impact human brain development, physiology, aging and disease. This knowledge may open doors for the development of novel biomarkers and preventive and disease-modifying treatments.

Freedom poverty: a new tool to identify the multiple disadvantages affecting those with CVD.

PubMed

Callander, Emily J; Schofield, Deborah J; Shrestha, Rupendra N

2013-06-20

It is recognised that CVD affects an individual's financial situation, placing them in income poverty. However, recent developments in poverty measurement practice recognises other forms of disadvantage other than low income, such as poor health and insufficient education also affect living standards. Using the Freedom Poverty Measure, the multiple forms of disadvantage experienced by those with no health condition, heart disease, other diseases of the circulatory system, and all other health conditions was assessed using data on the adult Australian population contained in the 2003 Survey of Disability, Ageing and Carers. 24% of those with heart disease and 23% of those with other diseases of the circulatory system were in freedom poverty, suffering from multiple forms of disadvantage. Those with heart disease and those with other diseases of the circulatory system were around three times more likely to be in freedom poverty (OR 3.02, 95% CI: 2.29-3.99, p<.0001; OR 2.78, 95% CI: 1.94-3.98, p<.0001) than those with no health condition. Recognising the multiple forms of disadvantage suffered by those with CVD provides a clearer picture of their living standards than just looking at their income alone and the high proportion of individuals with CVD that are suffering from multiple forms of disadvantage should make them a target for policy makers wishing to improve living standards. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Second Trimester Maternal Serum Screening for Fetal Down Syndrome: as a Screening Test for Hemoglobin Bart's Disease: A Prospective Population-based Study.

PubMed

Wanapirak, Chanane; Piyamomgkol, Wirawit; Sirichotiyakul, Supatra; Tongprasert, Fuanglada; Srisupundit, Kasemsri; Luewan, Suchaya; Traisrisilp, Kuntharee; Jatavan, Phudit; Tongsong, Theera

2018-06-21

To determine the effectiveness of second-trimester maternal serum screening (MSS) for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20,254 pregnancies) was conducted to compare the levels of MSS, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses, (1.96 vs. 1.12 multiple of the median (MoM); p<0.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cut-off value of 1.5 MoM. The serum free b-hCG levels were slightly, but significantly, higher in the affected pregnancies, while the serum uE3 levels were minimally, but significantly, lower among the affected pregnancies. Second trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis. This article is protected by copyright. All rights reserved.

Somatic, but not cognitive–affective, symptoms are associated with reduced heart rate variability in individuals with dysphoria

PubMed Central

Benvenuti, Simone Messerotti; Buodo, Giulia; Mennella, Rocco; Palomba, Daniela

2015-01-01

Background: Somatic, but not cognitive–affective, symptoms of depression have been associated with reduced heart rate variability (HRV), and with poor prognosis in cardiovascular patients. However, factors concomitant with cardiovascular diseases may confound the relationship between somatic symptoms of depression and reduced HRV. Therefore, this study examined whether reduced HRV was differentially associated with cognitive–affective and somatic symptoms of depression in medically healthy individuals with and without dysphoria. Methods: Self-reported cognitive–affective and somatic symptoms as measured with the Beck Depression Inventory-II questionnaire and time and frequency domain parameters of HRV were collected in 62 medically healthy individuals, of whom 25 with and 37 without dysphoria. Results: Somatic, but not cognitive–affective, symptoms of depression were inversely associated with SD of NN intervals (β = -0.476, p < 0.05), number of interval differences of successive NN intervals greater than 50 ms (NN50; β = -0.498, p < 0.03), and HRV total power (β = -0.494, p < 0.04) in the group with dysphoria, after controlling for sex, anxiety, and lifestyle factors. Cognitive–affective and somatic symptoms were not related to any of the HRV parameters in the group without dysphoria (all ps > 0.24). Conclusion: By showing that the relationship between somatic depressive symptoms and reduced HRV extends to medically healthy individuals with dysphoria, the present findings suggest that this association is independent of factors concomitant with cardiovascular diseases. The present study also suggests that individuals with somatic rather than cognitive–affective subsets of depressive symptoms may be at greater risk for developing cardiovascular diseases. PMID:25999905

Global epidemiology of hyperthyroidism and hypothyroidism.

PubMed

Taylor, Peter N; Albrecht, Diana; Scholz, Anna; Gutierrez-Buey, Gala; Lazarus, John H; Dayan, Colin M; Okosieme, Onyebuchi E

2018-05-01

Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. Iodine nutrition is a key determinant of thyroid disease risk; however, other factors, such as ageing, smoking status, genetic susceptibility, ethnicity, endocrine disruptors and the advent of novel therapeutics, including immune checkpoint inhibitors, also influence thyroid disease epidemiology. In the developed world, the prevalence of undiagnosed thyroid disease is likely falling owing to widespread thyroid function testing and relatively low thresholds for treatment initiation. However, continued vigilance against iodine deficiency remains essential in developed countries, particularly in Europe. In this report, we review the global incidence and prevalence of hyperthyroidism and hypothyroidism, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data. We also highlight the pressing need for detailed epidemiological surveys of thyroid dysfunction and iodine status in developing countries.

The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes.

PubMed

Bekkering, Pjotr; Jafri, Ismael; van Overveld, Frans J; Rijkers, Ger T

2013-11-01

It has been proposed that changes in the composition of gut microbiota contribute to the development of diabetes Types 1, 2 and 3 (the latter known as Alzheimer's disease). The onset of these diseases is affected by complex interactions of genetic and several environmental factors. Alterations in gut microbiota in combination with specific diets can result in increased intestinal permeability leading via a continuous state of low-grade inflammation to the development of insulin resistance. Since a change in composition of gut microbiota is also suggested to be the underlying factor for the development of obesity, it is obvious to link gut microbiota with the pathogenesis of diabetes. In addition, insulin resistance in the brain has been recently associated with Alzheimer's disease. These new paradigms in combination with data from studies with prebiotics and probiotics may lead to a novel way to control and even prevent diabetes in general.

Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

PubMed Central

Jamieson, Sarra E.; de Roubaix, Lee-Anne; Cortina-Borja, Mario; Tan, Hooi Kuan; Mui, Ernest J.; Cordell, Heather J.; Kirisits, Michael J.; Miller, E. Nancy; Peacock, Christopher S.; Hargrave, Aubrey C.; Coyne, Jessica J.; Boyer, Kenneth; Bessieres, Marie-Hélène; Buffolano, Wilma; Ferret, Nicole; Franck, Jacqueline; Kieffer, François; Meier, Paul; Nowakowska, Dorota E.; Paul, Malgorzata; Peyron, François; Stray-Pedersen, Babill; Prusa, Andrea-Romana; Thulliez, Philippe; Wallon, Martine; Petersen, Eskild; McLeod, Rima; Gilbert, Ruth E.; Blackwell, Jenefer M.

2008-01-01

Background Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute. Methods and Findings In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting. Conclusions These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite. PMID:18523590

Consumers' disease information-seeking behaviour on the Internet in Korea.

PubMed

Yun, Eun Kyoung; Park, Hyeoun-Ae

2010-10-01

This study was conducted to explain the relationships of the factors affecting consumers' disease information-seeking behaviour on the Internet in Korea. Similar to other countries, Korea is facing an increasing use of Internet as a resource of health information. With the paradigm shifts towards consumer-centred health service, it is expected that more health care consumers will use the Internet actively in the future. A survey was conducted using a self-selected convenience sample. A conceptual model was derived by extending technology acceptance model and tested via structural equation modelling. The overall goodness of fit of the conceptual model was acceptable. Consumers' health consciousness, perceived health risk and Internet health information use efficacy were found to influence consumers' beliefs, attitude and intention of use disease information on the Internet. But Internet health information use efficacy did not significantly influence perceived usefulness. It was also identified that consumers' perceived credibility of the information in the websites was the main determinant in forming of attitude towards disease information on the Internet. Technology acceptance model has been extended and examined successfully in explaining consumers' disease information-seeking behaviour on the Internet. It was found that consumers' cognitive and affective characteristics, determined as initiators in health-related behaviour, also impacted consumers' disease information-seeking behaviour on the Internet. These findings may be used to help nurses to predict and identify the factors affecting individual's use of disease information on the Internet. Based on this knowledge, nurses will be able to develop nursing intervention programmes for the patients' health management. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

What Works for Asthma Education Programs: Lessons from Experimental Evaluations of Social Programs and Interventions for Children. Fact Sheet. Publication #2012-01

ERIC Educational Resources Information Center

Chrisler, Alison

2012-01-01

Asthma is a chronic respiratory disease that affects millions of children and adolescents each year. In 2009, 7.1 million children ages 0 to 17 years were reported to have asthma. Unfortunately, when children and teens are unable to manage and cope with their disease, it can compromise their physical, academic, and social development. Therefore,…

Development and Application of Advanced Ophthalmic Imaging Technology to Enhance Military Ocular Health Capabilities

DTIC Science & Technology

2009-04-01

active military personnel and veterans, are affected by three major blinding diseases of the retina and optic nerve: diabetic retinopathy , age-related...disease is detected early. New advanced detection methods are available, but are only interpretable by very experienced specialists. The goal of this...consist of several steps [1-3]: feature detection ; transform model estimation; optimization function design; and optimization strategies. We do not

A high-resolution melting (HRM) assay for the differentiation between Israeli field and Neethling vaccine lumpy skin disease viruses.

PubMed

Menasherow, Sophia; Erster, Oran; Rubinstein-Giuni, Marisol; Kovtunenko, Anita; Eyngor, Evgeny; Gelman, Boris; Khinich, Evgeny; Stram, Yehuda

2016-06-01

Lumpy skin disease (LSD) is a constant threat to the Middle East including the State of Israel. During vaccination programs it is essential for veterinary services and farmers to be able to distinguish between animals affected by the cattle-borne virulent viruses and vaccinated animals, subsequently affected by the vaccine strain. This study describes an improved high resolution-melting (HRM) test that exploits a 27 base pair (bp) fragment of the LSDV126 extracellular enveloped virion (EEV) gene that is present in field viruses but is absent from the Neethling vaccine strain. This difference leads to ∼0.5 °C melting point change in the HRM assay, when testing the quantitative PCR (qPCR) products generated from the virulent field viruses compared to the attenuated vaccine. By exploiting this difference, it could be shown using the newly developed HRM assay that virus isolated from vaccinated cattle that developed disease symptoms behave similarly to vaccine virus control, indicating that the vaccine virus can induce disease symptoms. This assay is not only in full agreement with the previously published PCR gradient and restriction fragment length polymorphism (RFLP) tests but it is faster with, fewer steps, cheaper and dependable. Copyright © 2016 Elsevier B.V. All rights reserved.

Exploring the influence of the Global Fund and the GAVI Alliance on health systems in conflict-affected countries.

PubMed

Patel, Preeti; Cummings, Rachael; Roberts, Bayard

2015-01-01

Global Health Initiatives (GHIs) respond to high-impact communicable diseases in resource-poor countries, including health systems support, and are major actors in global health. GHIs could play an important role in countries affected by armed conflict given these countries commonly have weak health systems and a high burden of communicable disease. The aim of this study is to explore the influence of two leading GHIs, the Global Fund and the GAVI Alliance, on the health systems of conflict-affected countries. This study used an analytical review approach to identify evidence on the role of the Global Fund and the GAVI Alliance with regards to health systems support to 19 conflict-affected countries. Primary and secondary published and grey literature were used, including country evaluations from the Global Fund and the GAVI Alliance. The WHO heath systems building blocks framework was used for the analysis. There is a limited evidence-base on the influence of GHIs on health systems of conflict-affected countries. The findings suggest that GHIs are increasingly investing in conflict-affected countries which has helped to rapidly scale up health services, strengthen human resources, improve procurement, and develop guidelines and protocols. Negative influences include distorting priorities within the health system, inequitable financing of disease-specific services over other health services, diverting staff away from more essential health care services, inadequate attention to capacity building, burdensome reporting requirements, and limited flexibility and responsiveness to the contextual challenges of conflict-affected countries. There is some evidence of increasing engagement of the Global Fund and the GAVI Alliance with health systems in conflict-affected countries, but this engagement should be supported by more context-specific policies and approaches.

A Comparative Analysis of Economic Cost of Podoconiosis and Leprosy on Affected Households in the Northwest Region of Cameroon

PubMed Central

Tembei, Ayok M.; Kengne-Ouaffo, Jonas A.; Ngoh, Elvis A.; John, Bonekeh; Nji, Theobald M.; Deribe, Kebede; Enyong, Peter; Nkuo-Akenji, Theresa; Davey, Gail; Wanji, Samuel

2018-01-01

Abstract. Leprosy and podoconiosis (podo) are neglected tropical diseases that cause severe disfigurement and disability, and may lead to catastrophic health expenditure and hinder economic development of affected persons and households. This study compared economic costs of both diseases on affected households with unaffected neighboring households in the Northwest Region (N.W.R.) of Cameroon. A matched comparative cross-sectional design was used enrolling 170 households (43 podo case households, 41 podo control households, 43 leprosy case households, and 43 leprosy control households) from three health districts in the N.W.R. Direct treatment costs for podo averaged 142 United State dollar (USD), compared with zero for leprosy (P < 0.001). This was also reflected in the proportion of annual household income consumed (0.4 versus 0.0, respectively, P < 0.001). Both diseases caused considerable reductions in working days (leprosy 115 versus podo 135 days. P for comparison < 0.001). The average household income was considerably lower in podo-affected households than unaffected households (410 versus 913 USD, P = 0.01), whereas income of leprosy-affected households was comparable to unaffected households (329 versus 399 USD, P = 0.23). Both leprosy and podo cause financial burdens on affected households, but those on podo-affected families are much greater. These burdens occur through direct treatment costs and reduced ability to work. Improved access to public health interventions for podo including prevention, morbidity management and disability prevention are likely to result in economic returns to affected families. In Cameroon, one approach to this would be through subsidized health insurance for these economically vulnerable households. PMID:29460727

A Comparative Analysis of Economic Cost of Podoconiosis and Leprosy on Affected Households in the Northwest Region of Cameroon.

PubMed

Tembei, Ayok M; Kengne-Ouaffo, Jonas A; Ngoh, Elvis A; John, Bonekeh; Nji, Theobald M; Deribe, Kebede; Enyong, Peter; Nkuo-Akenji, Theresa; Davey, Gail; Wanji, Samuel

2018-04-01

Leprosy and podoconiosis (podo) are neglected tropical diseases that cause severe disfigurement and disability, and may lead to catastrophic health expenditure and hinder economic development of affected persons and households. This study compared economic costs of both diseases on affected households with unaffected neighboring households in the Northwest Region (N.W.R.) of Cameroon. A matched comparative cross-sectional design was used enrolling 170 households (43 podo case households, 41 podo control households, 43 leprosy case households, and 43 leprosy control households) from three health districts in the N.W.R. Direct treatment costs for podo averaged 142 United State dollar (USD), compared with zero for leprosy ( P < 0.001). This was also reflected in the proportion of annual household income consumed (0.4 versus 0.0, respectively, P < 0.001). Both diseases caused considerable reductions in working days (leprosy 115 versus podo 135 days. P for comparison < 0.001). The average household income was considerably lower in podo-affected households than unaffected households (410 versus 913 USD, P = 0.01), whereas income of leprosy-affected households was comparable to unaffected households (329 versus 399 USD, P = 0.23). Both leprosy and podo cause financial burdens on affected households, but those on podo-affected families are much greater. These burdens occur through direct treatment costs and reduced ability to work. Improved access to public health interventions for podo including prevention, morbidity management and disability prevention are likely to result in economic returns to affected families. In Cameroon, one approach to this would be through subsidized health insurance for these economically vulnerable households.

Dietary supplements and disease prevention: a global overview

USDA-ARS?s Scientific Manuscript database

Undernutrition and micronutrient malnutrition are prevalent conditions that affect global public health. Dietary supplements are widely used in many developed countries. However, it remains unclear whether supplementation with individual or combined vitamins, minerals, and other nutrients are effe...

Nanotechnology and nanocarrier-based approaches on treatment of degenerative diseases

NASA Astrophysics Data System (ADS)

Chowdhury, Anindita; Kunjiappan, Selvaraj; Panneerselvam, Theivendren; Somasundaram, Balasubramanian; Bhattacharjee, Chiranjib

2017-04-01

Degenerative diseases are results of deterioration of cells and tissues with aging either by unhealthy lifestyle or normal senescence. The degenerative disease likely affects central nervous system and cardiovascular system to a great extent. Certain medications and therapies have emerged for the treatment of degenerative diseases, but in most cases bearing with poor solubility, lower bioavailability, drug resistance, and incapability to cross the blood-brain barrier (BBB). Hence, it has to be overcome with conventional treatment system; in this connection, nanotechnology has gained a great deal of interest in recent years. Moreover, nanotechnology and nanocarrier-based approach drug delivery system could revolutionize the treatment of degenerative diseases by faster absorption of drug, targeted interaction at specific site, and its release in a controlled manner into human body with minimal side effects. The core objective of this review is to customize and formulate therapeutically active molecules with specific site of action and without affecting other organs and tissues to obtain effective result in the improvement of quality of health. In addition, the review provides a concise insight into the recent developments and applications of nanotech and nanocarrier-based drug delivery for the treatment of various degenerative diseases.

Diet regulates liver autophagy differentially in murine acute Trypanosoma cruzi infection

PubMed Central

Lizardo, Kezia; Almonte, Vanessa; Law, Calvin; Aiyyappan, Janeesh Plakkal; Cui, Min-Hui; Nagajyothi, Jyothi F

2017-01-01

Chagas disease is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi, which affects about 10 million people in its endemic regions of Latin America. After the initial acute stage of infection, 60–80% of infected individuals remain asymptomatic for several years to a lifetime; however, the rest develop the debilitating symptomatic stage, which affects the nervous system, digestive system and heart. The challenges of Chagas disease have become global due to immigration. Despite well documented dietary changes accompanying immigration, as well as a transition to a western style diet in the Chagas endemic regions, the role of host metabolism in the pathogenesis of Chagas disease remains underexplored. We have previously used a mouse model to show that host diet is a key factor regulating cardiomyopathy in Chagas disease. In this study we investigated the effect of a high fat diet on liver morphology and physiology, lipid metabolism, immune signaling, energy homeostasis, and stress responses in the murine model of acute T. cruzi infection. Our results indicate that in T. cruzi infected mice diet differentially regulates several liver processes, including autophagy, a stress response mechanism, with corresponding implications for human Chagas disease patients. PMID:27987056

Aggressive and acute periodontal diseases.

PubMed

Albandar, Jasim M

2014-06-01

Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid-course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early-onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans-JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small-effect genes, and there is also evidence of gene-gene and gene-environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon-Lefèvre syndrome, Chediak-Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra-oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Infections and parasitic diseases of the gray wolf and their potential effects on wolf populations in North America.

USGS Publications Warehouse

Brand, C.J.; Pybus, M.J.; Ballard, W.B.; Peterson, R.O.

1995-01-01

Numerous infections and parasitic diseases have been reported for the gray wolf, including more than 10 viral, bacterial, and mycotic disease and more than 70 species of helminths and ectoparasites. However, few studies have documented the role of diseases in population dynamics. Disease can affect wolf populations directly by causing mortality or indirectly by affecting physiological and homeostatic processes, thriftiness, reproduction, behavior, or social structure. In addition, wolves are hosts to diseases that can affect prey species, thus affecting wolf populations indirectly by reducing prey abundance or increasing vulnerability to predation. Diseases such as canine distemper and infectious canine hepatitis are enzootic in wolf populations, whereas rabies occurs in wolves primarily as a result of transmission from other species such as artic and red foxes. Contact between wolves and domestic pets and livestock may affect the composition of diseases in wolves and their effects on wolf populations. Dogs were suspected of introducing lice and canine parovirus to several wolf populations. THe potential for disease to affect wolf populations and other wild and domestic animals should be considered in wolf management plans, particularly in plans for reintroduction of wolves to area within their former range.

A Risk Analysis Approach to Prioritizing Epidemics: Ebola Virus Disease in West Africa as a Case Study.

PubMed

Ajisegiri, Whenayon Simeon; Chughtai, Abrar Ahmad; MacIntyre, C Raina

2018-03-01

The 2014 Ebola virus disease (EVD) outbreak affected several countries worldwide, including six West African countries. It was the largest Ebola epidemic in the history and the first to affect multiple countries simultaneously. Significant national and international delay in response to the epidemic resulted in 28,652 cases and 11,325 deaths. The aim of this study was to develop a risk analysis framework to prioritize rapid response for situations of high risk. Based on findings from the literature, sociodemographic features of the affected countries, and documented epidemic data, a risk scoring framework using 18 criteria was developed. The framework includes measures of socioeconomics, health systems, geographical factors, cultural beliefs, and traditional practices. The three worst affected West African countries (Guinea, Sierra Leone, and Liberia) had the highest risk scores. The scores were much lower in developed countries that experienced Ebola compared to West African countries. A more complex risk analysis framework using 18 measures was compared with a simpler one with 10 measures, and both predicted risk equally well. A simple risk scoring system can incorporate measures of hazard and impact that may otherwise be neglected in prioritizing outbreak response. This framework can be used by public health personnel as a tool to prioritize outbreak investigation and flag outbreaks with potentially catastrophic outcomes for urgent response. Such a tool could mitigate costly delays in epidemic response. © 2017 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Biomedical research, a tool to address the health issues that affect African populations

PubMed Central

2013-01-01

Traditionally, biomedical research endeavors in low to middle resources countries have focused on communicable diseases. However, data collected over the past 20 years by the World Health Organization (WHO) show a significant increase in the number of people suffering from non-communicable diseases (e.g. heart disease, diabetes, cancer and pulmonary diseases). Within the coming years, WHO predicts significant decreases in communicable diseases while non-communicable diseases are expected to double in low and middle income countries in sub-Saharan Africa. The predicted increase in the non-communicable diseases population could be economically burdensome for the basic healthcare infrastructure of countries that lack resources to address this emerging disease burden. Biomedical research could stimulate development of healthcare and biomedical infrastructure. If this development is sustainable, it provides an opportunity to alleviate the burden of both communicable and non-communicable diseases through diagnosis, prevention and treatment. In this paper, we discuss how research using biomedical technology, especially genomics, has produced data that enhances the understanding and treatment of both communicable and non-communicable diseases in sub-Saharan Africa. We further discuss how scientific development can provide opportunities to pursue research areas responsive to the African populations. We limit our discussion to biomedical research in the areas of genomics due to its substantial impact on the scientific community in recent years however, we also recognize that targeted investments in other scientific disciplines could also foster further development in African countries. PMID:24143865

Rift Valley Fever.

PubMed

Hartman, Amy

2017-06-01

Rift Valley fever (RVF) is a severe veterinary disease of livestock that also causes moderate to severe illness in people. The life cycle of RVF is complex and involves mosquitoes, livestock, people, and the environment. RVF virus is transmitted from either mosquitoes or farm animals to humans, but is generally not transmitted from person to person. People can develop different diseases after infection, including febrile illness, ocular disease, hemorrhagic fever, or encephalitis. There is a significant risk for emergence of RVF into new locations, which would affect human health and livestock industries. Copyright © 2017 Elsevier Inc. All rights reserved.

Information systems for administration, clinical documentation and quality assurance in an Austrian disease management programme.

PubMed

Beck, Peter; Truskaller, Thomas; Rakovac, Ivo; Bruner, Fritz; Zanettin, Dominik; Pieber, Thomas R

2009-01-01

5.9% of the Austrian population is affected by diabetes mellitus. Disease Management is a structured treatment approach that is suitable for application to the diabetes mellitus area and often is supported by information technology. This article describes the information systems developed and implemented in the Austrian disease management programme for type 2 diabetes. Several workflows for administration as well as for clinical documentation have been implemented utilizing the Austrian e-Health infrastructure. De-identified clinical data is available for creating feedback reports for providers and programme evaluation.

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease

PubMed Central

Ravichandran, Srikanth; Michelucci, Alessandro; del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases. PMID:29551980

Integrative Computational Network Analysis Reveals Site-Specific Mediators of Inflammation in Alzheimer's Disease.

PubMed

Ravichandran, Srikanth; Michelucci, Alessandro; Del Sol, Antonio

2018-01-01

Alzheimer's disease (AD) is a major neurodegenerative disease and is one of the most common cause of dementia in older adults. Among several factors, neuroinflammation is known to play a critical role in the pathogenesis of chronic neurodegenerative diseases. In particular, studies of brains affected by AD show a clear involvement of several inflammatory pathways. Furthermore, depending on the brain regions affected by the disease, the nature and the effect of inflammation can vary. Here, in order to shed more light on distinct and common features of inflammation in different brain regions affected by AD, we employed a computational approach to analyze gene expression data of six site-specific neuronal populations from AD patients. Our network based computational approach is driven by the concept that a sustained inflammatory environment could result in neurotoxicity leading to the disease. Thus, our method aims to infer intracellular signaling pathways/networks that are likely to be constantly activated or inhibited due to persistent inflammatory conditions. The computational analysis identified several inflammatory mediators, such as tumor necrosis factor alpha (TNF-a)-associated pathway, as key upstream receptors/ligands that are likely to transmit sustained inflammatory signals. Further, the analysis revealed that several inflammatory mediators were mainly region specific with few commonalities across different brain regions. Taken together, our results show that our integrative approach aids identification of inflammation-related signaling pathways that could be responsible for the onset or the progression of AD and can be applied to study other neurodegenerative diseases. Furthermore, such computational approaches can enable the translation of clinical omics data toward the development of novel therapeutic strategies for neurodegenerative diseases.

Gaucher disease: the role of the specialist on metabolic bone diseases.

PubMed

Masi, Laura; Brandi, Maria Luisa

2015-01-01

According to European legislation, a disease can be considered rare or "orphan" when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible.

Maternal high-fat diet is associated with impaired fetal lung development

PubMed Central

Mayor, Reina S.; Finch, Katelyn E.; Zehr, Jordan; Morselli, Eugenia; Neinast, Michael D.; Frank, Aaron P.; Hahner, Lisa D.; Wang, Jason; Rakheja, Dinesh; Palmer, Biff F.; Rosenfeld, Charles R.; Savani, Rashmin C.

2015-01-01

Maternal nutrition has a profound long-term impact on infant health. Poor maternal nutrition influences placental development and fetal growth, resulting in low birth weight, which is strongly associated with the risk of developing chronic diseases, including heart disease, hypertension, asthma, and type 2 diabetes, later in life. Few studies have delineated the mechanisms by which maternal nutrition affects fetal lung development. Here, we report that maternal exposure to a diet high in fat (HFD) causes placental inflammation, resulting in placental insufficiency, fetal growth restriction (FGR), and inhibition of fetal lung development. Notably, pre- and postnatal exposure to maternal HFD also results in persistent alveolar simplification in the postnatal period. Our novel findings provide a strong association between maternal diet and fetal lung development. PMID:26092997

New developments in occupational dermatology.

PubMed

Diepgen, Thomas L

2016-09-01

Occupational skin diseases according to BK No. 5101 - "severe or recurrent skin diseases which have forced the person to discontinue all occupational activities that caused or could cause the development, worsening, or recurrence of the disease" - is the most commonly reported notifiable occupational diseases in Germany. Following the optimization of measures of primary, secondary, and tertiary prevention, today most individuals affected are able to continue their profession. With the revision of the German ordinance on occupational diseases (BKV) in January 2015, skin cancer caused by UV irradiation was added to the list of occupational diseases. The new occupational disease (BK) 5103 is defined as "squamous cell carcinoma or multiple actinic keratoses of the skin caused by natural UV irradiation". In this context, "multiple" signifies the occurrence of either more than five individual actinic keratosis lesions over the course of 12 months or the presence of field cancerization of > 4 cm(2) . In the following review, important aspects of this new occupational disease will be highlighted and discussed. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Gastrointestinal parasites: potential therapy for refractory inflammatory bowel diseases.

PubMed

Moreels, Tom G; Pelckmans, Paul A

2005-02-01

Crohn's disease and ulcerative colitis are chronic relapsing inflammatory bowel diseases (IBDs). Different pharmacological agents are currently used in several combinations to control the inflammatory process. Recently, antibodies against the proinflammatory cytokine tumor necrosis factor-alpha appeared to be very effective in treating patients with Crohn's disease. However, due to the fact that the pathogen causing IBD is still unknown, no causative treatment is currently available that is able to make the disease disappear. Recently, the hygiene hypothesis of the development of immunological diseases was proposed, stating that raising children in extremely hygienic environments with less exposure to parasite infections may negatively affect the development of the immune system, predisposing them to immunologic diseases such as IBD. This hypothesis is supported by experimental data showing that helminthic parasites protect against T helper (TH) type 1 cell-mediated gastrointestinal inflammations like Crohn's disease. Both TH-2 cells and regulatory T cells may be involved in this immunomodulatory mechanism. Here, we review the experimental and clinical studies in favor of the hygiene hypothesis, opening perspectives on new therapies for IBD.

Developing treatments for inborn errors: incentives available to the clinician.

PubMed

Haffner, Marlene E

2004-04-01

Disorders resulting from inborn errors of metabolism (IEM) affect very small numbers of individuals. The entire population, however, of patients suffering the results of inherited metabolic disorders is large, and has been of increasing concern to patient groups and health care professionals in the United States as well as other countries throughout the world. The 1983 US Orphan Drug Act (ODA) serves to facilitate the development of drugs to treat rare diseases by providing several economic incentives. The sponsor of a product designated as an orphan by the Food & Drugs Administration (FDA) Office of Orphan Products Development (OPD) qualifies for tax credits on clinical trial expenses, the award of grant funding by FDA, through the OPD, and 7 years of marketing exclusivity for a designated drug, or biological product that receives FDA market approval. Orphan drug legislation in the US has benefited victims of IEM by encouraging development of drugs for metabolic deficiencies affecting populations that otherwise would be ignored. America's solution to the orphan drug problem has had worldwide impact. The success of this legislation was a factor leading to the 1993 orphan drug law in Japan; the 1997 implementation of a process whereby most FDA-approved orphan drugs and biological products will be similarly approved in Australia; and, in 1999, regulation on orphan medicinal products in the European Union (EU). Today, international support for rare disease research is providing stimulus and motivation to overcome the financial barriers and encourage development of treatment for very rare diseases throughout the world.

Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases

PubMed Central

Lamontagne, Jason; Steel, Laura F; Bouchard, Michael J

2015-01-01

Chronic infection with the hepatitis B virus (HBV) is the leading risk factor for the development of hepatocellular carcinoma (HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, microRNAs (miRNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of miRNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between miRNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some miRNAs, such as miR-122, and miR-125 and miR-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and miRNAs, including how HBV affects cellular miRNAs, how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and miRNAs, and propose potential applications of miRNA-related techniques that could enhance our understanding of the role miRNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes. PMID:26139985

Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases.

PubMed

Lamontagne, Jason; Steel, Laura F; Bouchard, Michael J

2015-06-28

Chronic infection with the hepatitis B virus (HBV) is the leading risk factor for the development of hepatocellular carcinoma (HCC). With nearly 750000 deaths yearly, hepatocellular carcinoma is the second highest cause of cancer-related death in the world. Unfortunately, the molecular mechanisms that contribute to the development of HBV-associated HCC remain incompletely understood. Recently, microRNAs (miRNAs), a family of small non-coding RNAs that play a role primarily in post-transcriptional gene regulation, have been recognized as important regulators of cellular homeostasis, and altered regulation of miRNA expression has been suggested to play a significant role in virus-associated diseases and the development of many cancers. With this in mind, many groups have begun to investigate the relationship between miRNAs and HBV replication and HBV-associated disease. Multiple findings suggest that some miRNAs, such as miR-122, and miR-125 and miR-199 family members, are playing a role in HBV replication and HBV-associated disease, including the development of HBV-associated HCC. In this review, we discuss the current state of our understanding of the relationship between HBV and miRNAs, including how HBV affects cellular miRNAs, how these miRNAs impact HBV replication, and the relationship between HBV-mediated miRNA regulation and HCC development. We also address the impact of challenges in studying HBV, such as the lack of an effective model system for infectivity and a reliance on transformed cell lines, on our understanding of the relationship between HBV and miRNAs, and propose potential applications of miRNA-related techniques that could enhance our understanding of the role miRNAs play in HBV replication and HBV-associated disease, ultimately leading to new therapeutic options and improved patient outcomes.

Polymorphisms in miRNA genes and their involvement in autoimmune diseases susceptibility.

PubMed

Latini, Andrea; Ciccacci, Cinzia; Novelli, Giuseppe; Borgiani, Paola

2017-08-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate the expression of multiple protein-encoding genes at the post-transcriptional level. MicroRNAs are involved in different pathways, such as cellular proliferation and differentiation, signal transduction and inflammation, and play crucial roles in the development of several diseases, such as cancer, diabetes, and cardiovascular diseases. They have recently been recognized to play a role also in the pathogenesis of autoimmune diseases. Although the majority of studies are focused on miRNA expression profiles investigation, a growing number of studies have been investigating the role of polymorphisms in miRNA genes in the autoimmune diseases development. Indeed, polymorphisms affecting the miRNA genes can modify the set of targets they regulate or the maturation efficiency. This review is aimed to give an overview about the available studies that have investigated the association of miRNA gene polymorphisms with the susceptibility to various autoimmune diseases and to their clinical phenotypes.

Prognostic interaction patterns in diabetes mellitus II: A random-matrix-theory relation

NASA Astrophysics Data System (ADS)

Rai, Aparna; Pawar, Amit Kumar; Jalan, Sarika

2015-08-01

We analyze protein-protein interactions in diabetes mellitus II and its normal counterpart under the combined framework of random matrix theory and network biology. This disease is the fifth-leading cause of death in high-income countries and an epidemic in developing countries, affecting around 8 % of the total adult population in the world. Treatment at the advanced stage is difficult and challenging, making early detection a high priority in the cure of the disease. Our investigation reveals specific structural patterns important for the occurrence of the disease. In addition to the structural parameters, the spectral properties reveal the top contributing nodes from localized eigenvectors, which turn out to be significant for the occurrence of the disease. Our analysis is time-efficient and cost-effective, bringing a new horizon in the field of medicine by highlighting major pathways involved in the disease. The analysis provides a direction for the development of novel drugs and therapies in curing the disease by targeting specific interaction patterns instead of a single protein.

Clinical consequences of diet-induced dysbiosis.

PubMed

Chan, Yee Kwan; Estaki, Mehrbod; Gibson, Deanna L

2013-01-01

Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium. This is followed by a summary of clinical evidence of diet-induced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial profile will be reviewed. © 2013 S. Karger AG, Basel.

Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis.

PubMed

Black, G C; Perveen, R; Bonshek, R; Cahill, M; Clayton-Smith, J; Lloyd, I C; McLeod, D

1999-10-01

Coats' disease is characterized by abnormal retinal vascular development (so-called 'retinal telangiectasis') which results in massive intraretinal and subretinal lipid accumulation (exudative retinal detachment). The classical form of Coats' disease is almost invariably isolated, unilateral and seen in males. A female with a unilateral variant of Coats' disease gave birth to a son affected by Norrie disease. Both carried a missense mutation within the NDP gene on chromosome Xp11.2. Subsequently analysis of the retinas of nine enucleated eyes from males with Coats' disease demonstrated in one a somatic mutation in the NDP gene which was not present within non-retinal tissue. We suggest that Coats' telangiectasis is secondary to somatic mutation in the NDP gene which results in a deficiency of norrin (the protein product of the NDP gene) within the developing retina. This supports recent observations that the protein is critical for normal retinal vasculogenesis.

Interventions for age-related diseases: Shifting the paradigm.

PubMed

Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra; Lopez-Contreras, Andres; Henriques, Catarina M; Selman, Colin; Ferreiro, Elisabete; Gonos, Efstathios S; Trejo, José Luis; Misra, Juhi; Rasmussen, Lene Juel; Xapelli, Sara; Ellam, Timothy; Bellantuono, Ilaria

2016-12-01

Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management?

PubMed

Tsagalioti, Eftyhia; Trifonos, Christina; Morari, Aggeliki; Vadikolias, Konstantinos; Giaginis, Constantinos

2018-04-01

Neurodegenerative diseases constitute a major problem of public health that is associated with an increased risk of mortality and poor quality of life. Malnutrition is considered as a major problem that worsens the prognosis of patients suffering from neurodegenerative diseases. In this aspect, the present review is aimed to critically collect and summarize all the available existing clinical data regarding the clinical impact of nutritional assessment in neurodegenerative diseases, highlighting on the crucial role of nutritional status in disease progression and management. According to the currently available clinical data, the nutritional status of patients seems to play a very important role in the development and progression of neurodegenerative diseases. A correct nutritional evaluation of neurodegenerative disease patients and a right nutrition intervention is essential in monitoring their disease.

Epigenomics and allergic disease.

PubMed

Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

2013-12-01

Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment.

Early and late blight potential on Russet Burbank potato as affected by microclimate, cropping systems and irrigation management in North-eastern United States

USDA-ARS?s Scientific Manuscript database

Soil and irrigation management have been used to optimize crop production; however,their effects on microclimate, development, and potato diseases have not been adequately quantified. The effects of soil, crop, and water management on development of potato early blight and late blight were quantifie...

A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

USDA-ARS?s Scientific Manuscript database

We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

PubMed

Sun, Meng-Fei; Shen, Yan-Qin

2018-04-26

Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed. Copyright © 2018. Published by Elsevier B.V.

Norovirus Gastroenteritis Outbreak with a Secretor-independent Susceptibility Pattern, Sweden

PubMed Central

Nordgren, Johan; Kindberg, Elin; Lindgren, Per-Eric; Matussek, Andreas

2010-01-01

Norovirus (NoV) is recognized as the commonest cause of acute gastroenteritis among adults. Susceptibility to disease has been associated with histo-blood group antigens and secretor status; nonsecretors are almost completely resistant to disease. We report a foodborne outbreak of GI.3 NoV gastroenteritis that affected 33/83 (40%) persons. Symptomatic disease was as likely to develop in nonsecretors as in secretors (odds ratio [OR] 1.41, 95% confidence interval [CI] 0.46–4.36 vs. OR 0.71, 95% CI 0.23–2.18, p = 0.57). Moreover, no statistical difference in susceptibility was found between persons of different Lewis or ABO phenotypes. The capsid gene of the outbreak strain shares high amino acid homology with the Kashiwa645 GI.3 strain, previously shown to recognize nonsecretor saliva, as well as synthetic Lewis a. This norovirus outbreak affected persons regardless of secretor status or Lewis or ABO phenotypes. PMID:20031047

The poorest of the poor: a poverty appraisal of households affected by visceral leishmaniasis in Bihar, India.

PubMed

Boelaert, M; Meheus, F; Sanchez, A; Singh, S P; Vanlerberghe, V; Picado, A; Meessen, B; Sundar, S

2009-06-01

To provide data about wealth distribution in visceral leishmaniasis (VL)-affected communities compared to that of the general population of Bihar State, India. After extensive disease risk mapping, 16 clusters with high VL transmission were selected in Bihar. An exhaustive census of all households in the clusters was conducted and socio-economic household characteristics were documented by questionnaire. Data on the general Bihar population taken from the National Family Health Survey of India were used for comparison. An asset index was developed based on Principal Components Analysis and the distribution of this asset index for the VL communities was compared with that of the general population of Bihar. 83% of households in communities with high VL attack rates belonged to the two lowest quintiles of the Bihar wealth distribution. All socio-economic indicators showed significantly lower wealth for those households. Visceral leishmaniasis clearly affects the poorest of the poor in India. They are most vulnerable, as this vector-born disease is linked to poor housing and unhealthy habitats. The disease leads the affected households to more destitution because of its impact on household income and wealth. Support for the present VL elimination initiative is important in the fight against poverty.

Identification of inflammation sites in arthritic joints using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Paluchowski, Lukasz A.; Milanic, Matija; Bjorgan, Asgeir; Grandaunet, Berit; Dhainaut, Alvilde; Hoff, Mari; Randeberg, Lise L.

2014-03-01

Inflammatory arthritic diseases have prevalence between 2 and 3% and may lead to joint destruction and deformation resulting in a loss of function. Patient's quality of life is often severely affected as the disease attacks hands and finger joints. Pathology involved in arthritis includes angiogenesis, hyper-vascularization, hyper-metabolism and relative hypoxia. We have employed hyperspectral imaging to study the hemodynamics of affected- and non-affected joints and tissue. Two hyperspectral, push-broom cameras were used (VNIR-1600, SWIR-320i, Norsk Elektro Optikk AS, Norway). Optical spectra (400nm - 1700nm) of high spectral resolution were collected from 15 patients with visible symptoms of arthritic rheumatic diseases in at least one joint. The control group consisted of 10 healthy individuals. Concentrations of dominant chromophores were calculated based on analytical calculations of light transport in tissue. Image processing was used to analyze hyperspectral data and retrieve information, e.g. blood concentration and tissue oxygenation maps. The obtained results indicate that hyperspectral imaging can be used to quantify changes within affected joints and surrounding tissue. Further improvement of this method will have positive impact on diagnosis of arthritic joints at an early stage. Moreover it will enable development of fast, noninvasive and noncontact diagnostic tool of arthritic joints

Immunomodulation as a neuroprotective and therapeutic strategy for Parkinson's disease.

PubMed

Olson, Katherine E; Gendelman, Howard E

2016-02-01

While immune control is associated with nigrostriatal neuroprotection for Parkinson's disease, direct cause and effect relationships have not yet been realized, and modulating the immune system for therapeutic gain has been openly debated. Here, we review how innate and adaptive immunity affect disease pathobiology, and how each could be harnessed for treatment. The overarching idea is to employ immunopharmacologics as neuroprotective strategies for disease. The aim of the current work is to review disease-modifying treatments that are currently being developed as neuroprotective strategies for PD in experimental animal models and for human disease translation. The long-term goal of this research is to effectively harness the immune system to slow or prevent PD pathobiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Autophagy and oxidative stress in non-communicable diseases: A matter of the inflammatory state?

PubMed

Peña-Oyarzun, Daniel; Bravo-Sagua, Roberto; Diaz-Vega, Alexis; Aleman, Larissa; Chiong, Mario; Garcia, Lorena; Bambs, Claudia; Troncoso, Rodrigo; Cifuentes, Mariana; Morselli, Eugenia; Ferreccio, Catterina; Quest, Andrew F G; Criollo, Alfredo; Lavandero, Sergio

2018-05-30

Non-communicable diseases (NCDs), also known as chronic diseases, are long-lasting conditions that affect millions of people around the world. Different factors contribute to their genesis and progression; however they share common features, which are critical for the development of novel therapeutic strategies. A persistently altered inflammatory response is typically observed in many NCDs together with redox imbalance. Additionally, dysregulated proteostasis, mainly derived as a consequence of compromised autophagy, is a common feature of several chronic diseases. In this review, we discuss the crosstalk among inflammation, autophagy and oxidative stress, and how they participate in the progression of chronic diseases such as cancer, cardiovascular diseases, obesity and type II diabetes mellitus. Copyright © 2018 Elsevier Inc. All rights reserved.

A PCR-based diagnostic assay for the detection of Roseovarius crassostreae in Crassostrea virginica affected by juvenile oyster disease (JOD)

USGS Publications Warehouse

Maloy, A.P.; Barber, B.J.; Boettcher, K.J.

2005-01-01

We have developed a PCR-assay for the diagnosis of juvenile oyster disease (JOD) based on the detection of Roseovarius crassostreae directly from affected oysters. Species-specific primers are used to amplify the 16S-23S rDNA internal transcribed spacer (ITS) of R. crassostreae, and confirmation of product identity is accomplished by restriction enzyme analysis. No false positives were obtained with either closely related bacterial species or from other DNAs present in oyster samples. The assay has the potential to detect as few as 10 cells of R. crassostreae per oyster when samples are taken from the inner valve surfaces of the animal. Inclusion of material from soft body surfaces is not necessary, and may reduce sensitivity approximately 10-fold. In a JOD-affected population, a positive PCR result was obtained from all oysters from which these bacteria were subsequently cultured. The assay also detected the presence of R. crassostreae in 2 oysters from which no R. crassostreae isolates were recovered. No R. crassostreae was detected by either PCR or bacteriology in oysters from a population that was not exhibiting JOD-signs. This assay is expected to advance regional disease management efforts and provide valuable insights into the disease process and epizootiology of JOD. ?? Inter-Research 2005.

Unbiased approaches to biomarker discovery in neurodegenerative diseases

PubMed Central

Chen-Plotkin, Alice S.

2014-01-01

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and frontotemporal dementia have several important features in common. They are progressive, they affect a relatively inaccessible organ, and we have no disease-modifying therapies for them. For these brain-based diseases, current diagnosis and evaluation of disease severity rely almost entirely on clinical examination, which may only be a rough approximation of disease state. Thus, the development of biomarkers – objective, relatively easily measured and precise indicators of pathogenic processes – could improve patient care and accelerate therapeutic discovery. Yet existing, rigorously tested neurodegenerative disease biomarkers are few, and even fewer biomarkers have translated into clinical use. To find new biomarkers for these diseases, an unbiased, high-throughput screening approach may be needed. In this review, I will describe the potential utility of such an approach to biomarker discovery, using Parkinson’s disease as a case example. PMID:25442938

Effectiveness of knowledge translation tools addressing multiple high-burden chronic diseases affecting older adults: protocol for a systematic review alongside a realist review.

PubMed

Kastner, Monika; Perrier, Laure; Hamid, Jemila; Tricco, Andrea C; Cardoso, Roberta; Ivers, Noah M; Liu, Barbara; Marr, Sharon; Holroyd-Leduc, Jayna; Wong, Geoff; Graves, Lisa; Straus, Sharon E

2015-02-03

The burden of chronic disease is a global phenomenon, particularly among people aged 65 years and older. More than half of older adults have more than one chronic disease and their care is not optimal. Chronic disease management (CDM) tools have the potential to meet this challenge but they are primarily focused on a single disease, which fails to address the growing number of seniors with multiple chronic conditions. We will conduct a systematic review alongside a realist review to identify effective CDM tools that integrate one or more high-burden chronic diseases affecting older adults and to better understand for whom, under what circumstances, how and why they produce their outcomes. We will search MEDLINE, EMBASE, CINAHL, AgeLine and the Cochrane Library for experimental, quasi-experimental, observational and qualitative studies in any language investigating CDM tools that facilitate optimal disease management in one or more high-burden chronic diseases affecting adults aged ≥65 years. Study selection will involve calibration of reviewers to ensure reliability of screening and duplicate assessment of articles. Data abstraction and risk of bias assessment will also be performed independently. Analysis will include descriptive summaries of study and appraisal characteristics, effectiveness of each CDM tool (meta-analysis if appropriate); and a realist programme theory will be developed and refined to explain the outcome patterns within the included studies. Ethics approval is not required for this study. We anticipate that our findings, pertaining to gaps in care across high-burden chronic diseases affecting seniors and highlighting specific areas that may require more research, will be of interest to a wide range of knowledge users and stakeholders. We will publish and present our findings widely, and also plan more active dissemination strategies such as workshops with our key stakeholders. Our protocol is registered with PROSPERO (registration number CRD42014014489). 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.

Experimental Actinobacillus pleuropneumoniae challenge in swine: Comparison of computed tomographic and radiographic findings during disease

PubMed Central

2012-01-01

Background In pigs, diseases of the respiratory tract like pleuropneumonia due to Actinobacillus pleuropneumoniae (App) infection have led to high economic losses for decades. Further research on disease pathogenesis, pathogen-host-interactions and new prophylactic and therapeutic approaches are needed. In most studies, a large number of experimental animals are required to assess lung alterations at different stages of the disease. In order to reduce the required number of animals but nevertheless gather information on the nature and extent of lung alterations in living pigs, a computed tomographic scoring system for quantifying gross pathological findings was developed. In this study, five healthy pigs served as control animals while 24 pigs were infected with App, the causative agent of pleuropneumonia in pigs, in an established model for respiratory tract disease. Results Computed tomographic (CT) findings during the course of App challenge were verified by radiological imaging, clinical, serological, gross pathology and histological examinations. Findings from clinical examinations and both CT and radiological imaging, were recorded on day 7 and day 21 after challenge. Clinical signs after experimental App challenge were indicative of acute to chronic disease. Lung CT findings of infected pigs comprised ground-glass opacities and consolidation. On day 7 and 21 the clinical scores significantly correlated with the scores of both imaging techniques. At day 21, significant correlations were found between clinical scores, CT scores and lung lesion scores. In 19 out of 22 challenged pigs the determined disease grades (not affected, slightly affected, moderately affected, severely affected) from CT and gross pathological examination were in accordance. Disease classification by radiography and gross pathology agreed in 11 out of 24 pigs. Conclusions High-resolution, high-contrast CT examination with no overlapping of organs is superior to radiography in the assessment of pneumonic lung lesions after App challenge. The new CT scoring system allows for quantification of gross pathological lung alterations in living pigs. However, computed tomographic findings are not informative of the etiology of respiratory disease. PMID:22546414

Barth Syndrome (BTHS)

MedlinePlus

... mitochondrial diseases through a better understanding of mitochondrial biology. Because people affected by mitochondrial disease often have ... mitochondrial diseases through a better understanding of mitochondrial biology. Because people affected by mitochondrial disease often have ...

Building a foundation for 'One Health': an education strategy for enhancing and sustaining national and regional capacity in endemic and emerging zoonotic disease management.

PubMed

Vink, W D; McKenzie, Joanna S; Cogger, Naomi; Borman, Barry; Muellner, Petra

2013-01-01

The rapid global spread of diseases such as SARS, H5N1, and H1N1 influenza has emphasized the pressing need for trans-disciplinary collaboration and cross-border action, and has also exposed a serious deficit of capacity and coordination in dealing effectively with emerging disease threats. The need for capacity development is particularly acute in the developing world, which is the least well-equipped to respond adequately. Such capacity development can be achieved through education and the implementation of applied 'One Health' activities. This chapter describes the establishment of a 'One Health' capacity development program in South Asia, consisting of two phases. The first phase provides Masters level training for public health doctors and veterinarians, with a focus on epidemiology, and disease control. The second phase reinforces the postgraduate training by establishing a sustainable framework for the implementation of collaborative 'One Health' activities such as the development of multidisciplinary professional networks, implementation of applied zoonotic disease investigation projects, and support for continuing professional development. The objectives are to provide individual skills required to strengthen capacity; to develop an appreciation of the cross-cutting issues which affect human and animal health, set within an institutional context; and to facilitate the development of regional professional networks which will be instrumental in implementing 'One Health' activities.

[RARE DISEASES DTC: DIAGNOSIS, TREATMENT AND CARE].

PubMed

Mendlovic, Joseph; Barash, Hila; Yardeni, Hadar; Banet-Levi, Yonit; Yonath, Hagith; Raas-Rothschild, Annick

2016-04-01

Rare diseases are chronic, progressive genetic disorders, which affect around 6-8% of the general population, mainly children. Therefore, in Israel approximately 500,000 people are probably affected by a rare disease. In this article, we review some of the issues pertaining to rare diseases, such as the need for accurate diagnosis which is necessary not only for specific care and treatment but also for informed family planning. In addition, we review the impact of the activities of patients' organizations on the awareness of rare diseases and their involvement in the creation of the Orphan Drug Act, which was the leading point on the way to drug development worldwide. During the last few years networks for reaching leading specialists' opinions on the way to proper diagnosis were created. Thereafter, the next generation genetic technologies, such as exome sequencing, have been a revolution in terms of options and hope for patients with rare undiagnosed diseases. Patients with rare diseases and their families are a challenge to the health care system, not only in terms of diagnosis and therapy, but also in terms of special needs. In addition, deciphering molecular pathways of rare diseases might be the key for understanding molecular events involved in common disorders. We emphasize the duty to ensure appropriate capacity and equal access to follow-up and clinical management of patients with rare diseases in Israel.

Early-life influences on obesity: from preconception to adolescence

PubMed Central

Wahlqvist, Mark L.; Krawetz, Stephen A.; Rizzo, Nico S.; Dominguez-Bello, Maria Gloria; Szymanski, Linda M.; Barkin, Shari; Yatkine, Ann; Waterland, Robert A.; Mennella, Julie A.; Desai, Mina; Ross, Michael G.; Krebs, Nancy F.; Young, Bridget E.; Wardle, Jane; Wrann, Christiane D.; Kral, John G.

2015-01-01

The double burden of under- and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity and diabetes rates have almost doubled worldwide since 1980 and, in 2011, more than 40 million children less than 5 years of age were overweight. Ecologic factors, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life—in particular, diabesity and its comorbidities. PMID:26037603

Xenopus: An Emerging Model for Studying Congenital Heart Disease

PubMed Central

Kaltenbrun, Erin; Tandon, Panna; Amin, Nirav M.; Waldron, Lauren; Showell, Chris; Conlon, Frank L.

2011-01-01

Congenital heart defects affect nearly 1% of all newborns and are a significant cause of infant death. Clinical studies have identified a number of congenital heart syndromes associated with mutations in genes that are involved in the complex process of cardiogenesis. The African clawed frog, Xenopus, has been instrumental in studies of vertebrate heart development and provides a valuable tool to investigate the molecular mechanisms underlying human congenital heart diseases. In this review, we discuss the methodologies that make Xenopus an ideal model system to investigate heart development and disease. We also outline congenital heart conditions linked to cardiac genes that have been well-studied in Xenopus and describe some emerging technologies that will further aid in the study of these complex syndromes. PMID:21538812

Conceptualization, development and validation of T-QoL© (Teenagers' Quality of Life): a patient-focused measure to assess quality of life of adolescents with skin diseases.

PubMed

Basra, M K A; Salek, M S; Fenech, D; Finlay, A Y

2018-01-01

Skin disease can affect the quality of life (QoL) of teenagers in a variety of different ways, some being unique to this age group. To develop and validate a dermatology-specific QoL instrument for adolescents with skin diseases. Qualitative semistructured interviews were conducted with adolescents with skin disease to gain in-depth understanding of how skin diseases affect their QoL. A prototype instrument based on the themes identified from content analysis of interviews was tested in several stages, using classical test theory and item response theory models to develop this new tool and conduct its psychometric evaluation. Thirty-three QoL issues were identified from semistructured interviews with 50 adolescents. A questionnaire based on items derived from content analysis of interviews was subjected to Rasch analysis: factor analysis identified three domains, therefore not supporting the validity of T-QoL as a unidimensional measure. Psychometric evaluation of the final 18-item questionnaire was carried out in a cohort of 203 adolescents. Convergent validity was demonstrated by significant correlation with Skindex-Teen and Dermatology Life Quality Index (DLQI) or Children's DLQI. The T-QoL showed excellent internal consistency reliability: Cronbach's α = 0·89 for total scale score and 0·85, 0·60 and 0·74, respectively, for domains 1, 2 and 3. Test-retest reliability was high in stable volunteers. T-QoL showed sensitivity to change in two subgroups of patients who indicated change in their self-assessed disease severity. Built on rich qualitative data from patients, the T-QoL is a simple and valid tool to quantify the impact of skin disease on adolescents' QoL; it could be used as an outcome measure in both clinical practice and clinical research. © 2017 British Association of Dermatologists.

SeqSIMLA2_exact: simulate multiple disease sites in large pedigrees with given disease status for diseases with low prevalence.

PubMed

Yao, Po-Ju; Chung, Ren-Hua

2016-02-15

It is difficult for current simulation tools to simulate sequence data in a pre-specified pedigree structure and pre-specified affection status. Previously, we developed a flexible tool, SeqSIMLA2, for simulating sequence data in either unrelated case-control or family samples with different disease and quantitative trait models. Here we extended the tool to efficiently simulate sequences with multiple disease sites in large pedigrees with a given disease status for each pedigree member, assuming that the disease prevalence is low. SeqSIMLA2_exact is implemented with C++ and is available at http://seqsimla.sourceforge.net. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Conflict and diarrheal and related diseases: A global analysis

PubMed Central

Kerridge, Bradley T.; Khan, Maria R.; Rehm, Jürgen; Sapkota, Amir

2015-01-01

The purpose of this study was to determine the association between deaths owing to terrorism, civil war and one-sided violence from 1994–2000 and disability-adjusted life years (DALYs) attributable to diarrheal and related diseases, schistosomiasis, trachoma and the nematode infections (DSTN diseases) in 2002 among World Health Organization Member States. Deaths resulting from terrorism, civil war and one-sided violence were significantly related to DSTN DALYs across the majority of sex–age subgroups of the populace, after controlling for baseline levels of improved water/sanitation and a variety of economic measures: overall, a 1.0% increase in deaths owing to terrorism and related violence was associated with an increase of 0.16% in DALYs lost to DSTN diseases. Associations were greatest among 0-to-4-year olds. The results of the present study suggest that DSTN disease control efforts should target conflict-affected populations with particular attention to young children who suffer disproportionately from DSTN diseases in these settings. In view of the evidence that terrorism and related violence may influence DSTN DALYs in the longer term, control strategies should move beyond immediate responses to decrease the incidence and severity of DSTN diseases to seek solutions through bolstering health systems infrastructure development among conflict-affected populations. PMID:24206798

Conflict and diarrheal and related diseases: a global analysis.

PubMed

Kerridge, Bradley T; Khan, Maria R; Rehm, Jürgen; Sapkota, Amir

2013-12-01

The purpose of this study was to determine the association between deaths owing to terrorism, civil war and one-sided violence from 1994-2000 and disability-adjusted life years (DALYs) attributable to diarrheal and related diseases, schistosomiasis, trachoma and the nematode infections (DSTN diseases) in 2002 among World Health Organization Member States. Deaths resulting from terrorism, civil war and one-sided violence were significantly related to DSTN DALYs across the majority of sex-age subgroups of the populace, after controlling for baseline levels of improved water/sanitation and a variety of economic measures: overall, a 1.0% increase in deaths owing to terrorism and related violence was associated with an increase of 0.16% in DALYs lost to DSTN diseases. Associations were greatest among 0-to-4-year olds. The results of the present study suggest that DSTN disease control efforts should target conflict-affected populations with particular attention to young children who suffer disproportionately from DSTN diseases in these settings. In view of the evidence that terrorism and related violence may influence DSTN DALYs in the longer term, control strategies should move beyond immediate responses to decrease the incidence and severity of DSTN diseases to seek solutions through bolstering health systems infrastructure development among conflict-affected populations. Copyright © 2013. Published by Elsevier Ltd.

Reporting diet-related health issues through newspapers: portrayal of cardiovascular disease and Type 2 diabetes.

PubMed

Hellyer, Nicole Elizabeth; Haddock-Fraser, Janet

2011-02-01

This study identifies (i) the extent to which newsprint media communicate to their readers the lifestyle factors associated with the development of cardiovascular disease and Type 2 diabetes and (ii) newspaper portrayal of social determinants affecting onset of disease. A content analysis of five leading UK national newspapers and their Sunday equivalents was conducted over a 3-month period between January and March 2008. This study shows that cardiovascular disease had much higher press interest than Type 2 diabetes. 'Middle-market' and 'Quality' papers had higher levels of reporting than the 'Popular' press, but the patterns were more complex when the comprehensiveness of reporting was measured within each article. Social determinants affecting disease onset were poorly reported by newspapers, supporting similar research conducted in other countries. This research identifies that there is potential for newspapers to improve their reporting of lifestyle diseases, by including individual and social determinants of disease onset. Lower social classes who read the popular press receive the lowest frequency of reporting and could benefit most from this information. While the research identifies that newspapers are missing the potential to actively communicate and reinforce government health policy, it recognises that the commercial context of the print media may counter such behaviour.

Opposing effects of allogrooming on disease transmission in ant societies

PubMed Central

Theis, Fabian J.; Ugelvig, Line V.; Marr, Carsten; Cremer, Sylvia

2015-01-01

To prevent epidemics, insect societies have evolved collective disease defences that are highly effective at curing exposed individuals and limiting disease transmission to healthy group members. Grooming is an important sanitary behaviour—either performed towards oneself (self-grooming) or towards others (allogrooming)—to remove infectious agents from the body surface of exposed individuals, but at the risk of disease contraction by the groomer. We use garden ants (Lasius neglectus) and the fungal pathogen Metarhizium as a model system to study how pathogen presence affects self-grooming and allogrooming between exposed and healthy individuals. We develop an epidemiological SIS model to explore how experimentally observed grooming patterns affect disease spread within the colony, thereby providing a direct link between the expression and direction of sanitary behaviours, and their effects on colony-level epidemiology. We find that fungus-exposed ants increase self-grooming, while simultaneously decreasing allogrooming. This behavioural modulation seems universally adaptive and is predicted to contain disease spread in a great variety of host–pathogen systems. In contrast, allogrooming directed towards pathogen-exposed individuals might both increase and decrease disease risk. Our model reveals that the effect of allogrooming depends on the balance between pathogen infectiousness and efficiency of social host defences, which are likely to vary across host–pathogen systems. PMID:25870394

Development of Group A streptococcal vaccines: an unmet global health need.

PubMed

Sheel, Meru; Moreland, Nicole J; Fraser, John D; Carapetis, Jonathan

2016-01-01

Group A Streptococcus (GAS) infections are a significant global cause of morbidity and mortality. GAS diseases disproportionally affect those living in conditions characterized by poverty and social injustice, in both developing countries and in marginalized populations of industrialized nations. In Australia and New Zealand, GAS-associated Acute Rheumatic Fever (ARF) is a major cause of health inequality disproportionally affecting indigenous children. Recognition of these inequalities by the governments of Australia and New Zealand has resulted in the formation of a Trans-Tasman Coalition to Advance New Vaccines for group A Streptococcus (CANVAS). This review provides an update on the current status of GAS vaccine development, and describes global efforts by CANVAS and others to accelerate the development of GAS vaccines.

Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.

PubMed

Targher, Giovanni; Lonardo, Amedeo; Byrne, Christopher D

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.

NIEHS/EPA CEHCs: Perinatal Exposures, Epigenetics, Child Obesity and Sexual Maturation - University of Michigan

EPA Pesticide Factsheets

Scientists are seeking to understand how early exposure to chemicals such as lead, bisphenol A (BPA), and phthalates affects growth and sexual development during childhood and adolescence and the risk for diseases in adulthood.

Dysphagia after Stroke: an Overview

PubMed Central

González-Fernández, Marlís; Ottenstein, Lauren; Atanelov, Levan; Christian, Asare B.

2013-01-01

Dysphagia affects the vast majority of acute stroke patients. Although it improves within 2 weeks for most, some face longstanding swallowing problems that place them at risk for pneumonia, malnutrition, dehydration, and significantly affect quality of life. This paper discusses the scope, the disease burden, and the tools available for screening and formal evaluation of dysphagia. The most common and recently developed treatment interventions that might be useful in the treatment of this population are discussed. PMID:24977109

Humans as holobionts: implications for prevention and therapy.

PubMed

van de Guchte, Maarten; Blottière, Hervé M; Doré, Joël

2018-05-01

The human gut microbiota is increasingly recognized for its important or even decisive role in health. As it becomes clear that microbiota and host mutually affect and depend on each other in an intimate relationship, a holistic view of the gut microbiota-host association imposes itself. Ideally, a stable state of equilibrium, homeostasis, is maintained and serves health, but signs are that perturbation of this equilibrium beyond the limits of resilience can propel the system into an alternative stable state, a pre-disease state, more susceptible to the development of chronic diseases. The microbiota-host equilibrium of a large and growing proportion of individuals in Western society may represent such a pre-disease state and explain the explosive development of chronic diseases such as inflammatory bowel disease, obesity, and other inflammatory diseases. These diseases themselves represent other alternative stable states again and are therefore hard to cure. The holistic view of the microbiota-host association where feedback loops between microbiota and host are thought to maintain the system in a stable state-be it a healthy, pre-disease, or disease state-implies that integrated approaches, addressing host processes and microbiota, should be used to treat or prevent (pre-)disease.

Impulse control disorders in Parkinson's disease: the role of personality and cognitive status.

PubMed

Poletti, Michele; Bonuccelli, Ubaldo

2012-11-01

This study reviews empirical findings on two debated issues related to the phenomenon of impulse control disorders (ICD) in patients with Parkinson's disease (PD) treated with dopamine agonists: the role of "premorbid" or "baseline" personality traits and the role of cognitive status. A review of both these issues may help clinicians to understand why only some PD patients, when treated with dopamine agonists, develop an ICD: besides the treatment, which other neuropsychiatric characteristics represent a risk factor to develop an ICD? A literature review was performed on studies of ICD in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in January 2011. In the general population, impulsivity, depression and difficulties with executive functions, especially of inhibitory control, are factors associated with ICD development. As regards cognitive functions, PD patients present executive difficulties, and patients with ICD present more difficulties in comparison to patients without ICD. As regards personality characteristics, PD patients present a trait of negative affect, which could predispose them to affective disorders and could represent an affective risk factor for the development of ICD; as regards impulsivity, preliminary findings support the hypothesis that premorbid "baseline" levels may moderate the decrease of impulsivity because of the progressive dopaminergic deficit in PD patients and therefore also moderate the development of ICD. Longitudinal psychometric and cognitive studies, following PD patients since the clinical diagnosis and during dopaminergic treatment, are needed to confirm the role of personality traits and cognitive status on ICD development in this clinical population.

Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

PubMed Central

Fonseca, Wendy; Lukacs, Nicholas W.; Ptaschinski, Catherine

2018-01-01

Respiratory syncytial virus (RSV) is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection. PMID:29515570

Early Childhood Caries: A Review.

PubMed

Alazmah, Abdulfatah

2017-08-01

To review and update the current knowledge about early childhood caries (ECC) and its etiology, prevalence, risk factors, management, and preventive strategies. Early childhood caries is a disease affecting significantly both well-developed and industrial nations. The ECC can significantly affect the child's quality of life, as it may lead to infection, swelling, pain, and other symptoms. The ECC affects children after eruption of primary teeth until age of around 5 years. The ECC affects all parts of the tooth including the smooth surface. Upper anterior teeth and primary molars are usually affected. The lower anterior teeth are less likely affected. The risk factors for ECC are diet, bacteria, and host susceptibility. The additional factors, such as presence of enamel defect and the feeding practices also contribute to the initiation and progress of ECC. Dentists must focus on utilizing existing techniques to distinguish indications of right on time and propelled caries and give guidance on the best way to counteract and control caries in children. Approaches should be directed to preventive caries control strategies among children. Preventing and controlling the development of ECC among children is important to maintain effective eating, speech development, and formation of a positive self-image.

Does terrestrial epidemiology apply to marine systems?

USGS Publications Warehouse

McCallum, Hamish I.; Kuris, Armand M.; Harvell, C. Drew; Lafferty, Kevin D.; Smith, Garriet W.; Porter, James

2004-01-01

Most of epidemiological theory has been developed for terrestrial systems, but the significance of disease in the ocean is now being recognized. However, the extent to which terrestrial epidemiology can be directly transferred to marine systems is uncertain. Many broad types of disease-causing organism occur both on land and in the sea, and it is clear that some emergent disease problems in marine environments are caused by pathogens moving from terrestrial to marine systems. However, marine systems are qualitatively different from terrestrial environments, and these differences affect the application of modelling and management approaches that have been developed for terrestrial systems. Phyla and body plans are more diverse in marine environments and marine organisms have different life histories and probably different disease transmission modes than many of their terrestrial counterparts. Marine populations are typically more open than terrestrial ones, with the potential for long-distance dispersal of larvae. Potentially, this might enable unusually rapid propagation of epidemics in marine systems, and there are several examples of this. Taken together, these differences will require the development of new approaches to modelling and control of infectious disease in the ocean.

Using microRNA as an alternative treatment for hyperlipidemia and cardiovascular disease: cardio-miRs in the pipeline.

PubMed

Hennessy, Elizabeth J; Moore, Kathryn J

2013-09-01

It is now appreciated that over 90% of the human genome is comprised of noncoding RNAs that have the ability to affect other components of the genome and regulate gene expression. This has galvanized the development of RNA-based therapeutics for a myriad of diseases, including cancer, inflammatory conditions, and cardiovascular disease. Several classes of RNA therapeutics are currently under clinical development, including antisense oligonucleotides, small interfering RNA, and microRNA mimetics and inhibitors. The field of antisense technology saw a huge leap forward with the recent Food and Drug Administration approval of the first antisense therapy, directed against apolipoprotein B, for the treatment of familial hypercholesterolemia. In addition, recent progress in the development of approaches to inhibit microRNAs has helped to illuminate their roles in repressing gene networks and also revealed their potential as therapeutic targets. In this review, these exciting opportunities in the field of drug discovery, with a focus on emerging therapeutics in the field of cardiovascular disease, are summarized.

Development of the Korean Academy of Medical Sciences Guideline for Rating the Impairment in the Brain Injured and Brain Diseased Persons with Motor Dysfunction

PubMed Central

Baik, Jong Sam; Jang, Seong Ho; Park, Dong Sik

2009-01-01

To develop an objective and scientific method to evaluate the brain injured and brain diseased persons with motor dysfunction, American Medical Association's Guides to the Evaluation of Permanent Impairment was used as an exemplar. After the motor dysfunction due to brain injury or brain disease was confirmed, active range of motion and muscle strength of affected extremities were measured. Also, the total function of extremities was evaluated through the assessment of activities of daily living, fine coordination of hand, balance and gait. Then, the total score of manual muscle test and functional assessment of impaired upper and lower extremity were added, respectively. Spasticity of upper and lower extremity was used as minus factors. Patients with movement disorder such as Parkinson's disease were assessed based on the degree of dysfunction in response to medication. We develop a new rating system based on the concept of total score. PMID:19503680

Parasitic, fungal and prion zoonoses: an expanding universe of candidates for human disease.

PubMed

Akritidis, N

2011-03-01

Zoonotic infections have emerged as a burden for millions of people in recent years, owing to re-emerging or novel pathogens often causing outbreaks in the developing world in the presence of inadequate public health infrastructure. Among zoonotic infections, those caused by parasitic pathogens are the ones that affect millions of humans worldwide, who are also at risk of developing chronic disease. The present review discusses the global effect of protozoan pathogens such as Leishmania sp., Trypanosoma sp., and Toxoplasma sp., as well as helminthic pathogens such as Echinococcus sp., Fasciola sp., and Trichinella sp. The zoonotic aspects of agents that are not essentially zoonotic are also discussed. The review further focuses on the zoonotic dynamics of fungal pathogens and prion diseases as observed in recent years, in an evolving environment in which novel patient target groups have developed for agents that were previously considered to be obscure or of minimal significance. © 2011 The Author. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Molecular Regulation of Endothelial Cells by NF-1

DTIC Science & Technology

2012-07-01

disease. Patients with NF1 disease make up a significant portion of all those patients presenting with renal artery stenosis and early-onset cerebral...affected individuals can be quite variable. Perhaps the most common is renal artery stenosis and hypertension. The renal artery is also a site of...aneurysms and aortic coarctation (Zochodne 1984). Recently a model was developed in the Epstein lab where NF1 was knocked out specifically in the smooth

Rabies: risk, prognosis and prevention.

PubMed

Driver, Carolyn

While the UK was declared free from rabies over 100 years ago, the disease remains a significant cause of death in many other countries around the world. It is hoped that eradication programmes in affected countries will succeed in the long term but, until then, prompt and thorough treatment can prevent people who have potentially been in contact with the rabies virus from developing this infection. This article provides a review of the disease and its prevention.

The pre-morbid personality of patients with Parkinson's disease.

PubMed Central

Todes, C J; Lees, A J

1985-01-01

A review of the extensive descriptive literature suggests that many Parkinsonian patients exhibit an emotional and attitudinal inflexibility, a lack of affect and a predisposition to depressive illness, which may antecede the development of motor abnormalities by several decades. Introspective, over-controlled, anhedonic personality traits together with suppressed aggresivity are frequently found. It is unclear whether these behavioural patterns are relevant aetiological factors or prodromal symptoms of the disease. PMID:3884742

Current understanding of the relationship between periodontal and systemic diseases

PubMed Central

Mawardi, Hani H.; Elbadawi, Lena S.; Sonis, Stephen T.

2015-01-01

Periodontal disease (PD) is among the most common infectious diseases affecting humans. While the burden of periodontal disease on oral health has been extensively investigated, a possible specific relationship between the disease and systemic health is a relatively new area of interest. More recently it has been suggested that PD has an etiological role in the development of atherosclerotic cardiovascular disease, diabetes mellitus, and preterm low-birth weight, among others. In this review, we critically evaluate the current knowledge on the relation between PD and systemic diseases overall, and specifically with cardiovascular diseases. The best available evidence today suggests that the infection and inflammatory reaction associated with PD may contribute toward systemic disease. It is critical that dentists and physicians are well informed of the potential general health impact of periodontal disease so that they are in a position to knowledgeably counsel patients. PMID:25719577

Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature.

PubMed

Luhmann, Ulrich F O; Lin, Jihong; Acar, Niyazi; Lammel, Stefanie; Feil, Silke; Grimm, Christian; Seeliger, Mathias W; Hammes, Hans-Peter; Berger, Wolfgang

2005-09-01

To characterize developmental defects and the time course of Norrie disease in retinal and hyaloid vasculature during retinal development and to identify underlying molecular angiogenic pathways that may be affected in Norrie disease, exudative vitreoretinopathy, retinopathy of prematurity, and Coats' disease. Norrie disease pseudoglioma homologue (Ndph)-knockout mice were studied during retinal development at early postnatal (p) stages (p5, p10, p15, and p21). Histologic techniques, quantitative RT-PCR, ELISA, and Western blot analyses provided molecular data, and scanning laser ophthalmoscopy (SLO) angiography and electroretinography (ERG) were used to obtain in vivo data. The data showed that regression of the hyaloid vasculature of Ndph-knockout mice occurred but was drastically delayed. The development of the superficial retinal vasculature was strongly delayed, whereas the deep retinal vasculature did not form because of the blockage of vessel outgrowth into the deep retinal layers. Subsequently, microaneurysm-like lesions formed. Several angiogenic factors were differentially transcribed during retinal development. Increased levels of hypoxia inducible factor-1alpha (HIF1alpha) and VEGFA, as well as a characteristic ERG pattern, confirmed hypoxic conditions in the inner retina of the Ndph-knockout mouse. These data provide evidence for a crucial role of Norrin in hyaloid vessel regression and in sprouting angiogenesis during retinal vascular development, especially in the development of the deep retinal capillary networks. They also suggest an early and a late phase of Norrie disease and may provide an explanation for similar phenotypic features of allelic retinal diseases in mice and patients as secondary consequences of pathologic hypoxia.

How Ebola impacts social dynamics in gorillas: a multistate modelling approach.

PubMed

Genton, Céline; Pierre, Amandine; Cristescu, Romane; Lévréro, Florence; Gatti, Sylvain; Pierre, Jean-Sébastien; Ménard, Nelly; Le Gouar, Pascaline

2015-01-01

Emerging infectious diseases can induce rapid changes in population dynamics and threaten population persistence. In socially structured populations, the transfers of individuals between social units, for example, from breeding groups to non-breeding groups, shape population dynamics. We suggest that diseases may affect these crucial transfers. We aimed to determine how disturbance by an emerging disease affects demographic rates of gorillas, especially transfer rates within populations and immigration rates into populations. We compared social dynamics and key demographic parameters in a gorilla population affected by Ebola using a long-term observation data set including pre-, during and post-outbreak periods. We also studied a population of undetermined epidemiological status in order to assess whether this population was affected by the disease. We developed a multistate model that can handle transition between social units while optimizing the number of states. During the Ebola outbreak, social dynamics displayed increased transfers from a breeding to a non-breeding status for both males and females. Six years after the outbreak, demographic and most of social dynamics parameters had returned to their initial rates, suggesting a certain resilience in the response to disruption. The formation of breeding groups increased just after Ebola, indicating that environmental conditions were still attractive. However, population recovery was likely delayed because compensatory immigration was probably impeded by the potential impact of Ebola in the surrounding areas. The population of undetermined epidemiological status behaved similarly to the other population before Ebola. Our results highlight the need to integrate social dynamics in host-population demographic models to better understand the role of social structure in the sensitivity and the response to disease disturbances. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

GGDonto ontology as a knowledge-base for genetic diseases and disorders of glycan metabolism and their causative genes.

PubMed

Solovieva, Elena; Shikanai, Toshihide; Fujita, Noriaki; Narimatsu, Hisashi

2018-04-18

Inherited mutations in glyco-related genes can affect the biosynthesis and degradation of glycans and result in severe genetic diseases and disorders. The Glyco-Disease Genes Database (GDGDB), which provides information about these diseases and disorders as well as their causative genes, has been developed by the Research Center for Medical Glycoscience (RCMG) and released in April 2010. GDGDB currently provides information on about 80 genetic diseases and disorders caused by single-gene mutations in glyco-related genes. Many biomedical resources provide information about genetic disorders and genes involved in their pathogenesis, but resources focused on genetic disorders known to be related to glycan metabolism are lacking. With the aim of providing more comprehensive knowledge on genetic diseases and disorders of glycan biosynthesis and degradation, we enriched the content of the GDGDB database and improved the methods for data representation. We developed the Genetic Glyco-Diseases Ontology (GGDonto) and a RDF/SPARQL-based user interface using Semantic Web technologies. In particular, we represented the GGDonto content using Semantic Web languages, such as RDF, RDFS, SKOS, and OWL, and created an interactive user interface based on SPARQL queries. This user interface provides features to browse the hierarchy of the ontology, view detailed information on diseases and related genes, and find relevant background information. Moreover, it provides the ability to filter and search information by faceted and keyword searches. Focused on the molecular etiology, pathogenesis, and clinical manifestations of genetic diseases and disorders of glycan metabolism and developed as a knowledge-base for this scientific field, GGDonto provides comprehensive information on various topics, including links to aid the integration with other scientific resources. The availability and accessibility of this knowledge will help users better understand how genetic defects impact the metabolism of glycans as well as how this impaired metabolism affects various biological functions and human health. In this way, GGDonto will be useful in fields related to glycoscience, including cell biology, biotechnology, and biomedical, and pharmaceutical research.

Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: A Systematic Review

PubMed Central

Alvarez, Carolina; Gotuzzo, Eduardo; Vandamme, Anne-Mieke; Verdonck, Kristien

2016-01-01

Human T-lymphotropic virus 1 (HTLV-1) is a retrovirus that produces a persistent infection. Two transmission routes (from mother to child and via sexual intercourse) favor familial clustering of HTLV-1. It is yet unknown why most HTLV-1 carriers remain asymptomatic while about 10% of them develop complications. HTLV-1 associated diseases were originally described as sporadic entities, but familial presentations have been reported. To explore what is known about family aggregation of HTLV-1-associated diseases we undertook a systematic review. We aimed at answering whether, when, and where family aggregation of HTLV-1-associated diseases was reported, which relatives were affected and which hypotheses were proposed to explain aggregation. We searched MEDLINE, abstract books of HTLV conferences and reference lists of selected papers. Search terms used referred to HTLV-1 infection, and HTLV-1-associated diseases, and family studies. HTLV-1-associated diseases considered are adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-1-associated uveitis, and infective dermatitis. Seventy-four records reported HTLV-1-associated diseases in more than one member of the same family and were included. Most reports came from HTLV-1-endemic countries, mainly Japan (n = 30) and Brazil (n = 10). These reports described a total of 270 families in which more than one relative had HTLV-1-associated diseases. In most families, different family members suffered from the same disease (n = 223). The diseases most frequently reported were ATLL (115 families) and HAM/TSP (102 families). Most families (n = 144) included two to four affected individuals. The proportion of ATLL patients with family history of ATLL ranged from 2 to 26%. The proportion of HAM/TSP patients with family history of HAM/TSP ranged from 1 to 48%. The predominant cluster types for ATLL were clusters of siblings and parent-child pairs and for HAM/TSP, an affected parent with one or more affected children. The evidence in the literature, although weak, does suggest that HTLV-1-associated diseases sometimes cluster in families. Whether familial transmission of HTLV-1 is the only determining factor, or whether other factors are also involved, needs further research. PMID:27840624

Gaucher disease: the role of the specialist on metabolic bone diseases

PubMed Central

Masi, Laura; Brandi, Maria Luisa

2015-01-01

Summary According to European legislation, a disease can be considered rare or “orphan” when it affects less than 1 subject of 2000 (1). Often these diseases affecting the pediatric age, are complex diseases and chronically debilitating and for this motive need the intervention of multidisciplinary skills specific. Among the rare disease as affecting the skeleton more than 400 are characterized by dysplastic changes of the skeleton (2). Alongside the disorders affecting the skeleton primitively, many systemic diseases can have a bone involvement. Among these, the Gaucher disease (GD), an heterogeneous lysosomal storage determined by hereditary enzyme deficiency of β-glucosidase. Patients with this disease have skeletal disorders of varying severity (Erlenmeyer flask deformity, lytic lesions and osteonecrosis, pathological fractures) that affects both the bone marrow, both mineralized bone with progressive damage of the tissue. The bone disease is the most debilitating of GD and can have a significant impact on the quality of life of patients. Thorough evaluations by monitoring biochemical markers of bone turnover and instrumental, with a quantitative and qualitative evaluation of the bone, are of fundamental importance to intervene early so they can prevent complications irreversible. PMID:26604943

Conventional Therapy and Promising Plant-Derived Compounds Against Trypanosomatid Parasites

PubMed Central

Alviano, Daniela Sales; Barreto, Anna Léa Silva; Dias, Felipe de Almeida; Rodrigues, Igor de Almeida; Rosa, Maria do Socorro dos Santos; Alviano, Celuta Sales; Soares, Rosangela Maria de Araújo

2012-01-01

Leishmaniasis and trypanosomiasis are two neglected and potentially lethal diseases that affect mostly the poor and marginal populations of developing countries around the world and consequently have an important impact on public health. Clinical manifestations such as cutaneous, mucocutaneous, and visceral disorders are the most frequent forms of leishmaniasis, a group of diseases caused by several Leishmania spp. American trypanosomiasis, or Chagas disease, is caused by Trypanosoma cruzi, a parasite that causes progressive damage to different organs, particularly the heart, esophagus, and lower intestine. African trypanosomiasis, or sleeping sickness, is caused by Trypanosoma brucei and is characterized by first presenting as an acute form that affects blood clotting and then becoming a chronic meningoencephalitis. The limited number, low efficacy, and side effects of conventional anti-leishmania and anti-trypanosomal drugs and the resistance developed by parasites are the major factors responsible for the growth in mortality rates. Recent research focused on plants has shown an ingenious way to obtain a solid and potentially rich source of drug candidates against various infectious diseases. Bioactive phytocompounds present in the crude extracts and essential oils of medicinal plants are components of an important strategy linked to the discovery of new medicines. These compounds have proven to be a good source of therapeutic agents for the treatment of leishmaniasis and trypanosomiasis. This work highlights some chemotherapeutic agents while emphasizing the importance of plants as a source of new and powerful drugs against these widespread diseases. PMID:22888328

Review of MRI-based measurements of pulse wave velocity: a biomarker of arterial stiffness

PubMed Central

Wentland, Andrew L.; Grist, Thomas M.

2014-01-01

Atherosclerosis is the leading cause of cardiovascular disease (CVD) in the Western world. In the early development of atherosclerosis, vessel walls remodel outwardly such that the vessel luminal diameter is minimally affected by early plaque development. Only in the late stages of the disease does the vessel lumen begin to narrow—leading to stenoses. As a result, angiographic techniques are not useful for diagnosing early atherosclerosis. Given the absence of stenoses in the early stages of atherosclerosis, CVD remains subclinical for decades. Thus, methods of diagnosing atherosclerosis early in the disease process are needed so that affected patients can receive the necessary interventions to prevent further disease progression. Pulse wave velocity (PWV) is a biomarker directly related to vessel stiffness that has the potential to provide information on early atherosclerotic disease burden. A number of clinical methods are available for evaluating global PWV, including applanation tonometry and ultrasound. However, these methods only provide a gross global measurement of PWV—from the carotid to femoral arteries—and may mitigate regional stiffness within the vasculature. Additionally, the distance measurements used in the PWV calculation with these methods can be highly inaccurate. Faster and more robust magnetic resonance imaging (MRI) sequences have facilitated increased interest in MRI-based PWV measurements. This review provides an overview of the state-of-the-art in MRI-based PWV measurements. In addition, both gold standard and clinical standard methods of computing PWV are discussed. PMID:24834415

Biomarker detection of global infectious diseases based on magnetic particles.

PubMed

Carinelli, Soledad; Martí, Mercè; Alegret, Salvador; Pividori, María Isabel

2015-09-25

Infectious diseases affect the daily lives of millions of people all around the world, and are responsible for hundreds of thousands of deaths, mostly in the developing world. Although most of these major infectious diseases are treatable, the early identification of individuals requiring treatment remains a major issue. The incidence of these diseases would be reduced if rapid diagnostic tests were widely available at the community and primary care level in low-resource settings. Strong research efforts are thus being focused on replacing standard clinical diagnostic methods, such as the invasive detection techniques (biopsy or endoscopy) or expensive diagnostic and monitoring methods, by affordable and sensitive tests based on novel biomarkers. The development of new methods that are needed includes solid-phase separation techniques. In this context, the integration of magnetic particles within bioassays and biosensing devices is very promising since they greatly improve the performance of a biological reaction. The diagnosis of clinical samples with magnetic particles can be easily achieved without pre-enrichment, purification or pretreatment steps often required for standard methods, simplifying the analytical procedures. The biomarkers can be specifically isolated and preconcentrated from complex biological matrixes by magnetic actuation, increasing specificity and the sensitivity of the assay. This review addresses these promising features of the magnetic particles for the detection of biomarkers in emerging technologies related with infectious diseases affecting global health, such as malaria, influenza, dengue, tuberculosis or HIV. Copyright © 2015 Elsevier B.V. All rights reserved.

Land use change and human health

NASA Astrophysics Data System (ADS)

Patz, Jonathan A.; Norris, Douglas E.

Disease emergence events have been documented following several types of land use change. This chapter reviews several health-relevant land use changes recognized today, including: 1) urbanization and urban sprawl; 2) water projects and agricultural development; 3) road construction and deforestation in the tropics; and 4) regeneration of temperate forests. Because habitat or climatic change substantially affects intermediate invertebrate hosts involved in many prevalent diseases, this chapter provides a basic description of vector-borne disease biology as a foundation for analyzing the effects of land use change. Urban sprawl poses health challenges stemming from heat waves exacerbated by the "urban heat island" effect, as well as from water contamination due to expanses of impervious road and concrete surfaces. Dams, irrigation and agricultural development have long been associated with diseases such as schistosomiasis and filariasis. Better management methods are required to address the trade-offs between expanded food production and altered habitats promoting deadly diseases. Deforestation can increase the nature and number of breeding sites for vector-borne diseases, such as malaria and onchocerciasis. Human host and disease vector interaction further increases risk, as can a change in arthropod-vector species composition.

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

PubMed Central

Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

2013-01-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

PubMed

Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J

2012-09-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

The Influence of Adipose Tissue on Brain Development, Cognition, and Risk of Neurodegenerative Disorders.

PubMed

Letra, Liliana; Santana, Isabel

2017-01-01

The brain is a highly metabolic organ and thus especially vulnerable to changes in peripheral metabolism, including those induced by obesity-associated adipose tissue dysfunction. In this context, it is likely that the development and maturation of neurocognitive circuits may also be affected and modulated by metabolic environmental factors, beginning in utero. It is currently recognized that maternal obesity, either pre-gestational or gestational, negatively influences fetal brain development and elevates the risk of cognitive impairment and neuropsychiatric disorders in the offspring. During infancy and adolescence, obesity remains a limiting factor for healthy neurodevelopment, especially affecting executive functions but also attention, visuospatial ability, and motor skills. In middle age, obesity seems to induce an accelerated brain aging and thus may increase the risk of age-related neurodegenerative diseases such as Alzheimer's disease. In this chapter we review and discuss experimental and clinical evidence focusing on the influence of adipose tissue dysfunction on neurodevelopment and cognition across lifespan, as well as some possible mechanistic links, namely the role of the most well studied adipokines.

Intestinal commensal microbes as immune modulators

PubMed Central

Ivanov, Ivaylo I.; Honda, Kenya

2012-01-01

Commensal bacteria are necessary for the development and maintenance of a healthy immune system. Harnessing the ability of microbiota to affect host immunity is considered an important therapeutic strategy for many mucosal and non-mucosal immune-related conditions, such as inflammatory bowel diseases (IBD), celiac disease, metabolic syndrome, diabetes and microbial infections. In addition to well-established immunostimulatory effects of the microbiota, the presence of individual mutualistic commensal bacteria with immunomodulatory effects has been described. These organisms are permanent members of the commensal microbiota and affect host immune homeostasis in specific ways. Identification of individual examples of such immunomodulatory commensals and understanding their mechanisms of interaction with the host will be invaluable in designing therapeutic strategies to reverse intestinal dysbiosis and recover immunological homeostasis. PMID:23084918

Congenital heart disease linked to maternal autoimmunity against cardiac myosin.

PubMed

Cole, Charles R; Yutzey, Katherine E; Brar, Anoop K; Goessling, Lisa S; Van Vickle-Chavez, Sarah J; Cunningham, Madeleine W; Eghtesady, Pirooz

2014-05-01

Structural congenital heart disease (CHD) has not previously been linked to autoimmunity. In our study, we developed an autoimmune model of structural CHD that resembles hypoplastic left heart syndrome (HLHS), a life-threatening CHD primarily affecting the left ventricle. Because cardiac myosin (CM) is a dominant autoantigen in autoimmune heart disease, we hypothesized that immunization with CM might lead to transplacental passage of maternal autoantibodies and a prenatal HLHS phenotype in exposed fetuses. Elevated anti-CM autoantibodies in maternal and fetal sera, as well as IgG reactivity in fetal myocardium, were correlated with structural CHD that included diminished left ventricular cavity dimensions in the affected progeny. Further, fetuses that developed a marked HLHS phenotype had elevated serum titers of anti-β-adrenergic receptor Abs, as well as increased protein kinase A activity, suggesting a potential mechanism for the observed pathological changes. Our maternal-fetal model presents a new concept linking autoimmunity against CM and cardiomyocyte proliferation with cardinal features of HLHS. To our knowledge, this report shows the first evidence in support of a novel immune-mediated mechanism for pathogenesis of structural CHD that may have implications in its future diagnosis and treatment.

Current status of the microbiome in renal transplantation.

PubMed

Ahmad, Sarwat; Bromberg, Jonathan S

2016-11-01

An imbalance between pathogenic and protective microbiota characterizes dysbiosis. Presence of dysbiosis may affect immunity, tolerance, or disease depending on a variety of conditions. In the transplant patient population, the need for immunosuppression and widespread use of prophylactic and therapeutic antimicrobial agents create new posttransplant microbiota communities that remain to be fully defined. Studies in mice have demonstrated significant bidirectional interactions between microbiota-derived products and host immune cells. The stimulation of regulatory T cell and T helper cell type 17 cells by specific products leads to maintenance of immune homeostasis versus activation of inflammation, respectively. Dysbiosis may lead to development of antigen cross-reactivity, which may affect alloreactivity. Certain immunologic sequelae of microbiota are pronounced in chronic kidney disease, because of uremia and renal metabolism of microbiota metabolites. Dietary modifications, probiotics, and fecal microbiota transplant have been investigated for alteration of microbiota in humans. Researchers have begun to identify dysbioses associated with clinical conditions, including chronic kidney disease, posttransplant infection, and rejection. This information will allow clinicians not only to select at-risk patients for early intervention, but also to develop therapies that restore the microbiota to a state of homeostasis or tolerance.

Epigenetic mechanisms in the development of memory and their involvement in certain neurological diseases.

PubMed

Rosales-Reynoso, M A; Ochoa-Hernández, A B; Juárez-Vázquez, C I; Barros-Núñez, P

Today, scientists accept that the central nervous system of an adult possesses considerable morphological and functional flexibility, allowing it to perform structural remodelling processes even after the individual is fully developed and mature. In addition to the vast number of genes participating in the development of memory, different known epigenetic mechanisms are involved in normal and pathological modifications to neurons and therefore also affect the mechanisms of memory development. This study entailed a systematic review of biomedical article databases in search of genetic and epigenetic factors that participate in synaptic function and memory. The activation of gene expression in response to external stimuli also occurs in differentiated nerve cells. Neural activity induces specific forms of synaptic plasticity that permit the creation and storage of long-term memory. Epigenetic mechanisms play a key role in synaptic modification processes and in the creation and development of memory. Changes in these mechanisms result in the cognitive and memory impairment seen in neurodegenerative diseases (Alzheimer disease, Huntington disease) and in neurodevelopmental disorders (Rett syndrome, fragile X, and schizophrenia). Nevertheless, results obtained from different models are promising and point to potential treatments for some of these diseases. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The epidemiology of smoking: health consequences and benefits of cessation.

PubMed

Fagerström, Karl

2002-01-01

Tobacco use is the single most important preventable health risk in the developed world, and an important cause of premature death worldwide. Smoking causes a wide range of diseases, including many types of cancer, chronic obstructive pulmonary disease, coronary heart disease, stroke, peripheral vascular disease, and peptic ulcer disease. In addition, smoking during pregnancy adversely affects fetal and neonatal growth and development. Recent decades have seen a massive expansion in tobacco use in the developing world and accelerating growth in smoking among women in the developed world. Globally, smoking-related mortality is set to rise from 3 million annually (1995 estimate) to 10 million annually by 2030, with 70% of these deaths occurring in developing countries. Many of the adverse health effects of smoking are reversible, and smoking cessation treatments represent some of the most cost effective of all healthcare interventions. Although the greatest benefit accrues from ceasing smoking when young, even quitting in middle age avoids much of the excess healthcare risk associated with smoking. In order to improve smoking cessation rates, effective behavioural and pharmacological treatments, coupled with professional counselling and advice, are required. Since smoking duration is the principal risk factor for smoking-related morbidity, the treatment goal should be early cessation and prevention of relapse.

Epidemiological and Surveillance Response to Ebola Virus Disease Outbreak in Lofa County, Liberia (March-September, 2014); Lessons Learned.

PubMed

Kouadio, Koffi Isidore; Clement, Peter; Bolongei, Josephus; Tamba, Alpha; Gasasira, Alex Ntale; Warsame, Abdihamid; Okeibunor, Joseph Chukwudi; Ota, Martin Okechukwu; Tamba, Boima; Gumede, Nicksy; Shaba, Keith; Poy, Alain; Salla, Mbaye; Mihigo, Richard; Nshimirimana, Deo

2015-05-06

Ebola Virus Disease (EVD) outbreak was confirmed in Liberia on March 31st 2014. A response comprising of diverse expertise was mobilized and deployed to the country to contain transmission of Ebola and give relief to a people already impoverished from protracted civil war. This paper describes the epidemiological and surveillance response to the EVD outbreak in Lofa County in Liberia from March to September 2014. Five of the 6 districts of Lofa were affected. The most affected districts were Voinjama/Guardu Gbondi and Foya. By 26th September, 2014, a total of 619 cases, including 19.4% probable cases, 20.3% suspected cases and 44.2% confirmed cases were recorded by the Ebola Emergency Response Team (EERT) of Lofa County. Adults (20-50 years) were the most affected. Overall fatality rate was 53.3%.  Twenty two (22) cases were reported among the Health Care Workers with a fatality rate of 81.8%. Seventy eight percent (78%) of the contacts successfully completed 21 days follow-up while 134 (6.15%) that developed signs and symptoms of EVD were referred to the ETU in Foya. The contributions of the weak health systems as well as socio-cultural factors in fueling the epidemic are highlighted. Importantly, the lessons learnt including the positive impact of multi-sectorial and multidisciplinary and coordinated response led by the government and community.  Again, given that the spread of infectious disease can be considered a security threat every effort has to put in place to strengthen the health systems in developing countries including the International Health Regulation (IHR)'s core capacities. Key words:  Ebola virus disease, outbreak, epidemiology and surveillance, socio-cultural factors, health system, West Africa.

Nanotechnology in dentistry: drug delivery systems for the control of biofilm-dependent oral diseases.

PubMed

de Sousa, Francisco Fabio Oliveira; Ferraz, Camila; Rodrigues, Lidiany K Arla de Azevedo; Nojosa, Jacqueline de Santiago; Yamauti, Monica

2014-01-01

Dental disorders, such as caries, periodontal and endodontic diseases are major public health issues worldwide. In common, they are biofilm-dependent oral diseases, and the specific conditions of oral cavity may develop infectious foci that could affect other physiological systems. Efforts have been made to develop new treatment routes for the treatment of oral diseases, and therefore, for the prevention of some systemic illnesses. New drugs and materials have been challenged to prevent and treat these conditions, especially by means of bacteria elimination. "Recent progresses in understanding the etiology, epidemiology and microbiology of the microbial flora in those circumstances have given insight and motivated the innovation on new therapeutic approaches for the management of the oral diseases progression". Some of the greatest advances in the medical field have been based in nanosized systems, ranging from the drug release with designed nanoparticles to tissue scaffolds based on nanotechnology. These systems offer new possibilities for specific and efficient therapies, been assayed successfully in preventive/curative therapies to the oral cavity, opening new challenges and opportunities to overcome common diseases based on bacterial biofilm development. The aim of this review is to summarize the recent nanotechnological developments in the drug delivery field related to the prevention and treatment of the major biofilm-dependent oral diseases and to identify those systems, which may have higher potential for clinical use.

Post-traumatic unilateral plantar hyperhidrosis.

PubMed

Eren, Y; Yavasoglu, N G; Comoglu, S S

2016-02-01

Localized unilateral hyperhidrosis is rare and poorly understood, sometimes stemming from trauma. Feet, quite vulnerable to trauma are affected by disease-mediated plantar hyperhidrosis, usually bilaterally. This report describes partial hyperhidrosis developing post-traumatically on the left plantar region of a 52-year-old male.

Bridging scales in the evolution of infectious disease life histories: application.

PubMed

Mideo, Nicole; Nelson, William A; Reece, Sarah E; Bell, Andrew S; Read, Andrew F; Day, Troy

2011-11-01

Within- and between-host disease processes occur on the same timescales, therefore changes in the within-host dynamics of parasites, resources, and immunity can interact with changes in the epidemiological dynamics to affect evolutionary outcomes. Consequently, studies of the evolution of disease life histories, that is, infection-age-specific patterns of transmission and virulence, have been constrained by the need for a mechanistic understanding of within-host disease dynamics. In a companion paper (Day et al. 2011), we develop a novel approach that quantifies the relevant within-host aspects of disease through genetic covariance functions. Here, we demonstrate how to apply this theory to data. Using two previously published datasets from rodent malaria infections, we show how to translate experimental measures into disease life-history traits, and how to quantify the covariance in these traits. Our results show how patterns of covariance can interact with epidemiological dynamics to affect evolutionary predictions for disease life history. We also find that the selective constraints on disease life-history evolution can vary qualitatively, and that "simple" virulence-transmission trade-offs that are often the subject of experimental investigation can be obscured by trade-offs within one trait alone. Finally, we highlight the type and quality of data required for future applications. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

Peripheral arterial disease and revascularization of the diabetic foot.

PubMed

Forsythe, R O; Brownrigg, J; Hinchliffe, R J

2015-05-01

Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi-level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised--treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non-revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell-based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches. © 2014 John Wiley & Sons Ltd.

Impact of ethnicity, geography, and disease on the microbiota in health and inflammatory bowel disease.

PubMed

Prideaux, Lani; Kang, Seungha; Wagner, Josef; Buckley, Michael; Mahar, Jackie E; De Cruz, Peter; Wen, Zhonghui; Chen, Liping; Xia, Bing; van Langenberg, Daniel R; Lockett, Trevor; Ng, Siew C; Sung, Joseph J Y; Desmond, Paul; McSweeney, Chris; Morrison, Mark; Kirkwood, Carl D; Kamm, Michael A

2013-12-01

The gut microbiota is central to health and disorders such as inflammatory bowel disease. Differences in microbiota related to geography and ethnicity may hold the key to recent changes in the incidence of microbiota-related disorders. Gut mucosal microbiota was analyzed in 190 samples from 87 Caucasian and Chinese subjects, from Australia and Hong Kong, comprising 22 patients with Crohn's disease, 30 patients with ulcerative colitis, 29 healthy controls, and 6 healthy relatives of patients with Crohn's disease. Bacterial 16S rRNA microarray and 454 pyrosequencing were performed. The microbiota was diverse in health, regardless of ethnicity or geography (operational taxonomic unit number and Shannon diversity index). Ethnicity and geography, however, did affect microbial composition. Crohn's disease resulted in reduced bacterial diversity, regardless of ethnicity or geography, and was the strongest determinant of composition. In ulcerative colitis, diversity was reduced in Chinese subjects only, suggesting that ethnicity is a determinant of bacterial diversity, whereas composition was determined by disease and ethnicity. Specific phylotypes were different between health and disease. Chinese patients with inflammatory bowel disease more often than healthy Chinese tended to have had a Western diet in childhood, in the East and West. The healthy microbiota is diverse but compositionally affected by geographical and ethnic factors. The microbiota is substantially altered in inflammatory bowel disease, but ethnicity may also play an important role. This may be key to the changing epidemiology in developing countries, and emigrants to the West.

Study designs for identification of rare disease variants in complex diseases: the utility of family-based designs.

PubMed

Ionita-Laza, Iuliana; Ottman, Ruth

2011-11-01

The recent progress in sequencing technologies makes possible large-scale medical sequencing efforts to assess the importance of rare variants in complex diseases. The results of such efforts depend heavily on the use of efficient study designs and analytical methods. We introduce here a unified framework for association testing of rare variants in family-based designs or designs based on unselected affected individuals. This framework allows us to quantify the enrichment in rare disease variants in families containing multiple affected individuals and to investigate the optimal design of studies aiming to identify rare disease variants in complex traits. We show that for many complex diseases with small values for the overall sibling recurrence risk ratio, such as Alzheimer's disease and most cancers, sequencing affected individuals with a positive family history of the disease can be extremely advantageous for identifying rare disease variants. In contrast, for complex diseases with large values of the sibling recurrence risk ratio, sequencing unselected affected individuals may be preferable.

Can Human Pluripotent Stem Cell-Derived Cardiomyocytes Advance Understanding of Muscular Dystrophies?

PubMed

Kalra, Spandan; Montanaro, Federica; Denning, Chris

2016-08-30

Muscular dystrophies (MDs) are clinically and molecularly a highly heterogeneous group of single-gene disorders that primarily affect striated muscles. Cardiac disease is present in several MDs where it is an important contributor to morbidity and mortality. Careful monitoring of cardiac issues is necessary but current management of cardiac involvement does not effectively protect from disease progression and cardiac failure. There is a critical need to gain new knowledge on the diverse molecular underpinnings of cardiac disease in MDs in order to guide cardiac treatment development and assist in reaching a clearer consensus on cardiac disease management in the clinic. Animal models are available for the majority of MDs and have been invaluable tools in probing disease mechanisms and in pre-clinical screens. However, there are recognized genetic, physiological, and structural differences between human and animal hearts that impact disease progression, manifestation, and response to pharmacological interventions. Therefore, there is a need to develop parallel human systems to model cardiac disease in MDs. This review discusses the current status of cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) to model cardiac disease, with a focus on Duchenne muscular dystrophy (DMD) and myotonic dystrophy (DM1). We seek to provide a balanced view of opportunities and limitations offered by this system in elucidating disease mechanisms pertinent to human cardiac physiology and as a platform for treatment development or refinement.

Decoding Mechanisms by which Silent Codon Changes Influence Protein Biogenesis and Function

PubMed Central

Bali, Vedrana; Bebok, Zsuzsanna

2015-01-01

Scope Synonymous codon usage has been a focus of investigation since the discovery of the genetic code and its redundancy. The occurrences of synonymous codons vary between species and within genes of the same genome, known as codon usage bias. Today, bioinformatics and experimental data allow us to compose a global view of the mechanisms by which the redundancy of the genetic code contributes to the complexity of biological systems from affecting survival in prokaryotes, to fine tuning the structure and function of proteins in higher eukaryotes. Studies analyzing the consequences of synonymous codon changes in different organisms have revealed that they impact nucleic acid stability, protein levels, structure and function without altering amino acid sequence. As such, synonymous mutations inevitably contribute to the pathogenesis of complex human diseases. Yet, fundamental questions remain unresolved regarding the impact of silent mutations in human disorders. In the present review we describe developments in this area concentrating on mechanisms by which synonymous mutations may affect protein function and human health. Purpose This synopsis illustrates the significance of synonymous mutations in disease pathogenesis. We review the different steps of gene expression affected by silent mutations, and assess the benefits and possible harmful effects of codon optimization applied in the development of therapeutic biologics. Physiological and medical relevance Understanding mechanisms by which synonymous mutations contribute to complex diseases such as cancer, neurodegeneration and genetic disorders, including the limitations of codon-optimized biologics, provides insight concerning interpretation of silent variants and future molecular therapies. PMID:25817479

The impact of thalassemia on Southeast Asian and Asian Indian families in the United States: a qualitative study.

PubMed

Liem, Robert I; Gilgour, Brynnan; Pelligra, Stephanie A; Mason, Maryann; Thompson, Alexis A

2011-01-01

To describe the challenges, including sociocultural and socioeconomic barriers, faced by an urban immigrant population in the United States affected by thalassemia major. Ethnographic, semi-structured, 1-on-1 interviews using an interview guide developed for this study. Digital recordings were transcribed and data analyzed using constant comparative method. University-based, Comprehensive Thalassemia Program at Children's Memorial Hospital, Chicago, IL, USA. Fourteen Southeast Asian and Asian Indian parents of children with transfusion dependent thalassemia. Qualitative descriptions of parental experiences, frequency of codes applied to interviews and emergent themes. Thalassemia has its greatest impact on the emotional and social well-being of affected children and their parents. Current and future concerns were related to disease-specific complications and challenges with management such as transfusions and chelation therapy. These perceptions were tied to parental hope for a cure, a frequently coded coping mechanism. Despite their availability, few parents relied on support systems beyond immediate family members due to perceived public knowledge gaps about thalassemia. Culturally based past experiences and barriers did not emerge as dominant themes in our analysis. The impact of thalassemia is tremendous for affected children and their parents and is due more to factors that were either disease-specific or common to other chronic disease models rather than those influenced by culture. The unmet needs of these families require additional investigation to facilitate the development of initiatives aimed at improving quality of life and lessening overall impact of thalassemia

EPIDEMIC TREMOR, AN ENCEPHALOMYELITIS AFFECTING YOUNG CHICKENS

PubMed Central

Jones, E. Elizabeth

1934-01-01

A new disease having a characteristic and well defined symptom complex is described as occurring in young chickens in four New England states. Tremor, principally of the head and neck, and progressive ataxia are the characteristic symptoms, either or both of which may be present in a single bird. Age at onset in field epidemics ranges from 3 days to 6 weeks, with a majority of cases reported at 3 weeks. Morbidity in commercial flocks ranges from 5 to 50 per cent; mortality in affected hatches may be 50 per cent. The disease may or may not recur in successive hatches, and in the same flock in successive years. Although birds may survive an attack of the disease, nervous symptoms persist in a majority of cases. There is no evidence that nutritional factors are involved. Normal chickens have not contracted the disease by contact with affected birds. The disease has been reproduced in normal chickens by intracerebral inoculation of brain and spinal cord from affected birds. Twenty brain-to-brain passages have been made up to the present time. The incubation period in laboratory passages ranges from 6 to 44 days with symptoms appearing usually between 21 and 28 days. The proportion of inoculated birds developing symptoms has increased with successive passages. The infective agent in the brain has survived in 50 per cent glycerine for 69 days. No organism has been cultivated. The disease has been reproduced after inoculation with bacteriologically sterile filtrates obtained with Seitz and Berkefeld N filters. Attempts to demonstrate the presence of the infective agent in the chicken embryo have been inconclusive. Chicks hatched from eggs laid by birds which had survived the disease were not infected, nor were they immune to inoculation at 6 weeks of age. The characteristic lesion of the disease consists of microscopic focal collections of glia cells, perivascular infiltration, degeneration of Purkinje's cells, and degeneration of nerve cells. Foci of infiltration are present throughout the brain and spinal cord. In the viscera of birds from field epidemics, microscopic focal infiltrations of cells of the lymphoid series are often found. Their presence is most notable in the pancreas and heart. No cell inclusions have been demonstrated. PMID:19870279

The bacterial skin microbiome in psoriatic arthritis, an unexplored link in pathogenesis: challenges and opportunities offered by recent technological advances.

PubMed

Castelino, Madhura; Eyre, Stephen; Upton, Mathew; Ho, Pauline; Barton, Anne

2014-05-01

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both the skin and gastrointestinal tract as sources of microbial triggers for PsA. In parallel with genetic studies, characterization of the host microbiota may benefit our understanding of the microbial contribution to disease pathogenesis-knowledge that may eventually inform the development of novel therapeutics.

Mobile Phone–based Infectious Disease Surveillance System, Sri Lanka

PubMed Central

Sawford, Kate; Daniel, Samson L.A.; Nelson, Trisalyn A.; Stephen, Craig

2010-01-01

Because many infectious diseases are emerging in animals in low-income and middle-income countries, surveillance of animal health in these areas may be needed for forecasting disease risks to humans. We present an overview of a mobile phone–based frontline surveillance system developed and implemented in Sri Lanka. Field veterinarians reported animal health information by using mobile phones. Submissions increased steadily over 9 months, with ≈4,000 interactions between field veterinarians and reports on the animal population received by the system. Development of human resources and increased communication between local stakeholders (groups and persons whose actions are affected by emerging infectious diseases and animal health) were instrumental for successful implementation. The primary lesson learned was that mobile phone–based surveillance of animal populations is acceptable and feasible in lower-resource settings. However, any system implementation plan must consider the time needed to garner support for novel surveillance methods among users and stakeholders. PMID:20875276

Thyroid Hormones and Growth in Health and Disease

PubMed Central

Tarım, Ömer

2011-01-01

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

Ethical aspects on rare diseases.

PubMed

Barrera, Luis A; Galindo, Gilberto Cely

2010-01-01

In this chapter we discuss several of the most relevant subjects related to ethics on Rare Diseases. Some general aspects are discussed such as the socio-psychological problems that confront the patients and their families that finally lead to marginalization and exclusion of patients affected by these diseases from the health programs, even in wealthy countries. Then we address problems related to diagnosis and some ethical aspects of newborn screening, prenatal, pre-implantation diagnosis and reference centers, as well as some conditions that should be met by the persons and institutions performing such tasks. Alternatives of solutions for the most critical situations are proposed. Subsequently the orphan drugs subject is discussed not only from the availability point of view, prizes, industrial practices, and purchasing power in developed and developing societies. The research related to rare disease in children and other especially vulnerable conditions, the need for informed consent, review boards or ethics comities, confidentiality of the information, biobanks and pharmacogenetics are discussed.

Climate change and respiratory disease: European Respiratory Society position statement.

PubMed

Ayres, J G; Forsberg, B; Annesi-Maesano, I; Dey, R; Ebi, K L; Helms, P J; Medina-Ramón, M; Windt, M; Forastiere, F

2009-08-01

Climate change will affect individuals with pre-existing respiratory disease, but the extent of the effect remains unclear. The present position statement was developed on behalf of the European Respiratory Society in order to identify areas of concern arising from climate change for individuals with respiratory disease, healthcare workers in the respiratory sector and policy makers. The statement was developed following a 2-day workshop held in Leuven (Belgium) in March 2008. Key areas of concern for the respiratory community arising from climate change are discussed and recommendations made to address gaps in knowledge. The most important recommendation was the development of more accurate predictive models for predicting the impact of climate change on respiratory health. Respiratory healthcare workers also have an advocatory role in persuading governments and the European Union to maintain awareness and appropriate actions with respect to climate change, and these areas are also discussed in the position statement.

Advances in Nanotechnology for the Treatment of Osteoporosis.

PubMed

Barry, Mikayla; Pearce, Hannah; Cross, Lauren; Tatullo, Marco; Gaharwar, Akhilesh K

2016-06-01

Osteoporosis is a degenerative bone disease commonly related to aging. With an increase in life expectancies worldwide, the prevalence of the disease is expected to rise. Current clinical therapeutic treatments are not able to offer long-term solutions to counter the bone mass loss and the increased risk of fractures, which are the primary characteristics of the disease. However, the combination of bioactive nanomaterials within a biomaterial scaffold shows promise for the development of a localized, long-term treatment for those affected by osteoporosis. This review summarizes the unique characteristics of engineered nanoparticles that render them applicable for bone regeneration and recaps the current body of knowledge on nanomaterials with potential for osteoporosis treatment and bone regeneration. Specifically, we highlight new developments that are shaping this emerging field and evaluate applications of recently developed nanomaterials for osteoporosis treatment. Finally, we will identify promising new research directions in nanotechnology for bone regeneration.

Diabetes and cardiovascular disease: the potential benefit of incretin-based therapies.

PubMed

Addison, Daniel; Aguilar, David

2011-04-01

The health burden of type 2 diabetes mellitus continues to increase worldwide. A substantial portion of this burden is due to the development of cardiovascular disease in patients with diabetes. Recent failures of clinical trials of intensive glucose control to reduce macrovascular events, coupled with reports of potential harm of certain diabetic therapy, have led to increased scrutiny as new diabetic therapies are developed. Incretin peptides are a group of gastrointestinal proteins that regulate glucose metabolism through multiple mechanisms, and incretin-based therapies have been developed to treat type 2 diabetes. These agents include glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-IV (DPP-IV) inhibitors. In addition to effects on glucose homeostasis, growing evidence suggest that these peptides may also affect the cardiovascular system. In this review, we discuss recent findings concerning the potential, yet untested, benefits of incretin-based pharmacotherapy in the treatment of cardiovascular disease.

Photobacteriosis: Prevention and Diagnosis

PubMed Central

2014-01-01

Photobacteriosis or fish pasteurellosis is a bacterial disease affecting wild and farm fish. Its etiological agent, the gram negative bacterium Photobacterium damselae subsp. piscicida, is responsible for important economic losses in cultured fish worldwide, in particular in Mediterranean countries and Japan. Efforts have been focused on gaining a better understanding of the biology of the pathogenic microorganism and its natural hosts with the aim of developing effective vaccination strategies and diagnostic tools to control the disease. Conventional vaccinology has thus far yielded unsatisfactory results, and recombinant technology has been applied to identify new antigen candidates for the development of subunit vaccines. Furthermore, molecular methods represent an improvement over classical microbiological techniques for the identification of P. damselae subsp. piscicida and the diagnosis of the disease. The complete sequencing, annotation, and analysis of the pathogen genome will provide insights into the pathogen laying the groundwork for the development of vaccines and diagnostic methods. PMID:24982922

Fragment-based drug discovery as alternative strategy to the drug development for neglected diseases.

PubMed

Mello, Juliana da Fonseca Rezende E; Gomes, Renan Augusto; Vital-Fujii, Drielli Gomes; Ferreira, Glaucio Monteiro; Trossini, Gustavo Henrique Goulart

2017-12-01

Neglected diseases (NDs) affect large populations and almost whole continents, representing 12% of the global health burden. In contrast, the treatment available today is limited and sometimes ineffective. Under this scenery, the Fragment-Based Drug Discovery emerged as one of the most promising alternatives to the traditional methods of drug development. This method allows achieving new lead compounds with smaller size of fragment libraries. Even with the wide Fragment-Based Drug Discovery success resulting in new effective therapeutic agents against different diseases, until this moment few studies have been applied this approach for NDs area. In this article, we discuss the basic Fragment-Based Drug Discovery process, brief successful ideas of general applications and show a landscape of its use in NDs, encouraging the implementation of this strategy as an interesting way to optimize the development of new drugs to NDs. © 2017 John Wiley & Sons A/S.

Perinatal tuberculosis: new challenges in the diagnosis and treatment of tuberculosis in infants and the newborn.

PubMed

Whittaker, Elizabeth; Kampmann, Beate

2008-12-01

With increasing rates of tuberculosis (TB) infection and disease worldwide, the rate of perinatal TB is also affected. A high index of suspicion by health professionals, in both the developed and developing world, is required to detect and manage tuberculosis in pregnancy and the early newborn period. Differences in immune responses in the fetus and neonate add to the diagnostic difficulties already recognised in young children. Although specific guidelines for the treatment of this potentially devastating disease are lacking due to paucity of experience, outcome is favourable, if the condition is recognised and treated according to existing TB protocols. HIV co-infection, multi- and extensively-drug resistant (MDR/XDR) TB contribute to the challenges. New diagnostic and vaccine developments hold future promise, but much work is needed to completely understand the complex immune responses to tuberculosis and control this disease.

DNA methylation links genetics, fetal environment, and an unhealthy lifestyle to the development of type 2 diabetes.

PubMed

Nilsson, Emma; Ling, Charlotte

2017-01-01

Type 2 diabetes is a complex trait with both environmental and hereditary factors contributing to the overall pathogenesis. One link between genes, environment, and disease is epigenetics influencing gene transcription and, consequently, organ function. Genome-wide studies have shown altered DNA methylation in tissues important for glucose homeostasis including pancreas, liver, skeletal muscle, and adipose tissue from subjects with type 2 diabetes compared with nondiabetic controls. Factors predisposing for type 2 diabetes including an adverse intrauterine environment, increasing age, overweight, physical inactivity, a family history of the disease, and an unhealthy diet have all shown to affect the DNA methylation pattern in target tissues for insulin resistance in humans. Epigenetics including DNA methylation may therefore improve our understanding of the type 2 diabetes pathogenesis, contribute to development of novel treatments, and be a useful tool to identify individuals at risk for developing the disease.

Pleiotropy of tissue-specific growth factors: from neurons to vessels via the bone marrow

PubMed Central

Duda, Dan G.; Jain, Rakesh K.

2005-01-01

Recent evidence has demonstrated that endothelial-specific growth factors affect the development of apparently unrelated organs and cells. Expanding this evidence further, new findings in this issue of the JCI show that neurotrophic factors can affect neovascularization. Neurotrophic factors achieve proangiogenic effects not only by directly affecting endothelial cells, but also by recruiting hematopoietic precursors. Further understanding of the biology of angiogenic factors, as well as of the function of hematopoietic cells in tissue neovascularization, will lead to improved therapeutic strategies for the treatment of diseases ranging from ischemia to cancer. PMID:15765145

Emerging role of Twist1 in fibrotic diseases.

PubMed

Ning, Xiaoxuan; Zhang, Kun; Wu, Qingfeng; Liu, Minna; Sun, Shiren

2018-03-01

Epithelial-mesenchymal transition (EMT) is a pathological process that occurs in a variety of diseases, including organ fibrosis. Twist1, a basic helix-loop-helix transcription factor, is involved in EMT and plays significant roles in various fibrotic diseases. Suppression of the EMT process represents a promising approach for the treatment of fibrotic diseases. In this review, we discuss the roles and the underlying molecular mechanisms of Twist1 in fibrotic diseases, including those affecting kidney, lung, skin, oral submucosa and other tissues. We aim at providing new insight into the pathogenesis of various fibrotic diseases and facilitating the development of novel diagnostic and therapeutic methods for their treatment. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Use of Giovanni System in Public Health Application

NASA Technical Reports Server (NTRS)

Soebiyanto, Radina; Kiang, Richard K.

2012-01-01

The role of environment and climate in propagating infectious disease has long been recognized since the 5th century. The effect is particularly evident in vector-borne diseases such as malaria where temperature, precipitation and humidity influence the lifecycle of the pathogens and mosquitoes. Likewise, the transmission of respiratory diseases is also often associated with climatic factors. For example, a recent study showed that low humidity and temperature provides efficient condition for seasonal influenza transmission. Understanding of how environment and climate affect infectious diseases would essentially provide guides to prevent and control the spread of disease. Toward this end, our group has developed models for infectious disease risk such as for malaria, dengue and influenza that are driven by climatic and environmental inputs. Results will be presented, especially those that used TRMM data from GIOVANNI.

Bridging Knowledge Gaps to Understand How Zika Virus Exposure and Infection Affect Child Development.

PubMed

Kapogiannis, Bill G; Chakhtoura, Nahida; Hazra, Rohan; Spong, Catherine Y

2017-05-01

The Zika virus (ZIKV) epidemic has profoundly affected the lives of children and families across the Americas. As the number of children born with ZIKV-related complications continues to grow, the long-term developmental trajectory for these children and the effect on their families remains largely unknown. In September 2016, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and partner National Institutes of Health institutes convened a workshop to develop a research agenda to improve the evaluation, monitoring, and management of neonates, infants, or children affected by ZIKV and its complications. The agenda also aims to optimally address the prospective effect of ZIKV exposure on the developing child. The full clinical spectrum of congenital ZIKV syndrome has yet to be elucidated. In addition to the well-described anatomic and neurologic manifestations, clinicians are now describing infants with exaggerated primitive reflexes, epilepsy, acquired hydrocephalus and microcephaly, neurodevelopmental delay, gastrointestinal motility problems, and respiratory complications, such as pneumonia. While we are still learning more about the myriad clinical presentations in these severely affected children, it is also paramount to address the larger proportion of ZIKV-exposed infants who are asymptomatic at birth but, we assume, may develop problems later in life. The available evidence for neurologic, neurodevelopmental, neurobehavioral, auditory, and vision assessments and management for infants with congenital ZIKV syndrome was critically evaluated. Lessons from other congenital infections provide valuable clues about the complexities of management and the optimal approaches for evaluating, treating, and caring for the children, which include engaging and involving parents and caregivers in their treatment. Rigorous research is key to improving the identification of ZIKV-infected mothers and babies. Research also is critical to increasing basic understanding of the neuropathogenesis of congenital ZIKV disease and of the spectrum of clinical presentations of ZIKV infection so that agents to prevent and treat this devastating disease can be rapidly developed and studied.

FACTORS AFFECTING SUSCEPTIBILITY OF THE CORAL MONTASTRAEA FAVEOLATE TO BLACK-BAND DISEASE

EPA Science Inventory

Black-band disease affects many species of tropical reef-building corals, but it is unclear what factors contribute to the disease-susceptibility of individual corals or how the disease is transmitted between colonies. Studies have suggested that the ability of black-band disease...

The Contributions of Onchocerciasis Control and Elimination Programs toward the Achievement of the Millennium Development Goals

PubMed Central

Dunn, Caitlin; Callahan, Kelly; Katabarwa, Moses; Richards, Frank; Hopkins, Donald; Withers, P. Craig; Buyon, Lucas E.; McFarland, Deborah

2015-01-01

In 2000, 189 member states of the United Nations (UN) developed a plan for peace and development, which resulted in eight actionable goals known as the Millennium Development Goals (MDGs). Since their inception, the MDGs have been considered the international standard for measuring development progress and have provided a blueprint for global health policy and programming. However, emphasis upon the achievement of priority benchmarks around the “big three” diseases—namely HIV, tuberculosis (TB), and malaria—has influenced global health entities to disproportionately allocate resources. Meanwhile, several tropical diseases that almost exclusively impact the poorest of the poor continue to be neglected, despite the existence of cost-effective and feasible methods of control or elimination. One such Neglected Tropical Disease (NTD), onchocerciasis, more commonly known as river blindness, is a debilitating and stigmatizing disease primarily affecting individuals living in remote and impoverished areas. Onchocerciasis control is considered to be one of the most successful and cost-effective public health campaigns ever launched. In addition to improving the health and well-being of millions of individuals, these programs also lead to improvements in education, agricultural production, and economic development in affected communities. Perhaps most pertinent to the global health community, though, is the demonstrated effectiveness of facilitating community engagement by allowing communities considerable ownership with regard to drug delivery. This paper reviews the contributions that such concentrated efforts to control and eliminate onchocerciasis make to achieving select MDGs. The authors hope to draw the attention of public policymakers and global health funders to the importance of the struggle against onchocerciasis as a model for community-directed interventions to advance health and development, and to advocate for NTDs inclusion in the post 2015 agenda. PMID:25996946

Paediatric HIV infection.

PubMed

Scarlatti, G

1996-09-28

By the year 2000 there will be six million pregnant women and five to ten million children infected with HIV-1. Intervention strategies have been planned and in some instances already started. A timely and cost-effective strategy needs to take into account that most HIV-1 infected individuals reside in developing countries. Further studies are needed on immunological and virological factors affecting HIV-1 transmission from mother to child, on differential disease progression in affected children, and on transient infection.

Epigenomics and allergic disease

PubMed Central

Lockett, Gabrielle A; Patil, Veeresh K; Soto-Ramírez, Nelís; Ziyab, Ali H; Holloway, John W; Karmaus, Wilfried

2014-01-01

Allergic disease development is affected by both genes and the environment, and epigenetic mechanisms are hypothesized to mediate these environmental effects. In this article, we discuss the link between the environment, DNA methylation and allergic disease, as well as questions of causality inherent to analyses of DNA methylation. From the practical side, we describe characteristics of allergic phenotypes and contrast different epidemiologic study designs used in epigenetic research. We examine methodological considerations, how best to conduct preprocessing and analysis of DNA methylation data sets, and the latest methods, technologies and discoveries in this rapidly advancing field. DNA methylation and other epigenetic marks are firmly entwined with allergic disease, a link that may hold the basis for future allergic disease diagnosis and treatment. PMID:24283882

A novel mutation in the Norrie disease gene.

PubMed

Ott, S; Patel, R J; Appukuttan, B; Wang, X; Stout, J T

2000-04-01

Norrie disease is an X-linked recessive disorder characterized by congenital blindness and in some cases mental retardation and deafness.(1) The variability of signs among patients often complicates diagnosis. Signs such as an ocular pseudoglioma, progressive deafness, and mental disturbance are considered classic features.(2) Only one third of patients with Norrie disease have sensorineural deafness, and approximately one half of the affected individuals exhibit mental retardation, often with psychotic features.(3) Histologic analysis has suggested that retinal dysgenesis occurs early in eye development and involves cells in the inner wall of the optic cup.(4) The gene associated with Norrie disease was identified in 1992. (5,6) We report a novel mutation identified in a patient in whom Norrie disease was diagnosed.

Update on Orofacial Granulomatosis.

PubMed

Hullah, Esther A; Escudier, Michael P

2016-02-01

Orofacial granulomatosis (OFG) is a condition manifesting clinically with chronic swelling of the mouth and/or face, notably with swelling of the lips and oral mucosa, a full-thickness, erythematous gingivitis and mucosal ulceration of various clinical types. Some patients may also present with neurological findings, for example facial palsy. Biopsy of affected tissue shows lymphoedema, with or without granulomatous inflammation. The oral lesions in OFG are histologically indistinguishable from the oral lesions in Crohn's disease (CD) and other systemic granulomatous disorders. It is a condition which may respond to the exclusion of certain food-related chemicals from the diet in up to 60% of patients and, as such, is distinct from gastrointestinal CD. CD is a relapsing systemic inflammatory disease which predominantly affects the gut, and patients suffering from this disease frequently present with abdominal pain, fever and altered bowel habit. A proportion of patients with clinical OFG (without other systemic disease) may have asymptomatic gastrointestinal involvement or go on to develop gut CD suggesting an association between the two diseases. It is estimated that 1% of CD sufferers may have a diagnosis of OFG, but the majority of patients in specialist OFG clinics do not have gut symptoms.

Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workers

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

Ates, I.; Suzen, H.S.; Yucesoy, B.

2008-10-15

Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR=3.47: 95% CI, 1.12-10.77 and OR=4.30: 95% CI, 1.25-14.74, respectively) and alsomore » risk of CWP (OR=3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity, of CWP while TNFA (-308) variant seems to be important only in disease severity On the other hand, IL6 variant may have a protective effect on the development and disease severity.« less

The co-occurrence of Hashimoto thyroiditis in primary Sjogren's syndrome defines a subset of patients with milder clinical phenotype.

PubMed

Caramaschi, Paola; Biasi, Domenico; Caimmi, Cristian; Scambi, Cinzia; Pieropan, Sara; Barausse, Giovanni; Adami, Silvano

2013-05-01

To evaluate in a cohort of 100 consecutive patients affected by primary Sjogren's syndrome (pSS) the incidence of Hashimoto thyroiditis (HT) and to compare the clinical features and the laboratory parameters of patients affected by pSS with and without concomitant HT. In 100 consecutive patients affected by pSS, the occurrence of other autoimmune diseases was recorded and a full examination of thyroid function obtained. HT was associated with pSS in 27 cases. The comparison between pSS cases with and without HT showed that only patients with isolated pSS had low C4 level [p = 0.032, OR (IC 95 %) 230 (13.13-4,046)]. In addition, only patients affected by pSS without HT had evidence of cryoglobulins, cutaneous vasculitis with palpable purpura, peripheral neuropathy, and development of lymphoma, although all these manifestations were observed in a 4.1-8.2 % of the cases, without reaching statistical significance. The association of HT in patients suffering from pSS defines a subset of patients with milder disease and normal C4 levels.

Vaccines against poverty

PubMed Central

MacLennan, Calman A.; Saul, Allan

2014-01-01

With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

Clinical trials in neonates and children: Report of the pulmonary hypertension academic research consortium pediatric advisory committee

PubMed Central

Adatia, Ian; Haworth, Sheila G.; Wegner, Max; Barst, Robyn J.; Ivy, Dunbar; Stenmark, Kurt R.; Karkowsky, Abraham; Rosenzweig, Erika; Aguilar, Christopher

2013-01-01

Drug trials in neonates and children with pulmonary hypertensive vascular disease pose unique but not insurmountable challenges. Childhood is defined by growth and development. Both may influence disease and outcomes of drug trials. The developing pulmonary vascular bed and airways may be subjected to maldevelopment, maladaptation, growth arrest, or dysregulation that influence the disease phenotype. Drug therapy is influenced by developmental changes in renal and hepatic blood flow, as well as in metabolic systems such as cytochrome P450. Drugs may affect children differently from adults, with different clearance, therapeutic levels and toxicities. Toxicity may not be manifested until the child reaches physical, endocrine and neurodevelopmental maturity. Adverse effects may be revealed in the next generation, should the development of ova or spermatozoa be affected. Consideration of safe, age-appropriate tablets and liquid formulations is an obvious but often neglected prerequisite to any pediatric drug trial. In designing a clinical trial, precise phenotyping and genotyping of disease is required to ensure appropriate and accurate inclusion and exclusion criteria. We need to explore physiologically based pharmacokinetic modeling and simulations together with statistical techniques to reduce sample size requirements. Clinical endpoints such as exercise capacity, using traditional classifications and testing cannot be applied routinely to children. Many lack the necessary neurodevelopmental skills and equipment may not be appropriate for use in children. Selection of endpoints appropriate to encompass the developmental spectrum from neonate to adolescent is particularly challenging. One possible solution is the development of composite outcome scores that include age and a developmentally specific functional classification, growth and development scores, exercise data, biomarkers and hemodynamics with repeated evaluation throughout the period of growth and development. In addition, although potentially costly, we recommend long-term continuation of blinded dose ranging after completion of the short-term, double-blind, placebo-controlled trial for side-effect surveillance, which should include neurodevelopmental and peripubertal monitoring. The search for robust evidence to guide safe therapy of children and neonates with pulmonary hypertensive vascular disease is a crucial and necessary goal. PMID:23662203

CASP-19 special section: how does chronic disease status affect CASP quality of life at older ages? Examining the WHO ICF disability domains as mediators of this relationship.

PubMed

Sexton, E; King-Kallimanis, B L; Layte, R; Hickey, A

2015-07-01

The effect of chronic disease status on quality of life (QoL) has been well established. However, less is known about how chronic diseases affect QoL. This article examines impairment in three domains of the WHO International Classification of Functioning, Health and Disability (ICF) - body function, activity and participation, as well as affective well-being, - as potential mediators of the relationship between chronic disease and QoL. A cross-sectional sample (n = 4961) of the general Irish community-dwelling population aged 50+ years was obtained from the Irish Longitudinal Study of Ageing (TILDA). The CASP measure of QoL was examined as two dimensions - control/autonomy and self-realisation/pleasure. Structural equation modelling was used to test the direct and indirect effects of chronic disease on QoL, via variables capturing body function, activity, participation and positive affect. A factor analysis showed that indicators of body function and activity loaded onto a single overall physical impairment factor. This physical impairment factor fully mediated the effect of chronic disease on positive affect and QoL. The total effect of chronic disease on control/autonomy (-0.160) was primarily composed of an indirect effect via physical impairment (-0.86), and via physical impairment and positive affect (-0.45). The decomposition of effects on self-realisation/pleasure was similar, although the direct effect of physical impairment was weaker. The model fitted the data well (RMSEA = 0.02, TLI = 0.96, CFI = 0.96). Chronic disease affects QoL through increased deficits in physical body function and activity. This overall physical impairment affects QoL both directly and indirectly via reduced positive affect.

Fisheries and aquatic resources--fish health

USGS Publications Warehouse

Panek, Frank

2008-01-01

Fish health research at Leetown had its origin in the 1930’s when the Leetown Fish Hatchery and Experiment Station was constructed. In 1978, the National Fish Health Research Laboratory, now a component of the Leetown Science Center, was established to solve emerging and known disease problems affecting fish and other aquatic organisms critical to species restoration programs. Center scientists develop methods for the isolation, detection, and identification of fish pathogens and for prevention and control of fish diseases.

Musculoskeletal involvements in sarcoidosis: A narrative review.

PubMed

Salari, Roshanak; Shariatmaghani, Somayeh; Sahebari, Maryam; Shalchiantabrizi, Payman; Salari, Masoumeh

2018-05-14

Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF-α inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Musculoskeletal manifestations of sarcoidosis: A review article.

PubMed

Shariatmaghani, Somayeh; Salari, Roshanak; Sahebari, Maryam; Shalchiantabrizi, Payman; Salari, Masoumeh

2018-04-24

Sarcoidosis is a multisystem inflammatory disease with an etiology that is not clearly understood. Amongst the different organs that may be affected, the lungs are the most common. Musculoskeletal manifestations of the disease are uncommon. They include arthropathy, bone lesions, or myopathy, all of which may occur as initial symptoms or develop during the course of the disease. Articular involvement my present as arthralgia or arthritis. Skeletal complications usually develop in the chronic state of the disease. Muscular disease is rare and usually asymptomatic. Appropriate imaging modalities including X-ray, MRI, FDG-PET/CT assist in the diagnosis of rheumatic sarcoidosis. However, biopsy is necessary for definite diagnosis. In most cases of musculoskeletal involvement, NSAIDs and corticosteroids are sufficient for symptomatic management. For more resistant cases immunosuppressive drugs (i.e., methotrexate) and TNF-? inhibitors are used. Our aim is to review various types of musculoskeletal involvement in sarcoidosis and their existing treatment options. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multiple sclerosis pathways: an innovative nursing role in disease management.

PubMed

Madonna, M G; Keating, M M

1999-12-01

Multiple sclerosis (MS), a chronic disease of the central nervous system, is characterized by a variable and unpredictable course. The most common pattern of the disease is the relapsing-remitting form in which clearly defined relapses (also called exacerbations) are followed by complete or incomplete recovery. Interferon beta-1b (Betaseron), a drug that affects the natural course of the disease, was developed for the treatment of relapsing-remitting MS. Multiple Sclerosis Pathways (MSP), a disease management program, was developed to provide comprehensive and personal support to MS patients taking interferon beta-1b and to serve as an information resource for all people with MS, their families, and healthcare professionals. The MSP program includes personal patient assistance, reimbursement services, a 24-hour nurse hotline, training program, educational resources, and injection supplies. The nurse hotline counselor (NHC) utilizes the nursing process in a unique telephone nursing practice in this program. The positive impact of education and support on adherence to therapy has been validated by training and nurse hotline data.

Promoting cardiovascular health worldwide: strategies, challenges, and opportunities.

PubMed

Castellano, José M; Narula, Jagat; Castillo, Javier; Fuster, Valentín

2014-09-01

Cardiovascular disease is the leading cause of death in the world, affecting not only industrialized but, above all, low- and middle-income countries, where it has overtaken infectious diseases as the first cause of death and its impact threatens social and economic development. The increased prevalence of cardiovascular disease in recent years together with projected mortality for the coming decades constitute an irrefutable argument for the urgent implementation of well-planned interventions to control the pandemic of cardiovascular diseases, especially in the more economically deprived countries. The combination of behavioral, social, environmental, and biological factors, and others related to health care systems, that contribute to the development of cardiovascular diseases requires a multi-sector strategy that promotes a healthy lifestyle, reduces cardiovascular risk factors, and cuts mortality and morbidity through quality health care services. These proposals should be guided by leaders in the scientific community, government, civil society, private sector, and local communities. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Climate warming and disease risks for terrestrial and marine biota

USGS Publications Warehouse

Harvell, C.D.; Mitchell, C.E.; Ward, J.R.; Altizer, S.; Dobson, A.P.; Ostfeld, R.S.; Samuel, M.D.

2002-01-01

Infectious diseases can cause rapid population declines or species extinctions. Many pathogens of terrestrial and marine taxa are sensitive to temperature, rainfall, and humidity, creating synergisms that could affect biodiversity. Climate warming can increase pathogen development and survival rates, disease transmission, and host susceptibility. Although most host-parasite systems are predicted to experience more frequent or severe disease impacts with warming, a subset of pathogens might decline with warming, releasing hosts from disease. Recently, changes in El Niño–Southern Oscillation events have had a detectable influence on marine and terrestrial pathogens, including coral diseases, oyster pathogens, crop pathogens, Rift Valley fever, and human cholera. To improve our ability to predict epidemics in wild populations, it will be necessary to separate the independent and interactive effects of multiple climate drivers on disease impact.

Climate Warming and Disease Risks for Terrestrial and Marine Biota

NASA Astrophysics Data System (ADS)

Harvell, C. Drew; Mitchell, Charles E.; Ward, Jessica R.; Altizer, Sonia; Dobson, Andrew P.; Ostfeld, Richard S.; Samuel, Michael D.

2002-06-01

Infectious diseases can cause rapid population declines or species extinctions. Many pathogens of terrestrial and marine taxa are sensitive to temperature, rainfall, and humidity, creating synergisms that could affect biodiversity. Climate warming can increase pathogen development and survival rates, disease transmission, and host susceptibility. Although most host-parasite systems are predicted to experience more frequent or severe disease impacts with warming, a subset of pathogens might decline with warming, releasing hosts from disease. Recently, changes in El Niño-Southern Oscillation events have had a detectable influence on marine and terrestrial pathogens, including coral diseases, oyster pathogens, crop pathogens, Rift Valley fever, and human cholera. To improve our ability to predict epidemics in wild populations, it will be necessary to separate the independent and interactive effects of multiple climate drivers on disease impact.

Cardiovascular diseases and diabetes as economic and developmental challenges in Africa.

PubMed

Kengne, Andre Pascal; June-Rose McHiza, Zandile; Amoah, Albert George Baidoe; Mbanya, Jean-Claude

2013-01-01

Current estimates and projections suggest that the burden of cardiovascular diseases (CVDs), diabetes and related risk factors in African countries is important, somewhat unique and rapidly growing. Various segments of the population are affected; however, the group mostly affected is young adults residing in urban areas, and increasingly those in the low socioeconomic strata. The African milieu/environment is compounded by weak health systems, which are unable to cope with the looming double burden of communicable and chronic non-communicable diseases. This review discusses the economic and developmental challenges posed by CVDs and diabetes in countries in Africa. Using several lines of evidence, we demonstrate that the cost of care for major CVDs and diabetes is beyond the coping capacities of individuals, households, families and governments in most African countries. We have reviewed modeling studies by the International Diabetes Federation (IDF) and other major international agencies on the current and projected impact that CVDs and diabetes have on the economy and development of countries in the region. Locally, appropriate strategies to limit the impact of the conditions on the economies and development of countries in Africa are suggested and discussed. These include monitoring diseases and risk factors, and primordial, primary and secondary preventions implemented following a life-course perspective. Structural, logistic, human capacity and organizational challenges to be surmounted during the implementations of these strategies will be reviewed. © 2013.

Toxicological assessment of drugs that affect the endocrine system in puberty-related disorders.

PubMed

Maranghi, Francesca; Tassinari, Roberta; Mantovani, Alberto

2013-10-01

Toxicologists must ensure that clinical risk-to-benefit analysis should be made both for genders and age groups, with any treatment. Puberty concerns physiological changes leading to organism's maturation. Pubertal growth disorders are increasing in last decades: besides causing physical and psychological distress, they may signal underlying endocrine-metabolic abnormalities with serious health consequences later on. Therapeutic approaches for some health conditions in childhood and adolescence are considered. The authors discuss how some diseases and treatments can impact pubertal growth. The authors look at particular immunological disorders such as asthma and how both the disease and treatment affects pubertal growth. They also discuss how the provision of available data can help to assess the dose-response of the drug, in these cases, and minimize the chance of side effects. The authors also discuss pediatric inflammatory bowel disease and how both the disease and treatment can mitigate the growth delay. Last, but not least, the authors discuss how the effects of the drugs used in the treatment of psychiatric disorders may accentuate endocrine issues in juvenile patients. Hyperprolactinemia induction by some antipsychotics is highlighted as an example. Appropriate risk-benefit analysis of drugs prescribed during childhood and adolescence and intended to be used in the long term is required. Furthermore, future treatment strategies and safer compounds development should be supported by the knowledge of mechanisms underlying adverse side effects in pubertal growth and development.

A conceptual framework for evaluating impairments in myasthenia gravis.

PubMed

Barnett, Carolina; Bril, Vera; Kapral, Moira; Kulkarni, Abhaya; Davis, Aileen M

2014-01-01

Myasthenia gravis is characterized by weakness and fatigability of different muscle groups, including ocular, bulbar and the limbs. Therefore, a measure of disease severity at the impairment level in myasthenia needs to reflect all the relevant impairments, as well as their variations with activity and fatigue. We conducted a qualitative study of patients with myasthenia, to explore their experiences and related impairments, aimed at developing a conceptual framework of disease severity at the impairment level in myasthenia gravis. Twenty patients representing the spectrum of disease participated in semi-structured interviews. Interviews were recorded and the transcripts were analyzed by content analysis using an inductive approach with line-by-line open coding. Themes were generated from these codes. Two main themes were identified: the severity of the impairments and fatigability (i.e., triggering or worsening of an impairment with activity). The impairments were further classified within body regions (ocular, bulbar and axial/limbs). Fatigability was described as a phenomenon affecting the whole body but also affecting specific impairments, and was associated with fluctuation of the symptoms. Patients were concerned that clinical examination at a single point in time might not reflect their true clinical state due to fatigability and fluctuations in severity. This conceptual framework reflects the relevance of both severity and fatigability in understanding impairment-based disease severity in myasthenia. This framework could inform the development of impairment measures in myasthenia gravis.

Specialized metabolites from the microbiome in health and disease

PubMed Central

Sharon, Gil; Garg, Neha; Debelius, Justine; Knight, Rob; Dorrestein, Pieter C.; Mazmanian, Sarkis K.

2015-01-01

The microbiota, and the genes that comprise its microbiome, play key roles in human health. Host-microbe interactions affect immunity, metabolism, development, and behavior, and dysbiosis of gut bacteria contributes to disease. Despite advances in correlating changes in the microbiota with various conditions, specific mechanisms of host-microbiota signaling remain largely elusive. We discuss the synthesis of microbial metabolites, their absorption, and potential physiological effects on the host. We propose that the effects of specialized metabolites may explain present knowledge gaps linking the gut microbiota to biological host mechanisms during initial colonization, and in health and disease. PMID:25440054

[The Application of Magnetic Resonance Imaging in Alzheimer's Disease].

PubMed

Matsuda, Hiroshi

2017-07-01

In Alzheimer's disease (AD), magnetic resonance imaging (MRI) is essential for early diagnosis, differential diagnosis, and evaluation of disease progression. In structural MRI, the automatic diagnosis of atrophy by computers, even when it is not visually noticeable, is possible in daily clinical practice. Furthermore, subfield volumetric measurements of the medial temporal structures, as well as longitudinal volume measurements with high accuracy, have been developed and are useful for calculating the needed sample size in clinical trials. In addition to detecting local atrophy, graph theory has been applied to structural MRI for evaluation of alterations of the brain networks potentially affected in AD.

Exercise: the data on its role in health, mental health, disease prevention, and productivity.

PubMed

Diehl, Jason J; Choi, Haemi

2008-12-01

How would you define exercise? If you look up exercise in the dictionary, it is defined as physical activity used for the purpose of conditioning any part of the body. Exercise is an important topic because in the United States less than 50% of the total population exercises on a regular basis. The lack of regular physical activity is linked to an increased rate of obesity, development of chronic diseases, and an overall decline in health. This article uses an evidence-based approach to demonstrate how exercise affects health, mental health, disease prevention, and productivity.

[Microbiota and autoimmunity].

PubMed

Miyake, Sachiko

2014-01-01

The microbiota plays a fundamental role in the development and the maintenance of the host immune system. Since microbiota is important in the induction and the expansion of Th17 cells and regulatory T cells, growing evidence supports that microbiome affect the induction and the disease course of autoimmune disorders. In this review, we describe the recent studies on the involvement of microbes in animal models of autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) using germ-free conditions, antibiotics treatment and gnotobiotic mice. Furthermore, we introduce the studies on analysis of microbiota in human autoimmune diseases including RA and MS.

Current interventions in the management of knee osteoarthritis

PubMed Central

Bhatia, Dinesh; Bejarano, Tatiana; Novo, Mario

2013-01-01

Osteoarthritis (OA) is progressive joint disease characterized by joint inflammation and a reparative bone response and is one of the top five most disabling conditions that affects more than one-third of persons > 65 years of age, with an average estimation of about 30 million Americans currently affected by this disease. Global estimates reveal more than 100 million people are affected by OA. The financial expenditures for the care of persons with OA are estimated at a total annual national cost estimate of $15.5-$28.6 billion per year. As the number of people >65 years increases, so does the prevalence of OA and the need for cost-effective treatment and care. Developing a treatment strategy which encompasses the underlying physiology of degenerative joint disease is crucial, but it should be considerate to the different age ranges and different population needs. This paper focuses on different exercise and treatment protocols (pharmacological and non-pharmacological), the outcomes of a rehabilitation center, clinician-directed program versus an at home directed individual program to view what parameters are best at reducing pain, increasing functional independence, and reducing cost for persons diagnosed with knee OA. PMID:23559821

Dysbiotic infection in the stomach.

PubMed

Iizasa, Hisashi; Ishihara, Shyunji; Richardo, Timmy; Kanehiro, Yuichi; Yoshiyama, Hironori

2015-10-28

Microbiota in human alimentary tract plays important roles for homeostatic maintenance of the body. Compositional difference of gut microbiota is tightly associated with susceptibility of many diseases, including inflammatory diseases, obesity, diabetes mellitus, cancer, and atherosclerosis. "Dysbiosis" refers to a state of imbalance among the colonies of microorganisms within the body, which brings abnormal increase of specific minor components and decrease in the normally dominant species. Since stomach secrets strong acid for its digestive role, this organ has long been thought a sterile organ. However, the discovery of Helicobacter pylori (H. pylori) has changed the concept. This bacterium has proven to cause gastritis, peptic ulcer, and gastric cancer. However, recent cross-sectional studies revealed that H. pylori carriers had a decreased risk of developing immunological diseases, such as asthma. H. pylori coinfection also suppresses inflammatory bowel diseases. This review describes human gastric microbiota by discussing its mutual interaction and pathogenic enrollment. Gastric "dysbiosis" may affect host inflammatory response and play important role for gastric pathogenesis. We will topically discuss enrollment of dysbiosis for genesis of gastric cancer as well as for disruption of immunological homeostasis affecting oncogenic resistance.

The Fragile X Mental Retardation Syndrome 20 Years After the FMR1 Gene Discovery: an Expanding Universe of Knowledge

PubMed Central

Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

2011-01-01

The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations. PMID:21912443

MicroRNAs in right ventricular remodelling.

PubMed

Batkai, Sandor; Bär, Christian; Thum, Thomas

2017-10-01

Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Clinical implications and treatment of dengue.

PubMed

Chawla, Pooja; Yadav, Amrita; Chawla, Viney

2014-03-01

Dengue is a common pathogenic disease often proving fatal, more commonly affecting the tropics. Aedes mosquito is the vector for this disease, and outbreaks of dengue often cause mass damage to life. The current review is an effort to present an insight into the causes, etiology, symptoms, transmission, diagnosis, major organs affected, mitigation and line of treatment of this disease with special emphasis on drugs of natural origin. The disease has a potential to spread as an endemic, often claiming several lives and thus requires concerted efforts to work out better treatment options. Traditional medicine offers an alternative solution and could be explored as a safer treatment option. Development of a successful vaccine and immunization technique largely remains a challenge and a better antiviral approach needs to be worked out to complement the supportive therapy. No single synthetic molecule has found to be wholly effective enough to offer curative control and the line of treatment mostly utilizes a combination of fluid replacement and antipyretics-analgesics like molecules to provide symptomatic relief. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

The fragile x mental retardation syndrome 20 years after the FMR1 gene discovery: an expanding universe of knowledge.

PubMed

Rousseau, François; Labelle, Yves; Bussières, Johanne; Lindsay, Carmen

2011-08-01

The fragile X mental retardation (FXMR) syndrome is one of the most frequent causes of mental retardation. Affected individuals display a wide range of additional characteristic features including behavioural and physical phenotypes, and the extent to which individuals are affected is highly variable. For these reasons, elucidation of the pathophysiology of this disease has been an important challenge to the scientific community. 1991 marks the year of the discovery of both the FMR1 gene mutations involved in this disease, and of their dynamic nature. Although a mouse model for the disease has been available for 16 years and extensive research has been performed on the FMR1 protein (FMRP), we still understand little about how the disease develops, and no treatment has yet been shown to be effective. In this review, we summarise current knowledge on FXMR with an emphasis on the technical challenges of molecular diagnostics, on its prevalence and dynamics among populations, and on the potential of screening for FMR1 mutations.

Maternal Influences on Epigenetic Programming of the Developing Hypothalamic-Pituitary-Adrenal Axis

EPA Science Inventory

Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing risk of disease later in life. Underlying mechanisms are beginning to be elucidated, and effects on a number of organ...

Bound for Sydney town: health surveillance on international cruise vessels visiting the Port of Sydney.

PubMed

Ferson, Mark J; Ressler, Kelly-Anne

2005-04-18

A program for routine health surveillance on international cruise ships visiting the Port of Sydney has been developed since 1998. Before introduction of this program, ships only reported quarantinable diseases and were not aware of the Australian requirement to report other infectious diseases. Voluntary routine reporting, developed in partnership with the cruise ship industry, provides timely information on all infectious diseases of public health interest during every cruise. During 1999-2003, the program resulted in detection of and response to 14 outbreaks of gastroenteritis or acute respiratory infection, affecting more than 1400 passengers and crew. The program has improved preventive action, and risk communication and management by cruise ship operators, and led to more timely investigation and support by public health authorities.

Sleep and Cardio-Metabolic Disease.

PubMed

Cappuccio, Francesco P; Miller, Michelle A

2017-09-19

This review summarises and discusses the epidemiological evidence suggesting a causal relationship between sleep duration and cardio-metabolic risk and outcomes in population. Sleep duration is affected by a variety of cultural, social, psychological, behavioural, pathophysiological and environmental influences. Changes in modern society-like longer working hours, more shift-work, 24/7 availability of commodities and 24-h global connectivity-have been associated with a gradual reduction in sleep duration and sleeping patterns across westernised populations. We review the evidence of an association between sleep disturbances and the development of cardio-metabolic risk and disease and discuss the implications for causality of these associations. Prolonged curtailment of sleep duration is a risk factor for the development of obesity, diabetes, hypertension, heart disease and stroke and may contribute, in the long-term, to premature death.

Linkage mapping of the primary disease locus for collie eye anomaly.

PubMed

Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

2003-07-01

Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

[Benign multicystic peritoneal mesothelioma (BMPM) - a surprising differential diagnosis in case of an expected intraabdominal abscess formation].

PubMed

Lipp, Michael Josef; Jusufi, Maximilian Stanley; Backer, Christoph; Feyerabend, Bernd; Weilert, Hauke; Oldhafer, Karl Jürgen

2017-03-01

The benign multicystic peritoneal mesothelioma is a rare disease. Most frequently, young women in reproductive age are affected by this disease. Nevertheless, there are known cases of multicystic peritoneal mesothelioma in male patients. The pathogenesis remains uncertain. Whereas asbestos fibers can cause the development of malignant mesothelioma, the exposure to asbestos particles cannot induce this type of mesothelioma. An inflammatory genesis is discussed as well as the idea of a neoplastic development. Since a high rate of recurrence after surgery is observed, an aggressive surgical treatment is recommended. The complete resection of affected tissue is recently considered to be the therapy of choice. The combination of complete surgical tumor reduction with an intraperitoneal hyperthermic chemotherapy (HIPEC) seems to be promising. Although malignant transformation is detected very rarely a close follow up in centers with high surgical and oncological expertise is recommended. © Georg Thieme Verlag KG Stuttgart · New York.

Food allergies: the basics.

PubMed

Valenta, Rudolf; Hochwallner, Heidrun; Linhart, Birgit; Pahr, Sandra

2015-05-01

IgE-associated food allergy affects approximately 3% of the population and has severe effects on the daily life of patients-manifestations occur not only in the gastrointestinal tract but also affect other organ systems. Birth cohort studies have shown that allergic sensitization to food allergens develops early in childhood. Mechanisms of pathogenesis include cross-linking of mast cell- and basophil-bound IgE and immediate release of inflammatory mediators, as well as late-phase and chronic allergic inflammation, resulting from T-cell, basophil, and eosinophil activation. Researchers have begun to characterize the molecular features of food allergens and have developed chip-based assays for multiple allergens. These have provided information about cross-reactivity among different sources of food allergens, identified disease-causing food allergens, and helped us to estimate the severity and types of allergic reactions in patients. Importantly, learning about the structure of disease-causing food allergens has allowed researchers to engineer synthetic and recombinant vaccines. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

No genetic effect of {alpha}{sub 1}-antichymotrypsin in Alzheimer disease

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

Haines, J.L.; Pritchard, M.L.; Saunders, A.M.

1996-04-01

Alzheimer disease (AD) is the most common neurodegenerative disorder for individuals over the age of 40.AD has a complex etiology, and it is likely that multiple genes, acting independently and/or interacting, affect the risk of developing AD. Several genes involved with AD have been described already, but only the APOE gene on chromosome 19q has been shown to affect the risk of the common late onset form of AD. {alpha}{sub 1}-Antichymotrypsin (AACT) is a major component of the amyloid plaques found in the brains of AD patients, and an allele in its gene has been proposed to increase the riskmore » of developing AD when also associated with the APOE-4 allele. We have examined the role of this AACT polymorphism in a large set of families and sporadic cases, and do not see any effect, either alone or in combination with the APOE-4 allele. 18 refs., 3 tabs.« less

Mucosal expression of basic fibroblastic growth factor, Syndecan 1 and tumor necrosis factor-alpha in diverticular disease of the colon: a case-control study.

PubMed

Tursi, A; Elisei, W; Brandimarte, G; Giorgetti, G M; Inchingolo, C D; Nenna, R; Picchio, M; Giorgio, F; Ierardi, E

2012-09-01

Inflammation may be detected in diverticular disease (DD), and fibrosis may also develop. We assessed the mucosal expression of bFGF, SD1, and TNF-α in DD according to the severity of the disease. Moreover, we assessed the response to therapy of these cytokines in acute uncomplicated diverticulitis (AUD). Fifteen patients affected by AUD and seven patients affected by symptomatic uncomplicated diverticular disease (SUDD) were enrolled. Patients with asymptomatic diverticulosis (AD), segmental colitis associated with diverticulosis (SCAD), ulcerative colitis (UC), and healthy subjects (HC) served as control groups. The expression of bFGF, SD1, and TNF-α was significantly higher in diverticulitis than in healthy controls, in diverticulosis, and in uncomplicated diverticular disease. Cytokines were significantly higher in uncomplicated diverticular disease than in healthy controls. Cytokine expression in diverticulitis did not differ significantly from that of ulcerative colitis. After treatment, TNF-α expression dropped significantly. Mucosal TNF-α is overexpressed only in symptomatic DD, while SD1 and bFGF are already overexpressed in AD. Finally, TNF-α but not SD1 or bFGF expression seems to be influenced by the treatment in AUD. © 2012 Blackwell Publishing Ltd.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) – Differences and Similarities

PubMed Central

Cukic, Vesna; Lovre, Vladimir; Dragisic, Dejan; Ustamujic, Aida

2012-01-01

Bronchial asthma and COPD (chronic obstructive pulmonary disease) are obstructive pulmonary diseases that affected millions of people all over the world. Asthma is a serious global health problem with an estimated 300 million affected individuals. COPD is one of the major causes of chronic morbidity and mortality and one of the major public health problems worldwide. COPD is the fourth leading cause of death in the world and further increases in its prevalence and mortality can be predicted. Although asthma and COPD have many similarities, they also have many differences. They are two different diseases with differences in etiology, symptoms, type of airway inflammation, inflammatory cells, mediators, consequences of inflammation, response to therapy, course. Some similarities in airway inflammation in severe asthma and COPD and good response to combined therapy in both of these diseases suggest that they have some similar patophysiologic characteristics. The aim of this article is to show similarities and differences between these two diseases. Today asthma and COPD are not fully curable, not identified enough and not treated enough and the therapy is still developing. But in future better understanding of pathology, adequate identifying and treatment, may be and new drugs, will provide a much better quality of life, reduced morbidity and mortality of these patients. PMID:23678316

Treatment for Patients With Malignant Pheochromocytomas and Paragangliomas: A Perspective From the Hallmarks of Cancer

PubMed Central

Jimenez, Camilo

2018-01-01

Malignant pheochromocytomas and paragangliomas affect a very small percentage of the general population. A substantial number of these patients have a hereditary predisposition for the disease and consequently, bear the risk of developing these tumors throughout their entire lives. It is, however, unclear why some patients with no hereditary predisposition develop these tumors, which frequently share a similar molecular phenotype with their hereditary counterparts. Both hereditary and sporadic tumors usually appear at an early age, and affected people often die before reaching their expected lifespans. Unfortunately, there is currently no systemic therapy approved for patients with this orphan disease. Therefore, pheochromocytomas and paragangliomas are very challenging malignancies. The recognition of genetic and molecular abnormalities responsible for the development of these tumors as well as the identification of effective therapies for other malignancies that share a similar pathogenesis is leading to the development of exciting clinical trials. Tyrosine kinase inhibitors, radiopharmaceutical agents, and immunotherapy are currently under evaluation in prospective clinical trials. A phase 2 clinical trial of the highly specific metaiodobenzylguanidine, iobenguane 131I, has provided impressive results; this radiopharmaceutical agent may become the first approved systemic therapy for patients with malignant pheochromocytoma and paraganglioma by the United States Food and Drug Administration. Nevertheless, systemic therapies are still not able to cure the disease. This review will discuss the development of systemic therapeutic approaches using the hallmarks of cancer as a framework. This approach will help the reader to understand where research efforts currently stand and what the future for this difficult field may be.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide☆☆☆★

PubMed Central

Thompson, Paul M.; Andreassen, Ole A.; Arias-Vasquez, Alejandro; Bearden, Carrie E.; Boedhoe, Premika S.; Brouwer, Rachel M.; Buckner, Randy L.; Buitelaar, Jan K.; Bulayeva, Kazima B.; Cannon, Dara M.; Cohen, Ronald A.; Conrod, Patricia J.; Dale, Anders M.; Deary, Ian J.; Dennis, Emily L.; de Reus, Marcel A.; Desrivieres, Sylvane; Dima, Danai; Donohoe, Gary; Fisher, Simon E.; Fouche, Jean-Paul; Francks, Clyde; Frangou, Sophia; Franke, Barbara; Ganjgahi, Habib; Garavan, Hugh; Glahn, David C.; Grabe, Hans J.; Guadalupe, Tulio; Gutman, Boris A.; Hashimoto, Ryota; Hibar, Derrek P.; Holland, Dominic; Hoogman, Martine; Pol, Hilleke E. Hulshoff; Hosten, Norbert; Jahanshad, Neda; Kelly, Sinead; Kochunov, Peter; Kremen, William S.; Lee, Phil H.; Mackey, Scott; Martin, Nicholas G.; Mazoyer, Bernard; McDonald, Colm; Medland, Sarah E.; Morey, Rajendra A.; Nichols, Thomas E.; Paus, Tomas; Pausova, Zdenka; Schmaal, Lianne; Schumann, Gunter; Shen, Li; Sisodiya, Sanjay M.; Smit, Dirk J.A.; Smoller, Jordan W.; Stein, Dan J.; Stein, Jason L.; Toro, Roberto; Turner, Jessica A.; van den Heuvel, Martijn P.; van den Heuvel, Odile L.; van Erp, Theo G.M.; van Rooij, Daan; Veltman, Dick J.; Walter, Henrik; Wang, Yalin; Wardlaw, Joanna M.; Whelan, Christopher D.; Wright, Margaret J.; Ye, Jieping

2016-01-01

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others1, ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far. PMID:26658930

North-South benefit sharing arrangements in bioprospecting and genetic research: a critical ethical and legal analysis.

PubMed

Schüklenk, Udo; Kleinsmidt, Anita

2006-12-01

Most pharmaceutical research carried out today is focused on the treatment and management of the lifestyle diseases of the developed world. Diseases that affect mainly poor people are neglected in research advancements in treatment because they cannot generate large financial returns on research and development costs. Benefit sharing arrangements for the use of indigenous resources and genetic research could only marginally address this gap in research and development in diseases that affect the poor. Benefit sharing as a strategy is conceptually problematic, even if one, as we do, agrees that impoverished indigenous communities should not be exploited and that they should be assisted in improving their living conditions. The accepted concept of intellectual property protection envisages clearly defined originators and owners of knowledge, whereas the concept of community membership is fluid and indigenous knowledge is, by its very nature, open, with the originator(s) lost in the mists of time. The delineation of 'community' presents serious conceptual and practical difficulties as few communities form discrete, easily discernable groups, and most have problematic leadership structures. Benefit sharing is no substitute for governments' responsibility to uplift impoverished communities. Benefit sharing arrangements may be fraught with difficulties but considerations of respect and equity demand that prior informed consent and consultation around commercialisation of knowledge take place with the source community and their government.

The visual difficulties of selected artists and limitations of ophthalmological care during the 19th and early 20th centuries (an AOS thesis).

PubMed

Ravin, James G

2008-01-01

To investigate the effects of eye diseases on several important artists who have been given little attention from a medical-historical viewpoint. The examples chosen demonstrate problems artists have had to face from different types of eye disease, including cataract, glaucoma, and retinal diseases. The ophthalmological care provided is described in terms of scientific knowledge at the time. Investigation of primary and secondary source material. Discussion with art historians and ophthalmic historians. Examination of work by the artists. Artists can be markedly affected by ocular diseases that change their ability to see the world. The individuals described here worked during the 19th century and first half of the 20th century. Homer Martin suffered from cataracts, and his works reveal changes in details and color as he aged. Henri Harpignies, who had an extremely long career, undoubtedly had cataracts and may also have had macular degeneration. Angle-closure glaucoma blinded Jules Chéret. Auguste Ravier suffered from neovascular glaucoma in one eye and was able to work with his remaining eye, which developed a cataract. Louis Valtat suffered from what was in all likelihood open-angle glaucoma, but specific changes due to this disease are not apparent in his work. Roger Bissière developed glaucoma and did well following filtration surgery. George Du Maurier lost one eye from what was probably a retinal detachment and later suffered from a central retinal problem in the other eye. Diseases of the eye may profoundly influence artists by altering their perception of the world. The specific effects may vary, depending on the disease, its severity, and the psychology of the artist. Cataracts typically affect an artist's ability to depict color and detail. The effect of glaucoma generally depends on whether central vision is preserved. Disease that affects the center of the retina has a substantial effect on an artist's ability to depict fine details. Ophthalmological care was limited during the lifetimes of the artists under consideration, by comparison to 21st century standards. When medical or surgical therapy was ineffective, the most important thing a physician could offer these artists was consolation against anxiety and depression.

The Visual Difficulties of Selected Artists and Limitations of Ophthalmological Care During The 19th and Early 20th Centuries (An AOS Thesis)

PubMed Central

Ravin, James G.

2008-01-01

Purpose To investigate the effects of eye diseases on several important artists who have been given little attention from a medical-historical viewpoint. The examples chosen demonstrate problems artists have had to face from different types of eye disease, including cataract, glaucoma, and retinal diseases. The ophthalmological care provided is described in terms of scientific knowledge at the time. Methods Investigation of primary and secondary source material. Discussion with art historians and ophthalmic historians. Examination of work by the artists. Results Artists can be markedly affected by ocular diseases that change their ability to see the world. The individuals described here worked during the 19th century and first half of the 20th century. Homer Martin suffered from cataracts, and his works reveal changes in details and color as he aged. Henri Harpignies, who had an extremely long career, undoubtedly had cataracts and may also have had macular degeneration. Angle-closure glaucoma blinded Jules Chéret. Auguste Ravier suffered from neovascular glaucoma in one eye and was able to work with his remaining eye, which developed a cataract. Louis Valtat suffered from what was in all likelihood open-angle glaucoma, but specific changes due to this disease are not apparent in his work. Roger Bissière developed glaucoma and did well following filtration surgery. George Du Maurier lost one eye from what was probably a retinal detachment and later suffered from a central retinal problem in the other eye. Conclusions Diseases of the eye may profoundly influence artists by altering their perception of the world. The specific effects may vary, depending on the disease, its severity, and the psychology of the artist. Cataracts typically affect an artist’s ability to depict color and detail. The effect of glaucoma generally depends on whether central vision is preserved. Disease that affects the center of the retina has a substantial effect on an artist’s ability to depict fine details. Ophthalmological care was limited during the lifetimes of the artists under consideration, by comparison to 21st century standards. When medical or surgical therapy was ineffective, the most important thing a physician could offer these artists was consolation against anxiety and depression. PMID:19277248

Proteases in cardiometabolic diseases: Pathophysiology, molecular mechanisms and clinical applications

PubMed Central

Hua, Yinan; Nair, Sreejayan

2014-01-01

Cardiovascular disease is the leading cause of death in the U.S. and other developed country. Metabolic syndrome, including obesity, diabetes/insulin resistance, hypertension and dyslipidemia is major threat for public health in the modern society. It is well established that metabolic syndrome contributes to the development of cardiovascular disease collective called as cardiometabolic disease. Despite documented studies in the research field of cardiometabolic disease, the underlying mechanisms are far from clear. Proteases are enzymes that break down proteins, many of which have been implicated in various diseases including cardiac disease. Matrix metalloproteinase (MMP), calpain, cathepsin and caspase are among the major proteases involved in cardiac remodeling. Recent studies have also implicated proteases in the pathogenesis of cardiometabolic disease. Elevated expression and activities of proteases in atherosclerosis, coronary heart disease, obesity/insulin-associated heart disease as well as hypertensive heart disease have been documented. Furthermore, transgenic animals that are deficient in or overexpress proteases allow scientists to understand the causal relationship between proteases and cardiometabolic disease. Mechanistically, MMPs and cathepsins exert their effect on cardiometabolic diseases mainly through modifying the extracellular matrix. However, MMP and cathepsin are also reported to affect intracellular proteins, by which they contribute to the development of cardiometabolic diseases. On the other hand, activation of calpain and caspases has been shown to influence intracellular signaling cascade including the NF-κB and apoptosis pathways. Clinically, proteases are reported to function as biomarkers of cardiometabolic diseases. More importantly, the inhibitors of proteases are credited with beneficial cardiometabolic profile, although the exact molecular mechanisms underlying these salutary effects are still under investigation. A better understanding of the role of MMPs, cathepsins, calpains and caspases in cardiometabolic diseases process may yield novel therapeutic targets for threating or controlling these diseases. PMID:24815358

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

PubMed Central

Santana, Genoile; Bendicho, Maria Teresita; Santana, Tamara Celi; dos Reis, Lidiane Bianca; Lemaire, Denise; Lyra, André Castro

2011-01-01

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease. PMID:21915486

Dietary Approaches that Delay Age-Related Diseases

PubMed Central

Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

2006-01-01

Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2–15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet—disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood and even in the fetus may influence the later development of aging diseases and lifespan. PMID:18047254