Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.

PubMed

Frisch, Amos; Colombo, Roberto; Michaelovsky, Elena; Karpati, Mazal; Goldman, Boleslaw; Peleg, Leah

2004-03-01

The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To investigate the genetic history of this mutation in the AJ population, a conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15 homozygotes and 40 heterozygotes for the TSD mutation), suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the insertion was found to be 40+/-12 generations (95% confidence interval: 30-50 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 8th-9th century. This corresponds with the demographic expansion of AJs in central Europe, following the founding of the Ashkenaz settlement in the early Middle Ages. The results are consistent with the geographic distribution of the main TSD mutation, 1278insTATC being more common in central Europe, and with the coalescent times of mutations causing two other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence of a determinant positive selection (heterozygote advantage) over the mutation is provided by a comparison between the estimated age of 1278insTATC and the probability of the current AJ frequency of the mutant allele as a function of its age, calculated by use of a branching-process model. Therefore, the founder effect in a rapidly expanding population arising from a bottleneck provides a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in AJ individuals.

Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease

PubMed Central

Karumuthil-Melethil, Subha; Kalburgi, Sahana Nagabhushan; Thompson, Patrick; Tropak, Michael; Kaytor, Michael D.; Keimel, John G.; Mark, Brian L.; Mahuran, Don; Walia, Jagdeep S.; Gray, Steven J.

2016-01-01

GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 ganglioside (GM2) in neuronal tissue. Two of these are due to the deficiency of the heterodimeric (α–β), “A” isoenzyme of lysosomal β-hexosaminidase (HexA). Mutations in the α-subunit (encoded by HEXA) lead to Tay-Sachs disease (TSD), whereas mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). The third form results from a deficiency of the GM2 activator protein (GM2AP), a substrate-specific cofactor for HexA. In their infantile, acute forms, these diseases rapidly progress with mental and psychomotor deterioration resulting in death by approximately 4 years of age. After gene transfer that overexpresses one of the deficient subunits, the amount of HexA heterodimer formed would empirically be limited by the availability of the other endogenous Hex subunit. The present study used a new variant of the human HexA α-subunit, μ, incorporating critical sequences from the β-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP– GM2 complex. We report the design of a compact adeno-associated viral (AAV) genome using a synthetic promoter–intron combination to allow self-complementary (sc) packaging of the HEXM gene. Also, a previously published capsid mutant, AAV9.47, was used to deliver the gene to brain and spinal cord while having restricted biodistribution to the liver. The novel capsid and cassette design combination was characterized in vivo in TSD mice for its ability to efficiently transduce cells in the central nervous system when delivered intravenously in both adult and neonatal mice. This study demonstrates that the modified HexM is capable of degrading long-standing GM2 storage in mice, and it further demonstrates the potential of this novel scAAV vector design to facilitate widespread distribution of the HEXM gene or potentially other similar-sized genes to the

Sandhoff Disease

MedlinePlus

... Coordinating Committees CounterACT Rigor & Transparency Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene ... virus-delivered gene therapy seen in an animal model of Tay-Sachs and Sandhoff diseases for use ...

UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

ClinicalTrials.gov

2018-03-15

Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

A double mutation in exon 6 of the [beta]-hexosaminidase [alpha] subunit in a patient with the B1 variant of Tay-Sachs disease

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

Ainsworth, P.J.; Coulter-Mackie, M.B.

1992-10-01

The B1 variant form of Tay-Sachs disease is enzymologically unique in that the causative mutation(s) appear to affect the active site in the [alpha] subunit of [beta]-hexosaminidase A without altering its ability to associate with the [beta] subunit. Most previously reported B1 variant mutations were found in exon 5 within codon 178. The coding sequence of the [alpha] subunit gene of a patient with the B1 variant form was examined with a combination of reverse transcription of mRNA to cDNA, PCR, and dideoxy sequencing. A double mutation in exon 6 has been identified: a G[sub 574][yields]C transversion causing a val[submore » 192][yields]leu change and a G[sub 598][yields] A transition resulting in a val[sub 200][yields]met alteration. The amplified cDNAs were otherwise normal throughout their sequence. The 574 and 598 alterations have been confirmed by amplification directly from genomic DNA from the patient and her mother. Transient-expression studies of the two exon 6 mutations (singly or together) in COS-1 cells show that the G[sub 574][yields]C change is sufficient to cause the loss of enzyme activity. The biochemical phenotype of the 574 alteration in transfection studies is consistent with that expected for a B1 variant mutation. As such, this mutation differs from previously reported B1 variant mutations, all of which occur in exon 5. 31 refs., 2 figs., 2 tabs.« less

GM2 gangliosidosis in British Jacob sheep.

PubMed

Wessels, M E; Holmes, J P; Jeffrey, M; Jackson, M; Mackintosh, A; Kolodny, E H; Zeng, B J; Wang, C B; Scholes, S F E

2014-01-01

GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Genetics Home Reference: Tay-Sachs disease

MedlinePlus

... NIH Resources (4 links) GeneEd National Human Genome Research Institute National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet National Institute of Neurological ...

A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

PubMed

Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

2009-01-02

Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.

Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis.

PubMed

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-06-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

PubMed Central

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-01-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

Stem Cell Transplant for Inborn Errors of Metabolism

ClinicalTrials.gov

2017-12-03

Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported.

PubMed

Maegawa, Gustavo H B; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T R

2006-11-01

Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal beta-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, beta-hexosaminidase enzyme activity, and mutation analysis was collected. In our cohort of patients, the mean (+/-SD) age of onset of symptoms was 5.3 +/- 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 +/- 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 +/- 5.5 years. The mean age of onset of speech problems was 7.0 +/- 5.6 years, with a mean time of progression to anarthria of 5.6 +/- 5.3 years. Muscle wasting (10.6 +/- 7.4 years), proximal weakness (11.1 +/- 7.7 years), and incontinence of sphincters (14.6 +/- 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence of R178H and R

Tay-Sachs and Sandhoff Diseases

MedlinePlus

... birth and infant mortality. Solving premature birth Featured articles Accomplishments and lessons learned since the establishment of ... The impact of premature birth on society Featured articles How long should you wait before getting pregnant ...

Learning about Tay-Sachs Disease

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... New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About ... Genome Exhibition Talking Glossary: English Talking Glossary: Español Issues ... Contacts Media Resources NHGRI-Related News Journal Articles ...

NN′-Diacetylchitobiase activity in Tay–Sachs disease and Sandhoff's disease (Short Communication)

PubMed Central

Stirling, John L.

1974-01-01

In Tay–Sachs disease and Sandhoff's disease respectively, one of the N-acetyl-β-hexosaminidases (form A) or both (forms A and B) are absent, but glycosaminoglycans containing N-acetylhexosamines are not accumulated. The presence of NN′-diacetylchitobiase in livers from patients with these diseases raises the possibility that this new enzyme is involved in the metabolism of glycosaminoglycans rather than the enzymes previously described. PMID:4455225

The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

PubMed Central

Maegawa, Gustavo H. B.; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T. R.

2010-01-01

OBJECTIVE Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. METHODS A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, β-hexosaminidase enzyme activity, and mutation analysis was collected. RESULTS In our cohort of patients, the mean (±SD) age of onset of symptoms was 5.3 ± 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 ± 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 ± 5.5 years. The mean age of onset of speech problems was 7.0 ± 5.6 years, with a mean time of progression to anarthria of 5.6 ± 5.3 years. Muscle wasting (10.6 ± 7.4 years), proximal weakness (11.1 ± 7.7 years), and incontinence of sphincters (14.6 ± 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence

Hypotonia

MedlinePlus

... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ...

Tay-Sachs disease preconception screening in Australia: self-knowledge of being an Ashkenazi Jew predicts carrier state better than does ancestral origin, although there is an increased risk for c.1421 + 1G > C mutation in individuals with South African heritage.

PubMed

Lew, Raelia; Burnett, Leslie; Proos, Anné

2011-12-01

The Australasian Community Genetics Program provided a preconception screening for Tay-Sachs disease (TSD) to 4,105 Jewish high school students in Sydney and Melbourne over the 12-year period 1995-2007. By correlating the frequencies of mutant HEXA, MIM *606869 (gene map locus 15q23-q24) alleles with subjects' nominated ethnicity (Ashkenazi/Sephardi/Mixed) and grandparental birthplaces, we established that Ashkenazi ethnicity is a better predictor of TSD carrier status than grandparental ancestral origins. Screening self-identified Ashkenazi subjects detected 95% of TSD carriers (carrier frequency 1:25). Having mixed Ashkenazi and non-Ashkenazi heritage reduced the carrier frequency (1:97). South African heritage conveyed a fourfold risk of c.1421 + 1G > C mutation compared with other AJ subjects (odds ratio (OR), 4.19; 95% confidence interval (CI), 1.83-9.62, p = 0.001), but this was the only specific case of ancestral origin improving diagnostic sensitivity over that based on determining Ashkenazi ethnicity. Carriers of c.1278insTATC mutations were more likely to have heritage from Western Europe (OR, 1.65 (95% CI, 1.04-2.60), p = 0.032) and South Eastern Europe (OR, 1.77 (95% CI, 1.14-2.73), p = 0.010). However, heritage from specific European countries investigated did not significantly alter the overall odds of TSD carrier status.

SAChES: Scalable Adaptive Chain-Ensemble Sampling.

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

Swiler, Laura Painton; Ray, Jaideep; Ebeida, Mohamed Salah

We present the development of a parallel Markov Chain Monte Carlo (MCMC) method called SAChES, Scalable Adaptive Chain-Ensemble Sampling. This capability is targed to Bayesian calibration of com- putationally expensive simulation models. SAChES involves a hybrid of two methods: Differential Evo- lution Monte Carlo followed by Adaptive Metropolis. Both methods involve parallel chains. Differential evolution allows one to explore high-dimensional parameter spaces using loosely coupled (i.e., largely asynchronous) chains. Loose coupling allows the use of large chain ensembles, with far more chains than the number of parameters to explore. This reduces per-chain sampling burden, enables high-dimensional inversions and the usemore » of computationally expensive forward models. The large number of chains can also ameliorate the impact of silent-errors, which may affect only a few chains. The chain ensemble can also be sampled to provide an initial condition when an aberrant chain is re-spawned. Adaptive Metropolis takes the best points from the differential evolution and efficiently hones in on the poste- rior density. The multitude of chains in SAChES is leveraged to (1) enable efficient exploration of the parameter space; and (2) ensure robustness to silent errors which may be unavoidable in extreme-scale computational platforms of the future. This report outlines SAChES, describes four papers that are the result of the project, and discusses some additional results.« less

Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

ClinicalTrials.gov

2017-11-15

Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

Therapeutic evaluation of GM2 gangliosidoses by ELISA using anti-GM2 ganglioside antibodies.

PubMed

Tsuji, Daisuke; Higashine, Yukari; Matsuoka, Kazuhiko; Sakuraba, Hitoshi; Itoh, Kohji

2007-03-01

GM2 gangliosidoses, including Tay-Sachs disease, Sandhoff disease and the AB variant, comprise deficiencies of beta-hexosaminidase isozymes and GM2 ganglioside activator protein associated with accumulation of GM2 ganglioside (GM2) in lysosomes and neurosomatic clinical manifestations. A simple assay system for intracellular quantification of GM2 is required to evaluate the therapeutic effects on GM2-gangliosidoses. We newly established a cell-ELISA system involving anti-GM2 monoclonal antibodies for measuring GM2 storage in fibroblasts from Tay-Sachs and Sandhoff disease patients. We succeeded in detecting the corrective effect of enzyme replacement on elimination of GM2 in the cells with this ELISA system. This simple and sensitive system should be useful as additional diagnosis tool as well as therapeutic evaluation of GM2 gangliosidoses.

[Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

PubMed

Tsuji, Daisuke

2013-01-01

Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice.

75 FR 14379 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG (RRD) Models Tay 620-15, Tay 650-15...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-25

...: Following a review of operational data of the Tay 651-54 engine, it has been found that the actual stress... found that the actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3... actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3, 6, 7 and 12...

An economic evaluation of a genetic screening program for Tay-Sachs disease.

PubMed Central

Nelson, W B; Swint, J M; Caskey, C T

1978-01-01

The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives. PMID:418675

An economic evaluation of a genetic screening program for Tay-Sachs disease.

PubMed

Nelson, W B; Swint, J M; Caskey, C T

1978-03-01

The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives.

An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).

PubMed

Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

2011-01-01

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were

Longitudinal Study of Neurodegenerative Disorders

ClinicalTrials.gov

2018-01-31

MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

Animal models of GM2 gangliosidosis: utility and limitations.

PubMed

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.

GM1 and GM2 gangliosides: recent developments.

PubMed

Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

2014-03-01

GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction.

Genetic Counseling in Mental Retardation.

ERIC Educational Resources Information Center

Bowen, Peter

The task of the genetic counselor who identifies genetic causes of mental retardation and assists families to understand risk of recurrence is described. Considered are chromosomal genetic disorders such as Down's syndrome, inherited disorders such as Tay-Sachs disease, identification by testing the amniotic fluid cells (amniocentresis) in time…

75 FR 24825 - Airworthiness Directives; Rolls-Royce Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... for corrosion attack are required. The action specified by this European Aviation Safety Agency (EASA... Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay 651-54 Turbofan Engines AGENCY: Federal Aviation...-pressure turbine disks stage 2 and stage 3. The corrosion is considered to be caused by the environment in...

Judaism, genetic screening and genetic therapy.

PubMed

Rosner, F

1998-01-01

Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.

PubMed

Sheth, Jayesh; Datar, Chaitanya; Mistri, Mehul; Bhavsar, Riddhi; Sheth, Frenny; Shah, Krati

2016-07-11

GM2 gangliosidosis-AB variants a rare autosomal recessive neurodegenerative disorder occurring due to deficiency of GM2 activator protein resulting from the mutation in GM2A gene. Only seven mutations in nine cases have been reported from different population except India. Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. Horizontal nystagmus and cherry red spot was detected during ophthalmic examination. MRI of brain revealed putaminal hyperintensity and thalamic hypointensity with some unmyelinated white matter in T2/T1 weighted images. Initially he was suspected having Tay-Sachs disease and finally diagnosed as GM2 gangliosidosis, AB variant due to truncated protein caused by nonsense mutation c.472 G > T (p.E158X) in GM2Agene. Children with phenotypic presentation as GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) and normal enzyme activity of β-hexosaminidase-A and -B in leucocytes need to be investigated for GM2 activator protein deficiency.

Compulsory DNA Sampling of Service Members for Inclusion in the DOD DNA Registry: Remains Identification With a Risk

DTIC Science & Technology

1996-04-01

for Tay-Sachs disease, cystic fibrosis, Huntingtons disease, Duchenne muscular dystrophy , 26alcoholism, and susceptibility to certain types of cancer...and an increased risk of infection and injury to muscle , nerves, and blood vessels was sufficiently compelling to outweigh the state’s interest in...them into electrical impulses. These surgically implanted devices could produce electronic impulses to induce paralyzed muscles to contract and

Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

PubMed Central

Kingsmore, Stephen

2012-01-01

Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

[Physician satire and patient scorn in Hans Sachs' old Nürnberg and the physicians].

PubMed

Sauerbeck, K O

1993-01-01

Among the best poems of Hans Sachs quite a few describe patient-physician relationships in 16th century Nuremberg. These poems offer a vivid impression of the technical aspects as well as of the social context of medical treatment at the time. Hans Sachs ridiculed the doctors and their patients, implying that everybody attempted to cheat the other side, and he provides evidence of a great influence of charlatans on the country population. The poems of Hans Sachs are extraordinary pieces or art; their aesthetics, though, appear unusual to us today. Medical satire is part of all European cultures, and has been written throughout medical history. Most motives of later satires focussing on physicians may be traced to Hans Sachs' poetry.

In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

PubMed

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J; Samulski, R Jude; Wakarchuk, Warren; Mark, Brian L; Mahuran, Don J

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

In Cellulo Examination of a Beta-Alpha Hybrid Construct of Beta-Hexosaminidase A Subunits, Reported to Interact with the GM2 Activator Protein and Hydrolyze GM2 Ganglioside

PubMed Central

Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J.; Samulski, R. Jude; Wakarchuk, Warren; Mark, Brian L.; Mahuran, Don J.

2013-01-01

The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

PubMed

Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

2011-03-01

Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

Gangliosidoses.

PubMed

Patterson, Marc C

2013-01-01

The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. Copyright © 2013 Elsevier B.V. All rights reserved.

Tay's syndrome: MRI.

PubMed

Porto, L; Weis, R; Schulz, C; Reichel, P; Lanfermann, H; Zanella, F E

2000-11-01

Tay's syndrome is a trichothiodystrophy associated with congenital ichthyosis. We report the findings on MRI and spectroscopy in a young girl with sparse, short, ruffled hair, dry skin and delayed milestones. T2-weighted images showed prominent diffuse confluent increase in signal symmetrically in all the supratentorial white matter. These findings are similar to those in a previously described case, and consistent with dysmyelination. Spectroscopy showed increased myoinositol and decreased choline.

Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

PubMed

Levin, M

1999-01-01

Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions Using Homologous Osteochondral Allograft.

PubMed

Alkaduhimi, Hassanin; van den Bekerom, Michel P J; van Deurzen, Derek F P

2017-06-01

Posterior shoulder dislocations are accompanied by high forces and can result in an anteromedial humeral head impression fracture called a reverse Hill-Sachs lesion. This reverse Hill-Sachs lesion can result in serious complications including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis, persistent joint stiffness, and loss of shoulder function. Treatment is challenging and depends on the amount of bone loss. Several techniques have been reported to describe the surgical treatment of lesions larger than 20%. However, there is still limited evidence with regard to the optimal procedure. Favorable results have been reported by performing segmental reconstruction of the reverse Hill-Sachs lesion with bone allograft. Although the procedure of segmental reconstruction has been used in several studies, its technique has not yet been well described in detail. In this report we propose a step-by-step description of the technique how to perform a segmental reconstruction of a reverse Hill-Sachs defect.

Constant mean curvature slicings of Kantowski-Sachs spacetimes

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

Heinzle, J. Mark

2011-04-15

We investigate existence, uniqueness, and the asymptotic properties of constant mean curvature (CMC) slicings in vacuum Kantowski-Sachs spacetimes with positive cosmological constant. Since these spacetimes violate the strong energy condition, most of the general theorems on CMC slicings do not apply. Although there are in fact Kantowski-Sachs spacetimes with a unique CMC foliation or CMC time function, we prove that there also exist Kantowski-Sachs spacetimes with an arbitrary number of (families of) CMC slicings. The properties of these slicings are analyzed in some detail.

Julius Sachs (1868): The father of plant physiology.

PubMed

Kutschera, Ulrich; Niklas, Karl J

2018-05-17

The year 2018 marks the 150th anniversary of the first publication of Julius von Sachs' (1832-1897) Lehrbuch der Botanik (Textbook of Botany), which provided a comprehensive summary of what was then known about the plant sciences. Three years earlier, in 1865, Sachs produced the equally impressive Handbuch der Experimental-Physiologie der Pflanzen (Handbook of Experimental Plant Physiology), which summarized the state of knowledge in all aspects of the discipline known today as plant physiology. Both of these books provided numerous insights based on Sachs' seminal experiments. By virtue of a reliance on detailed empirical observation and the rigorous application of chemical and physical principles, it is fair to say that the publication of these two monumental works marked the beginning of what can be called "modern-day" plant science. Moreover, Sachs' Lehrbuch der Botanik prefigured the ascendance of plant molecular biology and the systems biology of photoautotrophic organisms. Regrettably, many of the insights of this great scientist have been forgotten by the generations who followed. It is only fitting, therefore, that the anniversary of the publication of the Lehrbuch der Botanik and the career of "the father of plant physiology" should be honored and reviewed, particularly because Sachs established the physiology of green organisms as an integral branch of botany and incorporated a Darwinian perspective into plant biology. Here we highlight key insights, with particular emphasis on Sachs' detailed discussion of sexual reproduction at the cellular level and his endorsement of Darwinian evolution. © 2018 Botanical Society of America.

Classification of Kantowski-Sachs metric via conformal Ricci collineations

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Khan, Fawad; Bokhari, Ashfaque H.; Akhtar, Sumaira Saleem

In this paper, we present a classification of the Kantowski-Sachs spacetime metric according to its conformal Ricci collineations (CRCs). Solving the CRC equations, it is shown that the Kantowski-Sachs metric admits 15-dimensional Lie algebra of CRCs when its Ricci tensor is non-degenerate and an infinite dimensional group of CRCs when the Ricci tensor is degenerate. Some examples of Kantowski-Sachs metric admitting nontrivial CRCs are presented and their physical interpretation is provided.

Establishment of the Fox Chase Network Breast Cancer Risk Registry

DTIC Science & Technology

1996-10-01

Neurofibromatosis, type I h) Non-insulin dependent diabetes i) Turner Syndrome j) Tay Sachs Disease k) Marfan Syndrome 1) Cancer (tricky!) 2. Human chromosomes are...gastrointestinal and genitourinary cancers (4). Altogether, over 12 genetic-cancer syndromes have been localized to a specific gene (5). Some families suffer...component of the rare help test the best ways to Risk Registry._5, cases of breast cancer tions are likely to result Li-Fraumeni syndrome , only and up to

Tectonic Evolution of Jabal Tays Ophiolite Complex, Eastern Arabian Shield, Saudi Arabia

NASA Astrophysics Data System (ADS)

AlHumidan, Saad; Kassem, Osama; Almutairi, Majed; Al-Faifi, Hussain; Kahal, Ali

2017-04-01

Microstructural analysis is important for investigation of tectonic evaluation of Jable Tays area. Furthermore, the Jable Tays ophiolite complex is effected by Al Amar -Idsas fault. The nature of the Al Amar-Idsas fault is a part of the Eastern Arabian Shield, which was subjected to multiple interpretations. Through fieldwork investigation, microscopic examination, and microstructural analysis, we aim to understand the evolution and tectonic setting of the Jable Tays area. Finite-strain data displays that the Abt schist, the metavolcanics and the metagranites are highly to moderately deformed. The axial ratios in the XZ section range from 1.40 to 2.20. The long axes of the finite-strain ellipsoids trend NW- SE and W-E in the Jable Tays area while, their short axes are subvertical to subhorizontal foliations. The strain magnitude does not increase towards the tectonic contacts between the Abt schist and metavolcano-sedimentary. While majority of the obtained data indicate a dominant oblate with minor prolate strain symmetries in the Abt schist, metavolcano-sedimentary and metagranites. The strain data also indicate flattening with some constriction. We assume that the Abt schist and the metavolcano-sedimentry rocks have similar deformation behavior. The finite strain in the studied rocks accumulated during the metamorphism that effected by thrusting activity. Based on these results, we finally concluded that the contact between Abt schist and metavolcano-sedimentary rocks were formed during the progressive thrusting under brittle to semi-ductile deformation conditions by simple shear that also involved a component of vertical shortening, causing subhorizontal foliation in Jable Tays area.

Lysosomal storage diseases

PubMed Central

Ferreira, Carlos R.; Gahl, William A.

2016-01-01

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.

PubMed

Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

2016-01-01

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

PubMed Central

Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

2016-01-01

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

Julius Sachs (1832–1897) and the Unity of Life

PubMed Central

Kutschera, Ulrich; Baluška, František

2015-01-01

In 1865, the German botanist Julius Sachs published a seminal monograph entitled Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) and hence became the founder of a new scientific discipline that originated 150 y ago. Here, we outline the significance of the achievements of Sachs. In addition, we document, with reference to his Vorlesungen über Pflanzen-Physiologie (Lectures on the Physiology of Plants, 1882), that Sachs was one of the first experimentalists who proposed the functional unity of all organisms alive today (humans, animals, plants and other “vegetable” organisms, such as algae, cyanophyceae, fungi, myxomycetes, and bacteria). PMID:26359706

Fingerprinting of bed sediment in the Tay Estuary, Scotland: an environmental magnetism approach

NASA Astrophysics Data System (ADS)

Jenkins, Pierre A.; Duck, Rob W.; Rowan, John S.; Walden, John

Sediment fingerprinting is commonly used for sediment provenance studies in lakes, rivers and reservoirs and on hillslopes and floodplains. This investigation explores the mixing of terrestrial and marine-derived sediment in the Tay Estuary, Scotland, using mineral magnetic attributes for fingerprinting. Samples representative of the estuary sediments and of four sources (end-members) were subjected to a suite of magnetic susceptibility and remanence measurements. Sediment samples from the beds of the Rivers Tay and Earn represented fluvial inputs while samples from the Angus and Fife coasts represented marine input. Multivariate discriminant and factor analysis showed that the sources could be separated on the basis of six magnetic parameters in a simple multivariate unmixing model to identify source contributions to estuarine bed sediments. Multi-domain magnetite signatures, characteristic of unweathered bedrock, dominate the magnetic measurements. Overall contributions of 3% from the River Earn, 17% from the River Tay, 29% from the Angus coast and 51% from the Fife coast source end-members, demonstrated the present-day regime of marine sediment derivation in the Tay Estuary. However, this conceals considerable spatial variability both along-estuary and in terms of sub-environments, with small-scale variations in sediment provenance reflecting local morphology, particularly areas of channel convergence.

GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed.

PubMed

Smith, Nicholas J; Winstone, Anne Marie; Stellitano, Lesley; Cox, Timothy M; Verity, Christopher M

2012-02-01

To report the demographic, phenotypic, and time-to-diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK-based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay-Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile-onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile-onset Tay-Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile-onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile- and juvenile-onset disease respectively. GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high-risk ethnic groups. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

17 CFR 249.619 - Form TA-Y2K, information required of transfer agents pursuant to section 17 of the Securities...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form TA-Y2K, information... Certain Exchange Members, Brokers, and Dealers § 249.619 Form TA-Y2K, information required of transfer... affecting Form TA-Y2K, see the List of CFR Sections Affected, which appears in the Finding Aids section of...

Proper Conformal Killing Vectors in Kantowski-Sachs Metric

NASA Astrophysics Data System (ADS)

Hussain, Tahir; Farhan, Muhammad

2018-04-01

This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

CO2 Storage Potential of the Eocene Tay Sandstone, Central North Sea, UK

NASA Astrophysics Data System (ADS)

Gent, Christopher; Williams, John

2017-04-01

Carbon Capture and Storage (CCS) is crucial for low-carbon industry, climate mitigation and a sustainable energy future. The offshore capacity of the UK is substantial and has been estimated at 78 Gt of CO2 in saline aquifers and hydrocarbon fields. The early-mid Eocene Tay Sandstone Member of the Central North Sea (CNS) is a submarine-fan system and potential storage reservoir with a theoretical capacity of 123 Mt of CO2. The Tay Sandstone comprises of 4 sequences, amalgamating into a fan complex 125km long and 40 km at a minimum of 1500 m depth striking NW-SE, hosting several hydrocarbon fields including Gannett A, B, D and Pict. In order to better understand the storage potential and characteristics, the Tay Sandstone over Quadrant 21 has been interpreted using log correlation and 3D seismic. Understanding the internal and external geometry of the sandstone as well as the lateral extent of the unit is essential when considering CO2 vertical and horizontal fluid flow pathways and storage security. 3D seismic mapping of a clear mounded feature has revealed the youngest sequence of the Tay complex; a homogenous sand-rich channel 12 km long, 1.5 km wide and on average 100 m thick. The sandstone has porosity >35%, permeability >5 D and a net to gross of 0.8, giving a total pore volume of 927x106 m3. The remaining three sequences are a series of stacked channels and interbedded mudstones which are more quiescent on the seismic, however, well logs indicate each subsequent sequence reduce in net to gross with age as mud has a greater influence in the early fan system. Nevertheless, the sandstone properties remain relatively consistent and are far more laterally extensive than the youngest sequence. The Tay Sandstone spatially overlaps several other potential storage sites including the older Tertiary sandstones of the Cromarty, Forties and Mey Members and deeper Jurassic reservoirs. This favours the Tay Sandstone to be considered in a secondary or multiple stacked

78 FR 26407 - Goldman Sachs Trust II, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-06

... Sachs Trust II, et al.; Notice of Application April 29, 2013. AGENCY: Securities and Exchange Commission... would grant relief from certain disclosure requirements. APPLICANTS: Goldman Sachs Trust II (the ``Trust...'', each of GSAM and GSAMI an ``Adviser'' and collectively, ``Advisers,'' and together with the Trust...

Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

PubMed

Oddoux, C; Guillen-Navarro, E; Ditivoli, C; Dicave, E; Cilio, M R; Clayton, C M; Nelson, H; Sarafoglou, K; McCain, N; Peretz, H; Seligsohn, U; Luzzatto, L; Nafa, K; Nardi, M; Karpatkin, M; Aksentijevich, I; Kastner, D; Axelrod, F; Ostrer, H

1999-12-01

The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried the connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin.

Basic versus applied research: Julius Sachs (1832-1897) and the experimental physiology of plants.

PubMed

Kutschera, Ulrich

2015-01-01

The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This "plant-microbe-view" of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845-1920), so that the term "Sachs-Pfeffer-Principle of Experimental Plant Research" appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria).

Posterior shoulder dislocation with a reverse Hill-Sachs lesion treated with frozen femoral head bone allograft combined with osteochondral autograft transfer.

PubMed

Mastrokalos, Dimitrios S; Panagopoulos, Georgios N; Galanopoulos, Ioannis P; Papagelopoulos, Panayiotis J

2017-10-01

Management of a posterior shoulder dislocation with an associated reverse Hill-Sachs lesion is challenging, both diagnostically and therapeutically. Diagnosis is frequently delayed or missed, whereas the resulting humeral head defect is often larger and more difficult to salvage than in anterior shoulder dislocations. This report presents the case of a 29-year-old male with a recurrent posterior shoulder dislocation associated with a large reverse Hill-Sachs defect, treated with bone augmentation of the lesion with a combination of fresh femoral head allograft and a locally harvested humeral head autograft transfer, with a successful outcome. Level of evidence V.

75 FR 44031 - Goldman, Sachs & Co., et al.; Notice of Application and Temporary Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-27

... International (``GSAMI''), Goldman Sachs Hedge Fund Strategies LLC (``GSHFS''), Commonwealth Annuity and Life... marketing materials used in connection with residential mortgage-related securities offerings by Goldman... marketing materials, (iv) where Goldman Sachs is the lead underwriter of an offering of residential mortgage...

GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.

PubMed

Kaya, Namik; Al-Owain, Mohammad; Abudheim, Nada; Al-Zahrani, Jawaher; Colak, Dilek; Al-Sayed, Moeen; Milanlioglu, Aysel; Ozand, Pinar T; Alkuraya, Fowzan S

2011-06-01

The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. Copyright © 2011 Wiley-Liss, Inc.

Natural History of Infantile GM2 Gangliosidosis

PubMed Central

Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.

2011-01-01

OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. PMID:22025593

Basic versus applied research: Julius Sachs (1832–1897) and the experimental physiology of plants

PubMed Central

Kutschera, Ulrich

2015-01-01

The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This “plant-microbe-view” of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845–1920), so that the term “Sachs-Pfeffer-Principle of Experimental Plant Research” appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria). PMID:26146794

The white matter of the human cerebrum: Part I The occipital lobe by Heinrich Sachs

PubMed Central

Forkel, Stephanie J.; Mahmood, Sajedha; Vergani, Francesco; Catani, Marco

2015-01-01

This is the first complete translation of Heinrich Sachs' outstanding white matter atlas dedicated to the occipital lobe. This work is accompanied by a prologue by Prof Carl Wernicke who for many years was Sachs' mentor in Breslau and enthusiastically supported his work. PMID:25527430

GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease.

PubMed

Sanders, Douglas N; Zeng, Rong; Wenger, David A; Johnson, Gary S; Johnson, Gayle C; Decker, Jared E; Katz, Martin L; Platt, Simon R; O'Brien, Dennis P

2013-01-01

GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of G(M2) gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins. Copyright © 2012 Elsevier Inc. All rights reserved.

Calculating the Sachs-Wolfe Effect from Solutions of Null Geodesics in Perturbed FRW Spacetime

NASA Astrophysics Data System (ADS)

Arroyo-Cárdenas, C. A.; Muñoz-Cuartas, J. C.

2017-07-01

In the upcoming precision era in cosmology, fine grained effects will be measured accurately. In particular, the late integrated Sachs-Wolfe (ISW) effect measurements will be improved to levels of unprecedented precision. The ISW consists on temperature fluctuations in the CMB due to gravitational redshift induced by the evolving potential well of large scale structure in the Universe. Currently there is large controversy related to the actual observability of the ISW effect. In principle, it is expected that, as an effect of the late accelerated expansion of the universe motivated by the current amount of dark energy, large scale structures may evolve rapidly, inducing an observable signature in the CMB photons in the way of a ISW anisotropy in the CMB. Tension arises since using galaxy redshift surveys some works report a temperature fluctuations with amplitude smaller than predicted by the Lambda-CDM. We argue that these discrepancies may be originated in the approximation that one has to make to get the classic Sachs-Wolfe effect. In this work, we compare the classic Sachs-Wolfe approximation with an exact solution to the propagation of photons in a dynamical background. We solve numerically the null geodesics on a perturbed FRW spacetime in the Newtonian gauge. From null geodesics, temperature fluctuations in the CMB due to the evolving potential has been calculated. Since solving geodesics accounts for more terms than solving the Sachs-Wolfe (approximated) integral, our results are more accurate. We have been able to substract the background cosmological redshift with the information provided by null geodesics, which allows to get an estimate of the integrated Sachs-Wolfe effect contribution to the temperature of the CMB.

Diagnosing Lysosomal Storage Disorders: The GM2 Gangliosidoses.

PubMed

Hall, Patricia; Minnich, Sara; Teigen, Claire; Raymond, Kimiyo

2014-10-01

The GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by defective β-hexosaminidase. There are three clinical conditions in this group: Tay-Sachs disease (TSD), Sandhoff disease (SD), and hexosaminidase activator deficiency. The three conditions are clinically indistinguishable. TSD and SD have been identified with infantile, juvenile, and adult onset forms. The activator deficiency is only known to present with infantile onset. Diagnosis of TSD and SD is based on decreased hexosaminidase activity and a change in the percentage of activity between isoforms. There are no biochemical tests currently available for activator deficiency. This unit provides a detailed procedure for identifying TSD and SD in affected individuals and carriers from leukocyte samples, the most robust sample type available. Copyright © 2014 John Wiley & Sons, Inc.

Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection

PubMed Central

Risch, Neil; Tang, Hua; Katzenstein, Howard; Ekstein, Josef

2003-01-01

The presence of four lysosomal storage diseases (LSDs) at increased frequency in the Ashkenazi Jewish population has suggested to many the operation of natural selection (carrier advantage) as the driving force. We compare LSDs and nonlysosomal storage diseases (NLSDs) in terms of the number of mutations, allele-frequency distributions, and estimated coalescence dates of mutations. We also provide new data on the European geographic distribution, in the Ashkenazi population, of seven LSD and seven NLSD mutations. No differences in any of the distributions were observed between LSDs and NLSDs. Furthermore, no regular pattern of geographic distribution was observed for LSD versus NLSD mutations—with some being more common in central Europe and others being more common in eastern Europe, within each group. The most striking disparate pattern was the geographic distribution of the two primary Tay-Sachs disease mutations, with the first being more common in central Europe (and likely older) and the second being exclusive to eastern Europe (primarily Lithuania and Russia) (and likely much younger). The latter demonstrates a pattern similar to two other recently arisen Lithuanian mutations, those for torsion dystonia and familial hypercholesterolemia. These observations provide compelling support for random genetic drift (chance founder effects, one ∼11 centuries ago that affected all Ashkenazim and another ∼5 centuries ago that affected Lithuanians), rather than selection, as the primary determinant of disease mutations in the Ashkenazi population. PMID:12612865

Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

PubMed

de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

2016-10-04

Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

CMB anisotropies at all orders: the non-linear Sachs-Wolfe formula

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

Roldan, Omar, E-mail: oaroldan@if.ufrj.br

2017-08-01

We obtain the non-linear generalization of the Sachs-Wolfe + integrated Sachs-Wolfe (ISW) formula describing the CMB temperature anisotropies. Our formula is valid at all orders in perturbation theory, is also valid in all gauges and includes scalar, vector and tensor modes. A direct consequence of our results is that the maps of the logarithmic temperature anisotropies are much cleaner than the usual CMB maps, because they automatically remove many secondary anisotropies. This can for instance, facilitate the search for primordial non-Gaussianity in future works. It also disentangles the non-linear ISW from other effects. Finally, we provide a method which canmore » iteratively be used to obtain the lensing solution at the desired order.« less

The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

PubMed Central

Gan-Or, Ziv; Ozelius, Laurie J.; Bar-Shira, Anat; Saunders-Pullman, Rachel; Mirelman, Anat; Kornreich, Ruth; Gana-Weisz, Mali; Raymond, Deborah; Rozenkrantz, Liron; Deik, Andres; Gurevich, Tanya; Gross, Susan J.; Schreiber-Agus, Nicole; Giladi, Nir; Bressman, Susan B.

2013-01-01

Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD). Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex. Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9–22.8, p < 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions: The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development. PMID:23535491

Cloning and sequence analysis of a cDNA encoding the alpha-subunit of mouse beta-N-acetylhexosaminidase and comparison with the human enzyme.

PubMed Central

Beccari, T; Hoade, J; Orlacchio, A; Stirling, J L

1992-01-01

cDNAs encoding the mouse beta-N-acetylhexosaminidase alpha-subunit were isolated from a mouse testis library. The longest of these (1.7 kb) was sequenced and showed 83% similarity with the human alpha-subunit cDNA sequence. The 5' end of the coding sequence was obtained from a genomic DNA clone. Alignment of the human and mouse sequences showed that all three putative N-glycosylation sites are conserved, but that the mouse alpha-subunit has an additional site towards the C-terminus. All eight cysteines in the human sequence are conserved in the mouse. There are an additional two cysteines in the mouse alpha-subunit signal peptide. All amino acids affected in Tay-Sachs-disease mutations are conserved in the mouse. Images Fig. 1. PMID:1379046

Sachs' free data in real connection variables

NASA Astrophysics Data System (ADS)

De Paoli, Elena; Speziale, Simone

2017-11-01

We discuss the Hamiltonian dynamics of general relativity with real connection variables on a null foliation, and use the Newman-Penrose formalism to shed light on the geometric meaning of the various constraints. We identify the equivalent of Sachs' constraint-free initial data as projections of connection components related to null rotations, i.e. the translational part of the ISO(2) group stabilising the internal null direction soldered to the hypersurface. A pair of second-class constraints reduces these connection components to the shear of a null geodesic congruence, thus establishing equivalence with the second-order formalism, which we show in details at the level of symplectic potentials. A special feature of the first-order formulation is that Sachs' propagating equations for the shear, away from the initial hypersurface, are turned into tertiary constraints; their role is to preserve the relation between connection and shear under retarded time evolution. The conversion of wave-like propagating equations into constraints is possible thanks to an algebraic Bianchi identity; the same one that allows one to describe the radiative data at future null infinity in terms of a shear of a (non-geodesic) asymptotic null vector field in the physical spacetime. Finally, we compute the modification to the spin coefficients and the null congruence in the presence of torsion.

Simultaneous quantification of GM1 and GM2 gangliosides by isotope dilution tandem mass spectrometry.

PubMed

Gu, Jianghong; Tifft, Cynthia J; Soldin, Steven J

2008-04-01

Gangliosides (GGs) are considered as diagnostic biomarkers and therapeutic targets and agents. The goal of this study was to develop a tandem mass spectrometry (MS/MS) method for the simultaneous measurement of both GM1 and GM2 gangliosides in human cerebrospinal fluid (CSF) samples in order to be able to determine their concentrations in patients with Tay-Sachs and Sandhoff disease and assess whether drugs or transplantation affect their concentrations. An API-4000 tandem mass spectrometer equipped with TurboIonSpray source and Shimadzu HPLC system was employed to perform the analysis using isotope dilution with deuterium labeled internal standards. To a 1.5 mL conical plastic Eppendorf centrifuge tube, 40 microL of human CSF sample was added and mixed with 400 microL of internal standard solution for deproteinization. After centrifugation, 100 microL of supernatant was injected onto a C-18 column. After a 2.5 min wash, the switching valve was activated and the analytes were eluted from the column with a water/methanol gradient into the MS/MS system. Quantification by multiple reaction-monitoring (MRM) analysis was performed in the negative mode. The within-day coefficients of variation were <3% for GM1 and <2% for GM2 and the between-day coefficients of variation were <5% for both GM1 and GM2 at all concentrations tested. Accuracy ranged between 98% and 102% for both analytes. Good linearity was also obtained within the concentration range of 10-200 ng/mL (6.5-129.3 nmol/L) for GM1 and 5-100 ng/mL (3.6-72.3 nmol/L) for GM2 (r> or =0.995). A new simple, accurate, and fast isotope dilution tandem mass spectrometry method was developed for the simultaneous quantification of GM1 and GM2 gangliosides in a small amount of human CSF. Concentrations were measured in "normal" CSF and in CSF from patients with Tay-Sachs disease.

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

Petroulakis, E.; Cao, Z.; Salo, T.

Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affectedmore » brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.« less

Stigmatization of carrier status: social implications of heterozygote genetic screening programs.

PubMed Central

Kenen, R H; Schmidt, R M

1978-01-01

Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585

78 FR 24447 - Goldman Sachs Trust, et al.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-25

... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30471; 812-14075] Goldman Sachs Trust, et al.; Notice of Application April 19, 2013. AGENCY: Securities and Exchange Commission..., or cause more than 10% of the acquired company's voting stock to be owned by investment companies and...

Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory of gravitation

NASA Astrophysics Data System (ADS)

Pawar, D. D.; Shahare, S. P.; Dagwal, V. J.

2018-02-01

Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory for perfect fluid has been investigated. The general solution of field equations in Brans-Dicke theory for the combined scalar and tensor field are obtained by using power law relation. Also, some physical and geometrical parameters are obtained and discussed.

Current practices of commercial cryobanks in screening prospective donors for genetic disease and reproductive risk.

PubMed

Conrad, E A; Fine, B; Hecht, B R; Pergament, E

1996-01-01

To determine how the screening practices of commercial semen banks vary from published guidelines, which factors influence cryobanks to exclude prospective semen donors for genetic reasons, and the current role of clinical geneticists/genetic counselors in evaluating prospective semen donors. The genetic screening of prospective donors by commercial semen banks was evaluated using written questionnaires completed by bank directors. Responses were analyzed to determine exclusion criteria, adherence to published guidelines, and contribution of genetic professionals. Semen banks were selected on the basis of membership in the American Association of Tissue Banks and commercial use of semen for artificial insemination by donor. Semen bank practices as reported by commercial semen bank directors. Of 37 eligible banks, 16 responded. All screen prospective donors by medical/family history and physical examination, 94% have upper age limits; 63% examine for minor physical defects; 56% routinely karyotype; 81% screen men of ethnic groups at risk for Tay Sachs disease, sickle cell disease and thalassemia; 19% screen all donors; 25% screen all donors for cystic fibrosis and 50% only screen if family history positive. Donor rejection was based on three criteria: mode of inheritance of familial disorder, severity of disease, and availability of carrier/confirmatory testing of donor genotype. Ten of 16 banks have no genetic professional on staff. Commercial semen banks primarily rely on family history as the major exclusion criterion in genetic screening of donors. Considerable differences exist among semen bank practices in accordance with guidelines published by national agencies. Genetic professionals have a minimal effect overall on evaluation of semen donors.

Mapping the integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Manzotti, A.; Dodelson, S.

2014-12-01

On large scales, the anisotropies in the cosmic microwave background (CMB) reflect not only the primordial density field but also the energy gain when photons traverse decaying gravitational potentials of large scale structure, what is called the integrated Sachs-Wolfe (ISW) effect. Decomposing the anisotropy signal into a primordial piece and an ISW component, the main secondary effect on large scales, is more urgent than ever as cosmologists strive to understand the Universe on those scales. We present a likelihood technique for extracting the ISW signal combining measurements of the CMB, the distribution of galaxies, and maps of gravitational lensing. We test this technique with simulated data showing that we can successfully reconstruct the ISW map using all the data sets together. Then we present the ISW map obtained from a combination of real data: the NRAO VLA sky survey (NVSS) galaxy survey, temperature anisotropies, and lensing maps made by the Planck satellite. This map shows that, with the data sets used and assuming linear physics, there is no evidence, from the reconstructed ISW signal in the Cold Spot region, for an entirely ISW origin of this large scale anomaly in the CMB. However a large scale structure origin from low redshift voids outside the NVSS redshift range is still possible. Finally we show that future surveys, thanks to a better large scale lensing reconstruction will be able to improve the reconstruction signal to noise which is now mainly coming from galaxy surveys.

Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

PubMed

Olkhovych, N V; Gorovenko, N G

2016-01-01

The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may

The Kantowski-Sachs Quantum Model with Stiff Matter Fluid

NASA Astrophysics Data System (ADS)

Alvarenga, F. G.; Fracalossi, R.; Freitas, R. C.; Gonçalves, S. V. B.

2018-05-01

In this paper, we study the quantum cosmological Kantowski-Sachs model and we solve the Wheeler-DeWitt equation in minisuperspace to obtain the wave function of the corresponding universe. The perfect fluid is described by Schutz's canonical formalism, which allows to attribute dynamical degrees of freedom to matter. The time is introduced phenomenologically using the fluid's degrees of freedom. In particular, we adopt a stiff matter fluid. The viability of this model is analyzed and discussed.

Black Hole Entropy from Bondi-Metzner-Sachs Symmetry at the Horizon.

PubMed

Carlip, S

2018-03-09

Near the horizon, the obvious symmetries of a black hole spacetime-the horizon-preserving diffeomorphisms-are enhanced to a larger symmetry group with a three-dimensional Bondi-Metzner-Sachs algebra. Using dimensional reduction and covariant phase space techniques, I investigate this augmented symmetry and show that it is strong enough to determine the black hole entropy in any dimension.

Application of DNA Machineries for the Barcode Patterned Detection of Genes or Proteins.

PubMed

Zhou, Zhixin; Luo, Guofeng; Wulf, Verena; Willner, Itamar

2018-06-05

The study introduces an analytical platform for the detection of genes or aptamer-ligand complexes by nucleic acid barcode patterns generated by DNA machineries. The DNA machineries consist of nucleic acid scaffolds that include specific recognition sites for the different genes or aptamer-ligand analytes. The binding of the analytes to the scaffolds initiate, in the presence of the nucleotide mixture, a cyclic polymerization/nicking machinery that yields displaced strands of variable lengths. The electrophoretic separation of the resulting strands provides barcode patterns for the specific detection of the different analytes. Mixtures of DNA machineries that yield, upon sensing of different genes (or aptamer ligands), one-, two-, or three-band barcode patterns are described. The combination of nucleic acid scaffolds acting, in the presence of polymerase/nicking enzyme and nucleotide mixture, as DNA machineries, that generate multiband barcode patterns provide an analytical platform for the detection of an individual gene out of many possible genes. The diversity of genes (or other analytes) that can be analyzed by the DNA machineries and the barcode patterned imaging is given by the Pascal's triangle. As a proof-of-concept, the detection of one of six genes, that is, TP53, Werner syndrome, Tay-Sachs normal gene, BRCA1, Tay-Sachs mutant gene, and cystic fibrosis disorder gene by six two-band barcode patterns is demonstrated. The advantages and limitations of the detection of analytes by polymerase/nicking DNA machineries that yield barcode patterns as imaging readout signals are discussed.

The effect of a combined glenoid and Hill-Sachs defect on glenohumeral stability: a biomechanical cadaveric study using 3-dimensional modeling of 142 patients.

PubMed

Arciero, Robert A; Parrino, Anthony; Bernhardson, Andrew S; Diaz-Doran, Vilmaris; Obopilwe, Elifho; Cote, Mark P; Golijanin, Petr; Mazzocca, Augustus D; Provencher, Matthew T

2015-06-01

Bone loss in anterior glenohumeral instability occurs on both the glenoid and the humerus; however, existing biomechanical studies have evaluated glenoid and humeral head defects in isolation. Thus, little is known about the combined effect of these bony lesions in a clinically relevant model on glenohumeral stability. The purpose of this study was to determine the biomechanical efficacy of a Bankart repair in the setting of bipolar (glenoid and humeral head) bone defects determined via computer-generated 3-dimensional (3D) modeling of 142 patients with recurrent anterior shoulder instability. The null hypothesis was that adding a bipolar bone defect will have no effect on glenohumeral stability after soft tissue Bankart repair. Controlled laboratory study. A total of 142 consecutive patients with recurrent anterior instability were analyzed with 3D computed tomography scans. Two Hill-Sachs lesions were selected on the basis of volumetric size representing the 25th percentile (0.87 cm(3); small) and 50th percentile (1.47 cm(3); medium) and printed in plastic resin with a 3D printer. A total of 21 cadaveric shoulders were evaluated on a custom shoulder-testing device permitting 6 degrees of freedom, and the force required to translate the humeral head anteriorly 10 mm at a rate of 2.0 mm/s with a compressive load of 50 N was determined at 60° of glenohumeral abduction and 60° of external rotation. All Bankart lesions were made sharply from the 2- to 6-o'clock positions for a right shoulder. Subsequent Bankart repair with transosseous tunnels using high-strength suture was performed. Hill-Sachs lesions were made in the cadaver utilizing a plastic mold from the exact replica off the 3D printer. Testing was conducted in the following sequence for each specimen: (1) intact, (2) posterior capsulotomy, (3) Bankart lesion, (4) Bankart repair, (5) Bankart lesion with 2-mm glenoid defect, (6) Bankart repair, (7) Bankart lesion with 2-mm glenoid defect and Hill-Sachs lesion

What influences participation in genetic carrier testing? Results from a discrete choice experiment.

PubMed

Hall, Jane; Fiebig, Denzil G; King, Madeleine T; Hossain, Ishrat; Louviere, Jordan J

2006-05-01

This study explores factors that influence participation in genetic testing programs and the acceptance of multiple tests. Tay Sachs and cystic fibrosis are both genetically determined recessive disorders with differing severity, treatment availability, and prevalence in different population groups. We used a discrete choice experiment with a general community and an Ashkenazi Jewish sample; data were analysed using multinomial logit with random coefficients. Although Jewish respondents were more likely to be tested, both groups seem to be making very similar tradeoffs across attributes when they make genetic testing choices.

[The plant physiologist Julius von Sachs and the academic education of women].

PubMed

Gimmler, Hartmut

2005-01-01

The attitude of the famous plant physiologist Julius von Sachs (1832-1897) to higher education of women is described on the basis of some new documents. Generally, Sachs was in favour of academic education of women at universities, but initially wanted to exclude females from the study of medicine. However, by the example of a bright young Russian lady, who studied medicine in St. Petersburg and who worked 1871 in his laboratory in Würzburg on lower fungi for some time (presumably illegally, since the access for woman to the university was at that time officially forbidden in Würzburg), he changed his mind: 1) In contrast to many colleagues of his time he granted females similar intelligence and skills as males and stated that women had legal rights for the access to the university. 2) He favoured the general necessity of higher education (in particular in science) for women and did not see any contrast in respect to this to the role of women in the society as wives, mothers, and housewives. 3) Access to the university would stimulate the development of young women and thereby would be an improvement for our society. However, in conclusion he asked himself, whether the higher education of females should take place at special women colleges (not existing at that time in Germany) or at universities and whether girl students should preferentially become teachers at high schools for daughters of the high society. He admitted that he also felt uncomfortable because of the threatening job competition between young academic male (traditionally the majority of students in science) and female students. The liberal view of Sachs in respect to higher education of women is compared to the rather conservative view of his former student and friend Hugo Thiel.

Simple, explicitly time-dependent, and regular solutions of the linearized vacuum Einstein equations in Bondi-Sachs coordinates

NASA Astrophysics Data System (ADS)

Mädler, Thomas

2013-05-01

Perturbations of the linearized vacuum Einstein equations in the Bondi-Sachs formulation of general relativity can be derived from a single master function with spin weight two, which is related to the Weyl scalar Ψ0, and which is determined by a simple wave equation. By utilizing a standard spin representation of tensors on a sphere and two different approaches to solve the master equation, we are able to determine two simple and explicitly time-dependent solutions. Both solutions, of which one is asymptotically flat, comply with the regularity conditions at the vertex of the null cone. For the asymptotically flat solution we calculate the corresponding linearized perturbations, describing all multipoles of spin-2 waves that propagate on a Minkowskian background spacetime. We also analyze the asymptotic behavior of this solution at null infinity using a Penrose compactification and calculate the Weyl scalar Ψ4. Because of its simplicity, the asymptotically flat solution presented here is ideally suited for test bed calculations in the Bondi-Sachs formulation of numerical relativity. It may be considered as a sibling of the Bergmann-Sachs or Teukolsky-Rinne solutions, on spacelike hypersurfaces, for a metric adapted to null hypersurfaces.

Pathology of GM2 gangliosidosis in Jacob sheep.

PubMed

Porter, B F; Lewis, B C; Edwards, J F; Alroy, J; Zeng, B J; Torres, P A; Bretzlaff, K N; Kolodny, E H

2011-07-01

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model. © The Authors 2011

Identification of an active acidic residue in the catalytic site of beta-hexosaminidase.

PubMed

Tse, R; Vavougios, G; Hou, Y; Mahuran, D J

1996-06-11

Human beta-hexosaminidases A and B (EC 3.2.1.52) are dimeric lysosomal glycosidases composed of evolutionarily related alpha and/or beta subunits. Both isozymes hydrolyze terminal beta-linked GalNAc or GlcNAc residues from numerous artificial and natural substrates; however, in vivo GM2 ganglioside is a substrate for only the heterodimeric A isozyme. Thus, mutations in either gene encoding its alpha or beta subunits can result in GM2 ganglioside storage and Tay-Sachs or Sandhoff disease, respectively. All glycosyl hydrolases ae believed to have one or more acidic residues in their catalytic site. We demonstrate that incubation of hexosaminidase with a chemical modifier specific for carboxyl side chains produces a time-dependent loss of activity, and that this effect can be blocked by the inclusion of a strong competitive inhibitor in the reaction mix. We hypothesized that the catalytic acid residue(s) should be located in a region of overall homology and be invariant within the aligned deduced primary sequences of the human alpha and beta subunits, as well as hexosaminidases from other species, including bacteria. Such a region is encoded by exons 5-6 of the HEXA and HEXB genes. This region includes beta Arg211 (invariant in 15 sequences), which we have previously shown to be an active residue. This region also contains two invariant and one conserved acidic residues. A fourth acidic residue, Asp alpha 258, beta 290, in exon 7 was also investigated because of its association with the B1 variant of Tay-Sachs disease. Conservative substitutions were made at each candidate residue by in vitro mutagenesis of a beta cDNA, followed by cellular expression. Of these, only the beta Asp196Asn substitution decreased the kcat (350-910-fold) without any noticeable effect on the K(m). Mutagenesis of either beta Asp240 or beta Asp290 to Asn decreased kcat by 10- or 1.4-fold but also raised the K(m) of the enzyme 11- of 3-fold, respectively. The above results strongly suggest that

Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

PubMed Central

Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Stevens, Christine; Pirinen, Matti; Neale, Benjamin M.; Ganna, Andrea; Graham, Daniel; Glaser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levine, Adam P.; Schiff, Elena; Weisburd, Ben; Lek, Monkol; Bloom, Jonathan; Minikel, Eric V.; Petersen, Britt-Sabina; Beaugerie, Laurent; Seksik, Philippe; Cosnes, Jacques; Schreiber, Stefan; Bokemeyer, Bernd; Bethge, Johannes; Ahmad, Tariq; Plagnol, Vincent; Segal, Anthony W.; Targan, Stephan; Turner, Dan; Saavalainen, Paivi; Farkkila, Martti; Kontula, Kimmo; Palotie, Aarno; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Weersma, Rinse K.; Franke, Andre; Jostins, Luke; Barrett, Jeffrey C.; MacArthur, Daniel G.; Jalas, Chaim; Sokol, Harry; Xavier, Ramnik J.; Pulver, Ann; Cho, Judy H.; McGovern, Dermot P. B.; Daly, Mark J.

2018-01-01

As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10–100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel

Fragments of Science: Festschrift for Mendel Sachs

NASA Astrophysics Data System (ADS)

Ram, Michael

1999-11-01

The Table of Contents for the full book PDF is as follows: * Preface * Sketches at a Symposium * For Mendel Sachs * The Constancy of an Angular Point of View * Information-Theoretic Logic and Transformation-Theoretic Logic * The Invention of the Transistor and the Realization of the Hole * Mach's Principle, Newtonian Gravitation, Absolute Space, and Einstein * The Sun, Our Variable Star * The Inconstant Sun: Symbiosis of Time Variations of Sunspots, Atmospheric Radiocarbon, Aurorae, and Tree Ring Growth * Other Worlds * Super-Classical Quantum Mechanics * A Probabilistic Approach to the Phase Problem of X-Ray Crystallography * A Nonlinear Twist on Inertia Gives Unified Electroweak Gravitation * Neutrino Oscillations * On an Incompleteness in the General-Relativistic Description of Gravitation * All Truth is One * Ideas of Physics: Correspondence between Colleagues * The Influence of the Physics and Philosophy of Einstein's Relativity on My Attitudes in Science: An Autobiography

Generalized Bondi-Sachs equations for characteristic formalism of numerical relativity

NASA Astrophysics Data System (ADS)

Cao, Zhoujian; He, Xiaokai

2013-11-01

The Cauchy formalism of numerical relativity has been successfully applied to simulate various dynamical spacetimes without any symmetry assumption. But discovering how to set a mathematically consistent and physically realistic boundary condition is still an open problem for Cauchy formalism. In addition, the numerical truncation error and finite region ambiguity affect the accuracy of gravitational wave form calculation. As to the finite region ambiguity issue, the characteristic extraction method helps much. But it does not solve all of the above issues. Besides the above problems for Cauchy formalism, the computational efficiency is another problem. Although characteristic formalism of numerical relativity suffers the difficulty from caustics in the inner near zone, it has advantages in relation to all of the issues listed above. Cauchy-characteristic matching (CCM) is a possible way to take advantage of characteristic formalism regarding these issues and treat the inner caustics at the same time. CCM has difficulty treating the gauge difference between the Cauchy part and the characteristic part. We propose generalized Bondi-Sachs equations for characteristic formalism for the Cauchy-characteristic matching end. Our proposal gives out a possible same numerical evolution scheme for both the Cauchy part and the characteristic part. And our generalized Bondi-Sachs equations have one adjustable gauge freedom which can be used to relate the gauge used in the Cauchy part. Then these equations can make the Cauchy part and the characteristic part share a consistent gauge condition. So our proposal gives a possible new starting point for Cauchy-characteristic matching.

δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders*

PubMed Central

Xu, Miao; Liu, Ke; Swaroop, Manju; Porter, Forbes D.; Sidhu, Rohini; Finkes, Sally; Ory, Daniel S.; Marugan, Juan J.; Xiao, Jingbo; Southall, Noel; Pavan, William J.; Davidson, Cristin; Walkley, Steven U.; Remaley, Alan T.; Baxa, Ulrich; Sun, Wei; McKew, John C.; Austin, Christopher P.; Zheng, Wei

2012-01-01

Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca2+ response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. PMID:23035117

Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

PubMed

Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

2012-08-01

The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.

Defect Characteristics of Reverse Hill-Sachs Lesions.

PubMed

Moroder, Philipp; Tauber, Mark; Scheibel, Markus; Habermeyer, Peter; Imhoff, Andreas B; Liem, Dennis; Lill, Helmut; Buchmann, Stefan; Wolke, Julia; Guevara-Alvarez, Alberto; Salmoukas, Katharina; Resch, Herbert

2016-03-01

Little scientific evidence regarding reverse Hill-Sachs lesions (RHSLs) in posterior shoulder instability exists. Recently, standardized measurement methods of the size and localization were introduced, and the biomechanical effect of the extent and position of the defects on the risk of re-engagement was determined. To analyze the characteristics and patterns of RHSLs in a large case series using standardized measurements and to interpret the results based on the newly available biomechanical findings. Case series; Level of evidence, 4. In this multicenter study, 102 cases of RHSLs in 99 patients were collected from 7 different shoulder centers between 2004 and 2013. Patient- as well as injury-specific information was gathered, and defect characteristics in terms of the size, localization, and depth index were determined on computed tomography or magnetic resonance imaging scans by means of standardized measurements. Additionally, the position (gamma angle) of the posterior defect margin as a predictor of re-engagement was analyzed. Three types of an RHSL were distinguished based on the pathogenesis and chronicity of the lesion: dislocation (D), locked dislocation (LD), and chronic locked dislocation (CLD). While the localization of the defects did not vary significantly between the subgroups (P = .072), their mean size differed signficantly (D: 32.6° ± 11.7°, LD: 49.4° ± 17.2°, CLD: 64.1° ± 20.7°; P < .001). The mean gamma angle as a predictor of re-engagement was similarly significantly different between groups (D: 83.8° ± 14.5°, LD: 96.5° ± 17.9°, CLD: 108.7° ± 18.4°; P < .001). The orientation of the posterior defect margin was consistently quite parallel to the humeral shaft axis, with a mean difference of 0.3° ± 8.1°. The distinction between the 3 different RHSL types based on the pathogenesis and chronicity of the defect helps identify defects prone to re-engagement. The gamma angle as a measurement of the position of the posterior

Integrated Sachs-Wolfe effect in massive bigravity

NASA Astrophysics Data System (ADS)

Enander, Jonas; Akrami, Yashar; Mörtsell, Edvard; Renneby, Malin; Solomon, Adam R.

2015-04-01

We study the integrated Sachs-Wolfe (ISW) effect in ghost-free, massive bigravity. We focus on the infinite-branch bigravity (IBB) model which exhibits viable cosmic expansion histories and stable linear perturbations, while the cosmological constant is set to zero and the late-time accelerated expansion of the Universe is due solely to the gravitational interaction terms. The ISW contribution to the CMB auto-correlation power spectrum is predicted, as well as the cross-correlation between the CMB temperature anisotropies and large-scale structure. We use ISW amplitudes as inferred from the WMAP 9-year temperature data together with galaxy and AGN data provided by the WISE mission in order to compare the theoretical predictions to the observations. The ISW amplitudes in IBB are found to be larger than the corresponding ones in the standard Λ CDM model by roughly a factor of 1.5, but are still consistent with the observations.

Genetics and Therapies for GM2 Gangliosidosis.

PubMed

Cachon-Gonzalez, María Begona; Zaccariotto, Eva; Cox, Timothy Martin

2018-04-04

Tay-Sachs disease, caused by impaired β-N-acetylhexosaminidase activity, was the first GM2 gangliosidosis to be studied and one of the most severe and earliest lysosomal diseases to be described. The condition, associated with the pathological build-up of GM2 ganglioside, has acquired almost iconic status and serves as a paradigm in the study of lysosomal storage diseases. Inherited as a classical autosomal recessive disorder, this global disease of the nervous system induces developmental arrest with regression of attained milestones; neurodegeneration progresses rapidly to cause premature death in young children. There is no effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular and cellular events, from disease-causing mutations and glycosphingolipid storage to disease manifestations, remain to be fully delineated. Several therapeutic approaches has been attempted in patients, including enzymatic augmentation, bone marrow transplantation, enzyme enhancement, and substrate reduction therapy. Hitherto, none of these stratagems has materially altered the course of the disease. Authentic animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, shows great promise. This review outlines current knowledge pertaining the pathobiology as well as potential innovative treatments for the GM2 gangliosidoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Dr Mavro Sachs (1817-1888): the first lecturer of Zagreb University].

PubMed

Dugacki, Vladimir

2010-01-01

Mavro Sachs (Jánosháza, Hungary, 1817 % emdash; Rijeka, 1888.) was a Zagreb student since 1828. In 1846 he graduated in medicine from the University of Vienna and returned to Zagreb to be the city physician. In 1849, he started to teach forensic medicine at the School of Law of the Royal Academy of Sciences in Zagreb and continued teaching the same subject at the Zagreb University Faculty of Law in the capacity of docent (corresponds to lecturer in the British system). He also taught medical law at pharmaceutical studies of Zagreb University. From 1855 to 1860, he presided over the Jewish Community of Zagreb.

The effect of a Hill-Sachs defect on glenohumeral translations, in situ capsular forces, and bony contact forces.

PubMed

Sekiya, Jon K; Jolly, John; Debski, Richard E

2012-02-01

Hill-Sachs defects have been associated with failed repairs for anterior shoulder instability. However, the biomechanical consequences of these defects are not well understood because of the complicated interaction between the passive soft tissue and bony stabilizers. The creation of a 25% Hill-Sachs defect would not significantly alter the glenohumeral translations but would increase the in situ forces in the glenohumeral capsule as well as the glenohumeral bony contact forces. Controlled laboratory study. A robotic/universal force-moment sensor (UFS) testing system was used to apply joint compression (22 N) and an anterior or posterior load (44 N) to cadaveric shoulders (n = 9) with the skin and deltoid removed (intact) at 3 glenohumeral joint positions (abduction/external rotation): 0°/0°, 30°/30°, and 60°/60° (corresponds to 90°/90° of shoulder abduction/external rotation). A 25% bony defect on the posterolateral humeral head (defect) was then created in the most common position of anterior shoulder dislocation (90°/90°), and the loading protocol was repeated. A nonparametric repeated-measures Friedman test with a Wilcoxon signed-rank post hoc test was performed to compare translations, in situ forces in the capsule, and bony contact forces between each state (P < .05). At 0°/0°, anterior translation significantly increased from 15.3 ± 8.2 mm to 16.6 ± 9.0 mm (P < .05) in response to an anterior load. At 30°/30°, anterior and posterior translations, respectively, significantly increased in response to both anterior (intact: 13.6 ± 7.1 mm vs defect: 14.2 ± 7 mm; P < .05) and posterior loads (intact: 15.7 ± 5.8 mm vs defect: 17.7 ± 5.1 mm; P < .05). In situ force in the capsule during anterior loading was increased in the defect state at both 60°/60° (intact: 38.9 ± 14.4 N vs defect: 43.2 ± 15.9 N; P < .05) and 30°/30° (intact: 39.6 ± 13.8 N vs defect: 45.6 ± 9.3 N; P < .05). The medial bony contact forces were also increased in the

Kantowski-Sachs Einstein-æther perfect fluid models

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

Latta, Joey; Leon, Genly; Paliathanasis, Andronikos, E-mail: lattaj@mathstat.dal.ca, E-mail: genly.leon@pucv.cl, E-mail: anpaliat@phys.uoa.gr

We investigate Kantowski-Sachs models in Einstein-æ ther theory with a perfect fluid source using the singularity analysis to prove the integrability of the field equations and dynamical system tools to study the evolution. We find an inflationary source at early times, and an inflationary sink at late times, for a wide region in the parameter space. The results by A.A. Coley, G. Leon, P. Sandin and J. Latta ( JCAP 12 (2015) 010), are then re-obtained as particular cases. Additionally, we select other values for the non-GR parameters which are consistent with current constraints, getting a very rich phenomenology. Inmore » particular, we find solutions with infinite shear, zero curvature, and infinite matter energy density in comparison with the Hubble scalar. We also have stiff-like future attractors, anisotropic late-time attractors, or both, in some special cases. Such results are developed analytically, and then verified by numerics. Finally, the physical interpretation of the new critical points is discussed.« less

Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

PubMed Central

Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi

2016-01-01

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.

PubMed

Kitakaze, Keisuke; Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi; Itoh, Kohji

2016-05-02

GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses.

Sachs equations for light bundles in a cold plasma

NASA Astrophysics Data System (ADS)

Schulze-Koops, Karen; Perlick, Volker; Schwarz, Dominik J.

2017-11-01

We study the propagation of light bundles in non-empty spacetime, as most of the Universe is filled by baryonic matter in the form of a (dilute) plasma. Here we restrict to the case of a cold (i.e. pressureless) and non-magnetised plasma. Then the influence of the medium on the light rays is encoded in the spacetime dependent plasma frequency. Our result for a general spacetime generalises the Sachs equations to the case of a cold plasma Universe. We find that the reciprocity law (Etherington theorem), the relation that connects area distance with luminosity distance, is modified. Einstein’s field equation is not used, i.e. our results apply independently of whether or not the plasma is self-gravitating. As an example, our findings are applied to a homogeneous plasma in a Robertson-Walker spacetime. We find small modifications of the cosmological redshift of frequencies and of the Hubble law.

Non-minimally coupled scalar field in Kantowski-Sachs model and symmetry analysis

NASA Astrophysics Data System (ADS)

Dutta, Sourav; Lakshmanan, Muthusamy; Chakraborty, Subenoy

2018-06-01

The paper deals with a non-minimally coupled scalar field in the background of homogeneous but anisotropic Kantowski-Sachs space-time model. The form of the coupling function of the scalar field with gravity and the potential function of the scalar field are not assumed phenomenologically, rather they are evaluated by imposing Noether symmetry to the Lagrangian of the present physical system. The physical system gets considerable mathematical simplification by a suitable transformation of the augmented variables (a , b , ϕ) →(u , v , w) and by the use of the conserved quantities due to the geometrical symmetry. Finally, cosmological solutions are evaluated and analyzed from the point of view of the present evolution of the Universe.

On the structure and applications of the Bondi-Metzner-Sachs group

NASA Astrophysics Data System (ADS)

Alessio, Francesco; Esposito, Giampiero

This work is a pedagogical review dedicated to a modern description of the Bondi-Metzner-Sachs (BMS) group. Minkowski space-time has an interesting and useful group of isometries, but, for a generic space-time, the isometry group is simply the identity and hence provides no significant informations. Yet symmetry groups have important role to play in physics; in particular, the Poincaré group describing the isometries of Minkowski space-time plays a role in the standard definitions of energy-momentum and angular-momentum. For this reason alone it would seem to be important to look for a generalization of the concept of isometry group that can apply in a useful way to suitable curved space-times. The curved space-times that will be taken into account are the ones that suitably approach, at infinity, Minkowski space-time. In particular we will focus on asymptotically flat space-times. In this work, the concept of asymptotic symmetry group of those space-times will be studied. In the first two sections we derive the asymptotic group following the classical approach which was basically developed by Bondi, van den Burg, Metzner and Sachs. This is essentially the group of transformations between coordinate systems of a certain type in asymptotically flat space-times. In the third section the conformal method and the notion of “asymptotic simplicity” are introduced, following mainly the works of Penrose. This section prepares us for another derivation of the BMS group which will involve the conformal structure, and is thus more geometrical and fundamental. In the subsequent sections we discuss the properties of the BMS group, e.g. its algebra and the possibility to obtain as its subgroup the Poincaré group, as we may expect. The paper ends with a review of the BMS invariance properties of classical gravitational scattering discovered by Strominger, that are finding application to black hole physics and quantum gravity in the literature.

[The "Chapter on health preservation" in the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr by Avenzoar (1095-1162)].

PubMed

Peña, Carmen; Girón, Fernando

2010-01-01

The Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr (The Method of Preparing Medicines and Diet) was written in Arabic by Avenzoar (1095-1162). It has yet to be translated into any Western modern language, and we wish to take on this task. We begin by offering an annotated Spanish translation (with commentary) of its preliminary "Chapter on the preservation of health". The Al-mohad caliph 'Abd al-Mu'min, for whom Avenzoar served as court physician, requested the book for his personal use. The work begins with this chapter, which contains measures for preventing and curing certain diseases. This section is followed by the main body of the book. It consists of a complete list of diseases working from head to toe and including their description, symptoms and treatment. The translated chapter is an atypical and concise treatise on the subject. It is presented in a quasi-aphoristic style that appears to have been used by Avenzoar to rapidly deal with the prevention area, in order to concentrate his efforts on what is surely one of the finest and most extensive mediaeval nosographies. We make this claim because our author does not exclusively use for this purpose the so-called "non-naturals"--the usual focus of health preservation measures of the time. Rather, he makes wide use of simple medicines with preventative ends--an unusual practice. Moreover, he indiscriminately intersperses prevention elements with others that are intended to cure. In order to better understand the meaning of this text, we previously refer to the foundations of health preservation practices in the mediaeval world, to the reasons why Avenzoar wrote the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr, and to the characteristics of its translated chapter. We also examine the medical sources and contents of this chapter.

Challenges and Gaps in Understanding Substance Use Problems in Transitional Age Youth.

PubMed

Bukstein, Oscar G

2017-04-01

Transitional age youth (TAY), developing from adolescence to adulthood, exhibit the highest level of alcohol and other drug use of any other age group. Risk factors mirror those for the development of problems and disorders in adolescents. Early screening of both college students and noncollege high-risk TAY in the community is critical to early and effective intervention. Brief interventions using motivational techniques are effective for many TAY, particularly for those in early stages of problem use on college campuses. Professionals in contact with TAY should be aware of evidence-based interventions and providers for substance use disorders in the community. Copyright © 2016 Elsevier Inc. All rights reserved.

Representations of the Bondi—Metzner—Sachs group in three space—time dimensions

NASA Astrophysics Data System (ADS)

Melas, Evangelos

2017-01-01

The original Bondi-Metzner-Sachs group B is the common asymptotic symmetry group of all asymptotically at Lorentzian 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, P. J. McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here, we construct the IRS of B(2, 1), the analogue of B, in 3 space-time dimensions. The IRS are induced from ‘little groups’ which are compact. The finite ‘little groups’ are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

Conserved charges of the extended Bondi-Metzner-Sachs algebra

NASA Astrophysics Data System (ADS)

Flanagan, Éanna É.; Nichols, David A.

2017-02-01

Isolated objects in asymptotically flat spacetimes in general relativity are characterized by their conserved charges associated with the Bondi-Metzner-Sachs (BMS) group. These charges include total energy, linear momentum, intrinsic angular momentum and center-of-mass location, and, in addition, an infinite number of supermomentum charges associated with supertranslations. Recently, it has been suggested that the BMS symmetry algebra should be enlarged to include an infinite number of additional symmetries known as super-rotations. We show that the corresponding charges are finite and well defined, and can be divided into electric parity "super center-of-mass" charges and magnetic parity "superspin" charges. The supermomentum charges are associated with ordinary gravitational-wave memory, and the super center-of-mass charges are associated with total (ordinary plus null) gravitational-wave memory, in the terminology of Bieri and Garfinkle. Superspin charges are associated with the ordinary piece of spin memory. Some of these charges can give rise to black hole hair, as described by Strominger and Zhiboedov. We clarify how this hair evades the no-hair theorems.

Synthesis and electrochemical characterization of TixTayAlzN1-δOγ for fuel cell catalyst supports

NASA Astrophysics Data System (ADS)

Wakabayashi, Ryo H.; Abruña, Héctor D.; DiSalvo, Francis J.

2017-02-01

Quinary TixTayAlzN1-δOγ of various compositions have been prepared by a co-precipitation method followed by ammonolysis. The nitride samples were examined as potential catalyst supports in polymer electrolyte membrane fuel cells. The nitride products crystallized in the rock salt (NaCl) structure over a wide range of compositions. The addition of Ta and Al was highly beneficial towards improving the chemical and electrochemical stability of TiN, without a significant loss of electrical conductivity. Platinum particles were successfully deposited on the (oxy)nitride samples, and the composite samples at some compositions were found to be comparable to Pt/carbon in their stability and catalytic activity even without optimizing the Pt deposition and dispersion processes.

Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

PubMed

Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

2016-02-01

The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

Strengthening Chronic Disease Prevention Programming: The Toward Evidence-Informed Practice (TEIP) Program Evidence Tool

PubMed Central

Albert, Dayna; Fortin, Rebecca; Herrera, Christine; Hanning, Rhona; Lessio, Anne; Rush, Brian

2013-01-01

In public health and chronic disease prevention there is increasing priority for effective use of evidence in practice. In Ontario, Canada, despite various models being advanced, public health practitioners are seeking ways to identify and apply evidence in their work in practical and meaningful ways. In a companion article, “Strengthening Chronic Disease Prevention Programming: The Toward Evidence-Informed Practice (TEIP) Program Assessment Tool,” we describe use of a tool to assess and strengthen program planning and implementation processes using 19 criteria derived from best and promising practices literature. In this article, we describe use of a complementary Program Evidence Tool to identify, synthesize, and apply a range of evidence sources to strengthen the content of chronic disease prevention programming. The Program Evidence Tool adapts tools of evidence-based medicine to the unique contexts of community-based health promotion and chronic disease prevention. Knowledge management tools and a guided dialogue process known as an Evidence Forum enable community stakeholders to make appropriate use of evidence in diverse social, political, and structural contexts. Practical guidelines and worksheets direct users through 5 steps: 1) define an evidence question, 2) develop a search strategy, 3) collect and synthesize evidence, 4) interpret and adapt evidence, and 5) implement and evaluate. We describe the Program Evidence Tool’s benefits, strengths, challenges, and what was learned from its application in 4 Ontario public health departments. The Program Evidence Tool contributes to the development and understanding of the complex use of evidence in community-based chronic disease prevention. PMID:23721788

The integrated Sachs-Wolfe signal from BOSS superstructures

NASA Astrophysics Data System (ADS)

Granett, B. R.; Kovács, A.; Hawken, A. J.

2015-12-01

Cosmic structures leave an imprint on the microwave background radiation through the integrated Sachs-Wolfe (ISW) effect. We construct a template map of the linear signal using the Sloan Digital Sky Survey-III Baryon Acoustic Oscillation Survey at redshift 0.43 < z < 0.65. We verify the imprint of this map on the Planck cosmic microwave background (CMB) temperature map at the 97 per cent confidence level and show consistency with the density-temperature cross-correlation measurement. Using this ISW reconstruction as a template, we investigate the presence of ISW sources and further examine the properties of the Granett-Neyrinck-Szapudi supervoid and supercluster catalogue. We characterize the three-dimensional density profiles of these structures for the first time and demonstrate that they are significant structures. Model fits demonstrate that the supervoids are elongated along the line of sight and we suggest that this special orientation may be picked out by the void-finding algorithm in photometric redshift space. We measure the mean temperature profiles in Planck maps from public void and cluster catalogues. In an attempt to maximize the stacked ISW signal, we construct a new catalogue of superstructures based upon local peaks and troughs of the gravitational potential. However, we do not find a significant correlation between these structures and the CMB temperature.

Right services to right patients at right time in right setting in Tays Eye Centre.

PubMed

Tuulonen, Anja; Kataja, Marko; Syvänen, Ulla; Miettunen, Sirpa; Uusitalo, Hannu

2016-11-01

The report describes the concepts behind procedures implemented in Tays Eye Centre to enable improved access to care and improved productivity. The strategy was developed in 2009 after hospital district decided to construct a new eye hospital which was opened in 2012. The following principles were implemented: (i) identification of high-volume patient groups: the 'big four' eye diseases accounting for 70% of patient visits and costs: age-related macular degeneration (AMD), glaucoma, retinal diseases and cataract; (ii) stratification and prioritization of patient care based on risk of permanent visual disability; (iii) standardization of services for low-risk patients; (iv) maximization of productivity; and (v) shared care. The impact of the new strategy on access to care and productivity is reported for years 2011-2015. In 2011-2015, the total number of services provided increased 46% while the work contribution increased 15%. The number of referrals increased 76% and the number of outpatient appointments increased 2.5-fold. Simultaneously, the number of delayed follow-up visits decreased to zero. Age-related macular degeneration (AMD) injections increased 1.8-fold. However, after 50% yearly increase in Age-related macular degeneration (AMD) injections, a plateau was reached in 2014 with a 3% decline in 2014-2015 with no changes in treatment indications. In the beginning of 2016, the number of injections has started to increase again (+9% compared to 2015).  The total number of surgical procedures increased 98%. The annual number of cataract surgeries increased 64% and bilateral surgeries from 11% to 39%. Revised operational concepts and new facilities together with a 15% increase in work contribution led to a 46% increase in overall productivity, improved access to care and the clearance of delayed services. Efforts continue to further refine cost-effective care and to define the appropriate levels of services. © 2016 Acta Ophthalmologica Scandinavica Foundation

Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

PubMed

Pan, Xuefang; De Aragão, Camila De Britto Pará; Velasco-Martin, Juan P; Priestman, David A; Wu, Harry Y; Takahashi, Kohta; Yamaguchi, Kazunori; Sturiale, Luisella; Garozzo, Domenico; Platt, Frances M; Lamarche-Vane, Nathalie; Morales, Carlos R; Miyagi, Taeko; Pshezhetsky, Alexey V

2017-08-01

Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, G M3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of G M1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of G M2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of β-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. © FASEB.

Quaternions, Torsion and the Physical Vacuum: Theories of M. Sachs and G. Shipov Compared

NASA Astrophysics Data System (ADS)

Cyganski, David; Page, William S.

Of several developments of unified field theories in the spirit of Einstein's original objective of a fully geometric description of all classical fields as well as quantum mechanics, two are particularly noteworthy. The works of Mendel Sachs and Gennady Shipov stand apart as major life works comprising tens of papers, several monographs and decades of effort. Direct comparison of these theories is hampered however by differences in notation and conceptual view-point. Despite these differences, there are many parallels between the fundamental mathematical structures appearing in each. In this paper we discuss the main tenets of the two approaches and demonstrate that they both give rise to a factorization of the invariant interval of general relativity.

Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity[S

PubMed Central

Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

2015-01-01

Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

Evidence-based medicine in metastatic spine disease.

PubMed

Dea, Nicolas; Fisher, Charles G

2014-06-01

Treatment modalities for metastatic spine disease have significantly expanded over the last two decades. This expansion occurred in many different fields. Improvement in surgical techniques and instrumentation now allow the oncologic spine surgeons to effectively circumferentially decompress the neural elements without compromising stability. Percutaneous techniques, both vertebral augmentation and pre-operative endovascular embolization procedures, also greatly benefit patients suffering from spinal column metastasis. Imaging technology advances has contributed to better pre-operative planning and the development of highly conformational radiation techniques, thus permitting the delivery of high-dose radiation to tumors, while avoiding radiotoxicity to the spinal cord and other vital structures. These new developments, combined with evidence-based stability and disease-specific quality of life scores now allow not only better treatment, but also a solid foundation for high-quality research. Spine oncology literature currently suffers from a lack of high-quality evidence due to low prevalence of the disease and complex methodological issues. However, when following evidence-based medicine principles, which incorporate best available evidence, clinical expertise and patient preference, sound, evidence-based recommendations can be made regarding the abovementioned treatment modalities.

[Transhumeral head plasty and massive osteocartilaginous allograft transplantation for the management of large hill-sachs lesions].

PubMed

Hart, R; Okál, F; Komzák, M

2010-10-01

The aim of this presentation is to inform the medical community about causal therapy (transhumeral head plasty or massive osteochondral allograft transplantation) for large Hill-Sachs lesions which frequently cause failure of anterior stabilisation following ventral shoulder dislocations. Seven men with an average age of 26 years (19 to 33 years) undergoing surgery in 2006 and 2007 were evaluated. The minimum follow-up was 18 months (41 to 18 months). Impressions on more than 30 % of the articular surface, or those whose critical size was larger than one-eighth of the humeral diameter (on CT scan) were taken as indications for surgery. Four patients had had previous surgery for anterior instability and three had a primary procedure. Four men underwent acute surgery and three had elective operations.Trans- humeral head plasty was used in five and massive osteochondral allograft in two patients. In the patients with large lesions in the anterior aspect of the shoulder joint, transhumeral head plasty involving repair of the ventral structures from the anterior approach was indicatedúúú in those with an isolated posterior bony defect, a massive osteochondral allograft was transplanted through the posterior approach. The Constant-Murley score was used to assess clinical status before (not in acute conditions) and after surgery. All patients reported improved clinical status. The average Constant-Murley score at final follow-up was 95.9 points (83-100 points). In the patients not having an acute procedure in whom pre-operative Constant-Murley scores were obtained, the average improvement was by 22.7 points (8 - 37 points). No general surgical complications were recorded. All patients reported subjective satisfaction and willingness to undergo surgery under the same conditions again. A Hill-Sachs lesion is a frequent injury to the humeral head resulting from anterior shoulder dislocation. To distinguish between major and minor defects in terms of clinical significance

A SENSITIVE FLUORESCENCE-BASED ASSAY FOR MONITORING GM2 GANGLIOSIDE HYDROLYSIS IN LIVE PATIENT CELLS AND THEIR LYSATES

PubMed Central

Tropak, Michael B.; Bukovac, Scott W.; Rigat, Brigitte A.; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J.

2010-01-01

Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is anattractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are alsoinhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Herewe demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the β-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant β-hexosaminidase A and substrate-hydrolysis as compared to mock treated cells. PMID:19917668

A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates.

PubMed

Tropak, Michael B; Bukovac, Scott W; Rigat, Brigitte A; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J

2010-03-01

Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is an attractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are also inhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Here we demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the beta-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant beta-hexosaminidase A and substrate-hydrolysis as compared to mock-treated cells.

Carrier screening in the era of expanding genetic technology.

PubMed

Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

2016-12-01

The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

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

McDowell, G.A.; Blitzer, M.G.; Mules, E.H.

A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the [beta]-hexosaminidase A (Hex A) [alpha]-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes. The mutation in the remaining allele was a single-base transition in the donor splice site of the [alpha]-subunit intron 9. To determine the origins of these two mutations in the Cajun population, the TSD carrier status was enzymatically determined formore » 90 members of four of the six families, and extensive pedigrees were constructed for all carriers. A single ancestral couple from France was found to be common to most of the carriers of the exon 11 insertion. Pedigree data suggest that this mutation has been in the Cajun population since its founding over 2 centuries ago and that it may be widely distributed within the population. In contrast, the intron 9 mutation apparently was introduced within the last century and probably is limited to a few Louisiana families. 29 refs., 4 figs.« less

Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

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

Verlander, P.C.; Kaporis, A.G.; Qian, L.

1994-09-01

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutationsmore » are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.« less

Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.

PubMed

Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

2015-09-01

Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Qualitative analysis of Kantowski-Sachs metric in a generic class of f(R) models

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

Leon, Genly; Roque, Armando A., E-mail: genly.leon@ucv.cl, E-mail: arestrada@ucf.edu.cu

2014-05-01

In this paper we investigate, from the dynamical systems perspective, the evolution of a Kantowski-Sachs metric in a generic class of f(R) models. We present conditions (i.e., differentiability conditions, existence of minima, monotony intervals, etc.) for a free input function related to the f(R), that guarantee the asymptotic stability of well-motivated physical solutions, specially, self-accelerated solutions, allowing to describe both inflationary- and late-time acceleration stages of the cosmic evolution. We discuss which f(R) theories allows for a cosmic evolution with an acceptable matter era, in correspondence to the modern cosmological paradigm. We find a very rich behavior, and amongst othersmore » the universe can result in isotropized solutions with observables in agreement with observations, such as de Sitter, quintessence-like, or phantom solutions. Additionally, we find that a cosmological bounce and turnaround are realized in a part of the parameter-space as a consequence of the metric choice.« less

The evidence basis for coenzyme Q therapy in oxidative phosphorylation disease.

PubMed

Haas, Richard H

2007-06-01

The evidence supporting a treatment benefit for coenzyme Q10 (CoQ10) in primary mitochondrial disease (mitochondrial disease) whilst positive is limited. Mitochondrial disease in this context is defined as genetic disease causing an impairment in mitochondrial oxidative phosphorylation (OXPHOS). There are no treatment trials achieving the highest Level I evidence designation. Reasons for this include the relative rarity of mitochondrial disease, the heterogeneity of mitochondrial disease, the natural cofactor status and easy 'over the counter availability' of CoQ10 all of which make funding for the necessary large blinded clinical trials unlikely. At this time the best evidence for efficacy comes from controlled trials in common cardiovascular and neurodegenerative diseases with mitochondrial and OXPHOS dysfunction the etiology of which is most likely multifactorial with environmental factors playing on a background of genetic predisposition. There remain questions about dosing, bioavailability, tissue penetration and intracellular distribution of orally administered CoQ10, a compound which is endogenously produced within the mitochondria of all cells. In some mitochondrial diseases and other commoner disorders such as cardiac disease and Parkinson's disease low mitochondrial or tissue levels of CoQ10 have been demonstrated providing an obvious rationale for supplementation. This paper discusses the current state of the evidence supporting the use of CoQ10 in mitochondrial disease.

Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis.

PubMed

Tsuji, Daisuke; Akeboshi, Hiromi; Matsuoka, Kazuhiko; Yasuoka, Hiroko; Miyasaki, Eri; Kasahara, Yoshiko; Kawashima, Ikuo; Chiba, Yasunori; Jigami, Yoshifumi; Taki, Takao; Sakuraba, Hitoshi; Itoh, Kohji

2011-04-01

Novel recombinant human lysosomal β-hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay-Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency. A recombinant human HexA (Om4HexA) with a high mannose 6-phosphate (M6P)-type-N-glycan content, which was produced by a methylotrophic yeast strain, Ogataea minuta, overexpressing the OmMNN4 gene, was intracerebroventricularly (ICV) administered to Sandhoff disease model mice (Hexb⁻/⁻ mice) at different doses (0.5-2.5 mg/kg), and then the replacement and therapeutic effects were examined. The Om4HexA was widely distributed across the ependymal cell layer, dose-dependently restored the enzyme activity due to uptake via cell surface cation-independent M6P receptor (CI-M6PR) on neural cells, and reduced substrates, including GM2 ganglioside (GM2), asialo GM2 (GA2), and oligosaccharides with terminal N-acetylglucosamine residues (GlcNAc-oligosaccharides), accumulated in brain parenchyma. A significant inhibition of chemokine macrophage inflammatory protein-1 α (MIP-1α) induction was also revealed, especially in the hindbrain (< 63%). The decrease in central neural storage correlated with an improvement of motor dysfunction as well as prolongation of the lifespan. This lysosome-directed recombinant human enzyme drug derived from methylotrophic yeast has the high therapeutic potential to improve the motor dysfunction and quality of life of the lysosomal storage diseases (LSDs) patients with neurological manifestations. We emphasize the importance of neural cell surface M6P receptor as a delivery target of neural cell-directed enzyme replacement therapy (NCDERT) for neurodegenerative metabolic diseases. Copyright © 2010 American Neurological Association.

Evidence-Based Management Guidelines on Peyronie's Disease.

PubMed

Chung, Eric; Ralph, David; Kagioglu, Ates; Garaffa, Guilio; Shamsodini, Ahmed; Bivalacqua, Trinity; Glina, Sidney; Hakim, Lawrence; Sadeghi-Nejad, Hossein; Broderick, Gregory

2016-06-01

Despite recent advances in our knowledge and treatment strategies in Peyronie's Disease (PD), much remained unknown about this disease. To provide a clinical framework and key guideline statements to assist clinicians in an evidence-based management of PD. A systematic literature search was conducted to identify published literature relevant to PD. The search included all relevant articles published up to June 2015, including preclinical studies and published guidelines. References used in the text were assessed according to their level of evidence, and guideline recommendations were graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Owing to the paucity of larger series and randomized placebo-controlled trials with regard to surgical intervention, guideline statements are provided as clinical principle or expert opinion. This literature was discussed at a panel meeting, and selected articles with the highest evidence available were used to create consensus guideline statements for the Fourth International Consultation on Sexual Medicine guidelines on PD. In addition to existing Third International Consultation on Sexual Medicine guidelines on PD, seven new summary recommendations were created. A greater understanding of the scientific basis of PD is greatly needed to address our understanding of the pathophysiology, clinical epidemiology, psychosocial, and diagnostic assessment as well as treatment strategies. Copyright © 2016 International Society for Sexual Medicine. All rights reserved.

Pesticides and human chronic diseases: Evidences, mechanisms, and perspectives

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

Mostafalou, Sara; Abdollahi, Mohammad, E-mail: Mohammad.Abdollahi@UToronto.Ca

Along with the wide use of pesticides in the world, the concerns over their health impacts are rapidly growing. There is a huge body of evidence on the relation between exposure to pesticides and elevated rate of chronic diseases such as different types of cancers, diabetes, neurodegenerative disorders like Parkinson, Alzheimer, and amyotrophic lateral sclerosis (ALS), birth defects, and reproductive disorders. There is also circumstantial evidence on the association of exposure to pesticides with some other chronic diseases like respiratory problems, particularly asthma and chronic obstructive pulmonary disease (COPD), cardiovascular disease such as atherosclerosis and coronary artery disease, chronic nephropathies,more » autoimmune diseases like systemic lupus erythematous and rheumatoid arthritis, chronic fatigue syndrome, and aging. The common feature of chronic disorders is a disturbance in cellular homeostasis, which can be induced via pesticides' primary action like perturbation of ion channels, enzymes, receptors, etc., or can as well be mediated via pathways other than the main mechanism. In this review, we present the highlighted evidence on the association of pesticide's exposure with the incidence of chronic diseases and introduce genetic damages, epigenetic modifications, endocrine disruption, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum stress and unfolded protein response (UPR), impairment of ubiquitin proteasome system, and defective autophagy as the effective mechanisms of action. - Highlights: ► There is a link between exposure to pesticides and incidence of chronic diseases. ► Genotoxicity and proteotoxicity are two main involved mechanisms. ► Epigenetic knowledge may help diagnose the relationships. ► Efficient policies on safe use of pesticides should be set up.« less

The Influence of Arthroscopic Remplissage for Engaging Hill-Sachs Lesions Combined with Bankart Repair on Redislocation and Shoulder Function Compared with Bankart Repair Alone.

PubMed

Ko, Sang-Hun; Cha, Jae-Ryong; Lee, Chae-Chil; Hwang, Il-Yeong; Choe, Chang-Gyu; Kim, Min-Seok

2016-12-01

Recurrence of glenohumeral dislocation after arthroscopic Bankart repair can be associated with a large osseous defect in the posterosuperior part of the humeral head. Our hypothesis is that remplissage is more effective to prevent recurrence of glenohumeral instability without a severe motion deficit. Engaging Hill-Sachs lesions were observed in 48 of 737 patients (6.5%). Twenty-four patients underwent arthroscopic Bankart repair combined with remplissage (group I) and the other 24 patients underwent arthroscopic Bankart repair alone (group II). Clinical outcomes were prospectively evaluated by assessing the range of motion. Complications, recurrence rates, and functional results were assessed utilizing the American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and the Korean Shoulder Score for Instability (KSSI) score. Capsulotenodesis healing after remplissage was evaluated with magnetic resonance imaging. The average ASES, Rowe, and KSSI scores were statistically significantly higher in group I than group II. The frequency of recurrence was statistically significantly higher in group II. The average loss in external rotation measured with the arm positioned at the side of the trunk was greater in group II and that in abduction was also higher in group II. Compared to single arthroscopic Bankart repair, the remplissage procedure combined with arthroscopic Bankart repair was more effective to prevent the recurrence of anterior shoulder instability without significant impact on shoulder mobility in patients who had huge Hill-Sachs lesions.

Shift work and chronic disease: the epidemiological evidence

PubMed Central

Armstrong, M. E. G.; Cairns, B. J.; Key, T. J.; Travis, R. C.

2011-01-01

Background Shift work, including night work, has been hypothesized to increase the risk of chronic diseases, including cancer, cardiovascular disease (CVD), metabolic syndrome and diabetes. Recent reviews of evidence relating to these hypotheses have focussed on specific diseases or potential mechanisms, but no general summary of the current data on shift work and chronic disease has been published. Methods Systematic and critical reviews and recent original studies indexed in PubMed prior to 31 December 2009 were retrieved, aided by manual searches of reference lists. The main conclusions from reviews and principle results from recent studies are presented in text and tables. Results Published evidence is suggestive but not conclusive for an adverse association between night work and breast cancer but limited and inconsistent for cancers at other sites and all cancers combined. Findings on shift work, in relation to risks of CVD, metabolic syndrome and diabetes are also suggestive but not conclusive for an adverse relationship. Conclusions Heterogeneity of study exposures and outcomes and emphasis on positive but non-significant results make it difficult to draw general conclusions. Further data are needed for additional disease endpoints and study populations. PMID:21355031

The cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Zieser, Britta; Merkel, Philipp M.

2016-06-01

We present the first calculation of the cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe (iSW) effect. Both signals are combined in a single formalism, which permits the computation of the full covariance matrix. In order to avoid the uncertainties presented by the non-linear evolution of the matter power spectrum and intrinsic alignments of galaxies, our analysis is restricted to large scales, I.e. multipoles below ℓ = 1000. We demonstrate in a Fisher analysis that this reduction compared to other studies of 3D weak lensing extending to smaller scales is compensated by the information that is gained if the additional iSW signal and in particular its cross-correlation with lensing data are considered. Given the observational standards of upcoming weak-lensing surveys like Euclid, marginal errors on cosmological parameters decrease by 10 per cent compared to a cosmic shear experiment if both types of information are combined without a cosmic wave background (CMB) prior. Once the constraining power of CMB data is added, the improvement becomes marginal.

Degeneracy between nonadiabatic dark energy models and Λ CDM : Integrated Sachs-Wolfe effect and the cross correlation of CMB with galaxy clustering data

NASA Astrophysics Data System (ADS)

Velten, Hermano; Fazolo, Raquel Emy; von Marttens, Rodrigo; Gomes, Syrios

2018-05-01

As recently pointed out in [Phys. Rev. D 96, 083502 (2017), 10.1103/PhysRevD.96.083502] the evolution of the linear matter perturbations in nonadiabatic dynamical dark energy models is almost indistinguishable (quasidegenerated) to the standard Λ CDM scenario. In this work we extend this analysis to CMB observables in particular the integrated Sachs-Wolfe effect and its cross-correlation with large scale structure. We find that this feature persists for such CMB related observable reinforcing that new probes and analysis are necessary to reveal the nonadiabatic features in the dark energy sector.

GM2 Activator Deficiency Caused by a Homozygous Exon 2 Deletion in GM2A.

PubMed

Hall, Patricia L; Laine, Regina; Alexander, John J; Ankala, Arunkanth; Teot, Lisa A; Lidov, Hart G W; Anselm, Irina

2018-01-01

GM2 activator (GM2A) deficiency (OMIM 613109) is a rare lysosomal storage disorder, with onset typically in infancy or early childhood. Clinically, it is almost indistinguishable from Tay-Sachs disease (OMIM 272800) or Sandhoff disease (OMIM 268800); however, traditionally available biochemical screening tests will most likely reveal normal results. We report a 2-year-old male with initially normal development until the age of 9 months, when he presented with developmental delay and regression. Workup at that time was unrevealing; at 15 months, he had abnormal brain MRI findings and a cherry red spot on ophthalmological examination. Family history and all laboratory studies were uninformative. The combination of a cherry red spot and developmental regression was strongly suggestive of a lysosomal storage disorder. Sequence analysis of GM2A did not reveal any pathogenic variants; however, exon 2 of GM2A could not be amplified by PCR, raising suspicion for a large, homozygous deletion. Subsequent copy number analysis confirmed a homozygous deletion of exon 2 in GM2A. This is the first reported case of GM2A deficiency being caused by a whole exon deletion. We describe previously unreported electron microscopy findings in this disease, thus expanding the clinical and variant spectrum for GM2 activator deficiency. These findings demonstrate the increased degree of suspicion required for diagnosis of this rare disorder. Brief Summary: This case of GM2 activator deficiency was caused by a homozygous deletion in GM2A, demonstrating the need to include exon level copy number analysis in any workup to fully exclude this disorder.

Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts.

PubMed

Kitakaze, Keisuke; Tasaki, Chikako; Tajima, Youichi; Hirokawa, Takatsugu; Tsuji, Daisuke; Sakuraba, Hitoshi; Itoh, Kohji

2016-09-01

GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA , HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses.

Gastroesophageal reflux disease: exaggerations, evidence and clinical practice.

PubMed

Ferreira, Cristina Targa; Carvalho, Elisa de; Sdepanian, Vera Lucia; Morais, Mauro Batista de; Vieira, Mário César; Silva, Luciana Rodrigues

2014-01-01

there are many questions and little evidence regarding the diagnosis and treatment of gastroesophageal reflux disease (GERD) in children. The association between GERD and cow's milk protein allergy (CMPA), overuse of abdominal ultrasonography for the diagnosis of GERD, and excessive pharmacological treatment, especially proton-pump inhibitors (PPIs) are some aspects that need clarification. This review aimed to establish the current scientific evidence for the diagnosis and treatment of GERD in children. a search was conducted in the MEDLINE, PubMed, LILACS, SciELO, and Cochrane Library electronic databases, using the following keywords: gastroesophageal reflux; gastroesophageal reflux disease; proton-pump inhibitors; and prokinetics; in different age groups of the pediatric age range; up to May of 2013. abdominal ultrasonography should not be recommended to investigate gastroesophageal reflux (GER). Simultaneous treatment of GERD and CMPA often results in unnecessary use of medication or elimination diet. There is insufficient evidence for the prescription of prokinetics to all patients with GER/GERD. There is little evidence to support acid suppression in the first year of life, to treat nonspecific symptoms suggestive of GERD. Conservative treatment has many benefits and with low cost and no side-effects. there have been few randomized controlled trials that assessed the management of GERD in children and no examination can be considered the gold standard for GERD diagnosis. For these reasons, there are exaggerations in the diagnosis and treatment of this disease, which need to be corrected. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam.

PubMed

Poyarkov, Nikolay A; Kropachev, Ivan I; Gogoleva, Svetlana S; Orlov, Nikolai L

2018-04-20

A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8-26.4 mm); (7) head longer than wide; ED/SVL ratio 13%-15%; ESL/SVL ratio 16%-20%; (8) small tympanum (TD/EL ratio 50%-60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2-2¼ II 1½-2¾ III 2-3¼ IV 3-1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3-5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma auratum sp. nov. to

78 FR 71532 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-29

... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. [[Page 71533... (AD) 2007-03- 02 for all Rolls-Royce Deutschland (RRD) Tay 620-15, Tay 650-15, and Tay 651-54 turbofan..., January 29, 2007) (``AD 2007-03-02'') for certain RRD Tay 611-8 and Tay 620-15 turbofan engines with LP...

9 CFR 354.130 - Diseases or conditions evident which require condemnation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Diseases or conditions evident which... PRODUCTS THEREOF Disposition of Diseased Rabbit Carcasses and Parts § 354.130 Diseases or conditions... the following named diseases or conditions shall be condemned: Tularemia, anthrax, hemorrhagic...

9 CFR 354.130 - Diseases or conditions evident which require condemnation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Diseases or conditions evident which... PRODUCTS THEREOF Disposition of Diseased Rabbit Carcasses and Parts § 354.130 Diseases or conditions... the following named diseases or conditions shall be condemned: Tularemia, anthrax, hemorrhagic...

9 CFR 354.130 - Diseases or conditions evident which require condemnation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Diseases or conditions evident which... PRODUCTS THEREOF Disposition of Diseased Rabbit Carcasses and Parts § 354.130 Diseases or conditions... the following named diseases or conditions shall be condemned: Tularemia, anthrax, hemorrhagic...

9 CFR 354.130 - Diseases or conditions evident which require condemnation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Diseases or conditions evident which... PRODUCTS THEREOF Disposition of Diseased Rabbit Carcasses and Parts § 354.130 Diseases or conditions... the following named diseases or conditions shall be condemned: Tularemia, anthrax, hemorrhagic...

9 CFR 354.130 - Diseases or conditions evident which require condemnation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Diseases or conditions evident which... PRODUCTS THEREOF Disposition of Diseased Rabbit Carcasses and Parts § 354.130 Diseases or conditions... the following named diseases or conditions shall be condemned: Tularemia, anthrax, hemorrhagic...

Sugar restriction: the evidence for a drug-free intervention to reduce cardiovascular disease risk.

PubMed

Thornley, S; Tayler, R; Sikaris, K

2012-10-01

Uncertainty exists about what dietary component is most likely to cause coronary heart disease. Over the last thirty years, attention has focused on saturated fat and salt as guilty parties. More recently, evidence suggests that excess sugar intake is more likely than either traditional factor to lead to atherosclerotic disease. Some researchers have also speculated that sugar is addictive, in a similar manner to caffeine and established drugs of abuse. Here we review the epidemiological, biochemical and psychological evidence that implicates excess sugar intake as an important cause of ill-health. We found relatively consistent evidence of association between markers of sugar intake and risk factors for cardiovascular disease, or the disease itself. This evidence contrasted with rather weaker evidence which linked either saturated fat or salt with cardiovascular disease endpoints. We also found some evidence of a sugar addiction syndrome. We suggest that advice to restrict sugar intake should be a routine part of clinical care, particularly when patients are being counselled about cardiovascular risk. © 2012 The Authors; Internal Medicine Journal © 2012 Royal Australasian College of Physicians.

MPNs as Inflammatory Diseases: The Evidence, Consequences, and Perspectives

PubMed Central

Hasselbalch, Hans Carl; Bjørn, Mads Emil

2015-01-01

In recent years the evidence is increasing that chronic inflammation may be an important driving force for clonal evolution and disease progression in the Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF). Abnormal expression and activity of a number of proinflammatory cytokines are associated with MPNs, in particular MF, in which immune dysregulation is pronounced as evidenced by dysregulation of several immune and inflammation genes. In addition, chronic inflammation has been suggested to contribute to the development of premature atherosclerosis and may drive the development of other cancers in MPNs, both nonhematologic and hematologic. The MPN population has a substantial inflammation-mediated comorbidity burden. This review describes the evidence for considering the MPNs as inflammatory diseases, A Human Inflammation Model of Cancer Development, and the role of cytokines in disease initiation and progression. The consequences of this model are discussed, including the increased risk of second cancers and other inflammation-mediated diseases, emphasizing the urgent need for rethinking our therapeutic approach. Early intervention with interferon-alpha2, which as monotherapy has been shown to be able to induce minimal residual disease, in combination with potent anti-inflammatory agents such as JAK-inhibitors is foreseen as the most promising new treatment modality in the years to come. PMID:26604428

Strengthening Chronic Disease Prevention Programming: the Toward Evidence-Informed Practice (TEIP) Program Assessment Tool

PubMed Central

Albert, Dayna; Fortin, Rebecca; Lessio, Anne; Herrera, Christine; Hanning, Rhona; Rush, Brian

2013-01-01

Best practices identified solely on the strength of research evidence may not be entirely relevant or practical for use in community-based public health and the practice of chronic disease prevention. Aiming to bridge the gap between best practices literature and local knowledge and expertise, the Ontario Public Health Association, through the Toward Evidence-Informed Practice initiative, developed a set of resources to strengthen evidence-informed decision making in chronic disease prevention programs. A Program Assessment Tool, described in this article, emphasizes better processes by incorporating review criteria into the program planning and implementation process. In a companion paper, “Strengthening Chronic Disease Prevention Programming: The Toward Evidence-Informed Practice (TEIP) Program Evidence Tool,” we describe another tool, which emphasizes better evidence by providing guidelines and worksheets to identify, synthesize, and incorporate evidence from a range of sources (eg, peer-reviewed literature, gray literature, local expertise) to strengthen local programs. The Program Assessment Tool uses 19 criteria derived from literature on best and promising practices to assess and strengthen program planning and implementation. We describe the benefits, strengths, and challenges in implementing the tool in 22 community-based chronic disease prevention projects in Ontario, Canada. The Program Assessment Tool helps put best processes into operation to complement adoption and adaptation of evidence-informed practices for chronic disease prevention. PMID:23721789

Integrated Sachs-Wolfe map reconstruction in the presence of systematic errors

NASA Astrophysics Data System (ADS)

Weaverdyck, Noah; Muir, Jessica; Huterer, Dragan

2018-02-01

The decay of gravitational potentials in the presence of dark energy leads to an additional, late-time contribution to anisotropies in the cosmic microwave background (CMB) at large angular scales. The imprint of this so-called integrated Sachs-Wolfe (ISW) effect to the CMB angular power spectrum has been detected and studied in detail, but reconstructing its spatial contributions to the CMB map, which would offer the tantalizing possibility of separating the early- from the late-time contributions to CMB temperature fluctuations, is more challenging. Here, we study the technique for reconstructing the ISW map based on information from galaxy surveys and focus in particular on how its accuracy is impacted by the presence of photometric calibration errors in input galaxy maps, which were previously found to be a dominant contaminant for ISW signal estimation. We find that both including tomographic information from a single survey and using data from multiple, complementary galaxy surveys improve the reconstruction by mitigating the impact of spurious power contributions from calibration errors. A high-fidelity reconstruction further requires one to account for the contribution of calibration errors to the observed galaxy power spectrum in the model used to construct the ISW estimator. We find that if the photometric calibration errors in galaxy surveys can be independently controlled at the level required to obtain unbiased dark energy constraints, then it is possible to reconstruct ISW maps with excellent accuracy using a combination of maps from two galaxy surveys with properties similar to Euclid and SPHEREx.

Chronic kidney disease in congenital heart disease patients: a narrative review of evidence.

PubMed

Morgan, Catherine; Al-Aklabi, Mohammed; Garcia Guerra, Gonzalo

2015-01-01

Patients with congenital heart disease have a number of risk factors for the development of chronic kidney disease (CKD). It is well known that CKD has a large negative impact on health outcomes. It is important therefore to consider that patients with congenital heart disease represent a population in whom long-term primary and secondary prevention strategies to reduce CKD occurrence and progression could be instituted and significantly change outcomes. There are currently no clear guidelines for clinicians in terms of renal assessment in the long-term follow up of patients with congenital heart disease. Consolidation of knowledge is critical for generating such guidelines, and hence is the purpose of this view. This review will summarize current knowledge related to CKD in patients with congenital heart disease, to highlight important work that has been done to date and set the stage for further investigation, development of prevention strategies, and re-evaluation of appropriate renal follow-up in patients with congenital heart disease. The literature search was conducted using PubMed and Google Scholar. Current epidemiological evidence suggests that CKD occurs in patients with congenital heart disease at a higher frequency than the general population and is detectable early in follow-up (i.e. during childhood). Best evidence suggests that approximately 30 to 50 % of adult patients with congenital heart disease have significantly impaired renal function. The risk of CKD is higher with cyanotic congenital heart disease but it is also present with non-cyanotic congenital heart disease. Although significant knowledge gaps exist, the sum of the data suggests that patients with congenital heart disease should be followed from an early age for the development of CKD. There is an opportunity to mitigate CKD progression and negative renal outcomes by instituting interventions such as stringent blood pressure control and reduction of proteinuria. There is a need to

78 FR 17079 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

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2013-03-20

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... Tay 620-15 and Tay 650-15 turbofan engines with a low-pressure compressor (LPC) rotor disc assembly...

Reproductive health and genetic testing in the Third World.

PubMed

Penchaszadeh, V B

1993-09-01

New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.

Improving Chronic Diseases Management Through the Development of an Evidence-Based Resource.

PubMed

Khalil, Hanan; Chambers, Helen; Munn, Zachary; Porritt, Kylie

2015-06-01

There is a large gap between evidence and practice within health care, particularly within the field of chronic disease. To reduce this gap and improve the management of chronic disease, a collaborative partnership between two schools within a large university and two industry partners (a large regional rural hospital and a rural community health center) in rural Victoria, Australia, was developed. The aim of the collaboration was to promote the development of translation science and the implementation of evidence-based health care in chronic disease with a specific focus on developing evidence-based resources that are easily accessed by clinicians. A working group consisting of members of the collaborating organizations and an internationally renowned expert reference group was formed. The group acted as a steering committee and was tasked with developing a taxonomy of the resources. In addition, a peer review process of all resources was established. A corresponding reference group consisting of researchers and clinicians who are clinical experts in various fields was involved in the review process. The resources developed by the group include evidence summaries and recommended practices made available on a web-based database, which can be accessed via subscription by clinicians and researchers worldwide. As of mid-2014, there were 109 new evidence summaries and 25 recommended practices detailing the best available evidence on topics related to chronic disease management including asthma, diabetes, heart failure, dementia, and others. Training sessions and a newsletter were developed for clinicians within the node to enable them to use the content effectively. This paper describes the processes involved in the successful development of the collaborative partnership and its evolution into producing a valuable resource for the translation of evidence into practice in the areas of chronic disease management. The resource developed is being used by clinicians to

Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

PubMed Central

Brandt-Rauf, Sherry I.; Raveis, Victoria H.; Drummond, Nathan F.; Conte, Jill A.; Rothman, Sheila M.

2006-01-01

We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay–Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815

A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam

PubMed Central

Poyarkov, Nikolay A.; Kropachev, Ivan I.; Gogoleva, Svetlana S.; Orlov, Nikolai L.

2018-01-01

A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8–26.4 mm); (7) head longer than wide; ED/SVL ratio 13%–15%; ESL/SVL ratio 16%–20%; (8) small tympanum (TD/EL ratio 50%–60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2–2¼ II 1½–2¾ III 2–3¼ IV 3–1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3–5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma

PRECEPT: an evidence assessment framework for infectious disease epidemiology, prevention and control.

PubMed

Harder, Thomas; Takla, Anja; Eckmanns, Tim; Ellis, Simon; Forland, Frode; James, Roberta; Meerpohl, Joerg J; Morgan, Antony; Rehfuess, Eva; Schünemann, Holger; Zuiderent-Jerak, Teun; de Carvalho Gomes, Helena; Wichmann, Ole

2017-10-01

Decisions in public health should be based on the best available evidence, reviewed and appraised using a rigorous and transparent methodology. The Project on a Framework for Rating Evidence in Public Health (PRECEPT) defined a methodology for evaluating and grading evidence in infectious disease epidemiology, prevention and control that takes different domains and question types into consideration. The methodology rates evidence in four domains: disease burden, risk factors, diagnostics and intervention. The framework guiding it has four steps going from overarching questions to an evidence statement. In step 1, approaches for identifying relevant key areas and developing specific questions to guide systematic evidence searches are described. In step 2, methodological guidance for conducting systematic reviews is provided; 15 study quality appraisal tools are proposed and an algorithm is given for matching a given study design with a tool. In step 3, a standardised evidence-grading scheme using the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) methodology is provided, whereby findings are documented in evidence profiles. Step 4 consists of preparing a narrative evidence summary. Users of this framework should be able to evaluate and grade scientific evidence from the four domains in a transparent and reproducible way.

PRECEPT: an evidence assessment framework for infectious disease epidemiology, prevention and control

PubMed Central

Harder, Thomas; Takla, Anja; Eckmanns, Tim; Ellis, Simon; Forland, Frode; James, Roberta; Meerpohl, Joerg J; Morgan, Antony; Rehfuess, Eva; Schünemann, Holger; Zuiderent-Jerak, Teun; de Carvalho Gomes, Helena; Wichmann, Ole

2017-01-01

Decisions in public health should be based on the best available evidence, reviewed and appraised using a rigorous and transparent methodology. The Project on a Framework for Rating Evidence in Public Health (PRECEPT) defined a methodology for evaluating and grading evidence in infectious disease epidemiology, prevention and control that takes different domains and question types into consideration. The methodology rates evidence in four domains: disease burden, risk factors, diagnostics and intervention. The framework guiding it has four steps going from overarching questions to an evidence statement. In step 1, approaches for identifying relevant key areas and developing specific questions to guide systematic evidence searches are described. In step 2, methodological guidance for conducting systematic reviews is provided; 15 study quality appraisal tools are proposed and an algorithm is given for matching a given study design with a tool. In step 3, a standardised evidence-grading scheme using the Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) methodology is provided, whereby findings are documented in evidence profiles. Step 4 consists of preparing a narrative evidence summary. Users of this framework should be able to evaluate and grade scientific evidence from the four domains in a transparent and reproducible way. PMID:29019317

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed

Verbeek, Jos

2012-06-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely.

Evidence for the effect of disease management: is $1 billion a year a good investment?

PubMed

Mattke, Soeren; Seid, Michael; Ma, Sai

2007-12-01

To assess the evidence for the effect of disease management on quality of care, disease control, and cost, with a focus on population-based programs. Literature review. We conducted a literature search for and a structured review of studies on population-based disease management programs, as well as for reviews and meta-analyses of disease management interventions. We identified 3 evaluations of large-scale population-based programs, as well as 10 meta-analyses and 16 systematic reviews, covering 317 unique studies. We found consistent evidence that disease management improves processes of care and disease control but no conclusive support for its effect on health outcomes. Overall, disease management does not seem to affect utilization except for a reduction in hospitalization rates among patients with congestive heart failure and an increase in outpatient care and prescription drug use among patients with depression. When the costs of the intervention were appropriately accounted for and subtracted from any savings, there was no conclusive evidence that disease management leads to a net reduction of direct medical costs. Although disease management seems to improve quality of care, its effect on cost is uncertain. Most of the evidence to date addresses small-scale programs targeting high-risk individuals, while only 3 studies evaluate large population-based interventions, implying that little is known about their effect. Payers and policy makers should remain skeptical about vendor claims and should demand supporting evidence based on transparent and scientifically sound methods.

Novel Evidence-Based Classification of Cavernous Venous Occlusive Disease.

PubMed

Pathak, Ram A; Rawal, Bhupendra; Li, Zhuo; Broderick, Gregory A

2016-10-01

The primary aim of our study was to determine whether an evidence-based rationale could categorize cavernous venous occlusive disease into mild, moderate and severe erectile dysfunction. A total of 863 patients underwent color duplex Doppler ultrasound from January 2010 to June 2013 performed by a single urologist. We identified a cohort of 75 patients (8.7%) with a diagnosis of cavernous venous occlusive disease based on a unilateral resistive index less than 0.9, and right and left peak systolic velocity 35 cm per second or less after visual sexual stimulation. At a median followup of 13 months patients were evaluated for treatment efficacy. A total of 75 patients with a median age of 60 years (range 19 to 83) and a mean body mass index of 26.3 kg/m(2) (range 19.0 to 39.3) satisfied the criteria of cavernous venous occlusive disease. When substratified into tertiles, resistive index cutoffs were obtained, including mild cavernous venous occlusive disease-81.6 to 94.0, moderate disease-72.6 to 81.5 and severe disease-59.5 to 72.5. Using these 3 groups the phosphodiesterase type 5-inhibitor failure rate (p = 0.017) and SHIM (Sexual Health Inventory for Men) score categories (1 to 10 vs 11 to 20, p = 0.030) were statistically significantly different for mild, moderate and severe cavernous venous occlusive disease. Treatment satisfaction was also statistically significantly different. Penile prosthetic placement was a more common outcome among patients with erectile dysfunction and more severe cavernous venous occlusive disease. Our retrospective analysis supports a correlation between the phosphodiesterase type 5 inhibitor failure rate, SHIM score and the rate of surgical intervention using resistive index values. Our data further suggest that an evidence-based classification of cavernous venous occlusive disease by color Doppler ultrasound is possible and can triage patients to penile prosthetic placement. Copyright © 2016 American Urological Association

When Work is Related to Disease, What Establishes Evidence for a Causal Relation?

PubMed Central

2012-01-01

Establishing a causal relationship between factors at work and disease is difficult for occupational physicians and researchers. This paper seeks to provide arguments for the judgement of evidence of causality in observational studies that relate work factors to disease. I derived criteria for the judgement of evidence of causality from the following sources: the criteria list of Hill, the approach by Rothman, the methods used by International Agency for Research on Cancer (IARC), and methods used by epidemiologists. The criteria are applied to two cases of putative occupational diseases; breast cancer caused by shift work and aerotoxic syndrome. Only three of the Hill criteria can be applied to an actual study. Rothman stresses the importance of confounding and alternative explanations than the putative cause. IARC closely follows Hill, but they also incorporate other than epidemiological evidence. Applied to shift work and breast cancer, these results have found moderate evidence for a causal relationship, but applied to the aerotoxic syndrome, there is an absence of evidence of causality. There are no ready to use algorithms for judgement of evidence of causality. Criteria from different sources lead to similar results and can make a conclusion of causality more or less likely. PMID:22993715

Integrative Therapies and Pediatric Inflammatory Bowel Disease: The Current Evidence

PubMed Central

Misra, Sanghamitra M.

2014-01-01

Inflammatory bowel disease (IBD) primarily describes two distinct chronic conditions with unknown etiology, ulcerative colitis (UC) and Crohn’s disease (CD). UC is limited to the colon, while CD may involve any portion of the gastrointestinal tract from mouth to anus. These diseases exhibit a pattern of relapse and remission, and the disease processes are often painful and debilitating. Due to the chronic nature of IBD and the negative side effects of many of the conventional therapies, many patients and their families turn to complementary and alternative medicine (CAM) for symptom relief. This article focuses on the current available evidence behind CAM/integrative therapies for IBD. PMID:27417473

Magnification-temperature correlation: The dark side of integrated Sachs-Wolfe measurements

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

LoVerde, Marilena; Hui, Lam; Gaztanaga, Enrique

2007-02-15

Integrated Sachs-Wolfe (ISW) measurements, which involve cross-correlating the microwave background anisotropies with the foreground large-scale structure (e.g. traced by galaxies/quasars), have proven to be an interesting probe of dark energy. We show that magnification bias, which is the inevitable modulation of the foreground number counts by gravitational lensing, alters both the scale dependence and amplitude of the observed ISW signal. This is true especially at high redshifts because (1) the intrinsic galaxy-temperature signal diminishes greatly back in the matter-dominated era, (2) the lensing efficiency increases with redshift and (3) the number count slope generally steepens with redshift in a magnitudemore » limited sample. At z > or approx. 2, the magnification-temperature correlation dominates over the intrinsic galaxy-temperature correlation and causes the observed ISW signal to increase with redshift, despite dark energy subdominance--a result of the fact that magnification probes structures all the way from the observer to the sources. Ignoring magnification bias therefore can lead to (significantly) erroneous conclusions about dark energy. While the lensing modulation opens up an interesting high z window for ISW measurements, high redshift measurements are not expected to add much new information to low redshift ones if dark energy is indeed the cosmological constant. This is because lensing introduces significant covariance across redshifts. The most compelling reasons for pursuing high redshift ISW measurements are to look for potential surprises such as early dark energy domination or signatures of modified gravity. We conclude with a discussion of existing measurements, the highest redshift of which is at the margin of being sensitive to the magnification effect. We also develop a formalism which might be of more general interest: to predict biases in estimating parameters when certain physical effects are ignored in interpreting

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective

PubMed Central

Axelrad, Jordan E; Roy, Abhik; Lawlor, Garrett; Korelitz, Burton; Lichtiger, Simon

2016-01-01

The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn’s disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications. PMID:28028358

Thiopurines and inflammatory bowel disease: Current evidence and a historical perspective.

PubMed

Axelrad, Jordan E; Roy, Abhik; Lawlor, Garrett; Korelitz, Burton; Lichtiger, Simon

2016-12-14

The use of thiopurines in inflammatory bowel disease (IBD) has been examined in numerous prospective, controlled trials, with a majority demonstrating a clinical benefit. We conducted this review to describe the historical and current evidence in the use of thiopurines in IBD. A systematic search was performed on MEDLINE between 1965 and 2016 to identify studies on thiopurines in IBD. The most robust evidence for thiopurines in IBD includes induction of remission in combination with anti-tumor necrosis factor (anti-TNF) agents, and maintenance of remission and post-operative maintenance in Crohn's disease. Less evidence exists for thiopurine monotherapy in induction of remission, maintenance of ulcerative colitis, chemoprevention of colorectal cancer, and in preventing immunogenicity to anti-TNF. Evidence was often limited by trial design. Overall, thiopurines have demonstrated efficacy in a broad range of presentations of IBD. With more efficacious novel therapeutic agents, the positioning of thiopurines in the management of IBD will change and future studies will analyze the benefit of thiopurines alone and in conjunction with these new medications.

HGPEC: a Cytoscape app for prediction of novel disease-gene and disease-disease associations and evidence collection based on a random walk on heterogeneous network.

PubMed

Le, Duc-Hau; Pham, Van-Huy

2017-06-15

Finding gene-disease and disease-disease associations play important roles in the biomedical area and many prioritization methods have been proposed for this goal. Among them, approaches based on a heterogeneous network of genes and diseases are considered state-of-the-art ones, which achieve high prediction performance and can be used for diseases with/without known molecular basis. Here, we developed a Cytoscape app, namely HGPEC, based on a random walk with restart algorithm on a heterogeneous network of genes and diseases. This app can prioritize candidate genes and diseases by employing a heterogeneous network consisting of a network of genes/proteins and a phenotypic disease similarity network. Based on the rankings, novel disease-gene and disease-disease associations can be identified. These associations can be supported with network- and rank-based visualization as well as evidences and annotations from biomedical data. A case study on prediction of novel breast cancer-associated genes and diseases shows the abilities of HGPEC. In addition, we showed prominence in the performance of HGPEC compared to other tools for prioritization of candidate disease genes. Taken together, our app is expected to effectively predict novel disease-gene and disease-disease associations and support network- and rank-based visualization as well as biomedical evidences for such the associations.

Air pollution and Parkinson's disease - evidence and future directions.

PubMed

Palacios, Natalia

2017-12-20

Parkinson's disease (PD) is a neurodegenerative disease of unknown etiology that is thought to be caused by a complex combination of environmental and/or genetic factors. Air pollution exposure is linked to numerous adverse effects on human health, including brain inflammation and oxidative stress, processes that are believed to contribute to the development and progression of PD. This review provides an overview of recent advances in the epidemiology of air pollution and PD, including evidence of the effects of various pollutants (ozone, PM10, PM2.5, PM2.5-10, NOx, NO2, CO, traffic air pollution, second-hand smoking) on PD risk. Based on this evidence, promising opportunities for future research are outlined, including: (1) studies of smaller particle sizes that cross the blood-brain barrier, (2) studies of the effects of air pollution on PD mortality and/or progression; (3) studies of interactions of air pollution with gene environment and other environmental factors.

The concept of wrongful life in the law.

PubMed

Kasper, A S

1983-01-01

In the history of the law the concept of wrongful life is not new, but it has become of interest recently due to changing social attitudes and advances in contraceptive and genetic technologies. This discussion tries to assess the effects of wrongful life as a legal concept on the rights of childbearing women and their offspring. An unborn child had no rights under common law, which held that a fetus in utero had no existence separate from its mother. Consequently, a child had no right of action for personal harm brought upon it by another person. On occasion early courts disagreed with this view, but the majority of courts maintained that a child had no existence as a human being during gestation. The effect that this concept of common law would have on current abortion laws would be to make it considerably easier to argue for a woman's right to choose an abortion. The notion of wrongful life initially appeared in cases of illegitimate births. In Zepeda v. Zepeda, 1963, and Williams v. State of New York, 1966, the plaintiffs maintained that the children's births and existence were wrongful because they were unintended and illegitimate. In Williams the court ruled that birth under 1 set of circumstances and not another is not a recoverable injury. These cases failed to meet the requirements of tort law, and the court rejected the notion of children finding legal recourse for being born to a poor family or being born to a less desired race or class. A series of cases followed in which recovery for physical injury or birth deformities were claimed by parents for themselves and their children. In June 1980 a California appeals court reversed the decision of a lower court, addressing the fundamental principles of wrongful life as a legal concept. In Curlender v. Bio-Science Laboratories an infant brought suit alleging that the laboratories failed to correctly inform her parents of their status as carriers of Tay-Sachs disease during the mother's pregnancy. The infant

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

Probiotics and Diverticular Disease: Evidence-based?

PubMed

Lahner, Edith; Annibale, Bruno

Diverticular disease (DD) is a common gastrointestinal condition. Clinical spectrum ranges from asymptomatic diverticulosis to symptomatic uncomplicated or complicated DD. Symptoms related to uncomplicated DD are not specific and may be indistinguishable from those of irritable bowel syndrome. Low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors potentially contributing to symptoms. Probiotics may modify the gut microbial balance leading to health benefits. Probiotics, due to their anti-inflammatory effects and ability to maintain an adequate bacterial colonization in the colon, are promising treatment options for DD. This review focuses on the available evidence on the efficacy of prebiotics in uncomplicated DD.

The epidemiology of bovine respiratory disease: What is the evidence for preventive measures?

PubMed Central

Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.

2010-01-01

Bovine respiratory disease (BRD) is the most common and costly disease of beef cattle in North America. Despite extensive research, industry practices are often more informed by dogma than by fact. Frequently advocated interventions, including vaccination, various processing procedures, and nutritional manipulation, have limited impact on morbidity and mortality. Evidence for use of oral antimicrobials, either in feed or water, appears to be equivocal. In contrast, preconditioning and metaphylaxis have significant scientific evidence of efficacy, with weaning prior to sale potentially being the most important component of preconditioning. The inability to reach more definitive conclusions in preventing BRD may be attributable to difficulties in investigating the disease. Study challenges include potential for extensive confounding, tremendous variability, the multi-factorial nature of the disease, and inadequate methods for diagnosis. PMID:21358927

Description of new species of Pterygorhabditis Timm, and Aspidonema (Sachs, ) Andrássy, (Nematoda: Bunonematoidea) in aquatic habitats from India.

PubMed

Tahseen, Q; Khan, R; Ahlawat, S

2016-07-01

The paper contains descriptions of two new species of the genera Pterygorhabditis Timm, 1957 and Aspidonema (Sachs, 1949) Andrássy, 1958 belonging to the families Pterygorhabditidae Goodey 1963 and Bunonematidae Micoletzky 1922, respectively. Species were procured from fixed samples, collected earlier from aquatic habitats. Pterygorhabditis punctata n. sp. is characterized by a cuticle with flattened hexagonal blocks arranged in eight longitudinal rows in both sexes; each metastegostomal plate with a minute denticle, and males with long, slender, fused spicules and nine pairs of post-cloacal, prominently setose genital papillae. Aspidonema formosa n. sp. is the first report of the genus from India. The species is characterized by the right side provided with 35-48 pairs of warts flanking a row of smooth membranous shields and surrounded by a well-developed network and an anisomorphic metastegostom without discernible armature. Species are compared with other congeners, together with the diagnoses of amended genera, and keys to the identification of species are provided.

Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework.

PubMed

Wilhide Iii, Calvin C; Peeples, Malinda M; Anthony Kouyaté, Robin C

2016-02-16

Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to systematically expand mobile health interventions and validate

Evidence-Based mHealth Chronic Disease Mobile App Intervention Design: Development of a Framework

PubMed Central

Peeples, Malinda M; Anthony Kouyaté, Robin C

2016-01-01

Background Mobile technology offers new capabilities that can help to drive important aspects of chronic disease management at both an individual and population level, including the ability to deliver real-time interventions that can be connected to a health care team. A framework that supports both development and evaluation is needed to understand the aspects of mHealth that work for specific diseases, populations, and in the achievement of specific outcomes in real-world settings. This framework should incorporate design structure and process, which are important to translate clinical and behavioral evidence, user interface, experience design and technical capabilities into scalable, replicable, and evidence-based mobile health (mHealth) solutions to drive outcomes. Objective The purpose of this paper is to discuss the identification and development of an app intervention design framework, and its subsequent refinement through development of various types of mHealth apps for chronic disease. Methods The process of developing the framework was conducted between June 2012 and June 2014. Informed by clinical guidelines, standards of care, clinical practice recommendations, evidence-based research, best practices, and translated by subject matter experts, a framework for mobile app design was developed and the refinement of the framework across seven chronic disease states and three different product types is described. Results The result was the development of the Chronic Disease mHealth App Intervention Design Framework. This framework allowed for the integration of clinical and behavioral evidence for intervention and feature design. The application to different diseases and implementation models guided the design of mHealth solutions for varying levels of chronic disease management. Conclusions The framework and its design elements enable replicable product development for mHealth apps and may provide a foundation for the digital health industry to

What is the evidence behind the evidence-base? The premature death of block-replace antithyroid drug regimens for Graves' disease.

PubMed

Razvi, Salman; Vaidya, Bijay; Perros, Petros; Pearce, Simon H S

2006-06-01

Block-replace and titration antithyroid drug regimens both give similar rates of medium- to long-term remission of hyperthyroid Graves' disease. Recent meta-analysis, however, has suggested that titration regimens may be preferable owing to a higher rate of adverse events seen in the block-replace arms of published comparative studies. This article critically re-evaluates the evidence upon which these meta-analyses were based. We suggest that there is little objective evidence that is pertinent to current clinical practice to separate block-replace from titration antithyroid drug regimens and that both remain satisfactory approaches to the medical management of hyperthyroid Graves' disease.

Evidence for the role of infectious disease in species extinction and endangerment

USGS Publications Warehouse

Smith, Katherine F.; Sax, Dov F.; Lafferty, Kevin D.

2006-01-01

Infectious disease is listed among the top five causes of global species extinctions. However, the majority of available data supporting this contention is largely anecdotal. We used the IUCN Red List of Threatened and Endangered Species and literature indexed in the ISI Web of Science to assess the role of infectious disease in global species loss. Infectious disease was listed as a contributing factor in <4% of species extinctions known to have occurred since 1500 (833 plants and animals) and as contributing to a species' status as critically endangered in <8% of cases (2852 critically endangered plants and animals). Although infectious diseases appear to play a minor role in global species loss, our findings underscore two important limitations in the available evidence: uncertainty surrounding the threats to species survival and a temporal bias in the data. Several initiatives could help overcome these obstacles, including rigorous scientific tests to determine which infectious diseases present a significant threat at the species level, recognition of the limitations associated with the lack of baseline data for the role of infectious disease in species extinctions, combining data with theory to discern the circumstances under which infectious disease is most likely to serve as an agent of extinction, and improving surveillance programs for the detection of infectious disease. An evidence-based understanding of the role of infectious disease in species extinction and endangerment will help prioritize conservation initiatives and protect global biodiversity.

Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice.

PubMed

Osmon, Karlaina J L; Woodley, Evan; Thompson, Patrick; Ong, Katalina; Karumuthil-Melethil, Subha; Keimel, John G; Mark, Brian L; Mahuran, Don; Gray, Steven J; Walia, Jagdeep S

2016-07-01

mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay-Sachs disease (α-subunit deficiency) and similar brain disorders.

Developing a Framework to Generate Evidence of Health Outcomes From Social Media Use in Chronic Disease Management

PubMed Central

Gray, Kathleen; Martin-Sanchez, Fernando

2013-01-01

Background While there is an abundance of evidence-based practice (EBP) recommendations guiding management of various chronic diseases, evidence suggesting best practice for using social media to improve health outcomes is inadequate. The variety of social media platforms, multiple potential uses, inconsistent definitions, and paucity of rigorous studies, make it difficult to measure health outcomes reliably in chronic disease management. Most published investigations report on an earlier generation of online tools, which are not as user-centered, participatory, engaging, or collaborative, and thus may work differently for health self-management. Objective The challenge to establish a sound evidence base for social media use in chronic disease starts with the need to define criteria and methods to generate and evaluate evidence. The authors’ key objective is to develop a framework for research and practice that addresses this challenge. Methods This paper forms part of a larger research project that presents a conceptual framework of how evidence of health outcomes can be generated from social media use, allowing social media to be utilized in chronic disease management more effectively. Using mixed methods incorporating a qualitative literature review, a survey and a pilot intervention, the research closely examines the therapeutic affordances of social media, people with chronic pain (PWCP) as a subset of chronic disease management, valid outcome measurement of patient-reported (health) outcomes (PRO), the individual needs of people living with chronic disease, and finally translation of the combined results to improve evidence-based decision making about social media use in this context. Results Extensive review highlights various affordances of social media that may prove valuable to understanding social media’s effect on individual health outcomes. However, without standardized PRO instruments, we are unable to definitively investigate these effects. The

Developing a framework to generate evidence of health outcomes from social media use in chronic disease management.

PubMed

Merolli, Mark; Gray, Kathleen; Martin-Sanchez, Fernando

2013-01-01

While there is an abundance of evidence-based practice (EBP) recommendations guiding management of various chronic diseases, evidence suggesting best practice for using social media to improve health outcomes is inadequate. The variety of social media platforms, multiple potential uses, inconsistent definitions, and paucity of rigorous studies, make it difficult to measure health outcomes reliably in chronic disease management. Most published investigations report on an earlier generation of online tools, which are not as user-centered, participatory, engaging, or collaborative, and thus may work differently for health self-management. The challenge to establish a sound evidence base for social media use in chronic disease starts with the need to define criteria and methods to generate and evaluate evidence. The authors' key objective is to develop a framework for research and practice that addresses this challenge. This paper forms part of a larger research project that presents a conceptual framework of how evidence of health outcomes can be generated from social media use, allowing social media to be utilized in chronic disease management more effectively. Using mixed methods incorporating a qualitative literature review, a survey and a pilot intervention, the research closely examines the therapeutic affordances of social media, people with chronic pain (PWCP) as a subset of chronic disease management, valid outcome measurement of patient-reported (health) outcomes (PRO), the individual needs of people living with chronic disease, and finally translation of the combined results to improve evidence-based decision making about social media use in this context. Extensive review highlights various affordances of social media that may prove valuable to understanding social media's effect on individual health outcomes. However, without standardized PRO instruments, we are unable to definitively investigate these effects. The proposed framework that we offer outlines

Beta blockers in patients with end-stage renal disease-Evidence-based recommendations.

PubMed

Weir, Matthew A; Herzog, Charles A

2018-05-01

For patients who require hemodialysis, beta blockers offer a simultaneous opportunity and challenge in the treatment of cardiovascular disease. Beta blockers are well supported by data from nondialysis populations and directly mitigate the sympathetic overactivity that links chronic kidney disease with cardiovascular sequelae. However, the evidence supporting their use in patients receiving hemodialysis is sparse and the heterogeneity of the beta blocker class makes it difficult to prescribe these medications with confidence. Despite these limitations, both trial and observational data exist that can help guide the use of these medications. In this review, we outline the reasons to consider beta blockers for patients receiving hemodialysis, discuss the barriers to their use, and provide specific evidence-based recommendations for beta blocker use in patients with heart failure, hypertension, ischemic heart disease and arrhythmia. © 2018 Wiley Periodicals, Inc.

Approaches to the Surveillance of Foodborne Disease: A Review of the Evidence.

PubMed

Ford, Laura; Miller, Megge; Cawthorne, Amy; Fearnley, Emily; Kirk, Martyn

2015-12-01

Foodborne disease surveillance aims to reduce the burden of illness due to contaminated food. There are several different types of surveillance systems, including event-based surveillance, indicator-based surveillance, and integrated food chain surveillance. These approaches are not mutually exclusive, have overlapping data sources, require distinct capacities and resources, and can be considered a hierarchy, with each level being more complex and resulting in a greater ability to detect and control foodborne disease. Event-based surveillance is generally the least resource-intensive system and makes use of informal data sources. Indicator-based surveillance is seen as traditional notifiable disease surveillance and consists of routinely collected data. Integrated food chain surveillance is viewed as the optimal practice for conducting continuous risk analysis for foodborne diseases, but also requires significant ongoing resources and greater multisectoral collaboration compared to the other systems. Each country must determine the most appropriate structure for their surveillance system for foodborne diseases based on their available resources. This review explores the evidence on the principles, minimum capabilities, and minimum requirements of each type of surveillance and discusses examples from a range of countries. This review forms the evidence base for the Strengthening the Surveillance and Response for Foodborne Diseases: A Practical Manual.

Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

DOE PAGES

Ade, P. A. R.; Aghanim, N.; Arnaud, M.; ...

2016-09-20

Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

Planck 2015 results. XXI. The integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartolo, N.; Basak, S.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bock, J. J.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Bucher, M.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Casaponsa, B.; Catalano, A.; Challinor, A.; Chamballu, A.; Chiang, H. C.; Christensen, P. R.; Church, S.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Désert, F.-X.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dupac, X.; Efstathiou, G.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Fergusson, J.; Fernandez-Cobos, R.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Frejsel, A.; Galeotta, S.; Galli, S.; Ganga, K.; Génova-Santos, R. T.; Giard, M.; Giraud-Héraud, Y.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Leonardi, R.; Lesgourgues, J.; Levrier, F.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Ma, Y.-Z.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Marcos-Caballero, A.; Maris, M.; Martin, P. G.; Martínez-González, E.; Masi, S.; Matarrese, S.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rossetti, M.; Roudier, G.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savelainen, M.; Savini, G.; Schaefer, B. M.; Scott, D.; Seiffert, M. D.; Shellard, E. P. S.; Spencer, L. D.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sunyaev, R.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Valenziano, L.; Valiviita, J.; Van Tent, F.; Vielva, P.; Villa, F.; Wade, L. A.; Wandelt, B. D.; Wehus, I. K.; Yvon, D.; Zacchei, A.; Zonca, A.

2016-09-01

This paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and the NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that ΩΛ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by combining the

Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

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

Ade, P. A. R.; Aghanim, N.; Arnaud, M.

Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

Impact of global warming on viral diseases: what is the evidence?

PubMed

Zell, Roland; Krumbholz, Andi; Wutzler, Peter

2008-12-01

Global warming is believed to induce a gradual climate change. Hence, it was predicted that tropical insects might expand their habitats thereby transmitting pathogens to humans. Although this concept is a conclusive presumption, clear evidence is still lacking--at least for viral diseases. Epidemiological data indicate that seasonality of many diseases is further influenced by strong single weather events, interannual climate phenomena, and anthropogenic factors. So far, emergence of new diseases was unlinked to global warming. Re-emergence and dispersion of diseases was correlated with translocation of pathogen-infected vectors or hosts. Coupled ocean/atmosphere circulations and 'global change' that also includes shifting of demographic, social, and economical conditions are important drivers of viral disease variability whereas global warming at best contributes.

Integrated Sachs-Wolfe effect from the cross correlation of WMAP 3year and the NRAO VLA sky survey data: New results and constraints on dark energy

NASA Astrophysics Data System (ADS)

Pietrobon, Davide; Balbi, Amedeo; Marinucci, Domenico

2006-08-01

We cross correlate the new 3 year Wilkinson Microwave Anistropy Probe (WMAP) cosmic microwave background data with the NRAO VLA Sky Survey radio galaxy data and find further evidence of late integrated Sachs-Wolfe (ISW) effect taking place at late times in cosmic history. Our detection makes use of a novel statistical method (P. Baldi, G. Kerkyacharian, D. Marinucci, and D. Picard, math.ST/0606154 and P. Baldi, G. Kerkyacharian, D. Marinucci, D. Picard, math.ST/0606599) based on a new construction of spherical wavelets, called needlets. The null hypothesis (no ISW) is excluded at more than 99.7% confidence. When we compare the measured cross correlation with the theoretical predictions of standard, flat cosmological models with a generalized dark energy component parameterized by its density, ΩDE, equation of state w and speed of sound cs2, we find 0.3≤ΩDE≤0.8 at 95% C.L., independently of cs2 and w. If dark energy is assumed to be a cosmological constant (w=-1), the bound on density shrinks to 0.41≤ΩDE≤0.79. Models without dark energy are excluded at more than 4σ. The bounds on w depend rather strongly on the assumed value of cs2. We find that models with more negative equation of state (such as phantom models) are a worse fit to the data in the case cs2=1 than in the case cs2=0.

Constraining neutrino masses with the integrated-Sachs-Wolfe-galaxy correlation function

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

Lesgourgues, Julien; Valkenburg, Wessel; Gaztanaga, Enrique

2008-03-15

Temperature anisotropies in the cosmic microwave background (CMB) are affected by the late integrated Sachs-Wolfe (lISW) effect caused by any time variation of the gravitational potential on linear scales. Dark energy is not the only source of lISW, since massive neutrinos induce a small decay of the potential on small scales during both matter and dark energy domination. In this work, we study the prospect of using the cross correlation between CMB and galaxy-density maps as a tool for constraining the neutrino mass. On the one hand massive neutrinos reduce the cross-correlation spectrum because free-streaming slows down structure formation; onmore » the other hand, they enhance it through their change in the effective linear growth. We show that in the observable range of scales and redshifts, the first effect dominates, but the second one is not negligible. We carry out an error forecast analysis by fitting some mock data inspired by the Planck satellite, Dark Energy Survey (DES) and Large Synoptic Survey Telescope (LSST). The inclusion of the cross correlation data from Planck and LSST increases the sensitivity to the neutrino mass m{sub {nu}} by 38% (and to the dark energy equation of state w by 83%) with respect to Planck alone. The correlation between Planck and DES brings a far less significant improvement. This method is not potentially as good for detecting m{sub {nu}} as the measurement of galaxy, cluster, or cosmic shear power spectra, but since it is independent and affected by different systematics, it remains potentially interesting if the total neutrino mass is of the order of 0.2 eV; if instead it is close to the lower bound from atmospheric oscillations, m{sub {nu}}{approx}0.05 eV, we do not expect the ISW-galaxy correlation to be ever sensitive to m{sub {nu}}.« less

Language Deficits in Pre-Symptomatic Huntington's Disease: Evidence from Hungarian

ERIC Educational Resources Information Center

Nemeth, Dezso; Dye, Cristina D.; Sefcsik, Tamas; Janacsek, Karolina; Turi, Zsolt; Londe, Zsuzsa; Klivenyi, Peter; Kincses, Zsigmond Tamas; Szabo, Nikoletta; Vecsei, Laszlo; Ullman, Michael T.

2012-01-01

A limited number of studies have investigated language in Huntington's disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as…

Validation of the technique for absolute total electron content and differential code biases estimation

NASA Astrophysics Data System (ADS)

Mylnikova, Anna; Yasyukevich, Yury; Yasyukevich, Anna

2017-04-01

We have developed a technique for vertical total electron content (TEC) and differential code biases (DCBs) estimation using data from a single GPS/GLONASS station. The algorithm is based on TEC expansion into Taylor series in space and time (TayAbsTEC). We perform the validation of the technique using Global Ionospheric Maps (GIM) computed by Center for Orbit Determination in Europe (CODE) and Jet Propulsion Laboratory (JPL). We compared differences between absolute vertical TEC (VTEC) from GIM and VTEC evaluated by TayAbsTEC for 2009 year (solar activity minimum - sunspot number about 0), and for 2014 year (solar activity maximum - sunspot number 110). Since there is difference between VTEC from CODE and VTEC from JPL, we compare TayAbsTEC VTEC with both of them. We found that TayAbsTEC VTEC is closer to CODE VTEC than to JPL VTEC. The difference between TayAbsTEC VTEC and GIM VTEC is more noticeable for solar activity maximum (2014) than for solar activity minimum (2009) for both CODE and JPL. The distribution of VTEC differences is close to Gaussian distribution, so we conclude that results of TayAbsTEC are in the agreement with GIM VTEC. We also compared DCBs evaluated by TayAbsTEC and DCBs from GIM, computed by CODE. The TayAbsTEC DCBs are in good agreement with CODE DCBs for GPS satellites, but differ noticeable for GLONASS. We used DCBs to correct slant TEC to find out which DCBs give better results. Slant TEC correction with CODE DCBs produces negative and nonphysical TEC values. Slant TEC correction with TayAbsTEC DCBs doesn't produce such artifacts. The technique we developed is used for VTEC and DCBs calculation given only local GPS/GLONASS networks data. The evaluated VTEC data are in GIM framework which is handy when various data analyses are made.

Evidence-based practice in Behçet’s disease: identifying areas of unmet need for 2014

PubMed Central

2014-01-01

Background Behçet’s Disease (BD) is characterized by a relapsing-remitting course, with symptoms of varying severity across almost all organ systems. There is a diverse array of therapeutic options with no universally accepted treatment regime, and it is thus important that clinical practice is evidence-based. We reviewed all currently available literature describing management of BD, and investigated whether evidence-based practice is possible for all disease manifestations, and assessed the range of therapeutic options tested. Methods We conducted an internet search of all literature describing management of BD up to August 2013, including pharmacological and non-pharmacological interventions. We recorded treatment options investigated and disease manifestations reported as primary and secondary study outcomes. Quality of data was assessed according to the Scottish Intercollegiate Guideline Network (SIGN) hierarchy of evidence. Results Whilst there is much literature describing treatment of ocular and mucocutaneous disease, there is little to guide management of rheumatoid, cardiovascular and neurological disease. This broadly reflects the prevalence of disease manifestations of BD, but not the severity. Biologic therapies are the most commonly investigated intervention. The proportion of SIGN-1 graded studies is declining, and there are no SIGN-1 graded studies investigating neurological or gastrointestinal manifestations of BD. Conclusions This is the first study to investigate trends in published literature for management of BD over time. It identifies neurological, cardiovascular and gastro-intestinal disease as particular areas of unmet need and suggests that overall quality of evidence is declining. Future research should be designed to address these areas of insufficiency to facilitate evidence-based practice in BD. PMID:24475935

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease.

PubMed

Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

2014-09-01

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions - the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1-13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols.

Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease

PubMed Central

Cameron, Daniel J; Johnson, Lorraine B; Maloney, Elizabeth L

2014-01-01

Evidence-based guidelines for the management of patients with Lyme disease were developed by the International Lyme and Associated Diseases Society (ILADS). The guidelines address three clinical questions – the usefulness of antibiotic prophylaxis for known tick bites, the effectiveness of erythema migrans treatment and the role of antibiotic retreatment in patients with persistent manifestations of Lyme disease. Healthcare providers who evaluate and manage patients with Lyme disease are the intended users of the new ILADS guidelines, which replace those issued in 2004 (Exp Rev Anti-infect Ther 2004;2:S1–13). These clinical practice guidelines are intended to assist clinicians by presenting evidence-based treatment recommendations, which follow the Grading of Recommendations Assessment, Development and Evaluation system. ILADS guidelines are not intended to be the sole source of guidance in managing Lyme disease and they should not be viewed as a substitute for clinical judgment nor used to establish treatment protocols. PMID:25077519

The oxidative stress theory of disease: levels of evidence and epistemological aspects.

PubMed

Ghezzi, Pietro; Jaquet, Vincent; Marcucci, Fabrizio; Schmidt, Harald H H W

2017-06-01

The theory that oxidative stress (OS) is at the root of several diseases is extremely popular. However, so far, no antioxidant has been recommended or offered by healthcare systems neither has any been approved as therapy by regulatory agencies that base their decisions on evidence-based medicine. This is simply because, so far, despite many preclinical and clinical studies indicating a beneficial effect of antioxidants in many disease conditions, randomised clinical trials have failed to provide the evidence of efficacy required for drug approval. In this review, we discuss the levels of evidence required to claim causality in preclinical research on OS, the weakness of the oversimplification associated with OS theory of disease and the importance of the narrative in its popularity. Finally, from a more translational perspective, we discuss the reasons why antioxidants acting by scavenging ROS might not only prevent their detrimental effects but also interfere with essential signalling roles. We propose that ROS have a complex metabolism and are generated by different enzymes at diverse sites and at different times. Aggregating this plurality of systems into a single theory of disease may not be the best way to develop new drugs, and future research may need to focus on specific oxygen-toxifying pathways rather than on non-specific ROS scavengers. Finally, similarly to what is nowadays required for clinical trials, we recommend making unpublished data available in repositories (open data), as this will allow big data approaches or meta-analyses, without the drawbacks of publication bias. This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc. © 2016 The British Pharmacological Society.

Nuclear Accident Crisis and Liver Disease: A Summary on Evidences

PubMed Central

Wiwanitkit, Viroj

2013-01-01

The present global concern is on the adverse effect due to exposure to nuclides expelled from the disrupted nuclear power plant accident in Japan. The exposure can induce several adverse effects. In this specific brief review, the author summarizes the evidences on the effect on liver. Discussion is focused on several liver diseases. PMID:25125994

Further evidence for periodontal disease as a risk indicator for adverse pregnancy outcomes.

PubMed

Turton, Mervyn; Africa, Charlene W J

2017-06-01

Although there is increasing evidence to suggest an association between periodontal disease and adverse pregnancy outcomes, the issue remains controversial. This study tested the hypothesis that periodontal disease is a risk indicator for preterm delivery of low-birthweight infants. The study sample comprised 443 pregnant women with a mean (± standard deviation) age of 24.13 (±5.30) years. At first visit, maternal oral health status was assessed by the measurement of probing pocket depth and clinical attachment loss, and periodontal status was graded as absent, mild, moderate or severe. An association was sought between pregnancy outcomes and maternal periodontal status. While controlling for other factors, significant associations were found between pregnancy outcomes and maternal periodontal index scores. This study provides further evidence that periodontal disease is a risk indicator for adverse pregnancy outcomes. © 2016 FDI World Dental Federation.

Evidence-based disease management: its role in cardiovascular risk reduction.

PubMed

Fanning, Etta L

2004-01-01

Cardiovascular disease remains the most pressing healthcare problem in the United States. Traditional risk factors--hypertension, obesity, and diabetes-are still unresolved issues; and new risk factors--pre-diabetes, insulin resistance, and pediatric and adolescent diabetes-have emerged. There is an urgent need to identify the risk factors for cardiovascular disease, and address risk reduction with disease management and treatment for each factor, based on qualitative and quantitative approaches for developing the evidence base for public health action. The objectives of this paper are to review (i) the burden of cardiovascular illness-morbidity, mortality, and cost; (ii) risk factors and the emerging epidemic of adolescent obesity; (iii) the challenges of attaining target endpoints; and (iv) the attributes of a successful programmatic healthcare initiative for potential impact on cardiovascular care and, eventually, public health.

Evidence for early disease-modifying drugs in rheumatoid arthritis

PubMed Central

Scott, David L

2004-01-01

Some research evidence supports early aggressive treatment of rheumatoid arthritis (RA) using combination therapy with two or more disease modifying anti-rheumatic drugs (DMARDs) plus steroids, or even DMARDs plus an anti-TNF. By contrast, conservatively delayed DMARD monotherapy, given after non-steroidal anti-inflammatory drugs have failed, has been criticised. However, recent long-term studies highlight the complexities in evaluating whether to abandon pyramidal treatment in favour of early DMARDs. Although patients given early DMARD therapy show short-term benefits, longer-term results show no prolonged clinical advantages from early DMARDs. By 5 years patients receiving early DMARDs had similar disease activity and comparable health assessment questionnaire scores to patients who received DMARDs later in their disease course. X-ray progression was persistent and virtually identical in both groups. These negative findings do not invalidate the case for early DMARD therapy, as it is gives sustained reductions in disease activity in the early years of treatment without excessive risks from adverse effects. However, early DMARDs alone do not adequately control RA in the longer term. This may require starting with very aggressive therapy or treating patients more aggressively after early DMARD therapy has been initiated. PMID:14979927

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2012 CFR

2012-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2013 CFR

2013-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2014 CFR

2014-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... particular occupational diseases. The medical report should also include the information specified on the...

Physical activity in the prevention of the most frequent chronic diseases: an analysis of the recent evidence.

PubMed

Kruk, Joanna

2007-01-01

Physical activity is widely recognized as a means for the primary prevention of chronic diseases as well as in patients' treatment and rehabilitation. Moreover, activity has beneficial effects on an individual's health and well-being. Despite the benefits of regular physical activity, the percentage of physically inactive adults in the world is high. Environmental and policy approaches aimed to increase physical activity require continual stress of the epidemiological evidence from studies investigating disease mechanisms as well as controlled clinical trials. To update the evidence that physical activity/exercise is important for reducing the chronic diseases (cardiovascular and heart, diabetes, cancer, obesity, osteoporosis, and fall-related injuries, depression and emotional stress) and for mechanisms that may operate in the relation between physical activity and a disease risk. Research studies published from 2004 through to March 2007 were identified through a review of the literature available on the NLM PubMed, Medline, Current Contents, and Elsevier-Science Direct databases. Recent evidence on physical activity/exercise and reduction of chronic major diseases incidence and rehabilitation of patients replicates previous findings. The strongest evidence exists for colon cancer, breast cancer, and cardiovascular diseases. The maximal magnitudes of the risk reduction reported were: 75% for breast cancer, 49% for cardiovascular and heart diseases, 35% for diabetes, 22% for colorectal cancer. Increased physical activity also prevented the weight gain associated with aging at least 2-times greater in individuals who were more active compared with those who were inactive. Limited new findings has been reported for the beneficial role of physical activity in fall-related injures, depression and emotional distress. Recent evidence confirms previous findings that engaging in moderate physical activity is very important for the primary prevention of chronic diseases

The Late Integrated Sachs-Wolfe Effect and its detectability in galaxy-redshift surveys

NASA Astrophysics Data System (ADS)

Valencia-Díaz, D. R.; Muñoz-Cuartas, J. C.

2017-07-01

The late Integrated Sachs-Wolfe (ISW) effect is underwent by the Cosmic Microwave Background (CMB) photons due to the presence of the Large-Scale Structures (LSS) in an expanding Universe and can be measured through the temperature fluctuations of the CMB. In this work we use numerical simulations of structure formation to study the detectability of the ISW effect. Our method comprises the estimation of the density field through a Cloud-In-Cell mass assignment scheme. With the help of Fourier transforms we estimate the time derivative of the gravitational potential field in Fourier and in coordinate's space. Finally, this field is integrated numerically to know the ISW contribution. We study the time derivative of the potential in two approaches. First, an exact solution that makes use of the full velocity field. Second, a linear approximation related with the linear theory for the formation of LSS. We apply the method to three cosmological simulations. First, a box of 400 h-1 Mpc; second, the MultiDark1 simulation; third, the MultiDark-Plank simulation. For all cases we obtain coherent results with the expected in the literature for a ΛCDM cosmology: with the exact solution the temperature fluctuation is near the ± 30 μ K; the linear approximation shows a signal in the expected range of ± 20 μ K. This positive detection on simulations is important in order to know an expectation for the results we should obtain when working with observational data and will have important implications due to the lack of consensus about the detection of the ISW effect in previous works. Acknowledgements: This work was supported by Colciencias and Universidad de Antioquia, Convenio Beca-Pasantía Joven Investigador Convocatoria 645 de 2014.

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2011 CFR

2011-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

20 CFR 10.116 - What additional evidence is needed in cases based on occupational disease?

Code of Federal Regulations, 2010 CFR

2010-04-01

... based on occupational disease? 10.116 Section 10.116 Employees' Benefits OFFICE OF WORKERS' COMPENSATION... of Proof § 10.116 What additional evidence is needed in cases based on occupational disease? (a) The... occupational diseases. The medical report should also include the information specified on the checklist for...

CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

PubMed

Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

2016-04-01

Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

A Review of Current Evidence of Olmesartan Medoxomil Mimicking Symptoms of Celiac Disease.

PubMed

Sanford, Michele L; Nagel, Angela K

2015-04-01

Objective:To review the evidence of an association between olmesartan medoxomil and symptoms mimicking celiac disease.Data Sources:Literature was searched in PubMed (1965-November 2013) using the key words or MeSH terms olmesartan, enteropathy, celiac disease, sprue, and diarrhea. References from the Food and Drug Administration (FDA) and Dipiro's Pharmacotherapy eighth edition textbook were also reviewed.Data Synthesis:There have been recent implications of olmesartan medoxomil being linked to symptoms mimicking celiac disease. Investigators first identified the association in 22 patients who presented with presumed refractory celiac disease. Upon further evaluation, it was discovered that these symptoms improved when olmesartan was discontinued. In response to this report, additional case studies have been published. DeGaetani et al also further analyzed patients with seronegative villous atrophy from the Celiac Disease Center and found that olmesartan accounted for 22% of previously unclassified sprue cases. Conversely, the authors of the ROADMAP trial, which compared olmesartan to placebo, found no significant differences in the incidence of gastrointestinal adverse effects.Conclusions:There is growing evidence supporting the association between olmesartan and sprue-like symptoms; however, further research is warranted. These symptoms can be life threatening and clinicians should be aware of the potential association.

Role of dietary salt and potassium intake in cardiovascular health and disease: a review of the evidence.

PubMed

Aaron, Kristal J; Sanders, Paul W

2013-09-01

The objective of this review was to provide a synthesis of the evidence on the effect of dietary salt and potassium intake on population blood pressure, cardiovascular disease, and mortality. Dietary guidelines and recommendations are outlined, current controversies regarding the evidence are discussed, and recommendations are made on the basis of the evidence. Designed search strategies were used to search various databases for available studies. Randomized trials of the effect of dietary salt intake reduction or increased potassium intake on blood pressure, target organ damage, cardiovascular disease, and mortality were included. Fifty-two publications from January 1, 1990, to January 31, 2013, were identified for inclusion. Consideration was given to variations in the search terms used and the spelling of terms so that studies were not overlooked, and search terms took the following general form: (dietary salt or dietary sodium or [synonyms]) and (dietary potassium or [synonyms]) and (blood pressure or hypertension or vascular disease or heart disease or chronic kidney disease or stroke or mortality or [synonyms]). Evidence from these studies demonstrates that high salt intake not only increases blood pressure but also plays a role in endothelial dysfunction, cardiovascular structure and function, albuminuria and kidney disease progression, and cardiovascular morbidity and mortality in the general population. Conversely, dietary potassium intake attenuates these effects, showing a linkage to reduction in stroke rates and cardiovascular disease risk. Various subpopulations, such as overweight and obese individuals and aging adults, exhibit greater sensitivity to the effects of reduced salt intake and may gain the most benefits. A diet that includes modest salt restriction while increasing potassium intake serves as a strategy to prevent or control hypertension and decrease cardiovascular morbidity and mortality. Thus, the body of evidence supports population

Evidence of Aujeszky's disease in wild boar in Serbia.

PubMed

Milicevic, V; Radojicic, S; Valcic, M; Ivovic, V; Radosavljevic, V

2016-06-30

Aujeszky's disease is a viral disease of suids caused by Suid Herpesvirus 1. The disease has worldwide distribution with significant economic impact. In Serbia, there is neither an Aujeszky's disease eradication nor national vaccination programme of domestic pigs. Since clinical symptoms of Aujeszky's disease are not specific, it is important to establish a link between clinical signs and presence of ADV active infection in wild boars. The aim of this study was to investigate the possibility of active infection within wild boar showing signs of ADV and also to examine relationship between isolates from domestic pigs and wild boar. Having in mind that virus has not been previously isolated from wild boars in Serbia, we report the first isolation of Suid Herpesvirus 1 from this species in Serbia. Tissue and serum samples from 40 wild boars from eastern Serbia were examined for evidence of Aujeszky's disease (AD). Suid Herpesvirus 1 (SHV1), the cause of AD was isolated on PK15 cell line from three tissue samples, inducing cytopathic effect (CPE) with syncytia forming, and viral genome was detected by polymerase chain reaction (PCR) in eight samples. Genetic analysis of us4, us9 and ul49.5 partial sequences showed high homology between ADV isolates from wild boars and between isolates from wild boars and domestic animals. Neutralizing antibodies were not detected by virus neutralisation test (VNT) in sera from four out of eight PCR positive wild boars suggesting recent infection in those animals. This is the first demonstration of Aujeszky's disease virus (ADV) in the wild boar population in Serbia although seroconversion has been detected previously.

Posttraumatic Stress Disorder, Cardiovascular and Metabolic Disease: A Review of the Evidence

PubMed Central

Dedert, Eric A.; Calhoun, Patrick S.; Watkins, Lana L.; Sherwood, Andrew; Beckham, Jean C.

2011-01-01

Background Posttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease. Purpose The purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes. Methods A systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted. Results The literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers. Conclusions Although the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research. PMID:20174903

Factors Associated with Suicidal Thought and Help-Seeking Behaviour in Transition-Aged Youth versus Adults.

PubMed

MacKinnon, Nathalie; Colman, Ian

2016-12-01

Suicide is a leading cause of death for transition-aged youth (TAY), and yet few studies examine correlates of suicidal ideation specifically in this age demographic (age 18-24 years). The transition to adulthood is a unique context, marked by novel stressors (e.g., joining the workforce) and increased independence, which may influence risk factors for suicidal ideation. This study examined correlates of suicidal ideation in TAY and adults and contrasted profiles across age. We used 4 biannual cycles (2005, 2007, 2009, 2011) of the Canadian Community Health Survey, a population-based cross-sectional survey on health. We used logistic regression to assess the association between suicidal ideation and depression, distress, alcohol use, smoking, exercise, sedentary behaviour, chronic illness, restrictions to daily living, perceived physical and mental health, and perceived social support independently in both TAY ( n = 4427) and adults ( n = 14,452). We subsequently assessed possible interactions with age (18-24 v. 25-44 years) and sex and differences in help-seeking behaviour in a combined model. TAY exhibited higher rates of suicidal ideation than adults did ( P < 0.001). Numerous factors were associated with suicidal ideation in TAY. Notably, alcohol abstinence was associated with decreased suicidal ideation in TAY but not for adults. Moreover, when depressed, TAY were significantly less likely to have received professional mental health help than adults (odds ratio = 0.64, 95% CI, 0.43 to 0.94). Suicidal ideation is more prevalent in TAY than adults, and its consequences may be aggravated by poor treatment-seeking behaviour in at-risk (i.e. depressed) individuals. These different risk profiles substantiate the recent shift toward clinical interventions focusing on transition-aged youth, rather than traditional child (<18 years) and adult (>18 years) services.

Evolutionary evidence of the effect of rare variants on disease etiology.

PubMed

Gorlov, I P; Gorlova, O Y; Frazier, M L; Spitz, M R; Amos, C I

2011-03-01

The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single-nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk-associated rare SNPs. © 2010 John Wiley & Sons A/S.

Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

PubMed

Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

2016-01-01

Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fasting therapy for treating and preventing disease - current state of evidence.

PubMed

Michalsen, Andreas; Li, Chenying

2013-01-01

Periods of deliberate fasting with restriction of solid food intake are practiced worldwide, mostly based on traditional, cultural or religious reasons. There is large empirical and observational evidence that medically supervised modified fasting (fasting cure, 200-500 kcal nutritional intake per day) with periods of 7-21 days is efficacious in the treatment of rheumatic diseases, chronic pain syndromes, hypertension, and metabolic syndrome. The beneficial effects of fasting followed by vegetarian diet in rheumatoid arthritis are confirmed by randomized controlled trials. Further beneficial effects of fasting are supported by observational data and abundant evidence from experimental research which found caloric restriction and intermittent fasting being associated with deceleration or prevention of most chronic degenerative and chronic inflammatory diseases. Intermittent fasting may also be useful as an accompanying treatment during chemotherapy of cancer. A further beneficial effect of fasting relates to improvements in sustainable lifestyle modification and adoption of a healthy diet, possibly mediated by fasting-induced mood enhancement. Various identified mechanisms of fasting point to its potential health-promoting effects, e.g., fasting-induced neuroendocrine activation and hormetic stress response, increased production of neurotrophic factors, reduced mitochondrial oxidative stress, general decrease of signals associated with aging, and promotion of autophagy. Fasting therapy might contribute to the prevention and treatment of chronic diseases and should be further evaluated in controlled clinical trials and observational studies. © 2014 S. Karger GmbH, Freiburg.

Improving Chronic Disease in the Caribbean through Evidence-based Behavioral and Social In

Cancer.gov

The Office for Behavioral and Social Sciences Research and the NCI’s Center for Global Health held a workshop entitled “Improving Chronic Disease in the Caribbean through Evidence-based Behavioral and Social Interventions”, which took place in Bridgetown, Barbados from July 21 to 24, 2015. The objectives of the workshop were to encourage the generation of research to more rapidly accelerate chronic disease prevention and management.

Childhood growth and chronic disease: evidence from countries undergoing the nutrition transition.

PubMed

Stein, Aryeh D; Thompson, Angela M; Waters, Ashley

2005-07-01

Evidence is accumulating that the pattern of growth in childhood is associated with development of cardiovascular disease in adulthood, but such evidence comes mostly from developed countries. We conducted a review of studies from countries undergoing the nutrition transition. Five birth cohorts with measures of child growth and outcomes through adolescence were identified, from China, India, Guatemala, Brazil and the Philippines. Across studies there are major differences in data availability and in statistical approaches to modelling child growth and its effects. Nevertheless, generally consistent associations of growth failure in early childhood and development of overweight in later childhood with the risk of elevated blood pressure, glucose, and serum lipids in adulthood were observed. As these cohorts mature they will provide a wealth of critical information on the relation between early life factors and later disease risk, and efforts should be made to ensure ongoing follow-up using standardized approaches and more comprehensive assessments.

A systematic literature review of evidence-based clinical practice for rare diseases: what are the perceived and real barriers for improving the evidence and how can they be overcome?

PubMed

Rath, Ana; Salamon, Valérie; Peixoto, Sandra; Hivert, Virginie; Laville, Martine; Segrestin, Berenice; Neugebauer, Edmund A M; Eikermann, Michaela; Bertele, Vittorio; Garattini, Silvio; Wetterslev, Jørn; Banzi, Rita; Jakobsen, Janus C; Djurisic, Snezana; Kubiak, Christine; Demotes-Mainard, Jacques; Gluud, Christian

2017-11-22

Evidence-based clinical practice is challenging in all fields, but poses special barriers in the field of rare diseases. The present paper summarises the main barriers faced by clinical research in rare diseases, and highlights opportunities for improvement. Systematic literature searches without meta-analyses and internal European Clinical Research Infrastructure Network (ECRIN) communications during face-to-face meetings and telephone conferences from 2013 to 2017 within the context of the ECRIN Integrating Activity (ECRIN-IA) project. Barriers specific to rare diseases comprise the difficulty to recruit participants because of rarity, scattering of patients, limited knowledge on natural history of diseases, difficulties to achieve accurate diagnosis and identify patients in health information systems, and difficulties choosing clinically relevant outcomes. Evidence-based clinical practice for rare diseases should start by collecting clinical data in databases and registries; defining measurable patient-centred outcomes; and selecting appropriate study designs adapted to small study populations. Rare diseases constitute one of the most paradigmatic fields in which multi-stakeholder engagement, especially from patients, is needed for success. Clinical research infrastructures and expertise networks offer opportunities for establishing evidence-based clinical practice within rare diseases.

Exercise and gastrointestinal function and disease: an evidence-based review of risks and benefits.

PubMed

Bi, Luke; Triadafilopoulos, George

2003-09-01

Exercise is beneficial to health because it reduces the risk of cardiovascular and endocrine diseases, improves bone and muscle conditioning, and lessens anxiety and depression. However, the impact of exercise on the gastrointestinal system has been conflicting. This systematic literature review evaluates the effect of the different modes and intensity levels of exercise on gastrointestinal function and disease using an evidence-based approach. Although more applicable to trained athletes and individuals who are highly active and, as such, at risk to experience the side-effects of exercise, an effort was made to state the level or degree of exercise or the lack of such evidence. Light and moderate exercise is well tolerated and can benefit patients with inflammatory bowel disease and liver disease. Physical activity can also improve gastric emptying and lower the relative risk of colon cancer in most populations. Severe, exhaustive exercise, however, inhibits gastric emptying, interferes with gastrointestinal absorption, and causes many gastrointestinal symptoms, most notably gastrointestinal bleeding. This knowledge will enable physicians to prescribe physical exercise in health and disease and to better manage patients with exercise-related gastrointestinal disorders. Our understanding of exercise and its gastrointestinal manifestations as well as risks and benefits warrants further investigation.

Vitamin D and Cardiovascular Disease: An Appraisal of the Evidence

PubMed Central

Schnatz, Peter F.; Manson, JoAnn E.

2013-01-01

Background Supplementation with vitamin D (VitD) has received attention as a potential cardioprotective strategy. Biologically plausible mechanisms have been proposed to link VitD to coronary heart disease (CHD) prevention and observational studies suggest an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and CHD. Few randomized clinical trials of VitD supplementation and CHD have been conducted, however, and no completed trial has been done with CHD as the primary pre-specified outcome. Content A search was conducted in PubMed to find prospective studies on the use of vitamin D supplementation and cardiovascular risk factors (RFs) and/or cardiovascular disease. The exact search query was ((vitamin D supplement*[Title/Abstract]) AND cardiovascular [Title/Abstract]) AND prospective [Title/Abstract]. This query yielded 42 results. Randomized Controlled Trial (article type) was employed as a filter in a subsequent query with the same search terms. We review the evidence that VitD supplementation modifies coronary RFs, such as blood pressure, lipids, and glucose tolerance, and/or affects the development of clinical CHD events. We address potential sources of confounding in observational epidemiologic studies of the relationship between serum 25OHD and CHD. We also address laboratory assay issues relevant to the reliable measurement of 25OHD. Summary Most VitD supplementation trials have not demonstrated improvement in cardiovascular disease, but have tested relatively low doses of VitD. Thus, the evidence remains inconclusive, highlighting the need for rigorous randomized trials of higher VitD doses, with cardiovascular events as prespecified outcomes. While awaiting ongoing trial results, the recommended dietary allowances from the Institute of Medicine remain the best guidepost for nutritional requirements. PMID:24193116

Stress echocardiography for the diagnosis of coronary artery disease: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas">www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based Analysis64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis

Evidence-based veterinary dentistry: a systematic review of homecare for prevention of periodontal disease in dogs and cats.

PubMed

Roudebush, Philip; Logan, Ellen; Hale, Fraser A

2005-03-01

Successful treatment and prevention of periodontal disease in pet animals requires a multidimensional approach to identify and eliminate exacerbating factors, provide scheduled professional examinations and care, and plan and implement a dental homecare program. Over the years, many therapeutic and preventive interventions have been developed or advocated for periodontal disease, but evidence of efficacy or effectiveness is highly variable. Accordingly, the main objective of this systematic review is to identify and critically appraise the evidence supporting various aspects of homecare for prevention of canine and feline periodontal disease.

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

NASA Technical Reports Server (NTRS)

Patel, Zarana; Huff, Janice; Saha, Janapriya; Wang, Minli; Blattnig, Steve; Wu, Honglu; Cucinotta, Francis

2015-01-01

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray

Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence.

PubMed

Agossa, K; Dendooven, A; Dubuquoy, L; Gower-Rousseau, C; Delcourt-Debruyne, E; Capron, M

2017-06-01

Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

PubMed

Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

2016-09-21

Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association.

Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions?

PubMed Central

Lira-Junior, Ronaldo; Figueredo, Carlos Marcelo

2016-01-01

Periodontal disease and inflammatory bowel disease (IBD) are both chronic inflammatory diseases. Their pathogenesis is mediated by a complex interplay between a dysbiotic microbiota and the host immune-inflammatory response, and both are influenced by genetic and environmental factors. This review aimed to provide an overview of the evidence dealing with a possible pathogenic interaction between periodontal disease and IBD. There seems to be an increased prevalence of periodontal disease in patients with IBD when compared to healthy controls, probably due to changes in the oral microbiota and a higher inflammatory response. Moreover, the induction of periodontitis seems to result in gut dysbiosis and altered gut epithelial cell barrier function, which might contribute to the pathogenesis of IBD. Considering the complexity of both periodontal disease and IBD, it is very challenging to understand the possible pathways involved in their coexistence. In conclusion, this review points to a complex pathogenic interaction between periodontal disease and IBD, in which one disease might alter the composition of the microbiota and increase the inflammatory response related to the other. However, we still need more data derived from human studies to confirm results from murine models. Thus, mechanistic studies are definitely warranted to clarify this possible bidirectional association. PMID:27672291

[National Disease Management Guideline for Asthma: recommendations and evidence for "asthma prevention" issues].

PubMed

Berdel, Dietrich; Buhl, Roland; Dierkesmann, Rainer; Niebling, Wilhelm; Schultz, Konrad; Ukena, Dieter; Worth, Heinrich; von Wichert, Peter; Ollenschläger, Günter; Kopp, Ina

2006-01-01

The National Disease Management Program (NDM Program) represents the basic content of structured, cross-sectoral healthcare. In particular, the NDM Program is directed towards coordinating different disciplines and areas of healthcare. The recommendations are developed through interdisciplinary consensus of the scientific medical societies on the basis of the best available evidence. Within this scope the scientific medical societies concerned with the prevention, diagnosis, therapy and rehabilitation of asthma consented upon a National Disease Management Guideline for Asthma in 2005. Among other things, the following cornerstones of asthma prevention were agreed upon: Breastfeeding and non-smoking were suggested as primary prevention measures for (expectant) parents. With respect to secondary prevention, recommendations have been made for allergen avoidance, active/passive smoking and immunotherapy. Regarding tertiary prevention, position statements on vaccination and specific immunotherapy are developed. The present paper presents both the original texts of the recommendations and the evidence underlying them.

Public policies and reproductive technology: a feminist critique.

PubMed

Mccormack, T

1991-01-01

Reproductive technology comprises abortion, contraception, amniocentesis (more than 40 genetic disorders can be diagnosed), chorionic villus sampling, genetic screening (to reduce the risk of chromosomal defects such as Down syndrome, sickle cell anemia, Tay-Sachs disease, and cystic fibrosis), in vitro fertilization, artificial insemination by spouse or donor, the development of sperm banks, storage of frozen sperm (cryopreservation), the development of artificial wombs, techniques for predetermining the sex of a fetus, and nursery environments to maintain a fetus removed from the womb in the 1st trimester. In recent years, the demand for these services has increased because of higher infertility and the drop in the number of babies available for adoption. Surrogacy is especially controversial: it has become a symbol of the dehumanization of modern life and the exploitation of women. The feminist perspective discloses how patriarchal values about the subordinate status of women, about the nature of motherhood, infertility, and the family are both implicit and explicit in prevailing thinking about reproduction. The new technology offers women who wish to remain unmarried the opportunity to have a family, and it enables lesbian women to bear children. The research literature favors a Eurocentric nuclear family without any awareness that in Canada, and in the Western world, new forms of family life have been evolving as couples marry, divorce, and remarry. There is no awareness either that in other cultures this Eurocentric nuclear model is dysfunctional. Because of the rigid notion of the 2-parent nuclear family, the 3rd parties who are involved in either surrogate relationships or artificial insemination are deprecated. The feminist literature is more critical of the nuclear family, but it has been sometimes inconsistent on the relevant issues.

Expression of the GM2 activator protein in mouse testis.

PubMed

Li, Yu-Teh; Li, Su-Chen; Chen, I-Li

2017-12-01

The GM2-activator protein (GM2-AP), revealed by Li et al. in 1973 in human liver, was initially identified as a protein cofactor that stimulated β-hexosaminidase A to hydrolyze N-acetylgalactosamine from GM2 ganglioside. This cofactor was found to be missing in human variant AB Tay-Sachs disease. Over the years, the GM2-AP has also been shown to be involved in kidney vesicular transport, lipid presentation by CD1 molecule to T-cells, and interaction of human sperm with zona pellucida. Since the expression of the GM2-AP via mRNA detection in mouse tissues was found to be the highest in testis, we became interested in the localization of the GM2-AP at cellular level in mouse testis during spermatogenesis. Using immunohistochemical analysis and electron microscopy, we found that the GM2-AP was predominantly localized in the basal cytoplasm and the attenuated processes of Sertoli cells. The stained structure appeared to be lysosomes. The most interesting finding was the association of the GM2-AP with the acrosomal apparatus in early spermatids. A modest to intense staining was observed in some acrosomal granules and acrosomal caps. The GM2-AP seemed to disappear from acrosomal caps in the later stage of spermatids, in which the nucleus became elongated and condensed. These results suggest that the GM2-AP may be involved in the normal functions of Sertoli cells and play important roles during the development of acrosomal caps in the early spermatids. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A Novel Mechanism for Desulfation of Mucin: Identification and Cloning of a Mucin-Desulfating Glycosidase (Sulfoglycosidase) from Prevotella Strain RS2

PubMed Central

Rho, Jung-hyun; Wright, Damian P.; Christie, David L.; Clinch, Keith; Furneaux, Richard H.; Roberton, Anthony M.

2005-01-01

A novel enzyme which may be important in mucin degradation has been discovered in the mucin-utilizing anaerobe Prevotella strain RS2. This enzyme cleaves terminal 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sulfate (6-SO3-GlcNAc) residues from sulfomucin and from the model substrate 4-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sodium sulfate. The existence of this mucin-desulfating glycosidase (sulfoglycosidase) suggests an alternative mechanism by which this bacterium may desulfate sulfomucins, by glycosidic removal of a sulfated sugar from mucin oligosaccharide chains. Previously, mucin desulfation was thought to take place by the action of a specific desulfating enzyme, which then allowed glycosidases to remove desulfated sugar. Sulfate removal from sulfomucins is thought to be a rate-limiting step in mucin degradation by bacteria in the regions of the digestive tract with a significant bacterial flora. The sulfoglycosidase was induced by growth of the Prevotella strain on mucin and was purified 284-fold from periplasmic extracts. Tryptic digestion and sequencing of peptides from the 100-kDa protein enabled the sulfoglycosidase gene to be cloned and sequenced. Active recombinant enzyme was made in an Escherichia coli expression system. The sulfoglycosidase shows sequence similarity to hexosaminidases. The only other enzyme that has been shown to remove 6-SO3-GlcNAc from glycoside substrates is the human lysosomal enzyme β-N-acetylhexosaminidase A, point mutations in which cause the inheritable, lysosomal storage disorder Tay-Sachs disease. The human enzyme removes GlcNAc from glycoside substrates also, in contrast to the Prevotella enzyme, which acts on a nonsulfated substrate at a rate that is only 1% of the rate observed with a sulfated substrate. PMID:15716424

Diabetes mellitus disease management in a safety net hospital system: translating evidence into practice.

PubMed

Butler, Michael K; Kaiser, Michael; Johnson, Jolene; Besse, Jay; Horswell, Ronald

2010-12-01

The Louisiana State University Health Care Services Division system assessed the effectiveness of implementing a multisite disease management program targeting diabetes mellitus in an indigent patient population. A population-based disease management program centered on evidence-based clinical care guidelines was applied from the system level. Specific clinic modifications and models were used, as well as ancillary services such as medication assistance and equipment subsidies. Marked improvement in process goals led to improved clinical outcomes. From 2001 to 2008, the percentage of patients with a hemoglobin A1c < 7.0 increased from 45% to 55% on the system level, with some sites experiencing a more dramatic shift. Results were similar across sites, which included both small provider groups and academic health centers. In order to achieve these results, the clinical environment changed to promote those evidence-based interventions. Even in complex environments such as academic health centers with several provider levels, or those environments with limited care resources, disease management programs can be successfully implemented and achieve statistically significant results.

Non-Malignant Respiratory Disease Among Workers in Industries Using Styrene—A Review of the Evidence

PubMed Central

Nett, Randall J.; Cox-Ganser, Jean M.; Hubbs, Ann F.; Ruder, Avima M.; Cummings, Kristin J.; Huang, Yuh-Chin T.; Kreiss, Kathleen

2017-01-01

Background Asthma and obliterative bronchiolitis (OB) cases have occurred among styrene-exposed workers. We aimed to investigate styrene as a risk factor for non-malignant respiratory disease (NMRD). Methods From a literature review, we identified case reports and assessed cross-sectional and mortality studies for strength of evidence of positive association (i.e., strong, intermediate, suggestive, none) between styrene exposure and NMRD-related morbidity and mortality. Results We analyzed 55 articles and two unpublished case reports. Ten OB cases and eight asthma cases were identified. Six (75%) asthma cases had abnormal styrene inhalation challenges. Thirteen (87%) of 15 cross-sectional studies and 12 (50%) of 24 mortality studies provided at least suggestive evidence that styrene was associated with NMRD-related morbidity or mortality. Six (66%) of nine mortality studies assessing chronic obstructive pulmonary disease-related mortality indicated excess mortality. Conclusions Available evidence suggests styrene exposure is a potential risk factor for NMRD. Additional studies of styrene-exposed workers are warranted. PMID:28079275

Animal models of GM2 gangliosidosis: utility and limitations

PubMed Central

Lawson, Cheryl A; Martin, Douglas R

2016-01-01

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

Evidence of chronic kidney disease in veterans with incident diabetes mellitus.

PubMed

Gatwood, Justin; Chisholm-Burns, Marie; Davis, Robert; Thomas, Fridtjof; Potukuchi, Praveen; Hung, Adriana; Kovesdy, Csaba P

2018-01-01

While chronic kidney disease (CKD) is regularly evaluated among patients with diabetes, kidney function may be significantly impaired before diabetes is diagnosed. Moreover, disparities in the severity of CKD in such a population are likely. This study evaluated the extent of CKD in a national cohort of 36,764 US veterans first diagnosed with diabetes between 2003 and 2013 and prior to initiating oral antidiabetic therapy. Evidence of CKD (any stage) at the time of diabetes diagnosis was determined using eGFR and urine-albumin-creatinine ratios, the odds of which were assessed using logistic regression controlling for patient characteristics. CKD was evident in 31.6% of veterans prior to being diagnosed with diabetes (age and gender standardized rates: 241.8 per 1,000 adults [overall] and 247.7 per 1,000 adult males), over half of whom had at least moderate kidney disease (stage 3 or higher). The odds of CKD tended to increase with age (OR: 1.88; 95% CI: 1.82-1.93), hemoglobin A1C (OR: 1.05; 95% CI: 1.04-1.06), systolic blood pressure (OR: 1.04; 95% CI: 1.027-1.043), and BMI (OR: 1.016; 95% CI: 1.011-1.020). Both Asian Americans (OR: 1.53; 95% CI: 1.15-2.04) and African Americans (OR: 1.11; 95% CI: 1.03-1.20) had higher adjusted odds of CKD compared to whites, and prevalence was highest in the Upper Midwest and parts of the Mid-South. Results suggest that evidence of CKD is common among veterans before a diabetes diagnosis, and certain populations throughout the country, such as minorities, may be afflicted at higher rates.

Current Evidence and Insights about Genetics in Thoracic Aorta Disease

PubMed Central

Muneretto, Claudio

2013-01-01

Thoracic aortic aneurysms have been historically considered to be caused by etiologic factors similar to those implied in abdominal aortic aneurysms. However, during the past decade, there has been increasing evidence that almost 20% of thoracic aortic aneurysms may be associated with a genetic disease, often within a syndromic or familial disorder. Moreover, the presence of congenital anomalies, such as bicuspid aortic valve, may have a unique common genetic underlying cause. Finally, also sporadic forms have been found to be potentially associated with genetic disorders, as highlighted by the analysis of rare variants and expression of specific microRNAs. We therefore sought to perform a comprehensive review of the role of genetic causes in the development of thoracic aortic aneurysms, by analyzing in detail the current evidence of genetic alterations in syndromes such as Marfan, Loeys-Dietz, and Ehler-Danlos, familial or sporadic forms, or forms associated with bicuspid aortic valve. PMID:24453931

DISEASE RISK ANALYSIS--A TOOL FOR POLICY MAKING WHEN EVIDENCE IS LACKING: IMPORT OF RABIES-SUSCEPTIBLE ZOO MAMMALS AS A MODEL.

PubMed

Hartley, Matt; Roberts, Helen

2015-09-01

Disease control management relies on the development of policy supported by an evidence base. The evidence base for disease in zoo animals is often absent or incomplete. Resources for disease research in these species are limited, and so in order to develop effective policies, novel approaches to extrapolating knowledge and dealing with uncertainty need to be developed. This article demonstrates how qualitative risk analysis techniques can be used to aid decision-making in circumstances in which there is a lack of specific evidence using the import of rabies-susceptible zoo mammals into the United Kingdom as a model.

Development of Evidence-Based Disease Education Literature for Pakistani Rheumatoid Arthritis Patients.

PubMed

Naqvi, Atta Abbas; Hassali, Mohamed Azmi; Aftab, Muhammad Tariq; Naqvi, Syed Baqir Shyum; Zehra, Fatima; Ahmad, Rizwan; Ahmad, Niyaz

2017-11-20

Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing an evidence-based disease education literature for rheumatoid arthritis patients of Pakistan in Urdu language with culturally relevant illustrations. A study was conducted to develop disease education literature using Delphi consensus, content validity, and patient feedback. A panel of experts comprised of university professors and health care experts, including health practitioners and pharmacists as well as a social scientist, was set up to assess the need. Eight patients were randomly selected and were asked to give their feedback. Their feedback was incorporated in the development process. The entire process was carried out in eight steps. A disease education literature for patients of rheumatoid arthritis was developed and edited in the form of a booklet. The booklet contained evidence-based information that must be provided to patients in both Urdu and English languages with culturally relevant illustrations. The availability of such literature is significant, as it enables the patients to seek knowledge at home at their convenience. This home-based knowledge support is as helpful as any other means of medical care. The developed literature is planned to be used in further studies which will evaluate its impact in improving knowledge of RA patients.

Updated tomographic analysis of the integrated Sachs-Wolfe effect and implications for dark energy

NASA Astrophysics Data System (ADS)

Stölzner, Benjamin; Cuoco, Alessandro; Lesgourgues, Julien; Bilicki, Maciej

2018-03-01

We derive updated constraints on the integrated Sachs-Wolfe (ISW) effect through cross-correlation of the cosmic microwave background with galaxy surveys. We improve with respect to similar previous analyses in several ways. First, we use the most recent versions of extragalactic object catalogs, SDSS DR12 photometric redshift (photo-z ) and 2MASS Photo-z data sets, as well as those employed earlier for ISW, SDSS QSO photo-z and NVSS samples. Second, we use for the first time the WISE × SuperCOSMOS catalog, which allows us to perform an all-sky analysis of the ISW up to z ˜0.4 . Third, thanks to the use of photo-z s , we separate each data set into different redshift bins, deriving the cross-correlation in each bin. This last step leads to a significant improvement in sensitivity. We remove cross-correlation between catalogs using masks which mutually exclude common regions of the sky. We use two methods to quantify the significance of the ISW effect. In the first one, we fix the cosmological model, derive linear galaxy biases of the catalogs, and then evaluate the significance of the ISW using a single parameter. In the second approach we perform a global fit of the ISW and of the galaxy biases varying the cosmological model. We find significances of the ISW in the range 4.7 - 5.0 σ thus reaching, for the first time in such an analysis, the threshold of 5 σ . Without the redshift tomography we find a significance of ˜4.0 σ , which shows the importance of the binning method. Finally we use the ISW data to infer constraints on the dark energy redshift evolution and equation of state. We find that the redshift range covered by the catalogs is still not optimal to derive strong constraints, although this goal will be likely reached using future datasets such as from Euclid, LSST, and SKA.

Leveraging Real-World Evidence in Disease-Management Decision-Making with a Total Cost of Care Estimator.

PubMed

Nguyen, Thanh-Nghia; Trocio, Jeffrey; Kowal, Stacey; Ferrufino, Cheryl P; Munakata, Julie; South, Dell

2016-12-01

Health management is becoming increasingly complex, given a range of care options and the need to balance costs and quality. The ability to measure and understand drivers of costs is critical for healthcare organizations to effectively manage their patient populations. Healthcare decision makers can leverage real-world evidence to explore the value of disease-management interventions in shifting total cost trends. To develop a real-world, evidence-based estimator that examines the impact of disease-management interventions on the total cost of care (TCoC) for a patient population with nonvalvular atrial fibrillation (NVAF). Data were collected from a patient-level real-world evidence data set that uses the IMS PharMetrics Health Plan Claims Database. Pharmacy and medical claims for patients meeting the inclusion or exclusion criteria were combined in longitudinal cohorts with a 180-day preindex and 360-day follow-up period. Descriptive statistics, such as mean and median patient costs and event rates, were derived from a real-world evidence analysis and were used to populate the base-case estimates within the TCoC estimator, an exploratory economic model that was designed to estimate the potential impact of several disease-management activities on the TCoC for a patient population with NVAF. Using Microsoft Excel, the estimator is designed to compare current direct costs of medical care to projected costs by varying assumptions on the impact of disease-management activities and applying the associated changes in cost trends to the affected populations. Disease-management levers are derived from literature-based concepts affecting costs along the NVAF disease continuum. The use of the estimator supports analyses across 4 US geographic regions, age, cost types, and care settings during 1 year. All patients included in the study were continuously enrolled in their health plan (within the IMS PharMetrics Health Plan Claims Database) between July 1, 2010, and June 30

Leveraging Real-World Evidence in Disease-Management Decision-Making with a Total Cost of Care Estimator

PubMed Central

Nguyen, Thanh-Nghia; Trocio, Jeffrey; Kowal, Stacey; Ferrufino, Cheryl P.; Munakata, Julie; South, Dell

2016-01-01

Background Health management is becoming increasingly complex, given a range of care options and the need to balance costs and quality. The ability to measure and understand drivers of costs is critical for healthcare organizations to effectively manage their patient populations. Healthcare decision makers can leverage real-world evidence to explore the value of disease-management interventions in shifting total cost trends. Objective To develop a real-world, evidence-based estimator that examines the impact of disease-management interventions on the total cost of care (TCoC) for a patient population with nonvalvular atrial fibrillation (NVAF). Methods Data were collected from a patient-level real-world evidence data set that uses the IMS PharMetrics Health Plan Claims Database. Pharmacy and medical claims for patients meeting the inclusion or exclusion criteria were combined in longitudinal cohorts with a 180-day preindex and 360-day follow-up period. Descriptive statistics, such as mean and median patient costs and event rates, were derived from a real-world evidence analysis and were used to populate the base-case estimates within the TCoC estimator, an exploratory economic model that was designed to estimate the potential impact of several disease-management activities on the TCoC for a patient population with NVAF. Using Microsoft Excel, the estimator is designed to compare current direct costs of medical care to projected costs by varying assumptions on the impact of disease-management activities and applying the associated changes in cost trends to the affected populations. Disease-management levers are derived from literature-based concepts affecting costs along the NVAF disease continuum. The use of the estimator supports analyses across 4 US geographic regions, age, cost types, and care settings during 1 year. Results All patients included in the study were continuously enrolled in their health plan (within the IMS PharMetrics Health Plan Claims Database

The diversity-disease relationship: evidence for and criticisms of the dilution effect.

PubMed

Huang, Z Y X; VAN Langevelde, F; Estrada-Peña, A; Suzán, G; DE Boer, W F

2016-08-01

The dilution effect, that high host species diversity can reduce disease risk, has attracted much attention in the context of global biodiversity decline and increasing disease emergence. Recent studies have criticized the generality of the dilution effect and argued that it only occurs under certain circumstances. Nevertheless, evidence for the existence of a dilution effect was reported in about 80% of the studies that addressed the diversity-disease relationship, and a recent meta-analysis found that the dilution effect is widespread. We here review supporting and critical studies, point out the causes underlying the current disputes. The dilution is expected to be strong when the competent host species tend to remain when species diversity declines, characterized as a negative relationship between species' reservoir competence and local extinction risk. We here conclude that most studies support a negative competence-extinction relationship. We then synthesize the current knowledge on how the diversity-disease relationship can be modified by particular species in community, by the scales of analyses, and by the disease risk measures. We also highlight the complex role of habitat fragmentation in the diversity-disease relationship from epidemiological, evolutionary and ecological perspectives, and construct a synthetic framework integrating these three perspectives. We suggest that future studies should test the diversity-disease relationship across different scales and consider the multiple effects of landscape fragmentation.

Discrepancy between Medical Evidence Form 2728 and Renal Biopsy for Glomerular Diseases

PubMed Central

Hogan, Susan L.; Jennette, Caroline E.; Kenderes, Barbara; Krisher, Jenna; Jennette, J. Charles; McClellan, William M.

2010-01-01

Background and objectives: The United States Renal Data System (USRDS) is a commonly utilized database for epidemiologic research of ESRD patients. USRDS uses Medical Evidence Form 2728 to collect medical information about ESRD patients. The validity of the Form 2728 “primary cause of renal failure” field for glomerular diseases has not been evaluated, although inconsistencies between Form 2728 information and medical records have been documented previously with respect to comorbidities. Design, setting, participants, & measurements: Form 2728 information was linked with renal biopsy results from the Glomerular Disease Collaborative Network (GDCN) for 217 patients with biopsy-confirmed glomerular diseases who had reached ESRD. Biopsy results were compared with the Form 2728 “primary cause of renal failure” field. Diseases were considered individually, and also categorized into commonly used disease groups. Percentage of agreement and disease-specific measures of validity were calculated. Results: Overall agreement between renal biopsy and Form 2728 was low (14.8% overall, 23.0% when categorized). Agreement was better after Form 2728 was revised in 1995 (10.0% before versus 23.2% after overall). The cause of ESRD field was left blank in 57% of the forms submitted for glomerular disease patients. Individual glomerular diseases had very low specificities, but tended to have high positive predictive values. Conclusions: Form 2728 does not accurately reflect the renal pathology diagnosis as captured by biopsy. The large degree of missing data and misclassification should be of concern to those performing epidemiologic research using Form 2728 information on glomerular diseases. PMID:20688886

Chronic obstructive pulmonary disease exacerbations: latest evidence and clinical implications

PubMed Central

Qureshi, Hammad; Sharafkhaneh, Amir

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The natural history of COPD is punctuated by exacerbations which have major short- and long-term implications on the patient and healthcare system. Evidence-based guidelines stipulate that early detection and prompt treatment of exacerbations are essential to ensure optimal outcomes and to reduce the burden of COPD. Several factors can identify populations at risk of exacerbations. Implementing prevention measures in patients at risk is a major goal in the management of COPD. PMID:25177479

Burnout and Risk of Cardiovascular Disease: Evidence, Possible Causal Paths, and Promising Research Directions

ERIC Educational Resources Information Center

Melamed, Samuel; Shirom, Arie; Toker, Sharon; Berliner, Shlomo; Shapira, Itzhak

2006-01-01

Burnout is characterized by emotional exhaustion, physical fatigue, and cognitive weariness, resulting from prolonged exposure to work-related stress. The authors review the accumulated evidence suggesting that burnout and the related concept of vital exhaustion are associated with increased risk of cardiovascular disease and…

Does Forest Loss Increase Human Disease? Evidence from Nigeria.

PubMed

Berazneva, Julia; Byker, Tanya S.

2017-05-01

It is estimated that about one quarter of the global disease burden in terms of healthy life years lost and about one quarter of all premature deaths can be attributed to modifiable environmental factors (Pruss-Ustun and Corvalan 2006). Three infectious diseases--diarrhea, respiratory infections, and malaria--account for the largest absolute burden in developing countries with children facing the greatest impacts. There is a growing body of evidence demonstrating the health burden of air and water pollution, as well as important productivity and income effects (see, for example, reviews of the literature in Pattanayak and Pfaff 2009 and Greenstone and Jack 2016). Studies that focus on the impacts of natural resource degradation are fewer. Notably, Garg (2016) provides the first causal estimates of the impact of sustained forest cover on reduced malarial incidence in Indonesia, demonstrating a large and previously understudied cost of forest cover loss. In this paper, we extend this new literature on the health impacts of environmental degradation by estimating the causal impact of forest loss on infectious disease incidence in young children using temporal and spatial variation in the last decade in Nigeria. Our estimation strategy involves geolinking a new high-resolution dataset of global forest change to child-level health data from the Nigeria Demographic and Health Surveys from 2008 and 2013. We find that forest loss significantly increases the incidence of malaria, though it does not affect the incidence of diarrhea and respiratory diseases. The impact of forest loss on malaria is large (one standard deviation of forest loss increases malaria incidence by around 4.5 percent in children under five) and the dynamic pattern of the impact suggests a temporary ecological disturbance consistent with findings in Garg (2016) and the tropical medicine literature.

78 FR 17075 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) Tay 611-8 turbofan engines. This AD requires inspection... (RRD) Tay 611-8 turbofan engines, serial numbers 16245, 16256, 16417, 16418, 16584, 16585, 16639, 16640...

Evidence-based guidelines for supportive care of patients with Ebola virus disease.

PubMed

Lamontagne, François; Fowler, Robert A; Adhikari, Neill K; Murthy, Srinivas; Brett-Major, David M; Jacobs, Michael; Uyeki, Timothy M; Vallenas, Constanza; Norris, Susan L; Fischer, William A; Fletcher, Thomas E; Levine, Adam C; Reed, Paul; Bausch, Daniel G; Gove, Sandy; Hall, Andrew; Shepherd, Susan; Siemieniuk, Reed A; Lamah, Marie-Claude; Kamara, Rashida; Nakyeyune, Phiona; Soka, Moses J; Edwin, Ama; Hazzan, Afeez A; Jacob, Shevin T; Elkarsany, Mubarak Mustafa; Adachi, Takuya; Benhadj, Lynda; Clément, Christophe; Crozier, Ian; Garcia, Armando; Hoffman, Steven J; Guyatt, Gordon H

2018-02-17

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive care to patients admitted to Ebola treatment units. Key recommendations include administration of oral and, as necessary, intravenous hydration; systematic monitoring of vital signs and volume status; availability of key biochemical testing; adequate staffing ratios; and availability of analgesics, including opioids, for pain relief. Copyright © 2018 Elsevier Ltd. All rights reserved.

Translating evidence into policy for cardiovascular disease control in India

PubMed Central

2011-01-01

Cardiovascular diseases (CVD) are leading causes of premature mortality in India. Evidence from developed countries shows that mortality from these can be substantially prevented using population-wide and individual-based strategies. Policy initiatives for control of CVD in India have been suggested but evidence of efficacy has emerged only recently. These initiatives can have immediate impact in reducing morbidity and mortality. Of the prevention strategies, primordial involve improvement in socioeconomic status and literacy, adequate healthcare financing and public health insurance, effective national CVD control programme, smoking control policies, legislative control of saturated fats, trans fats, salt and alcohol, and development of facilities for increasing physical activity through better urban planning and school-based and worksite interventions. Primary prevention entails change in medical educational curriculum and improved healthcare delivery for control of CVD risk factors-smoking, hypertension, dyslipidemia and diabetes. Secondary prevention involves creation of facilities and human resources for optimum acute CVD care and secondary prevention. There is need to integrate various policy makers, develop effective policies and modify healthcare systems for effective delivery of CVD preventive care. PMID:21306620

In-home care for optimizing chronic disease management in the community: an evidence-based analysis.

PubMed

2013-01-01

The emerging attention on in-home care in Canada assumes that chronic disease management will be optimized if it takes place in the community as opposed to the health care setting. Both the patient and the health care system will benefit, the latter in terms of cost savings. To compare the effectiveness of care delivered in the home (i.e., in-home care) with no home care or with usual care/care received outside of the home (e.g., health care setting). A literature search was performed on January 25, 2012, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 1, 2006, until January 25, 2012. An evidence-based analysis examined whether there is a difference in mortality, hospital utilization, health-related quality of life (HRQOL), functional status, and disease-specific clinical measures for in-home care compared with no home care for heart failure, atrial fibrillation, coronary artery disease, stroke, chronic obstructive pulmonary disease, diabetes, chronic wounds, and chronic disease / multimorbidity. Data was abstracted and analyzed in a pooled analysis using Review Manager. When needed, subgroup analysis was performed to address heterogeneity. The quality of evidence was assessed by GRADE. The systematic literature search identified 1,277 citations from which 12 randomized controlled trials met the study criteria. Based on these, a 12% reduced risk for in-home care was shown for the outcome measure of combined events including all-cause mortality and hospitalizations (relative risk [RR]: 0.88; 95% CI: 0.80-0.97). Patients receiving in-home care had an average of 1 less unplanned hospitalization (mean difference [MD]: -1.03; 95% CI: -1.53 to -0.53) and an average of 1 less emergency department (ED) visit (MD: -1.32; 95% CI: -1.87 to -0.77). A

A marketing perspective on disseminating evidence-based approaches to disease prevention and health promotion.

PubMed

Maibach, Edward W; Van Duyn, Mary Ann S; Bloodgood, Bonny

2006-07-01

Evidence-based disease prevention practice guidelines can provide a rationale for health programming decisions, which should, in turn, lead to improved public health outcomes. This logic has stimulated the creation of a growing number of evidence-based prevention practice guidelines, including the Guide to Community Preventive Services. Few systematic efforts have been made to document the degree of adoption and implementation of these approaches, although the evidence on translation of research into practice in other health fields indicates that the adoption and implementation rate is low. Drawing on the marketing literature, we suggest three approaches to enhance the adoption and implementation of evidence-based approaches: 1) conducting consumer research with prospective adopters to identify their perspectives on how evidence-based prevention programs can advance their organization's mission, 2) building sustainable distribution channels to promote and deliver evidence-based programs to prospective adopters, and 3) improving access to easily implemented programs that are consistent with evidence-based guidelines. Newly emerging paradigms of prevention research (e.g., RE-AIM) that are more attuned to the needs of the marketplace will likely yield a new generation of evidence-based preventive approaches that can be more effectively disseminated. We suggest that the public health community prioritize the dissemination of evidence-based prevention approaches, because doing so is a potent environmental change strategy for enhancing health.

Promoting state health department evidence-based cancer and chronic disease prevention: a multi-phase dissemination study with a cluster randomized trial component

PubMed Central

2013-01-01

Background Cancer and other chronic diseases reduce quality and length of life and productivity, and represent a significant financial burden to society. Evidence-based public health approaches to prevent cancer and other chronic diseases have been identified in recent decades and have the potential for high impact. Yet, barriers to implement prevention approaches persist as a result of multiple factors including lack of organizational support, limited resources, competing emerging priorities and crises, and limited skill among the public health workforce. The purpose of this study is to learn how best to promote the adoption of evidence based public health practice related to chronic disease prevention. Methods/design This paper describes the methods for a multi-phase dissemination study with a cluster randomized trial component that will evaluate the dissemination of public health knowledge about evidence-based prevention of cancer and other chronic diseases. Phase one involves development of measures of practitioner views on and organizational supports for evidence-based public health and data collection using a national online survey involving state health department chronic disease practitioners. In phase two, a cluster randomized trial design will be conducted to test receptivity and usefulness of dissemination strategies directed toward state health department chronic disease practitioners to enhance capacity and organizational support for evidence-based chronic disease prevention. Twelve state health department chronic disease units will be randomly selected and assigned to intervention or control. State health department staff and the university-based study team will jointly identify, refine, and select dissemination strategies within intervention units. Intervention (dissemination) strategies may include multi-day in-person training workshops, electronic information exchange modalities, and remote technical assistance. Evaluation methods include pre

Psychosocial issues in evidence-based guidelines on inflammatory bowel diseases: A review

PubMed Central

Häuser, Winfried; Moser, Gabriele; Klose, Petra; Mikocka-Walus, Antonina

2014-01-01

AIM: To study statements and recommendations on psychosocial issues as presented in international evidence-based guidelines on the management of inflammatory bowel diseases (IBD). METHODS: MEDLINE, guidelines International Network, National Guideline Clearing House and National Institute for Health and Care Excellence were searched from January 2006 to June 30, 2013 for evidence-based guidelines on the management of IBD. RESULTS: The search yielded 364 hits. Thirteen guidelines were included in the review, of which three were prepared in Asia, eight in Europe and two in the United States. Eleven guidelines made statements and recommendations on psychosocial issues. The guidelines were concordant in that mental health disorders and stress do not contribute to the aetiology of IBD, but that they can influence its course. It was recommended that IBD-patients should be screened for psychological distress. If indicated, psychotherapy and/or psychopharmacological therapy should be recommended. IBD-centres should collaborate with mental health care specialists. Tobacco smoking patients with Crohn’s disease should be advised to quit. CONCLUSION: Patients and mental health specialists should be able to participate in future guideline groups to contribute to establishing recommendations on psychosocial issues in IBD. Future guidelines should acknowledge the presence of psychosocial problems in IBD-patients and encourage screening for psychological distress. PMID:24707152

Marital Status, Cardiovascular Diseases, and Cardiovascular Risk Factors: A Review of the Evidence.

PubMed

Manfredini, Roberto; De Giorgi, Alfredo; Tiseo, Ruana; Boari, Benedetta; Cappadona, Rosaria; Salmi, Raffaella; Gallerani, Massimo; Signani, Fulvia; Manfredini, Fabio; Mikhailidis, Dimitri P; Fabbian, Fabio

2017-06-01

There is evidence showing that marital status (MS) and marital disruption (i.e., separation, divorce, and being widowed) are associated with poor physical health outcomes, including for all-cause mortality. We checked for the available evidence on the association between MS and cardiovascular (CV) diseases, outcomes, and CV risk factors. A search across the PubMed database of all articles, including the term "marital status" in their title, was performed. All articles were then manually checked for the presence of the following terms or topic: CV diseases, acute myocardial infarction, acute coronary syndrome, coronary artery disease, cardiac arrest, heart failure, heart diseases, and CV mortality. Moreover, other search terms were: CV risk factors, hypertension, cholesterol, obesity, smoking, alcohol, fitness and/or physical activity, and health. Systematic reviews, meta-analyses, controlled trials, cohort studies, and case-control studies were potentially considered pertinent for inclusion. Case reports, comments, discussion letters, abstracts of scientific conferences, articles in other than English language, and conference abstracts or proceedings were excluded. In total, 817 references containing the title words "marital status" were found. After elimination of articles dealing with other topics, 70 records were considered pertinent. Twenty-two were eliminated for several reasons, such as old articles, no abstract, full text unavailable, other than English language, comments, and letters. Out of the remaining 48 articles, 13 were suitable for the discussion, and 35 (accounting for 1,245,967 subjects) were included in this study. Most studies showed better outcomes for married persons, and men who were single generally had the poorest results. Moreover, being married was associated with lower risk factors and better health status, even in the presence of many confounding effects.

A comparison between health research output and burden of disease in Arab countries: evidence from Palestine.

PubMed

Albarqouni, Loai; Elessi, Khamis; Abu-Rmeileh, Niveen M E

2018-03-15

Research conducted on conditions responsible for the greatest disease burden should be given the highest priority, particularly in resource-limited settings. The present study aimed to assess the research output in relation to disease burden in Palestine and to identify the conditions which are under- or over-investigated, if any. We searched PubMed and Scopus for reports of original research relevant to human health or healthcare authored by researchers affiliated with Palestinian institutions and published between January 2000 and December 2015. We categorised the condition studied in included articles using the Global Burden of Disease (GBD) taxonomy. Data regarding burden of disease (percentage of deaths and disability-adjusted life years (DALYs)) was obtained from the Palestine profile in the GBD study. We examined the degree of discordance between the observed number of published articles for each disease/condition with the expected number based on the proportion of disease burden of that disease/condition. Our search identified 2469 potentially relevant records, from which 1650 were excluded following the screening of titles and abstracts. Of the remaining 819 full-text articles, we included 511 in our review. Communicable (infectious) diseases (n = 103; 20%) was the condition with the highest number of published studies. However, cancer (n = 15; 3%) and chronic respiratory diseases (n = 15; 3%) were the conditions with the lowest number of published studies. Research output was poorly associated with disease burden, irrespective of whether it was measured in terms of DALYs (rho = -0.116, P = 0.7) or death (rho = 0.217, P = 0.5). Cardiovascular disease, cancer, and maternal and neonatal deaths accounted for more than two-thirds of the total deaths in Palestine (67%), but were infrequently addressed (23%) in published articles. There is evidence of research waste measured by a mismatch between the health burden of certain diseases/conditions and the number of

78 FR 35574 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for all Rolls-Royce Deutschland Ltd & Co KG (RRD) model Tay 650-15 turbofan engines... Compliance We estimate that this proposed AD affects 52 Tay turbofan engines installed on airplanes of U.S...

Health technologies for the improvement of chronic disease management: a review of the Medical Advisory Secretariat evidence-based analyses between 2006 and 2011.

PubMed

Nikitovic, M; Brener, S

2013-01-01

As part of ongoing efforts to improve the Ontario health care system, a mega-analysis examining the optimization of chronic disease management in the community was conducted by Evidence Development and Standards, Health Quality Ontario (previously known as the Medical Advisory Secretariat [MAS]). The purpose of this report was to identify health technologies previously evaluated by MAS that may be leveraged in efforts to optimize chronic disease management in the community. The Ontario Health Technology Assessment Series and field evaluations conducted by MAS and its partners between January 1, 2006, and December 31, 2011. Technologies related to at least 1 of 7 disease areas of interest (type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds) or that may greatly impact health services utilization were reviewed. Only technologies with a moderate to high quality of evidence and associated with a clinically or statistically significant improvement in disease management were included. Technologies related to other topics in the mega-analysis on chronic disease management were excluded. Evidence-based analyses were reviewed, and outcomes of interest were extracted. Outcomes of interest included hospital utilization, mortality, health-related quality of life, disease-specific measures, and economic analysis measures. Eleven analyses were included and summarized. Technologies fell into 3 categories: those with evidence for the cure of chronic disease, those with evidence for the prevention of chronic disease, and those with evidence for the management of chronic disease. The impact on patient outcomes and hospitalization rates of new health technologies in chronic disease management is often overlooked. This analysis demonstrates that health technologies can reduce the burden of illness; improve patient outcomes; reduce resource utilization intensity; be cost

(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

PubMed Central

Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH. PMID:22916194

(S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.

PubMed

Zhang, Hao; Yu, Huan; Wang, Xia; Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2012-01-01

α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

The Impact of Economic Crises on Communicable Disease Transmission and Control: A Systematic Review of the Evidence

PubMed Central

Suhrcke, Marc; Stuckler, David; Suk, Jonathan E.; Desai, Monica; Senek, Michaela; McKee, Martin; Tsolova, Svetla; Basu, Sanjay; Abubakar, Ibrahim; Hunter, Paul; Rechel, Boika; Semenza, Jan C.

2011-01-01

There is concern among public health professionals that the current economic downturn, initiated by the financial crisis that started in 2007, could precipitate the transmission of infectious diseases while also limiting capacity for control. Although studies have reviewed the potential effects of economic downturns on overall health, to our knowledge such an analysis has yet to be done focusing on infectious diseases. We performed a systematic literature review of studies examining changes in infectious disease burden subsequent to periods of crisis. The review identified 230 studies of which 37 met our inclusion criteria. Of these, 30 found evidence of worse infectious disease outcomes during recession, often resulting from higher rates of infectious contact under poorer living circumstances, worsened access to therapy, or poorer retention in treatment. The remaining studies found either reductions in infectious disease or no significant effect. Using the paradigm of the “SIR” (susceptible-infected-recovered) model of infectious disease transmission, we examined the implications of these findings for infectious disease transmission and control. Key susceptible groups include infants and the elderly. We identified certain high-risk groups, including migrants, homeless persons, and prison populations, as particularly vulnerable conduits of epidemics during situations of economic duress. We also observed that the long-term impacts of crises on infectious disease are not inevitable: considerable evidence suggests that the magnitude of effect depends critically on budgetary responses by governments. Like other emergencies and natural disasters, preparedness for financial crises should include consideration of consequences for communicable disease control. PMID:21695209

Evidence of selection as a cause for racial disparities in fibroproliferative disease

PubMed Central

Velez Edwards, Digna R.

2017-01-01

Fibroproliferative diseases are common complex traits featuring scarring and overgrowth of connective tissue which vary widely in presentation because they affect many organ systems. Most fibroproliferative diseases are more prevalent in African-derived populations than in European populations, leading to pronounced health disparities. It is hypothesized that the increased prevalence of these diseases in African-derived populations is due to selection for pro-fibrotic alleles that are protective against helminth infections. We constructed a genetic risk score (GRS) of fibroproliferative disease risk-increasing alleles using 147 linkage disequilibrium-pruned variants identified through genome-wide association studies of seven fibroproliferative diseases with large African-European prevalence disparities. A comparison of the fibroproliferative disease GRS between 1000 Genomes Phase 3 populations detected a higher mean GRS in AFR (mean = 148 risk alleles) than EUR (mean = 136 risk alleles; T-test p-value = 1.75x10-123). To test whether differences in GRS burden are systematic and may be due to selection, we employed the quantitative trait loci (QTL) sign test. The QTL sign test result indicates that population differences in risk-increasing allele burdens at these fibroproliferative disease variants are systematic and support a model featuring selective pressure (p-value = 0.011). These observations were replicated in an independent sample and were more statistically significant (T-test p-value = 7.26x10-237, sign test p-value = 0.015). This evidence supports the role of selective pressure acting to increase frequency of fibroproliferative alleles in populations of African relative to European ancestry populations. PMID:28792542

77 FR 74123 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... proposing this AD to prevent failure of the LPC rotor disc assembly, uncontained engine failure, and damage...

Iron dosing in kidney disease: inconsistency of evidence and clinical practice

PubMed Central

Gaweda, Adam E.; Ginzburg, Yelena Z.; Chait, Yossi; Germain, Michael J.; Aronoff, George R.; Rachmilewitz, Eliezer

2015-01-01

The management of anemia in patients with chronic kidney disease (CKD) is difficult. The availability of erythropoiesis-stimulating agents (ESAs) has increased treatment options for previously transfusion-requiring patients, but the recent evidence of ESA side effects has prompted the search for complementary or alternative approaches. Next to ESA, parenteral iron supplementation is the second main form of anemia treatment. However, as of now, no systematic approach has been proposed to balance the concurrent administration of both agents according to individual patient's needs. Furthermore, the potential risks of excessive iron dosing remain a topic of controversy. How, when and whether to monitor CKD patients for potential iron overload remain to be elucidated. This review addresses the question of risk and benefit of iron administration in CKD, highlights the evidence supporting current practice, provides an overview of standard and potential new markers of iron status and outlines a new pharmacometric approach to physiologically compatible individualized dosing of ESA and iron in CKD patients. PMID:24821751

Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.

PubMed

Jeon, Seong Ran; Chai, Jocelyn; Kim, Christiana; Lee, Christine H

2018-05-26

Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD. Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.

Specialized nursing practice for chronic disease management in the primary care setting: an evidence-based analysis.

PubMed

2013-01-01

1) based on moderate quality evidence, with consistent results among a subgroup analysis of patients with diabetes based on low quality evidence. Model 2 showed an overall improvement in appropriate process measures, disease-specific measures, and patient satisfaction based on low to moderate quality evidence. There was low quality evidence that nurses working under Model 2 may reduce hospitalizations for patients with coronary artery disease. The specific role of the nurse in supplementing or substituting physician care was unclear, making it difficult to determine the impact on efficiency. Nurses with additional skills, training, or scope of practice may help improve the primary care of patients with chronic diseases. This review found that specialized nurses working on their own could achieve health outcomes that were similar to those of doctors. It also found that specialized nurses who worked with doctors could reduce hospital visits and improve certain patient outcomes related to diabetes, coronary artery disease, or heart failure. Patients who had nurse-led care were more satisfied and tended to receive more tests and medications. It is unclear whether specialized nurses improve quality of life or doctor workload.

Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.

PubMed

Charles, Ellen F; Lambert, Christophe G; Kerner, Berit

2016-12-01

Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex

Twenty years of telemedicine in chronic disease management – an evidence synthesis

PubMed Central

Wootton, Richard

2012-01-01

A literature review was conducted to obtain a high-level view of the value of telemedicine in the management of five common chronic diseases (asthma, COPD, diabetes, heart failure, hypertension). A total of 141 randomised controlled trials (RCTs) was identified, in which 148 telemedicine interventions of various kinds had been tested in a total of 37,695 patients. The value of each intervention was categorised in terms of the outcomes specified by the investigators in that trial, i.e. no attempt was made to extract a common outcome from all studies, as would be required for a conventional meta-analysis. Summarizing the value of these interventions shows, first, that most studies have reported positive effects (n = 108), and almost none have reported negative effects (n = 2). This suggests publication bias. Second, there were no significant differences between the chronic diseases, i.e. telemedicine seems equally effective (or ineffective) in the diseases studied. Third, most studies have been relatively short-term (median duration 6 months). It seems unlikely that in a chronic disease, any intervention can have much effect unless applied for a long period. Finally, there have been very few studies of cost-effectiveness. Thus the evidence base for the value of telemedicine in managing chronic diseases is on the whole weak and contradictory. PMID:22674020

World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based guideline.

PubMed

Reményi, Bo; Wilson, Nigel; Steer, Andrew; Ferreira, Beatriz; Kado, Joseph; Kumar, Krishna; Lawrenson, John; Maguire, Graeme; Marijon, Eloi; Mirabel, Mariana; Mocumbi, Ana Olga; Mota, Cleonice; Paar, John; Saxena, Anita; Scheel, Janet; Stirling, John; Viali, Satupaitea; Balekundri, Vijayalakshmi I; Wheaton, Gavin; Zühlke, Liesl; Carapetis, Jonathan

2012-02-28

Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease (RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the development of new international echocardiographic guidelines that address the full spectrum of the rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave, and color-Doppler echocardiography: 'definite RHD', 'borderline RHD', and 'normal'. Four subcategories of 'definite RHD' and three subcategories of 'borderline RHD' exist, to reflect the various disease patterns. The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However, important unanswered questions remain about the importance of subclinical disease (borderline or definite RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing screening programs. These standardized criteria will help enable new studies to be designed to evaluate the role of echocardiographic screening in RHD control.

Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan.

PubMed

Herbort, Carl P; Mochizuki, Manabu

2007-01-01

To delineate the historical steps associated with the genesis of the name and the definition of Vogt-Koyanagi-Harada (VKH) disease. A bibliographical review of the major publications that were relevant to the original development of the name of the clinical entity known today as Vogt-Koyanagi-Harada disease, in the historical context of the early 20th century. Three distinct time periods can be considered to be important in terms of providing a historical perspective on VKH disease. Given that the cutaneous manifestations of VKH disease are so characteristic, these could not have been missed even before the actual clinical entity of VKH was recognized in the early 20th century. Indeed, several authors, including the Arabic doctor Mohammad-al-Ghâfiqî in the 12th century as well as Jacobi, Nettelship and Tay in the 19th century, described poliosis, neuralgias and hearing disorders. Many of these cases were probably due to sympathetic ophthalmia, but some were clearly VKH cases. The second phase is characterized by the surge of articles that appeared early in the 20th century that defined the disease more precisely. A number of these authors subsequently became associated with the disease name, the first being Alfred Vogt from Switzerland, followed by Japanese researchers. Yoshizo Koyanagi was in fact not the first Japanese author to describe the disease; this honor goes to the first Japanese Professor of Ophthalmology at the University of Tokyo, Dr. Jujiro Komoto, who published in a German language journal, Klinische Monatsblätter für Augenheilkunde in 1911. Yoshizo Koyanagi published his first report in the Nippon Ganka Gakkai Zasshi 3 years later, in 1914, but it was a much later article, one published in 1929, that definitively associated his name with the disease. In this review article, Koyanagi reported 16 cases, of which six were his own cases, that beautifully illustrate the natural course of the disease. In this same time period, Einosuke Harada, in an

Striatal degeneration impairs language learning: evidence from Huntington's disease.

PubMed

De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

2008-11-01

Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly

Omega-3 Fatty Acids and Cardiovascular Disease: Summary of the 2016 Agency of Healthcare Research and Quality Evidence Review.

PubMed

Balk, Ethan M; Lichtenstein, Alice H

2017-08-11

We summarize the 2016 update of the 2004 Agency of Healthcare Research and Quality's evidence review of omega-3 fatty acids and cardiovascular disease (CVD). The overall findings for the effects of marine oil supplements on intermediate CVD outcomes remain largely unchanged. There is high strength of evidence, based on numerous trials, of no significant effects of marine oils on systolic or diastolic blood pressures, but there are small, yet statistically significant increases in high density lipoprotein and low density lipoprotein cholesterol concentrations. The clinical significance of these small changes, particularly in combination, is unclear. The strongest effect of marine oils is on triglyceride concentrations. Across studies, this effect was dose-dependent and related to studies' mean baseline triglyceride concentration. In observational studies, there is low strength of evidence that increased marine oil intake lowers ischemic stroke risk. Among randomized controlled trials and observational studies, there is evidence of variable strength of no association with increased marine oil intake and lower CVD event risk. Evidence regarding alpha-linolenic acid intake is sparser. There is moderate strength of evidence of no effect on blood pressure or lipoprotein concentrations and low strength of evidence of no association with coronary heart disease, atrial fibrillation and congestive heart failure.

Promoting innovation in small markets: Evidence from the market for rare and intractable diseases.

PubMed

Iizuka, Toshiaki; Uchida, Gyo

2017-07-01

In many medical care markets with limited profit potential, firms often have little incentive to innovate. These include the market for rare diseases, "neglected" tropical diseases, and personalized medicine. Governments and not-for-profit organizations promote innovation in such markets but empirical evidence on the policy effect is limited. We study this issue by analyzing the impact of a demand-side policy in Japan, which reduces the cost sharing of patients with some rare and intractable diseases and attempts to establish and promote the treatment of those diseases. Using clinical trials data taken from public registries, we identify the effect of the policy using a difference-in-difference approach. We find that the demand-side policy increased firms' incentive to innovate: firm-sponsored clinical trials increased 181% (0.16 per disease per year) when covered by the policy. This result indicates that the demand-side policy can be an important part of innovation policies in markets with limited profit potential. Copyright © 2017 Elsevier B.V. All rights reserved.

Water-based Tai Chi: theoretical benefits in musculoskeletal diseases. Current evidence

PubMed Central

Macías-Hernández, Salvador Israel; Vázquez-Torres, Lucio; Morones-Alba, Juan Daniel; Coronado-Zarco, Roberto; de los Angeles Soria-Bastida, María; Cruz-Medina, Eva; Nava-Bringas, Tania Inés

2015-01-01

Tai Chi is a low-impact and moderate intensity exercise that has shown positive effects in patients with musculoskeletal disorders. Recently have been developed clinical studies on the benefits of Tai Chi techniques combined with hydrotherapy. Both types of treatment include physical training of balance, mobility, strength, coordination and sensory input that could complement each other. This report aims to present the current evidence about the benefits of the combination of water based Tai Chi in musculoskeletal diseases in order to establish whether the combined intervention is better than Tai Chi or hydrotherapy alone. PMID:26171376

The evidence for the use of nutritional support in liver disease.

PubMed

Koretz, Ronald L

2014-03-01

Although there is a well established association between malnutrition and poorer clinical outcomes in patients with liver disease, that fact alone does not prove that improving the malnutrition will improve outcome. The best way to determine if nutritional interventions are effective is to compare them to untreated control groups in well designed and executed randomized clinical trials. A recent systematic review assessed 37 trials that compared parenteral nutrition, enteral nutrition, or nutritional supplements to no nutritional therapy in patients with a variety of liver diseases. Since the publication of that review, an additional three trials have become available. Whereas all but one of the trials did have methodologic shortcomings that may have allowed the introduction of bias (which usually results in an overestimation of benefit), the trials failed to show much, if any, benefit. In fact, the single trial at low risk of bias found that more deaths occurred in the recipients of the supplements. Although malnutrition may be associated with a poor outcome, the current best evidence indicates that the provision of adjunctive nutritional support (parenteral or enteral nutrition, or nutritional supplements) to patients with a variety of liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, liver surgery, liver transplantation, obstructive jaundice, hepatitis C antiviral treatment) does not improve clinical outcomes.

On the representation theory of the Bondi-Metzner-Sachs group and its variants in three space-time dimensions

NASA Astrophysics Data System (ADS)

Melas, Evangelos

2017-07-01

The original Bondi-Metzner-Sachs (BMS) group B is the common asymptotic symmetry group of all asymptotically flat Lorentzian radiating 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here we introduce the analogue B(2, 1) of the BMS group B in 3 space-time dimensions. B(2, 1) itself admits thirty-four analogues both real in all signatures and in complex space-times. In order to find the IRS of both B(2, 1) and its analogues, we need to extend Wigner-Mackey's theory of induced representations. The necessary extension is described and is reduced to the solution of three problems. These problems are solved in the case where B(2, 1) and its analogues are equipped with the Hilbert topology. The extended theory is necessary in order to construct the IRS of both B and its analogues in any number d of space-time dimensions, d ≥3 , and also in order to construct the IRS of their supersymmetric counterparts. We use the extended theory to obtain the necessary data in order to construct the IRS of B(2, 1). The main results of the representation theory are as follows: The IRS are induced from "little groups" which are compact. The finite "little groups" are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

Continuity of care to optimize chronic disease management in the community setting: an evidence-based analysis.

PubMed

2013-01-01

This evidence-based analysis reviews relational and management continuity of care. Relational continuity refers to the duration and quality of the relationship between the care provider and the patient. Management continuity ensures that patients receive coherent, complementary, and timely care. There are 4 components of continuity of care: duration, density, dispersion, and sequence. The objective of this evidence-based analysis was to determine if continuity of care is associated with decreased health resource utilization, improved patient outcomes, and patient satisfaction. MEDLINE, EMBASE, CINAHL, the Cochrane Library, and the Centre for Reviews and Dissemination database were searched for studies on continuity of care and chronic disease published from January 2002 until December 2011. Systematic reviews, randomized controlled trials, and observational studies were eligible if they assessed continuity of care in adults and reported health resource utilization, patient outcomes, or patient satisfaction. Eight systematic reviews and 13 observational studies were identified. The reviews concluded that there is an association between continuity of care and outcomes; however, the literature base is weak. The observational studies found that higher continuity of care was frequently associated with fewer hospitalizations and emergency department visits. Three systematic reviews reported that higher continuity of care is associated with improved patient satisfaction, especially among patients with chronic conditions. Most of the studies were retrospective cross-sectional studies of large administrative databases. The databases do not capture information on trust and confidence in the provider, which is a critical component of relational continuity of care. The definitions for the selection of patients from the databases varied across studies. There is low quality evidence that: Higher continuity of care is associated with decreased health service utilization.There is

Evidence of semantic processing impairments in behavioural variant frontotemporal dementia and Parkinson's disease.

PubMed

Cousins, Katheryn A Q; Grossman, Murray

2017-12-01

Category-specific impairments caused by brain damage can provide important insights into how semantic concepts are organized in the brain. Recent research has demonstrated that disease to sensory and motor cortices can impair perceptual feature knowledge important to the representation of semantic concepts. This evidence supports the grounded cognition theory of semantics, the view that lexical knowledge is partially grounded in perceptual experience and that sensory and motor regions support semantic representations. Less well understood, however, is how heteromodal semantic hubs work to integrate and process semantic information. Although the majority of semantic research to date has focused on how sensory cortical areas are important for the representation of semantic features, new research explores how semantic memory is affected by neurodegeneration in regions important for semantic processing. Here, we review studies that demonstrate impairments to abstract noun knowledge in behavioural variant frontotemporal degeneration (bvFTD) and to action verb knowledge in Parkinson's disease, and discuss how these deficits relate to disease of the semantic selection network. Findings demonstrate that semantic selection processes are supported by the left inferior frontal gyrus (LIFG) and basal ganglia, and that disease to these regions in bvFTD and Parkinson's disease can lead to categorical impairments for abstract nouns and action verbs, respectively.

The Sachs report: investing in health for economic development--or increasing the size of the crumbs from the rich man's table? Part II.

PubMed

Katz, Alison

2005-01-01

The Commission on Macroeconomics and Health report (Sachs report of 2001) has been heralded as inspiring and groundbreaking and is being adopted as the blueprint for global health policymaking. This article argues that the report is deeply conservative and unoriginal. It encourages medico-technical solutions to public health problems; it ignores macroeconomic determinants and other root causes of both poor health and poverty; it reverses public health logic and history; it is based on a set of flawed assumptions; it reflects one particular economic perspective to the exclusion of all others; and it recommends greater amounts of charity while preserving the status quo of a deeply unjust and irrational international economic order. Wishful thinking and ideology are presented as established facts to legitimize globalization, and health is conceived primarily as an input to productivity rather than as a human right. The benefits that would result from simple, macroeconomic measures directed toward social justice and the meeting of basic needs are incomparably greater than those that would result from following CMH recommendations in terms of sustainable improvements in both health and economic well-being. The ultimate source of poor health status and miserable living conditions is the extreme concentration of power, nationally and internationally, in the hands of the few.

How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular Diseases be Improved?

PubMed

Sawata, Hiroshi; Tsutani, Kiichiro

2011-06-29

Clinical investigations are important for obtaining evidence to improve medical treatment. Large-scale clinical trials with thousands of participants are particularly important for this purpose in cardiovascular diseases. Conducting large-scale clinical trials entails high research costs. This study sought to investigate global trends in large-scale clinical trials in cardiovascular diseases. We searched for trials using clinicaltrials.gov (URL: http://www.clinicaltrials.gov/) using the key words 'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials with 300 or more participants examining cardiovascular diseases. The search revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized controlled trials, 15% involved more than 10,000 participants, and 59% were funded by industry. In RCTs whose results were disclosed, 55% of industry-funded trials and 25% of non-industry funded trials reported statistically significant superiority over control (p = 0.012, 2-sided Fisher's exact test). Our findings highlighted concerns regarding potential bias related to funding sources, and that researchers should be aware of the importance of trial information disclosures and conflicts of interest. We should keep considering management and training regarding information disclosures and conflicts of interest for researchers. This could lead to better clinical evidence and further improvements in the development of medical treatment worldwide.

Cardiac magnetic resonance imaging for the diagnosis of coronary artery disease: an evidence-based analysis.

PubMed

2010-01-01

In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlSINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based AnalysisSTRESS ECHOCARDIOGRAPHY WITH CONTRAST FOR THE DIAGNOSIS OF CORONARY ARTERY DISEASE: An Evidence-Based Analysis64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based AnalysisCARDIAC MAGNETIC RESONANCE IMAGING FOR

Cell Surface Expression of Biologically Active Influenza C Virus HEF Glycoprotein Expressed from cDNA

PubMed Central

Pekosz, Andrew; Lamb, Robert A.

1999-01-01

The hemagglutinin, esterase, and fusion (HEF) glycoprotein of influenza C virus possesses receptor binding, receptor destroying, and membrane fusion activities. The HEF cDNAs from influenza C/Ann Arbor/1/50 (HEF-AA) and influenza C/Taylor/1223/47 (HEF-Tay) viruses were cloned and expressed, and transport of HEF to the cell surface was monitored by susceptibility to cleavage by exogenous trypsin, indirect immunofluorescence microscopy, and flow cytometry. Previously it has been found in studies with the C/Johannesburg/1/66 strain of influenza C virus (HEF-JHB) that transport of HEF to the cell surface is severely inhibited, and it is thought that the short cytoplasmic tail, Arg-Thr-Lys, is involved in blocking HEF cell surface expression (F. Oeffner, H.-D. Klenk, and G. Herrler, J. Gen. Virol. 80:363–369, 1999). As the cytoplasmic tail amino acid sequences of HEF-AA and HEF-Tay are identical to that of HEF-JHB, the data indicate that cell surface expression of HEF-AA and HEF-Tay is not inhibited by this amino acid sequence. Furthermore, the abundant cell surface transport of HEF-AA and HEF-Tay indicates that their cell surface expression does not require coexpression of another viral protein. The HEF-AA and HEF-Tay HEF glycoproteins bound human erythrocytes, promoted membrane fusion in a low-pH and trypsin-dependent manner, and displayed esterase activity, indicating that the HEF glycoprotein alone mediates all three known functions at the cell surface. PMID:10482635

Why prioritize when there isn't enough money?

PubMed

Wikler, Daniel

2003-02-26

In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs - Chairperson of the WHO Commission on Macroeconomics and Health - maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones.Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources.

Why prioritize when there isn't enough money?

PubMed Central

Wikler, Daniel

2003-01-01

In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs – Chairperson of the WHO Commission on Macroeconomics and Health – maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones. Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources. PMID:12773216

Obtaining evidence for use by healthcare payers on the success of chronic obstructive pulmonary disease management.

PubMed

Mapel, D; Pearson, M

2002-08-01

Healthcare payers make decisions on funding for treatments for diseases, such as chronic obstructive pulmonary disease (COPD), on a population level, so require evidence of treatment success in appropriate populations, using usual routine care as the comparison for alternative management approaches. Such health outcomes evidence can be obtained from a number of sources. The 'gold standard' method for obtaining evidence of treatment success is usually taken as the randomized controlled prospective clinical trial. Yet the value of such studies in providing evidence for decision-makers can be questioned due to the restricted entry criteria limiting the ability to generalize to real life populations, narrow focus on individual parameters, use of placebo for comparison rather than usual therapy and unrealistic intense monitoring of patients. Evidence obtained from retrospective and observational studies can supplement that from randomized clinical trials, providing that care is taken to guard against bias and confounders. However, very large numbers of patients must be investigated if small differences between drugs and treatment approaches are to be detected. Administrative databases from healthcare systems provide an opportunity to obtain observational data on large numbers of patients. Such databases have shown that high healthcare costs in patients with COPD are associated with co-morbid conditions and current smoking status. Analysis of an administrative database has also shown that elderly patients with COPD who received inhaled corticosteroids within 90 days of discharge from hospital had 24% fewer repeat hospitalizations for COPD and were 29% less likely to die during the 1-year follow-up period. In conclusion, there are a number of sources of meaningful evidence of the health outcomes arising from different therapeutic approaches that should be of value to healthcare payers making decisions on resource allocation.

Coffee and non-alcoholic fatty liver disease: brewing evidence for hepatoprotection?

PubMed

Chen, Shaohua; Teoh, Narci C; Chitturi, Shiv; Farrell, Geoffrey C

2014-03-01

Coffee is one of the most popular beverages in the world. Several studies consistently show that coffee drinkers with chronic liver disease have a reduced risk of cirrhosis and a lower incidence of hepatocellular carcinoma regardless of primary etiology. With the increasing prevalence of non-alcoholic fatty liver disease (NAFLD) worldwide, there is renewed interest in the effect of coffee intake on NAFLD severity and positive clinical outcomes. This review gives an overview of growing epidemiological and clinical evidence which indicate that coffee consumption reduces severity of NAFLD. These studies vary in methodology, and potential confounding factors have not always been completely excluded. However, it does appear that coffee, and particular components other than caffeine, reduce NAFLD prevalence and inflammation of non-alcoholic steatohepatitis. Several possible mechanisms underlying coffee's hepatoprotective effects in NAFLD include antioxidative, anti-inflammatory, and antifibrotic effects, while a chemopreventive effect against hepatocarcinogenesis seems likely. The so-far limited data supporting such effects will be discussed, and the need for further study is highlighted. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Language deficits in Pre-Symptomatic Huntington's Disease: Evidence from Hungarian

PubMed Central

Németh, Dezso; Dye, Cristina D.; Sefcsik, Tamás; Janacsek, Karolina; Turi, Zsolt; Londe, Zsuzsa; Klivenyi, Péter; Kincses, Tamás Zs.; Nikoletta, Szabó; Vecsei, László; Ullman, Michael T.

2012-01-01

A limited number of studies have investigated language in Huntington's disease (HD). These have generally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and morphology. Several studies of verbal inflectional morphology in English and French have reported evidence of over-active rule processing, such as over-suffixation errors (e.g., walkeded) and over-regularizations (e.g., digged). Here we extend the investigation to noun inflection in Hungarian, a Finno-Ugric agglutinative language with complex morphology, and to genetically proven pre-symptomatic Huntington's disease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, the underlying pathology may already have begun, and thus sensitive behavioral measures might reveal already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients made both over-suffixation and over-regularization errors. The findings suggest the generality of over-active rule processing in both HD and pre-HD, across languages from different families with different morphological systems, and for both verbal and noun inflection. Because the neuropathology in pre-HD appears to be largely restricted to the caudate nucleus and related structures, the findings further implicate these structures in language, and in rule-processing in particular. Finally, the need for effective treatments in HD, which will likely depend in part on the ability to sensitively measure early changes in the disease, suggests the possibility that inflectional morphology, and perhaps other language measures, may provide useful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HD and HD. PMID:22538085

Urbanization and non-communicable disease in Southeast Asia: a review of current evidence.

PubMed

Angkurawaranon, C; Jiraporncharoen, W; Chenthanakij, B; Doyle, P; Nitsch, D

2014-10-01

Non-communicable diseases (NCDs) have been highlighted as a major public health issue in the Southeast (SE) Asian region. One of the major socio-environmental factors that are considered to be associated with such a rise in NCDs is urbanization. Urbanization is associated with behavioural changes such as eating an unhealthy diet, and a decrease in physical activities, which may result in associated obesity. The SE Asian region also has a substantive burden of infectious disease such as HIV and malaria, which may modify associations between urbanization and development of NCDs. A systematic review was conducted until April 2013. Using four databases: EMBASE, PubMed, GlobalHealth and DigitalJournal, the systematic review pools existing evidence on urban-rural gradients in NCD prevalence/incidence. The study found that in SE Asia, urban exposure was positively associated with coronary heart disease, diabetes and respiratory diseases in children. Urban exposure was negatively associated with rheumatic heart diseases. The stages of economic development may also modify the association between urbanization and NCDs such as diabetes. There was pronounced heterogeneity between associations. It is recommended that future studies examine the major constituents of NCDs separately and also focus on the interplay between lifestyle and infectious risk factors for NCDs. Prospective studies are needed to understand the diverse causal pathways between urbanization and NCDs in SE Asia.

Gastric motor dysfunctions in Parkinson's disease: Current pre-clinical evidence.

PubMed

Pellegrini, Carolina; Antonioli, Luca; Colucci, Rocchina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bernardini, Nunzia; Blandizzi, Corrado; Fornai, Matteo

2015-12-01

Parkinson's disease (PD) is associated with several non-motor symptoms, such as behavioral changes, urinary dysfunction, sleep disorders, fatigue and, above all, gastrointestinal (GI) dysfunction, including gastric dysmotility, constipation and anorectal dysfunction. Delayed gastric emptying, progressing to gastroparesis, is reported in up to 100% of patients with PD, and it occurs at all stages of the disease with severe consequences to the patient's quality of life. The presence of α-synuclein (α-syn) aggregates in myenteric neurons throughout the digestive tract, as well as morpho-functional alterations of the enteric nervous system (ENS), have been documented in PD. In particular, gastric dysmotility in PD has been associated with an impairment of the brain-gut axis, involving the efferent fibers of the vagal pathway projecting directly to the gastric myenteric plexus. The present review intends to provide an integrated overview of available knowledge on the possible role played by the ENS, considered as a semi-autonomous nervous network, in the pathophysiology of gastric dysmotility in PD. Particular attention has been paid review how translational evidence in humans and studies in pre-clinical models are allowing a better understanding of the functional, neurochemical and molecular alterations likely underlying gastric motor abnormalities occurring in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.

PubMed

Painter, Jodie N; O'Mara, Tracy A; Morris, Andrew P; Cheng, Timothy H T; Gorman, Maggie; Martin, Lynn; Hodson, Shirley; Jones, Angela; Martin, Nicholas G; Gordon, Scott; Henders, Anjali K; Attia, John; McEvoy, Mark; Holliday, Elizabeth G; Scott, Rodney J; Webb, Penelope M; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Rübner, Matthias; Hall, Per; Czene, Kamila; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo; Lambrechts, Diether; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Vanderstichele, Adriaan; Goode, Ellen L; Cunningham, Julie M; Dowdy, Sean C; Winham, Stacey J; Trovik, Jone; Hoivik, Erling; Werner, Henrica M J; Krakstad, Camilla; Ashton, Katie; Otton, Geoffrey; Proietto, Tony; Tham, Emma; Mints, Miriam; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Pharoah, Paul D P; Dunning, Alison M; Dennis, Joe; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Zondervan, Krina T; Nyholt, Dale R; MacGregor, Stuart; Montgomery, Grant W; Tomlinson, Ian; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2018-05-01

Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (r g  = 0.23, P = 9.3 × 10 -3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10 -3 ) and concordance in effect direction (P = 2.0 × 10 -3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10 -5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10 -8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Emergency Medicine Management of Sickle Cell Disease Complications: An Evidence-Based Update.

PubMed

Simon, Erica; Long, Brit; Koyfman, Alex

2016-10-01

Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States. Due to alterations in the structural conformation of hemoglobin molecules under deoxygenated conditions, patients with SCD are predisposed to numerous sequelae, many of which require acute intervention. Our aim was to provide emergency physicians with an evidence-based update regarding the diagnosis and management of SCD complications. SCD patients experience significant morbidity and mortality secondary to cerebrovascular accident, acute chest syndrome, acute vaso-occlusive pain crises, SCD-related multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration, priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely management and determine patient disposition. A comprehensive review of the emergency department management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus decreasing the morbidity and mortality associated with this hemoglobinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Polyphenol-based nutraceuticals for the prevention and treatment of cardiovascular disease: Review of human evidence.

PubMed

Tomé-Carneiro, Joao; Visioli, Francesco

2016-10-15

In addition to prescription drugs, nutraceuticals/functional foods/medical foods are being increasingly added as adjunct treatment of cardiovascular disease (CVD), even though most of them have been exclusively studied in vitro. We review the available evidence (focusing on when the amount of polyphenols' intake was measured) coming from randomized controlled trials (RCTs) of (poly)phenol-based supplements. We conclude that (poly)phenol-based nutraceuticals and functional foods might be indeed used as adjunct therapy of CVD, but additional long-term RCTs with adequate numerosity and with clinically relevant end points are needed to provide unequivocal evidence of their clinical usefulness. Copyright © 2015. Published by Elsevier GmbH.

Is There Convincing Evidence that Intermediate Repeats in the HTT Gene Cause Huntington's Disease?

PubMed

Oosterloo, Mayke; Van Belzen, Martine J; Bijlsma, Emilia K; Roos, Raymund A C

2015-01-01

Huntington's disease (HD) is a neurodegenerative disease associated with a CAG repeat expansion in the Huntingtin (HTT) gene. A trinucleotide size between 27 and 35 is considered 'intermediate' and not to cause symptoms and signs of HD. There are articles claiming otherwise, however publishing only the cases that have a HD phenotype introduces a significant publication bias. Our objective is to determine if there is convincing evidence that intermediate repeats (IA) cause HD. Previously published case reports on HTT intermediate repeat sizes and all cases from the Netherlands with an IA were reviewed for clinical symptoms and signs. Four patients had a clinical presentation of Huntington's disease and an IA out of ten reported cases in literature. Between 2001 and 2012, 1,690 patients were tested for HD in the Netherlands. One case out of 60 with an IA had a phenotype resembling HD, but had already been published in a case report. Given the high background frequency of intermediate alleles in several populations, the possibility of developing HD would have huge implications for 1-7% of the normal population. It is possible that IAs present as an endophenotype with the potential of subsequent clinical manifestations. However, given the scarcity of convincing cases, the lack of convincing biological evidence for pathogenicity of intermediate alleles, and many genes still to be discovered for HD mimics, we find that it is premature to claim that IAs can cause HD. We recommend systematic follow up of this group of individuals and if possible brain pathology for confirmation or exclusion of HD.

Review: Epidemiological evidence of groundwater contribution to global enteric disease, 1948-2015

NASA Astrophysics Data System (ADS)

Murphy, Heather M.; Prioleau, Morgan D.; Borchardt, Mark A.; Hynds, Paul D.

2017-06-01

Globally, approximately 2.2 billion people rely on groundwater for daily consumption. It is widely accepted that groundwater is more pristine than surface water but while this assumption is frequently the case, groundwater is not ubiquitously free of contaminants; accordingly, this presumption can result in an unfounded and potentially hazardous sense of security among owners, operators and users. The current paper presents a review of published literature providing epidemiological evidence of the contribution of groundwater to global human enteric infection. An emphasis is placed on enteric pathogens transmitted via the faecal-oral route, and specifically those associated with acute gastrointestinal illness (AGI). The review identified 649 published groundwater outbreaks globally between 1948 and 2013 and several epidemiological studies that show there is an increased risk of AGI associated with the consumption of untreated groundwater. The review identified that the following five pathogens were responsible for most outbreaks: norovirus, Campylobacter, Shigella, Hepatitis A and Giardia. Crudely, the authors estimate that between 35.2 and 59.4 million cases of AGI per year globally could be attributable to the consumption of groundwater. Although groundwater is frequently presumed to be a microbiologically safe source of water for consumption, this review demonstrates that consumers served by an untreated groundwater supply remain at risk to enteric disease. The authors conclude that collaboration between microbiologists, hydrogeologists and epidemiologists is needed to better understand pathogen occurrence, persistence, detection and transport in groundwater as well as build stronger epidemiological evidence documenting the true magnitude of disease associated with groundwater globally.

Rhythmic auditory cueing to improve walking in patients with neurological conditions other than Parkinson's disease--what is the evidence?

PubMed

Wittwer, Joanne E; Webster, Kate E; Hill, Keith

2013-01-01

To investigate whether synchronising over-ground walking to rhythmic auditory cues improves temporal and spatial gait measures in adults with neurological clinical conditions other than Parkinson's disease. A search was performed in June 2011 using the computerised databases AGELINE, AMED, AMI, CINAHL, Current Contents, EMBASE, MEDLINE, PsycINFO and PUBMED, and extended using hand-searching of relevant journals and article reference lists. Methodological quality was independently assessed by two reviewers. A best evidence synthesis was applied to rate levels of evidence. Fourteen studies, four of which were randomized controlled trials (RCTs), met the inclusion criteria. Patient groups included those with stroke (six studies); Huntington's disease and spinal cord injury (two studies each); traumatic brain injury, dementia, multiple sclerosis and normal pressure hydrocephalus (one study each). The best evidence synthesis found moderate evidence of improved velocity and stride length of people with stroke following gait training with rhythmic music. Insufficient evidence was found for other included neurological disorders due to low study numbers and poor methodological quality of some studies. Synchronising walking to rhythmic auditory cues can result in short-term improvement in gait measures of people with stroke. Further high quality studies are needed before recommendations for clinical practice can be made.

Vitamin A in Stargardt disease-an evidence-based update.

PubMed

Federspiel, Cecilie Aalund; Bertelsen, Mette; Kessel, Line

2018-06-25

High intake of vitamin A is suspected to be a risk factor for the progression of Stargardt disease (STGD1) and many health authorities recommend Stargardt patients not to use oral vitamin A supplements outside that provided naturally in the food. The present study provides the first systematic review of the current level of evidence regarding the role of supplementary vitamin A in STGD1. We conducted a systematic scientific literature search in the Pubmed database on studies reporting on the effect of oral vitamin A or serum retinol on visual function. In animal studies neither high nor low serum retinol in an Abca4 knockout mouse model of Stargardt showed any effect on electroretinography (ERG). In humans, significantly better visual function was reported in a cross-sectional study of patients with a low dietary intake of vitamin A, whereas a prospective study did not find any correlation between vitamin A supplementation and visual acuity. A newly introduced vitamin A substitute (C20-D(3)-vitamin A) has shown promising effects on ERG in a Stargardt mouse model. There are few studies on the effect of vitamin A in STGD1. The scarcity and inconclusiveness of evidence available impel further research efforts to reach a more confident conclusion. Currently, recommendations to avoid vitamin A dietary supplementation rely mainly on a theoretical background. Animal studies on vitamin A substitute as a possible therapeutic approach in preventing or slowing vision loss in STGD1 seems promising but further clinical trials are needed to verify the results.

Understanding evidence-based diagnosis.

PubMed

Kohn, Michael A

2014-01-01

The real meaning of the word "diagnosis" is naming the disease that is causing a patient's illness. The cognitive process of assigning this name is a mysterious combination of pattern recognition and the hypothetico-deductive approach that is only remotely related to the mathematical process of using test results to update the probability of a disease. What I refer to as "evidence-based diagnosis" is really evidence-based use of medical tests to guide treatment decisions. Understanding how to use test results to update the probability of disease can help us interpret test results more rationally. Also, evidence-based diagnosis reminds us to consider the costs and risks of testing and the dangers of over-diagnosis and over-treatment, in addition to the costs and risks of missing serious disease.

Hematopoietic Stem Cell Transplantation in Late-Onset Krabbe Disease: No Evidence of Worsening Demyelination and Axonal Loss 4 Years Post-allograft.

PubMed

Laule, Cornelia; Vavasour, Irene M; Shahinfard, Elham; Mädler, Burkhard; Zhang, Jing; Li, David K B; MacKay, Alex L; Sirrs, Sandra M

2018-05-01

Late-onset adult Krabbe disease is a very rare demyelinating leukodystrophy, affecting less than 1 in a million people. Hematopoietic stem cell transplantation (HSCT) strategies can stop the accumulation of toxic metabolites that damage myelin-producing cells. We used quantitative advanced imaging metrics to longitudinally assess the impact of HSCT on brain abnormalities in adult-onset Krabbe disease. A 42-year-old female with late-onset Krabbe disease and an age/sex-matched healthy control underwent annual 3T MRI (baseline was immediately prior to HSCT for the Krabbe subject). Imaging included conventional scans, myelin water imaging, diffusion tensor imaging, and magnetic resonance spectroscopy. Brain abnormalities far beyond those visible on conventional imaging were detected, suggesting a global pathological process occurs in Krabbe disease with adult-onset etiology, with myelin being more affected than axons, and evidence of wide-spread gliosis. After HSCT, our patient showed clinical stability in all measures, as well as improvement in gait, dysarthria, and pseudobulbar affect at 7.5 years post-transplant. No MRI evidence of worsening demyelination and axonal loss was observed up to 4 years post-allograft. Clinical evidence and stability of advanced MR measures related to myelin and axons supports HSCT as an effective treatment strategy for stopping progression associated with late-onset Krabbe disease. Copyright © 2018 by the American Society of Neuroimaging.

Lack of evidence for the efficacy of memantine in mild Alzheimer disease.

PubMed

Schneider, Lon S; Dagerman, Karen S; Higgins, Julian P T; McShane, Rupert

2011-08-01

We directly assessed the clinical trials' evidence for memantine's efficacy in mild Alzheimer disease (AD). Memantine is indicated in the United States and Europe for moderate to severe AD, which is diagnosed if a patient has a Mini-Mental State Examination (MMSE) score of less than 15 or less than 20, respectively. Yet memantine is very frequently prescribed for mild AD and mild cognitive impairment, and a manufacturer-sponsored meta-analysis claimed its efficacy in mild AD. Manufacturer-sponsored meta-analyses, registries, presentations, and publications were systematically searched for randomized placebo-controlled, parallel-group clinical trials of memantine in patients with mild to moderate AD. The trials' characteristics and outcomes were extracted by one reviewer and checked by another. Meta-analyses were performed as inverse variance-weighted averages of mean differences using fixed-effects models. Summary results for patients with mild AD were obtained by contrasting the summary results for patients with mild or moderate AD with the summary results for the subset of patients with moderate AD. Three trials were identified that included 431 patients with mild AD (ie, with MMSE scores of 20-23) and 697 patients with moderate AD (ie, with MMSE scores of 10-19). There were no significant differences between memantine and placebo on any outcome for patients with mild AD, either within any trial or when data were combined: mean differences (95% confidence intervals [CIs]) on the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog), the Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC-plus), the Alzheimer Disease Cooperative Study-activities of daily living (ADCS-ADL) scale, and the Neuropsychiatric Inventory (NPI) were -0.17 (95% CI, -1.60 to 1.26), -0.09 (95% CI, -0.30 to 0.12), 0.62 (95% CI, -1.64 to 2.71), and 0.09 (95% CI, -2.11 to 2.29), respectively. For patients with moderate AD, there were small differences on the

Vaccination in paediatric patients with auto-immune rheumatic diseases: a systemic literature review for the European League against Rheumatism evidence-based recommendations.

PubMed

Heijstek, M W; Ott de Bruin, L M; Borrow, R; van der Klis, F; Koné-Paut, I; Fasth, A; Minden, K; Ravelli, A; Abinun, M; Pileggi, G; Borte, M; Bijl, M; Wulffraat, N M

2011-12-01

To analyze available evidence on vaccinations in paediatric patients with rheumatic and autoinflammatory diseases. This evidence formed the basis of the recently constructed European League against Rheumatism (EULAR) recommendations for vaccination of these patients. A systematic literature review in the MEDLINE and EMBASE databases was conducted using various terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and immunosuppressive drugs. Only papers on paediatric patients (<18 years of age) were selected. A panel of 13 experts in the field graded methodological quality and extracted data using predefined criteria. 27 papers were available. No studies were found on autoinflammatory diseases. 14 studies considered live-attenuated vaccines. Evidence so far supports the safety and immunogenicity of non-live composite vaccines, although studies were underpowered to accurately assess safety. Live-attenuated vaccines did not cause disease flares or severe adverse events, not even in patients on methotrexate and low dose glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2) booster without severe adverse events. Data on safety and efficacy of vaccinations in paediatric patients with rheumatic diseases is reassuring, but too limited to draw definite conclusions. More research is needed on the safety and efficacy of especially live-attenuated vaccines in patients with rheumatic and autoinflammatory diseases using high dose immunosuppressive drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

The determinants of spread of Ebola virus disease - an evidence from the past outbreak experiences.

PubMed

Gałas, Aleksander

2014-01-01

The paper summarizes available evidence regarding the determinants of spread of Ebola virus disease, including health care and community related risk factors. It was observed that the level of uncertainty for the estimations is relatively high which may hinder to make some predictions for the future evolution of EVD outbreak. The natural history of EVD has shown that the disease may pose a problem to developed countries and may present a thread to individuals. Although observed modes of transmission mainly include direct contact and contaminated staff, high case fatality ratio and frequent contacts among individuals in developed countries are among determinants which may lead to the development of the EVD outbreak.

Management of Cardiovascular Risk in Patients with Chronic Inflammatory Diseases: Current Evidence and Future Perspectives.

PubMed

Lindhardsen, Jesper; Kristensen, Søren Lund; Ahlehoff, Ole

2016-02-01

An increased risk of cardiovascular disease (CVD) has been observed in a range of chronic inflammatory diseases (CID), including rheumatoid arthritis (RA), psoriasis, inflammatory bowel diseases (IBD), and systemic lupus erythematosus (SLE). The increased risk of CVDs and reduced life expectancy in these conditions has stimulated considerable research and started an ongoing discussion on the need for a multidisciplinary approach and dedicated guidelines on CVD prevention in these patients. In addition, the possibility of inhibiting inflammation as a means to preventing CVD in these patients has gained considerable interest in recent years. We briefly summarize the current level of evidence of the association between CIDs and CVD and cardiovascular risk management recommendations. Perspectives of ongoing and planned trials are discussed in consideration of potential ways to improve primary and secondary CVD prevention in patients with CID.

Community health workers for non-communicable diseases prevention and control in developing countries: Evidence and implications.

PubMed

Jeet, Gursimer; Thakur, J S; Prinja, Shankar; Singh, Meenu

2017-01-01

National programs for non-communicable diseases (NCD) prevention and control in different low middle income countries have a strong community component. A community health worker (CHW) delivers NCD preventive services using informational as well as behavioural approaches. Community education and interpersonal communication on lifestyle modifications is imparted with focus on primordial prevention of NCDs and screening is conducted as part of early diagnosis and management. However, the effectiveness of health promotion and screening interventions delivered through community health workers needs to be established. This review synthesised evidence on effectiveness of CHW delivered NCD primary prevention interventions in low and middle-income countries (LMICs). A systematic review of trials that utilised community health workers for primary prevention/ early detection strategy in the management of NCDs (Diabetes, cardiovascular diseases (CVD), cancers, stroke, Chronic Obstructive Pulmonary Diseases (COPD)) in LMICs was conducted. Digital databases like PubMed, EMBASE, OVID, Cochrane library, dissertation abstracts, clinical trials registry web sites of different LMIC were searched for such publications between years 2000 and 2015. We focussed on community based randomised controlled trial and cluster randomised trials without any publication language limitation. The primary outcome of review was percentage change in population with different behavioural risk factors. Additionally, mean overall changes in levels of several physical or biochemical parameters were studied as secondary outcomes. Subgroup analyses was performed by the age and sex of participants, and sensitivity analyses was conducted to assess the robustness of the findings. Sixteen trials meeting the inclusion criteria were included in the review. Duration, study populations and content of interventions varied across trials. The duration of the studies ranged from mean follow up of 4 months for some risk

Treatment of sexually transmitted diseases in Estonia: consistency with the evidence-based medicine principles.

PubMed

Uusküla, Anneli; McNutt, Louise Anne; Dehovitz, Jack

2004-10-01

Estonia is among those Eastern European countries that have witnessed an explosive intravenous drug use-driven HIV epidemic. Early sexually transmitted disease (STD) diagnosis and appropriate treatment is essential to prevent an STD-driven HIV epidemic. The objectives of this study were to define the schedule of antibiotic treatment doctors in Estonia used to treat STDs, and to determine if the treatments used correspond to evidence-based medicine treatment principles. Using an administrative database of the Estonian Health Insurance Fund on pharmaceuticals reimbursement, we obtained information on: drug (ATC 1998) prescribed with an STD diagnosis (International Classification of Diseases and Related Health Problems, syphilis, gonorrhea, genital Chlamydia trachomatis and Trichomonas vaginalis infections, and genital herpes), prescribing physician specialty, and patient demographics (date of birth, gender). To evaluate the correspondence of STD treatment to evidence-based medicine principles, the therapeutic regimens used were compared with recommendations from the European Sexually Transmitted Infections Management Guidelines. In 2001 and 2002, physicians ordered 17,077 prescriptions for systemic antibacterial medications to treat STDs in 12,823 different individuals: 2942 men (mean age, 31.8 years) and 9880 women (mean age, 29.5 years). The majority of STD treatments were prescribed by gynecologists (60%) or dermatovenerologists (29%); general practitioners treated 8% of STDs. In 11% of treatment episodes, the drug prescribed was inconsistent with guideline recommendations; additionally, in 9% of episodes, the recommended drug was chosen but the prescribed dose was too low. At least 20% of treatment episodes could therefore be considered inappropriate. Educational efforts are needed to increase physician awareness of evidence-based approaches for STD management and treatment to assure effective STD care.

Impact of chronic kidney disease on use of evidence-based therapy in stable coronary artery disease: a prospective analysis of 22,272 patients.

PubMed

Kalra, Paul R; García-Moll, Xavier; Zamorano, José; Kalra, Philip A; Fox, Kim M; Ford, Ian; Ferrari, Roberto; Tardif, Jean-Claude; Tendera, Michal; Greenlaw, Nicola; Steg, Ph Gabriel

2014-01-01

To assess the frequency of chronic kidney disease (CKD), define the associated demographics, and evaluate its association with use of evidence-based drug therapy in a contemporary global study of patients with stable coronary artery disease. 22,272 patients from the ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) were included. Baseline estimated glomerular filtration rate (eGFR) was calculated (CKD-Epidemiology Collaboration formula) and patients categorised according to CKD stage: >89, 60-89, 45-59 and <45 mL/min/1.73 m2. Mean (SD) age was 63.9±10.4 years, 77.3% were male, 61.8% had a history of myocardial infarction, 71.9% hypertension, 30.4% diabetes and 75.4% dyslipidaemia. Chronic kidney disease (eGFR<60 mL/min/1.73 m2) was seen in 22.1% of the cohort (6.9% with eGFR<45 mL/min/1.73 m2); lower eGFR was associated with increasing age, female sex, cardiovascular risk factors, overt vascular disease, other comorbidities and higher systolic but lower diastolic blood pressure. High use of secondary prevention was seen across all CKD stages (overall 93.4% lipid-lowering drugs, 95.3% antiplatelets, 75.9% beta-blockers). The proportion of patients taking statins was lower in patients with CKD. Antiplatelet use was significantly lower in patients with CKD whereas oral anticoagulant use was higher. Angiotensin-converting enzyme inhibitor use was lower (52.0% overall) and inversely related to declining eGFR, whereas angiotensin-receptor blockers were more frequently prescribed in patients with reduced eGFR. Chronic kidney disease is common in patients with stable coronary artery disease and is associated with comorbidities. Whilst use of individual evidence-based medications for secondary prevention was high across all CKD categories, there remains an opportunity to improve the proportion who take all three classes of preventive therapies. Angiotensin-converting enzyme inhibitors were used less frequently in

Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review

PubMed Central

Arab, Juan P; Candia, Roberto; Zapata, Rodrigo; Muñoz, Cristián; Arancibia, Juan P; Poniachik, Jaime; Soza, Alejandro; Fuster, Francisco; Brahm, Javier; Sanhueza, Edgar; Contreras, Jorge; Cuellar, M Carolina; Arrese, Marco; Riquelme, Arnoldo

2014-01-01

AIM: To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS: NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS: A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form of NAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION: Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events. PMID:25232252

Diet beverages and the risk of obesity, diabetes, and cardiovascular disease: a review of the evidence.

PubMed

Pereira, Mark A

2013-07-01

"Diet beverage" is a common term used to describe beverages that are sweetened with non-nutritive or artificial sweeteners (ASBs). Marketing strategies often imply that consuming these beverages holds promise for weight control or weight loss. The objective of the present review is to provide a synthesis of the literature on the effects of ASBs on body weight, cardiovascular disease, and type 2 diabetes. Consumption of diet beverages is much lower than that of sugar-sweetened beverages (SSBs), and people trying to lose weight report the highest levels of ASB consumption. To date, prospective observational studies have revealed mixed results, and it appears that reverse causality is a particular problem, since individuals who are at higher risk for weight gain may choose to consume ASBs in an attempt to control their weight or reduce disease risk. As for experimental studies, the evidence currently suggests that obesity risk may be lower when ASBs replace SSBs in the diet. Still, additional evidence from experimental studies is needed to more definitively determine the benefits and risks of frequent ASB consumption. © 2013 International Life Sciences Institute.

Evidence of the Role of Physical Activity and Cardiorespiratory Fitness in the Prevention of Coronary Heart Disease.

ERIC Educational Resources Information Center

Leon, Arthur S.; Norstrom, Jane

1995-01-01

This paper presents epidemiologic evidence on the contributions of physical inactivity and reduced cardiorespiratory fitness to risk of coronary heart disease (CHD). The types and dose of physical activity to reduce risk of CHD and plausible biologic mechanisms for the partial protective effect are reviewed. (Author/SM)

Radiographic Evidence of Sinonasal Inflammation in Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome: An Underrecognized Association.

PubMed

Hamada, Satoshi; Tatsumi, Shuji; Kobayashi, Yoshiki; Matsumoto, Hisako; Yasuba, Hirotaka

Sinonasal inflammation on both clinical examinations and imaging significantly impacts both asthma and chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the association between sinonasal inflammation and asthma-COPD overlap syndrome (ACOS). A total of 112 patients with a ratio of forced expiratory volume in 1 s to forced vital capacity of less than 70% were enrolled. COPD, asthma, and ACOS were clinically diagnosed according to the 2014 Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Sinonasal inflammatory condition was evaluated using sinus computed tomography, and its severity was assessed according to the Lund-Mackay staging (LMS) system. Ethmoid sinus-dominant shadow was defined as the presence of greater LMS scores for the anterior and posterior ethmoid sinuses than for the maxillary sinus. COPD, asthma, and ACOS were diagnosed in 55 (49.1%), 39 (34.8%), and 18 patients (16.1%), respectively. The frequency of radiographic evidence of sinonasal inflammation in patients with COPD, asthma, ACOS was 60.0%, 94.9%, and 72.2%, respectively. Patients with ACOS and COPD had only mild radiographic evidence of sinonasal inflammation (LMS score, 1-7), whereas moderate (LMS score, 8-11) and severe (LMS score, ≥12) radiographic evidence of sinonasal inflammation were detected only in patients with asthma. Furthermore, the frequency of ethmoid sinus-dominant shadow was significantly higher in patients with asthma than in those with COPD and ACOS. Radiographic evidence of sinonasal inflammation was a common comorbidity in ACOS. Future studies are required to examine the role of sinonasal inflammation in ACOS. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Disease and Development: Evidence from Hookworm Eradication in the American South*

PubMed Central

Bleakley, Hoyt

2013-01-01

This study evaluates the economic consequences of the successful eradication of hookworm disease from the American South. The hookworm-eradication campaign (c. 1910) began soon after (i) the discovery that a variety of health problems among Southerners could be attributed to the disease and (ii) the donation by John D. Rockefeller of a substantial sum to the effort. The Rockefeller Sanitary Commission (RSC) surveyed infection rates in the affected areas (eleven southern states) and found that an average of forty percent of school-aged children were infected with hookworm. The RSC then sponsored treatment and education campaigns across the region. Follow-up studies indicate that this campaign substantially reduced hookworm disease almost immediately. The sudden introduction of this treatment combines with the cross-area differences in pre-treatment infection rates to form the basis of the identification strategy. Areas with higher levels of hookworm infection prior to the RSC experienced greater increases in school enrollment, attendance, and literacy after the intervention. This result is robust to controlling for a variety of alternative factors, including differential trends across areas, changing crop prices, shifts in certain educational and health policies, and the effect of malaria eradication. No significant contemporaneous results are found for adults, who should have benefited less from the intervention owing to their substantially lower (prior) infection rates. A long-term follow-up of affected cohorts indicates a substantial gain in income that coincided with exposure to hookworm eradication. I also find evidence that eradication increased the return to schooling. PMID:24146438

Exclusion of 'nonRCT evidence' in guidelines for chronic diseases - is it always appropriate? The Look AHEAD study.

PubMed

Kones, Richard; Rumana, Umme; Merino, Jordi

2014-10-01

Evidence-based medicine (EBM) is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. The introduction of EBM was a conceptual and practical milestone in the history of medicine, with far-reaching impact yet to be fully realized. EBM has limitations, including inapplicability to populations dissimilar to those in studies, and may not reflect duration of exposure to risk factors, details of lifestyle, incubation period, latency, or environmental changes during chronic diseases. Routine exclusion of evidence other than randomized controlled trials (RCTs) or meta-analyses from consideration in treatment may not always be wise. This review is not a result of a search, but rather a conceptual unification of (a) the increasing restrictions in guideline-writing favoring more RCTs, and rejecting observational studies when chronic diseases with a long incubation period may sometimes be best probed by the latter; (b) the possibility RCTs may be inconclusive, nonapplicable, or result in 'negative' results which may misdirect future therapy by physicians and undermine adherence by patients; (c) the potential improvement in patient care from having all available information evaluated (especially epidemiological studies of chronic diseases) and synthesized in guidelines. The example of the Look AHEAD study is chosen - a 'negative' RCT with significant information overlooked by reviewers, who initially declared that weight loss and physical activity were ineffective in treating diabetes, or in preventing cardiovascular complications. In this review, placing this study in perspective, among others, suggests the opposite - exercise and weight loss are effective if done early and sufficiently. Synthesizing worthy data from many sources, including prospective and pathophysiological studies, particularly when RCTs are unavailable, has the potential to add depth and expand the understanding of disease. In

The role of fibrinogen glycation in ATTR: evidence for chaperone activity loss in disease.

PubMed

Fonseca, Daniel; Gilberto, Samuel; Ribeiro-Silva, Cristina; Ribeiro, Raquel; Guinote, Inês Batista; Saraiva, Susana; Gomes, Ricardo A; Mateus, Élia; Viana, Ana; Barroso, Eduardo; Freire, Ana Ponces; Freire, Patrick; Cordeiro, Carlos; da Costa, Gonçalo

2016-07-15

Transthyretin amyloidosis (ATTR) belongs to a class of disorders caused by protein misfolding and aggregation. ATTR is a disabling disorder of autosomal dominant trait, where transthyretin (TTR) forms amyloid deposits in different organs, causing dysfunction of the peripheral nervous system. We previously discovered that amyloid fibrils from ATTR patients are glycated by methylglyoxal. Even though no consensus has been reached about the actual role of methylglyoxal-derived advanced glycation end-products in amyloid diseases, evidence collected so far points to a role for protein glycation in conformational abnormalities, being ubiquitously found in amyloid deposits in Alzheimer's disease, dialysis-related amyloidosis and Parkinson's diseases. Human fibrinogen, an extracellular chaperone, was reported to specifically interact with a wide spectrum of stressed proteins and suppress their aggregation, being an interacting protein with TTR. Fibrinogen is differentially glycated in ATTR, leading to its chaperone activity loss. Here we show the existence of a proteostasis imbalance in ATTR linked to fibrinogen glycation by methylglyoxal. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

What is the strength of evidence for heart failure disease-management programs?

PubMed

Clark, Alexander M; Savard, Lori A; Thompson, David R

2009-07-28

Heart failure (HF) disease-management programs are increasingly common. However, some large and recent trials of programs have not reported positive findings. There have also been parallel recent advances in reporting standards and theory around complex nonpharmacological interventions. These developments compel reconsideration in this Viewpoint of how research into HF-management programs should be evaluated, the quality, specificity, and usefulness of this evidence, and the recommendations for future research. Addressing the main determinants of intervention effectiveness by using the PICO (Patient, Intervention, Comparison, and Outcome) approach and the recent CONSORT (Consolidated Standards of Reporting Trials) statement on nonpharmacological trials, we will argue that in both current trials and meta-analyses, interventions and comparisons are not sufficiently well described; that complex programs have been excessively oversimplified; and that potentially salient differences in programs, populations, and settings are not incorporated into analyses. In preference to more general meta-analyses of programs, adequate descriptions are first needed of populations, interventions, comparisons, and outcomes in past and future trials. This could be achieved via a systematic survey of study authors based on the CONSORT statement. These more detailed data on studies should be incorporated into future meta-analyses of comparable trials and used with other techniques such as patient-based outcomes data and meta-regression. Although trials and meta-analyses continue to have potential to generate useful evidence, a more specific evidence base is needed to support the development of effective programs for different populations and settings.

Community health workers for non-communicable diseases prevention and control in developing countries: Evidence and implications

PubMed Central

Jeet, Gursimer; Thakur, J. S.; Prinja, Shankar; Singh, Meenu

2017-01-01

Background National programs for non-communicable diseases (NCD) prevention and control in different low middle income countries have a strong community component. A community health worker (CHW) delivers NCD preventive services using informational as well as behavioural approaches. Community education and interpersonal communication on lifestyle modifications is imparted with focus on primordial prevention of NCDs and screening is conducted as part of early diagnosis and management. However, the effectiveness of health promotion and screening interventions delivered through community health workers needs to be established. Objective This review synthesised evidence on effectiveness of CHW delivered NCD primary prevention interventions in low and middle-income countries (LMICs). Methods A systematic review of trials that utilised community health workers for primary prevention/ early detection strategy in the management of NCDs (Diabetes, cardiovascular diseases (CVD), cancers, stroke, Chronic Obstructive Pulmonary Diseases (COPD)) in LMICs was conducted. Digital databases like PubMed, EMBASE, OVID, Cochrane library, dissertation abstracts, clinical trials registry web sites of different LMIC were searched for such publications between years 2000 and 2015. We focussed on community based randomised controlled trial and cluster randomised trials without any publication language limitation. The primary outcome of review was percentage change in population with different behavioural risk factors. Additionally, mean overall changes in levels of several physical or biochemical parameters were studied as secondary outcomes. Subgroup analyses was performed by the age and sex of participants, and sensitivity analyses was conducted to assess the robustness of the findings. Results Sixteen trials meeting the inclusion criteria were included in the review. Duration, study populations and content of interventions varied across trials. The duration of the studies ranged from

Relation between burden of disease and randomised evidence in sub-Saharan Africa: survey of research.

PubMed

Isaakidis, Petros; Swingler, George H; Pienaar, Elizabeth; Volmink, Jimmy; Ioannidis, John P A

2002-03-23

To evaluate whether the amount of randomised clinical research on various medical conditions is related to the burden of disease and health needs of the local populations in sub-Saharan Africa. Construction and analysis of comprehensive database of randomised controlled trials in sub-Saharan Africa based on Medline, the Cochrane Controlled Trials Register, and several African databases. Sub-Saharan Africa. Number of trials and randomised subjects for each category of disease in the global burden of disease taxonomy; ratios of disability adjusted life years (DALYs) per amount of randomised evidence. 1179 eligible randomised controlled trials were identified. The number of trials published each year increased over time. Almost half of the trials (n=565) had been done in South Africa. There was relatively good correlation between the estimated burden of disease at year 2000 and the number of trials performed (r=0.53, P=0.024) and the number of participants randomised (r=0.68, P=0.002). However,some conditions-for example, injuries (over 20 000 DALYs per patient ever randomised)-were more neglected than others. Despite recent improvements, few clinical trials are done in sub-Saharan Africa. Clinical research in this part of the world should focus more evenly on the major contributors to burden of disease.

Treatment of diverticular disease: an update on latest evidence and clinical implications.

PubMed

Carabotti, Marilia; Annibale, Bruno

2018-01-01

Diverticular disease (DD) is a common condition, especially in Western countries. In about 80% of patients, colonic diverticula remain asymptomatic (diverticulosis), while approximately 20% of patients may develop abdominal symptoms (symptomatic uncomplicated diverticular disease, SUDD) and, eventually complications as acute diverticulitis (AD). The management of this condition has been improved, and in the last five years European countries and the USA have published guidelines and recommendations. To summarize the latest evidence and clinical implication in treatment of DD focusing the attention either on the treatment of diverticulosis, SUDD and AD together with the primary and secondary prevention of diverticulitis. The present review was based on the latest evidence in the treatment of DD in the last 10 years. In the last 5 years, six countries issued guidelines on DD with differences regarding covered topics and recommendations regarding treatments. At present there is a lack of rationale for drug use in patients with asymptomatic diverticulosis, but there are limited indications to suggest an increase in dietary fibre to reduce risk of DD. To achieve symptomatic relief in SUDD patients, several therapeutic strategies with fibre, probiotics, rifaximin and mesalazine have been proposed even if a standard therapeutic approach remained to be defined. Agreement has been reached for the management of AD, since recent guidelines showed that antibiotics can be used selectively, rather than routinely in uncomplicated AD, although use of antibiotics remained crucial in the management of complicated cases. With regard to treatment for the primary and secondary prevention of AD, the efficacy of rifaximin and mesalazine has been proposed although with discordant recommendations among guidelines. Treatment of DD represented an important challenge in clinical practice, especially concerning management of SUDD and the primary and secondary prevention of AD.

Interpreting genetics in the context of eating disorders: Evidence of disease, not diversity

PubMed Central

Easter, Michele

2013-01-01

How is genetic involvement interpreted for disorders whose medicalisation is contested? Framing psychiatric and behavioral disorders in terms of genetics is expected to make them seem “more medical.” Yet, genetic etiology can also be used to frame behavior as acceptable human variation, rather than a medical problem (e.g., sexual orientation). I analyze responses to the idea of a genetic component in anorexia and bulimia nervosa (AN/BN) via semi-structured interviews with a sample of 50 women diagnosed with an eating disorder (25 recovered). All but three volunteered that genetics would medicalise AN/BN, by (1) making eating disorders seem more like “real” diseases; (2) implying a need for professional treatment; or (3) for biologically-based treatment. Results also indicate several “counter-logics,” by which genetic framing could support non-medical definitions of AN/BN. I argue that genetic framing reduces perceived individual responsibility, which can support definitions of behavior as either a reflection of disease (which entails intervention) or a reflection of normal human diversity (which does not). In the context of public skepticism as to the “reality” of AN/BN, genetic involvement was taken as evidence of disease in ongoing negotiations about the medical and moral status of people with eating disorders. PMID:24286479

Selective attention impairments in Alzheimer's disease: evidence for dissociable components.

PubMed

Levinoff, Elise J; Li, Karen Z H; Murtha, Susan; Chertkow, Howard

2004-07-01

Tasks emphasizing 3 different aspects of selective attention-inhibition, visuospatial selective attention, and decision making-were administered to subjects with mild Alzheimer's disease (AD) and to healthy elderly control (HEC) subjects to determine which components of selective attention were impaired in AD subjects and whether selective attention could be dissociated into different components. The tasks were administered with easy versus hard levels of difficulty to assess proportional slowing as the key variable across tasks. The results indicated that the inhibitory and visual search tasks showed greater proportional slowing in subjects with AD than in HEC subjects, and that the task involving inhibition was significantly more affected in subjects with AD. Furthermore, there were no significant intertask correlations, and the results cannot be explained simply in terms of generalized cognitive slowing. These results provide evidence that inhibition is the most strikingly affected aspect of selective attention that is observed to be impaired in early stages of AD.

Diagnosis and Management of Uncomplicated Chlamydia trachomatis Infections in Adolescents and Adults: Summary of Evidence Reviewed for the 2015 Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines.

PubMed

Geisler, William M

2015-12-15

In preparation for the 2015 Centers for Disease Control and Prevention (CDC) Sexually Transmitted Diseases (STD) Treatment Guidelines, the CDC convened an advisory group in 2013 to examine recent abstracts and published literature addressing the epidemiology, diagnosis, and management of STDs. This article summarizes the key questions, evidence, and recommendations for the diagnosis and management of uncomplicated Chlamydia trachomatis (CT) infection in adolescents and adults that were considered in development of the 2015 CDC STD Treatment Guidelines. The evidence reviewed primarily focused on CT infection risk factors in women, clinical significance of oropharyngeal CT detection, acceptability and performance of CT testing on self-collected specimens in men, performance of CT point-of-care tests, efficacy of recommended and investigational CT infection treatments, and timing of test of cure following CT infection treatment in pregnant women. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Diabetes and cardiovascular disease: from evidence to clinical practice – position statement 2014 of Brazilian Diabetes Society

PubMed Central

2014-01-01

There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology. PMID:24855495

Cardiovascular Disease Risk in Children With Kidney Disease.

PubMed

Sethna, Christine B; Merchant, Kumail; Reyes, Abigail

2018-05-01

Cardiovascular disease is a major cause of death in individuals diagnosed with kidney disease during childhood. Children with kidney disease often incur a significant cardiovascular burden that leads to increased risk for cardiovascular disease. Evidence has shown that children with kidney disease, including chronic kidney disease, dialysis, kidney transplantation, and nephrotic syndrome, develop abnormalities in cardiovascular markers such as hypertension, dyslipidemia, left ventricular hypertrophy, left ventricular dysfunction, atherosclerosis, and aortic stiffness. Early identification of modifiable risk factors and treatment may lead to a decrease of long-term cardiovascular morbidity and mortality, but evidence in this population is lacking. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk of transmission of sporadic Creutzfeldt-Jakob disease by surgical procedures: systematic reviews and quality of evidence.

PubMed

López, Fernando J García; Ruiz-Tovar, María; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; Calero, Miguel; de Pedro-Cuesta, Jesús

2017-10-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans. This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD. Firstly, we conducted systematic reviews and meta-analyses of case-control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments. Thirteen case-control studies met the inclusion criteria for the systematic review of case-control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case-control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments. The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.

Practical Diagnosis and Management of Dementia Due to Alzheimer’s Disease in the Primary Care Setting: An Evidence-Based Approach

PubMed Central

Kerwin, Diana R.

2013-01-01

Objective: To review evidence-based guidance on the primary care of Alzheimer’s disease and clinical research on models of primary care for Alzheimer’s disease to present a practical summary for the primary care physician regarding the assessment and management of the disease. Data Sources: References were obtained via search using keywords Alzheimer’s disease AND primary care OR collaborative care OR case finding OR caregivers OR guidelines. Articles were limited to English language from January 1, 1990, to January 1, 2013. Study Selection: Articles were reviewed and selected on the basis of study quality and pertinence to this topic, covering a broad range of data and opinion across geographical regions and systems of care. The most recent published guidelines from major organizations were included. Results: Practice guidelines contained numerous points of consensus, with most advocating a central role for the primary care physician in the detection, diagnosis, and treatment of Alzheimer’s disease. Review of the literature indicated that optimal medical and psychosocial care for people with Alzheimer’s disease and their caregivers may be best facilitated through collaborative models of care involving the primary care physician working within a wider interdisciplinary team. Conclusions: Evidence-based guidelines assign the primary care physician a critical role in the care of people with Alzheimer’s disease. Research on models of care suggests the need for an appropriate medical/nonmedical support network to fulfill this role. Given the diversity and breadth of services required and the necessity for close coordination, nationwide implementation of team-based, collaborative care programs may represent the best option for improving care standards for patients with Alzheimer’s disease. PMID:24392252

The Movement Disorder Society Evidence-Based Medicine Review Update: Treatments for the motor symptoms of Parkinson's disease.

PubMed

Fox, Susan H; Katzenschlager, Regina; Lim, Shen-Yang; Ravina, Bernard; Seppi, Klaus; Coelho, Miguel; Poewe, Werner; Rascol, Olivier; Goetz, Christopher G; Sampaio, Cristina

2011-10-01

The objective was to update previous evidence-based medicine reviews of treatments for motor symptoms of Parkinson's disease published between 2002 and 2005. Level I (randomized, controlled trial) reports of pharmacological, surgical, and nonpharmacological interventions for the motor symptoms of Parkinson's disease between January 2004 (2001 for nonpharmacological) and December 2010 were reviewed. Criteria for inclusion, clinical indications, ranking, efficacy conclusions, safety, and implications for clinical practice followed the original program outline and adhered to evidence-based medicine methodology. Sixty-eight new studies qualified for review. Piribedil, pramipexole, pramipexole extended release, ropinirole, rotigotine, cabergoline, and pergolide were all efficacious as symptomatic monotherapy; ropinirole prolonged release was likely efficacious. All were efficacious as a symptomatic adjunct except pramipexole extended release, for which there is insufficient evidence. For prevention/delay of motor fluctuations, pramipexole and cabergoline were efficacious, and for prevention/delay of dyskinesia, pramipexole, ropinirole, ropinirole prolonged release, and cabergoline were all efficacious, whereas pergolide was likely efficacious. Duodenal infusion of levodopa was likely efficacious in the treatment of motor complications, but the practice implication is investigational. Entacapone was nonefficacious as a symptomatic adjunct to levodopa in nonfluctuating patients and nonefficacious in the prevention/delay of motor complications. Rasagiline conclusions were revised to efficacious as a symptomatic adjunct, and as treatment for motor fluctuations. Clozapine was efficacious in dyskinesia, but because of safety issues, the practice implication is possibly useful. Bilateral subthalamic nucleus deep brain stimulation, bilateral globus pallidus stimulation, and unilateral pallidotomy were updated to efficacious for motor complications. Physical therapy was revised

Screening for cerebrovascular disease in microcephalic osteodysplastic primordial dwarfism type II (MOPD II): an evidence-based proposal.

PubMed

Perry, Luke D; Robertson, Fergus; Ganesan, Vijeya

2013-04-01

Microcephalic osteodysplastic primordial dwarfism type II (OMIM 210720) is a rare autosomal recessive condition frequently associated with early-onset cerebrovascular disease. Presymptomatic detection and intervention could prevent the adverse consequences associated with this. We reviewed published cases of microcephalic osteodysplastic primordial dwarfism type II to ascertain prevalence and characteristics of cerebrovascular disease and use these data to propose an evidence-based approach to cerebrovascular screening. Of 147 cases identified, 47 had cerebrovascular disease (32%), including occlusive arteriopathy (including moyamoya) and cerebral aneurysmal disease. Occlusive disease occurred in younger individuals, and progression can be both rapid and clinically silent. A reasonable screening approach would be magnetic resonance imaging and angiography of the cervical and intracranial circulation at diagnosis, repeated at yearly intervals until 10 years, and every 2 years thereafter, unless clinical concerns occur earlier. At present it would appear that this needs to be life-long. Families and professionals should be alerted to the potential significance of neurologic symptoms and measures should be taken to maintain good vascular health in affected individuals. Copyright © 2013 Elsevier Inc. All rights reserved.

Reaching Agreement in Uncertain Circumstances: The Practice of Evidence-Based Policy in the Case of the Swedish National Guidelines for Heart Diseases

ERIC Educational Resources Information Center

Eckard, Nathalie; Nedlund, Ann-Charlotte; Janzon, Magnus; Levin, Lars-Åke

2017-01-01

This paper explores the practice of evidence-based policy in a Swedish healthcare context. The study focused on how policymakers in the specific working group, the Priority-Setting Group (PSG), handled the various forms of evidence and values and their competing rationalities, when producing the Swedish National Guidelines for heart diseases that…

Advanced glycation end products and their receptor in age-related, non-communicable chronic inflammatory diseases; Overview of clinical evidence and potential contributions to disease.

PubMed

Reynaert, Niki L; Gopal, Poornima; Rutten, Erica P A; Wouters, Emiel F M; Schalkwijk, Casper G

2016-12-01

Age-related, non-communicable chronic inflammatory diseases represent the major 21st century health problem. Especially in Western countries, the prevalence of non-communicable diseases like chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis are exponentially rising as the population ages. These diseases are determined by common risk factors and share an age-related onset. The affected organs display evidence of accelerated ageing, and are hallmarked by chronic inflammation and oxidative stress. The receptor for advanced glycation end products (RAGE) has been implicated in a number of inflammatory diseases and plays a central role in amplifying inflammatory responses. Advanced glycation end product (AGE) formation and accumulation is accelerated under these conditions. Advanced glycation end products are not only linked to RAGE signaling and inflammation, but to various hallmarks of the ageing process. In addition to these biological functions, circulating levels of the soluble form of RAGE and of advanced glycation end products are candidate biomarkers for many age-related inflammatory diseases. The purpose of this review is to provide an overview of the mechanistic connections between RAGE and advanced glycation end products and the processes of inflammation and ageing. Furthermore, through the presented overview of AGE-RAGE alterations that have been described in clinical studies in chronic obstructive pulmonary disease, cardiovascular disease, type 2 diabetes and osteoporosis, and insight obtained from mechanistic in vitro and animal studies, it can be concluded that these AGE-RAGE disturbances are a common contributing factor to the inflammatory state and pathogenesis of these various conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Perspectives on death and an afterlife in relation to quality of life, depression, and hopelessness in cancer patients without evidence of disease and advanced cancer patients.

PubMed

van Laarhoven, Hanneke W M; Schilderman, Johannes; Verhagen, Constans A H H V M; Vissers, Kris C; Prins, Judith

2011-06-01

It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. To assess the relationship of attitudes and emotions towards death and an afterlife with quality of life, depression and hopelessness in cancer patients without evidence of disease and advanced cancer patients facing death. Ninety-one cancer patients without evidence of disease and 57 advanced cancer patients completed the Dutch Attitudes Toward Death and Afterlife Scale. Emotions toward death were measured using the Self-Confrontation Method. Quality of life was measured with the Satisfaction with Life Scale and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire. Depression and hopelessness were measured with the Beck Depression Inventory for Primary Care and the Beck Hopelessness Scale. Average scores on attitudes and emotions toward death and an afterlife were not significantly different between the two groups. However, in the no evidence of disease group, a negative association between negative emotions and social functioning was observed, which was not present in the advanced cancer group. In the advanced cancer group, associations were observed that were not present in the no evidence of disease group: positive associations between an explicitly religious attitude and global health status and between reincarnation belief and role and cognitive functioning, and a negative association between other-directed emotions and social functioning. Patients without evidence of disease and advanced cancer patients do not differ in attitudes or emotions toward death, but the relationship between these attitudes and emotions and aspects of quality of life varies. When there is no evidence of disease, negative emotions play the most important role, whereas in the advanced

Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease

PubMed Central

Crowe, Sonya; Knowles, Rachel; Wray, Jo; Tregay, Jenifer; Ridout, Deborah A; Utley, Martin; Franklin, Rodney; Bull, Catherine L; Brown, Katherine L

2016-01-01

Objectives Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3–5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. Design A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. Setting UK. Results A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. Conclusions Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations. PMID:27266768

Removal of two large-scale cosmic microwave background anomalies after subtraction of the integrated Sachs-Wolfe effect

NASA Astrophysics Data System (ADS)

Rassat, A.; Starck, J.-L.; Dupé, F.-X.

2013-09-01

Context. Although there is currently a debate over the significance of the claimed large-scale anomalies in the cosmic microwave background (CMB), their existence is not totally dismissed. In parallel to the debate over their statistical significance, recent work has also focussed on masks and secondary anisotropies as potential sources of these anomalies. Aims: In this work we investigate simultaneously the impact of the method used to account for masked regions as well as the impact of the integrated Sachs-Wolfe (ISW) effect, which is the large-scale secondary anisotropy most likely to affect the CMB anomalies. In this sense, our work is an update of previous works. Our aim is to identify trends in CMB data from different years and with different mask treatments. Methods: We reconstruct the ISW signal due to 2 Micron All-Sky Survey (2MASS) and NRAO VLA Sky Survey (NVSS) galaxies, effectively reconstructing the low-redshift ISW signal out to z ~ 1. We account for regions of missing data using the sparse inpainting technique. We test sparse inpainting of the CMB, large scale structure and ISW and find that it constitutes a bias-free reconstruction method suitable to study large-scale statistical isotropy and the ISW effect. Results: We focus on three large-scale CMB anomalies: the low quadrupole, the quadrupole/octopole alignment, and the octopole planarity. After sparse inpainting, the low quadrupole becomes more anomalous, whilst the quadrupole/octopole alignment becomes less anomalous. The significance of the low quadrupole is unchanged after subtraction of the ISW effect, while the trend amongst the CMB maps is that both the low quadrupole and the quadrupole/octopole alignment have reduced significance, yet other hypotheses remain possible as well (e.g. exotic physics). Our results also suggest that both of these anomalies may be due to the quadrupole alone. While the octopole planarity significance is reduced after inpainting and after ISW subtraction, however

Self-management support interventions for persons with chronic disease: an evidence-based analysis.

PubMed

Franek, J

2013-01-01

improvement in favour of CDSMP across all healthy behaviours, including aerobic exercise, cognitive symptom management, and communication with health care professionals (GRADE quality low).Self-efficacy: There was a small, statistically significant improvement in self-efficacy in favour of CDSMP (GRADE quality low).HEALTH CARE UTILIZATION OUTCOMES: There were no statistically significant differences between modalities with respect to visits with general practitioners, visits to the emergency department, days in hospital, or hospitalizations (GRADE quality very low).All results were measured over the short term (median 6 months of follow-up). Trials generally did not appropriately report data according to intention-to-treat principles. Results therefore reflect "available case analyses," including only those participants whose outcome status was recorded. For this reason, there is high uncertainty around point estimates. The Stanford CDSMP led to statistically significant, albeit clinically minimal, short-term improvements across a number of health status measures (including some measures of health-related quality of life), healthy behaviours, and self-efficacy compared to usual care. However, there was no evidence to suggest that the CDSMP improved health care utilization. More research is needed to explore longer-term outcomes, the impact of self-management on clinical outcomes, and to better identify responders and non-responders. Self-management support interventions are becoming more common as a structured way of helping patients learn to better manage their chronic disease. To assess the effects of these support interventions, we looked at the results of 10 studies involving a total of 6,074 people with various chronic diseases, such as arthritis and chronic pain, chronic respiratory diseases, depression, diabetes, heart disease, and stroke. Most trials focused on a program called the Stanford Chronic Disease Self-Management Program (CDSMP). When compared to usual care

[Between individuality and "evidence-based medicine"--the role of the general practitioner within the scope of disease management programs].

PubMed

Szecsenyi, Joachim; Schneider, Antonius

2003-06-01

In Germany, the change from the "traditional", experience-based general practitioner (GP) to the evidence-based practising co-ordinator may be accelerated by the introduction of disease management programmes. Here, we will discuss some tools that can help to meet this challenge. Also, a set of requirements will be defined that the health care system will have to provide in support of GPs. Maintaining the relationship between doctor and patient and also allowing for individual care on the basis of evidence-based medicine will remain a challenge.

Effects of Medicaid disease management programs on medical expenditures: Evidence from a natural experiment in Georgia.

PubMed

Kranker, Keith

2016-03-01

In recent decades, most states' Medicaid programs have introduced disease management programs for chronically ill beneficiaries. Interventions assist beneficiaries and their health care providers to appropriately manage chronic health condition(s) according to established clinical guidelines. Cost containment has been a key justification for the creation of these programs despite mixed evidence they actually save money. This study evaluates the effects of a disease management program in Georgia by exploiting a natural experiment that delayed the introduction of high-intensity services for several thousand beneficiaries. Expenditures for medical claims decreased an average of $89 per person per month for the high- and moderate-risk groups, but those savings were not large enough to offset the total costs of the program. Impacts varied by the intensity of interventions, over time, and across disease groups. Heterogeneous treatment effect analysis indicates that decreases in medical expenditures were largest at the most expensive tail of the distribution. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy.

PubMed

Byars, Sean G; Huang, Qin Qin; Gray, Lesley-Ann; Bakshi, Andrew; Ripatti, Samuli; Abraham, Gad; Stearns, Stephen C; Inouye, Michael

2017-06-01

Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

PubMed Central

Byars, Sean G.; Gray, Lesley-Ann; Ripatti, Samuli; Stearns, Stephen C.; Inouye, Michael

2017-01-01

Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD. PMID:28640878

Mobile phone text messaging interventions for HIV and other chronic diseases: an overview of systematic reviews and framework for evidence transfer.

PubMed

Mbuagbaw, Lawrence; Mursleen, Sara; Lytvyn, Lyubov; Smieja, Marek; Dolovich, Lisa; Thabane, Lehana

2015-01-22

Strong international commitment and the widespread use of antiretroviral therapy have led to higher longevity for people living with human immune deficiency virus (HIV). Text messaging interventions have been shown to improve health outcomes in people living with HIV. The objectives of this overview were to: map the state of the evidence of text messaging interventions, identify knowledge gaps, and develop a framework for the transfer of evidence to other chronic diseases. We conducted a systematic review of systematic reviews on text messaging interventions to improve health or health related outcomes. We conducted a comprehensive search of PubMed, EMBASE (Exerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science (WoS) and the Cochrane Library on the 17th April 2014. Screening, data extraction and assessment of methodological quality were done in duplicate. Our findings were used to develop a conceptual framework for transfer. Our search identified 135 potential systematic reviews of which nine were included, reporting on 37 source studies, conducted in 19 different countries. Seven of nine (77.7%) of these reviews were high quality. There was some evidence for text messaging as a tool to improve adherence to antiretroviral therapy. Text messages also improved attendance at appointments and behaviour change outcomes. The findings were inconclusive for self-management of illness, treatment of tuberculosis and communicating results of medical investigations. The geographical distribution of text messaging research was limited to specific regions of the world. Prominent knowledge gaps included the absence of data on long term outcomes, patient satisfaction, and economic evaluations. The included reviews also identified methodological limitations in many of the primary studies. Global evidence supports the use of text messaging as a tool to improve adherence to medication and attendance at scheduled

Ultrasonographic appearance of the major duodenal papilla in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease.

PubMed

Mortier, Jeremy R; Maddox, Thomas W; White, Gillian M; Blundell, Richard J; Monné, Josep M; Lillis, Susannah M

2016-06-01

OBJECTIVE To determine the ultrasonographic appearance of the major duodenal papilla (MDP) in dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease. ANIMALS 40 adult client-owned dogs examined because of conditions that did not include hepatobiliary, pancreatic, or gastrointestinal tract disease. PROCEDURES Ultrasonographic examination of the MDP was performed. Each MDP was measured in 3 planes. Intraobserver reliability of measurements was determined, and associations between MDP dimensions and characteristics of the dogs were investigated. Histologic examination of longitudinal sections of the MDP was performed for 1 dog to compare the ultrasonographic and histologic appearance. RESULTS The MDP appeared as a layered structure with a hyperechoic outer layer, hypoechoic middle layer, and hyperechoic inner layer that corresponded to the duodenal serosa, duodenal muscularis, and duodenal submucosa, respectively. Layers visible during ultrasonographic examinations were consistent with layers identified histologically. Intraobserver reliability was substantial for each plane of measurement. Mean ± SD length, width, and height of the MDP were 15.2 ± 3.5 mm, 6.3 ± 1.6 mm, and 4.3 ± 1.0 mm, respectively. An increase in body weight of dogs was significantly associated with increased values for all measurements. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic appearance and approximate dimensions of the MDP of dogs without evidence of hepatobiliary, pancreatic, or gastrointestinal tract disease were determined. Additional studies are needed to evaluate possible ultrasonographic lesions of the MDP in dogs with hepatobiliary, pancreatic, or intestinal diseases and to investigate clinical implications of these lesions with regard to diagnosis and prognosis.

Bridging the gap between evidence and policy for infectious diseases: How models can aid public health decision-making.

PubMed

Knight, Gwenan M; Dharan, Nila J; Fox, Gregory J; Stennis, Natalie; Zwerling, Alice; Khurana, Renuka; Dowdy, David W

2016-01-01

The dominant approach to decision-making in public health policy for infectious diseases relies heavily on expert opinion, which often applies empirical evidence to policy questions in a manner that is neither systematic nor transparent. Although systematic reviews are frequently commissioned to inform specific components of policy (such as efficacy), the same process is rarely applied to the full decision-making process. Mathematical models provide a mechanism through which empirical evidence can be methodically and transparently integrated to address such questions. However, such models are often considered difficult to interpret. In addition, models provide estimates that need to be iteratively re-evaluated as new data or considerations arise. Using the case study of a novel diagnostic for tuberculosis, a framework for improved collaboration between public health decision-makers and mathematical modellers that could lead to more transparent and evidence-driven policy decisions for infectious diseases in the future is proposed. The framework proposes that policymakers should establish long-term collaborations with modellers to address key questions, and that modellers should strive to provide clear explanations of the uncertainty of model structure and outputs. Doing so will improve the applicability of models and clarify their limitations when used to inform real-world public health policy decisions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mast cells in airway diseases and interstitial lung disease.

PubMed

Cruse, Glenn; Bradding, Peter

2016-05-05

Mast cells are major effector cells of inflammation and there is strong evidence that mast cells play a significant role in asthma pathophysiology. There is also a growing body of evidence that mast cells contribute to other inflammatory and fibrotic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. This review discusses the role that mast cells play in airway diseases and highlights how mast cell microlocalisation within specific lung compartments and their cellular interactions are likely to be critical for their effector function in disease. Published by Elsevier B.V.

Enhancing the Capacity of Policy-Makers to Develop Evidence-Informed Policy Brief on Infectious Diseases of Poverty in Nigeria

PubMed Central

Uneke, Chigozie Jesse; Ezeoha, Abel Ebeh; Uro-Chukwu, Henry; Ezeonu, Chinonyelum Thecla; Ogbu, Ogbonnaya; Onwe, Friday; Edoga, Chima

2015-01-01

Background: The lack of effective use of research evidence in policy-making is a major challenge in most low- and middle-income countries (LMICs). There is need to package research data into effective policy tools that will help policy-makers to make evidence-informed policy regarding infectious diseases of poverty (IDP). The objective of this study was to assess the usefulness of training workshops and mentoring to enhance the capacity of Nigerian health policy-makers to develop evidence-informed policy brief on the control of IDP. Methods: A modified "before and after" intervention study design was used in which outcomes were measured on the target participants both before the intervention is implemented and after. A 4-point Likert scale according to the degree of adequacy; 1 = "grossly inadequate," 4 = "very adequate" was employed. The main parameter measured was participants’ perceptions of their own knowledge/understanding. This study was conducted at subnational level and the participants were the career health policy-makers drawn from Ebonyi State in the South-Eastern Nigeria. A one-day evidence-to-policy workshop was organized to enhance the participants’ capacity to develop evidence-informed policy brief on IDP in Ebonyi State. Topics covered included collaborative initiative; preparation and use of policy briefs; policy dialogue; ethics in health policy-making; and health policy and politics. Results: The preworkshop mean of knowledge and capacity ranged from 2.49-3.03, while the postworkshop mean ranged from 3.42–3.78 on 4-point scale. The percentage increase in mean of knowledge and capacity at the end of the workshop ranged from 20.10%–45%. Participants were divided into 3 IDP mentorship groups (malaria, schistosomiasis, lymphatic filariasis [LF]) and were mentored to identify potential policy options/recommendations for control of the diseases for the policy briefs. These policy options were subjected to research evidence synthesis by each

Enhancing the Capacity of Policy-Makers to Develop Evidence-Informed Policy Brief on Infectious Diseases of Poverty in Nigeria.

PubMed

Uneke, Chigozie Jesse; Ezeoha, Abel Ebeh; Uro-Chukwu, Henry; Ezeonu, Chinonyelum Thecla; Ogbu, Ogbonnaya; Onwe, Friday; Edoga, Chima

2015-05-20

The lack of effective use of research evidence in policy-making is a major challenge in most low- and middle-income countries (LMICs). There is need to package research data into effective policy tools that will help policy-makers to make evidence-informed policy regarding infectious diseases of poverty (IDP). The objective of this study was to assess the usefulness of training workshops and mentoring to enhance the capacity of Nigerian health policy-makers to develop evidence-informed policy brief on the control of IDP. A modified "before and after" intervention study design was used in which outcomes were measured on the target participants both before the intervention is implemented and after. A 4-point Likert scale according to the degree of adequacy; 1 = "grossly inadequate," 4 = "very adequate" was employed. The main parameter measured was participants' perceptions of their own knowledge/understanding. This study was conducted at subnational level and the participants were the career health policy-makers drawn from Ebonyi State in the South-Eastern Nigeria. A one-day evidence-to-policy workshop was organized to enhance the participants' capacity to develop evidence-informed policy brief on IDP in Ebonyi State. Topics covered included collaborative initiative; preparation and use of policy briefs; policy dialogue; ethics in health policy-making; and health policy and politics. The preworkshop mean of knowledge and capacity ranged from 2.49-3.03, while the postworkshop mean ranged from 3.42-3.78 on 4-point scale. The percentage increase in mean of knowledge and capacity at the end of the workshop ranged from 20.10%-45%. Participants were divided into 3 IDP mentorship groups (malaria, schistosomiasis, lymphatic filariasis [LF]) and were mentored to identify potential policy options/recommendations for control of the diseases for the policy briefs. These policy options were subjected to research evidence synthesis by each group to identify the options that have

Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2015.

PubMed

Iwakiri, Katsuhiko; Kinoshita, Yoshikazu; Habu, Yasuki; Oshima, Tadayuki; Manabe, Noriaki; Fujiwara, Yasuhiro; Nagahara, Akihito; Kawamura, Osamu; Iwakiri, Ryuichi; Ozawa, Soji; Ashida, Kiyoshi; Ohara, Shuichi; Kashiwagi, Hideyuki; Adachi, Kyoichi; Higuchi, Kazuhide; Miwa, Hiroto; Fujimoto, Kazuma; Kusano, Motoyasu; Hoshihara, Yoshio; Kawano, Tatsuyuki; Haruma, Ken; Hongo, Michio; Sugano, Kentaro; Watanabe, Mamoru; Shimosegawa, Tooru

2016-08-01

As an increase in gastroesophageal reflux disease (GERD) has been reported in Japan, and public interest in GERD has been increasing, the Japanese Society of Gastroenterology published the Evidence-based Clinical Practice Guidelines for GERD (1st edition) in 2009. Six years have passed since its publication, and there have been a large number of reports in Japan concerning the epidemiology, pathophysiology, treatment, and Barrett's esophagus during this period. By incorporating the contents of these reports, the guidelines were completely revised, and a new edition was published in October 2015. The revised edition consists of eight items: epidemiology, pathophysiology, diagnosis, internal treatment, surgical treatment, esophagitis after surgery of the upper gastrointestinal tract, extraesophageal symptoms, and Barrett's esophagus. This paper summarizes these guidelines, particularly the parts related to the treatment for GERD. In the present revision, aggressive proton pump inhibitor (PPI) maintenance therapy is recommended for severe erosive GERD, and on-demand therapy or continuous maintenance therapy is recommended for mild erosive GERD or PPI-responsive non-erosive GERD. Moreover, PPI-resistant GERD (insufficient symptomatic improvement and/or esophageal mucosal break persisting despite the administration of PPI at a standard dose for 8 weeks) is defined, and a standard-dose PPI twice a day, change in PPI, change in the PPI timing of dosing, addition of a prokinetic drug, addition of rikkunshito (traditional Japanese herbal medicine), and addition of histamine H2-receptor antagonist are recommended for its treatment. If no improvement is observed even after these treatments, pathophysiological evaluation with esophageal impedance-pH monitoring or esophageal manometry at an expert facility for diseases of the esophagus is recommended.

Omega-3 fatty acids and cardiovascular disease: summary of the 2016 agency of healthcare research and quality evidence review

USDA-ARS?s Scientific Manuscript database

We summarize the 2016 update of the 2004 Agency of Healthcare Research and Quality's evidence review of omega-3 fatty acids and cardiovascular disease (CVD). The overall findings for the effects of marine oil supplements on intermediate CVD outcomes remain largely unchanged. There is high strength o...

Prevalence of Chagas heart disease in a region endemic for Trypanosoma cruzi: evidence from a central Bolivian community.

PubMed

Yager, Jessica E; Lozano Beltran, Daniel F; Torrico, Faustino; Gilman, Robert H; Bern, Caryn

2015-09-01

Though the incidence of new Trypanosoma cruzi infections has decreased significantly in endemic regions in the Americas, medical professionals continue to encounter a high burden of resulting Chagas disease among infected adults. The current prevalence of Chagas heart disease in a community setting is not known; nor is it known how recent insecticide vector control measures may have impacted the progression of cardiac disease in an infected population. We sought to determine the current prevalence of T. cruzi infection and associated Chagas heart disease in a Bolivian community endemic for T. cruzi. Nested within a community serosurvey in rural and periurban communities in central Bolivia, we performed a cross-sectional cardiac substudy to evaluate adults for historical, clinical, and electrocardiographic evidence of cardiac disease. All adults between the ages of 20 and 60 years old with T. cruzi infection and those with a clinical history, physical exam, or electrocardiogram consistent with cardiac abnormalities were also scheduled for echocardiography. Of the 604 cardiac substudy participants with definitive serology results, 183 were seropositive for infection with T. cruzi (30.3%). Participants who were seropositive for T. cruzi infection were more likely to have conduction system defects (1.6% vs. 0% for complete right bundle branch block and 10.4% vs. 1.9% for any bundle branch block; p = 0.008 and p < 0.001, respectively). However, there was no statistically significant difference in the prevalence of bradycardia among seropositive versus seronegative participants. Echocardiogram findings were not consistent with a high burden of Chagas cardiomyopathy: valvulopathies were the most common abnormality, and few participants were found to have low ejection fraction or left ventricular dilatation. No participants had significant heart failure. Though almost one-third of adults in the community were seropositive for T. cruzi infection, few had evidence of

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes.

PubMed

Ross, Kenneth Andrew

2011-02-03

During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study.

Dietary (Poly)phenolics in Human Health: Structures, Bioavailability, and Evidence of Protective Effects Against Chronic Diseases

PubMed Central

Del Rio, Daniele; Rodriguez-Mateos, Ana; Spencer, Jeremy P.E.; Tognolini, Massimiliano; Borges, Gina

2013-01-01

Abstract Human intervention trials have provided evidence for protective effects of various (poly)phenol-rich foods against chronic disease, including cardiovascular disease, neurodegeneration, and cancer. While there are considerable data suggesting benefits of (poly)phenol intake, conclusions regarding their preventive potential remain unresolved due to several limitations in existing studies. Bioactivity investigations using cell lines have made an extensive use of both (poly)phenolic aglycones and sugar conjugates, these being the typical forms that exist in planta, at concentrations in the low-μM-to-mM range. However, after ingestion, dietary (poly)phenolics appear in the circulatory system not as the parent compounds, but as phase II metabolites, and their presence in plasma after dietary intake rarely exceeds nM concentrations. Substantial quantities of both the parent compounds and their metabolites pass to the colon where they are degraded by the action of the local microbiota, giving rise principally to small phenolic acid and aromatic catabolites that are absorbed into the circulatory system. This comprehensive review describes the different groups of compounds that have been reported to be involved in human nutrition, their fate in the body as they pass through the gastrointestinal tract and are absorbed into the circulatory system, the evidence of their impact on human chronic diseases, and the possible mechanisms of action through which (poly)phenol metabolites and catabolites may exert these protective actions. It is concluded that better performed in vivo intervention and in vitro mechanistic studies are needed to fully understand how these molecules interact with human physiological and pathological processes. Antioxid. Redox Signal. 18, 1818–1892. PMID:22794138

Treatment inferred disease severity in Crohn's disease: evidence for a European gradient of disease course.

PubMed

Wolters, Frank L; Joling, Catelijne; Russel, Maurice G; Sijbrandij, Jildou; De Bruin, Marion; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Bodini, Paolo; Ryan, Barbara; O'Morain, Colm; Mouzas, Ioannis A; Tsianos, Epameinondas; Vermeire, Severine; Monteiro, Estela; Limonard, Charles; Vatn, Morten; Fornaciari, Giovanni; Rodriguez, Dolores; Groot, Wim; Moum, Bjørn; Stockbrügger, Reinhold W

2007-03-01

Geographic differences in disease course of Crohn's disease (CD) might possibly be related to differences in genetic and environmental factors encountered in different parts of the world. The aim of this study was to assess differences in treatment regimens within a European cohort of CD patients as a reflection of disease course, and to identify associated phenotypic risk factors at diagnosis. A prospective European population-based inception cohort of 380 CD patients was studied. The patients were classified for phenotype according to the Vienna classification. Differences between Northern and Southern European centres in treatment over the first 10 years of disease were analysed using a competing risks survival analysis method. Patients in the North were more likely to have had surgery (p<0.01), whereas patients in the South were more likely to have been treated medically (p<0.01). Phenotype at diagnosis was not predictive of differences in treatment regimens between North and South. In this study, a difference in management of CD was observed between Northern and Southern European centres. This suggests that there may be a North-South disease severity gradient across Europe. Phenotypic differences between patients in the North and South did not explain this observed difference.

Evidence basis for integrated management of mineral metabolism in patients with end-stage renal disease.

PubMed

Scialla, Julia J

2018-07-01

Treatment of mineral metabolism is a mainstay of dialysis care including some of its most widely used and costly pharmaceuticals. Although many mineral metabolites are associated with increased risk of mortality, cardiovascular disease, and other morbidities, few clinical trials are available to guide therapy and most focus on single drug approaches. In practice, providers manage many aspects of mineral metabolism simultaneously in integrated treatment approaches that incorporate multiple agents and changes in the dialysis prescription. The present review discusses the rationale and existing evidence for evaluating integrated, as opposed to single drug, approaches in mineral metabolism. Drugs used to treat mineral metabolism have numerous, and sometimes, opposing effects on biochemical risk factors, such as fibroblast growth factor 23 (FGF23), calcium, and phosphorus. Although vitamin D sterols raise these risk markers when lowering parathyroid hormone (PTH), calcimimetics lower them. Trials demonstrate that combined approaches best 'normalize' the mineral metabolism axis in end-stage renal disease (ESRD). Observations embedded within major trials of calcimimetics reveal that adjustment of calcium-based binders and dialysate calcium is a common approach to adverse effects of these drugs with some initial, but inconclusive, evidence that these co-interventions may impact outcomes. The multiple, and often opposing, biochemical effects of many mineral metabolism drugs provides a strong rationale for studying integrated management strategies that consider combinations of drugs and co-interventions as a whole. This remains a current gap in the field with opportunities for clinical trials.

Interpreting genetics in the context of eating disorders: evidence of disease, not diversity.

PubMed

Easter, Michele

2014-07-01

How is genetic involvement interpreted for disorders whose medicalisation is contested? Framing psychiatric and behavioural disorders in terms of genetics is expected to make them seem more medical. Yet a genetic aetiology can also be used to frame behaviour as acceptable human variation, rather than a medical problem (for example, sexual orientation). I analyse responses to the idea that there is a genetic component in anorexia and bulimia nervosa (AN or BN) via semi-structured interviews with a sample of 50 women diagnosed with an eating disorder (25 had recovered). All but three volunteered that genetics would medicalise AN or BN by (i) making eating disorders seem more like 'real diseases'; implying that these disorders need (ii) professional treatment or (iii) a biologically based treatment. The results also indicate there are several counter-logics by which genetic framing could support non-medical definitions of AN or BN. I argue that genetic framing reduces perceived individual responsibility, which can support definitions of behaviour as either a reflection of disease (which entails intervention) or a reflection of normal human diversity (which does not). In the context of public scepticism as to the 'reality' of AN or BN, genetic involvement was taken as evidence of disease in ongoing negotiations about the medical and moral status of people with eating disorders. © 2013 The Author. Sociology of Health & Illness © 2013 Foundation for the Sociology of Health & Illness/John Wiley & Sons Ltd.

Bioresorbable Scaffolds: Current Evidences in the Treatment of Coronary Artery Disease

PubMed Central

2016-01-01

Percutaneous coronary revascularization strategies have gradually progressed over a period of last few decades. The advent of newer generation drug-eluting stents has significantly improved the outcomes of Percutaneous Coronary Intervention (PCI) by substantially reducing in-stent restenosis and stent thrombosis. However, vascular inflammation, restenosis, thrombosis, and neoatherosclerosis due to the permanent presence of a metallic foreign body within the artery limit their usage in complex Coronary Artery Disease (CAD). Bioresorbable Scaffolds (BRS) represent a novel approach in coronary stent technology. Complete resorption of the scaffold liberates the treated vessel from its cage and restores pulsatility, cyclical strain, physiological shear stress, and mechanotransduction. In this review article, we describe the advances in this rapidly evolving technology, present the evidence from the pre-clinical and clinical evaluation of these devices, and provide an overview of the ongoing clinical trials that were designed to examine the effectiveness of BRS in the clinical setting. PMID:27891384

Evidence of trem2 variant associated with triple risk of Alzheimer's disease.

PubMed

Abduljaleel, Zainularifeen; Al-Allaf, Faisal A; Khan, Wajahatullah; Athar, Mohammad; Shahzad, Naiyer; Taher, Mohiuddin M; Elrobh, Mohamed; Alanazi, Mohammed S; El-Huneidi, Waseem

2014-01-01

Alzheimer's disease is one of the main causes of dementia among elderly individuals and leads to the neurodegeneration of different areas of the brain, resulting in memory impairments and loss of cognitive functions. Recently, a rare variant that is associated with 3-fold higher risk of Alzheimer's disease onset has been found. The rare variant discovered is a missense mutation in the loop region of exon 2 of Trem2 (rs75932628-T, Arg47His). The aim of this study was to investigate the evidence for potential structural and functional significance of Trem2 gene variant (Arg47His) through molecular dynamics simulations. Our results showed the alteration caused due to the variant in TREM2 protein has significant effect on the ligand binding affinity as well as structural configuration. Based on molecular dynamics (MD) simulation under salvation, the results confirmed that native form of the variant (Arg47His) might be responsible for improved compactness, hence thereby improved protein folding. Protein simulation was carried out at different temperatures. At 300K, the deviation of the theoretical model of TREM2 protein increased from 2.0 Å at 10 ns. In contrast, the deviation of the Arg47His mutation was maintained at 1.2 Å until the end of the simulation (t = 10 ns), which indicated that Arg47His had reached its folded state. The mutant residue was a highly conserved region and was similar to "immunoglobulin V-set" and "immunoglobulin-like folds". Taken together, the result from this study provides a biophysical insight on how the studied variant could contribute to the genetic susceptibility to Alzheimer's disease.

Evidence that disease-induced population decline changes genetic structure and alters dispersal patterns in the Tasmanian devil

PubMed Central

Lachish, S; Miller, K J; Storfer, A; Goldizen, A W; Jones, M E

2011-01-01

Infectious disease has been shown to be a major cause of population declines in wild animals. However, there remains little empirical evidence on the genetic consequences of disease-mediated population declines, or how such perturbations might affect demographic processes such as dispersal. Devil facial tumour disease (DFTD) has resulted in the rapid decline of the Tasmanian devil, Sarcophilus harrisii, and threatens to cause extinction. Using 10 microsatellite DNA markers, we compared genetic diversity and structure before and after DFTD outbreaks in three Tasmanian devil populations to assess the genetic consequences of disease-induced population decline. We also used both genetic and demographic data to investigate dispersal patterns in Tasmanian devils along the east coast of Tasmania. We observed a significant increase in inbreeding (FIS pre/post-disease −0.030/0.012, P<0.05; relatedness pre/post-disease 0.011/0.038, P=0.06) in devil populations after just 2–3 generations of disease arrival, but no detectable change in genetic diversity. Furthermore, although there was no subdivision apparent among pre-disease populations (θ=0.005, 95% confidence interval (CI) −0.003 to 0.017), we found significant genetic differentiation among populations post-disease (θ=0.020, 0.010–0.027), apparently driven by a combination of selection and altered dispersal patterns of females in disease-affected populations. We also show that dispersal is male-biased in devils and that dispersal distances follow a typical leptokurtic distribution. Our results show that disease can result in genetic and demographic changes in host populations over few generations and short time scales. Ongoing management of Tasmanian devils must now attempt to maintain genetic variability in this species through actions designed to reverse the detrimental effects of inbreeding and subdivision in disease-affected populations. PMID:20216571

Caring for patients with kidney disease: shifting the paradigm from evidence-based medicine to patient-centered care

PubMed Central

O'Hare, Ann M.; Rodriguez, Rudolph A.; Bowling, Christopher Barrett

2016-01-01

The last several decades have witnessed the emergence of evidence-based medicine as the dominant paradigm for medical teaching, research and practice. Under an evidence-based approach, populations rather than individuals become the primary focus of investigation. Treatment priorities are largely shaped by the availability, relevance and quality of evidence and study outcomes and results are assumed to have more or less universal significance based on their implications at the population level. However, population-level treatment goals do not always align with what matters the most to individual patients—who may weigh the risks, benefits and harms of recommended treatments quite differently. In this article we describe the rise of evidence-based medicine in historical context. We discuss limitations of this approach for supporting real-world treatment decisions—especially in older adults with confluent comorbidity, functional impairment and/or limited life expectancy—and we describe the emergence of more patient-centered paradigms to address these limitations. We explain how the principles of evidence-based medicine have helped to shape contemporary approaches to defining, classifying and managing patients with chronic kidney disease. We discuss the limitations of this approach and the potential value of a more patient-centered paradigm, with a particular focus on the care of older adults with this condition. We conclude by outlining ways in which the evidence-base might be reconfigured to better support real-world treatment decisions in individual patients and summarize relevant ongoing initiatives. PMID:25637639

Limited evidence of abnormal intra-colonic pressure profiles in diverticular disease - a systematic review.

PubMed

Jaung, R; Robertson, J; O'Grady, G; Milne, T; Rowbotham, D; Bissett, I P

2017-06-01

Abnormal colonic pressure profiles and high intraluminal pressures are postulated to contribute to the formation of sigmoid colon diverticulosis and the pathophysiology of diverticular disease. This study aimed to review evidence for abnormal colonic pressure profiles in diverticulosis. All published studies investigating colonic pressure in patients with diverticulosis were searched in three databases (Medline, Embase, Scopus). No language restrictions were applied. Any manometry studies in which patients with diverticulosis were compared with controls were included. The Newcastle-Ottawa Quality Assessment Scale (NOS) for case-control studies was used as a measure of risk of bias. A cut-off of five or more points on the NOS (fair quality in terms of risk of bias) was chosen for inclusion in the meta-analysis. Ten studies (published 1962-2005) met the inclusion criteria. The studies followed a wide variety of protocols and all used low-resolution manometry (sensor spacing range 7.5-15 cm). Six studies compared intra-sigmoid pressure, with five of six showing higher pressure in diverticulosis vs controls, but only two reached statistical significance. A meta-analysis was not performed as only two studies were above the cut-off and these did not have comparable outcomes. This systematic review of manometry data shows that evidence for abnormal pressure in the sigmoid colon in patients with diverticulosis is weak. Existing studies utilized inconsistent methodology, showed heterogeneous results and are of limited quality. Higher quality studies using modern manometric techniques and standardized reporting methods are needed to clarify the role of colonic pressure in diverticulosis. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Brain dopamine neurone 'damage': methamphetamine users vs. Parkinson's disease - a critical assessment of the evidence.

PubMed

Kish, Stephen J; Boileau, Isabelle; Callaghan, Russell C; Tong, Junchao

2017-01-01

The objective of this review is to evaluate the evidence that recreational methamphetamine exposure might damage dopamine neurones in human brain, as predicted by experimental animal findings. Brain dopamine marker data in methamphetamine users can now be compared with those in Parkinson's disease, for which the Oleh Hornykiewicz discovery in Vienna of a brain dopamine deficiency is established. Whereas all examined striatal (caudate and putamen) dopamine neuronal markers are decreased in Parkinson's disease, levels of only some (dopamine, dopamine transporter) but not others (dopamine metabolites, synthetic enzymes, vesicular monoamine transporter 2) are below normal in methamphetamine users. This suggests that loss of dopamine neurones might not be characteristic of methamphetamine exposure in at least some human drug users. In methamphetamine users, dopamine loss was more marked in caudate than in putamen, whereas in Parkinson's disease, the putamen is distinctly more affected. Substantia nigra loss of dopamine-containing cell bodies is characteristic of Parkinson's disease, but similar neuropathological studies have yet to be conducted in methamphetamine users. Similarly, it is uncertain whether brain gliosis, a common feature of brain damage, occurs after methamphetamine exposure in humans. Preliminary epidemiological findings suggest that methamphetamine use might increase risk of subsequent development of Parkinson's disease. We conclude that the available literature is insufficient to indicate that recreational methamphetamine exposure likely causes loss of dopamine neurones in humans but does suggest presence of a striatal dopamine deficiency that, in principle, could be corrected by dopamine substitution medication if safety and subject selection considerations can be resolved. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The Community Connection Model: implementation of best evidence into practice for self-management of chronic diseases.

PubMed

Liddy, C; Johnston, S; Irving, H; Nash, K

2013-06-01

With chronic diseases becoming an increasing burden for healthcare systems worldwide, self-management support has gained traction in many health regions and organizations. However, the real-world application of the findings from clinical trials into actual community programming is not self-evident. The aim of this study was to present a model of programme implementation, namely the Community Connection Model. The process of implementing a chronic disease self-management programme has been documented in detail from its initial inception through to a sustainable programme. This account includes a description of the strategic activities undertaken (e.g. alignment with local policy and the formation of community partnerships) and the specific steps taken on the path to programme implementation (e.g. a scoping literature review, an environmental scan and a pilot programme with an evaluation component). Reflection on this case example suggests that a cognizance of the interactions between policy, partnership, planning and programme could act as a useful tool to guide programme implementation, evaluation and sustainability. Multiple types of self-management support have been implemented (as part of the Living Health Champlain programme), and are being evaluated and adapted in response to new evidence, shifting priorities and direction from more partners. The widespread access means that self-management support programmes are becoming part of the culture of care in the study region. Establishing a connection around an important health problem, ensuring active partnerships, adequate planning and early implementation of a programme grounded on the principles of applying best-available evidence can lead to successful solutions. The Community Connection Model is proposed as a way of conceptualizing these processes. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Appraising the evidence for public health policy components using the quality and impact of component evidence assessment.

PubMed

Barbero, Colleen; Gilchrist, Siobhan; Schooley, Michael W; Chriqui, Jamie F; Luke, Douglas A; Eyler, Amy A

2015-03-01

An essential strategy expected to reduce the global burden of chronic and cardiovascular disease is evidence-based policy. However, it is often unknown what specific components should constitute an evidence-based policy intervention. We have developed an expedient method to appraise and compare the strengths of the evidence bases suggesting that individual components of a policy intervention will contribute to the positive public health impact of that intervention. Using a new definition of "best available evidence," the Quality and Impact of Component (QuIC) Evidence Assessment analyzes dimensions of evidence quality and evidence of public health impact to categorize multiple policy component evidence bases along a continuum of "emerging," "promising impact," "promising quality," and "best." QuIC was recently applied to components from 2 policy interventions to prevent and improve the outcomes of cardiovascular disease: public-access defibrillation and community health workers. Results illustrate QuIC's utility in international policy practice and research. Copyright © 2015 World Heart Federation (Geneva). All rights reserved.

Evidence for somatic gene conversion and deletion in bipolar disorder, Crohn's disease, coronary artery disease, hypertension, rheumatoid arthritis, type-1 diabetes, and type-2 diabetes

PubMed Central

2011-01-01

Background During gene conversion, genetic information is transferred unidirectionally between highly homologous but non-allelic regions of DNA. While germ-line gene conversion has been implicated in the pathogenesis of some diseases, somatic gene conversion has remained technically difficult to investigate on a large scale. Methods A novel analysis technique is proposed for detecting the signature of somatic gene conversion from SNP microarray data. The Wellcome Trust Case Control Consortium has gathered SNP microarray data for two control populations and cohorts for bipolar disorder (BD), cardiovascular disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type-1 diabetes (T1D) and type-2 diabetes (T2D). Using the new analysis technique, the seven disease cohorts are analyzed to identify cohort-specific SNPs at which conversion is predicted. The quality of the predictions is assessed by identifying known disease associations for genes in the homologous duplicons, and comparing the frequency of such associations with background rates. Results Of 28 disease/locus pairs meeting stringent conditions, 22 show various degrees of disease association, compared with only 8 of 70 in a mock study designed to measure the background association rate (P < 10-9). Additional candidate genes are identified using less stringent filtering conditions. In some cases, somatic deletions appear likely. RA has a distinctive pattern of events relative to other diseases. Similarities in patterns are apparent between BD and HT. Conclusions The associations derived represent the first evidence that somatic gene conversion could be a significant causative factor in each of the seven diseases. The specific genes provide potential insights about disease mechanisms, and are strong candidates for further study. Please see Commentary: http://www.biomedcentral.com/1741-7015/9/13/abstract. PMID:21291537

Free radicals, antioxidants and eye diseases: evidence from epidemiological studies on cataract and age-related macular degeneration.

PubMed

Fletcher, A E

2010-01-01

Cataract and age-related macular degeneration (AMD) are the major causes of vision impairment and blindness worldwide. Both conditions are strongly age related with earlier signs (usually asymptomatic) occurring in middle age and becoming severer and more prevalent with increasing age. The aetiology of these conditions is thought to fit with the 'free radical theory' of ageing which postulates that ageing and age-related diseases result from the accumulation of cellular damage from reactive oxygen species (ROS). Mitochondrial energy production is a major source of endogenous ROS. External sources of ROS include environmental sources especially solar radiation, biomass fuels and tobacco smoking. There is strong evidence from epidemiological studies that smoking is a risk factor for both cataract and AMD. There is moderate evidence for an association with sunlight and cataract but weak evidence for sunlight and AMD. The few studies that have investigated this suggest an adverse effect of biomass fuels on cataract risk. The antioxidant defence system of the lens and retina include antioxidant vitamins C and E and the carotenoids lutein and zinc, and there is mixed evidence on their associations with cataract and AMD from epidemiological studies. Most epidemiological studies have been conducted in well-nourished western populations but evidence is now emerging from other populations with different dietary patterns and antioxidant levels. Copyright 2010 S. Karger AG, Basel.

Electroconvulsive therapy for depression in Parkinson's disease: systematic review of evidence and recommendations.

PubMed

Borisovskaya, Anna; Bryson, William Culbertson; Buchholz, Jonathan; Samii, Ali; Borson, Soo

2016-04-01

We performed a systematic review of evidence regarding treatment of depression in Parkinson's disease (PD) utilizing electroconvulsive therapy. The search led to the inclusion of 43 articles, mainly case reports or case series, with the largest number of patients totaling 19. The analysis included 116 patients with depression and PD; depression improved in 93.1%. Where motor symptoms' severity was reported, 83% of patients improved. Cognition did not worsen in the majority (94%). Many patients experienced delirium or transient confusion, sometimes necessitating discontinuation of electroconvulsive therapy (ECT). Little is known about maintenance ECT in this population. ECT can benefit patients suffering from PD and depression. We recommend an algorithm for treatment of depression in PD, utilizing ECT sooner rather than later.

Does evidence influence policy? Resource allocation and the Indigenous Burden of Disease study.

PubMed

Doran, Christopher M; Ling, Rod; Searles, Andrew; Hill, Peter

2016-01-01

Objective The Indigenous Burden of Disease (IBoD) report is the most comprehensive assessment of Indigenous disease burden in Australia. The aim of the present study was to investigate the potential effect of the IBoD report on Australian Indigenous health policy, service expenditure and research funding. Findings have significance for understanding factors that may influence Indigenous health policy. Methods The potential effect of the IBoD report was considered by: (1) conducting a text search of pertinent documents published by the federal government, Council of Australian Governments and the National Health and Medical Research Council of Australia (NHMRC) and observing the quantity and quality of references to IBoD; (2) examining data on government Indigenous healthcare expenditure for trends consistent with the findings and policy implications of the IBoD report; and (3) examining NHMRC Indigenous grant allocation trends consistent with the findings and policy implications of the IBoD report. Results Of 110 government and NHMRC documents found, IBoD was cited in 27. Immediately after publication of the IBoD report, federal and state governments increased Indigenous health spending (relative to non-Indigenous), notably for community health and public health at the state level. Expenditure on Indigenous hospital separations for chronic diseases also increased. These changes are broadly consistent with the findings of the IBoD report on the significance of chronic disease and the need to address certain risk factors. However, there is no evidence that such changes had a causal connection with the IBoD study. After publication of the IBoD report, changes in NHMRC Indigenous research funding showed little consistency with the findings of the IBoD report. Conclusions The present study found only indirect and inconsistent correlational evidence of the potential influence of the IBoD report on Indigenous health expenditure and research funding. Further assessment of

Disease Comorbidity Network Guides the Detection of Molecular Evidence for the Link Between Colorectal Cancer and Obesity.

PubMed

Chen, Yang; Li, Li; Xu, Rong

2015-01-01

Epidemiological studies suggested that obesity increases the risk of colorectal cancer (CRC). The genetic connection between CRC and obesity is multifactorial and inconclusive. In this study, we hypothesize that the study of shared comorbid diseases between CRC and obesity can offer unique insights into common genetic basis of these two diseases. We constructed a comorbidity network based on mining health data for millions of patients. We developed a novel approach and extracted the diseases that play critical roles in connecting obesity and CRC in the comorbidity network. Our approach was able to prioritize metabolic syndrome and diabetes, which are known to be associated with obesity and CRC through insulin resistance pathways. Interestingly, we found that osteoporosis was highly associated with the connection between obesity and CRC. Through gene expression meta-analysis, we identified novel genes shared among CRC, obesity and osteoporosis. Literature evidences support that these genes may contribute in explaining the genetic overlaps between obesity and CRC.

The Evidence for α-Linolenic Acid and Cardiovascular Disease Benefits: Comparisons with Eicosapentaenoic Acid and Docosahexaenoic Acid12

PubMed Central

Fleming, Jennifer A.; Kris-Etherton, Penny M.

2014-01-01

Our understanding of the cardiovascular disease (CVD) benefits of α-linolenic acid (ALA, 18:3n–3) has advanced markedly during the past decade. It is now evident that ALA benefits CVD risk. The expansion of the ALA evidence base has occurred in parallel with ongoing research on eicosapentaenoic acid (EPA, 20:5n–3) and docosahexaenoic acid (DHA, 22:6n–3) and CVD. The available evidence enables comparisons to be made for ALA vs. EPA + DHA for CVD risk reduction. The epidemiologic evidence suggests comparable benefits of plant-based and marine-derived n–3 (omega-3) PUFAs. The clinical trial evidence for ALA is not as extensive; however, there have been CVD event benefits reported. Those that have been reported for EPA + DHA are stronger because only EPA + DHA differed between the treatment and control groups, whereas in the ALA studies there were diet differences beyond ALA between the treatment and control groups. Despite this, the evidence suggests many comparable CVD benefits of ALA vs. EPA + DHA. Thus, we believe that it is time to revisit what the contemporary dietary recommendation should be for ALA to decrease the risk of CVD. Our perspective is that increasing dietary ALA will decrease CVD risk; however, randomized controlled clinical trials are necessary to confirm this and to determine what the recommendation should be. With a stronger evidence base, the nutrition community will be better positioned to revise the dietary recommendation for ALA for CVD risk reduction. PMID:25398754

Evidence that non-alcoholic fatty liver disease and polycystic ovary syndrome are associated by necessity rather than chance: a novel hepato-ovarian axis?

PubMed

Targher, Giovanni; Rossini, Maurizio; Lonardo, Amedeo

2016-02-01

Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are associated with obesity, insulin resistance, metabolic syndrome, cardiovascular disease, cirrhosis, and liver tumors. On these grounds, we have hypothesized that NAFLD and PCOS occur more frequently than expected by chance alone. We have tested this hypothesis by reviewing the clinical and biological evidence that supports a significant association between NAFLD and PCOS. PubMed was extensively searched for articles published through March 2015 using the keywords "nonalcoholic fatty liver disease" or "fatty liver" combined with "PCOS." Several cross-sectional and case-control studies have consistently demonstrated that the prevalence of NAFLD is remarkably increased in young women with PCOS, independent of overweight/obesity and other coexisting metabolic syndrome features, and that these women are more likely to have the more severe forms of NAFLD (non-alcoholic steatohepatitis, advanced fibrosis, and cirrhosis). Accumulating evidence suggests that NAFLD, especially its necro-inflammatory form, may exacerbate hepatic and systemic insulin resistance and releases multiple pro-inflammatory, pro-coagulant, and pro-fibrogenic mediators that may play important roles in the pathophysiology of PCOS. These findings call for more active and systematic search for NAFLD among women with PCOS. Conversely, gastroenterologists/hepatologists need to be aware of the presence of PCOS among female patients with NAFLD and compatible clinical features. Finally, all these patients should undergo regular follow-up not only for liver-related complications but also for cardio-metabolic diseases.

Effectiveness of Conservative, Surgical, and Postsurgical Interventions for Trigger Finger, Dupuytren Disease, and De Quervain Disease: A Systematic Review.

PubMed

Huisstede, Bionka M; Gladdines, Saskia; Randsdorp, Manon S; Koes, Bart W

2017-08-30

To provide an evidence-based overview of the effectiveness of conservative and (post)surgical interventions for trigger finger, Dupuytren disease, and De Quervain disease. Cochrane Library, Physiotherapy Evidence Database, PubMed, Embase, and CINAHL were searched to identify relevant systematic reviews and randomized controlled trials (RCTs). Two reviewers independently applied the inclusion criteria to select potential studies. Two reviewers independently extracted the data and assessed the methodologic quality. A best-evidence synthesis was performed to summarize the results. Two reviews (trigger finger and De Quervain disease) and 37 randomized controlled trials (RCTs) (trigger finger: n=8; Dupuytren disease: n=14, and De Quervain disease: n=15) were included. The trials reported on oral medication (Dupuytren disease), physiotherapy (De Quervain disease), injections and surgical treatment (trigger finger, Dupuytren disease, and De Quervain disease), and other conservative (De Qervain disease) and postsurgical treatment (Dupuytren disease). Moderate evidence was found for the effect of corticosteroid injection on the very short term for trigger finger, De Quervain disease, and for injections with collagenase (30d) when looking at all joints, and no evidence was found when looking at the PIP joint for Dupuytren disease. A thumb splint as additive to a corticosteroid injection seems to be effective (moderate evidence) for De Quervain disease (short term and midterm). For Dupuytren disease, use of a corticosteroid injection within a percutaneous needle aponeurotomy in the midterm and tamoxifen versus a placebo before or after a fasciectomy seems to promising (moderate evidence). We also found moderate evidence for splinting after Dupuytren surgery in the short term. In recent years, more and more RCTs have been conducted to study treatment of the aforementioned hand disorders. However, more high-quality RCTs are still needed to further stimulate evidence

Non-haemodynamic anti-anginal agents in the management of patients with stable coronary artery disease and diabetes: A review of the evidence.

PubMed

Ambrosio, Giuseppe; Tamargo, Juan; Grant, Peter J

2016-03-01

Patients with coronary artery disease and concomitant diabetes mellitus tend to have more extensive vessel disease than non-diabetes mellitus coronary artery disease patients, are at high risk of adverse cardiovascular events and suffer from a great anginal burden. Very few trials have specifically addressed the issue of optimal anti-anginal therapy in coronary artery disease patients who also have diabetes mellitus. Among 'classical' anti-anginal agents, recent guidelines do not specifically recommend any molecule over others; however, European Society of Cardiology guidelines acknowledge that favourable data in patients with concomitant diabetes mellitus and coronary artery disease are available for trimetazidine and ranolazine, two anti-anginal agents with a non-haemodynamic mechanism of action. The aim of this article is to review available evidence supporting the anti-anginal efficacy of these two drugs in the difficult-to-treat population of diabetes mellitus patients, including their effects on glycated haemoglobin (HbA1c), a measure of medium-term glycaemic control. Although direct head-to-head comparisons have not been performed, available evidence favours ranolazine as an effective anti-anginal agent over trimetazidine in this population. In addition, ranolazine lowers HbA1c, indicating that it may improve glycaemic control in patients with diabetes mellitus. Conversely, scanty data are available on the metabolic effects of trimetazidine in this cohort of patients. Thus, ranolazine may represent a valuable therapeutic option in stable coronary artery disease patients with diabetes mellitus. © The Author(s) 2015.

A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease.

PubMed

Mente, Andrew; de Koning, Lawrence; Shannon, Harry S; Anand, Sonia S

2009-04-13

Although a wealth of literature links dietary factors and coronary heart disease (CHD), the strength of the evidence supporting valid associations has not been evaluated systematically in a single investigation. We conducted a systematic search of MEDLINE for prospective cohort studies or randomized trials investigating dietary exposures in relation to CHD. We used the Bradford Hill guidelines to derive a causation score based on 4 criteria (strength, consistency, temporality, and coherence) for each dietary exposure in cohort studies and examined for consistency with the findings of randomized trials. Strong evidence supports valid associations (4 criteria satisfied) of protective factors, including intake of vegetables, nuts, and "Mediterranean" and high-quality dietary patterns with CHD, and associations of harmful factors, including intake of trans-fatty acids and foods with a high glycemic index or load. Among studies of higher methodologic quality, there was also strong evidence for monounsaturated fatty acids and "prudent" and "western" dietary patterns. Moderate evidence (3 criteria) of associations exists for intake of fish, marine omega-3 fatty acids, folate, whole grains, dietary vitamins E and C, beta carotene, alcohol, fruit, and fiber. Insufficient evidence (< or =2 criteria) of association is present for intake of supplementary vitamin E and ascorbic acid (vitamin C); saturated and polyunsaturated fatty acids; total fat; alpha-linolenic acid; meat; eggs; and milk. Among the dietary exposures with strong evidence of causation from cohort studies, only a Mediterranean dietary pattern is related to CHD in randomized trials. The evidence supports a valid association of a limited number of dietary factors and dietary patterns with CHD. Future evaluation of dietary patterns, including their nutrient and food components, in cohort studies and randomized trials is recommended.

Evidence for a membrane defect in Alzheimer disease brain

NASA Technical Reports Server (NTRS)

Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

1992-01-01

To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

Evidence-based decision-making in infectious diseases epidemiology, prevention and control: matching research questions to study designs and quality appraisal tools.

PubMed

Harder, Thomas; Takla, Anja; Rehfuess, Eva; Sánchez-Vivar, Alex; Matysiak-Klose, Dorothea; Eckmanns, Tim; Krause, Gérard; de Carvalho Gomes, Helena; Jansen, Andreas; Ellis, Simon; Forland, Frode; James, Roberta; Meerpohl, Joerg J; Morgan, Antony; Schünemann, Holger; Zuiderent-Jerak, Teun; Wichmann, Ole

2014-05-21

The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach. Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed. In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure. The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision-making in infectious disease epidemiology

Evidence-based decision-making in infectious diseases epidemiology, prevention and control: matching research questions to study designs and quality appraisal tools

PubMed Central

2014-01-01

Background The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach. Methods Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed. Results In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure. Conclusions The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision

Prevention and control of noncommunicable diseases through evidence-based public health: implementing the NCD 2020 action plan.

PubMed

Diem, Günter; Brownson, Ross C; Grabauskas, Vilius; Shatchkute, Aushra; Stachenko, Sylvie

2016-09-01

The control of noncommunicable diseases (NCDs) was addressed by the declaration of the 66th United Nations (UN) General Assembly followed by the World Health Organization's (WHO) NCD 2020 action plan. There is a clear need to better apply evidence in public health settings to tackle both behaviour-related factors and the underlying social and economic conditions. This article describes concepts of evidence-based public health (EBPH) and outlines a set of actions that are essential for successful global NCD prevention. The authors describe the importance of knowledge translation with the goal of increasing the effectiveness of public health services, relying on both quantitative and qualitative evidence. In particular, the role of capacity building is highlighted because it is fundamental to progress in controlling NCDs. Important challenges for capacity building include the need to bridge diverse disciplines, build the evidence base across countries and the lack of formal training in public health sciences. As brief case examples, several successful capacity-building efforts are highlighted to address challenges and further evidence-based decision making. The need for a more comprehensive public health approach, addressing social, environmental and cultural conditions, has led to government-wide and society-wide strategies that are now on the agenda due to efforts such as the WHO's NCD 2020 action plan and Health 2020: the European Policy for Health and Wellbeing. These efforts need research to generate evidence in new areas (e.g. equity and sustainability), training to build public health capacity and a continuous process of improvement and knowledge generation and translation. © The Author(s) 2015.

Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease.

PubMed

Goddard, Katrina A B; Olson, Jane M; Payami, Haydeh; van der Voet, Monique; Kuivaniemi, Helena; Tromp, Gerard

2004-06-01

Recently, we reported evidence of linkage on chromosome 20 for Alzheimer disease (AD) using a novel statistical approach to incorporate covariates (e.g., age, ApoE genotype) into the analysis. These results suggest that very elderly subjects (>85 years), and individuals who carry an epsilon2 allele at the ApoE locus are more likely to be linked to this candidate region. The region on chromosome 20 includes a strong candidate gene, cystatin C (CST3), which has previously been associated with AD in case-control studies. We investigated these findings further by genotyping additional markers to narrow the candidate region, and to identify evidence of linkage disequilibrium as additional support for a susceptibility locus on chromosome 20. We selected 43 elderly sibships (89 subjects) from the NIMH AD Genetics Initiative based on current age older than 84 years, and identified 129 unrelated control subjects who were older than 84 years from the Oregon Brain Aging Study to conduct linkage and association studies in this region. Fourteen additional markers were evaluated, including 4 markers located within or near CST3. We narrowed the candidate region on chromosome 20 to an 11.8-cM region between markers D20S174 and D20S471, which includes the CST3 candidate gene. In addition, we observed evidence of association for markers located near the CST3 candidate gene, with P values between 0.002 and 0.08 for two-locus haplotypes. These results support the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.

Evidence-based practice: management of glottic cancer.

PubMed

Hartl, Dana M

2012-10-01

The main issue in the management of glottic squamous cell carcinoma, as for all cancers, is adequate disease control while optimizing functional outcomes and minimizing morbidity. This is true for early-stage disease as for advanced tumors. This article evaluates the current evidence for the diagnostic and pretherapeutic workup for glottic squamous cell carcinoma and the evidence concerning different treatment options for glottic carcinoma, from early-stage to advanced-stage disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Underdetermination in evidence-based medicine.

PubMed

Chin-Yee, Benjamin H

2014-12-01

This article explores the philosophical implications of evidence-based medicine's (EBM's) epistemology in terms of the problem of underdetermination of theory by evidence as expounded by the Duhem-Quine thesis. EBM hierarchies of evidence privilege clinical research over basic science, exacerbating the problem of underdetermination. Because of severe underdetermination, EBM is unable to meaningfully test core medical beliefs that form the basis of our understanding of disease and therapeutics. As a result, EBM adopts an epistemic attitude that is sceptical of explanations from the basic biological sciences, and is relegated to a view of disease at a population level. EBM's epistemic attitude provides a limited research heuristic by preventing the development of a theoretical framework required for understanding disease mechanism and integrating knowledge to develop new therapies. Medical epistemology should remain pluralistic and include complementary approaches of basic science and clinical research, thus avoiding the limited epistemic attitude entailed by EBM hierarchies. © 2014 John Wiley & Sons, Ltd.

Coffee and Alzheimer’s disease - animal & cellular evidences

USDA-ARS?s Scientific Manuscript database

Increases in lifespan in modern times have put significant social and academic emphasis on age-related pathologies. Of the many chronic, non-acquired diseases, dementias are among the most fiscally and psychologically burdensome to society. Alzheimer’s disease (AD) is the most prevalent and well kno...

Trade-off between cancer and aging: What role do other diseases play? Evidence from experimental and human population studies

PubMed Central

Yashin, Anatoli I.; Ukraintseva, Svetlana V.; Akushevich, Igor V.; Arbeev, Konstantin G.; Kulminski, Alexander; Akushevich, Lucy

2009-01-01

The potential gain in life expectancy which could result from the complete elimination of mortality from cancer in the U.S. would not exceed 3 years if one were to consider cancer independently of other causes of death. In this paper, we review evidence of trade-offs between cancer and aging as well as between cancer and other diseases, which, if taken into account, may substantially increase estimates of gain in life expectancy resulting from cancer eradication. We also used the Multiple Causes of Death (MCD) data to evaluate correlations among mortalities from cancer and other major disorders including heart disease, stroke, diabetes, Alzheimer’s, Parkinson’s diseases, and asthma. Our analyses revealed significant negative correlations between cancer and other diseases suggesting stronger population effects of cancer eradication. Possible mechanisms of the observed dependencies and emerging perspectives of using dependent competing risks models for evaluating the effects of reduction of mortality from cancer on life expectancy are discussed. PMID:18452970

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management.

PubMed

Gomollón, Fernando; Dignass, Axel; Annese, Vito; Tilg, Herbert; Van Assche, Gert; Lindsay, James O; Peyrin-Biroulet, Laurent; Cullen, Garret J; Daperno, Marco; Kucharzik, Torsten; Rieder, Florian; Almer, Sven; Armuzzi, Alessandro; Harbord, Marcus; Langhorst, Jost; Sans, Miquel; Chowers, Yehuda; Fiorino, Gionata; Juillerat, Pascal; Mantzaris, Gerassimos J; Rizzello, Fernando; Vavricka, Stephan; Gionchetti, Paolo

2017-01-01

This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016]. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Lysosomal membrane permeabilization in cell death: new evidence and implications for health and disease.

PubMed

Serrano-Puebla, Ana; Boya, Patricia

2016-05-01

Recent studies have demonstrated that, in addition to their central role in cellular catabolic reactions, lysosomes are implicated in many cellular processes, including metabolism, membrane repair, and cell death. Lysosomal membrane permeabilization (LMP) has emerged as a pathway by which cell demise is regulated under physiological conditions and contributes to cell death in many pathological situations. Here, we review the latest evidence on LMP-mediated cell death, the upstream and downstream signals involved, and the role of LMP in the normal physiology of organisms. We also discuss the contributions of lysosomal damage and LMP to the pathogenic features of several disease states, such as lysosomal storage disorders and other neurodegenerative conditions. © 2015 New York Academy of Sciences.

Evidence of a major gene from Bayesian segregation analyses of liability to osteochondral diseases in pigs.

PubMed

Kadarmideen, Haja N; Janss, Luc L G

2005-11-01

Bayesian segregation analyses were used to investigate the mode of inheritance of osteochondral lesions (osteochondrosis, OC) in pigs. Data consisted of 1163 animals with OC and their pedigrees included 2891 animals. Mixed-inheritance threshold models (MITM) and several variants of MITM, in conjunction with Markov chain Monte Carlo methods, were developed for the analysis of these (categorical) data. Results showed major genes with significant and substantially higher variances (range 1.384-37.81), compared to the polygenic variance (sigmau2). Consequently, heritabilities for a mixed inheritance (range 0.65-0.90) were much higher than the heritabilities from the polygenes. Disease allele frequencies range was 0.38-0.88. Additional analyses estimating the transmission probabilities of the major gene showed clear evidence for Mendelian segregation of a major gene affecting osteochondrosis. The variants, MITM with informative prior on sigmau2, showed significant improvement in marginal distributions and accuracy of parameters. MITM with a "reduced polygenic model" for parameterization of polygenic effects avoided convergence problems and poor mixing encountered in an "individual polygenic model." In all cases, "shrinkage estimators" for fixed effects avoided unidentifiability for these parameters. The mixed-inheritance linear model (MILM) was also applied to all OC lesions and compared with the MITM. This is the first study to report evidence of major genes for osteochondral lesions in pigs; these results may also form a basis for underpinning the genetic inheritance of this disease in other animals as well as in humans.

Discovering disease-disease associations by fusing systems-level molecular data

PubMed Central

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-01-01

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion. PMID:24232732

Discovering disease-disease associations by fusing systems-level molecular data.

PubMed

Žitnik, Marinka; Janjić, Vuk; Larminie, Chris; Zupan, Blaž; Pržulj, Nataša

2013-11-15

The advent of genome-scale genetic and genomic studies allows new insight into disease classification. Recently, a shift was made from linking diseases simply based on their shared genes towards systems-level integration of molecular data. Here, we aim to find relationships between diseases based on evidence from fusing all available molecular interaction and ontology data. We propose a multi-level hierarchy of disease classes that significantly overlaps with existing disease classification. In it, we find 14 disease-disease associations currently not present in Disease Ontology and provide evidence for their relationships through comorbidity data and literature curation. Interestingly, even though the number of known human genetic interactions is currently very small, we find they are the most important predictor of a link between diseases. Finally, we show that omission of any one of the included data sources reduces prediction quality, further highlighting the importance in the paradigm shift towards systems-level data fusion.

An evidence-based update on vitamins.

PubMed

Orr, K Kelly; Hume, Anne L

2010-04-01

American adults take many types of vitamin supplements, despite limited evidence of their efficacy, especially in preventing chronic diseases such as cardiovascular disease and cancer. Supplements contain significant amounts of vitamins when consumed from multiple sources. Excess consumption of some vitamins may have detrimental health effects. Use of MMVM products appears to be safe; however, clinical outcomes have not been established. Although vitamin D and preconception folic acid may be appropriate for self care, a health care provider should monitor other vitamin supplements for disease prevention, such as niacin. Beyond supplementation as treatment for vitamin deficiencies, evidence is lacking.

Caring for patients with kidney disease: shifting the paradigm from evidence-based medicine to patient-centered care.

PubMed

O'Hare, Ann M; Rodriguez, Rudolph A; Bowling, Christopher Barrett

2016-03-01

The last several decades have witnessed the emergence of evidence-based medicine as the dominant paradigm for medical teaching, research and practice. Under an evidence-based approach, populations rather than individuals become the primary focus of investigation. Treatment priorities are largely shaped by the availability, relevance and quality of evidence and study outcomes and results are assumed to have more or less universal significance based on their implications at the population level. However, population-level treatment goals do not always align with what matters the most to individual patients-who may weigh the risks, benefits and harms of recommended treatments quite differently. In this article we describe the rise of evidence-based medicine in historical context. We discuss limitations of this approach for supporting real-world treatment decisions-especially in older adults with confluent comorbidity, functional impairment and/or limited life expectancy-and we describe the emergence of more patient-centered paradigms to address these limitations. We explain how the principles of evidence-based medicine have helped to shape contemporary approaches to defining, classifying and managing patients with chronic kidney disease. We discuss the limitations of this approach and the potential value of a more patient-centered paradigm, with a particular focus on the care of older adults with this condition. We conclude by outlining ways in which the evidence-base might be reconfigured to better support real-world treatment decisions in individual patients and summarize relevant ongoing initiatives. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Operationalizing Economics for Counterinsurgency and Stability Operations

DTIC Science & Technology

2009-05-01

as freedom, described by Amartya Sen provides an improved foundation for military operations and a more complete campaign framework. Within these...peacekeeping.7 Development described by Amartya Sen is based on a concept that promotes freedom, a cornerstone of democracy and U.S. national policy. The...poverty and disease promote state failure.19 The writings of Jeffery Sachs, Thomas Sowell, Paul Collier, Amartya Sen , the World Bank, and many others

Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

PubMed

Saito, Isao

2012-01-01

Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

Inflammatory bowel disease and airway diseases.

PubMed

Vutcovici, Maria; Brassard, Paul; Bitton, Alain

2016-09-14

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

Leptin dysfunction and Alzheimer’s disease: evidence from cellular, animal, and human studies

PubMed Central

McGuire, Matthew J.; Ishii, Makoto

2016-01-01

There is accumulating evidence from epidemiological studies that changes in body weight are associated with Alzheimer’s disease (AD) from mid-life obesity increasing the risk of developing AD to weight loss occurring at the earliest stages of AD. Therefore, factors that regulate body weight are likely to influence the development and progression of AD. The adipocyte-derived hormone leptin has emerged as a major regulator of body weight mainly by activating hypothalamic neural circuits. Leptin also has several pleotropic effects including regulating cognitive function and having neuroprotective effects, suggesting a potential link between leptin and AD. Here, we will examine the relationship between leptin and AD by reviewing the recent evidence from cellular and animal models to human studies. We present a model where leptin has a bidirectional role in AD. Not only can alterations in leptin levels and function worsen cognitive decline and progression of AD pathology, but AD pathology, in of itself, can disrupt leptin signaling, which together would lead to a downward spiral of progressive neurodegeneration and worsening body weight and systemic metabolic deficits. Collectively, these studies serve as a framework to highlight the importance of understanding the molecular mechanisms underlying the body weight and systemic metabolic deficits in AD, which has the potential to open new avenues that may ultimately lead to novel therapeutic targets and diagnostic tools. PMID:26993509

Scenarios, personas and user stories from design ethnography: Evidence-based design representations of communicable disease investigations

PubMed Central

Turner, Anne M; Reeder, Blaine; Ramey, Judith

2014-01-01

Purpose Despite years of effort and millions of dollars spent to create a unified electronic communicable disease reporting systems, the goal remains elusive. A major barrier has been a lack of understanding by system designers of communicable disease (CD) work and the public health workers who perform this work. This study reports on the application of User Center Design representations, traditionally used for improving interface design, to translate the complex CD work identified through ethnographic studies to guide designers and developers of CD systems. The purpose of this work is to: (1) better understand public health practitioners and their information workflow with respect to communicable disease (CD) monitoring and control at a local health department, and (2) to develop evidence-based design representations that model this CD work to inform the design of future disease surveillance systems. Methods We performed extensive onsite semi-structured interviews, targeted work shadowing and a focus group to characterize local health department communicable disease workflow. Informed by principles of design ethnography and user-centered design (UCD) we created persona, scenarios and user stories to accurately represent the user to system designers. Results We sought to convey to designers the key findings from ethnographic studies: 1) that public health CD work is mobile and episodic, in contrast to current CD reporting systems, which are stationary and fixed 2) health department efforts are focused on CD investigation and response rather than reporting and 3) current CD information systems must conform to PH workflow to ensure their usefulness. In an effort to illustrate our findings to designers, we developed three contemporary design-support representations: persona, scenario, and user story. Conclusions Through application of user centered design principles, we were able to create design representations that illustrate complex public health communicable

Management of Active Crohn Disease

PubMed Central

Cheifetz, Adam S.

2017-01-01

Importance Treatment of Crohn disease is rapidly evolving, with the induction of novel biologic therapies and newer, often more intensive treatment approaches. Knowing how to treat individual patients in this quickly changing milieu can be a challenge. Objective To review the diagnosis and management of moderate to severe Crohn disease, with a focus on newer treatments and goals of care. Evidence Review MEDLINE was searched from 2000 to 2011. Additional citations were procured from references of select research and review articles. Evidence was graded using the American Heart Association level-of-evidence guidelines. Results Although mesalamines are still often used to treat Crohn disease, the evidence for their efficacy is lacking. Corticosteroids can be effectively used to induce remission in moderate to severe Crohn disease, but they do not maintain remission. The mainstays of treatment are immunomodulators and biologics, particularly anti–tumor necrosis factor. Conclusion and Relevance Immunomodulators and biologics are now the preferred treatment options for Crohn disease. PMID:23695484

Jane Austen's lifelong health problems and final illness: New evidence points to a fatal Hodgkin's disease and excludes the widely accepted Addison's.

PubMed

Upfal, A

2005-06-01

Jane Austen is typically described as having excellent health until the age of 40 and the onset of a mysterious and fatal illness, initially identified by Sir Zachary Cope in 1964 as Addison's disease. Her biographers, deceived both by Cassandra Austen's destruction of letters containing medical detail, and the cheerful high spirits of the existing letters, have seriously underestimated the extent to which illness affected Austen's life. A medical history reveals that she was particularly susceptible to infection, and suffered unusually severe infective illnesses, as well as a chronic conjunctivitis that impeded her ability to write. There is evidence that Austen was already suffering from an immune deficiency and fatal lymphoma in January 1813, when her second and most popular novel, Pride and Prejudice, was published. Four more novels would follow, written or revised in the shadow of her increasing illness and debility. Whilst it is impossible now to conclusively establish the cause of her death, the existing medical evidence tends to exclude Addison's disease, and suggests there is a high possibility that Jane Austen's fatal illness was Hodgkin's disease, a form of lymphoma.

Evidence-based management of Kawasaki disease in the emergency department.

PubMed

Seaton, Kara K; Kharbanda, Anupam

2015-01-01

Kawasaki disease, also known as mucocutaneous lymph node syndrome, was first described in Japan in 1967. It is currently the leading cause of acquired heart disease in children in the United States. Untreated Kawasaki disease may lead to the formation of coronary artery aneurysms and sudden cardiac death in children. This vasculitis presents with fever for ≥ 5 days, plus a combination of key criteria. Because each of the symptoms commonly occurs in other childhood illnesses, the disease can be difficult to diagnose, especially in children who present with an incomplete form of the disease. At this time, the etiology of the disease remains unknown, and there is no single diagnostic test to confirm the diagnosis. This issue reviews the presentation, diagnostic criteria, and management of Kawasaki disease in the emergency department. Emergency clinicians should consider Kawasaki disease as a diagnosis in pediatric patients presenting with prolonged fever, as prompt evaluation and management can significantly decrease the risk of serious cardiac sequelae.

Economic evaluation of manual therapy for musculoskeletal diseases: a protocol for a systematic review and narrative synthesis of evidence.

PubMed

Kim, Chang-Gon; Mun, Su-Jeong; Kim, Ka-Na; Shin, Byung-Cheul; Kim, Nam-Kwen; Lee, Dong-Hyo; Lee, Jung-Han

2016-05-13

Manual therapy is the non-surgical conservative management of musculoskeletal disorders using the practitioner's hands on the patient's body for diagnosing and treating disease. The aim of this study is to systematically review trial-based economic evaluations of manual therapy relative to other interventions used for the management of musculoskeletal diseases. Randomised clinical trials (RCTs) on the economic evaluation of manual therapy for musculoskeletal diseases will be included in the review. The following databases will be searched from their inception: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Econlit, Mantis, Index to Chiropractic Literature, Science Citation Index, Social Science Citation Index, Allied and Complementary Medicine Database (AMED), Cochrane Database of Systematic Reviews (CDSR), National Health Service Database of Abstracts of Reviews of Effects (NHS DARE), National Health Service Health Technology Assessment Database (NHS HTA), National Health Service Economic Evaluation Database (NHS EED), CENTRAL, five Korean medical databases (Oriental Medicine Advanced Searching Integrated System (OASIS), Research Information Service System (RISS), DBPIA, Korean Traditional Knowledge Portal (KTKP) and KoreaMed) and three Chinese databases (China National Knowledge Infrastructure (CNKI), VIP and Wanfang). The evidence for the cost-effectiveness, cost-utility and cost-benefit of manual therapy for musculoskeletal diseases will be assessed as the primary outcome. Health-related quality of life and adverse effects will be assessed as secondary outcomes. We will critically appraise the included studies using the Cochrane risk of bias tool and the Drummond checklist. Results will be summarised using Slavin's qualitative best-evidence synthesis approach. The results of the study will be disseminated via a peer-reviewed journal and/or conference presentations

Evidence for Reverse Causality in the Association Between Blood Pressure and Cardiovascular Risk in Patients With Chronic Kidney Disease

PubMed Central

Herrington, William; Staplin, Natalie; Judge, Parminder K.; Mafham, Marion; Emberson, Jonathan; Haynes, Richard; Wheeler, David C.; Walker, Robert; Tomson, Charlie; Agodoa, Larry; Wiecek, Andrzej; Lewington, Sarah; Reith, Christina A.; Landray, Martin J.

2017-01-01

Among those with moderate-to-advanced chronic kidney disease, the relationship between blood pressure (BP) and cardiovascular disease seems U shaped but is loglinear in apparently healthy adults. The SHARP (Study of Heart and Renal Protection) randomized 9270 patients with chronic kidney disease to ezetimibe/simvastatin versus matching placebo and measured BP at each follow-up visit. Cox regression was used to assess the association between BP and risk of cardiovascular disease among (1) those with a self-reported history of cardiovascular disease and (2) those with no such history and, based on plasma troponin-I concentration, a low probability of subclinical cardiac disease. A total of 8666 participants had a valid baseline BP and troponin-I measurement, and 2188 had at least 1 cardiovascular event during follow-up. After adjustment for relevant confounders, the association between systolic BP and cardiovascular events was U shaped, but among participants without evidence of previous cardiovascular disease, there was a positive loglinear association throughout the range of values studied. Among those with the lowest probability of subclinical cardiac disease, each 10 mm Hg higher systolic BP corresponded to a 27% increased risk of cardiovascular disease (hazard ratio, 1.27; 95% confidence interval, 1.11–1.44). In contrast, the relationship between diastolic BP and cardiovascular risk remained U shaped irrespective of cardiovascular disease history or risk of subclinical disease. In conclusion, the lack of a clear association between systolic BP and cardiovascular risk in this population seems attributable to confounding, suggesting that more intensive systolic BP reduction may be beneficial in such patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00125593. PMID:28028192

Mondor's disease of penis: a forgotten disease.

PubMed

Kumar, B; Narang, T; Radotra, B D; Gupta, S

2005-12-01

Mondor's disease of penis is an uncommon genital condition involving the penile sulcus in a circumferential manner. Although this disorder is almost always self limited, it is associated with considerable psychological stress and sexual disharmony. All patients attending the sexually transmitted disease clinic during 1991-2003 were examined for evidence of Mondor's disease of penis. Detailed history and clinical findings were recorded in a specially designed proforma. Histopathological examination and staining with CD31 and CD34 monoclonal antibodies was also done in 11 patients. 18 out of 1296 patients attending the sexually transmitted diseases (STD) clinic during the study period were found to have penile Mondor's disease, giving an incidence of 1.39%. 17 patients had history of one or more episodes of STDs. Histopathological specimens showed prominent vessels with plump endothelial cells and thickened blood vessel walls. The occasional vessel showed complete occlusion of its lumen. In our study we did not find any evidence of lymphatic involvement. Non-lymphatic vessels, mainly veins, were predominantly involved. In our opinion Mondor's phlebitis of penis or Mondor's disease of penis are better terms to describe the condition rather than non-venereal sclerosing lymphangitis.

Changing CHANGE: adaptations of an evidence-based telehealth cardiovascular disease risk reduction intervention.

PubMed

Zullig, Leah L; McCant, Felicia; Silberberg, Mina; Johnson, Fred; Granger, Bradi B; Bosworth, Hayden B

2018-03-01

Relatively few successful medication adherence interventions are translated into real-world clinical settings. The Prevention of Cardiovascular Outcomes in African Americans with Diabetes (CHANGE) intervention was originally conceived as a randomized controlled trial to improve cardiovascular disease-related medication adherence and health outcomes. The purpose of the study was to describe the translation of the CHANGE trial into two community-based clinical programs. CHANGE 2 was available to Medicaid patients with diabetes and hypertension whose primary care homes were part of a care management network in the Northern Piedmont region of North Carolina. CHANGE 3 was available to low-income patients receiving care in three geographical areas with multiple chronic conditions at low or moderate risk for developing cardiovascular disease. Adaptations were made to ensure fit with available organizational resources and the patient population's health needs. Data available for evaluation are presented. For CHANGE 2, we evaluated improvement in A1c control using paired t test. For both studies, we describe feasibility measured by percentage of patients who completed the curriculum. CHANGE 2 involved 125 participants. CHANGE 3 had 127 participants. In CHANGE 2, 69 participants had A1c measurements at baseline and 12-month follow-up; A1c improved from 8.4 to 7.8 (p = .008). In CHANGE 3, interventionists completed 47% (n = 45) of calls to enroll participants at the 4-month encounter, and among those eligible for a 12-month call (n = 52), 21% of 12-month calls were completed with participants. In CHANGE 2, 40% of participants (n = 50) completed all 12 encounters. Thoughtful adaptation is critical to translate clinical trials into community-based clinic settings. Successful implementation of adapted evidence-based interventions may be feasible and can positively affect patients' disease control.

The role of phospholipid oxidation products in inflammatory and autoimmune diseases: evidence from animal models and in humans.

PubMed

Leitinger, Norbert

2008-01-01

Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues.A central role for OxPL in disease states associated with dyslipedemia, including atherosclerosis, diabetes and its complications, metabolic syndrome, and renal insufficiency, as well as general prothrombotic states, has been proposed. In addition, in organs which are constantly exposed to oxidative stress, including lung, skin, and eyes, increased levels of OxPL are suggested to contribute to inflammatory conditions. Moreover, accumulation of OxPL causes general immunmodulation and may lead to autoimmune diseases. Evidence is accumulating that OxPL play a role in lupus erythematosus, antiphospholipid syndrome, and rheumatoid arthritis. Last but not least, a role for OxPL in neurological disorders including multiple sclerosis (MS), Alzheimer's and Parkinson's disease has been suggested.This chapter will summarize recent findings obtained in animal models and from studies in humans that indicate that formation of OxPL represents a general mechanism that may play a major role in chronic inflammatory and autoimmune diseases.

Does Lyme disease exist in Australia?

PubMed

Collignon, Peter J; Lum, Gary D; Robson, Jennifer Mb

2016-11-07

There is no convincing evidence that classic Lyme disease occurs in Australia, nor is there evidence that the causative agent, Borrelia burgdorferi, is found in Australian animals or ticks. Lyme disease, however, can be acquired overseas but diagnosed in Australia; most people presenting with laboratory-confirmed Lyme disease in Australia were infected in Europe. Despite the lack of evidence that Lyme disease can be acquired in Australia, growing numbers of patients, their supporters, and some politicians demand diagnoses and treatment according to the protocols of the "chronic Lyme disease" school of thought. Antibiotic therapy for chronic "Lyme disease-like illness" can cause harm to both the individual (eg, cannula-related intravenous sepsis) and the broader community (increased antimicrobial resistance rates). Until there is strong evidence from well performed clinical studies that bacteria present in Australia cause a chronic debilitating illness that responds to prolonged antibiotics, treating patients with "Lyme disease-like illness" with prolonged antibiotic therapy is unjustified, and is likely to do much more harm than good.

Evidence based vaccinology.

PubMed

Nalin, David R

2002-02-22

Evidence based vaccinology (EBV) is the identification and use of the best evidence in making and implementing decisions during all of the stages of the life of a vaccine, including pre-licensure vaccine development and post-licensure manufacture and research, and utilization of the vaccine for disease control. Vaccines, unlike most pharmaceuticals, are in a continuous process of development both before and after licensure. Changes in biologics manufacturing technology and changes that vaccines induce in population and disease biology lead to periodic review of regimens (and sometimes dosage) based on changing immunologic data or public perceptions relevant to vaccine safety and effectiveness. EBV includes the use of evidence based medicine (EBM) both in clinical trials and in national disease containment programs. The rationale for EBV is that the highest evidentiary standards are required to maintain a rigorous scientific basis of vaccine quality control in manufacture and to ensure valid determination of vaccine efficacy, field effectiveness and safety profiles (including post-licensure safety monitoring), cost-benefit analyses, and risk:benefit ratios. EBV is increasingly based on statistically validated, clearly defined laboratory, manufacturing, clinical and epidemiological research methods and procedures, codified as good laboratory practices (GLP), good manufacturing practices (GMP), good clinical research practices (GCRP) and in clinical and public health practice (good vaccination practices, GVP). Implementation demands many data-driven decisions made by a spectrum of specialists pre- and post-licensure, and is essential to maintaining public confidence in vaccines.

Biodiversity and disease: a synthesis of ecological perspectives on Lyme disease transmission.

USGS Publications Warehouse

Wood, Chelsea L.; Lafferty, Kevin D.

2013-01-01

Recent reviews have argued that disease control is among the ecosystem services yielded by biodiversity. Lyme disease (LD) is commonly cited as the best example of the ‘diluting’ effect of biodiversity on disease transmission, but many studies document the opposite relationship, showing that human LD risk can increase with forestation. Here, we unify these divergent perspectives and find strong evidence for a positive link between biodiversity and LD at broad spatial scales (urban to suburban to rural) and equivocal evidence for a negative link between biodiversity and LD at varying levels of biodiversity within forests. This finding suggests that, across zoonotic disease agents, the biodiversity–disease relationship is scale dependent and complex.

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success

PubMed Central

Lemoine, Jean Frantz; Desormeaux, Anne Marie; Monestime, Franck; Fayette, Carl Renad; Desir, Luccene; Direny, Abdel Nasser; Carciunoiu, Sarah; Miller, Lior; Knipes, Alaine; Lammie, Patrick; Smith, Penelope; Stockton, Melissa; Trofimovich, Lily; Bhandari, Kalpana; Reithinger, Richard; Crowley, Kathryn; Ottesen, Eric; Baker, Margaret

2016-01-01

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti’s neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a “directly observed treatment” strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained– 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH—and the significant reduction in burden of infection– 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti’s very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of “best practices” for

Controlling Neglected Tropical Diseases (NTDs) in Haiti: Implementation Strategies and Evidence of Their Success.

PubMed

Lemoine, Jean Frantz; Desormeaux, Anne Marie; Monestime, Franck; Fayette, Carl Renad; Desir, Luccene; Direny, Abdel Nasser; Carciunoiu, Sarah; Miller, Lior; Knipes, Alaine; Lammie, Patrick; Smith, Penelope; Stockton, Melissa; Trofimovich, Lily; Bhandari, Kalpana; Reithinger, Richard; Crowley, Kathryn; Ottesen, Eric; Baker, Margaret

2016-10-01

Lymphatic filariasis (LF) and soil-transmitted helminths (STH) have been targeted since 2000 in Haiti, with a strong mass drug administration (MDA) program led by the Ministry of Public Health and Population and its collaborating international partners. By 2012, Haiti's neglected tropical disease (NTD) program had reached full national scale, and with such consistently good epidemiological coverage that it is now able to stop treatment for LF throughout almost all of the country. Essential to this success have been in the detail of how MDAs were implemented. These key programmatic elements included ensuring strong community awareness through an evidence-based, multi-channel communication and education campaign facilitated by voluntary drug distributors; strengthening community trust of the drug distributors by ensuring that respected community members were recruited and received appropriate training, supervision, identification, and motivation; enforcing a "directly observed treatment" strategy; providing easy access to treatment though numerous distribution posts and a strong drug supply chain; and ensuring quality data collection that was used to guide and inform MDA strategies. The evidence that these strategies were effective lies in both the high treatment coverage obtained- 100% geographical coverage reached in 2012, with almost all districts consistently achieving well above the epidemiological coverage targets of 65% for LF and 75% for STH-and the significant reduction in burden of infection- 45 communes having reached the target threshold for stopping treatment for LF. By taking advantage of sustained international financial and technical support, especially during the past eight years, Haiti's very successful MDA campaign resulted in steady progress toward LF elimination and development of a strong foundation for ongoing STH control. These efforts, as described, have not only helped establish the global portfolio of "best practices" for NTD control but

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

PubMed Central

Cho, Judy H.; Nicolae, Dan L.; Gold, Leslee H.; Fields, Carter T.; LaBuda, Michele C.; Rohal, Patrick M.; Pickles, Michael R.; Qin, Li; Fu, Yifan; Mann, Jasdeep S.; Kirschner, Barbara S.; Jabs, Ethylin Wang; Weber, James; Hanauer, Stephen B.; Bayless, Theodore M.; Brant, Steven R.

1998-01-01

The idiopathic inflammatory bowel diseases, Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, non-Mendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) = 2.29, P = 5.7 × 10−4), with greatest significance for non-Ashkenazim Caucasians (MLod = 3.39, P = 3.92 × 10−5), and at chromosome 1p (MLod = 2.65, P = 2.4 × 10−4) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod = 2.76, P = 1.9 × 10−4), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod = 1.69, P = 2.6 × 10−3), particularly among Ashkenazim (MLod = 1.51, P = 7.8 × 10−3); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC. PMID:9636179

Fat-soluble vitamins and atopic disease: what is the evidence?

PubMed Central

Litonjua, Augusto A.

2012-01-01

The prevalence of asthma and other atopic disorders continues to increase worldwide. Examination of the epidemiologic patterns has revealed that this rise has occurred primarily in western, industrialised countries and countries transitioning to this lifestyle. While many changes have occurred in human populations over the years, it has been hypothesised that some of the relevant changes that have led to the rise in asthma and atopic disorders have been the changes from a traditional diet to a more western diet consisting of decreased intake of fruits and vegetables (sources of antioxidant vitamins and carotenoids) leading to decreased intakes of vitamins E and A, and a decrease in sun exposure (e.g. greater time spent indoors and heavy use of sunscreen) leading to decreased circulating levels of vitamin D. This review will examine the evidence for an effect of fat-soluble vitamins (vitamins A, D and K) on the development and severity of asthma and allergies. While observational studies suggest that these vitamins may play a salutary role in asthma and allergies, large, well-designed clinical trials are lacking. Of the fat-soluble vitamins, vitamin D holds great promise as an agent for primary and secondary prevention of disease. Ongoing clinical trials will help determine whether results of observational studies can be applied to the clinical setting. PMID:22114947

Fat-soluble vitamins and atopic disease: what is the evidence?

PubMed

Litonjua, Augusto A

2012-02-01

The prevalence of asthma and other atopic disorders continues to increase worldwide. Examination of the epidemiologic patterns has revealed that this rise has occurred primarily in western, industrialised countries and countries transitioning to this lifestyle. While many changes have occurred in human populations over the years, it has been hypothesised that some of the relevant changes that have led to the rise in asthma and atopic disorders have been the changes from a traditional diet to a more western diet consisting of decreased intake of fruits and vegetables (sources of antioxidant vitamins and carotenoids) leading to decreased intakes of vitamins E and A, and a decrease in sun exposure (e.g. greater time spent indoors and heavy use of sunscreen) leading to decreased circulating levels of vitamin D. This review will examine the evidence for an effect of fat-soluble vitamins (vitamins A, D and K) on the development and severity of asthma and allergies. While observational studies suggest that these vitamins may play a salutary role in asthma and allergies, large, well-designed clinical trials are lacking. Of the fat-soluble vitamins, vitamin D holds great promise as an agent for primary and secondary prevention of disease. Ongoing clinical trials will help determine whether results of observational studies can be applied to the clinical setting.

Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse

PubMed Central

Vrooman, Lisa A.; Bartolomei, Marisa S.

2016-01-01

Millions of children have been born worldwide though assisted reproductive technologies (ART). Consistent with the Developmental Origins of Health and Disease hypothesis, there is concern that ART can induce adverse effects, especially because procedures coincide with epigenetic reprogramming events. Although the majority of studies investigating the effects of ART have focused on perinatal outcomes, more recent studies demonstrate that ART-conceived children may be at increased risk for postnatal effects. Here, we present the current epidemiological evidence that ART-conceived children have detectable differences in blood pressure, body composition, and glucose homeostasis. Similar effects are observed in the ART mouse model, which have no underlying infertility, suggesting that cardiometabolic effects are likely caused by ART procedures and not due to reasons related to infertility. We propose that the mouse system can, consequently, be used to adequately study, modify, and improve outcomes for ART children. PMID:27474254

Benefit-Cost Analysis of Foot-and-Mouth Disease Vaccination at the Farm-Level in South Vietnam.

PubMed

Truong, Dinh Bao; Goutard, Flavie Luce; Bertagnoli, Stéphane; Delabouglise, Alexis; Grosbois, Vladimir; Peyre, Marisa

2018-01-01

This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit-cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42-16.45], 9.93 (95% CI 3.45-16.47), and 3.02 (95% CI 0.76-7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.

A review of the clinical evidence for complementary and alternative therapies in Parkinson's disease.

PubMed

Bega, Danny; Gonzalez-Latapi, Paulina; Zadikoff, Cindy; Simuni, Tanya

2014-10-01

No conventional treatment has been convincingly demonstrated to slow or stop the progression of Parkinson's disease (PD). Dopaminergic therapy is the gold standard for managing the motor disability associated with PD, but it falls short of managing all of the aspects of the disease that contribute to quality of life. Perhaps for this reason, an increasing number of patients are searching for a more holistic approach to healthcare. This is not to say that they are abandoning the standard and effective symptomatic therapies for PD, but rather are complementing them with healthy living, mind-body practices, and natural products that empower patients to be active participants in their healthcare and widen the net under which disease modification might one day be achieved. Despite high rates of utilization of complementary and alternative medicine (CAM) practices, data on efficacy is generally limited, restricting physicians in providing guidance to interested patients. Exercise is now well-established as integral in the management of PD, but mind-body interventions such as Tai Chi that incorporate relaxation and mindfulness with physical activity should be routinely encouraged as well. While no comment can be made about neuroplastic or disease-modifying effects of mind-body interventions, patients should be encouraged to be as active as possible and engage with others in enjoyable and challenging activities such as dance, music therapy, and yoga. Many PD patients also choose to try herbs, vitamins, and neutraceuticals as part of a healthy lifestyle, with the added expectation that these products may lower free radical damage and protect them against further cell death. Evidence for neuroprotection is limited, but patients can be encouraged to maintain a healthy diet rich in "high-power," low-inflammatory foods, while at the same time receiving education that many promising natural products have produced disappointing results in clinical trials. It is vital that the

A critical evaluation of the clinical evidence for pomegranate preparations in the prevention and treatment of cardiovascular diseases.

PubMed

Vlachojannis, Christian; Erne, Paul; Schoenenberger, Andreas W; Chrubasik-Hausmann, Sigrun

2015-04-01

This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit. Copyright © 2015 John Wiley & Sons, Ltd.

Psychometric Properties of the Heart Disease Knowledge Scale: Evidence from Item and Confirmatory Factor Analyses

PubMed Central

Lim, Bee Chiu; Kueh, Yee Cheng; Arifin, Wan Nor; Ng, Kok Huan

2016-01-01

Background Heart disease knowledge is an important concept for health education, yet there is lack of evidence on proper validated instruments used to measure levels of heart disease knowledge in the Malaysian context. Methods A cross-sectional, survey design was conducted to examine the psychometric properties of the adapted English version of the Heart Disease Knowledge Questionnaire (HDKQ). Using proportionate cluster sampling, 788 undergraduate students at Universiti Sains Malaysia, Malaysia, were recruited and completed the HDKQ. Item analysis and confirmatory factor analysis (CFA) were used for the psychometric evaluation. Construct validity of the measurement model was included. Results Most of the students were Malay (48%), female (71%), and from the field of science (51%). An acceptable range was obtained with respect to both the difficulty and discrimination indices in the item analysis results. The difficulty index ranged from 0.12–0.91 and a discrimination index of ≥ 0.20 were reported for the final retained 23 items. The final CFA model showed an adequate fit to the data, yielding a 23-item, one-factor model [weighted least squares mean and variance adjusted scaled chi-square difference = 1.22, degrees of freedom = 2, P-value = 0.544, the root mean square error of approximation = 0.03 (90% confidence interval = 0.03, 0.04); close-fit P-value = > 0.950]. Conclusion Adequate psychometric values were obtained for Malaysian undergraduate university students using the 23-item, one-factor model of the adapted HDKQ. PMID:27660543

Psychometric Properties of the Heart Disease Knowledge Scale: Evidence from Item and Confirmatory Factor Analyses.

PubMed

Lim, Bee Chiu; Kueh, Yee Cheng; Arifin, Wan Nor; Ng, Kok Huan

2016-07-01

Heart disease knowledge is an important concept for health education, yet there is lack of evidence on proper validated instruments used to measure levels of heart disease knowledge in the Malaysian context. A cross-sectional, survey design was conducted to examine the psychometric properties of the adapted English version of the Heart Disease Knowledge Questionnaire (HDKQ). Using proportionate cluster sampling, 788 undergraduate students at Universiti Sains Malaysia, Malaysia, were recruited and completed the HDKQ. Item analysis and confirmatory factor analysis (CFA) were used for the psychometric evaluation. Construct validity of the measurement model was included. Most of the students were Malay (48%), female (71%), and from the field of science (51%). An acceptable range was obtained with respect to both the difficulty and discrimination indices in the item analysis results. The difficulty index ranged from 0.12-0.91 and a discrimination index of ≥ 0.20 were reported for the final retained 23 items. The final CFA model showed an adequate fit to the data, yielding a 23-item, one-factor model [weighted least squares mean and variance adjusted scaled chi-square difference = 1.22, degrees of freedom = 2, P-value = 0.544, the root mean square error of approximation = 0.03 (90% confidence interval = 0.03, 0.04); close-fit P-value = > 0.950]. Adequate psychometric values were obtained for Malaysian undergraduate university students using the 23-item, one-factor model of the adapted HDKQ.

[Tuberculosis as occupational disease].

PubMed

Mendoza-Ticona, Alberto

2012-06-01

There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupational disease among health care workers, presenting the current Peruvian law related.

Taste, umami-enhance effect and amino acid sequence of peptides separated from silkworm pupa hydrolysate.

PubMed

Yu, Zilin; Jiang, Hongrui; Guo, Rongcan; Yang, Bo; You, Gang; Zhao, Mouming; Liu, Xiaoling

2018-06-01

Four umami peptides were separated and purified by ultrafiltration, gel filtration chromatography and identified by ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS), the amino acid sequences of four peptides are Val-Pro-Tyr (VPY), Thr-Ala-Tyr (TAY), Ala-Ala-Pro-Tyr (AAPY) and Gly-Phe-Pro (GFP). The result illustrates that the umami amino acids are not the content of umami peptides, but bitter amino acids are included. The threshold of VPY, TAY, AAPY and GFP were 1.65 mmol/L, 1.76 mmol/L, 2.97 mmol/L and 6.26 mmol/L, respectively. The peptide TAY, VPY and AAPY had an umami-enhancement effect on the monosodium glutamate (MSG) + sodium chloride (NaCl) solution, their concentrations were 2.5 g/L, 5 g/L and 5 g/L, respectively, while GFP has no significant umami-enhancement effect in solution. In addition, the peptides have better taste than its composing amino acids, which indicates that the taste of peptide does not depend on its composing amino acids. Copyright © 2018. Published by Elsevier Ltd.

Evidence for regular ongoing introductions of mosquito disease vectors into the Galápagos Islands

PubMed Central

Bataille, Arnaud; Cunningham, Andrew A.; Cedeño, Virna; Cruz, Marilyn; Eastwood, Gillian; Fonseca, Dina M.; Causton, Charlotte E.; Azuero, Ronal; Loayza, Jose; Martinez, Jose D. Cruz; Goodman, Simon J.

2009-01-01

Wildlife on isolated oceanic islands is highly susceptible to the introduction of pathogens. The recent establishment in the Galápagos Islands of the mosquito Culex quinquefasciatus, a vector for diseases such as avian malaria and West Nile fever, is considered a serious risk factor for the archipelago's endemic fauna. Here we present evidence from the monitoring of aeroplanes and genetic analysis that C. quinquefasciatus is regularly introduced via aircraft into the Galápagos Archipelago. Genetic population structure and admixture analysis demonstrates that these mosquitoes breed with, and integrate successfully into, already-established populations of C. quinquefasciatus in the Galápagos, and that there is ongoing movement of mosquitoes between islands. Tourist cruise boats and inter-island boat services are the most likely mechanism for transporting Culex mosquitoes between islands. Such anthropogenic mosquito movements increase the risk of the introduction of mosquito-borne diseases novel to Galápagos and their subsequent widespread dissemination across the archipelago. Failure to implement and maintain measures to prevent the human-assisted transport of mosquitoes to and among the islands could have catastrophic consequences for the endemic wildlife of Galápagos. PMID:19675009

Mondor's disease of penis: a forgotten disease

PubMed Central

Kumar, B; Narang, T; Radotra, B; Gupta, S

2005-01-01

Background: Mondor's disease of penis is an uncommon genital condition involving the penile sulcus in a circumferential manner. Although this disorder is almost always self limited, it is associated with considerable psychological stress and sexual disharmony. Methods: All patients attending the sexually transmitted disease clinic during 1991–2003 were examined for evidence of Mondor's disease of penis. Detailed history and clinical findings were recorded in a specially designed proforma. Histopathological examination and staining with CD31 and CD34 monoclonal antibodies was also done in 11 patients. Results: 18 out of 1296 patients attending the sexually transmitted diseases (STD) clinic during the study period were found to have penile Mondor's disease, giving an incidence of 1.39%. 17 patients had history of one or more episodes of STDs. Histopathological specimens showed prominent vessels with plump endothelial cells and thickened blood vessel walls. The occasional vessel showed complete occlusion of its lumen. Conclusions: In our study we did not find any evidence of lymphatic involvement. Non-lymphatic vessels, mainly veins, were predominantly involved. In our opinion Mondor's phlebitis of penis or Mondor's disease of penis are better terms to describe the condition rather than non-venereal sclerosing lymphangitis. PMID:16326851

Biodiversity and disease: a synthesis of ecological perspectives on Lyme disease transmission.

PubMed

Wood, Chelsea L; Lafferty, Kevin D

2013-04-01

Recent reviews have argued that disease control is among the ecosystem services yielded by biodiversity. Lyme disease (LD) is commonly cited as the best example of the 'diluting' effect of biodiversity on disease transmission, but many studies document the opposite relationship, showing that human LD risk can increase with forestation. Here, we unify these divergent perspectives and find strong evidence for a positive link between biodiversity and LD at broad spatial scales (urban to suburban to rural) and equivocal evidence for a negative link between biodiversity and LD at varying levels of biodiversity within forests. This finding suggests that, across zoonotic disease agents, the biodiversity-disease relationship is scale dependent and complex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disease risk curves.

PubMed

Hughes, G; Burnett, F J; Havis, N D

2013-11-01

Disease risk curves are simple graphical relationships between the probability of need for treatment and evidence related to risk factors. In the context of the present article, our focus is on factors related to the occurrence of disease in crops. Risk is the probability of adverse consequences; specifically in the present context it denotes the chance that disease will reach a threshold level at which crop protection measures can be justified. This article describes disease risk curves that arise when risk is modeled as a function of more than one risk factor, and when risk is modeled as a function of a single factor (specifically the level of disease at an early disease assessment). In both cases, disease risk curves serve as calibration curves that allow the accumulated evidence related to risk to be expressed on a probability scale. When risk is modeled as a function of the level of disease at an early disease assessment, the resulting disease risk curve provides a crop loss assessment model in which the downside is denominated in terms of risk rather than in terms of yield loss.

Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach.

PubMed

Frazier, Dianne M; Allgeier, Courtney; Homer, Caroline; Marriage, Barbara J; Ogata, Beth; Rohr, Frances; Splett, Patricia L; Stembridge, Adrya; Singh, Rani H

2014-07-01

In an effort to increase harmonization of care and enable outcome studies, the Genetic Metabolic Dietitians International (GMDI) and the Southeast Regional Newborn Screening and Genetics Collaborative (SERC) are partnering to develop nutrition management guidelines for inherited metabolic disorders (IMD) using a model combining both evidence- and consensus-based methodology. The first guideline to be completed is for maple syrup urine disease (MSUD). This report describes the methodology used in its development: formulation of five research questions; review, critical appraisal and abstraction of peer-reviewed studies and unpublished practice literature; and expert input through Delphi surveys and a nominal group process. This report includes the summary statements for each research question and the nutrition management recommendations they generated. Each recommendation is followed by a standardized rating based on the strength of the evidence and consensus used. The application of technology to build the infrastructure for this project allowed transparency during development of this guideline and will be a foundation for future guidelines. Online open access of the full, published guideline allows utilization by health care providers, researchers, and collaborators who advise, advocate and care for individuals with MSUD and their families. There will be future updates as warranted by developments in research and clinical practice. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Scenarios, personas and user stories: user-centered evidence-based design representations of communicable disease investigations.

PubMed

Turner, Anne M; Reeder, Blaine; Ramey, Judith

2013-08-01

Despite years of effort and millions of dollars spent to create unified electronic communicable disease reporting systems, the goal remains elusive. A major barrier has been a lack of understanding by system designers of communicable disease (CD) work and the public health workers who perform this work. This study reports on the application of user-centered design representations, traditionally used for improving interface design, to translate the complex CD work identified through ethnographic studies to guide designers and developers of CD systems. The purpose of this work is to: (1) better understand public health practitioners and their information workflow with respect to CD monitoring and control at a local health agency, and (2) to develop evidence-based design representations that model this CD work to inform the design of future disease surveillance systems. We performed extensive onsite semi-structured interviews, targeted work shadowing and a focus group to characterize local health agency CD workflow. Informed by principles of design ethnography and user-centered design we created persona, scenarios and user stories to accurately represent the user to system designers. We sought to convey to designers the key findings from ethnographic studies: (1) public health CD work is mobile and episodic, in contrast to current CD reporting systems, which are stationary and fixed, (2) health agency efforts are focused on CD investigation and response rather than reporting and (3) current CD information systems must conform to public health workflow to ensure their usefulness. In an effort to illustrate our findings to designers, we developed three contemporary design-support representations: persona, scenario, and user story. Through application of user-centered design principles, we were able to create design representations that illustrate complex public health communicable disease workflow and key user characteristics to inform the design of CD information

Is Multiple Sclerosis an Autoimmune Disease?

PubMed Central

Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

2012-01-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

Lack of serologic evidence to link IgA nephropathy with celiac disease or immune reactivity to gluten.

PubMed

Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin

2014-01-01

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.

Lack of Serologic Evidence to Link IgA Nephropathy with Celiac Disease or Immune Reactivity to Gluten

PubMed Central

Moeller, Sina; Canetta, Pietro A.; Taylor, Annette K.; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H.; Kiryluk, Krzysztof; Alaedini, Armin

2014-01-01

IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy. PMID:24732864

Comparison of attitudes of guilt and forgiveness in cancer patients without evidence of disease and advanced cancer patients in a palliative care setting.

PubMed

van Laarhoven, Hanneke W M; Schilderman, Johannes; Verhagen, Constans A H H V M; Prins, Judith B

2012-01-01

: Attitudes toward guilt and forgiveness may be important factors determining distress in cancer patients. Direct comparative studies in patients with different life expectancies exploring attitudes toward guilt and forgiveness are lacking. Also, sociodemographic and religious characteristics determining the attitudes toward guilt and forgiveness are unknown. : The objective of this study was to compare attitudes toward guilt and forgiveness in cancer patients without evidence of disease and advanced cancer patients. : A descriptive research design was used. Ninety-seven patients without evidence of disease and 55 advanced cancer patients filled out the Dutch Guilt Measurement Instrument and the Forgiveness of Others Scale. : Both groups had an attitude of nonreligious guilt and forgiveness, but not of religious guilt. No significant differences in attitudes toward guilt and forgiveness were observed between the 2 groups. In contrast to sociodemographic characteristics, religious characteristics were relevant predictors for guilt and forgiveness. Significant differences in relations between images of God and attitudes toward guilt were observed between the 2 patient groups. : An attitude of nonreligious guilt and forgiveness was found in cancer patients, irrespective of the stage of disease. Religious characteristics were significantly associated with attitudes of guilt and forgiveness. This correlation differed in the early and the advanced setting of disease. : The observed relations between religious characteristics and attitudes of guilt and forgiveness suggest that a careful examination of the role of religious beliefs and values is relevant in the clinical care of patients with cancer, both in the setting of early and advanced disease.

Nitrergic system and plasmatic methylarginines: Evidence of their role in the perinatal programming of cardiovascular diseases.

PubMed

Bassareo, Pier Paolo; Mussap, Michele; Bassareo, Valentina; Flore, Giovanna; Mercuro, Giuseppe

2015-12-07

Atherosclerosis, in turn preceded by endothelial dysfunction, underlies a series of important cardiovascular diseases. Reduced bioavailability of endothelial nitric oxide, by increasing vascular tone and promoting platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, plays a key role in the onset of the majority of cardiovascular diseases. In addition, high blood levels of asymmetric dimethylarginine, a potent inhibitor of nitric oxide synthesis, are associated with future development of adverse cardiovascular events and cardiac death. Recent reports have demonstrated that another methylarginine, i.e., symmetric dimethylarginine, is also involved in the onset of endothelial dysfunction and hypertension. Almost a decade ago, prematurity at birth and intrauterine growth retardation were first associated with a potential negative influence on the cardiovascular apparatus, thus constituting risk factors or leading to early onset of cardiovascular diseases. This condition is referred to as cardiovascular perinatal programming. Accordingly, cardiovascular morbidity and mortality are higher among former preterm adults than in those born at term. The aim of this paper was to undertake a comprehensive literature review focusing on cellular and biochemical mechanisms resulting in both reduced nitric oxide bioavailability and increased methylarginine levels in subjects born preterm. Evidence of the involvement of these compounds in the perinatal programming of cardiovascular risk are also discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Management of active Crohn disease.

PubMed

Cheifetz, Adam S

2013-05-22

Treatment of Crohn disease is rapidly evolving, with the induction of novel biologic therapies and newer, often more intensive treatment approaches. Knowing how to treat individual patients in this quickly changing milieu can be a challenge. To review the diagnosis and management of moderate to severe Crohn disease, with a focus on newer treatments and goals of care. MEDLINE was searched from 2000 to 2011. Additional citations were procured from references of select research and review articles. Evidence was graded using the American Heart Association level-of-evidence guidelines. Although mesalamines are still often used to treat Crohn disease, the evidence for their efficacy is lacking. Corticosteroids can be effectively used to induce remission in moderate to severe Crohn disease, but they do not maintain remission. The mainstays of treatment are immunomodulators and biologics, particularly anti-tumor necrosis factor. Immunomodulators and biologics are now the preferred treatment options for Crohn disease.

MECHANISMS INVOLVED IN THE ASSOCIATION BETWEEN PERIDONTAL DISEASES AND CARDIOVASCULAR DISEASE

PubMed Central

Teles, Ricardo; Wang, Cun-Yu

2012-01-01

It is now well accepted that besides the cholesterol associated mechanisms of atherogenesis, inflammation plays a crucial role in all stages of the development of the atherosclerotic lesion. This “inflammation hypothesis” raises the possibility that, through systemic elevations of pro-inflammatory cytokines, periodontal diseases might also contribute to systemic inflammation and, therefore, to atherogenesis. In fact, there is evidence that periodontal diseases are associated with higher systemic levels of high-sensitivity C-reactive protein and a low grade systemic inflammation. This phenomenon has been explained based on mechanisms associated with either the infectious or the inflammatory nature of periodontal diseases. The purposes of this article are to review (1) the evidence suggesting a role for oral bacterial species, particularly periodontal pathogens, in atherogenesis; (2) the potential mechanisms explaining an etiological role for oral bacteria in atherosclerosis; (3) the evidence suggesting that periodontal infections are accompanied by a heightened state of systemic inflammation; (4) the potential sources of systemic inflammatory biomarkers associated with periodontal diseases; and (5) the effects of periodontal therapy on systemic inflammatory biomarkers and cardiovascular risk. PMID:21223455

Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer's disease.

PubMed

Ryan, Natalie S; Keihaninejad, Shiva; Shakespeare, Timothy J; Lehmann, Manja; Crutch, Sebastian J; Malone, Ian B; Thornton, John S; Mancini, Laura; Hyare, Harpreet; Yousry, Tarek; Ridgway, Gerard R; Zhang, Hui; Modat, Marc; Alexander, Daniel C; Rossor, Martin N; Ourselin, Sebastien; Fox, Nick C

2013-05-01

Amyloid imaging studies of presymptomatic familial Alzheimer's disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer's disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical

Environmental risk factors for inflammatory bowel diseases: Evidence based literature review

PubMed Central

Abegunde, Ayokunle T; Muhammad, Bashir H; Bhatti, Owais; Ali, Tauseef

2016-01-01

AIM: Advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases (IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation. RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD. CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research. PMID:27468219

Challenges with Evidence-Based Management of Stable Ischemic Heart Disease.

PubMed

Patel, Amit V; Bangalore, Sripal

2017-02-01

Stable ischemic heart disease (SIHD) is a highly prevalent condition associated with increased costs, morbidity, and mortality. Management goals of SIHD can broadly be thought of in terms of improving prognosis and/or improving symptoms. Treatment options include medical therapy as well as revascularization, either with percutaneous coronary intervention or coronary artery bypass grafting. Herein, we will review the current evidence base for treatment of SIHD as well as its challenges and discuss ongoing studies to help address some of these knowledge gaps. There has been no consistent reduction in death or myocardial infarction (MI) with revascularization vs. medical therapy in patients with SIHD in contemporary trials. Angina and quality of life have been shown to be relieved more rapidly with revascularization vs. optimal medical therapy; however, the durability of these results is uncertain. There have been challenges and limitations in several of the trials addressing the optimal treatment strategy for SIHD due to potential selection bias (due to knowledge of coronary anatomy prior to randomization), patient crossover, and advances in medical therapy and revascularization strategies since trial completion. The challenges inherent to prior trials addressing the optimal management strategy for SIHD have impacted the generalizability of results to real-world cohorts. Until the results of additional ongoing trials are available, the decision for revascularization or medical therapy should be based on patients' symptoms, weighing the risks and benefits of each approach, and patient preference.

Resolved: There is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases

PubMed Central

Hu, Frank B.

2017-01-01

Sugar-sweetened beverages (SSBs) are the single largest source of added sugar and the top source of energy intake in the US diet. In this review, we evaluate whether there is sufficient scientific evidence that decreasing SSB consumption will reduce the prevalence of obesity and its related diseases. Since prospective cohort studies address dietary determinants of long-term weight gain and chronic diseases, whereas randomized controlled trials (RCTs) typically evaluate short-term effects of specific interventions on weight change, both types of evidence are critical in evaluating causality. Findings from well-powered prospective cohorts have consistently shown a significant association, established temporality, and demonstrated a direct dose-response relationship between SSB consumption and long-term weight gain and risk of type 2 diabetes (T2D). A recently published meta-analysis of RCTs commissioned by the World Health Organization (WHO) found that decreased intake of added sugars significantly reduced body weight (0.80 kg, 95% CI 0.39 to 1.21; P<0.001), whereas increased sugar intake led to a comparable weight increase (0.75 kg, 0.30 to 1.19; P=0.001). A parallel meta-analysis of cohort studies also found that higher intake of SSBs among children was associated with 55% (95% CI 32%-82%) higher risk of being overweight or obese compared to those with lower intake. Another meta-analysis of eight prospective cohort studies found that 1–2 servings/day of SSB intake was associated with a 26% (95% CI 12–41%) greater risk of developing T2D compared to occasional intake (< 1 serving/month). Recently, two large RCTs with a high degree of compliance provided convincing data that reducing consumption of SSBs significantly decreases weight gain and adiposity in children and adolescents. Taken together, the evidence that decreasing SSBs will decrease the risk of obesity and related diseases such as T2D is compelling. Several additional issues warrant further discussion

Evidence-based approach for disaster preparedness authorities to inform the contents of repositories for prescription medications for chronic disease management and control.

PubMed

Brown, David W; Young, Stacy L; Engelgau, Michael M; Mensah, George A

2008-01-01

Chronic diseases are major causes of death and disability and often require multiple prescribed medications for treatment and control. Public health emergencies (e.g., disasters due to natural hazards) that disrupt the availability or supply of these medications may exacerbate chronic disease or even cause death. A repository of chronic disease pharmaceuticals and medical supplies organized for rapid response in the event of a public health emergency is desirable. However, there is no science base for determining the contents of such a repository. This study provides the first step in an evidence-based approach to inform the planning, periodic review, and revision of repositories of chronic disease medications. Data from the 2004 National Hospital Ambulatory Medical Care Survey (NHAMCS) were used to examine the prescription medication needs of persons presenting to US hospital emergency departments for chronic disease exacerbations. It was assumed that the typical distribution of cases for an emergency department will reflect the patient population treated in the days after a public health emergency. The estimated numbers of prescribed drugs for chronic conditions that represent the five leading causes of death, the five leading primary diagnoses for physician office visits, and the five leading causes of disease burden assessed by disability-adjusted life years are presented. The 2004 NHAMCS collected data on 36,589 patient visits that were provided by 376 emergency departments. Overall, the five drug classes mentioned most frequently for emergency department visits during 2004 were narcotic analgesics (30.7 million), non-steroidal anti-inflammatory drugs (25.2 million), non-narcotic analgesics (15.2 million), sedatives and hypnotics (10.4 million), and cephalosporins (8.2 million). The drug classes mentioned most frequently for chronic conditions were: (1) for heart disease, antianginal agents/vasodilators (715,000); (2) for cancer, narcotic analgesics (53

Evidence and evidence gaps in therapies of nasal obstruction and rhinosinusitis

PubMed Central

Rotter, Nicole

2016-01-01

Therapeutic decisions in otorhinolaryngology are based on clinical experience, surgical skills, and scientific evidence. Recently, evidence-based therapies have gained increased attention and importance due to their potential to improve the individual patient’s treatment and their potential at the same time to reduce treatment costs. In clinical practice, it is almost impossible to stay ahead of the increasing mass of literature and on the other hand critically assess the presented data. A solid scientific and statistical knowledge as well as a significant amount of spare time are required to detect systematic bias and other errors in study designs, also with respect to assessing whether or not a study should be part of an individual therapeutic decision. Meta-analyses, reviews, and clinical guidelines are, therefore, of increasing importance for evidence-based therapy in clinical practice. This review is an update of the availability of external evidence for the treatment of nasal obstruction and rhinosinusitis. It becomes evident that both groups of diseases differ significantly in the availability of external evidence. Furthermore, it becomes obvious that surgical treatment options are normally based on evidence of significantly lower quality than medical treatment options. PMID:28025606

Evidence-based medicine and epistemological imperialism: narrowing the divide between evidence and illness.

PubMed

Crowther, Helen; Lipworth, Wendy; Kerridge, Ian

2011-10-01

Evidence-based medicine (EBM) has been rapidly and widely adopted because it claims to provide a method for determining the safety and efficacy of medical therapies and public health interventions more generally. However, as others have noted, EBM may be riven through with cultural bias, both in the generation of evidence and in its translation. We suggest that technological and scientific advances in medicine accentuate and entrench these cultural biases, to the extent that they may invalidate the evidence we have about disease and its treatment. This creates a significant ethical, epistemological and ontological challenge for medicine. © 2011 Blackwell Publishing Ltd.