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pubmed_774_7355
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Immune-mediated diseases, such as celiac disease, type 1 diabetes or multiple sclerosis, are a clinically heterogeneous group of diseases that share many key genetic triggers. Although the pathogenic mechanisms responsible for the development of immune mediated disorders is not totally understood, high-throughput genomic studies, such as GWAS and Immunochip, performed in the past few years have provided intriguing hints about underlying mechanisms and pathways that lead to disease. More than a hundred gene variants associated with disease susceptibility have been identified through such studies, but the progress toward understanding the underlying mechanisms has been slow. The majority of the identified risk variants are located in non-coding regions of the genome making it difficult to assign a molecular function to the SNPs. However, recent studies have revealed that many of the non-coding regions bearing disease-associated SNPs generate long non-coding RNAs (lncRNAs). LncRNAs have been implicated in several inflammatory diseases, and many of them have been shown to function as regulators of gene expression. Many of the disease associated SNPs located in lncRNAs modify their secondary structure, or influence expression levels, thereby affecting their regulatory function, hence contributing to the development of disease.
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10.3389/fimmu.2019.00420
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pubmed_635_19336
|
INTRODUCTION
The mechanisms controlling the rate of adjustment of oxidative phosphorylation have been debated for several years. Although disagreement exists as to what the prevailing mechanisms controlling the speed of the oxygen uptake (V̇O₂) kinetics are in both young and older individuals, it seems tenable that the slower V̇O₂ kinetics response typically observed in older adults is at least partly imposed by an O2 delivery limitation.
RESULTS
Several studies have demonstrated that different interventions can speed V̇O₂ kinetics in older individuals so that this response can become similar to that observed in their young counterparts. These findings have opened the debate as to whether aging per se, or other factors that accompany aging, is responsible for the slower adjustment of oxidative metabolism in the elderly. This review focuses on the slower V̇O₂ kinetics often observed in older populations and discusses potential mechanisms that might mediate the slower adjustment in oxidative phosphorylation. Furthermore, interventions that have been successful in speeding V̇O₂ kinetics in the elderly are described to discriminate how the controlling factors determining the adjustment of V̇O₂ might be regulated by specific perturbations. Importantly, this review shows that the slower adjustment of oxidative phosphorylation typically seen in older compared with young individuals can be completely abolished in some exceptional situations such as chronic endurance-exercise training, despite the age-related decrease in maximal V̇O₂ still being present.
CONCLUSIONS
Thus, this review focuses on the concept that although V̇O₂ kinetics is often slower in the elderly, this slower increase in the rise of oxygen uptake during the exercise on-transient does not need to be considered an inevitable response.
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10.1249/MSS.0000000000000686
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pubmed_135_5897
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Antibiotics, especially fluoroquinolones, have been exhaustively used in animal husbandry. However, very limited information on the occurrence and exposure assessment of fluoroquinolone residues in chicken and pork in China is available to date. Thus, a total of 1754 chicken samples and 1712 pork samples were collected from 25 provinces in China and tested by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for residual determination of six common fluoroquinolones. The results revealed that the detection frequencies of fluoroquinolone residues were 3.99% and 1.69% in chicken and pork samples. The overall violation frequencies were 0.68% and 0.41% for chicken and pork. Enrofloxacin and its metabolite ciprofloxacin were found to be the most predominant fluoroquinolones. The occurrence of these antibiotics in different sampling regions and market types was analyzed. The %ADI values of enrofloxacin and ciprofloxacin were far less than 100, indicating the health risk associated with the exposure to these aforementioned fluoroquinolone residues via chicken and pork for Chinese children, adolescents, and adults was acceptable. The results provided useful references for Chinese consumers, and helped to appropriately use these antibiotics in poultry and livestock industry.
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10.3390/antibiotics11101292
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pubmed_381_5454
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Polyamine oxidases (PAOs), which are flavin adenine dinucleotide-dependent enzymes, catalyze polyamine (PA) catabolism, producing hydrogen peroxide (H2O2). Several PAO family members have been identified in plants, but their expression in pepper plants remains unclear. Here, six PAO genes were identified in the 'Zunla-1' pepper genome (named CaPAO1-CaPAO6 according to their chromosomal positions). The PAO proteins were divided into four subfamilies according to phylogenetics: CaPAO1 belongs to subfamily I; CaPAO3 and CaPAO5 belong to subfamily III; and CaPAO2, CaPAO4, and CaPAO6 belong to subfamily IV (none belong to subfamily II). CaPAO2, CaPAO4, and CaPAO6 were ubiquitously and highly expressed in all tissues, CaPAO1 was mainly expressed in flowers, whereas CaPAO3 and CaPAO5 were expressed at very low levels in all tissues. RNA-seq analysis revealed that CaPAO2 and CaPAO4 were notably upregulated by cold stress. CaPAO2 and CaPAO4 were localized in the peroxisome, and spermine was the preferred substrate for PA catabolism. CaPAO2 and CaPAO4 overexpression in Arabidopsis thaliana significantly enhanced freezing-stress tolerance by increasing antioxidant enzyme activity and decreasing malondialdehyde, H2O2, and superoxide accumulation, accompanied by the upregulation of cold-responsive genes (AtCOR15A, AtRD29A, AtCOR47, and AtKIN1). Thus, we identified candidate PAO genes for breeding cold-stress-tolerant transgenic pepper cultivars.
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10.3390/ijms23179999
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pubmed_583_17177
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The Escherichia coli Rsd protein forms 1 : 1 complexes with sigma(70) protein, which is the major factor in determining promoter recognition by RNA polymerase. Here we describe measurements of the levels of Rsd, RNA polymerase, sigma(70) and the alternative sigma(38) factor. Rsd levels are sufficient to sequester a significant proportion of sigma(70) and immunoaffinity pull-down experiments show that this occurs in stationary phase but not in exponentially growing cells. Rsd expression is controlled by two promoters, P1 and P2. Experiments with lac fusions show that the P2 promoter is stronger than P1, that P2 is active in all phases of growth, and that this accounts for the high levels of Rsd.
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10.1039/B904955j
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pubmed_584_6011
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The complete nucleotide sequence and organization of the Yersinia enterocolitica strain A127/90 serotype O:8 biotype 1B virulence plasmid (pYVa127/90) were determined. In contrast to other biotype 1B strains, usually isolated in the USA, strain A127/90 was isolated in Japan. The organization of the genes carried by the 66591-bp pYVa127/90 plasmid is globally similar to that of 67720-bp pYVe8081, the virulence plasmid from 8081, an American isolate of serotype O:8 biotype 1B. Differences are noticeable in the amino acid sequences of the SycH chaperone, the YopM cytotoxin and the plague-protective antigen LcrV. Interestingly, pYVa127/90 contains the entire coding sequence of the YlpA lipoprotein, which is missing from pYVe8081. In addition, we identified five potential new genes. Several vestigial insertion sequence elements appeared to be different between the two plasmids. These observations suggest that both pYV plasmids are from a common ancestor but may have evolved independently following the conquest of two distant ecological niches.
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10.1016/S0923-2508(03)00147-5
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pubmed_230_4792
|
BACKGROUND AND PURPOSE
The purpose of this study was to assess the effect of postcontrast CT (PCCT) leakage (PCL) on hematoma growth in CTA spot negative patients.
METHODS
A retrospective study of 61 patients presenting within 6 hours of primary ICH onset imaged with CT angiography (CTA) and PCCT. Presence of CTA spot sign and PCL were documented. PCL was defined as the presence of contrast extravasation on the PCCT study at a location remote from the CTA spot sign if present. Hematoma expansion was defined as >6 mL or 30% hematoma enlargement. Patients were dichotomized by CTA spot sign presence and PCL and compared for baseline demographic data, hematoma size, and growth using the unpaired t test and Mann-Whitney test for continuous and categorical data, respectively. A probability value <0.05 was considered significant.
RESULTS
PCL was present in 11/61 patients (18%), occurring in 5 without a spot sign (45%). Spot negative PCL patients demonstrated larger absolute (P=0.02) and percentage hematoma growth (P=0.02) compared to those without PCL. The mean volume and percent increase was 6.7 mL and 26%, respectively. Inclusion of PCL together with CTA spot sign as risk factor for hematoma expansion increased sensitivity from 0.78 (95% CI; 0.52 to 0.94) to 0.94 (95% CI; 0.72 to 1.00) and NPV from 0.90 (95% CI; 0.76 to 0.97) to 0.97 (95% CI; 0.85 to 1.00).
CONCLUSIONS
Inclusion of PCCT in the investigation of ICH patients allows detection of PCL which, together with the CTA spot sign, increases sensitivity and negative predictive value for predicting hematoma expansion. This finding should be validated in larger studies.
|
10.1161/STROKEAHA.108.541201
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pubmed_1057_13378
|
Comprehensive characterization of non-Poissonian, bursty temporal patterns observed in various natural and social processes is crucial for understanding the underlying mechanisms behind such temporal patterns. Among them bursty event sequences have been studied mostly in terms of interevent times (IETs), while the higher-order correlation structure between IETs has gained very little attention due to the lack of a proper characterization method. In this paper we propose a method of representing an event sequence by a burst tree, which is then decomposed into a set of IETs and an ordinal burst tree. The ordinal burst tree exactly captures the structure of temporal correlations that is entirely missing in the analysis of IET distributions. We apply this burst-tree decomposition method to various datasets and analyze the structure of the revealed burst trees. In particular, we observe that event sequences show similar burst-tree structure, such as heavy-tailed burst-size distributions, despite of very different IET distributions. This clearly shows that the IET distributions and the burst-tree structures can be separable. The burst trees allow us to directly characterize the preferential and assortative mixing structure of bursts responsible for the higher-order temporal correlations. We also show how to use the decomposition method for the systematic investigation of such correlations captured by the burst trees in the framework of randomized reference models. Finally, we devise a simple kernel-based model for generating event sequences showing appropriate higher-order temporal correlations. Our method is a tool to make the otherwise overwhelming analysis of higher-order correlations in bursty time series tractable by turning it into the analysis of a tree structure.
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10.1038/s41598-020-68157-1
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pubmed_70_11094
|
BACKGROUND
The validity of epidemiological studies assessing a lifetime cancer risk due to environmental factors, such as nutrition or smoking behavior strongly depends on the validity of the patient's history.
OBJECTIVES
This study assesses whether a standardized questionnaire is a valid tool to identify exposure with acrylamide by relating the self-reported food and smoking history with a biomarker, namely hemoglobin-adduct levels of acrylamide.
METHODS
Objective parameters of previous exposure, such as hemoglobin-adduct levels of acrylamide and of the smoking-specific acrylonitrile, respectively, were related to self-reported data in 1,008 volunteers of the general population in bivariate analyses and a multiple linear regression analysis using the log-transformed biomarker levels as outcome.
RESULTS
Smoking was significantly associated with adduct levels of acrylamide (p < 0.0001) and had a main contribution to the internal burden with acrylamide. In cigarette smokers a strong correlation between the number of cigarettes smoked daily and the corresponding biomarkers was observed. Focusing on non-smokers (n = 828), a significant but weak correlation was found in bivariate analyses (Spearman rank correlation coefficient: 0.178 (95% CI: 0.089-0.268) in females and 0.168 (95% CI: 0.063-0.273) in males. A multiple linear regression analysis similarly yielded evidence of a significant association between the highest intake category and adduct levels; however, explained variability was very small (R(2) = 0.08).
CONCLUSION
Self-reported data concerning smoking behavior were highly valid, while self-reported food intake is apparently not as useful for estimating food-related acrylamide exposure.
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10.1007/s10552-007-9090-9
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pubmed_162_22984
|
The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.
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pubmed_162_22984
|
pubmed_738_17363
|
BACKGROUND
Ileal pouch function is affected by several patient factors and pouch physiology. The significance of pouch physiology on optimal pouch function has not been well characterized. The purpose of this study was to examine specific post-ileal pouch anal anastomosis (IPAA) physiologic parameters to determine impact on pouch function and quality of life.
METHODS
Patients undergoing proctocolectomy with IPAA for ulcerative colitis were examined. Post-IPAA compliance, pouch anal pressure gradient (PAPG), and function were assessed 6-8 months postoperatively. Compliance was calculated as change in volume divided by change in pressure. PAPG was calculated as the difference between anal pressure and intra-pouch pressure at a fixed volume. Pouch function evaluation included stool frequency and episodes of incontinence. Quality of life was evaluated using the Rockwood Fecal Incontinence Quality of Life Scale.
RESULTS
A total of 125 patients were investigated. Post-IPAA resting anal pressure averaged 58.1 ± 15 mmHg. Mean volume and intra-pouch pressure at evacuation were 245 mL and 33.9 mmHg, respectively. Compliance averaged 11.2 mmHg/mL with a mean PAPG of - 29.3 mmHg. Compliance and PAPG correlated with 24-h (p = 0.003, p = 0.004) and nighttime stool frequency (p = 0.04, p = 0.03). Daytime continence was impacted by compliance (p = 0.04), PAPG (p = 0.02), and resting anal pressure (p = 0.02).
CONCLUSION
This unique evaluation reveals a significant correlation between IPAA physiologic properties and function. Optimal function and quality of life depend in part on maintaining optimal pouch compliance and pressure differentials between the pouch and anal canal, defined by the pouch anal pressure gradient.
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10.1007/s11605-020-04617-3
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pubmed_490_7667
|
Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.
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10.1186/s12943-017-0730-8
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pubmed_669_24840
|
Increasing evidence suggests that traditional Chinese medicine strategies are obviously beneficial for cancer treatment, but scientific research on the underlying molecular mechanisms is lacking. We report that ursolic acid, a bioactive ingredient isolated from Radix Actinidiae chinensis, has strong antitumour effects on osteosarcoma cells. Functional studies showed that ursolic acid inhibited tumour cell proliferation and promoted the apoptosis of a variety of osteosarcoma cells. Ursolic acid had a synergistic cytotoxic effect with cisplatin on osteosarcoma cells. In a mouse osteosarcoma xenograft model, low-dose cisplatin combined with ursolic acid significantly reduced tumour growth. Notably, ursolic acid reversed weight loss in mice treated with cisplatin. Mechanistic studies showed that ursolic acid degraded ferritin by activating autophagy and induced intracellular overload of ferrous ions, leading to ferroptosis. In addition, ursolic acid enhanced the DNA-damaging effect of cisplatin on osteosarcoma cells. Taken together, these findings suggest that ursolic acid is a nontoxic adjuvant that may enhance the effectiveness of chemotherapy in osteosarcoma.
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10.1155/2021/5192271
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pubmed_1061_3915
|
Centers and institutes are created to support interdisciplinary collaboration. However, all centers and institutes face the challenge of how best to evaluate their impact since traditional counts of productivity may not fully capture the interdisciplinary nature of this work. The authors applied techniques from social network analysis (SNA) to evaluate the impact of a center for interprofessional education (IPE), a growing area for centers because of the global emphasis on IPE.The authors created networks based on the connections between faculty involved in programs supported by an IPE center at Virginia Commonwealth University from 2014 to 2017. They used mathematical techniques to describe these networks and the change in the networks over time. The results of these analyses demonstrated that, while the number of programs and involved faculty grew, the faculty maintained a similar amount of connection between members. Additional faculty clusters emerged, and certain key faculty were important connectors between clusters. The analysis also confirmed the interprofessional nature of faculty collaboration within the network.SNA added important evaluation data beyond typical metrics such as counts of learners or faculty. This approach demonstrated how a center was evolving and what strategies might be needed to support further growth. With further development of benchmarks, SNA could be used to evaluate the effectiveness of centers and institutes relative to each other. SNA should guide strategic decisions about the future of centers and institutes as they strive to meet their overarching goal of tackling a social challenge through interdisciplinary collaboration.
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10.1097/ACM.0000000000003010
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pubmed_3_22969
|
Whereas the presence of a subjective memory complaint is a central criteria for mild cognitive impairment (MCI), little work has been done to empirically measure its nature and severity. The Self-Evaluation Questionnaire (QAM) assessed memory complaints relative to 10 domains of concrete activities of daily life in 68 persons with MCI, 26 persons with Alzheimer's disease (AD), and 81 healthy older adults. In addition, a neuropsychological battery was administered to assess whether subjective complaints were linked to actual cognitive performance. The findings indicate that individuals with MCI report more memory complaints than controls for a range of specific materials/circumstances. MCI and AD individuals did not differ in their level of memory complaints. Correlational analyses indicated that a higher level of memory complaints relative to conversations and to movies and books were associated with a higher level of objective cognitive deficits in persons with MCI but not in AD. Furthermore, complaints increased in parallel with global cognitive deficits in MCI. These results suggest that persons with MCI report more memory complaints than healthy older controls, but only in specific domains and circumstances, and that anosognosia is more characteristic of the demented than of the MCI phase of Alzheimer's disease.
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10.1017/S1355617708080260
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pubmed_1135_19686
|
OBJECTIVE
To compare fractures and fracture-related resource utilization (RU) among patients with a recent fracture and treated with teriparatide (TPTD) to a matched cohort of patients not treated with TPTD (non-TPTD).
RESEARCH DESIGN AND METHODS
Women aged 50 years or older initiating TPTD (N = 5314; index date between 1 January 2007 and 31 December 2012) were identified in an insurance claims database. Patients with fragility fracture (hip, pelvis, clavicle, humerus, wrist, leg or spine) during the 12 months prior to the index date (N = 1164) were selected to control for unmeasured confounding due to absence of bone mineral density test levels. TPTD patients were matched to the non-TPTD cohort using propensity score and exact matching (N = 912). Relative risk (RR) of fracture and fracture-related RU were estimated by Cox proportional hazard modeling, adjusted for potential fracture risk factors.
RESULTS
Fractures were observed in 4.6%, 8.6%, 10.3%, and 11.3% of TPTD patients and in 9.2%, 15.2%, 19.2% and 21.7% of non-TPTD patients over 6, 12, 18, and 24 months, respectively. The adjusted RR reduction in TPTD was 36% (RR = 0.64, 95% CI: 0.44-0.94) during 6 months, 27% (RR = 0.73, 95% CI: 0.54-0.97) during 12 months, 28% (RR = 0.72, 95% CI: 0.55-0.93) during 18 months, and 28% (RR = 0.72, 95% CI: 0.56-0.92) during 24 months versus matched non-TPTD patients. Fracture-related RU followed a similar trend to that observed for fracture risk.
CONCLUSIONS
This real-world study found TPTD to be more effective in reducing risk of fragility fractures as early as 6 months with continuous treatment benefit up to 24 months compared to a matched non-TPTD cohort. TPTD patients experienced lower rates of fracture-related RU than non-TPTD patients. Key study limitations include the inability to confirm reported diagnostic and procedural codes and the absence of uninsured and individually insured patients in the claims database.
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10.1185/03007995.2015.1066765
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pubmed_629_816
|
OBJECTIVE
To study the application of PCR-SSCP in forensic mtDNA typing.
METHODS
Primers flanking the mtDNA HV-I and HV-II regions were designed. By PCR-SSCP techniques, 70 family trios and 140 unrelated Wuhan Han individuals were investigated and analyzed.
RESULTS
In 70 family trios, the SSCP profiles in region HV-I and HV-II of children were not same to that of their fathers in 98.57% and 97.13% respectively but were identical with their mothers. In 140 unrelated Wuhan Han individuals, 21 haplotypes were found in HVI, GD = 0.9556; 16 haplotypes were found in HVII, GD = 0.9356.
CONCLUSION
PCR-SSCP technique may be useful in forensic mtDNA typing, especially for screening the suspects.
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pubmed_629_816
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pubmed_1090_13030
|
The Authors report a case of benign mucocele which was brought to their attention for emergency treatment. Following a review of the literature, they examine the clinical, anatomopathological, pathogenetic and therapeutic problems related to this rare disease. In conclusion, it is important to assess the benign nature or otherwise of the pathology before proceeding to the most suitable and radical form surgery.
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pubmed_1090_13030
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pubmed_232_848
|
Tissue cells generally pull on their matrix attachments and balance a quasi-static contractility against adequate adhesion, but any correlation with and/or influence on phenotype are not yet understood. Here, we begin to demonstrate how differentiation state couples to actomyosin-based contractility through adhesion and substrate compliance. Myotubes are differentiated from myoblasts on collagen-patterned coverslips that allow linear fusion but prevent classic myotube branching. Post-fusion, myotubes adhere to the micro-strips but lock into a stress fiber-rich state and do not differentiate significantly further. In contrast, myotubes grown on top of such cells do progress through differentiation, exhibiting actomyosin striations within one week. A compliant adhesion to these lower cells is suggested to couple to contractility and accommodate the reorganization needed for upper cell striation. Contractility is assessed in these adherent cells by mechanically detaching one end of the myotubes. All myotubes, whether striated or not, shorten with an exponential decay. The cell-on-cell myotubes relax more, which implies a greater contractile stress. The non-muscle myosin II inhibitor blebbistatin inhibits relaxation for either case. Myotubes in culture are thus clearly prestressed by myosin II, and this contractility couples to substrate compliance and ultimately influences actomyosin striation.
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10.1242/jcs.01496
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pubmed_133_16330
|
A parsimony approach was used to construct phylogenetic trees of the H1, H2 and H3 influenza hemagglutinin subtypes. The parsimony trees were then compared with randomly generated trees to identify regions of the proteins containing the most phylogenetic information, i.e. those regions making the parsimony trees shorter. We reasoned that any areas of the hemagglutinin protein that were phylogenetically 'information-rich' would be good candidates for sites involved in virus-host interactions and their identification might lead to a better understanding of the protein. Molecular modelling, based upon the crystal structure of the H3 hemagglutinin, demonstrated that most phylogenetically important regions of the H1 subtype were on the surface of the hemagglutinin trimer, primarily in the globular region. Many corresponded to known antigenic or receptor binding sites, while others appear to be novel and specific for H1.
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10.1016/s0168-1702(99)00098-2
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pubmed_1000_4146
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The open reading frame B438L, located within the EcoRI B fragment of the African swine fever virus genome, is predicted to encode a protein of 438 amino acids with a molecular mass of 49.3 kDa. It presents a cell attachment RGD (Arg-Gly-Asp) motif but no other significant similarity to protein sequences in databases. Northern blot and primer extension analysis showed that B438L is transcribed only at late times during virus infection. The B438L gene product has been expressed in Escherichia coli, purified and used as an antigen for antibody production. The rabbit antiserum specific for pB438L recognized a protein of about 49 kDa in virus-infected cell extracts. This protein was synthesized late in infection by all the virus strains tested, was located in cytoplasmic virus factories and appeared as a structural component of purified virus particles.
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10.1099/0022-1317-81-1-59
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pubmed_648_20566
|
BACKGROUND
Health care costs and utilization for those with an intellectual or developmental disability (IDD) have been shown to be higher than the general population.
OBJECTIVE
To investigate the services that contribute to higher costs and utilization among noninstitutionalized children with an IDD.
DESIGN
Matched case-control secondary analysis of the 2000-2017 Medical Expenditure Panel Survey. Pediatric (age 0-21) patients with an IDD were matched to non-IDD subjects. Health care utilization and costs were evaluated with zero-inflated negative binomial regressions and generalized linear models, respectively.
MEASURES
Outcome measures included high-acuity health care utilization [ie, emergency department (ED) visits and hospital admissions], and cost outcomes for total spending, ED use, hospitalization, medications, office visits, home health, and physical therapy.
RESULTS
There was no statistical difference in utilization of EDs among the 2 groups though subjects with an IDD showed more hospitalizations than their matched cohort (incidence rate ratios=1.63, P=0.00). Total health care spending was higher among patients with an IDD (coefficient=$5831, P=0.00). Pediatric spending was higher in all measures except for ED. The biggest discrepancies in spending were seen in home health (coefficient=$2558, P=0.00) and outpatient visits (coefficient=$1180, P=0.00).
CONCLUSIONS
Pediatric patients with an IDD had higher health care spending and utilization than non-IDD subjects in all categories except for ED use.
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10.1097/MLR.0000000000001293
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pubmed_857_1319
|
The above is a review of current concepts and theories in GDM. The initial approach to the gestational diabetic women is to discover the problem early in pregnancy, before any sequelae occur. Traditionally, insulin was instituted early in the course of the gestational diabetic pregnancy. With appropriate monitoring, exercise and diet also may provide the mainstay of therapy.
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pubmed_857_1319
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pubmed_541_20944
|
Streptomyces are Gram-positive, filamentous soil bacteria, which produce a wide variety of metabolites that are currently being exploited in both medicine and agriculture. Moreover, Streptomyces lividans is used as a host strain to effectively express and secrete heterologous proteins to culture media. Genes encoding Sec proteins responsible for the translocation of preproteins have been identified in S. lividans. SecYEG, a complex of integral membrane proteins SecY, SecE, and SecG in the cytoplasmic membrane, constitutes a pathway for polypeptide movement. SecA plays a central role in translocation as it is the site of preprotein entry into the translocase and it is the only ATPase essential for preprotein translocation. The role of SecD and SecF is to regulate the movement of the translocating protein. A better understanding of their regulatory mechanism could help to develop S. lividans strains with hyper-secretory capacity. In this study, a reporter system was used to investigate the regulatory mechanism of secE promoter. Upstream sequence (496 bp) of secE of S. lividans TK24 was cloned and characterized in a promoter probe vector pIJ4083 upstream of promoterless xylE. Sequencing analysis revealed that secE upstream sequence of S. lividans shares 99.8% homology with the secE promoter of S. coelicolor. The transcriptive activity of this fragment approximates vsi promoter in CMI medium, a strong promoter from S. venezuelae. The activity of secE promoter was observed in different growth phase, culture temperature and culture media. The expression level of secE was higher during the log phase, but decreased at the beginning of the stationary phase. At growth temperature of 28 degrees C, the expression level was much higher than that at 37 degrees C. When the bacteria were incubated in NB, Phage, and CM medium respectively, the expression level of secE promoter was different at a certain fermentation time, but all reached the highest level at log phase. Further analysis revealed that glucose may repress secE promoter expression.
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pubmed_541_20944
|
pubmed_868_19667
|
The native distribution of the small labyrinth fish species Pseudosphromenus cupanus includes southern India and Sri Lanka. According to literature it has a range including also Pakistan, Bangladesh, Myanmar, Malaysia, and Indonesia (Sumatra) but there are no voucher specimens or reliable observations from those areas. The distribution record of P. cupanus was inflated partly by including P. dayi as a synonym. Pseudosphronemus dayi is native to the Western Ghats in India, but the origin of the aquarium importation in 1907 was reported as both Cochin (=Kochi) and Malacca (=Malaysia), the latter locality obviously in error. The basis for the Sumatra record is an obviously mislabeled sample of P. dayi from Pulau Weh close to Sumatra. The basis for reporting the species from Pakistan, Myanmar or Bangladesh could not be located. Misidentified museum specimens from Myanmar and Pakistan identified as P. cupanus were never published on. Pseudosphromenus cupanus has been considered recently to be extinct in Bangladesh, but in fact it never occurred there.
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10.11646/zootaxa.3990.4.6
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pubmed_55_11693
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The new computer algorithm FOUND, which is implemented as an integrated module of the DYANA structure calculation program, is capable of performing systematic local conformation analyses by exhaustive grid searches for arbitrary contiguous fragments of proteins and nucleic acids. It uses torsion angles as the only degrees of freedom to identify all conformations that fulfill the steric and NMR-derived conformational restraints within a contiguous molecular fragment, as defined either by limits on the maximal restraint violations or by the fragment-based DYANA target function value. Sets of mutually dependent torsion angles, for example in ribose rings, are treated as a single degree of freedom. The results of the local conformation analysis include allowed torsion angle ranges and stereospecific assignments for diastereotopic substituents, which are then included in the input of a subsequent structure calculation. FOUND can be used for grid searches comprising up to 13 torsion angles, such as the backbone of a complete alpha-helical turn or dinucleotide fragments in nucleic acids, and yields a significantly higher number of stereospecific assignments than the precursor grid search algorithm HABAS.
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10.1023/A:1008391403193
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pubmed_672_11707
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Calcium and other divalent cations rapidly increase intracellular free Ca2+ ([Ca2+]i) in bovine parathyroid cells and inhibit PTH release. In other secretory cells, agonist-dependent generation of inositol trisphosphate (InsP3) through polyphosphoinositide turnover initiates the rise in [Ca2+]i by mobilizing Ca2+ from intracellular stores. To determine whether polyphosphoinositide breakdown is involved in mediating the response to Ca2+ and the divalent cations Ba2+, Mn2+, and Sr2+, we measured the production of inositol polyphosphates in parathyroid cells. Within 120 sec of increasing extracellular Ca2+ to 2.0 mM, InsP3, inositol bisphosphate (InsP2), and inositol monophosphate (InsP1) rose 95 +/- 37%, 87 +/- 17%, and 96 +/- 29%, respectively, vs. values in cells at 0.5 mM Ca2+ (n = 5). Raising extracellular Ca2+ from 0.5-3.0 mM produced even greater peak increments of 134 +/- 13%, 179 +/- 35%, and 313 +/- 65% in InsP3, InsP2, and InsP1, respectively, by 120 sec (n = 4). Similarly, within 10 sec of their addition, BaCl2 (2 mM), MnCl2 (2 mM), and SrCl2 (4 mM) stimulated the production of InsP3 56 +/- 2%, 152 +/- 31%, and 160 +/- 25%, respectively, vs. that in untreated cells at 0.5 mM Ca2+. At later time points, InsP2 and InsP1 were increased. The Ca2+ ionophore ionomycin at concentrations up to 500 nM had no effect on inositol phosphates, although it inhibited PTH release in a dose-dependent manner. Since high Ca2+ and other divalent cations depolarize parathyroid cells, we assessed the effect of high extracellular K+ on inositol polyphosphates. The addition of depolarizing concentrations of K+ (40 mM) did not change inositol phosphates. Thus, Ca2+ and other divalent cations increase the production of InsP3, InsP2, and InsP1 in parathyroid cells by a mechanism independent of increases in [Ca2+]i and of membrane depolarization. We conclude that parathyroid cells express membrane receptors or sensors for Ca2+ and other divalent cations linked to polyphosphoinositide turnover.
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10.1210/endo-123-1-382
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pubmed_31_20058
|
Antipsychotic pharmacotherapy is strongly obesogenic and is associated with increased oxidative stress in patients with schizophrenia. However, whether these changes reflect psychopathology, antipsychotic efficacy, or some other factor is not known. Our study aims to investigate the degree of oxidative stress in different BMI categories and to identify clinical symptomatology that may be paired with increased oxidative stress in a schizophrenia population. To this end, we performed a cross-sectional study and recruited 89 long-term inpatients with schizophrenia and collected the following variables: plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), routine biochemical analysis, and psychopathology through the Positive and Negative Syndrome Scale (PANSS). The results indicate that the levels of the lipid peroxidation product, MDA, were significantly higher in the high BMI group than the low (normal) BMI group. As expected, high BMI was associated with an atherogenic lipid profile; however, it was also associated with fewer psychopathological symptoms. Multiple regression analysis found that MDA levels, the PANSS general psychopathology subscore, and triglyceride levels (all p < 0.05) were independent contributors to the BMI in patients. These results suggested that oxidative stress may play an important role in antipsychotic-induced weight gain. Further investigations using the longitudinal design in first-episode schizophrenia patients are needed to explore the beneficial effect of antioxidants on the abnormal lipid metabolism mediated by antipsychotic treatment.
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10.1038/s41398-018-0303-7
|
pubmed_40_15687
|
There is a large literature focused on the color perception of matte surface. However, recent research showed that the component of surface specular reflection, such as glossiness, also affects categorical color perception. For instance, the color term "gold" was used to name high specular stimuli within a specific range of chromaticity, which overlaps with those of yellow and orange for low specular stimuli. In the present study, we investigated whether the component of surface specular reflectance affects the color perception of 5- to 8-month-old infants by using the preferential looking technique. In the first experiment, we conducted a simple test to determine whether infants perceive yellow and gold as the same color by comparing their preference for these colors over green. If the infants perceive yellow and gold as the same color, they would show similar preference scores over green. On the other hand, if infants show different preference scores over green, it indicates that infants do not perceive yellow and gold as the same color. Only the 7-8 month-old infants showed different preference scores for gold and yellow over green. This result indicates that the 7-8 month-old infants perceive gold and yellow as different colors. In Experiment 2, we eliminated the component of specular reflectance on the gold surface and presented it against green to infants. A similar preference score of yellow over green was obtained. This result suggests that the difference between the preference scores for gold and yellow over green in Experiment 1 was based on representations of glossiness.
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10.1371/journal.pone.0067535
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pubmed_190_5596
|
AIM
Dendroaspis natriuretic peptide (DNP) is the most recently identified member of the natriuretic peptide family. Although DNP has similar structure and function to other members, it is genetically different. The other members are known to cause vasorelaxation but the effects of DNP on vascular structure still remains unclear. In this study, we aimed to find out the role of DNP in the development of vasospasm following aneurysmal SAH (subarachnoid hemorrhage).
MATERIAL AND METHODS
DNP levels of 17 patients diagnosed with aneurysmal SAH and 25 volunteers as control were measured. All SAH patients were treated with aneurysm clip. Five ml of venous blood sample was obtained on postoperative 1, 3 and 7th days from each patient. Additionally, DNP levels were determined by obtaining cerebrospinal fluid (CSF) postoperative 1, 3 and 7th days.
RESULTS
Statistically significant difference was observed between cerebrospinal fluid DNP levels on day 1 and day 3 (P < 0.05).
CONCLUSION
This study suggests that DNP can be anticipated among molecules leading development of vasospasm. The findings of present study are believed to encourage further studies regarding receptors and receptor specific drugs.
|
10.5137/1019-5149.JTN.8016-13.2
|
pubmed_257_10994
|
The relationship between psychopathology and brain alterations, measured by computed tomography (CT), was investigated in 44 depressed patients. Comparisons of ventricle-brain ratio (VBR) between "endogenous" vs. "nonendogenous" subgroups, classified by six distinct diagnostic systems, revealed no significant differences. The VBR and the width of the third ventricle correlated significantly with scores on the Brief Psychiatric Rating Scale, the Global Assessment Scale, the Bech-Rafaelsen Melancholia Scale, the Rating for Emotional Blunting, and the Scale for the Assessment of Negative Symptoms, but not with scores on the Hamilton Rating Scale for Depression and the Hamilton Rating Scale for Anxiety. Item analyses of the Bech-Rafaelsen Melancholia Scale revealed that retardation-related items were most significantly correlated with ventricular size. The wider diameter of the third ventricle in psychotic patients was associated with higher scores on retardation in the psychotic subgroup, whereas the greater distances of both Sylvian fissures showed no relationship to psychomotor retardation. No significant correlations were found between CT values and anxiety, suicidal impulses, somatic complaints, and sleep disturbances.
|
10.1016/0165-1781(89)90037-1
|
pubmed_111_8821
|
The effect of monoclonal antibodies to fibronectin-binding acid polysaccharide (anti-FAPS) on differentiation of primary mesenchyme cells and spicule formation was examined in cultured embryonic cells isolated from the sea urchin, Hemicentrotus pulcherrimus. Spicule formation of micromere-derived cells was enhanced by anti-FAPS. The increase of spicule formation correlated with the increase of calcium uptake into micromere-derived cells and spicules. Furthermore, both spicule formation and calcium uptake were inhibited by calcium-channel blockers (verapamil, diltiazem and nicardipine) and divalent ions (manganese and cobalt). These results suggest that FAPS, a component of the blastocoelic extracellular matrix surrounding the primary mesenchyme cells, may regulate the level of calcium uptake and spicule formation.
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10.1016/0045-6039(85)90538-x
|
pubmed_806_18909
|
The concept of bioisosteric replacement matrices is applied to explore the chemical space of serotonin receptor ligands, aiming to determine the most efficient ways of manipulating the affinity for all 5-HT receptor subtypes. Analysis of a collection of over 1 million bioisosteres of compounds with measured activity towards serotonin receptors revealed that an average of 31 % of the ligands for each target are mutual bioisosteres. In addition, the collected dataset allowed the development of bioisosteric matrices-qualitative and quantitative descriptions of the biological effects of each predefined type of bioisosteric substitution, providing favored paths of modifying the compounds. The concept exemplified here for serotonin receptor ligands can likely be more broadly applied to other target classes, thus representing a useful guide for medicinal chemists designing novel ligands.
|
10.1002/cmdc.201402563
|
pubmed_254_7187
|
Parasites obtain energy and nutrients from the host, and their body size is also usually limited by host size. However, the regulatory mechanisms that control the plasticity of parasite body sizes and the stoichiometric relationships with their hosts remain unclear. Here we investigated the concentrations of 14 elements (C, H, O, N, P, S, K, Na, Ca, Mg, Al, Fe, Mn, and Zn) in the acorns of three oak species (Quercus spp.), in their endoparasitic weevil (Curculio davidi Fairmaire) (Coleoptera: Curculionidae) larvae and in the larval feces, and the weight of weevil larvae within different hosts in a warm-temperate zone of China. Our results showed that the three acorn species exhibited significant differences in C, H, O, P, K, Mg, and Mn concentrations. However, in the weevil larvae, only P, Mn, and C:P ratio revealed significant differences. Weevil larvae preferentially absorbed and retained N, Zn, Na, and P, whereas Mn, K, Ca, and O were passively absorbed and transported. The weevil larvae weight was associated with acorn stoichiometry, and positively correlated with acorn size. Weevil larvae P decreased, but Mn and C:P increased with their weight, implying highly variable in somatic stoichiometry are coupled with the plasticity of body size. Interestingly, weevil larvae weight was negatively correlated with acorn infection rate, indicating small-size parasitic insects might have higher fitness level in parasite-host systems than larger-size ones. Our results suggest that variation in P, Mn, and C:P in parasites may play critical roles in shaping their body size and in improving their fitness.
|
10.1093/jisesa/ieaa139
|
pubmed_1075_22050
|
OBJECTIVES
After pancreas transplantation (PTx), early capillary malperfusion and leukocyte recruitment indicate the manifestation of severe ischemia/reperfusion injury (IRI). Oscillatory blood-flow redistribution (intermittent capillary perfusion, IP), leading to an overall decrease in erythrocyte flux, precedes complete microvascular perfusion failure with persistent blood flow cessation. We addressed the role of intercellular adhesion molecule-1 (ICAM-1) for leukocyte-endothelial interactions (LEIs) after PTx and evaluated the contribution of IP and malperfusion.
METHODS
Pancreas transplantation was performed in rats after 18-hour preservation, receiving either isotype-matched IgG or monoclonal anti-ICAM-1 antibodies (10 mg/kg intravenously) once before reperfusion. Leukocyte-endothelial interaction, IP, erythrocyte flux, and functional capillary density, respectively, were examined in vivo during 2-hour reperfusion. Nontransplanted animals served as controls. Tissue samples were analyzed by histomorphometry.
RESULTS
In grafts of IgG-treated animals, IP was encountered already at an early stage after reperfusion and steadily increased over 2 hours, whereas erythrocyte flux declined continuously. In contrast, inhibition of ICAM-1 significantly improved erythrocyte flux and delayed IP appearance by 2 hours. Further, anti-ICAM-1 significantly reduced LEI and leukocyte tissue infiltration when compared to IgG; edema development was less pronounced in response to anti-ICAM-1 monoclonal antibody.
CONCLUSION
Intercellular adhesion molecule-1 blockade significantly attenuates IRI via immediate reduction of LEI and concomitant improvement of capillary perfusion patterns, emphasizing its central role during IRI in PTx.
|
10.1097/MPA.0b013e31824abb2c
|
pubmed_286_20817
|
Hybrid (organic-inorganic) multication lead halide perovskites hold promise for a new generation of easily processable solar cells. Best performing compositions to date are multiple-cation solid alloys of formamidinium (FA), methylammonium (MA), cesium, and rubidium lead halides which provide power conversion efficiencies up to around 22%. Here, we elucidate the atomic-level nature of Cs and Rb incorporation into the perovskite lattice of FA-based materials. We use 133Cs, 87Rb, 39K, 13C, and 14N solid-state MAS NMR to probe microscopic composition of Cs-, Rb-, K-, MA-, and FA-containing phases in double-, triple-, and quadruple-cation lead halides in bulk and in a thin film. Contrary to previous reports, we have found no proof of Rb or K incorporation into the 3D perovskite lattice in these systems. We also show that the structure of bulk mechanochemical perovskites bears close resemblance to that of thin films, making them a good benchmark for structural studies. These findings provide fundamental understanding of previously reported excellent photovoltaic parameters in these systems and their superior stability.
|
10.1021/jacs.7b07223
|
pubmed_450_911
|
BACKGROUND
Systemic inflammation is a key factor in tumor growth. C-reactive protein and albumin are parameters of systemic inflammation from the Glasgow Prognostic Score (GPS). The purpose was to evaluate the prognostic role of GPS in a homogeneous population of gastric cancer patients undergoing surgical treatment only.
METHODS
Patients underwent operations between 2009 and 2014. Those who had received perioperative treatment or had other malignancies or inflammatory diseases were excluded. Eighty-eight patients met all inclusion criteria (age >18 years, documented preoperative serum levels of albumin and C-reactive protein, histologically proven gastric cancer, curative operation, including lymphadenectomy). C-reactive protein and albumin levels were retrieved from our prospective database. GPS was correlated with clinicopathologic characteristics and outcome.
RESULTS
Increasing GPS was linked to aggressive tumor biology in terms of tumor size (GPS 0: 51.2% T1 and T2, 48.8% T3 and T4; GPS 1: 23.8% T1 and T2, 76.2% T3 and T4; GPS 2: 23.1% T1 and T2, 76.9% T3 and T4; P = .026), synchronous distant metastases (GPS 0: 47.1% M0, 0.0% M1; GPS 1: 25.9% M0, 0.0% M1; GPS 2: 27.1% M0, 100.0% M1; P = .030), venous vessel invasion (GPS 0: 91.2% V0, 8.8% V1; GPS 1: 66.7% V0, 33.3% V1; GPS 2: 55.0% V0, 45.0% V1; P = .008), resection margin status (GPS 0: 97.4% R0, 2.6% R1; GPS 1: 90.0% R0, 10.0% R1; GPS 2: 77.3% R0, 22.7% R1; P = .044), reduced overall survival (GPS 0: median 25.2 months [range 0.4-106.0]; GPS 1: 15.3 [0.2-59.5]; GPS 2: 5.8 [0.1-55.3]; P = .016) with median overall survival in the whole cohort being 16.2 months (range 0.1-106.0) and perioperative mortality (GPS 0: 0.0% of perioperative deaths, GPS 1: 20.0%, GPS 2: 80.0%; P = .036). Furthermore, GPS was identified as an independent prognosticator of overall survival (P = .033). A gradual decrease in survival between GPS subgroups was evident.
CONCLUSION
GPS represents an independent prognostic factor for long-term outcome in resected gastric cancer patients without perioperative treatment and is strongly associated with perioperative mortality.
|
10.1016/j.surg.2016.01.018
|
pubmed_129_9072
|
On the basis of 1518 values of concentration of glycosylated Hb in blood of workers responsible for safety in railroad transportation authors tried to calculate the range of normal values of this parameter. It was assumed that distribution of GHb in a healthy part of population is normal. From the primary set of data, values most distant from the arithmetic mean were gradually discarded until distribution of values was as close to the normal distribution as attainable. The best fit to the normal distribution was obtained for 1486 values. The normal range was then 4.6 to 8.6% (mean +/- 2 SD). The normal range was in a good agreement with published data as well as with own analytical experience.
|
pubmed_129_9072
|
pubmed_71_24248
|
T-2 toxin (T-2), one of the most toxic trichothecene A-type mycotoxins, is biotransformed in animal tissues to modified T-2s (mT-2s) including T-2-glucuronide (T-2-GlcA). In this study, the optimal conditions for T-2-GlcA synthesis were established, and the JAK/STAT pathway in RAW264.7 cells was used to study the toxicity of T-2-GlcA. Because many mT-2 standards are not readily available, optimal conditions for T-2-GlcA synthesis in vitro were established by incubating T-2 with rat liver microsomes, UDPGA, and 0.2% Triton X-100 for 90 min. qRT-PCR and Western blot results showed 21- and 760-fold increases in IL-6 mRNA expression induced by T-2-GlcA and T-2, respectively. Similar differences were observed in JAK3, SOCS2/3, and CIS mRNA expression. T-2-GlcA induced a dose-responsive decrease in STAT1 mRNA expression, whereas the result with T-2 was the opposite. Moreover, the phosphorylation of STAT3 induced by T-2-GlcA was higher than that by T-2, whereas the phosphorylation of STAT1 was to the contrary. Overall, the results show that T-2-GlcA was somewhat toxic, but activation of the JAK/STAT pathway in RAW264.7 was higher by T-2.
|
10.1021/acs.jafc.7b01250
|
pubmed_50_8742
|
Objective: We compared the clinical course of type 2 diabetic patients whose basal insulin preparations were replaced from insulin glargine (IGlar) 100 units/mL (U100) to IGlar biosimilar or IGlar 300 units/mL (U300). Methods: After propensity score matching, 34 patients whose basal insulin preparation was switched from IGlar U100 to IGlar biosimilar and 102 switched to IGlar U300 were observed for 6 months. Results: The HbA1c level and body weight did not change significantly after the replacement in the IGlar biosimilar or IGlar U300 groups. In the IGlar biosimilar group, the frequency of subjects who experienced hypoglycemia after the replacement (12%) was not different from before (12%). However, the frequency was significantly lower after the replacement (2%) than before (13%) in the IGlar U300 group. The change in the HbA1c level after the replacement showed a significant association with the HbA1c level at the baseline but not with the kind of IGlar. Hypoglycemia was frequently observed in subjects who had experienced hypoglycemia before the replacement. Conclusions: IGlar biosimilar and IGlar U300 induced similar HbA1c and body weight changes among type 2 diabetic patients. IGlar biosimilar is a suitable option for patients with a low risk for hypoglycemia.
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10.1080/21556660.2018.1513846
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pubmed_814_6466
|
Developments in genome editing offer potential solutions to challenges in agriculture, industry, medicine, and the environment. However, many technologies remain unexploited due to limitations in the use of genetically altered organisms. In this study, we use B. subtilis spores to explore the possibility of bioengineering organisms while leaving their genome intact. Taking advantage of the differential expression between the mother cell and the fore-spore compartments during sporulation, we created plasmids programmed to modify the spore phenotype from the mother cell compartment, but to "self-digest" in the fore-spore. At the end of sporulation, the mother cell undergoes lysis and releases the phenotypically engineered, genetically unaltered spores. Using this approach, we demonstrated the potential to express foreign proteins in B. subtilis spores without genome alterations by producing spores expressing GFP in their protective coats, where approximately 90% of the spore population had no detectable plasmid or chromosome alterations. In a separate demonstration, we programmed KinA overexpression during vegetative growth to artificially induce sporulation, and also obtained spores with nearly 90% of them free of detectable plasmid. Artificial induction of sporulation could potentially simplify the bioprocess for industrial spore production, as it reduces the number of steps involved. Overall, these findings demonstrate the potential to create genetically intact bioengineered organisms.
|
10.1021/acssynbio.0c00578
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pubmed_97_1088
|
Nutritional needs and dietary goals of the older athlete involve meeting basic physiologic requirements of aging and exercise, promoting weight control, and incorporating guidelines for reducing the risk of chronic disease. Conservative dietary approaches to weight loss in the obese patient and a high-carbohydrate diet for maximum exercise performance are sound approaches, although diets often need to be individualized. Recent dietary recommendations to reduce fat and increase fiber can be applied without risk of compromising nutritional status for most patients. Guidance away from extremes in caloric restriction and in the distribution of calories may help to promote health and the maintenance of exercise activities. Although requirements for certain micronutrients are affected by aging, vitamin and mineral supplements are unlikely to be necessary for healthy adults and should meet basic criteria for safety if they are prescribed. Diet sources of calcium may require attention, although iron requirements are reduced among postmenopausal women when compared with younger athletes. Adequate fluid replacement is essential for athletes of all ages. For the older athlete who is competing in high-intensity endurance exercise, evidence for the usefulness of 4% to 10% carbohydrate-containing sports drinks exists. Little evidence supports the use of ergogenic aids, such as supplements and unusual food products. Resources and personalized guidance from a registered dietitian can be helpful for many older athletes.
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pubmed_97_1088
|
pubmed_146_1620
|
PURPOSE
Individual case reports (observational or interventional) are thought to have a very low ranking for evidentiary significance. This clinical report examines the relationship between the evidentiary significance of case reports and their presentation.
METHODS
An observational report of unilateral keratoconus (KC), that developed in association with a corresponding unilateral chronic habit of abnormal rubbing, is examined to identify features that can raise the level of evidentiary significance.
RESULTS
A feature of this type of case is the opportunity to compare the eye with KC to the unaffected eye, for which there was an unremarkable rubbing history. The unaffected eye serves as a retrospective unintentional control for the affected eye. Detailed assessment to establish the normality of the apparently normal eye is crucial to the differential diagnosis between a markedly asymmetric presentation and a true unilateral presentation. Any history of systemic diseases that may be associated with the presenting disease can be important. Longitudinal follow-up, especially if postonset data are supplemented with preonset data, can contribute to the evidentiary base by allowing for comparison with the natural history of the relevant disease. Intervention to remove a suspected causal factor, when combined with appropriate follow-up, can provide additional evidence.
CONCLUSIONS
Depending on their presentation, some types of case report can have a significant evidence-based function in assessing causal hypotheses and, accordingly, provide a higher evidentiary ranking than generally assigned to case reports. The potential for a higher evidentiary ranking may be more important when randomized clinical trials are contraindicated for ethical reasons, or there are challenging problems with study design. Wider agreement regarding the quantitative and qualitative criteria for diagnosing the earliest stages of KC would aid the assessment of the evidentiary significance of case reports of this disease.
|
10.1097/OPX.0b013e318169287a
|
pubmed_270_4090
|
Glycolytic flux may increase over 100 times in skeletal muscle during rest-to-work transition, whereas glycolytic metabolite concentrations remain relatively constant. This constancy cannot be explained by an identical direct activation of all glycolytic enzymes because the concentrations of ATP, ADP, AMP, P(i), NADH and NAD+, modulators of the activity of different glycolytic enzymes, change. It is demonstrated in the present in silico study that a perfect homeostasis of glycolytic metabolite concentrations can be achieved if glycolysis is divided into appropriate blocks of enzymes that are directly activated to a different extent in order to compensate the effect of the modulators.
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10.1049/ip-syb:20060005
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pubmed_1076_1764
|
BACKGROUND
The purpose of this retrospective of prospectively acquired data was to evaluate and to compare global evolution in children with complete unilateral cleft lip and palate treated at the Brussels cleft centre following two different surgical treatment protocols.
METHODS
A series of forty-four patients operated for non-syndromic complete unilateral cleft lip and palate were included in this study at the age of approximately ten years. Twenty-six children (17 males, 9 females) were treated according to the Malek surgical treatment protocol: the soft palate was closed at a mean age of 3 months, followed by simultaneous repair of the lip and hard palate at a mean age of 6 months. Eighteen children (15 males, 3 females) underwent one-stage "all-in-one" closure of the lip, hard and soft palate at a mean age of 3 months. Craniofacial morphology was evaluated by means of digital lateral cephalometric analysis. Cephalometric data were compared to a control, non-cleft group (n = 40) matched according to age. Data concerning otological status and speech were collected in the same series of children.
RESULTS
Statistical analysis showed that the inclination of the maxillary (MxPVSN) plane to the anterior cranial base was significantly increased (p <0.001) in both cleft groups compared to the non-cleft group and significantly increased (p = 0.002) in the Malek cleft group compared to the "all-in-one" cleft group. Otological status was not improved by an early complete closure but by close follow-up and the repeated placement of ventilating tubes. Speech was found to be satisfactory in the majority of children of both groups at six years after speech therapy. Only 15% needed further surgery with pharyngeal flaps.
CONCLUSIONS
There were no significant differences in anteroposterior midfacial morphology between the Malek and "all-in-one" protocols at ten years of age. One-stage "all-in-one" closure resulted in less downward inclination of the maxillary plane to the anterior cranial base compared to the Malek protocol at ten years of age. Early complete closure of the cleft resulted in no significant change in otological status or the occurrence of nasality. However, early complete closure of the cleft allowed for earlier intelligibility of speech compared to the staged later closure.
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pubmed_1076_1764
|
pubmed_1013_25801
|
Field-effect transistors (FET) composed of transition metal dichalcogenide (TMDC) materials have gained huge importance as biosensors due to their added advantage of high sensitivity and moderate bandgap. However, the true potential of these biosensors highly depends upon the quality of TMDC material, as well as the orientation of receptors on their surfaces. The uncontrolled orientation of receptors and screening issues due to crossing the Debye screening length while functionalizing TMDC materials is a big challenge in this field. To address these issues, we introduce a combination of high-quality monolayer WSe2 with our designed Pyrene-based receptor moiety for its ordered orientation onto the WSe2 FET biosensor. A monolayer WSe2 sheet is utilized to fabricate an ideal FET for biosensing applications, which is characterized via Raman spectroscopy, atomic force microscopy, and electrical prob station. Our construct can sensitively detect our target protein (streptavidin) with 1 pM limit of detection within a short span of 2 min, through a one-step functionalizing process. In addition to having this ultra-fast response and high sensitivity, our biosensor can be a reliable platform for point-of-care-based diagnosis.
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10.3390/nano12081305
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pubmed_1067_1709
|
Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.
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10.1375/183242705774310079
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pubmed_446_11971
|
The finding of excess urinary glycosaminoglycans (GAG) is the first step in the laboratory diagnosis of mucopolysaccharidosis (MPS). Urinary screening tests are based upon the binding of GAG to dimethylmethylene blue. Alternatively, paper spot tests using toluidine blue are used in human and veterinary laboratory medicine. Positive samples undergo GAG isolation for subsequent characterization. Here, we describe a 3-year-old English Cocker Spaniel with a positive urinary GAG test, but without other clinical signs of MPS. Urine samples were strongly positive with the dimethylmethylene blue test, and isolated GAG subjected to electrophoresis on cellulose acetate revealed a band co-migrating with dermatan sulfate. However, the isolated GAG were resistant to digestion with chondroitinase ABC, suggesting that the band did not represent dermatan sulfate. This was confirmed by mobility of the isolated GAG different from dermatan sulfate on agarose gel electrophoresis. MPS types VI and VII were excluded by enzyme assay. To test the hypothesis of a nutritional source, a healthy control dog was fed the same dog food as the index case. His urine showed a comparable abnormal GAG screening test and electrophoretic pattern. In addition, the analysis of an algal supplement present in the administered dog food showed a similar electrophoretic GAG pattern. The Cocker Spaniel was not available for further testing after withdrawal of the supplement. Algae contain highly sulfated fucans and galactans, and it appears that commercial dog food containing such algal, and possibly other, supplements can give rise to false-positive urinary MPS screening tests.
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10.1111/vcp.12096
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pubmed_688_1591
|
Acenaphthene used as vapour increases the frequency of morphological mutations as well as mutations yielding strains with a reduced activity of respiration in Candida scottii. The diploid culture has more mutants than the haploid culture. The frequency of mutants depends on the duration of acenaphthene action. Cells more resistant to the action of acenaphthene vapour are selected in the haploid culture when C. scottii cells are transferred many times into new wort drops. As a result, the frequency of mutations decreases. When the diploid culture is exposed to the action of acenaphthene vapour for a longer time, the frequency of mutations rises. Apparently, the diploid culture has a lower activity of reparation of premutational damages than the haploid culture and therefore the number of mutant cells increases.
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pubmed_688_1591
|
pubmed_609_19639
|
The current study identifies characteristics that predict change in use of prescription and nonprescription drugs over a period of 3 years. A modified health care services use model was applied to information obtained from a probability-based sample of black (n = 1778) and white (n = 1446) community-resident elderly, interviewed in 1986-1987 and 1989-1990. Analysis was by means of logistic and ordinary least-squares regression, with sample weights and design effects taken into account. The number of users and average number of prescription drugs used increased over the 3 years, and was best predicted by extent of prior drug use, older age, white race, poorer health, and number of health care visits. Conversely, nonprescription drug use declined significantly, and was best predicted by prior use, white race, and female gender. The reduced use of prescription drugs by blacks as compared to whites is of concern, suggesting that attention is needed to assure equitable access to prescription drugs.
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10.1016/0895-4356(95)00563-3
|
pubmed_197_18844
|
A facile synthesis of chiral bicyclic amidines and imidazolines from readily available 1,2-diamines has been developed. The reported synthetic strategy relies on an intramolecular cyclization which involves a carboxylic amide derived imidoyl chloride as a key intermediate and aniline serving as a leaving group.
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10.1021/ol101747n
|
pubmed_625_439
|
OBJECTIVE
Hypoglossal nerve stimulation represents a novel therapy for the treatment of moderate-severe obstructive sleep apnea; nonetheless, its cardiovascular effects are not known. We examine the effects of hypoglossal nerve stimulation on heart rate variability, a measure of autonomic function.
STUDY DESIGN
Substudy of the STAR trial (Stimulation Therapy for Apnea Reduction): a multicenter prospective single-group cohort.
SETTING
Academic and private practice centers in the United States and Europe.
SUBJECTS AND METHODS
A subset of responder participants (n = 46) from the STAR trial was randomized to therapy withdrawal or therapy maintenance 12 months after surgery. Heart rate variability analysis included standard deviation of the R-R interval (SDNN), low-frequency power of the R-R interval, and high-frequency power of the R-R interval. Analysis was performed by sleep with 5-minute sliding window epochs during baseline, 12 months, and the maintenance/withdrawal period.
RESULTS
A significant improvement from baseline to 12 months in heart rate variability was seen for SDNN and low frequency across all sleep stages. SDNN analysis demonstrated no change in the wake period (mean ± SD: 0.042 ± 0.01 vs 0.077 ± 0.07, P = .19). Reduction in SDNN was correlated to improvement in apnea-hypopnea index ( r = 0.39, P = .03). In the therapy withdrawal group, no significant changes in SDNN were seen for N1/N2, N3, or rapid eye movement sleep.
CONCLUSION
Hypoglossal nerve stimulation therapy appears to reduce heart rate variability during sleep. This reduction was not affected by a 1-week withdrawal period. Larger prospective studies are required to better understand the effect of hypoglossal nerve stimulation on autonomic dysfunction in obstructive sleep apnea.
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10.1177/0194599818800284
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pubmed_855_10452
|
Histological changes and dynamics of morphometric parameters of ischemic lesion, organization and regeneration of bone marrow and osseous tissue were studied experimentally in rabbits with embolic aseptic infarction of long bones (on d 3-60). Correlation dependences were determined and regression equations were derived between morphometric parameters of lesion and regeneration of bone tissues. Close or medium connections were demonstrated between volume of ischemic necrosis of bone marrow and compact substance (exponential regression), those of compact substance and periosteal regenerate (exponential regression), volume of necrosis of compact substance and manifestation of reorganization (power regression), volume of periosteal regenerate and manifestation of reorganization of compact substance (rectilinear regression).
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pubmed_855_10452
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pubmed_121_6818
|
Dental caries is multifactorial and polymicrobial in nature and remains one of the most common oral diseases. While caries research has focused on Streptococcus mutans as the main etiological pathogen, its impact at the tooth level is not fully understood. In this cross-sectional study, the levels and distribution of S. mutans in the posterior teeth at different dentition stages were investigated along with the corresponding tooth-specific microbiome. Occlusal plaque samples of 87 individual posterior teeth were collected from thirty children in three dentition stages (primary, mixed, and permanent). The S. mutans levels in the occlusal plaque of individual posterior teeth were quantified with qPCR, and those with preferential colonization were selected for tooth-specific microbiome analysis using 16S rRNA sequencing. Results: Quantification of S. mutans levels in the occlusal plaque confirmed the preferential colonization on the first primary and permanent molars. These teeth were selected for further tooth-specific microbiome sequencing, as they also displayed high caries experience. There were significant differences in the relative abundance of the four most abundant genera: Neisseria, Streptococcus, Rothia, and Veillonella. Furthermore, the tooth-level caries experience was correlated with a reduction in the microbiome diversity. Analyzing the different tooth-associated microbial communities, distinct tooth-specific core microbiomes were identified. Conclusions: Our findings suggest that caries susceptibility at the tooth level, depending on tooth type and dentition stage, is influenced by individual species as well as plaque community.
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10.3390/microorganisms10061129
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pubmed_211_16242
|
Anti-Neospora caninum antibody was detected in anti-Toxoplasma gondii positive and negative human sera by ELISA, western blot and immunofluorescence assay (IFA). Twelve cases out of 172 (6.7%) Toxoplasma-positive sera cross-reacted with both T. gondii and N. caninum antigens, and one out of 110 Toxoplasma-negative sera reacted with N. caninum antigen by ELISA. By western blot, all 12 sera reacted with T. gondii antigens with various banding patterns but specifically at 30 kDa (SAG1) and 22 kDa (SAG2) bands. With N. caninum antigen, the number of reactive bands was reduced, however a 43 kDa band reacted in three cases in Toxoplasma-positive sera in addition to one in Toxoplasma-negative control sera. All sera of the Toxoplasma-positive group labeled surface membrane of T. gondii, but reacted differently with N. caninum. Fluorescence was detected in surface membrane, subcellular organelles, or both in N. caninum. And one case in the Toxoplasma-negative group also reacted with N. caninum strongly in subcellular organelles. This suggested that the antibody against N. caninum may be present in human sera although the positive rate was very low in this study. The possibility of human infection with N. caninum remains to be evaluated further.
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10.3347/kjp.1998.36.4.269
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pubmed_87_22452
|
OBJECTIVE
Bilateral adrenalectomy (BADX) is an important treatment option for patients with Cushing's syndrome (CS). Our aim is to analyze the long-term outcomes, surgical, biochemical, and clinical as well as morbidity and mortality, of patients who underwent BADX.
DESIGN
A total of 50 patients who underwent BADX since 1990 in two German centers were identified. Of them, 34 patients had Cushing's disease (CD), nine ectopic CS (ECS), and seven ACTH-independent bilateral adrenal hyperplasia (BAH).
METHODS
Standardized follow-up examination was performed in 36 patients with a minimum follow-up time of 6 months after BADX and a median follow-up time of 11 years.
RESULTS
Surgical morbidity and mortality were 6 and 4% respectively. All patients were found to be in remission after BADX. Almost all Cushing's-specific comorbidities except for psychiatric diseases improved significantly. Health-related quality of life remained impaired in 45.0% of female and 16.7% of male patients compared with a healthy population. The median number of adrenal crises per 100 patient-years was four. Nelson tumor occurred in 24% of CD patients after a median time span of 51 months. Long-term mortality after 10 years was high in ECS (44%) compared with CD (3%) and BAH (14%).
CONCLUSIONS
BADX is an effective and relatively safe treatment option especially in patients with CD. The majority of patients experience considerable improvement of Cushing's symptoms.
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10.1530/EJE-14-0214
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pubmed_994_5750
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Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8-12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2-3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe.
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10.1111/jns.12114
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pubmed_624_3004
|
In previous work we injected mitotic cells with fluorescent tubulin and photobleached them to mark domains on the spindle microtubules. We concluded that chromosomes move poleward along kinetochore fiber microtubules that remain stationary with respect to the pole while depolymerizing at the kinetochore. In those experiments, bleached zones in anaphase spindles showed some recovery of fluorescence with time. We wished to determine the nature of this recovery. Was it due to turnover of kinetochore fiber microtubules or of nonkinetochore microtubules or both? We also wished to investigate the question of turnover of kinetochore microtubules in metaphase. We microinjected cells with x-rhodamine tubulin (x-rh tubulin) and photobleached spindles in anaphase and metaphase. At various times after photobleaching, cells were detergent lysed in a cold buffer containing 80 microM calcium, conditions that led to the disassembly of almost all nonkinetochore microtubules. Quantitative analysis with a charge coupled device image sensor revealed that the bleached zones in anaphase cells showed no fluorescence recovery, suggesting that these kinetochore fiber microtubules do not turn over. Thus, the partial fluorescence recovery seen in our earlier anaphase experiments was likely due to turnover of nonkinetochore microtubules. In contrast fluorescence in metaphase cells recovered to approximately 70% the control level within 7 min suggesting that many, but perhaps not all, kinetochore fiber microtubules of metaphase cells do turn over. Analysis of the movements of metaphase bleached zones suggested that a slow poleward translocation of kinetochore microtubules occurred. However, within the variation of the data (0.12 +/- 0.24 micron/min), it could not be determined whether the apparent movement was real or artifactual.
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10.1083/jcb.109.2.653
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pubmed_748_1129
|
AIM
To build up the structure of human fibrinogen receptor GPIIb-IIIa, subsequently combined with its antagonist decorsin, and to investigate the interaction between decorsin and its receptor GPIIb-IIIa at the molecular level.
METHODS
A three-dimensional (3D) molecular model of human fibrinogen receptor GPIIb-IIIa was generated by InsightII, a distance geometry-based homologous modeling package. The structure of human fibrinogen receptor GPIIb-IIIa was built by the InsightII/Homology module using the corresponding of integrin alphaVbeta3 (PDB filecode 1JV2) as the template. Then the primary structures were optimized by energy minimization. Subsequently the structural model was docked with its antagonist decorsin (PDB filecode 1dec).
RESULTS
A good substrate-receptor interaction model was achieved. The interaction sites with decorsin converge at domain 8 (betaA domain of beta3 subunit) of GPIIb-IIIa. The direct interatomic contacts were made between 16 GPIIb/IIIa residues and 10 decorsin amino-acid residues. These included van der Waals contacts, electrostatic interaction, hydrogen bond, and salt bridge. Residues in contact were concentrated in four dispersed regions of human GPIIb-IIIa: the RGD reaction motif (118-132 of GPIIIa), the span from 210 to 213 of GPIIIa, Thr182 residue and Asp251 residue of GPIIIa; and they were distributed over five segments of decorsin: Asp10 residue, Asn18 and Lys19 residues, Arg28 residue, RGD motif, and Asp35-Pro36-Tyr37 segment.
CONCLUSION
This complex model plays an important role in development and research of some new drugs, especially a new guided fusion-type fibrinogen receptor antagonist.
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pubmed_748_1129
|
pubmed_73_23785
|
The occurrence and frequency of sympatric speciation in natural systems continue to be hotly debated issues in evolutionary biology. This might reflect the timescale over which evolution occurs resulting in there being few compelling observations of the phenomenon (lake fishes, phytophagous insects and Island trees). Despite predictions, few examples of sympatric speciation have been recorded in animal parasites, at least widely accepted as such. Here we show that, in New Caledonia, the monophasic (exploiting one individual host per generation) cattle tick Rhipicephalus microplus has evolved in contact with two sympatric host species into two differentiated genetic pools: on the cattle, its original host and on rusa deer, a new host for this tick. This sympatric isolation has occurred over a relative short period of time (i.e. less than 244 tick generations) as a consequence of differential selection pressure imposed by hosts. It is most likely that this phenomenon has occurred in many other places across the globe where this tick has come in contact with different host species in sympatry with cattle.
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10.1016/j.meegid.2010.06.005
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pubmed_889_1614
|
BACKGROUND
Among U.S. residents, tuberculosis (TB) disease disproportionally affects non-U.S.-born persons and varies substantially by country of birth. Yet TB disease incidence rates by country of birth are not routinely reported despite these large, known health disparities. This is in part due to the technical challenges of using standard regression analysis with a communicable disease. Here, we estimate tuberculosis disease incidence rates by country of birth and demonstrate methods for overcoming these challenges using TB surveillance data from Los Angeles County which has more than 3.5 million non-U.S.-born residents.
METHODS
Cross-sectional data on 5,447 cases of TB disease from Los Angeles County were combined with population estimates from the American Community Survey to calculate TB disease incidence rates for 2005 through 2011. Adjusted incidence rates were modelled using Poisson and negative binomial regressions. Bayesian models were used to account for the uncertainty in population estimates.
RESULTS
The unadjusted incidence rate among non-U.S.-born persons was 15 per 100,000 person-years in contrast to the rate among U.S-born persons, 2 per 100,000. The unadjusted incidence rates were 44 and 12 per 100,000 person-years among persons born in the Philippines and Mexico, respectively. In adjusted analysis, persons born in the Philippines were 2.6 (95% CI: 2.3-3.1) times as likely to be reported as a TB case than persons born in Mexico. Bayesian models showed similar results.
CONCLUSION
This study confirms substantial disparities in TB disease by country of birth in Los Angeles County. Accounting for age, gender, years in residence and year of diagnosis, persons from the Philippines, Vietnam and several other countries had much higher rates of reported TB disease than other foreign countries. We demonstrated that incidence rates by country of birth can be estimated using available data despite technical challenges.
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10.1371/journal.pone.0209051
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pubmed_597_3684
|
Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract resulting in inflammation, stricturing and fistulae secondary to transmural inflammation. Diagnosis relies on clinical history, abnormal laboratory parameters, characteristic radiologic and endoscopic changes within the gastrointestinal tract and most importantly a supportive histology. The article is intended mainly for the general gastroenterologist and for other interested physicians. Management of small bowel CD has been suboptimal and limited due to the inaccessibility of the small bowel. Enteroscopy has had a significant renaissance recently, thereby extending the reach of the endoscopist, aiding diagnosis and enabling therapeutic interventions in the small bowel. Radiologic imaging is used as the first line modality to visualise the small bowel. If the clinical suspicion is high, wireless capsule endoscopy (WCE) is used to rule out superficial and early disease, despite the above investigations being normal. This is followed by push enteroscopy or device assisted enteroscopy (DAE) as is appropriate. This approach has been found to be the most cost effective and least invasive. DAE includes balloon-assisted enteroscopy, [double balloon enteroscopy (DBE), single balloon enteroscopy (SBE) and more recently spiral enteroscopy (SE)]. This review is not going to cover the various other indications of enteroscopy, radiological small bowel investigations nor WCE and limited only to enteroscopy in small bowel Crohn's. These excluded topics already have comprehensive reviews. Evidence available from randomized controlled trials comparing the various modalities is limited and at best regarded as Grade C or D (based on expert opinion). The evidence suggests that all three DAE modalities have comparable insertion depths, diagnostic and therapeutic efficacies and complication rates, though most favour DBE due to higher rates of total enteroscopy. SE is quicker than DBE, but lower complete enteroscopy rates. SBE has quicker procedural times and is evolving but the least available DAE today. Larger prospective randomised controlled trial's in the future could help us understand some unanswered areas including the role of BAE in small bowel screening and comparative studies between the main types of enteroscopy in small bowel CD.
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10.4253/wjge.v5.i10.476
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pubmed_515_18057
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Cells infected by viruses utilize interferon (IFN)-mediated and p53-mediated irreversible cell cycle arrest and apoptosis as part of the overall host surveillance mechanism to ultimately block viral replication and dissemination. Viruses, in turn, have evolved elaborate mechanisms to subvert IFN- and p53-mediated host innate immune responses. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several viral IFN regulatory factors (vIRF1 to vIRF4) within a cluster of loci, their functions being primarily to inhibit host IFN-mediated innate immunity and deregulate p53-mediated cell growth control. Despite its significant homology and similar genomic location to other vIRFs, vIRF4 is distinctive, as it does not target and antagonize host IFN-mediated signal transduction. Here, we show that KSHV vIRF4 interacts with the murine double minute 2 (MDM2) E3 ubiquitin ligase, leading to the reduction of p53, a tumor suppressor, via proteasome-mediated degradation. The central region of vIRF4 is required for its interaction with MDM2, which led to the suppression of MDM2 autoubiquitination and, thereby, a dramatic increase in MDM2 stability. Consequently, vIRF4 expression markedly enhanced p53 ubiquitination and degradation, effectively suppressing p53-mediated apoptosis. These results indicate that KSHV vIRF4 targets and stabilizes the MDM2 E3 ubiquitin ligase to facilitate the proteasome-mediated degradation of p53, perhaps to circumvent host growth surveillance and facilitate viral replication in infected cells. Taken together, the indications are that the downregulation of p53-mediated cell growth control is a common characteristic of the four KSHV vIRFs and that p53 is indeed a key factor in the host's immune surveillance program against viral infections.
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10.1128/JVI.02353-08
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pubmed_1138_21837
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Young mature dogs received finasteride, a selective 5 alpha-reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size and morphology was evaluated macroscopically and microscopically. Changes in glandular and fibromuscular compartments were quantitated by a point counting method on trichrome-stained sections. Finasteride administration induced a decrease of mean prostatic weights and epithelial atrophy in all treated groups. No changes in testicular weights and morphology were observed. The greatest prostatic shrinkage was obtained in the group receiving 45 mg/kg/day for 53 weeks; compared to placebo controls, the percent decreases in absolute volumes occupied by epithelium, lumens, fibrovascular stroma, and smooth muscle were 88, 97, 51 and 72, respectively. These results clearly demonstrate that prostatic shrinkage following finasteride administration results from a decrease in both glandular and fibromuscular compartments.
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10.1002/pros.2990240207
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pubmed_646_9253
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This paper introduces the general framework, concepts, and procedures of anatomically informed basis functions (AIBF), a new method for the analysis of functional magnetic resonance imaging (fMRI) data. In contradistinction to existing voxel-based univariate or multivariate methods the approach described here can incorporate various forms of prior anatomical knowledge to specify sophisticated spatiotemporal models for fMRI time-series. In particular, we focus on anatomical prior knowledge, based on reconstructed gray matter surfaces and assumptions about the location and spatial smoothness of the blood oxygenation level dependent (BOLD) effect. After reconstruction of the grey matter surface from an individual's high-resolution T1-weighted MRI, we specify a set of anatomically informed basis functions, fit the model parameters for a single time point, using a regularized solution, and finally make inferences about the estimated parameters over time. Significant effects, induced by the experimental paradigm, can then be visualized in the native voxel-space or on the reconstructed folded, inflated, or flattened cortical surface. As an example, we apply the approach to a fMRI study (finger opposition task) and compare the results to those of a voxel-based analysis as implemented in the Statistical Parametric Mapping package (SPM99). Additionally, we show, using simulated data, that the approach offers several desirable features particularly in terms of superresolution and localization.
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10.1006/nimg.1999.0542
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pubmed_695_3888
|
We aimed to investigate Fontan associated liver disease in children by shear wave elastography (SWE). This is a single-center, prospective case-control study included 41 patients with Fontan physiology and 30 healthy controls. Hepatic and splenic shear wave elasticity values were exhibited both as kPa and m/s. The mean hepatic SWE values of Fontan patients (n = 41; 15.8 ± 3.2 kPa or 2.5 ± 1.8 m/s) were significantly higher than the control group (n = 30; 5.59 ± 0.6 kPa or 1.37 ± 0.07 m/s) (P < 0.001). The mean splenic SWE values of Fontan patients were (25.6 ± 4.61 kPa or 2.85 ± 0.22 m/s) significantly higher than the control group (15.9 ± 1.44 kPa or 2.29 ± 0.1 m/s) (P < 0.001). There were statistically significant positive correlations among the follow-up duration after the Fontan procedure with NT-proBNP (P = 0.008, r = 1) and prothrombin time (P = 0.009, r = 0.4) as well as the hepatic SWE values with alanine aminotransferase (P = 0.039, r = 0.32), gamma-glutamyl transferase (P = 0.045, r = 0.31), and PT (P = 0.011, r = 0.39). There has been statistically significant moderate positive correlations of splenic stiffness values with PT (P = 0.047, r = 0.34), and INR (P = 0.038, r = 0.35). The sensitivity and specificity of liver stiffness cutoff value as 11.1 kPa for detection of Fontan associated liver disease were 95% and 100%, respectively. The hepatic and splenic stiffness increase independently in Fontan patients due to parenchymal disease. Hepatic SWE is a reliable and noninvasive predictor of early hepatic alterations that could not be detected only by biochemical results or routine ultrasound examinations.
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10.1097/RUQ.0000000000000541
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pubmed_1111_1287
|
Photolithographic techniques have been used to fabricate polymer brush micro- and nanostructures. On exposure to UV light with a wavelength of 244 nm, halogens were selectively removed from films of chloromethylphenyltrichlorosilane and 3-(2-bromoisobutyramido)propyl-triethoxysilane on silicon dioxide. Patterning was achieved at the micrometer scale, by using a mask in conjunction with the incident laser beam, and at the nanometer scale, by utilizing interferometric lithography (IL). Friction force microscopy images of patterned surfaces exhibited frictional contrast due to removal of the halogen but no topographical contrast. In both cases the halogenated surface was used as an initiator for surface atom-transfer radical polymerization. Patterning of the surface by UV lithography enabled the definition of patterns of initiator from which micro- and nanostructured poly[oligo(ethylene glycol)methacrylate] bottle brushes were grown. Micropatterned brushes formed on both surfaces exhibited excellent resistance to protein adsorption, enabling the formation of protein patterns. Using IL, brush structures were formed that covered macroscopic areas (approximately 0.5 cm²) but exhibited a full width at half maximum height as small as 78 nm, with a period of 225 nm. Spatially selective photolytic removal of halogens that are immobilized on a surface thus appears to be a simple, rapid, and versatile method for the formation of micro- and nanostructured polymer brushes and for the control of protein adsorption.
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10.1116/1.3553579
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pubmed_989_9511
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RabA4 subfamily proteins, the key regulators of intracellular transport, are vital for tip growth of plant polar cells, but their unique distribution in the apical zone and role in vesicle targeting and trafficking in the tips remain poorly understood. Here, we found that loss of Arabidopsis (Arabidopsis thaliana) AMINOPHOSPHOLIPID ATPASE 3 (ALA3) function resulted in a marked decrease in YFP-RabA4b/ RFP-RabA4d- and FM4-64-labeled vesicles from the inverted-cone zone of the pollen tube tip, misdistribution of certain intramembrane compartment markers, and an obvious increase in pollen tube width. Additionally, we revealed that phosphatidylserine (PS) was abundant in the inverted-cone zone of the apical pollen tube in wild-type Arabidopsis and was mainly colocalized with the trans-Golgi network/early endosome, certain post-Golgi compartments, and the plasma membrane. Loss of ALA3 function resulted in loss of polar localization of apical PS and significantly decreased PS distribution, suggesting that ALA3 is a key regulator for establishing and maintaining the polar localization of apical PS in pollen tubes. We further demonstrated that certain Rab GTPases colocalized with PS in vivo and bound to PS in vitro. Moreover, ALA3 and RabA4d collectively regulated pollen tube growth genetically. Thus, we propose that the tip-localized PS established by ALA3 is crucial for Rab GTPase-mediated vesicle targeting/trafficking and polar growth of pollen tubes in Arabidopsis.
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10.1105/tpc.19.00844
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pubmed_670_3495
|
The purpose of this study was to determine whether the effects of estrogen on lordosis behavior in the male rat were related to the number of progesterone (P) receptors in the mediobasal hypothalamus (MBH) and/or dependent on blood P concentration. Two groups of gonadally intact male rats were given five successive doses of 1.0 or 2.5 micrograms estradiol benzoate (EB) and tested for lordosis behavior with a male stimulus at the end of the treatment. One month later they were again injected with EB and sacrificed under the same temporal schedule, but they were not tested for lordosis so as to prevent any emotionally stressful effects of intermale cohabitation. The males given 2.5 micrograms EB more frequently displayed lordosis responses to male mounts than those receiving 1 microgram EB, with a parallel increase in the number of MBH P receptors. The total number of MBH P receptors also appeared to be higher in the animals that displayed lordosis responses (lordosis group) than in those which did not (no lordosis group). In contrast, the display of lordosis behavior was negatively correlated with blood P concentration. Comparing MBH P receptors and blood P values in the EB treated and in nonhormonally treated gonadally intact animals which had been selected for either ability or inability to spontaneously display lordosis behavior, we observed that (1) EB was capable of increasing the number of MBH P receptors in the male rat; and (2) in the absence of EB treatment blood P values were higher in the animals showing lordosis than in those which did not. These data are discussed with respect to observations made in castrated male rats and in ovariectomized females.
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10.1016/0960-0760(91)90065-d
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pubmed_730_11723
|
Rises of intracellular Ca2+ ([Ca2+]i) are key signals for cell division, differentiation, and maturation. Similarly, they are likely to be important for the unique processes of meiosis and spermatogenesis, carried out exclusively by male germ cells. In addition, elevations of [Ca2+]i and intracellular pH (pHi) in mature sperm trigger at least two events obligatory for fertilization: capacitation and acrosome reaction. Evidence implicates the activity of Ca2+ channels modulated by pHi in the origin of these Ca2+ elevations, but their nature remains unexplored, in part because work in individual spermatozoa are hampered by formidable experimental difficulties. Recently, late spermatogenic cells have emerged as a model system for studying aspects relevant for sperm physiology, such as plasmalemmal ion fluxes. Here we describe the first study on the influence of controlled intracellular alkalinization on [Ca2+]i on identified spermatogenic cells from mouse adult testes. In BCECF [(2',7')-bis(carboxymethyl)- (5, 6)-carboxyfluorescein]-AM-loaded spermatogenic cells, a brief (30-60 s) application of 25 mM NH4Cl increased pHi by approximately 1.3 U from a resting pHi approximately 6.65. A steady pHi plateau was maintained during NH4Cl application, with little or no rebound acidification. In fura-2-AM-loaded cells, alkalinization induced a biphasic response composed of an initial [Ca2+]i drop followed by a two- to threefold rise. Maneuvers that inhibit either Ca2+ influx or intracellular Ca2+ release demonstrated that the majority of the Ca2+ rise results from plasma membrane Ca2+ influx, although a small component likely to result from intracellular Ca2+ release was occasionally observed. Ca2+ transients potentiated with repeated NH4Cl applications, gradually obliterating the initial [Ca2+]i drop. The pH-sensitive Ca2+ permeation pathway allows the passage of other divalents (Sr2+, Ba2+, and Mn2+) and is blocked by inorganic Ca2+ channel blockers (Ni2+ and Cd2+), but not by the organic blocker nifedipine. The magnitude of these Ca2+ transients increased as maturation advanced, with the largest responses being recorded in testicular sperm. By extrapolation, these findings suggest that the pH-dependent Ca2+ influx pathway could play significant roles in mature sperm physiology. Its pharmacology and ion selectivity suggests that it corresponds to an ion channel different from the voltage-gated T-type Ca2+ channel also present in spermatogenic cells. We postulate that the Ca2+ permeation pathway regulated by pHi, if present in mature sperm, may be responsible for the dihydropyridine-insensitive Ca2+ influx required for initiating the acrosome reaction and perhaps other important sperm functions.
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10.1085/jgp.112.1.33
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pubmed_944_15425
|
BACKGROUND AND OBJECTIVES
QRS duration (QRSd) and prolonged corrected QT interval (QTc) are associated with ventricular arrhythmic events. This study was designed to determine whether CRT by means of biventricular pacing alters the QTc and QRSd, and whether such changes are related to the risk of sustained ventricular tachyarrhythmias (sVTA).
METHODS AND RESULTS
A total of 127 patients (102 men, mean age 63.9 +/- 8.9 years) with drug-resistant heart failure and QRS duration > or = 130 ms underwent CRT/CRT-ICD. The aetiology of the heart failure was ischaemic in 41 patients (32.3%). After a median follow-up of 24 months, 42 sVTA occurred in 35 patients (27.6%). Twenty-nine patients had a single sVTA, in five patients two sVTA and in one patient three sVTA occurred. The paced QTc was longer in sVTA patients (505 +/- 55 ms) compared with no sVTA patients (486 +/- 44 ms, P < or = 0.003). Similar responses for paced QRSd were observed (182 +/- 27 ms in sVTA patients vs 167 +/- 27 ms in no-sVTA patients, P < or = 0.03). This effect was independent from intrinsic QTc and QRSd and the aetiology of the heart failure. The mortality rate was significantly higher in patients with ventricular fibrillation and fast VT (P < or = 0.004) who experienced shock therapies. However, the sVTA were not the immediate cause of death.
CONCLUSIONS
A pacing-induced increase in QTc and QRSd is related to sVTA in patients with CRT. Further studies are needed to determine whether optimization of CRT with the goal to achieve a narrow paced QRSd can reduce the occurrence of sVTA.
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10.1080/ac.66.4.2126587
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pubmed_686_18770
|
Dimethyl ether (DME) has been proposed for use as an alternative fuel or additive in diesel engines and as a potential fuel in solid oxide fuel cells. The oxidation chemistry of DME is a key element in understanding its role in these applications. The reaction between methoxymethyl radicals and O(2) has been examined over the temperature range 295-600 K and at pressures of 20-200 Torr. This reaction has two product pathways. The first produces methoxymethyl peroxy radicals, while the second produces OH radicals and formaldehyde molecules. Real-time kinetic measurements are made by transient infrared spectroscopy to monitor the yield of three main products-formaldehyde, methyl formate, and formic acid-to determine the branching ratio for the CH(3)OCH(2) + O(2) reaction pathways. The temperature and pressure dependence of this reaction is described by a Lindemann and Arrhenius mechanism. The branching ratio is described by f = 1/(1 + A(T)[M]), where A(T) = (1.6(+2.4)(-1.0) x 10(-20)) exp((1800 +/- 400)/T) cm(3) molecule(-1). The temperature dependent rate constant of the methoxymethyl peroxy radical self-reaction is calculated from the kinetics of the formaldehyde and methyl formate product yields, k(4) = (3.0 +/- 2.1) x 10(-13) exp((700 +/- 250)/T) cm(3) molecule(-1) s(-1). The experimental and kinetics modeling results support a strong preference for the thermal decomposition of alkoxy radicals versus their reaction with O(2) under our laboratory conditions. These characteristics of DME oxidation with respect to temperature and pressure might provide insight into optimizing solid oxide fuel cell operating conditions with DME in the presence of O(2) to maximize power outputs.
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10.1021/jp054223t
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pubmed_85_9085
|
Formulation provides a means to stabilize for storage and delivery biocontrol and bioremediation agents based on microbes such as bacteria and fungi. Typically it is difficult to both stabilize and deliver fragile non-spore-forming bacteria. Fungal spores might intuitively appear to be easy to stabilize; however, their tendency to germinate in low moisture environments presents challenges for the formulation scientist. Here we present a light background regarding issues with formulating microbes and strategies to help overcome instability and delivery issues.
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10.1007/978-1-4939-6367-6_5
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pubmed_122_16268
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Endocytosed biomacromolecule delivery systems must escape the endosomal trafficking pathway in order for their cargo to exert effects in other cellular compartments. Although endosomal release is well-recognized as one of the greatest barriers to efficacy of biologic drugs with intracellular targets, most drug carriers have relied on cationic materials that passively induce endosomal swelling and membrane rupture with low efficiency. To address the endosome release challenge, our lab has developed a diblock copolymer system for nucleic acid delivery that selectively displays a potent membrane-lytic peptide (melittin) in response to the pH drop during the endosomal maturation. To further optimize this system, we evaluated a panel of peptides with reported lytic activity in comparison to melittin. Nineteen different lytic peptides were synthesized and their membrane-lytic properties at both neutral and acidic pH characterized using a red blood cell hemolysis assay. The top five performing peptides were then conjugated to our pH-sensitive diblock copolymer via disulfide linkers and used to deliver a variety of nucleic acids to cultured mammalian cells as well as in vivo to the mouse brain. We demonstrate that the sharp pH-transition of VIPER compensates for potential advantages from pH-sensitive peptides, such that polymer-peptide conjugates with poorly selective but highly lytic peptides achieve safe and effective transfection both in vitro and in vivo. In addition, peptides that require release from polymer backbones for lysis were less effective in the VIPER system, likely due to limited endosomal reducing power of target cells. Finally, we show that certain peptides are potentiated in lytic ability by polymer conjugation and that these peptide-polymer constructs are most effective in vivo.
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10.1016/j.biomaterials.2018.11.004
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pubmed_1136_9767
|
OBJECTIVE
To investigate the predictive value of maternal serum pregnancy-associated plasma protein A (PAPP-A), free β subunit of human chorionic gonadotrophin (fβ-hCG), placental protein 13 (PP13), placental growth factor (PlGF) and a desintegrin and metalloproteinase 12 (ADAM12), for first-trimester identification of early-onset pre-eclampsia.
DESIGN
Nested case-control study.
SETTING
Routine first-trimester screening for trisomy 21 in the Netherlands.
POPULATION
Eighty-eight women who developed pre-eclampsia or haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 34 weeks of gestation and 480 controls.
METHODS
PP13, PlGF and ADAM12 were measured in stored first-trimester serum, previously tested for PAPP-A and fβ-hCG. All marker levels were expressed in multiples of the gestation-specific normal median (MoMs). Model predicted detection rates for fixed false-positive rates were obtained for statistically significant markers alone and in combination.
MAIN OUTCOME MEASURES
Development of pre-eclampsia or HELLP syndrome.
RESULTS
PP13 and PlGF were reduced in women with pre-eclampsia, with medians 0.68 MoM and 0.73 MoM respectively (P < 0.0001 for both). PAPP-A was reduced (median 0.82 MoM, P < 0.02) whereas ADAM12 and fβ-hCG did not differ between control women and those with pre-eclampsia. In pre-eclampsia complicated by a small-for-gestational-age fetus, all markers except fβ-hCG had lower values, compared with pregnancies involving fetuses of normal weight. The model-predicted pre-eclampsia detection rate for a combination of PP13 and PlGF was 44% and 54%, respectively, for a fixed 5% and 10% false-positive rate.
CONCLUSION
This study demonstrates that PP13 and PlGF in the first-trimester might be promising markers in risk assessment for early pre-eclampsia/HELLP syndrome but for an adequate screening test additional characteristics are necessary.
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10.1111/j.1471-0528.2010.02690.x
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pubmed_968_13518
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The aim of this paper is to take normative aspects of animal welfare in corporate practice from a blind spot into the spotlight, and thus connect the fields of business ethics and animal ethics. Using insights from business ethics and animal ethics, it argues that companies have a strong responsibility towards animals. Its rationale is that animals have a moral status, that moral actors have the moral obligation to take the interests of animals into account and thus, that as moral actors, companies should take the interests of animals into account, more specifically their current and future welfare. Based on this corporate responsibility, categories of corporate impact on animals in terms of welfare and longevity are offered, including normative implications for each of them. The article concludes with managerial implications for several business sectors, including the most animal-consuming and animal-welfare-threatening industry: the food sector. Welfare issues are discussed, including the issue of killing for food production.
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10.1007/s41055-021-00094-9
|
pubmed_520_1568
|
BACKGROUND
Nowadays, childhood obesity is literally a global pandemic health problem. According to current data, pediatric obesity is strongly associated with adult excess weight status as well as the development of certain co morbidities, already present in childhood, including cardiovascular disorders (dyslipidemia, hypertension), endocrine/metabolic (Type 2 diabetes, fatty liver disease, metabolic syndrome), respiratory, gastrointestinal, and musculoskeletal problems. Additionally, children with obesity frequently experience psychosocial issues, such as mood disorders, anxiety, prejudice and low self-esteem.
METHODS AND RESULTS
The aim of this article was to evaluate whether or not bariatric surgery is an effective and safe treatment option for childhood obesity. This paper is based on a literature search in Pub Med for articles referring to the medical co morbidities and the results of different types of bariatric surgery for the treatment of childhood obesity (up to 18 years) until December 2021. The following keywords were used as MESH terms: childhood obesity, adolescence obesity, co morbidities and bariatric surgery. The bibliographic references of the studies found in these databases were also reviewed.
CONCLUSION
Although some researchers demonstrate that surgical interventions in adolescents might be a reliable intervention to lose weight in a maintainable way and reverse many of the co morbidities associated with severe obesity, their safety and long-term efficacy are still not clarified. Thus, large long-term prospective studies, with detailed recording of complications and co morbidity resolution are obviously needed in order to determine the role of surgical treatment in childhood obesity.
|
10.1007/s12020-022-03210-9
|
pubmed_191_2725
|
Levels of swallowing disability, patterns of dysphagia rehabilitation and swallowing outcomes on discharge were retrospectively reviewed for 30 patients with thermal burn injury (with or without inhalation injury), referred to speech pathology services for dysphagia management. The average total surface burn area of the group was 50%. All patients were mechanically ventilated for an average of 24 days, with 80% of patients requiring subsequent tracheostomy. Initial dysphagia assessment occurred approximately 20 days after admission, whereas first safe oral intake was achieved by approximately 30 days. Supplementary nutrition and hydration was necessary for all patients. The time to achieve oral intake without supplementation was 53 days. Outcome measures revealed a significant improvement in swallowing function throughout the duration of inpatient stay, with 90% of patients discharged safely tolerating a normal diet, 6.7% of patients managing soft diet consistencies, and 3.3% managing soft puree consistencies on discharge.
|
10.1097/00004630-200111000-00017
|
pubmed_660_11753
|
BACKGROUND
Long-term antipsychotic treatment for schizophrenia is often associated with the emergence of tardive dyskinesia (TD), which is linked to greater cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays a critical role in cognitive function, and schizophrenia patients with TD have lower BDNF levels than those without TD.
OBJECTIVE
This study examines the BDNF levels, the cognitive function, and the association of BDNF with cognitive function in schizophrenia patients with or without TD.
METHODS
We recruited 83 male chronic patients with (n=35) and without TD (n=48) meeting DSM-IV criteria for schizophrenia and 52 male control subjects. We examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and BDNF levels for all subjects. Positive and Negative Symptom Scale (PANSS) and the Abnormal Involuntary Movement Scale (AIMS) were assessed in patients.
RESULTS
BDNF levels were lower in patients with than those without TD (p<0.05). RBANS total score (p<0.01) and subscales of immediate memory, visuospatial/constructional performance, and attention were lower in patients with than those without TD (all p<0.05). BDNF levels were positively associated with immediate memory in patients without TD, but negatively in TD patients (both p<0.05). Multiple regression analysis confirmed that in either TD or non-TD group, BDNF was an independent contributor to immediate memory (both p<0.05).
CONCLUSIONS
BDNF may be involved in the pathophysiology of TD. While the associations between BDNF and cognition in both TD and non-TD patients suggest a close relationship between BDNF and cognition, the different directions may implicate distinct mechanisms between TD and non-TD patients.
|
10.1007/s00213-014-3660-9
|
pubmed_827_20825
|
The Institute for Community Peace has conducted two demonstration projects to determine whether communities can be engaged to prevent violence as it is identified and defined locally and link primary prevention across multiple forms of violence. The projects present evidence that community engagement can effect primary violence prevention; the violence prevention field has much to learn about developing and sustaining strategies to address interrelated violence problems; and the violence prevention field and community residents are in vastly different places with respect to primary violence prevention.
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10.1177/0886260503261158
|
pubmed_228_21585
|
BACKGROUND
Prompt treatment of exposed partners is critical for preventing further transmission of chlamydia, reinfection, and sequelae among females. Patient-delivered partner therapy (PDPT) has been allowable in California since 2001; however, few data are available regarding PDPT use and treatment outcomes.
METHODS
Eight family planning clinics participated in a partner services evaluation from 2005 to 2006. Females aged 16 to 35 years with chlamydia were interviewed to determine the partner service received and partner treatment outcomes; a subset of partners was also interviewed. Determinants of reported partner treatment were assessed using multivariate logistic regression. Selected medical records were reviewed to assess reinfection rates.
RESULTS
Overall, 743 female patients disclosed 952 partners; 58% of whom were identified as steady partners. Reported partner services included concurrent patient-partner treatment visits (15% of partners), PDPT (19%), patient referral (55%), health department referral (0.1%), and no partner management (11%). On the basis of patient report, 82% of partners were notified and 54% received treatment. Of the 166 (17%) partners interviewed, 139 (84%) reported that they had received treatment, which correlated well with patient report. Reported partner treatment was higher for concurrent treatment visits and PDPT (79% and 80%, respectively) compared to patient referral (44%, P < 0.0001). Adjusted for clinic and relationship status, partners managed with concurrent treatment visits or PDPT were more likely to receive treatment compared with partners managed with patient referral (adjusted odds ratios, 3.5; 95% confidence interval, 2.1-5.8 and adjusted odds ratios, 4.3; 95% confidence interval, 2.6-7.2, respectively). Among the patients retested within 6 months after treatment, 18% were reinfected; reinfection rates did not differ by type of partner service.
CONCLUSIONS
Although overall rates of reported partner treatment were low, concurrent patient-partner treatment visits and PDPT were associated with significantly higher rates of partner treatment. However, these methods may be underutilized in California family planning settings.
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10.1097/OLQ.0b013e3182240366
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pubmed_239_24255
|
Oxytocin is a potent anorexigen and is believed to have a role in satiety signaling. We developed rat models to study the activity of oxytocin neurons in response to voluntary consumption or oral gavage of foods using c-Fos immunohistochemistry and in vivo electrophysiology. Using c-Fos expression as an indirect marker of neural activation, we showed that the percentage of magnocellular oxytocin neurons expressing c-Fos increased with voluntary consumption of sweetened condensed milk (SCM). To model the effect of food in the stomach, we gavaged anesthetized rats with SCM. The percentage of supraoptic nucleus and paraventricular nucleus magnocellular oxytocin-immunoreactive neurons expressing c-Fos increased with SCM gavage but not with gastric distention. To further examine the activity of the supraoptic nucleus, we made in vivo electrophysiological recordings from SON neurons, where anesthetized rats were gavaged with SCM or single cream. Pharmacologically identified oxytocin neurons responded to SCM gavage with a linear, proportional, and sustained increase in firing rate, but cream gavage resulted in a transient reduction in firing rate. Blood glucose increased after SCM gavage but not cream gavage. Plasma osmolarity and plasma sodium were unchanged throughout. We show that in response to high-sugar, but not high-fat, food in the stomach, there is an increase in the activity of oxytocin neurons. This does not appear to be a consequence of stomach distention or changes in osmotic pressure. Our data suggest that the presence of specific foods with different macronutrient profiles in the stomach differentially regulates the activity of oxytocin neurons.
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10.1210/en.2016-1640
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pubmed_964_14116
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Lipid-like substances incorporated in keratinized parts of the hair or appearing on its surface as sebaceous secretion act as detergents in water. At a sufficient concentration they decrease water surface tension to 0.03 N/m, and, contrary to widespread opinion, should contribute to fur wetting. The influence of these lipids on water surface tension markedly varies among both semiaquatic and land mammals, but in any case their natural concentration is too low to significantly affect the waterproof properties of the cover of the swimming animals.
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pubmed_964_14116
|
pubmed_1112_1744
|
Anaplastic thyroid carcinoma (ATC) is a very aggressive thyroid cancer. forkhead box protein M1 (FOXM1) is a member of the forkhead box family of transcription factors involved in control of cell proliferation, chromosomal stability, angiogenesis, and invasion. Here, we show that FOXM1 is significantly increased in ATCs compared with normal thyroid, well-differentiated thyroid carcinomas (papillary and/or follicular), and poorly differentiated thyroid carcinomas (P=0.000002). Upregulation of FOXM1 levels in ATC cells was mechanistically linked to loss-of-function of p53 and to the hyperactivation of the phosphatidylinositol-3-kinase/AKT/FOXO3a pathway. Knockdown of FOXM1 by RNA interference inhibited cell proliferation by arresting cells in G2/M and reduced cell invasion and motility. This phenotype was associated with decreased expression of FOXM1 target genes, like cyclin B1 (CCNB1), polo-like kinase 1 (PLK1), Aurora B (AURKB), S-phase kinase-associated protein 2 (SKP2), and plasminogen activator, urokinase: uPA (PLAU). Pharmacological inhibition of FOXM1 in an orthotopic mouse model of ATC reduced tumor burden and metastasization. All together, these findings suggest that FOXM1 represents an important player in thyroid cancer progression to the anaplastic phenotype and a potential therapeutic target for this fatal cancer.
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10.1530/ERC-12-0031
|
pubmed_1129_21813
|
OBJECTIVES
The aim of this project is to compare the effect of canagliflozin monotherapy on metabolic parameters between responders and nonresponders with this drug. This study is a prospective, unblinded, observational study.
SUBJECTS AND METHODS
Drug-naïve patients with type 2 diabetes mellitus received only 50-100 mg/day canagliflozin for 3 months (n = 39). They were divided into two groups according to the novel "A1c index" to assess glycemic efficacies; responders (n = 24) and nonresponders (n = 15).
RESULTS
At baseline, glycated hemoglobin (HbA1c) and fasting blood glucose (FBG) were significantly higher and homeostatic model assessment (HOMA)-B and body mass index (BMI) were significantly lower in responders. In both groups, similar, significant reductions of BMI (-1.9% with responder and -1.8% with nonresponder) and HOMA-R (-35.8% for responder and -31.5% for nonresponder) were observed. However, differences were seen with other parameters as follows: 1) responders: significant reductions of HbA1c (10.95%-8.44%), FBG (-29.6%) or free fatty acid (FFA) (-16.2%), and significant increases of HOMA-B (79.7%) were observed. 2) Nonresponders: significant reductions of serum uric acid (UA) (-8.6%) levels were seen. Significant correlations were observed between the baseline levels of serum UA and those of HOMA-B (R = 0.7259). However, this link became uncorrelated with the treatment with canagliflozin.
CONCLUSIONS
These results suggest that (1) responders with canagliflozin have lower BMI and beta-cell function. Reductions of body weight with canagliflozin were not associated with its glycemic efficacy, (2) reduced FFA levels and enhanced insulin sensitivity/beta-cell function could be a potential mechanism of good glycemic efficacy of canagliflozin, and (3) serum UA might be involved in modulating beta-cell function during canagliflozin treatment.
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10.4103/ijem.IJEM_578_17
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pubmed_972_14369
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The study was designed to determine whether methionine-enkephalin (met-Enk) or delta opioid receptor was present in the digestive system of Octopus ocellatus. The results showed that they were both in the bulbus oris, esophagus, crop, stomach, gastric cecum, intestine, posterior salivary glands of O. ocellatus, one of them, met-Enk in the rectum, anterior salivary glands, digestive gland. And the distributions were extensive in the digestive system. Strong or general met-Enk immunoreactivity was observed in the inner epithelial cells of the bulbus oris, esophagus, stomach, gastric cecum, intestine, anterior salivary glands and the adventitia of the intestine and rectum, and so was the delta opioid receptor immunoreactivity in the inner epithelial cells of the bulbus oris, esophagus, and crop, however, they were weak in other parts. Combining with delta opioid receptor, met-Enk may be involved in the regulations of food intake, absorption, movement of gastrointestinal smooth muscle and secretion of digestive gland. The different densities of met-Enk and delta opioid receptor may be related to the different functions in the digestive system of O. ocellatus.
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pubmed_972_14369
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pubmed_406_4069
|
The authors presented a rare case with localised congenital supravalvular aortic stenosis associated with bicuspid aortic valvular stenosis which has been surgically treated. The clinical diagnosis was suggested in the presented patient by typical "elfin" face and conformed by left cardiac catheterisation and angiography. The operative procedure with cardiopulmonary by pass consisted of longitudinal aortotomy and insertion of Dacron prosthesis. In addition "open" commissurotomy of partially fused commissures of the bicuspid aortic valve was done. This effectively released the obstruction and enlarged the orifice. The postoperative course was uneventful.
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pubmed_406_4069
|
pubmed_724_7973
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Non-invasive imaging of the heart is an expanding field in cardiology and appropriate test selection depends on the clinical question and test availability. This article reviews the role of single photon emission computed tomography myocardial perfusion scintigraphy, positron emission tomography and multi-detector computed tomography.
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10.12968/hmed.2008.69.3.28752
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pubmed_761_4007
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Two sensitive and accurate methods have been developed for the estimation of daclatasvir (DAC) in its raw material, dosage form and in biological fluids. Method I is based on the measurement of DAC native fluorescence in methanol at 385 nm after excitation at 315 nm. The relationship between fluorescence intensity and concentration was found to be rectilinear over the linearity range (3.0-30.0 ng/ml). There were good per cent recoveries both in the dosage form (99.87 ± 0.84) and in spiked human plasma (99.96 ± 1.54%). Method II utilized reversed-phase high performance liquid chromatography to estimate the antiviral agent daclatasvir hydrochloride against hepatitis C within 4.0 min on a C18 column (Eurosphere. 100-5 C18, 150 × 4.6 mm, Germany) using a mobile phase consisting of acetonitrile and 0.1 M sodium dihydrogen phosphate (30:70, v/v) at pH 3.0 and with a fluorescence detector adjusted to 315 nm and 385 nm for excitation and emission respectively. The calibration curve was linear over the range (20.0-200.0 ng/ml) with SD 1.38%, error 0.56%, recovery 99.99 ± 1.30% in tablets, recovery 100.28 ± 1.73% in spiked urine and recovery 99.63 ± 2.72% in spiked plasma.The new developed methods were successfully applied to the assay of the daclatasvir in tablet form and extended to its determination in real plasma, spiked human plasma and urine. The analytical performance of the proposed method was validated according to International Conference on Harmonization (ICH) guidelines. The proposed methods were compared with the results of a comparison method and it was found that there was no significant difference between the methods, as revealed by Student's t-test and variance ratio F-test.
|
10.1002/bio.3551
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pubmed_258_22342
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Oxidative stress in adipose tissue is a crucial pathogenic mechanism of obesity-associated cardiovascular diseases. Chronic low-grade inflammation caused by obesity increases ROS production and dysregulation of adipocytokines. Leonurine (LEO) is an active alkaloid extracted from Herba Leonuri and plays a protective role in the cardiovascular system. The present study tested whether LEO alleviates inflammation and oxidative stress, and improves vascular function in an obese mouse model. Here, we found that obesity leads to inflammation and oxidative stress in epididymal white adipose tissue (EWAT), as well as vascular dysfunction. LEO significantly improved inflammation and oxidative stress both in vivo and in vitro. Obesity-induced vascular dysfunction was also improved by LEO as evidenced by the ameliorated vascular tone and decreased mesenteric artery fibrosis. Using mass spectrometry, we identified YTHDF1 as the direct target of LEO. Taken together, we demonstrated that LEO improves oxidative stress and vascular remodeling induced by obesity and targets YTHDF1, raising the possibility of LEO treating other obesity-related metabolic syndromes.
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10.3390/antiox11071338
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pubmed_311_17403
|
Autoimmunity is a leading cause of chronic kidney disease and loss of native and transplanted kidneys. Conventional immunosuppressive therapies can be effective but are non-specific, noncurative, and risk serious side effects such as life-threatening infection and cancer. Novel therapies and targeted interventions are urgently needed. In this brief review we explore diverse strategies currently in development and under consideration to interrupt underlying disease mechanisms in immune-mediated renal injury. Because autoantibodies are prominent in diagnosis and pathogenesis in multiple human glomerulopathies, we highlight several promising therapies that interfere with functions of early mediators (IgG and complement) of the effector arm and with an epicenter (the germinal center) for induction of humoral immunity.
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10.1080/21645515.2018.1555569
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pubmed_21_20806
|
Comparative study of selenium (Se) speciation in hyperaccumulator plants offers an interesting challenge from the analytical point of view. In our study the application of a sophisticated sample clean-up procedure and the combination of elemental and molecular mass spectrometric methods led to the identification of several new selenocompounds. The difference between the Se speciation of the primary accumulator Lecythis minor and the secondary accumulator Bertholletia excelsa confirmed the current opinion that the speciation pattern in hyperaccumulator plants is principally related to the mechanism of accumulation and not to taxonomy. The most abundant new selenocompounds were found to be the derivatives of selenohomocysteine (SeHCy) and selenomethionine (SeMet), including fatty acid metabolism related compounds. A series of SeHCy derived species containing multiple Se atoms (>2) was also detected and their structures were validated by the synthesis of their S-Se analogues.
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10.1039/c3mt00140g
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pubmed_992_12313
|
BACKGROUND
Cardiopulmonary exercise testing (CPET) is frequently used for the evaluation of patients with pulmonary hypertension (PH). Non-operable distal chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subgroup of PH where microvascular disease resembling pulmonary arterial hypertension (PAH) may predominate and efficacious medical therapy is now available. However, little is known regarding the detailed CPET profile of patients with distal CTEPH, and whether ventilation and gas exchange responses are different from PAH.
METHODS
Forty-nine consecutive patients with non-operable distal CTEPH according to multidisciplinary team assessment and 45 PAH patients underwent CPET and right heart catheterization. Patients were followed up for a median of 3.2 years (interquartile range: 1.8 to 4.4).
RESULTS
Pulmonary hemodynamics were similar in distal CTEPH and PAH groups, but patients with distal CTEPH achieved a lower percent predicted peak oxygen consumption (59 ± 13% vs 66 ± 14%, p < 0.05). At peak exercise, higher physiologic dead-space fraction (VD/VT) (0.45 ± 0.07 vs 0.35 ± 0.07, p < 0.0001) and higher arterial-to-end-tidal carbon dioxide gradient (9 ± 3 vs 5 ± 3 mm Hg, p < 0.0001) were observed in distal CTEPH compared with PAH. Ventilatory efficiency, expressed as VE/VCO2 slope, was also more impaired in distal CTEPH (52.2 ± 10.1 vs 43.8 ± 8.4 liters/min, p < 0.0001). In the distal CTEPH group only, higher VD/VT was associated with lower peak oxygen consumption (r = -0.46, p = 0.003) and worse survival.
CONCLUSIONS
Compared with PAH, a distinct pattern of response to exercise was observed in distal CTEPH, characterized by increased dead-space ventilation that resulted in worse ventilatory efficiency and greater impairment of exercise capacity. In distal CTEPH, dead-space ventilation correlated with exercise capacity and was associated with survival.
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10.1016/j.healun.2017.05.024
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pubmed_1040_15251
|
The transfer of Syrian golden hamsters from a long to a short photoperiod (SP) leads to reduced circulating levels of several anterior pituitary hormones including thyrotropin stimulating hormone (TSH), luetinizing hormone (LH) and follicle stimulating hormone (FSH), while growth hormone (GH) is unaffected. These hormonal changes are associated with accelerated rates of body weight gain and gonadal atrophy in this species, but the effects on growth of other organs, specifically the kidney, are unknown. In this study, the effect of SP treatment on kidney and body weights of intact and uninephrectomized male Syrian golden hamsters was evaluated. Seventy-two young adult male hamsters were acclimatized to long photoperiod (LP) consisting of a light/dark schedule of 14/10 hours (LD 14:10). Two weeks later one half of the animals were transferred to SP (LD 10:14) Subgroups of six hamsters underwent either left nephrectomy or sham left nephrectomy two, five and eight weeks after transfer to SP and were sacrificed two weeks after surgery. The relative kidney weights (kidney weights/100 g body weight) of the sham operated animals were significantly reduced after seven and ten weeks of SP treatment (p less than 0.01). Absolute kidney weights were depressed after eight (p less than 0.05) and ten weeks in SP. The percentage increase in the weight of the hypertrophied kidney following uninephrectomy was unaffected by SP. Differences in body weights were due to increased fat in SP-treated hamsters; nonetheless, the logs of kidney and body weights were highly correlated in both LP (r = 0.73) and SP (r = 0.78). Lean body weights, determined by body compositional analysis, were less well correlated with kidney weights in LP (r = 0.53) and unrelated in SP (r = 0.16). The mechanism retarding kidney growth was not elucidated, but may include SP-induced changes in TSH, LH, or a specific LH-like pituitary renotropin proposed by Nomura et al. (1982). The observation that compensatory renal growth proceeds despite inhibition of kidney growth in intact animals suggests that separate mechanisms regulate these processes.
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pubmed_1040_15251
|
pubmed_278_24317
|
BACKGROUND
Ideal pulpectomy for primary dentition demands fast, simple procedures, with short treatment times and minimal appointments. Recently, exclusive pediatric rotary files are available for use in primary teeth. There is a paucity of literature on the clinical efficacy of pediatric rotary files. Hence, this study was planned to evaluate and compare pediatric rotary files and K-files.
AIM
The aim of this study was to evaluate and compare instrumentation time, obturation time, and radiographic quality of obturation using rotary systems (Kedo-S; Pro-AF Baby GOLD files) and manual (K-files) technique in primary molar pulpectomies.
MATERIALS AND METHODS
Forty-five primary mandibular molars from 42 children aged 5-9 were selected. Single-visit pulpectomy was performed after dividing selected teeth into three equal groups: (i) K-files, (ii) Kedo-S files, (iii) Pro-AF Baby GOLD files. Instrumentation and obturation times were recorded during the procedure. Immediate postoperative radiographs were taken and evaluated later for obturation quality by two independent evaluators blinded to the instrumentation technique. The results were then statistically analyzed.
RESULTS
Kedo-S (Group II) files required the least instrumentation time followed by Pro-AF (Group III) and K-files (Group I). The superior quality of obturation in lesser time was achieved using Pro-AF files (Group III) followed by Kedo-S (Group II) and K-files (Group I).
CONCLUSION
Pediatric rotary files are efficient alternatives to hand instrumentation and can be considered as the standard of care in pulpectomies of primary teeth.
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10.4103/ccd.ccd_83_20
|
pubmed_472_7054
|
La chirurgie de la cataracte a toujours consisté à extraire le cristallin opacifié de l'œil pour le remplacer par une lentille artificielle. Cette intervention rend la vision du patient plus nette, sans pour autant corriger l'erreur de réfraction, c'est-à-dire la nécessité de porter des lunettes ou des lentilles cornéennes après l'opération. Les instruments diagnostiques et chirurgicaux modernes permettent désormais de corriger ces erreurs de réfraction au moment de l'opération, ce qui a fait émerger une nouvelle notion, celle de la chirurgie réfractive de la cataracte. Même si cette correction n'est pas nécessaire sur le plan médical, de nombreux patients se réjouissent de la possibilité de ne plus porter de lunettes ou d'en porter moins après l'opération, même s'ils doivent engager des frais.
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10.1177/0840470416674401
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pubmed_898_12041
|
Obesity during pregnancy is associated with the development of gestational diabetes (GDM). This study aimed to assess if the result of an oral glucose tolerance test (OGTT) for GDM influences health (diet and physical activity) behaviours of pregnant women with obesity. In total, 1031 women who participated in the UK Pregnancies Better Eating and Activity Trial (UPBEAT) of a lifestyle intervention from early pregnancy were included. Changes in weight gain, dietary intake and physical activity following an OGTT undertaken between 27+0 and 28+6 weeks' and 34 and 36 weeks' gestation were examined using linear regression with appropriate adjustment for confounders. Obese women without GDM (IADPSG criteria) gained 1.9 kg (95% CI -2.2, -1.5, p < 0.001) more weight than women with GDM. Women with GDM demonstrated greater reductions in energy (-142kcal, 95%CI -242.2, -41.9, p = 0.006), carbohydrate intake (-1.5%E 95%CI -2.8, -0.3, p = 0.016) and glycaemic load (-15.2, 95%CI -23.6, -6.7, p < 0.001) and a greater increase in protein intake (2%E, 95%CI 1.3, 2.7, p < 0.001), compared to women without GDM. Trial intervention allocation did not influence any associations observed. The findings emphasise the need for strategies to optimise the health behaviours of pregnant women with obesity, following a negative OGTT for GDM.
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10.3390/nu12020359
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pubmed_455_13837
|
We examined whether low ambient temperatures influence foraging behavior of precocial Japanese quail chicks and alter the balance between investment in growth and thermogenic function. To test this, one group of chicks was exposed to 7 degrees C and one group to 24 degrees C during foraging throughout the developmental stage. Chicks adapted well to the temperatures through a high flexibility in behavior and physiological development. In response to cold, chicks shortened foraging bout lengths two- to sixfold, and increased cycle lengths (i.e. length of a brooding bout plus subsequent foraging bout), resulting in a decrease in total foraging time. Body temperature during foraging was lower in cold-exposed chicks but did not drop below 37.8 degrees C, suggesting that the direct cause to end a foraging bout was not body temperature. The metabolic rate of cold-exposed chicks was reduced by 48% to 60% when switching from foraging to brooding, which may be an important factor in determining foraging behavior of precocial chicks. Mass-specific food intake of the cold-exposed chicks exceeded that of warm chicks by 15%. Cold-exposed chicks doubled foraging efficiency to reach this intake during their reduced foraging time. Metabolic rates initially were similar in both groups, but increased rapidly and were elevated in cold-exposed chicks from 15 days of age onward. Growth rate initially was reduced in cold-exposed chicks, and exceeded growth of warm chicks only after 21 days of age. These results suggest that in response to cold, a shift occurs in the balance between growth rate and thermoregulatory function in favor of thermoregulatory function.
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10.1016/s0031-9384(03)00117-3
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pubmed_512_8953
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Ytterbium-doped wide-bandgap fluoride crystals CaF2, SrF2 and NaMgF3 have been measured using x-ray absorption near edge structure (XANES) on the L3 edge to determine the ratio of trivalent to divalent Yb ions present in the crystals. This study improves upon previous XANES measurements of dopant ion valency by taking into account the x-ray emission transition probabilities for the divalent and trivalent species instead of simply assuming that the relative concentrations may be determined by the ratio of the x-ray excitation band areas. Trivalent to divalent ratios as high as 5 are inferred even at low total dopant ion concentrations of 0.05 mol% Yb.
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10.1088/0953-8984/28/13/135502
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pubmed_855_2519
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has been associated, sometimes controversially, with polymorphisms in a number of genes. Recently the butyrylcholinesterase K variant (BCHE K) allele has been shown to act in synergy with the apolipoprotein E epsilon4 (APOE epsilon4) allele to promote risk for AD. Most subsequent replicative studies have been unable to confirm these findings. We have conducted a case-control association study using a clinically well defined group of late onset AD patients (n=175) and age and sex matched control subjects (n=187) from the relatively genetically homogeneous Northern Ireland population to test this association. The BCHE genotypes of patients were found to be significantly different from controls (chi(2)=23.68, df=2, p<<0.001). The frequency of the K variant allele was also found to differ significantly in cases compared to controls (chi(2)=16.39, df=1, p<<0.001) leading to an increased risk of AD in subjects with this allele (OR=3.50, 95% CI 2. 20-6.07). This risk increased in subjects 75 years and older (OR=5. 50, 95% CI 2.56-11.87). At the same time the APOE epsilon4 associated risk was found to decrease from 6.70 (95% CI 2.40-19.04) in 65-74 year olds to 3.05 (95% CI 1.34-6.95) in those subjects 75 years and older. However, we detected no evidence of synergy between BCHE K and APOE epsilon4. The results from this study suggest that possession of the BCHE K allele constitutes a significant risk for AD in the Northern Ireland population and, furthermore, this risk increases with increasing age.
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10.1136/jmg.37.3.182
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