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pubmed_638_9182
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OBJECTIVE
To evaluate the safety and efficacy of pre-stent plaque debulking strategy for percutaneous coronary intervention for CTO.
BACKGROUND
Drug-eluting stents (DES) reduce lesion recurrence after percutaneous coronary intervention for chronic total occlusion (CTO). However, massive plaque burden or calcified plaque sometime hinders optimal stenting. The aim of the study was to investigate the safety and the effectiveness of pre-stent plaque debulking in CTOs. The primary end-point was the angiographic restenosis rate at 6 months. Secondary end-points were the major adverse cardiac event (MACE) at 30 days and at 1 year.
METHOD
Between October 2000 and July 2003, 266 patients with CTOs were evaluated in 21 Japanese centers. After successful wire crossing, an operator judged the indications for a debulking strategy (177 patients for rotational and 89 for directional atherectomy). The subjects were then randomly assigned to a debulking (rotational: 90, directional: 48) or non-debulking (rotational: 87, directional: 41) group.
RESULT
Baseline clinical and lesion characteristics showed no differences between the groups. The debulking group tended to have the higher 30-day MACE rate than the non-debulking group (15.9% vs 8.5%, P=0.07). Although binary 6 month restenosis rates did not reach statistical significance (debulking 23.8% vs non-debulking 34.6%; P=0.072), the 1-year MACE rate was lower in the debulking group than in the non-debulking group (27.5% vs 39.8%; P=0.033).
CONCLUSION
This study demonstrated that pre-stent plaque debulking of CTO was associated with a favorable mid-term outcome with lower target revascularization rate in the debulking group than in the non-debulking group.
|
10.1016/j.ijcard.2007.07.117
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pubmed_1064_19831
|
Anthropometric data of Hong Kong schoolchildren have been collected and analysed in order to develop recommendations for the design of chairs and tables for use in Hong Kong Government coeducational schools. The anthropometric data for Hong Kong have been compared with data from a Western population (United Kingdom) and another Asian population (Japan). Five sizes of chair and table combinations have been proposed to accommodate six primary and seven secondary forms (pupils aged from 6 to 18 years). The recommended design dimensions, based on the anthropometric characteristics of the Hong Kong target populations, are discussed in relation to recommendations from previous research in this area.
|
10.1016/0003-6870(88)90005-1
|
pubmed_272_1626
|
In the first-trimester mammalian fetus, skin wounds heal with perfect reconstitution of the dermal architecture without scar formation. Understanding environmental molecular regulation in fetal wound healing may reveal scar-limiting therapeutical strategies for the prevention of postnatal scarring wound repair. Therefore, we performed studies on fetal skin oxygenation and skin and wound expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in the sheep model in vivo and performed studies on the potential relevance of HIF-1alpha during wound healing in vitro. Skin oxygen partial pressure levels were hypoxic throughout normal development. In nonscarring fetal skin at gestation day (GD)60, HIF-1alpha could be detected neither in healthy nor in wounded tissue. At GD100, in wounds with minimal scar formation, HIF-1alpha was expressed in fibroblasts and was markedly up-regulated at the wound edge. In scarring fetal wounds at GD120, HIF-1alpha was predominantly expressed in inflammatory cells. Expression of transforming growth factor beta3 (TGF-beta3), a potent antiscarring cytokine, overlapped with HIF-1a expression at GD100. HIF-1alpha-deficient mouse embryonic fibroblasts showed impaired migratory capabilities and demonstrated that TGF-beta3, but not proscarring TGF-beta1, manifests hypoxia- and HIF-1alpha-dependent regulation. In conclusion, HIF-1alpha-dependent regulation of a potent antiscarring cytokine may provide new strategies for antiscarring manipulation of wound healing.
|
10.1096/fj.01-0496fje
|
pubmed_675_1978
|
Pancreatic beta-cell dysfunction results in reductions of insulin synthesis/secretion, cell survival, and insulin sensitivity thereby inducing diabetes mellitus. In this study, how nanomolar melatonin regulates insulin synthesis and secretion in rat insulinoma INS-1E cells was investigated. At melatonin concentrations of 10 - 100 nM for 48 hours, melatonin significantly increased the insulin protein level in INS-1E cells above the level in control cells without melatonin or glucose treatments and decreased the insulin level in media with glucose: increases in insulin synthesis and decreases in insulin secretion occurred in dose-dependent manners. Luzindole or 4-phenyl-2-propionamidotetralin (4P-PDOT), melatonin receptor antagonists, inhibited the melatonin-induced insulin level in cells and media. Levels of membrane vesicle trafficking-related proteins including Rab5, GOPC, phospho-caveolin-1, EEA1, and clathrin proteins significantly increased with melatonin treatment above that in control cells without melatonin or glucose treatments, whereas expressions of APPL1 and syntaxin-6 proteins significantly decreased with melatonin treatment. The increases in the phosphorylation of mammalian target of rapamycin (p-mTOR), raptor protein, and mTOR complex 1 (mTORC1) levels were consistent with the increments in the expressions of p-Akt (Ser473, Thr308) and stress-induced IRE1α/p-eIF2α proteins in the endoplasmic reticulum following melatonin treatment. also, expression levels of Bcl-2 and Bcl-xl proteins were significantly increased compared to those in control cells without melatonin or glucose treatments, whereas the Bax protein level decreased. These results indicate that nanomolar melatonin regulates insulin synthesis and secretion associated with membrane vesicle trafficking-related proteins, including Rab5, GOPC, p-Caveolin-1, EEA1, and clathrin, through the Akt/mTOR pathway.
|
10.26402/jpp.2020.5.10
|
pubmed_742_19932
|
BACKGROUND/AIM
Providing a wheelchair or scooter is a complex therapy intervention aimed at enhancing the person's functioning. The research and experience has shown that a wheelchair which is poorly matched to the individual, adversely affects potential activities and participation, lifestyle goals, health status and can be costly. The development of an evidence-based clinical guideline will provide a synthesis of the evidence and recommendations for best practice.
METHODS
The guidelines were developed using a rigorous methodology of systematic search for primary studies, critical appraisal and synthesis of the evidence using an adaptation of the National Health and Medical Research Council recommendation grades in conjunction with a multidisciplinary working party.
RESULTS
Seventy-six recommendations were developed from 44 clinical questions related to goals, assessment and review, capacity and performance, upper limb capacity and injury risk, wheelchair features, propulsion, training, transport and maintenance. Resources were developed to support the use of the guidelines. Only examples of recommendations are provided here. The complete guidelines and technical report should be downloaded from http://www.lifetimecare.nsw.gov.au/Brain_Injury.aspx.
CONCLUSION
The guidelines provide appraisal and synthesis of the literature and recommendations for best practice on the prescription of a wheelchair or scooter for adults with spinal cord injury and/or traumatic brain injury. The guidelines are intended to reduce the potential for poor wheelchair prescription, inform and guide practice to enhance outcomes. Through judicious application of the available research, these guidelines provide best practice recommendations for prescribing the most appropriate wheelchair for a person with a traumatic brain injury/spinal cord injury.
|
10.1111/1440-1630.12077
|
pubmed_728_373
|
Rats exercise trained by swimming one hour daily five days per week for three months developed cardiac hypertrophy. The NE concentration (0.469 mug/g) and total NE content (0.741/mug) of the hypertrophied hearts were not significantly different from levels in hearts of unexercised control rats.
|
10.1378/chest.67.3.341
|
pubmed_617_5913
|
The triadic model of human infant temperament, involving Negative Affectivity, Orienting/Regulation, and Surgency/Extraversion factors, was applied to the rhesus neonate using exploratory factor analysis (EFA). Replicating and expanding earlier work in rhesus monkeys, the three-factor solution produced latent constructs comparable to human neonatal temperament.
|
10.1016/j.infbeh.2009.11.005
|
pubmed_308_5574
|
Although theoretical models have demonstrated that predator-prey population dynamics can depend critically on age (stage) structure and the duration and variability in development times of different life stages, experimental support for this theory is non-existent. We conducted an experiment with a host-parasitoid system to test the prediction that increased variability in the development time of the vulnerable host stage can promote interaction stability. Host-parasitoid microcosms were subjected to two treatments: Normal and High variance in the duration of the vulnerable host stage. In control and Normal-variance microcosms, hosts and parasitoids exhibited distinct population cycles. In contrast, insect abundances were 18-24% less variable in High- than Normal-variance microcosms. More significantly, periodicity in host-parasitoid population dynamics disappeared in the High-variance microcosms. Simulation models confirmed that stability in High-variance microcosms was sufficient to prevent extinction. We conclude that developmental variability is critical to predator-prey population dynamics and could be exploited in pest-management programs.
|
10.1111/ele.12571
|
pubmed_723_7855
|
The cerebellar lesions of bovine spongiform encephalopathy (BSE)-infected guinea pigs were characterized as severe atrophy of the cerebellar cortex associated with the loss of granule cells, decrease in the width of the molecular layer, and intense protease-resistant prion protein (PrPSc ) accumulations that are similar to cerebellar lesions in kuru and the VV2 type of sporadic Creutzfeldt-Jakob disease. The aim of this study is to assess the relationships between the distribution and localization of PrPSc and synapses expressing neurotransmitter transporters in order to reveal the pathogenesis of the disease. We used cell-type-specific immunohistochemical makers recognizing glutamatergic and γ-aminobutylic acid (GABA)ergic terminals to identify terminals impaired with PrPSc accumulations. The distribution of PrPSc accumulations and immunoreactivity of synaptic vesicles were studied throughout the neuroanatomical pathways in cerebellar lesions. Time course study demonstrated that PrPSc accumulation showed a tendency to spread from granular layer to molecular layer. The immunoreactivity of vesicular glutamate transporter 1 (VGluT1) was localized in axon terminals of cerebellar granule cells, and decreased in association with the severity of PrPSc accumulations and loss of granule cells. Immunoreactivities of vesicular glutamate transporter 2 (VGluT2) and vesicular GABA transporter (VGAT) that exist in axon terminals of inferior olivary neurons and GABAergic synapses of Purkinje cells, respectively, were preserved well in these lesions. In brainstem, VGluT1 immunoreactivity decreased selectively in pontine nuclei that are a component of the pontocerebellar pathway, although other neurotransmitter immunoreactivities were preserved well. Our findings suggest that the selective loss of VGluT1-immunoreactive synapses subsequent to PrPSc accumulations can contribute to the pathogenesis of cerebellar lesions of BSE-infected guinea pigs.
|
10.1111/neup.12613
|
pubmed_906_19716
|
The pineal recess (PR), a third ventricle (IIIV) evagination penetrating into the pineal gland, could constitute a site of melatonin passage to the cerebrospinal fluid (CSF) and explain the high concentrations of melatonin in this fluid. To test this hypothesis, we characterized melatonin distribution in the IIIV of sheep by CSF collection in the ventral part of IIIV (vIIIV) and in PR. At 30 microl/min collection rate, melatonin concentrations were much higher in PR than in vIIIV (19,934 +/- 6,388 vs. 178 +/- 70 pg/ml, mean +/- SEM, respectively, P < 0.005), and they increased in vIIIV when CSF collection stopped in the PR (P < 0.05). At 6 microl/min, levels increased to 1,682 +/- 585 pg/ml in vIIIV and were not influenced by CSF collection in the PR. This concentration difference between sites and the influence of PR collection on vIIIV levels suggest that melatonin reaches the PR and then diffuses to the IIIV. To confirm the role of PR, we demonstrated that its surgical sealing off decreased IIIV melatonin levels (1,020 +/- 305 pg/ml, compared with 5,984 +/- 1,706 and 6,917 +/- 1,601 pg/ml in shams or animals with a failed sealing off, respectively, P < 0.01) without changes in blood levels. Therefore, this study identified the localization of the main site of penetration of melatonin into the CSF, the pineal recess.
|
10.1210/endo.143.1.8585
|
pubmed_438_17425
|
OBJECTIVE
Epidemiological studies have shown that mental disorders are associated with reduced health-related quality of life, high levels of health care utilization, and work absenteeism. However, measurement of the burden of mental disorders by using population-based methods in large working populations, such as the U.S. military, has been limited.
METHOD
Analysis of hospitalizations among all active-duty military personnel (16.4 million person-years) from 1990 to 1999 and ambulatory visits from 1996 to 1999 was conducted by using the Defense Medical Surveillance System. Rates of hospitalization, ambulatory visits, and attrition from military service were compared for persons with mental disorder diagnoses and those with diagnoses in 15 other ICD-9 disease categories.
RESULTS
Mental disorders was the leading category of discharge diagnoses among men and the second leading category among women; 13% of all hospitalizations and 23% of all inpatient bed days were attributed to mental disorders. Six percent of the military population received ambulatory services for mental disorders annually in 1998 and 1999. Among a 1-year cohort of personnel, 47% of those hospitalized for the first time for a mental disorder left military service within 6 months. This attrition rate was significantly different from the rate of only 12% after hospitalization for any of the 15 other disease categories (range=11%-18%) (relative risk=4.04, 95% confidence interval=3.91-4.17). The difference remained significant after controlling for effects of age, gender, and duration of service.
CONCLUSIONS
Mental disorders appear to represent the most important source of medical and occupational morbidity among active-duty U.S. military personnel. These findings provide new population-based evidence that mental disorders are common, disabling, and costly to society.
|
10.1176/appi.ajp.159.9.1576
|
pubmed_955_15492
|
There are two major novel metabolism-based drug design concepts which have significant advantages when used in the design of safe, specific ophthalmic drugs. One is based on predictable enzymatic activation processes by enzymes found exclusively or preferentially at the site of action--in this case, within the eye, primarily in the iris-ciliary body. The second major retrometabolic design technique involves soft drug approaches. Among the various soft drug design strategies, it was found that the "inactive metabolite" and the "soft analog" approaches are the most useful for designing safe and selective ophthalmic drugs. In the first case, the design process starts with a known (or predicted) inactive metabolite (Mi) of the drug (D). This Mi is then structurally modified in the "chemical activation" stage to the soft drug (SD), which is isosteric and/or isoelectronic with D to produce activity at the target receptors, similar to that of D. By design, however, SD is also subject to a facile, predictable (generally hydrolytic) metabolism leading in one step to the starting inactive Mi. As this deactivation takes places everywhere in the body, the desired activities are produced virtually exclusively at the target site at or near the place of application. Successful use of this general concept has led to soft beta-blockers as safe antiglaucoma agents, soft anticholinergics as short acting mydriatic agents, and soft corticosteroids as a type of novel, safe anti-inflammatory agents, which due to their unique design, do not elevate intraocular pressure IOP and do not produce other systemic and local side effects.
|
10.1089/jop.1994.10.3
|
pubmed_511_16634
|
It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.
|
10.1152/ajpheart.00689.2017
|
pubmed_160_25290
|
BACKGROUND/PURPOSE
Traditionally, basic science research and publication record have led to a successful Pediatric Surgery Match. With changing applicant research backgrounds, we evaluated if these or other factors still apply.
METHODS
A SurveyMonkey questionnaire was distributed to 57 applicants with known contact information. We assessed demographic/financial data, application details and match results, research experience, publications, presence of a pediatric surgery fellowship at their home program, and applicant ranking criteria.
RESULTS
Forty-three (75%) responses were received. Twenty-five candidates matched, 12 (48%) to 1 of their first 3 choices. The median number of programs applied to was similar for matched and unmatched candidates (30), but matched candidates attended more interviews (21 vs 14.5; P = .03). Matched applicants had more publications (9.5 vs 5.1; P = .03), although research experience was similar to unmatched candidates. Research focus for matched vs total applicants included basic science (5 vs 12), clinical (4 vs 6), and both (11 vs 16). Five candidates matched without research experience. Ten (40%) applicants matched to institutions where they completed residency/research/fellowship training. Twelve (49%) applicants matched from programs without a fellowship program.
CONCLUSION
A strong publication record remains important, although clinical research is being valued more. Candidates from nonfellowship programs can be successful. This information may be useful to mentor future applicants and lays the foundation for a critical evaluation of the match process.
|
10.1016/j.jpedsurg.2011.02.030
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pubmed_942_19397
|
BACKGROUND
Autopsy studies show that C cells deriving from the ultimobranchial body and migrating into the thyroid do not reach the isthmus region and are distributed along the vertical axes of thyroid lobes. This was confirmed in a surgical series of 58 patients (34 with preoperatively normal and 24 with elevated serum calcitonin) where no calcitonin-positive cells were demonstrable immunohistochemically within separately investigated isthmi. Consequently, isthmus-preserving total bilateral lobectomy (IPTB) may be regarded as an adequate surgical procedure for C-cell hyperplasia (CCH).
PATIENTS AND METHODS
IPTB was performed from October 2001 to December 2004 in 64 patients, 59 patients with nodular goiter and slightly to moderately elevated serum calcitonin (stimulated under 500 pg/ml) (group A, apparently sporadic cases) and in 5 patients undergoing prophylactic surgery for hereditary medullary thyroid carcinoma (MTC) with intermediate- or low-risk RET mutations (non-634) (group B). The surgical procedure focused on meticulous total extracapsular resection of both thyroid lobes, preservation of an isthmus remnant of about 3 ml (smaller in children), and histologic workup of the border zones of resection in addition to that of the completely removed lobes. When malignancy could be proven intraoperatively (7 patients) or when the isthmus turned out to contain nodular lesions (4 patients), completion total thyroidectomy (plus lymphadenectomy) was performed as a one-stage procedure. Second-stage total thyroidectomy was performed in 3 cases. Thus, IPTB was the definitive surgical procedure in 50 patients (45 of group A and all 5 of group B).
RESULTS
In all of the 50 definite IPTB cases, postoperative serum calcitonin was below the measurable limit (2 pg/ml); stimulated calcitonin was below the measurable limit in 47 (including all of group B) and was measurable in 3 sporadic cases in a lower-normal range between 2.4 and 3.5 pg/ml. Genetic screening of the apparently sporadic cases with CCH was positive in one (codon 791). The risk of recurrent laryngeal nerve paralysis seems not to be elevated (0% permanent); permanent hypocalcemia occurred in 1 patient (2%). Follow-up data of 37 patients, median 18 (6-36) months, showed continuously nonmeasurable serum calcitonin with one exception, where it was in the normal range after 18 months. All IPTB patients are still under substitution therapy with L-thyroxine (median 125 mug/day) with decreasing tendency in all 3 children after prophylactic operation, the latter also showing an increasing volume of well-vascularized isthmi (from 1.5 to 2.5 ml).
CONCLUSION
IPTB reliably removes all C cells. There may not be need for total thyroidectomy (TTx) in cases with CCH. When necessary, completion TTx can be performed easily without additional risk. IPTB leaves a functionally relevant remnant, corresponding to that of a subtotal resection. This might be of importance especially for prophylactic surgery in children where the isthmus can compensate for the loss of thyroid function with time.
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10.1007/s00268-005-0424-z
|
pubmed_845_17282
|
One ring threaded by two other rings to form a non-intertwined ternary ring-in-rings motif is a challenging task in noncovalent synthesis. Constructing multicolor photoluminescence systems with tunable properties is also a fundamental research goal, which can lead to applications in multidimensional biological imaging, visual displays, and encryption materials. Herein, we describe the design and synthesis of binary and ternary ring-in-ring(s) complexes, based on an extended tetracationic cyclophane and cucurbit[8]uril. The formation of these complexes is accompanied by tunable multicolor fluorescence outputs. On mixing equimolar amounts of the cyclophane and cucurbit[8]uril, a 1:1 ring-in-ring complex is formed as a result of hydrophobic interactions associated with a favorable change in entropy. With the addition of another equivalent of cucurbit[8]uril, a 1:2 ring-in-rings complex is formed, facilitated by additional ion-dipole interactions involving the pyridinium units in the cyclophane and the carbonyl groups in cucurbit[8]uril. Because of the narrowing in the energy gaps of the cyclophane within the rigid hydrophobic cavities of cucurbit[8]urils, the binary and ternary ring-in-ring(s) complexes emit green and bright yellow fluorescence, respectively. A series of color-tunable emissions, such as sky blue, cyan, green, and yellow with increased fluorescence lifetimes, can be achieved by simply adding cucurbit[8]uril to an aqueous solution of the cyclophane. Notably, the smaller cyclobis(paraquat-p-phenylene), which contains the same p-xylylene linkers as the extended tetracationic cyclophane, does not form ring-in-ring(s) complexes with cucurbit[8]uril. The encapsulation of this extended tetracationic cyclophane by both one and two cucurbit[8]urils provides an incentive to design and synthesize more advanced supramolecular systems, as well as opening up a feasible approach toward achieving tunable multicolor photoluminescence with single chromophores.
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10.1021/jacs.0c07745
|
pubmed_977_20271
|
Johann Gregor Mendel, born 200 years ago, was supposed to be a farmer, intended to be a teacher, became a priest, turned to being a researcher, and later became a world famous scientist associated with genetics. Here, we look into his life through his own words.
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10.1371/journal.pbio.3001703
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pubmed_678_13667
|
Although previous research suggests that connection to large, mostly anonymous groups is important for the fulfillment of psychological needs and a sense of psychological well-being, no measure exists to assess individual differences in this area. In 5 studies, we developed and provided support for the validity of the Tendency for Effervescent Assembly Measure (TEAM). Utilizing data from student and community samples, we conducted exploratory factor analyses to guide item selection for the scale (Study 1), evaluated the structure of the scale in an independent sample (Study 2), examined the convergent, discriminant, and incremental validity of the scale (Study 3), and assessed measurement invariance of the scale across different demographic groups (Study 4). Study 5 explored the role of social needs fulfillment in effervescent assembly, as well as examined the relationship of the scale with recent collective effervescence experiences. Results revealed that our final 11-item scale was unidimensional, with excellent internal consistency and good test-retest reliability over 2 months. Measurement invariance was established across gender, ethnicity, and religion, providing support for the validity of the measure across demographic subgroups. Importantly, the TEAM predicted decreased loneliness, increased positive feelings, a sense of meaning in one's life, self-awareness, and spiritual transcendence, above and beyond the effects of the big 5 factors of personality and collective and relational interdependence. Furthermore, results suggested that positive outcomes associated with the TEAM are because of social need fulfillment. (PsycINFO Database Record
|
10.1037/pas0000434
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pubmed_1019_18527
|
The clustered protocadherins (Pcdhs), Pcdh-α, -β, and -γ, are transmembrane proteins constituting a subgroup of the cadherin superfamily. Each Pcdh cluster is arranged in tandem on the same chromosome. Each of the three Pcdh clusters shows stochastic and combinatorial expression in individual neurons, thus generating a hugely diverse set of possible cell surface molecules. Therefore, the clustered Pcdhs are candidates for determining neuronal molecular diversity. Here, we showed that the targeted deletion of DNase I hypersensitive (HS) site HS5-1, previously identified as a Pcdh-α regulatory element in vitro, affects especially the expression of specific Pcdh-α isoforms in vivo. We also identified a Pcdh-β cluster control region (CCR) containing six HS sites (HS16, 17, 17', 18, 19, and 20) downstream of the Pcdh-γ cluster. This CCR comprehensively activates the expression of the Pcdh-β gene cluster in cis, and its deletion dramatically decreases their expression levels. Deleting the CCR nonuniformly down-regulates some Pcdh-γ isoforms and does not affect Pcdh-α expression. Thus, the CCR effect extends beyond the 320-kb region containing the Pcdh-γ cluster to activate the upstream Pcdh-β genes. Thus, we concluded that the CCR is a highly specific regulatory unit for Pcdh-β expression on the clustered Pcdh genomic locus. These findings suggest that each Pcdh cluster is controlled by distinct regulatory elements that activate their expression and that the stochastic gene regulation of the clustered Pcdhs is controlled by the complex chromatin architecture of the clustered Pcdh locus.
|
10.1074/jbc.M111.245605
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pubmed_855_3417
|
Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NLS). When BL cells were exposed to PNA-myc(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited.
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10.1038/73745
|
pubmed_306_12384
|
BACKGROUND
The Angiotensin-Converting Enzyme-2 (ACE2) gene, located on chromosome X, is believed to be implicated in blood pressure regulation. However the few studies that have examined this association have yielded mixed results. The objective of this study was to assess the association between tag single nucleotide polymorphisms (SNPs) in the angiotensin-converting enzyme-2 gene with blood pressure and blood pressure change in adolescents.
METHODS
Participants in the Nicotine Dependence in Teens (NDIT) cohort study with blood or saliva samples and at least 3 blood pressure measurements over 5 years were included in the analytic sample (n = 555). Linear growth curve models stratified on sex and ethnicity were used to assess the association between four tag SNPs in the ACE2 gene and systolic (SBP) and diastolic blood pressure (DBP), and blood pressure change.
RESULTS
In males of European descent, rs2074192 and rs233575 were significantly associated with SBP and DBP, and rs2158083 was associated with SBP. In French Canadian males, rs233575 and rs2158083 were significantly associated with DBP. Among females of European descent, rs2074192, rs233575, and rs2158083 were significantly associated with change in SBP over 5 years.
CONCLUSIONS
This is the first study to assess the association between the ACE2 gene with blood pressure and blood pressure change in a cohort of adolescents. Results indicate that several ACE2 gene SNPs are associated with blood pressure or blood pressure change in persons of European descent. However the therapeutic potential of these SNPs should be explored.
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10.1186/1471-2350-14-117
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pubmed_465_2372
|
The workup of a pelvic mass should not be limited to intraperitoneally located organs. Pathologic conditions of the abdominal wall, although rare, can mimic an intraabdominal process. One example of such conditions is the spontaneous (atraumatic) appearance of an abscess in the retrofascial-prevesical space of Retzius.
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pubmed_465_2372
|
pubmed_406_1772
|
The value and drawbacks of xeroradiography were evaluated on 130 patients with benign and malignant bone tumors, 93 of which (72%) were submitted to histological control. Xeroradiography was compared to standard film radiography in 115 cases (88%). In 57 cases (50%), xeroradiography appeared to be more effective than film radiography; it was less effective in 17 cases (15%) and the two techniques were substantially equivalent in the remaining 41 (35%). The best results of xeroradiography were found in malignant tumors, in particular in the presence of an extraosseous spread of the lesion, and it was highly effective in Ewing's sarcoma. According to the sites examined, xeroradiography was more effective in the skeleton of the extremities, while the examination of the trunk and the head were frequently unsatisfactory due to the low sensitivity of this technique. Xeroradiography is held to be an useful second-line examination, to be performed in neoplastic lesions of the limb bones, for the search of small trabecular irregularities, of periosteal reactions or of extraosseous spread of the tumor.
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pubmed_406_1772
|
pubmed_441_13744
|
The mortality of 4559 Quebec chrysotile workers has been related to the findings from their last routine chest X-ray while still employed. In those 84 lung cancer cases who were X-rayed less than 10 years before their death, over two-thirds had 'less-than-normal' films; the abnormality was not specific, except for 'large opacities'. The three men who died from mesothelioma within about a year of X-ray were 'less-than-normal'. The findings of the completed project validated convincingly the 1967 UICC/Cincinnati classification.
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pubmed_441_13744
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pubmed_532_15417
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Understanding the interface between polymer and biomass in composite products is important for developing high performance products, as the quality of adhesion at the interface determines composite properties. For example, with greater stiffness compared to polymer matrix, such as that of high density polyethylene, the wood component enhances stiffness of wood-polymer composites, provided there is good adhesion between composite components. However, in composites made from wood flour (wood particles) and synthetic resins it is often difficult to clearly resolve particle-matrix interfaces in the conventionally employed microscopy method that involves SEM examination of fractured faces of composites. We developed a novel approach, where composites made from high density polyethylene and wood flour were examined and imaged with a FE-SEM (field emission scanning electron microscope) in transverse sections cut through the composites. Improved definition of the interface was achieved using this approach, which enabled a more thorough comparison to be made of the features of the interface between wood particles and the matrix in composites with and without a coupling agent, as it was possible to clearly resolve the interfaces for particles of all sizes, from large particles consisting of many cells down to tiny cell wall fragments, particularly in composites that did not incorporate the coupling agent used to enhance particle adhesion with the matrix polymer. The method developed would be suitable particularly for high definition SEM imaging of a wide range of composites made combining wood and agricultural residues with synthetic polymers.
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pubmed_532_15417
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pubmed_154_15200
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BACKGROUND
Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR).
OBJECTIVE
We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit.
METHODS
In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter.
RESULTS
Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo.
CONCLUSION
In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.
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10.1067/mai.2002.124657
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pubmed_597_10194
|
OBJECTIVE
Fracture is the major clinical outcome of osteoporosis. The vitamin D receptor (VDR) gene is thought to be a candidate gene for osteoporosis. Many genetic studies have suggested an association of VDR polymorphisms and fracture risk, but evidence remains conflicting. The aim of this study was to evaluate the genetic effect of the BsmI, TaqI, ApaI and FokI polymorphisms in the VDR gene on fracture risk in postmenopausal women.
METHODS
Relevant studies were identified from the following electronic databases: PubMed, Embase, and Web of Science before September 2013. Statistical analysis was performed by using the software STATA 12.0. A total 1975 fracture cases and 4565 controls in 14 studies with a total of 16 eligible comparisons were identified for data analysis.
RESULTS
No evidence of relationship between the VDR BsmI, TaqI, ApaI or FokI polymorphisms and fracture risk was observed with any genetic model in postmenopausal women (BsmI: b vs. B: odds ratio (OR) 1.07, 95% confidence interval (CI) 0.90-1.29; TaqI: T vs. t: OR 0.89, 95% CI 0.68-1.15; ApaI: A vs. a: OR 0.91, 95% CI 0.76-1.08; FokI: F vs. f: OR 1.20, 95% CI 0.76-1.90).
CONCLUSION
This meta-analysis suggests that ApaI, BsmI, TaqI and FokI polymorphisms may be not associated with the risk of fracture in postmenopausal women. Further studies in a larger sample population are required to confirm this finding.
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10.3109/13697137.2013.856401
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pubmed_1136_6846
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Refolding of the SH3 domain of PI3 kinase from the guanidine hydrochloride (GdnHCl)-unfolded state has been probed with millisecond (stopped flow) and sub-millisecond (continuous flow) measurements of the change in fluorescence, circular dichroism, ANS fluorescence and three-site fluorescence resonance energy transfer (FRET) efficiency. Fluorescence measurements are unable to detect structural changes preceding the rate-limiting step of folding, whereas measurements of changes in ANS fluorescence and FRET efficiency indicate that polypeptide chain collapse precedes the major structural transition. The initial chain collapse reaction is complete within 150 μs. The collapsed form at this time possesses hydrophobic clusters to which ANS binds. Each of the three measured intra-molecular distances has contracted to an extent predicted by the dependence of the FRET signal in completely unfolded protein on denaturant concentration, indicating that contraction is non-specific. The extent of contraction of each intra-molecular distance in the collapsed product of sub-millisecond folding increases continuously with a decrease in [GdnHCl]. The gradual contraction is continuous with the gradual contraction seen in completely unfolded protein, and its dependence on [GdnHCl] is not indicative of an all-or-none collapse reaction. The dependence of the extent of contraction on [GdnHCl] was similar for the three distances, indicating that chain collapse occurs in a synchronous manner across different segments of the polypeptide chain. The sub-millisecond measurements of folding in GdnHCl were unable to determine whether hydrophobic cluster formation, probed by ANS fluorescence measurement, precedes chain contraction probed by FRET. To determine whether hydrogen bonding plays a role in initial chain collapse, folding was initiated by dilution of the urea-unfolded state. The extent of contraction of at least one intra-molecular distance in the collapsed product of sub-millisecond folding in urea is similar to that seen in GdnHCl, and the initial contraction in urea too appears to be gradual.
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10.1016/j.jmb.2010.08.046
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pubmed_1107_7322
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A 34-year-old woman with extensive Klippel-Trenaunay syndrome is presented. Clinical and radiological tests demonstrated that three quadrants are affected with haemangiomas, varicose veins and bone abnormalities. In addition, our patient suffers from congenital lymphoedema of both legs. Associated findings such as intestinal haemangiomata, vascular hamartomas, lipoma or arteriovenous abnormalities of the spinal cord were not apparent. The treatment is only symptomatic with compression bandages and an orthopaedic appliance for compensation of the different leg length.
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10.1007/s001050050377
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pubmed_19_2593
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Psychomotor problems are common in children with congenital heart disease (CHD) but their neuropsychological basis remains unknown. This study investigated motor planning, motor control, and motor slowness, three subprocesses potentially underlying these psychomotor deficits. Using various drawing tasks, 45 school-age children with CHD were compared with 41 healthy peers on several kinematic properties. Taking longer to initiate and execute their movements than the controls, the children with CHD exhibited significant motor slowness. No evidence was found for deficits in planning or motor control. Thus, motor slowness appears to be the major determinant of psychomotor problems in school-age children with CHD.
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10.1080/87565641.2011.557456
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pubmed_1040_3144
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Measurement of local tissue PO2 using recessed microcathodes has again been criticized. Therefore, we reexamined electrode performance. Sharply beveled electrodes (3 micron external diameter) were fabricated with several tip recess lengths (4-10 micron), and some recesses were filled with hydrated polymer. In vitro, 2-mm agar (3%) sheets were equilibrated with solution of known PO2 (continuously flowing). Electrode currents at 100-micron intervals through the agar and of convected superfusion solution were compared. At the longest recess lumen length-to-diameter ratio of 10, minimum response midagar (1 mm) averaged 98%. Performance improved with the use of recess polymer and increased recess length. For in vivo studies, microcathodes (ratio approximately 10) were fluid calibrated, and PO2 was measured at 10-20 micron through canine femoral artery walls. PO2 distribution fit a model for radial diffusion with medial O2 consumption. After local cyanide application to the femoral wall, PO2 fit a model for radial diffusion without tissue O2 consumption. Carefully designed microcathodes and experiments measure accurate tissue PO2.
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10.1152/jappl.1985.58.4.1400
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pubmed_1134_339
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Ischemia-reperfusion (IR) causes human lung injury in association with the release of atrial and brain natriuretic peptides (ANP and BNP), but the role of ANP/BNP in IR lung injury is unknown. ANP and BNP bind to natriuretic peptide receptor-A (NPR-A) generating cGMP and to NPR-C, a clearance receptor that can decrease intracellular cAMP. To determine the role of NPR-A signaling in IR lung injury, we administered the NPR-A blocker anantin in an in vivo SWR mouse preparation of unilateral lung IR. With uninterrupted ventilation, the left pulmonary artery was occluded for 30 min and then reperfused for 60 or 150 min. Anantin administration decreased IR-induced Evans blue dye extravasation and wet weight in the reperfused left lung, suggesting an injurious role for NPR-A signaling in lung IR. In isolated mouse lungs, exogenous ANP (2.5 nM) added to the perfusate significantly increased the filtration coefficient sevenfold only if lungs were subjected to IR. This effect of ANP was also blocked by anantin. Unilateral in vivo IR increased endogenous plasma ANP, lung cGMP concentration, and lung protein kinase G (PKG(I)) activation. Anantin enhanced plasma ANP concentrations and attenuated the increase in cGMP and PKG(I) activation but had no effect on lung cAMP. These data suggest that lung IR triggered ANP release and altered endothelial signaling so that NPR-A activation caused increased pulmonary endothelial permeability.
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10.1152/ajplung.00185.2007
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pubmed_306_10917
|
IMPORTANCE
Data on the long-term cognitive outcomes of patients with PARKIN-associated Parkinson disease (PD) are unknown but may be useful when counseling these patients.
OBJECTIVE
Among patients with early-onset PD of long duration, we assessed cognitive and motor performances, comparing homozygotes and compound heterozygotes who carry 2 PARKIN mutations with noncarriers.
DESIGN, SETTING, AND PARTICIPANTS
Cross-sectional study of 44 participants at 17 different movement disorder centers who were in the Consortium on Risk for Early-Onset PD study with a duration of PD greater than the median duration (>14 years): 4 homozygotes and 17 compound heterozygotes (hereafter referred to as carriers) and 23 noncarriers.
MAIN OUTCOMES AND MEASURES
Unified Parkinson Disease Rating Scale Part III (UPDRS-III) and Clinical Dementia Rating scores and neuropsychological performance. Linear regression models were applied to assess the association between PARKIN mutation status and cognitive domain scores and UPDRS-III scores. Models were adjusted for age, education, disease duration, language, and levodopa equivalent daily dose.
RESULTS
Carriers had an earlier age at onset of PD (P < .001) and were younger (P = .004) at time of examination than noncarriers. They performed better than noncarriers on the Mini-Mental State Examination (P = .010) and were more likely to receive lower scores on the Clinical Dementia Rating (P = .003). In multivariate analyses, carriers performed better than noncarriers on the UPDRS-III (P = .02) and on tests of attention (P = .03), memory (P = .03), and visuospatial (P = .02) cognitive domains.
CONCLUSIONS AND RELEVANCE
In cross-sectional analyses, carriers demonstrated better cognitive and motor performance than did noncarriers with long disease duration, suggesting slower disease progression. A longitudinal follow-up study is required to confirm these findings.
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10.1001/jamaneurol.2013.4498
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pubmed_927_6784
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Incubation of chrysotile and amphibole asbestos fibers with normal human peripheral blood polymorphonuclear leukocytes (PMN) resulted in a significant stimulation of PMN metabolic activity and generation of toxic oxygen by-products as measured by chemiluminescence (CL). Although all asbestos fibers tested were cytotoxic to PMN, cytotoxicity and CL varied disproportionately with fiber type. Anthophyllite asbestos produced the greatest PMN cytotoxicity. It also depressed PMN phagocytosis of latex beads the most and induced the greatest PMN CL response of the fiber types examined. We postulate that asbestos-induced release of toxic oxygen by-products from PMN which have infiltrated into the pulmonary alveoli may contribute to disease pathogenesis in asbestosis.
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10.1159/000233061
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pubmed_223_15687
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Amyloid-β (Aβ) is a macromolecular structure of great interest because its misfolding and aggregation, along with changes in the secondary structure, have been correlated with its toxicity in various neurodegenerative diseases. Small drug-like molecules can modulate the amyloid secondary structure and therefore have raised significant interest in applications to active and passive therapies targeting amyloids. In this study, we investigate the interactions of epigallocatechin-3-gallate (EGCG), found in green tea, with Aβ polypeptides, using a combination of in vitro immuno-infrared sensor measurements, docking, molecular dynamics simulations, and ab initio calculations. We find that the interactions of EGCG are dominated by only a few residues in the fibrils, including hydrophobic π-π interactions with aromatic rings of side chains and hydrophilic interactions with the backbone of Aβ, as confirmed by extended (1-μs-long) molecular dynamics simulations. Immuno-infrared sensor data are consistent with degradation of Aβ fibril induced by EGCG and inhibition of Aβ fibril and oligomer formation, as manifested by the recovery of the amide-I band of monomeric Aβ, which is red-shifted by 26 cm-1 when compared to the amide-I band of the fibrillar form. The shift is rationalized by computations of the infrared spectra of Aβ42 model structures, suggesting that the conformational change involves interchain hydrogen bonds in the amyloid fibrils that are broken upon binding of EGCG.
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10.1016/j.bpj.2020.05.033
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pubmed_1041_3805
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The onset of Soret-driven instability in binary mixture heated from above is analysed using the linear stability theory. The horizontal fluid layer placed between two plates is in a thermally stable state but the Soret diffusion can induce buoyancy-driven convection in the case of a negative Soret coefficient. It is well known that convective motion sets in from both boundaries if the Rayleigh number exceeds its critical value. For the case of highly unstable density stratification the buoyancy-driven motion sets in during the transient diffusion stage. The new stability equations are derived and are solved analytically and numerically. Here the stability limits which are related to the onset time of instabilities and wave number are presented as a function of the Rayleigh number, Lewis number and the separation ratio. The present stability criteria are compared with the existing experimental data.
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10.1140/epje/i2011-11027-6
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pubmed_85_16369
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Individuals with diabetes develop lower extremity amputation for several reasons. Investigations into pathways to the development of complications are important both for treatment and prevention.
AIM
To evaluate the relationship between amputation and risk factors in people with diabetes mellitus.
MATERIALS AND METHOD
All participants included in this study (n=165) were recruited from the Diabetic Foot Program, developed in a Brazilian University, over seven years (2007-2014) and all information for this study was extracted from their clinical records.
RESULTS
The prevalence of amputation in patients with diabetes with four risk factors was up to 20% higher when compared to those with only one risk factor. The main predictive risk factors for amputation in this population were the presence of an ulcer and smoking.
CONCLUSION
The risk factors for amputation can be predicted for people with diabetes mellitus and, in the present study, the main factors were the presence of an ulcer and the smoking habit.
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10.1016/j.dsx.2016.08.002
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pubmed_1128_18184
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Recently defined formula diets are widely used for patients with digestive diseases. Long-term administration of such diets is presumed to change the absorptive characteristics of the small intestine. We investigated the influence of the defined formula diet on the absorptive capacity of growing rats by measuring the potential difference of sugars, amino acid, half-maximum concentration (kt) of these substrates, the activities of disaccharidase and dipeptidase, and the portal amino acid concentrations. There was no significant difference in the body weight of rats fed amino acid or peptide diets and those given the normal chow, but the administration of the defined formula diets reduced the absorption of amino acid and small peptide per serosal area and kt. On the other hand, absorption of sugars was not significantly influenced by the type of the diets. The differences in the absorptions of amino acid and peptide following the administration of the defined formula diet might be associated with the change in the resistance of the unstirred water layer or the alteration in the active transport system of amino acids or peptides in the small intestine. No significant differences were observed between the influences of the amino acid and the peptide diets.
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10.1097/00005176-199005000-00013
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pubmed_386_7009
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Phase separation in plasticized cellulose triacetate (CTA) films is investigated to produce a microporous film that can be used in optical devices. Hot-stretched CTA films containing diisodecyl adipate (DIDA) show negative orientation birefringence similar to the hot-stretched pure CTA. After extracting DIDA from the stretched films by immersion into an organic solvent, however, the films exhibit positive birefringence. Moreover, the magnitude of the birefringence increases with the wavelength, known as extraordinary dispersion, which is an essential property in the preparation of an ideal quarter-wave plate. Numerous ellipsoidal pores with micro-scale were detected in the film after the immersion, indicating that DIDA were segregated and formed ellipsoidal domains in the CTA matrix during annealing and stretching. These results indicate that extraordinary wavelength dispersion is given by the combinations of orientation birefringence from CTA and form birefringence from micropores. Furthermore, it was found that annealing time and stretching condition affect the phase separation as well as the shape and size of pores.
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pubmed_386_7009
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pubmed_266_2112
|
Primary epiploic appendagitis is uncommon and is estimated to induce 1.1-1.3% of all abdominal pain. We report a 42-year-old male who appeared in the morning in the emergency department with abdominal pain localized in the right lower abdomen and associated with anorexia and nausea. Clinical examination, laboratory tests, and abdominal ultrasound revealed deep tenderness at Mc Burney point and a mild elevation of CRP (0.7 mg/dL). In the evening, the symptoms were exacerbated, and a diagnostic laparoscopy was performed. Intra-operatively, the appendix was normal and a twisted, necrotic epiploic appendage originating from the antimesenteric border of the mid ascending colon was found. Laparoscopic resection of the necrotic epiploic appendage and prophylactic appendectomy was carried out. Histology indicated the diagnosis of the necrotic epiploic appendage. Postoperatively, the patient recovered without complications. Although the preoperative diagnosis of primary epiploic appendagitis has improved due to abdominal ultrasound and mainly CT, there are still cases which are diagnosed during laparoscopy. The treatment of choice is conservative management, while the use of antibiotics remains controversial. The relapse and complication rates are rare. Surgical excision, particularly laparoscopic, should be considered in cases of uncertain diagnosis, persistent symptoms, or recurrence.
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10.4166/kjg.2020.76.2.88
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pubmed_750_11623
|
The centromere plays an essential role in chromosome segregation. In most eukaryotes, centromeres are epigenetically defined by the conserved histone H3 variant CENP-A. Proper centromere assembly is dependent upon the tight regulation of CENP-A level. Cell cycle regulation of CENP-A transcription appears to be a universal feature across eukaryotes, but the molecular mechanism underlying the temporal control of CENP-A transcription and how such regulation contributes to centromere function remains elusive. CENP-A in fission yeast has been shown to be transcribed before S phase. Using various synchronization methods, we confirmed that CENP-A transcription occurs at G1, leading to an almost twofold increase of the protein during S phase. Through a genetic screen, we identified the MBF (MluI box-binding factors) complex as a key regulator of temporal control of CENP-A transcription. The periodic transcription of CENP-A is lost in MBF mutants, resulting in CENP-A mislocalization and chromosome segregation defects. We identified the MCB (MluI cell cycle box) motif in the CENP-A promoter, and further showed that the MBF complex binds to the motif to restrict CENP-A transcription to G1. Mutations of the MCB motif cause constitutive CENP-A expression and deleterious effects on cell survival. Using promoters driving transcription to different cell cycle stages, we found that timing of CENP-A transcription is dispensable for its centromeric localization. Our data instead indicate that cell cycle-regulated CENP-A transcription is a key step to ensure that a proper amount of CENP-A is generated across generations. This study provides mechanistic insights into the regulation of cell cycle-dependent CENP-A transcription, as well as its importance on centromere function.
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10.1534/genetics.118.301745
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pubmed_774_10655
|
Filamentous fungi are frequently involved in food spoilage and cause important food losses and substantial economic damage. Their rapid and accurate identification is a key step to better manage food safety and quality. In recent years, MALDI-TOF MS has emerged as a powerful tool to identify microorganisms and has successfully been applied to the identification of filamentous fungi especially in the clinical context. The aim of this study was to implement a spectral database representative of food spoilage molds. To this end, after application of a standardized extraction protocol, 6477 spectra were acquired from 618 fungal strains belonging to 136 species and integrated in the VITEK MS database. The performances of this database were then evaluated by cross-validation and ∼95% of correct identification to the species level was achieved, independently of the cultivation medium and incubation time. The database was also challenged with external isolates belonging to 52 species claimed in the database and 90% were correctly identified to the species level. To our best knowledge, this is the most comprehensive database of food-relevant filamentous fungi developed to date. This study demonstrates that MALDI-TOF MS could be an alternative to conventional techniques for the rapid and reliable identification of spoilage fungi in food and industrial environments.
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10.1016/j.fm.2018.05.001
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pubmed_328_6914
|
EU legislation requires that chemicals migrating from food packaging into food do not endanger human health. A proper safety assessment must go further than simply testing for known ingredients used to make the packaging materials. The identification of all potential migrants, including non-intentionally added substances (NIAS), is required to assess the safety of these materials. In this study, the benefits of using LC-ESI-Q-TOF-MS equipment combined with the data-independent acquisition method SWATH (Sequential Windowed Acquisition of All THeoretical MS) have been evaluated for the identification of unexpected migrants from multilayer plastic packaging materials. Identification of non-target peaks followed by filtering strategies facilitated the comprehensive identification procedure of unexpected migrants present in the food simulants. MS and MS/MS data from the most abundant ions in the samples were processed using formula finding and searched against open chemical and spectral databases, such as ChemSpider and METLIN, combined with bibliographic search. This approach has allowed the identification of 26 potential migrants, of which 23 were NIAS. Cyclic oligomers, possibly coming from polyurethane adhesives, were the main migrants in the studied materials. Evaluation of the toxicity of the tentatively identified migrants was carried out, showing that most of them were classified in the higher toxicity class according to Cramer rules. Most of the compounds detected in this study were previously reported in other studies of NIAS migration from plastic packaging materials, except for five of the tentatively identified oligomers that were found for the first time in this study. This study shows the high potential of non-targeted approaches using high resolution accurate mass spectrometry (HRAMS) with SWATH acquisition for the characterization of food packaging materials aimed at food safety evaluation.
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10.1016/j.talanta.2018.08.023
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pubmed_298_2697
|
BACKGROUND
Nationally representative Canadian data on the prevalence of child abuse and its relation with mental disorders are lacking. We used contemporary, nationally representative data to examine the prevalence of 3 types of child abuse (physical abuse, sexual abuse and exposure to intimate partner violence) and their association with 14 mental conditions, including suicidal ideation and suicide attempts.
METHODS
We obtained data from the 2012 Canadian Community Health Survey: Mental Health, collected from the 10 provinces. Respondents aged 18 years and older were asked about child abuse and were selected for the study sample (n = 23,395). The survey had a multistage stratified cluster design (household response rate 79.8%).
RESULTS
The prevalence of any child abuse was 32% (individual types ranged from 8% to 26%). All types of child abuse were associated with all mental conditions, including suicidal ideation and suicide attempts, after adjustment for sociodemographic variables (adjusted odds ratios ranged from 1.4 to 7.9). We found a dose-response relation, with increasing number of abuse types experienced corresponding with greater odds of mental conditions. Associations between child abuse and attention deficit disorder, suicidal ideation and suicide attempts showed stronger effects for women than men.
INTERPRETATION
We found robust associations between child abuse and mental conditions. Health care providers, especially those assessing patients with mental health problems, need to be aware of the relation between specific types of child abuse and certain mental conditions. Success in preventing child abuse could lead to reductions in the prevalence of mental disorders, suicidal ideation and suicide attempts.
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10.1503/cmaj.131792
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pubmed_449_9469
|
A recent epidemiological survey of the whole adult Micronesian population of Nauru has confirmed that Nauruans, along with Pima Indians, suffer the highest rate of abnormal glucose tolerance yet recorded. To establish the morbid effects of hyperglycaemia in this population, all responders to the diabetes survey were concurrently examined for diabetic retinopathy. In diabetic subjects, the crude prevalence of retinopathy was 24%. Specific rates were determined at various levels of the following characteristics: age, 2 hour post-load plasma glucose, body mass index, duration of diabetes and systolic blood pressure. Prevalence was found to rise with increasing 2 hour plasma glucose and duration, to fall with increasing body mass index and to have a quadratic relationship with age and systolic blood pressure. The multiple logistic regression model was used to determine whether the selected characteristics were significant in increasing the risk of retinopathy. Body mass index and systolic blood pressure did not contribute significantly to this risk after controlling for age. Increasing 2 hour plasma glucose significantly increased the risk of retinopathy, and duration of disease was the strongest predictor variable. This study shows that the consequences of hyperglycaemia in this Micronesian population are comparable to those already documented in European and American Indian communities.
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10.1620/tjem.141.suppl_343
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pubmed_1074_21533
|
Spintronics relies on the ability to transport and use the spin properties of an electron rather than its charge. We describe a spin ratchet at the single-electron level that produces spin currents with no net bias or charge transport. Our device is based on the ground-state energetics of a single-electron transistor comprising a superconducting island connected to normal leads via tunnel barriers with different resistances that break spatial symmetry. We demonstrate spin transport and quantify the spin ratchet efficiency by using ferromagnetic leads with known spin polarization. Our results are modeled theoretically and provide a robust route to the generation and manipulation of pure spin currents.
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10.1126/science.1196228
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pubmed_848_10837
|
Analytical methods for pentachlorophenol (PCP) residues in edible animal tissue have been reviewed, with particular reference to gas chromatographic methods of analysis. Results of analyses demonstrate that significant residues of PCP can persist for several weeks in animals exposed to contaminated bedding. National surveys in Canada have found that the incidence of PCP residues in pork in excess of 0.1 ppm was reduced from 32% of survey samples in 1981-1982 to 6.6% of samples tested in 1987-1988. An interlaboratory sample exchange among Canadian laboratories demonstrated that the PCP analytical method currently used by Agriculture Canada could be successfully transferred to other laboratories. An exchange of samples between regulatory laboratories of Agriculture Canada and the Food Safety and Inspection Service of the U.S. Department of Agriculture (USDA) demonstrated equivalency of results for the 2 methods currently used in the respective laboratories, with relative standard deviations for analytical results ranging from 4.4 to 22.2%.
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pubmed_848_10837
|
pubmed_781_15310
|
In the present study, the effect of sodium selenite on lead induced toxicity was studied in Wistar rats. Sodium selenite and lead nitrate were administered orally for 28 days to streptozotocin induced diabetic and non-diabetic rats. Eight groups of rats were used in the study: control, sodium selenite, lead nitrate, lead nitrate+sodium selenite, streptozotocin-induced diabetic-control, diabetic-sodium selenite, diabetic-lead nitrate, diabetic-lead nitrate+sodium selenite groups. Serum biochemical parameters, lipid peroxidation, antioxidant enzymes and histopathological changes in liver tissues were investigated in all groups. There were statistically significant changes in liver function tests, antioxidant enzyme activities and lipid peroxidation levels in lead nitrate and sodium selenite+lead nitrate treated groups, also in diabetic and non-diabetic groups. Furthermore, histopathological alterations were demonstrated in same groups. In the present study we found that sodium selenite treatment did not show completely protective effect on diabetes mellitus caused damages, but diabetic rats are more susceptible to lead toxicity than non-diabetic rats.
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pubmed_781_15310
|
pubmed_2_12978
|
Benzimidazoles act by disrupting microtubule polymerisation and are capable of inducing the formation of micronuclei. Considering the similarities in their mechanisms of action (inhibition of microtubule assembly by binding to the colchicine-binding site on tubulin monomers), combination effects according to the principles of concentration addition might occur. If so, it is to be expected that several benzimidazoles contribute to micronucleus formation even when each single one is present at or below threshold levels. This would have profound implications for risk assessment, but the idea has never been tested rigorously. To fill this gap, we analysed micronucleus frequencies for seven benzimidazoles, including the fungicide benomyl, its metabolite carbendazim, the anthelmintics albendazole, albendazole oxide, flubendazole, mebendazole and oxibendazole. Thiabendazole was also tested but was inactive. We used the cytochalasin-blocked micronucleus assay with CHO-K1 cells according to OECD guidelines, and employed an automated micronucleus scoring system based on image analysis to establish quantitative concentration-response relationships for the seven active benzimidazoles. Based on this information, we predicted additive combination effects for a mixture of the seven benzimidazoles by using the concepts of concentration addition and independent action. The observed effects of the mixture agreed very well with those predicted by concentration addition. Independent action underestimated the observed combined effects by a large margin. With a mixture that combined all benzimidazoles at their estimated threshold concentrations for micronucleus induction, micronucleus frequencies of ~15.5% were observed, correctly anticipated by concentration addition. On the basis of independent action, this mixture was expected to produce no effects. Our data provide convincing evidence that concentration addition is applicable to combinations of benzimidazoles that form micronuclei by disrupting microtubule polymerisation. They present a rationale for grouping these chemicals together for the purpose of cumulative risk assessment.
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10.1093/mutage/get019
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pubmed_660_1918
|
The potential of iron molybdates as catalysts in the Formox process stimulates research on aggregated but molecular iron-molybdenum oxo compounds. In this context, [(Me3TACN)Fe](OTf)2 was reacted with (nBu4N)2[MoO4], which led to an oxo cluster, [[(Me3TACN)Fe][μ-(MoO4-κ(3)O,O',O″)]]4 (1, Fe4Mo4) with a distorted cubic structure, where the corners are occupied by (Me3TACN)Fe(2+) and [Mo═O](4+) units in an alternating fashion, being bridged by oxido ligands. The cyclic voltammogram revealed four reversible oxidation waves that are assigned to four consecutive Fe(II) → Fe(III) transfers and motivated attempts to isolate compounds containing the respective cations. Indeed, a salt with a Fe(II)2Fe(III)2Mo(VI)4 constellation, [Fe4Mo4](TCNQ)2 (2), could be isolated after treatment with TCNQ. The Fe(II)Fe(III)3Mo(VI)4 stage could be reached via oxidation with DDQ or 3 equiv of thianthrenium hexafluorophosphate (ThPF6), giving [Fe4Mo4](DDQ)3 (4) or [Fe4Mo4](PF6)3 (5), respectively. The fully oxidized Fe(III)4Mo(VI)4 state was generated through oxidation with 4 equiv of ThPF6, leading to [Fe4Mo4](PF6)4, which showed a unique behavior: upon storage, one of the [Mo═O](4+) corners inverts, so that the terminal oxido ligand is located in the interior of the cage, leading to the formation of [[(Me3TACN)Fe]4[μ-([MoO4]3[MoO4(MeCN-κN)])-κ(3)O,O',O″)](PF6)4 (7). In this form, the compound could no longer be employed to enter the cyclic voltammogram recorded for 1, 3, and 5 from the oxidized side; no discrete redox events were observed. Compounds 1-3 and 7 were characterized structurally and 1, 3, and 7 additionally by SQUID measurements and Mössbauer spectroscopy. The data reveal a high degree of charge delocalization. (16)O/(18)O exchange experiments with labeled water performed with 1 revealed an interesting parallel with the Formox catalyst: water-(18)O exchanges its label with all of the oxido ligands (bridging and terminal). This property relates to the ion mobility being held responsible for the activity of iron molybdate catalysts compared to neat MoO3 or Fe2O3.
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10.1021/ic500584a
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pubmed_752_6367
|
Behavioral neuroscientists have shown that the neuropeptide oxytocin (OT) plays a key role in social attachment and affiliation in nonhuman mammals. Inspired by this initial research, many social scientists proceeded to examine the associations of OT with trust in humans over the past decade. To conduct this work, they have (a) examined the effects of exogenous OT increase caused by intranasal administration on trusting behavior, (b) correlated individual difference measures of OT plasma levels with measures of trust, and (c) searched for genetic polymorphisms of the OT receptor gene that might be associated with trust. We discuss the different methods used by OT behavioral researchers and review evidence that links OT to trust in humans. Unfortunately, the simplest promising finding associating intranasal OT with higher trust has not replicated well. Moreover, the plasma OT evidence is flawed by how OT is measured in peripheral bodily fluids. Finally, in recent large-sample studies, researchers failed to find consistent associations of specific OT-related genetic polymorphisms and trust. We conclude that the cumulative evidence does not provide robust convergent evidence that human trust is reliably associated with OT (or caused by it). We end with constructive ideas for improving the robustness and rigor of OT research.
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10.1177/1745691615600138
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pubmed_992_16260
|
Oligomeric amyloid-β 1-42 (Aβ-42) peptides are considered to be the most toxic species connected to the occurrence of Alzheimer's disease. However, not all aggregation conditions promote oligomer formation in vitro, raising the question whether oligomer formation in vivo also requires a specific suitable cellular environment. We recently found that interaction with neuronal membranes initiates aggregation of Aβ-42 and neuronal uptake. Our data suggest that small molecules in the extracellular space can facilitate the formation of membrane-active Aβ-42 oligomers. We analyzed the early stage of Aβ-42 aggregation in the presence of glucose and sucrose and found that these sugars strongly favor Aβ-42 oligomer formation. We characterized oligomers by dynamic light scattering, atomic force microscopy, immuno-transmission electron microscopy and fluorescence cross correlation spectroscopy. We found that Aβ-42 spontaneously and rapidly forms low molecular weight oligomers in the presence of sugars. Slightly acidic pH (6.7-7) greatly favors oligomer formation when compared to the extracellular physiological pH (7.4). Circular dichroism demonstrated that these Aβ-42 oligomers did not adopt a β-sheet structure. Unstructured oligomeric Aβ-42 interacted with membrane bilayers of giant unilamellar vesicles (GUV) and neuronal model cells, facilitated cellular uptake of Aβ-42, and inhibition of mitochondrial activity. Our data therefore suggest that elevated concentrations of glucose within the range observed in diabetic individuals (10 mM) facilitate the formation of membrane-active Aβ-42 oligomers.
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10.1039/c7cp02849k
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pubmed_1039_7981
|
A hybridoma is described that exhibits all the characteristic features of Mott cells. It has spherules (Russell bodies) in the cytoplasm made up of dilated rough endoplasmatic reticulum and containing condensed immunoglobulin (lambda 1 light chains). Some of the cells appear to be very fragile, and free spherules are often found on cell smears. Cells with the Mott cell characteristics are still able to divide, but they do not secrete immunoglobulin. Hybridomas of this kind should be useful for determining the place of the Mott cell within the scheme of B cell differentiation.
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10.1002/eji.1830140814
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pubmed_120_21344
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The discussion covers different aspects of application of programs of early prostatic cancer diagnosis. Arguments for and against the screening are presented. The existing methods of early prostatic cancer diagnosis are reviewed. How to improve the technique of taking prostatic biopsy is shown.
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pubmed_120_21344
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pubmed_1069_10663
|
The chemical similarities between vanadate and phosphate combined with the ability of vanadate to readily undergo changes in coordination geometry allows this ion to strongly influence the function of a large variety of phosphate-metabolizing enzymes. As transition state analogs, spontaneously formed vanadate complexes are potent inhibitors of a number of enzymes, including some ribonucleases, mutases, and phosphatases. In addition, vanadate is an effective inhibitor of many ATPases, kinases, lyases, and synthases. Vanadate oligomers tend to be weaker inhibitors than vanadate but do influence the function of dehydrogenases, mutases, aldolases, kinases, and others. Of the oligomers, decavanadate is unique in that it seems to bind only in polyphosphate binding domains. Peroxovanadate has not yet been well studied but it seems to inhibit enzymes that do not utilize a pentacoordinate vanadate in the catalysis cycle. Additional detailed studies of vanadate-initiated inhibition of enzymes will expand our understanding of the various mechanisms of action of vanadate and its derivatives that have been briefly described here and will doubtless provide insight into other functions of this unique material.
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pubmed_1069_10663
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pubmed_289_12038
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Three-dimensional (3D) medical imaging has been incorporated in routine clinical practice, since the required infrastructure has become increasingly affordable. New algorithms and applications are needed to serve the additional image processing and analysis functions in 3D space. In this work we propose a system for semi-automatic modeling and segmentation of elongated salient and anatomical objects in 3D medical images. The proposed methodology is based on a novel mathematical formalization of a well-known class of geometric primitives, namely generalized cylinders (GCs), which exhibits advantages over the existing parametric definition. Since the anatomical objects have to be modeled by their intersection with the transverse image planes, the proposed methodology includes also a new seeded region growing (SRG) segmentation algorithm for ellipse detection in 2D images, based on a priori shape knowledge. Finally, the resulting GC model is used to initialize an active surface (AS) segmentation method, in order to accurately delineate the required object. In this work we present the proposed algorithms in detail, along with the evaluation of the accuracy of the model-based segmentation by experts. Results show that elongated objects like the aorta and the trachea may be segmented with sensitivity between 90% and 95%. The proposed SRG-ellipse detector requires minimal user-initialization and its executions requires only few seconds for each image slice on an average laptop. The evolution of the AS requires less than one second per iteration for a typical CT image. Comparisons are provided with state of the art semi-automatic medical image processing software, which validate the merit of the proposed work.
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pubmed_289_12038
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pubmed_1090_18793
|
A 34 yr old heroin addict was referred because of chest pain caused by air-trapping in a bulla in the left lower lobe. There was a marked difference between the functional residual capacity measured by body-plethysmography and helium dilution. A slow wash-in and wash-out were demonstrated by ventilation scintigraphy with Xenon133. Bullous degeneration is a known complication of intravenous drug abuse. Usually these bullae are found in the upper lobes. Possible causative mechanisms are discussed.
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pubmed_1090_18793
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pubmed_487_21398
|
A 65-year-old Japanese male was diagnosed as multiple myeloma with Bence Jones kappa type, clinical stage IIIA. His disease status reached partial remission after chemotherapy. Thereafter, he received tandem transplantation, consisting of high-dose chemotherapy with autologous stem cell transplantation (ASCT), followed by unrelated cord blood transplantation (U-CBT). U-CBT with a reduced-intensity conditioning regimen (RI-CBT) was performed in August 2003. HLA mismatch between the patient and the CBT donor was present at two serological loci (B and DR). A total nucleated CBT cell dose of 2.45 x 10(7)/kg body weight was infused on day 0. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporine A and short-term methotrexate. Neutrophil engraftment (>0.5 x 10(9)/l) was obtained on day 46. He developed positive cytomegalovirus antigenemia, grade II acute GVHD involving skin and liver, varicella-zoster virus infection, septic shock, hemorrhagic cystitis caused by adenovirus and acute hepatitis B virus infection after U-CBT. We retrospectively analyzed T-cell receptor (TCR) repertoire diversity and found that TCR repertoire diversity decreased continuously after U-CBT. Therefore, low-TCR repertoire diversity in this patient appears to be associated with various infections caused by immunodeficiency.
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10.1111/j.1751-553X.2007.00903.x
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pubmed_616_8511
|
Tracheal bronchus is a congenital anatomical variant of patients with accessory bronchus in the right upper lobe deriving directly from the supracarinal trachea. Pre-operative consultation with the anesthesiologist is important for patient safety and can avoid adverse effects induced by endotracheal intubation. In this report, we described a case of tracheal bronchus in which general anesthesia was performed for video-assisted thoracoscopic surgery. We discussed some of the issues surrounding to complications in tracheal bronchus.
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10.1016/j.aja.2017.09.002
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pubmed_1044_26196
|
The results of many studies and register reports show that the frequency of primary hip arthroplasty per hospital, but also per surgeon, influence the outcome. In the large spectrum of revision hip arthroplasty volume-outcome effects have also partially been proven. It is obvious that with the increasing complexity of revision surgery and comorbidities, higher demands exist concerning collaborating disciplines as well as training and intervention frequency of the surgical team. Further aspects regarding organisation and structure such as the availability of specific revision implants and instruments must be ensured. In order to provide sustainable resources for revision surgery in an arthroplasty centre, organization of education and training for staff members in different disciplines and working levels must be ensured without quality impairment.
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10.1007/s00132-022-04275-0
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pubmed_192_22827
|
Objective: To compare the difference of preoperative planning parameters between 3D-printing non-coplanar template (3D-PNCT) and 3D-printing coplanar template (3D-PCT) in the treatment of pelvic wall recurrent gynecological malignant tumor with radioactive seeds implantation, and to guide the clinical application. Methods: From January 2016 to March 2018, 33 patients with pelvic wall recurrent gynecological malignant tumor were treated with radioactive seeds implantation assisted by 3D-printing template and in Peking University Third Hospital. All patients underwent 3D-PNCT and 3D-PCT preoperative planning. The D(90) of target remained similar for the same patient. The parameters were compared with Wilcoxon test or Kruskal-Wallis test. Results: D(90) was similar between the two groups (P>0.05). The number of inserting needles through intestine and bone in 3D-PNCT group was less than that in 3D-PCT group (0 (0-13), 0 (0-25), Z=-2.941, P<0.05;0 (0-3), 0 (0-25), Z=-2.232, P<0.05). Conclusion: For patients with gynecological malignancies with pelvic recurrence, both of the two peroperative plans could achieve prescription dose, but 3D-PNCT is more safer.
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10.3760/cma.j.issn.0376-2491.2019.11.009
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pubmed_879_9523
|
The care of metastatic colorectal cancers is based on combination chemotherapies including 5-fluorouracil, oxaliplatin, irinotecan, and monoclonal antibodies targeting the epidermal growth factor receptor or vascular endothelial growth factor. The regimen is determined based on the patient's molecular biology and general condition. Irinotecan bifractionation showed efficacy in chemorefractory patients in a previous study, FOLFIRI-3, but a desynchronized triplet has never been tested. The aim of bFOLFIRINOX-3 is to determine the safety, tolerance, and efficacy of a new regimen (FOLFIRINOX-3 bevacizumab) in chemorefractory patients. The aim of this study was to evaluate the safety and efficacy of FOLFIRINOX-3 bevacizumab in chemorefractory metastatic colorectal cancer (mCRC). A standard phase I, "3 + 3" design study was performed. The standard protocol comprised simplified FOLFOX 4 (folinic acid 400 mg/m2), 5-fluorouracil (a 400 mg/m2 bolus followed by 2400 mg/m2 for 46 h), oxaliplatin (85 mg/m2) and irinotecan (administered before and after 5-fluorouracil infusion), plus bevacizumab (5 mg/kg). In a "3 + 3" design, three different doses of irinotecan were tested: 60, 70 and 90 mg/m2. The primary endpoint was the maximum tolerable dose (MTD) of irinotecan. The secondary endpoints included the objective response (at 8 and 16 weeks) according to the RECIST 1.1 criteria and progression free survival. Thirteen patients were enrolled, and twelve patients were finally evaluated for dose-limiting toxicity (DLT). The dose level defined was 70 mg/m2 irinotecan. A total of three DLTs were observed (grade 3 diarrhea): two DLTs at the 90 mg/m2 dose level and one at the 70 mg/m2 dose level. The most frequently described adverse events were asthenia (93%), diarrhea (77%), nausea (62%) and peripheral sensory neuropathy (46%). The most frequent biological event was thrombopenia (54%). Regarding efficacy, among the 11 evaluable patients, no progression was observed at 8 weeks, and the partial response rate was 18.2%. At 16 weeks, a partial response rate of 27.3% was observed, and five patients had a stable disease. The new regimen of bFOLFIRINOX-3 with irinotecan at 70 mg/m2 was well tolerated. In chemorefractory patients, this protocol shows a high response rate.
|
10.3390/cancers13215472
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pubmed_897_3162
|
Recent studies have demonstrated a potential synergistic effect of the combination of amlodipine with atorvastatin to reduce acute inflammation. The intraluminal wire injury of the mouse femoral artery induced significant leukocyte recruitment to the injured area and oxidative stress within 24 h. Administration of low-dose amlodipine (0.5 mg kg(-1) per day) or atorvastatin (1 mg kg(-1) per day) alone for 7 days failed to modulate leukocyte adhesion, whereas their co-administration for 7 days significantly inhibited leukocyte adhesion. Moreover, flow cytometric analysis showed that injury-induced oxidative stress and CD11b expression in three leukocyte fractions were elevated after injury and then reduced after the co-administration. Next, adoptive transfer of mononuclear cells (MNCs) was performed and MNCs were harvested from mice after wire injury exhibited adhesion to the recipient injured artery. Furthermore, the co-administration of low-dose atorvastatin and amlodipine to MNCs or the vasculature reduced the recruitment of MNCs to the injured artery. Our findings indicate that amlodipine and atorvastatin synergistically inhibit vascular inflammation. The underlying mechanisms of their effect involve, at least in part, stabilizing oxidative stress at the point of injury, suggesting the clinical efficacy of this drug combination for the treatment of vascular diseases.
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10.1038/hr.2010.254
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pubmed_467_4436
|
Immune-competent animal models for the hepatitis C virus (HCV) are nonexistent, impeding studies of host-virus interactions and vaccine development. Experimental infection of laboratory rats with a rodent hepacivirus isolated from Rattus norvegicus (RHV) is a promising surrogate model due to its recapitulation of HCV-like chronicity. However, several aspects of rat RHV infection remain unclear, for instance, how RHV evades host adaptive immunity to establish persistent infection. Here, we analyzed the induction, differentiation, and functionality of RHV-specific CD8 T cell responses that are essential for protection against viral persistence. Virus-specific CD8 T cells targeting dominant and subdominant major histocompatibility complex class I epitopes proliferated considerably in liver after RHV infection. These populations endured long term yet never acquired antiviral effector functions or selected for viral escape mutations. This was accompanied by the persistent upregulation of programmed cell death-1 and absent memory cell formation, consistent with a dysfunctional phenotype. Remarkably, transient suppression of RHV viremia with a direct-acting antiviral led to the priming of CD8 T cells with partial effector function, driving the selection of a viral escape variant. These data demonstrate an intrinsic abnormality within CD8 T cells primed by rat RHV infection, an effect that is governed at least partially by the magnitude of early virus replication. Thus, this model could be useful in investigating mechanisms of CD8 T cell subversion, leading to the persistence of hepatotropic pathogens such as HCV.IMPORTANCE Development of vaccines against hepatitis C virus (HCV), a major cause of cirrhosis and cancer, has been stymied by a lack of animal models. The recent discovery of an HCV-like rodent hepacivirus (RHV) enabled the development of such a model in rats. This platform recapitulates HCV hepatotropism and viral chronicity necessary for vaccine testing. Currently, there are few descriptions of RHV-specific responses and why they fail to prevent persistent infection in this model. Here, we show that RHV-specific CD8 T cells, while induced early at high magnitude, do not develop into functional effectors capable of controlling virus. This defect was partially alleviated by short-term treatment with an HCV antiviral. Thus, like HCV, RHV triggers dysfunction of virus-specific CD8 T cells that are vital for infection resolution. Additional study of this evasion strategy and how to mitigate it could enhance our understanding of hepatotropic viral infections and lead to improved vaccines and therapeutics.
|
10.1128/JVI.00035-20
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pubmed_778_19169
|
Strategies for the preparation of new fluorescent oligopeptide conjugates labeled with 4-ethoxymethylene-2-[1]-naphthyl-5(4H)-oxazolone (naOx-OEt) at the N-terminal on solid support or in solution have been devised. These procedures are simple and easy to carry out by reacting naOx-OEt or N(alpha)-naOx-amino acid with side chain protected peptide chains attached to resins. The integrity of the N-alkyl bond was maintained even after the trifluoracetic acid or HF based cleavages procedures. Our data show that the naOx fluorophore is compatible with both Fmoc/tBu and Boc/Bzl methods and also suggest that naOx-amino acid could be utilized as building blocks for solid phase peptide synthesis. Comparative analysis of fluorescence properties of naOx-conjugates indicated that the spectral properties of the fluorophore do not change after incorporating into peptides. The compact size, the definite chemical reaction for its introduction in combination with the appropriate spectral features (e.g., intense emission, pH independent fluorescent characteristics, and beneficial photobleaching dose constant and rates) and with chemical and spectral stability, naOx-based labeling could be attractive for novel cellular fluorescent techniques (e.g., in laser scanning confocal FRET) to study peptide-protein and protein-protein interactions even in biological matrices.
|
10.1002/bip.20369
|
pubmed_970_1284
|
Early-onset scoliosis is defined as a spinal curvature greater than 10° in children prior to 10 years of age. Untreated EOS may lead to progressively severe spinal deformity, impaired pulmonary development, restrictive lung disease, and both increased morbidity and mortality. Limitations of established conservative treatments include inability to correct severe deformity, as well as challenges with compliance when casting and bracing is applied. In addition, surgical treatment in the form of traditional growing rods requires regular surgical lengthenings and is associated with complications inherent with repeated invasive procedures and exposure to general anesthesia. MAGEC is an evolving magnetically controlled growing rod system for the treatment of EOS. After initial implantation, lengthening is achieved non-invasively by using magnetic external remote control. MAGEC offers the potential to control moderate and severe EOS, while avoiding repeated surgical procedures and associated complications. In this review, we examine the results from clinical, radiological and explant studies following the use of MAGEC, in the context of other established and emerging treatments for EOS.
|
10.2147/MDER.S198176
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pubmed_355_4916
|
The aim of this double-blind, placebo-controlled, cross-over study was to assess the cardioprotective effect of intracoronary nifedipine during percutaneous transluminal coronary angioplasty balloon occlusion. A balloon inflation without drug injection was initially made to ascertain that a shift of the ST segment (> or = 2 mm, 0.08 s after the J point) appeared (inclusion criterion). Two other balloon inflations were preceded by intracoronary injection of either 0.2 mg nifedipine or placebo, distal to the stenosis through the balloon catheter. The evaluation criteria were (1) time to ST segment shift, and (2) maximal amplitude of ST segment shift caused by balloon occlusion. Comparison of the data used an analysis of variance. Sixty-seven patients (mean age 54 +/- 8 years; 54 male, 13 female) were studied; 50 patients had 1-, 16 patients 2- and 1 patient 3-vessel disease. The dilated vessel was the left anterior descending coronary artery (n = 51), the right coronary artery (n = 12) and the left circumflex coronary artery (n = 4). Balloon inflation time was 100 +/- 31 s in the nifedipine group and 93 +/- 29 s in the placebo group. Five patients were excluded (procedure stopped after the first inflation in 1 and ST segment shift < 2 mm during the first inflation in 4). The time to 2-mm ST segment shift was longer in the nifedipine group than in the placebo group (62 +/- 40 s versus 51 +/- 40 s, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1016/0167-5273(93)90295-r
|
pubmed_732_24550
|
BACKGROUND
Metformin (MET) therapy exerts positive effects improving glucose tolerance and preventing the evolution toward diabetes in insulin resistant patients. It has been shown that adding MET to exercise training does not improve insulin sensitivity. The aim of this study was to determine the effect of MET and exercise training alone or in combination on maximal aerobic capacity and, as a secondary end-point on quality of life indexes in individuals with insulin resistance.
METHODS
75 insulin resistant patients were enrolled and subsequently assigned to MET (M), MET with exercise training (MEx), and exercise training alone (Ex). 12-weeks of supervised exercise-training program was carried out in both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks of treatment.
RESULTS
Cardiopulmonary exercise test showed a significant increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (∆ VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ∆ VO2 MEx +0.19 [0.33 to 0.05] l/min; ∆ VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the MEx (58.3 ± 19 vs 77.3 ± 16; p < 0.01) and Ex (62.1 ± 17 vs 73.7 ± 12; p < 0.005) groups.
CONCLUSIONS
We evidenced that cardiopulmonary negative effects showed by MET therapy may be counterbalanced with the combination of exercise training. Given that exercise training associated with MET produced similar effects to exercise training alone in terms of maximal aerobic capacity and HRQoL, programmed exercise training remains the first choice therapy in insulin resistant patients.
|
10.1186/1475-2840-13-93
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pubmed_750_7310
|
For the past decades, quantitative serum proteomics in mammals have been widely applied in biomarker screening. Various serum protein removal methods have been developed to effectively sequester serum abundant proteins. However, few methods have been found for the removal of arthropod serum abundant proteins. Here, gel filtration chromatography and ultracentrifugation methods were applied to remove hemocyanin from Litopeaneus vannamei serum. When shrimps were challenged with white spot syndrome virus (WSSV), a total of 486 serum proteins were identified using mass spectrometry, and 18 upregulated WSSV responsive proteins were identified with isobaric tags for relative and absolute quantification (iTRAQ). These results provide an effective method to remove hemocyanin from shrimp serum. With this method some previously unidentified WSSV responsive serum proteins were revealed, which would give us a better insight into the response of crustaceans to WSSV infection.
|
10.1016/j.dci.2019.01.003
|
pubmed_536_19624
|
Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response.
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10.1016/j.ejca.2008.10.032
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pubmed_734_20934
|
OBJECTIVES
Family satisfaction with end-of-life care in the intensive care unit constitutes an important outcome for evaluating end-of-life care quality. Research on this topic focuses on linking end-of-life care processes to family-surrogate satisfaction with the patient's end-of-life care but has seldom examined patient- and family-surrogate-based factors. We aimed to comprehensively and simultaneously examine factors facilitating or deterring family satisfaction with end-of-life care in the intensive care unit from patient- and family-surrogate perspectives.
METHODS
For this secondary-analysis study, 278 Taiwanese family surrogates were surveyed one-month post-patient death using the Family Satisfaction in the Intensive Care Unit questionnaire (FS-ICU), which measures care and decision-making. Associations between family satisfaction with end-of-life care and patient and family characteristics, patient disease severity, and length of intensive care stay were examined by multivariate, multilevel linear regression models.
RESULTS
Female family surrogates were more satisfied with patients' end-of-life care than male family surrogates when patients had a higher APACHE II but a lower SOFA score. Adult-child surrogates had lower FS-ICU Care scores than other family surrogates. Higher satisfaction with ICU decision-making was associated with patients' higher APACHE II but lower SOFA scores, longer stay and family socio-demographics, including being unmarried, educational attainment above junior high school and reported financial sufficiency to make ends meet.
CONCLUSION
Patient disease severity and family-surrogate characteristics are significantly associated with surrogates' satisfaction with patients' end-of-life care in the intensive care unit. Specific interventions should be tailored to the needs of high-risk family surrogates to increase their satisfaction with this care.
|
10.1016/j.iccn.2022.103243
|
pubmed_600_3701
|
OBJECTIVE
The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort.
METHODS
Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables.
RESULTS
Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and 36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI 1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg.
CONCLUSION
An estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization.
|
10.1093/rheumatology/keu450
|
pubmed_764_9318
|
BACKGROUND
Increasing evidence suggests that nerve growth factor (NGF), and probably other neurotrophins, are involved in the control of lymphoid organs and immunocompetent cells that express neurotrophins and/or their receptors. In the rat thymus, mRNA for TrkA (an essential component of the NGF signal transducing receptor) has been found primarily in stromal cells. The present study was undertaken to analyze the occurrence and localization of TrkA in the rat and human thymus, using Western blot and immunohistochemical techniques.
METHODS
Thymuses from human fetuses (estimated gestational ages of 29 and 32 weeks) and newborns (3 and 4 weeks old), as well as from 3-month-old rats were used. Human and rat samples were fixed in buffered 10% formaldehyde, paraffin-embedded, and processed for immunohistochemistry. Moreover, rat thymus samples were processed for Western blot analysis.
RESULTS
A protein band consistent with full-length TrkA (approximately 140 kDa) was detected in the rat thymus. Immunoreactivity (IR) for TrkA was exclusively found in thymic epithelial cells of both rat and human, identified because they also displayed cytokeratin IR. Interestingly, species-specific differences were noted for the expression of TrkA in different subtypes of thymic epithelial cells. Apparently, no immunolabelling was observed in other stromal cells or in lymphocytes.
CONCLUSIONS
These results suggest that TrkA ligands may be involved in the control of thymic epithelial cells. This could be of potential importance because of the involvement of these cells in providing an appropriate microenvironment for maturation and selection of T lymphocytes.
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10.1002/(SICI)1097-0185(199711)249:3<373::AID-AR8>3.0.CO;2-V
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pubmed_1000_1471
|
Debate continues concerning the treatment of infants with end-stage renal disease. We evaluated progress and outcome of 20 infants with a mean age of 0.34 year (range, 0.02-1 year) in a long-term peritoneal dialysis program at a single center. Mean weight at the start of dialysis was 4.8 kg (range, 1.7-11.4 kg), and the duration of dialysis was 17.3 months (range, 1-59 months). Eleven infants received renal transplants, 4 were switched to hemodialysis and then received transplants, 4 died, and 1 continues to receive peritoneal dialysis. There was significant co-morbidity in 6 infants who died or required hemodialysis. Catheter interventions were frequent, with 12 infants requiring at least one replacement. There were 1.1 episodes of peritonitis per patient-year; 70% of infants had 0 to 1 episode. Mean weight standard deviation score (SDS) was -1.6 at the start, -0.3 at 1 year (P =.0008), and 0.3 at 2 years (P =.0008). Height SDSs were -1.8 at the start, -1.1 at 1 year (P =.046), and -0. 8 at 2 years (P =.06). Head circumference SDSs were -1.9 at the start, -1.3 at 6 months (P =.003), and -0.9 at 1 year (P =.015). Fourteen of 16 survivors are achieving normal developmental milestones or attend mainstream school. Peritoneal dialysis in infancy is a demanding treatment, but outcome for growth, development, and transplantation justifies this intensive approach. When parents are counseled, the importance of non-renal co-morbidity must be emphasized.
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10.1016/s0022-3476(00)90044-1
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pubmed_256_11936
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We have examined the effect of peripheral 3-hydroxybutyrate injections on food intake and the contribution of the vagus nerve in the resistance to dietary fat-induced obesity in a rodent model. S 5B/Pl rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to reverse light cycle. Food intake was measured for 24 h following the injection of 3-hydroxybutyrate, lactate, or glycerol (all 5 mMol/kg0.75, SC) at the onset of dark. Three-hydroxybutyrate reduced food intake (p < 0.0001) in S 5B/Pl rats only. Lactate reduced food intake slightly (p < 0.009) in both strains and glycerol had no effect on food intake. In a second experiment, S 5B/Pl and Osborne-Mendel rats were adapted to a high-fat diet and were then subjected to either selective hepatic vagotomy or sham operation. Vagotomy had no effect on weight gain of Osborne-Mendel rats but allowed weight gain in S 5B/Pl rats (p < 0.0001). Even in vagotomized S 5B/Pl rats, however, blood 3-hydroxybutyrate levels were inversely associated (r = -0.50) with food intake. These data suggest that the hepatic vagus nerve may contribute to the resistance of S 5B/Pl rats to dietary-fat induced obesity, but the data do not rule out a strictly central role for the regulation of food intake by 3-hydroxybutyrate in this strain.
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10.1016/0031-9384(94)00376-g
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pubmed_714_11990
|
Adherence of Plasmodium falciparum-infected erythrocytes (PRBCs) to the microvascular endothelium of specific organs and consequent sequestration is believed to be responsible for the development of malaria pathology. A number of studies have shown that cell adhesion molecules expressed on the surface of endothelial cells mediate the adherence. Recent studies indicate that a subpopulation of PRBCs adhere to chondroitin 4-sulfate (C4S). This adhesion can be effectively inhibited by C4S oligosaccharides. In pregnant women, the placenta specifically selects C4S-adherent PRBCs, and thus these phenotypes multiply and sequester in the intervillous spaces. Over successive pregnancies, women develop a protective humoral response to the C4S-adhesion phenotype. Disruption of C4S-mediated PRBCs adhesion using either a C4S oligosaccharide mimetic or an antiC4S-adhesion vaccine can be an efficient strategy for the treatment of malaria caused by C4S-adherent P. falciparum.
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10.1023/a:1020542206916
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pubmed_186_10234
|
OBJECTIVE
The aim was to investigate collagen fibers in giant cell fibroma, inflammatory fibrous hyperplasia, and oral normal mucosa.
MATERIALS AND METHODS
Sixty-six cases were stained with picrosirius red. The slides were observed under polarization, followed by the measurement of the area and the percentage of the type I and type III collagens. The age and gender were obtained from the clinical records.
RESULTS
No differences could be observed in both the area and percentage of the type I and type III collagens within the categories of lesions and normal mucosa. In the giant cells fibroma, a greater area and percentage of type I collagen could be identified in individuals of less than 41.5 years (p<0.05).
CONCLUSION
The distribution of type I and type III collagen fibers in the studied lesions followed a similar pattern to that observed in the normal mucosa, indicating a normal collagen maturation process of type III to I. The study supports that multinucleated and stellate cells of the giant cell fibroma appear to be functional within collagen types III and I turnover. The greater amount of type I collagen identified in giant cell fibroma in individuals of less than 41.5 years reinforce the neoplastic nature of lesion.
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pubmed_186_10234
|
pubmed_866_5075
|
OBJECTIVES
To evaluate the diagnostic performance of frozen section in thyroid nodules classified as follicular neoplasm.
METHODS
A diagnostic test meta-analysis was designed. Studies that assessed frozen section in patients with thyroid nodules and a fine-needle aspiration biopsy result of Bethesda IV were selected. The outcomes measured were the number of false- and true-positive and -negative results. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) instrument for methodological quality assessment and a bivariate mixed-effects regression framework and a likelihood-based estimation of the exact binomial approach.
RESULTS
Forty-six studies from 1991 to 2018 were included. Most studies had moderate methodological quality. The overall sensitivity and specificity were 43% (95% confidence internal [CI], 0.34-0.53) and 100% (95% CI, 0.99-1.00), respectively. The hierarchic summary receiver operating characteristic curve showed an area under the curve of 0.91 (95% CI, 0.80-0.97).
CONCLUSIONS
Frozen section demonstrates moderate diagnostic performance in patients with follicular neoplasm, and its utility for making intraoperative decisions is limited. Its routine use should be discouraged.
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10.1093/ajcp/aqz152
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pubmed_50_7243
|
BACKGROUND
Approximately 10% of all MRI-guided vacuum-assisted breast biopsies (MR-VAB) are histologically classified as B3 lesions. In most of these cases surgical excision is recommended. The aim of our study was to evaluate the malignancy rates of different B3 lesions which are visible on MRI to allow a lesion-adapted recommendation of further procedure.
METHODS
Retrospective analysis of 572 consecutive MR-VAB was performed. Inclusion criteria were a representative (=successful) MR-VAB, histologic diagnosis of a B3 lesion and either the existence of a definite histology after surgical excision or proof of stability or regression of the lesion on follow-up MRI. Malignancy rates were evaluated for different histologies of B3 lesions. Lesion size and lesion morphology (mass/non-mass enhancement) on MRI were correlated with malignancy.
RESULTS
Of all MR-VAB 43 lesions fulfilled the inclusion criteria. The malignancy rate of those B3 lesions was 23.3% (10/43). The highest malignancy rate was found in atypical ductal hyperplasia (ADH) lesions (50.0%; 4/8), 33.3% (2/6) in flat epithelial atypia (FEA), 28.6% (2/7) in lobular intraepithelial neoplasia (LIN) and 12.5% (2/16) in papillary lesions (PL). All 6 complex sclerosing lesions were benign. Mass findings were significantly more frequently malignant (31.3%, 10/32; p < 0.05) than non-mass findings (0/11). Small lesions measuring 5-10 mm were most often malignant (35.0%; 7/20). All large lesions (> 20 mm) were not malignant (0/10). Intermediate sized lesions (11-20 mm) turned out to be malignant in 23.1% (3/13).
CONCLUSIONS
The malignancy rate of B3 lesions which were diagnosed after MR-VAB was 23.3%. ADH, FEA and LIN showed considerable malignancy rates (50%, 33% and 29%) and should therefore undergo surgical excision. None of the cases, which were diagnosed as radial scars, non-mass enhancement or larger lesions (> 20 mm) were malignant. Here, a follow-up MRI seems to be advisable to avoid unnecessary operations.
TRIAL REGISTRATION
Retrospective study design, waived by the IRB.
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10.1186/s12880-018-0271-7
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pubmed_746_648
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Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase-activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR(2) agonists up-regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR(2) agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR(2) agonist also enhanced protective interferon (IFN)gamma-induced FcgammaRI expression at neutrophil cell surface. Of note, IFNgamma is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR(2) expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR(2) may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fcgamma receptor-mediated phagocytosis.
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10.1111/j.1600-0625.2007.00605.x
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pubmed_117_12297
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Type 2 diabetes mellitus (T2DM) is a pandemic metabolic disease worldwide. Multiple types of cancer, particularly liver cancer, are closely associated with T2DM. As a result, there is growing interest in investigating whether anti-diabetic medications could lower cancer risks in the population and even prolong patient survival among those with concurrent cancer. There are many types of anti-diabetic medications available in the clinic. The present study reviewed how different anti-diabetic drugs affect cancer risk and patient survival. On the one hand, multiple retrospective studies have shown that the different anti-diabetic medications have distinct effects on cancer risks. Insulin-raising drugs, including exogenous insulin, increased cancer risks, while drugs potentiating insulin sensitivity like metformin reduced cancer risks. On the other hand, the effects of anti-diabetic medications on patient survival are relatively less studied, except limited reports in liver cancer and pancreatic cancer. It seems that metformin could extend overall survival in patients of early-stage cancer. In contrast in the advanced cancer with metastasis, metformin has no effect or even worsens cancer mortality. It is yet unknown whether these distinct effects of metformin are attributable to the severity of the cancer staging or to the drug interactions between metformin and other medications. This question warrants reconsideration of the current clinical practice in the control of T2DM. Future large-scale prospective studies are needed to resolve this.
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pubmed_117_12297
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pubmed_917_8044
|
We studied pattern-shift visual (PSVEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potentials in 38 unselected patients with motor system diseases (MSD) (28 sporadic, 10 familial). PSVEPs were normal in all patients, and BAEPs were normal in all except one with clinical hearing loss who had absent waves I and III and prolonged wave V latencies. Median and tibial SEPs revealed definite CNS conduction abnormalities in only 1 of 30 and 1 of 18 patients, respectively. In addition, four patients had peripheral and four had peripheral or central delays on tibial nerve testing. There were no or only small group differences in central conduction SEP, BAEP, and PSVEP values in patients with normal studies compared with controls. This study suggests that central conduction SEP, BAEP, or PSVEP abnormalities can rarely be attributed to MSD and that their presence in patients suspected of having this disorder should prompt a search for an alternative diagnosis.
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10.1212/wnl.38.2.231
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pubmed_547_6629
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The pattern of CREB phosphorylation was investigated in the caudate nucleus and hippocampus 10 min or 3 h after i.p. injection of dopamine or NMDA receptor agonists alone, or in combination with antagonists. Ten minutes after C57BL/6 J mice were injected with either the dopamine D1 receptor agonist SKF-38393 hydrobromide or NMDA, immunoreactivity of phosphorylated CREB (pCREB) was significantly increased in all parts of the caudate nucleus but not in hippocampal regions. However, 3 h after the injection of SKF-38393, pCREB levels in the caudate nucleus did not differ significantly from the pCREB levels in control animals, whereas pCREB levels were still elevated 3 h after NMDA injection. Except for the D1 receptor antagonist SCH-23390, which induced CREB phosphorylation in the caudate nucleus, dopamine and NMDA receptor antagonists had little effect on pCREB levels by themselves. However, the NMDA receptor antagonist CGS-19755 injected i.p. blocked both the NMDA- and SKF-38393-induced rise of pCREB levels in the caudate nucleus. Similarly, the D1 receptor antagonist SCH-23390 inhibited the effects produced by SKF-38393 or NMDA. Interestingly, the D2 receptor antagonist sulpiride also blocked the SKF-38393-triggered rise of pCREB. The results demonstrated that NMDA and dopamine receptors modulate pCREB levels in the caudate nucleus and suggest mutual permissive roles for both receptors.
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10.1016/s1567-133x(01)00020-5
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pubmed_984_3289
|
This study combined artificial language learning (ALL) with conventional experimental techniques to test whether statistical speech segmentation outputs are integrated into adult listeners' mental lexicon. Lexicalization was assessed through inhibitory effects of novel neighbors (created by the parsing process) on auditory lexical decisions to real words. Both immediately after familiarization and post-one week, ALL outputs were lexicalized only when the cues available during familiarization (transitional probabilities and wordlikeness) suggested the same parsing (Experiments 1 and 3). No lexicalization effect occurred with incongruent cues (Experiments 2 and 4). Yet, ALL differed from chance, suggesting a dissociation between item knowledge and lexicalization. Similarly contrasted results were found when frequency of occurrence of the stimuli was equated during familiarization (Experiments 3 and 4). Our findings thus indicate that ALL outputs may be lexicalized as far as the segmentation cues are congruent, and that this process cannot be accounted for by raw frequency.
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10.1016/j.cognition.2009.05.002
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pubmed_1061_1316
|
BACKGROUND
Stress has been known to increase craving in individuals with Alcohol Use Disorders (AUD) and predict future alcohol relapse risk, but whether stress on a particular day affects craving on that day to impact prospective alcohol intake in the real world, particularly during early treatment and recovery, has not been studied thus far.
METHOD
The first study included 85 AUD individuals who reported their daily stress, craving, and alcohol intake in the first two weeks of early treatment. A second validation study included 28 AUD patients monitored daily during eight weeks of outpatient 12-Step based behavioral counseling treatment for AUD. Data were collected from telephone-based daily diaries for 903 days in Study 1 and 1488 in Study 2. Multilevel latent models tested if daily and person-averaged craving mediated the link between stressful events and next day drinking during treatment.
RESULTS
In both Study 1 and 2, exposure to a stressful event on a particular day predicted increased craving on that day (p's≤.002); and such increases in craving predicted the likelihood of drinking the next day (p's≤.014) and the drinking amount (p's< = 008). Individuals who experienced more stressful events reported higher craving (p's≤.012), and higher cravers reported greater next day drinking (p's<.001).
CONCLUSIONS
The results across two studies with separate samples are the first to establish that craving directly mediates the association between stress and next day alcohol intake in individuals with AUD. Findings suggest a need for novel treatment approaches to address stress-induced craving to improve alcohol use outcomes.
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10.1016/j.drugalcdep.2019.107569
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pubmed_154_538
|
The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein complex (gp120-gp41) promotes viral entry by mediating the fusion of viral and cellular membranes. Formation of a stable trimer-of-hairpins structure in the gp41 ectodomain brings the two membranes into proximity, leading to membrane fusion. The core of this hairpin structure is a six-helix bundle in which three carboxyl-terminal outer helices pack against an inner trimeric coiled coil. Here we investigate the role of these conserved interhelical interactions on the structure and function of both the envelope glycoprotein and the gp41 core. We have replaced each of the eight amino acids at the buried face of the carboxyl-terminal helix with a representative amino acid, alanine. Structural and physicochemical characterization of the alanine mutants shows that hydrophobic interactions are a dominant factor in the stabilization of the six-helix bundle. Alanine substitutions at the Trp628, Trp631, Ile635, and Ile642 residues also affected envelope processing and/or gp120-gp41 association and abrogated the ability of the envelope glycoprotein to mediate cell-cell fusion. These results suggest that the amino-terminal region of the gp41 outer-layer alpha-helix plays a key role in the sequence of events associated with HIV-1 entry and have implications for the development of antibodies and small-molecule inhibitors of this conserved element.
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10.1021/bi025648y
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pubmed_740_11324
|
AIM
The aim of this study was to investigate whether racial disparities in healthcare exist within a New Zealand pediatric surgical outreach service in a high indigenous Māori population.
METHODOLOGY
This retrospective study assessed all pediatric surgical procedures performed within a secondary center in New Zealand between May 2014 and May 2016. The days between the date of surgery booking on the waiting list and actual date of surgery were calculated and compared to their corresponding elective surgery waiting target times set by the New Zealand Ministry of Health (MoH). Patient demographic data were collated to then identify any discrepancy between ethnic groups.
RESULTS
A total of 203 pediatric surgical procedures were performed on 193 patients. Of the 194 (95%) procedures that were included in the study, 30 breached a maximum waiting time. Though this represented a small proportion of patients, Māori were significantly over represented in this group.
CONCLUSION
The majority of our patients with delayed elective surgery were of Māori ethnicity, for reasons not entirely accounted for by common socioeconomic determinants of health. Our study suggests the possibility of innate systemic causes not detected by standard models of health. However, further research with larger cohorts is needed.
LEVEL OF EVIDENCE
III.
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10.1016/j.jpedsurg.2018.02.037
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pubmed_170_5641
|
The study of membrane transporters may result in breakthroughs in the discovery of new drugs and the development of safer drugs. Membrane transporters are essential for fundamental cellular functions and normal physiological processes. These molecules influence drug absorption and distribution and play key roles in drug therapeutic effects. A primary goal of current research in drug discovery and development is to fully understand the interactions between transporters and drugs at both the system levels in the human body and the individual level for personalized therapy. Systematic studies of membrane transporters will help in not only better understanding of diseases from the systems biology point of view but also better drug design and development. The exploration of both pharmacogenomics and systems biology in transporters is necessary to connect individuals' genetic profiles with systematic drug responses in the human body. Understanding of gene-diet interactions and the effects of epigenetic changes on transporter gene expression may help improve clinical drug efficacy. The integration of pharmacogenomics, nutrigenomics, epigenetics, and systems biology may enable us to move from disease treatment to disease prevention and optimal health. The key issues in such integrative understanding include the correlations between structure and function, genotype and phenotype, and systematic interactions among transporters, other proteins, nutrients, drugs, and the environment. The exploration in these key issues may ultimately contribute to personalized medicine with high efficacy but less toxicity.
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10.1007/978-1-60761-700-6_1
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pubmed_942_372
|
Rabbit antibody was elicited against purified oat phytochrome polypeptides. Immunodiffusion and immunoelectrophoresis indicated the antibody elicited was predominantly a single precipitin system. No antigenic difference was detected between red-absorbing phytochrome and far red-absorbing phytochrome. Crude preparations of rye and corn phytochrome showed a line of identity when cross-reacted with oat polypeptide phytochrome; pea phytochrome showed a line of partial identity. Precipitin reactions with purified rye phytochrome analyzed with sucrose density gradient centrifugation and immunodiffusion confirmed that the same class of determinants was available to the antibody when the protein was known to be in a state which had not undergone extensive proteolytic attack.
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10.1104/pp.51.5.939
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pubmed_875_386
|
A new class of inertial fusion capsules is presented that combines multishell targets with laser direct drive at low intensity (2.8×10^{14} W/cm^{2}) to achieve robust ignition. The targets consist of three concentric, heavy, metal shells, enclosing a volume of tens of μg of liquid deuterium-tritium fuel. Ignition is designed to occur well "upstream" from stagnation, with minimal pusher deceleration to mitigate interface Rayleigh-Taylor growth. Laser intensities below thresholds for laser plasma instability and cross beam energy transfer facilitate high hydrodynamic efficiency (∼10%).
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10.1103/PhysRevLett.116.255003
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pubmed_692_12547
|
BACKGROUND
Low back pain (LBP) is chronic disease without a curative therapy. Alternative and complementary therapies are widely used in the management of this condition.
OBJECTIVES
To evaluate the efficacy of home application of Dead Sea mud compresses to the back of patients with chronic LBP.
METHODS
Forty-six consecutive patients suffering from chronic LBP were recruited. All patients were followed at the Soroka University Rheumatic Diseases Unit. The patients were randomized into two groups: one group was treated with mineral-rich mud compresses, and the other with mineral-depleted compresses. Mud compresses were applied five times a week for 3 consecutive weeks. The primary outcome was the patient's assessment of the overall back pain severity. The score of the Ronald & Morris questionnaire served as a secondary outcome.
RESULTS
Forty-four patients completed the therapy and the follow-up assessments: 32 were treated with real mud packs and 12 used the mineral-depleted packs. A significant decrease in intensity of pain, as described by the patients, was observed only in the treatment group. In this group, clinical improvement was clearly seen at completion of therapy and was sustained a month later. Significant improvement in the scores of the Roland & Morris questionnaire was observed in both groups.
CONCLUSIONS
The data suggest that pain severity was reduced in patients treated with mineral-rich mud compresses compared with those treated with mineral-depleted compresses. Whether this modest effect is the result of a "true" mud effect or other causes can not be determined in this study.
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pubmed_692_12547
|
pubmed_471_5990
|
Tick-borne diseases (TBDs) have a large impact on animal health and the livelihood of livestock owners, particularly in developing countries. Although climatic and ecological conditions in Pakistan may favour the transmission of tick-borne pathogens (TBPs), only a few systematic studies have been carried out on TBPs and the diseases that they cause in this country. To improve our understanding of the distribution of TBPs, 3,807 ticks were collected from ruminants (n = 369) on 108 livestock farms (semi-arid zone = 36, arid zone = 72) in Punjab Province. After morphological identification ticks were pooled into 405 pools (Hyalomma anatolicum = 300, Rhipicephalus microplus = 89, Hyalomma dromedarii = 9, Rhipicephalus turanicus = 7) based on their species, locality of collection, and the host. DNA from each pool was screened by a Reverse Line Blot (RLB) hybridization assay for the presence of Anaplasma, Ehrlichia, Rickettsia, Babesia, and Theileria species. DNA from at least one TBP was found in 142 (35.1%) pools. Among the positive pools, 91 (64.1%) had a mixed infection with two or more TBPs, whereas 51 (35.9%) pools were infected with a single TBP. The detected pathogens not only included species that were known to be endemic in Pakistan, such as Theileria annulata (6.7%), Theileria orientalis (3.5%), Anaplasma marginale (5.7%), Anaplasma centrale (2.7%), Anaplasma ovis (1.5%), Babesia bigemina (0.7%), and Babesia bovis (0.2%), but also several TBPs that had not been reported to occur in Pakistan before. This included Ehrlichia minasensis (3.2%), an Anaplasma platys-like organism (1.2%), Babesia occultans (0.2%), and Rickettsia massiliae (0.2%), as well as two previously uncharacterized species: Ehrlichia sp. Multan (18.0%) and Anaplasma sp. (BL099-6) (2.22%). The pathogenicity of these novel species remains to be examined. This study shows that a much broader spectrum of TBPs is present in Pakistan than previously thought, including several zoonotic pathogens.
|
10.1111/tbed.13059
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pubmed_708_19940
|
Bifunctional cross-linking reagents were used to probe the protein environment in the ER membrane of the signal sequence receptor (SSR), a 24-kD integral membrane glycoprotein (Wiedmann, M., T. V. Kurzchalia, E. Hartmann, and T. A. Rapoport. 1987. Nature [Lond.]. 328:830-833). The proximity of several polypeptides was demonstrated. A 22-kD glycoprotein was identified tightly bound to the 34-kD SSR even after membrane solubilization. The 34-kD polypeptide, now termed alpha SSR, and the 22-kD polypeptide, the beta SSR, represent a heterodimer. We report on the sequence of the beta SSR, its membrane topology, and on the mechanism of its integration into the membrane. Cross-linking also produced dimers of the alpha-subunit of the SSR indicating that oligomers of the SSR exist in the ER membrane. Various bifunctional cross-linking reagents were used to study the relation to ER membrane proteins of nascent chains of preprolactin and beta-lactamase at different stages of their translocation through the membrane. The predominant cross-linked products obtained in high yields contained the alpha SSR, indicating in conjunction with previous results that it is a major membrane protein in the neighborhood of translocating nascent chains of secretory proteins. The results support the existence of a translocon, a translocation complex involving the SSR, which constitutes the specific site of protein translocation across the ER membrane.
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10.1083/jcb.111.6.2283
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pubmed_908_3961
|
BACKGROUND
Out of hospital cardiac arrest management of patients with non-ST myocardial infarction per current American Heart Association and European Resuscitation Council guidelines leave the decision in regard to early angiography up to the physician operators. Guidelines are clear on the positive impact of early intervention on survival and improvement on left ventricular function in patients presenting with cardiac arrest and ST elevation myocardial infarction on electrocardiogram. This review aims to analyze the data that current guidelines are based upon in regards to out of hospital cardiac arrest with electrocardiogram findings of non-ST elevation myocardial infarction as well as review of other clinical trials that support early angiography and reperfusion strategies.
CONCLUSION
Analysis of current literature shows that early coronary evaluation in patients with no finding of ST elevation on ECG can help improve survival in patients suffering out of hospital cardiac arrest.
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10.2174/1573403X14666180507154107
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pubmed_174_15546
|
The proportion of glomerular basement membrane (GBM) solubilised following pepsin treatment increased with age when the digestion was carried out at 4 degrees C, but remained constant at 50% of the membrane when the digestion was carried out at 10 degrees C irrespective of rat age. Amino-acid analysis of the solubilised material indicated that it became more collagen-like with age, as judged by the increase in glycine, hydroxyproline and hydroxylysine content, if the digestion was carried out at 10 degrees C. Polyacrylamide gel electrophoresis of pepsin-solubilised material demonstrated that components with apparent molecular weights of 180,000, 160,000 and 130,000 increased in intensity with age. Components with apparent molecular weights less than 85,000 were only present in pepsin-soluble material prepared from GBM isolated from young rats. The intensity of the bands in the pro-alpha-region varied with age and some procollagen-like material was not solubilised by pepsin treatment. These studies confirm that aging of rat GBM is characterised by an increase in the proportion of the collagenous components present in rat GBM.
|
10.1159/000173043
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pubmed_708_2492
|
The Escherichia coli uhpT protein catalyzes the active transport of sugar-phosphates by an obligatory exchange mechanism. To examine its transmembrane topology, we isolated a collection of uhpT-phoA fusions encoding hybrid proteins of different lengths from the N terminus of UhpT fused to alkaline phosphatase by using transposon TnphoA. These fusions displayed different levels of alkaline phosphatase activity, although comparable levels of full-length UhpT-PhoA proteins were produced in maxicells of both high- and low-activity fusions. The full-length protein species were unstable and were degraded to the size of the alkaline phosphatase moiety in the case of a high-activity fusion or to small fragments in the case of a low-activity fusion. The enzyme activity present in low-activity fusions appeared to result from export of a small proportion of the fusion proteins to the periplasmic space. Although fusions were not obtained in all predicted extramembranous loops, the deduced topology of UhpT was consistent with a model of 12 membrane-spanning regions oriented with the amino and carboxyl termini in the cytoplasm.
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10.1128/jb.172.4.1688-1693.1990
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pubmed_35_12087
|
The activity concentrations of radionuclides (60Co, 54Mn, 137Cs, 40K) in whole plants of Fucus vesiculosus of different ages, and also in tissues of different ages from the same plants were investigated in the vicinity of the Barsebäck nuclear power plant in southern Sweden. Activity concentration differed between the tissues of different age of the plants, depending on the radionuclide as well as the time of year. The highest concentrations of 60Co and 54Mn were measured in the older parts of the plants in spring and summer, while the activity concentrations of 137Cs and 40K were highest in receptacles and new vegetative fronds. The discharge of radionuclides from the nuclear power plant was reflected in the measured activity concentration in the algae. For 60Co, the response seemed to be smoothed out when considering the whole plant, while the new vegetative tissue better reflected the discharge during the autumn. Thus, it is important to have knowledge about the autecology of the organism when it is used as an indicator for radionuclides.
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10.1016/0269-7491(91)90096-f
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pubmed_830_9715
|
Further insight into the dissociative adsorption of NH3 on Si(001) has been obtained using a combined computational and experimental approach. A novel route leading to the dissociation of the chemisorbed NH3 is proposed, based on H-bonding interactions between the gas phase and the chemisorbed NH3 molecules. Our model, complemented by synchrotron radiation photoelectron spectroscopy measurements, demonstrates that the low temperature dissociation of molecular chemisorbed NH3 is driven by the continuous flux of ammonia molecules from the gas phase.
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10.1103/PhysRevLett.109.036102
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pubmed_875_21421
|
Cardiovascular (CV) screening in young athletes remains challenging and a topic of considerable debate. Recent criticisms of ECG screening have perpetuated arguments that ECG screening is neither indicated nor effective by applying outdated incidence data and flawed methodology. In response, this article provides a critical review of the arguments in favour of ECG screening in athletes and the early detection of CV disorders at elevated risk of sudden cardiac death (SCD). Importantly, no study to date has demonstrated that screening by history and physical examination alone is effective in detecting athletes at risk or in preventing SCD. ECG screening using current athlete-specific interpretation standards provides a low false-positive rate and improves detection of potentially lethal CV conditions. Further, risk reduction in athletes identified with CV disorders can be effectively achieved through modern strategies for risk stratification and disease-specific management. By every definition of the purpose of CV screening, ECG-inclusive programmes will better meet the stated objective of early detection when proper ECG interpretation and adequate cardiology resources are available. Less debate on screening protocols and more emphasis on advancing physician skills and infrastructure in sports cardiology is needed to more effectively screen targeted athlete populations.
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10.1136/bjsports-2016-096606
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pubmed_1110_21087
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We previously reported that CD8+ T cells in human gastrointestinal mucosa exhibit reduced perforin expression and weak or impaired cytotoxic capacity compared with their counterparts in blood. Nevertheless, these cells degranulate and express cytokines and chemokines in response to cognate Ag. In addition to weak expression of perforin, earlier studies suggested differential regulation of perforin and granzymes (Gzms), with GzmA and B expressed by significantly higher percentages of mucosal CD8+ T cells than perforin. However, this topic has not been fully explored. The goal of this study was to elucidate the expression and coexpression patterns of GzmA, B, and K in conjunction with perforin in rectosigmoid CD8+ T cells during HIV-1 infection. We found that expression of both perforin and GzmB, but not GzmA or GzmK, was reduced in mucosa compared with blood. A large fraction of rectosigmoid CD8+ T cells either did not express Gzms or were single-positive for GzmA. Rectosigmoid CD8+ T cells appeared skewed toward cytokine production rather than cytotoxic responses, with cells expressing multiple cytokines and chemokines generally lacking in perforin and Gzm expression. These data support the interpretation that perforin and Gzms are differentially regulated, and display distinct expression patterns in blood and rectosigmoid T cells. These studies may help inform the development of strategies to combat HIV-1 and other mucosal pathogens.
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10.4049/jimmunol.1701532
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