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pubmed_46_9653
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Gross examination of a 24-month-old, male cynomolgus monkey (Macaca fascicularis) revealed obstruction of the ileum by a mass that entrapped and compressed the ileocecal junction. The mass was well circumscribed, firm, and white on cut surface. Histologically, the mass consisted of spindle-shaped cells arranged in interweaving bundles or as narrow cords and individual cells widely separated by dense collagen. A diagnosis of localized retroperitoneal fibromatosis was made based on the characteristic gross and microscopic findings and isolation of type D simian retrovirus, serotype-2, from spleen and mesenteric lymph node. Monkeys with localized retroperitoneal fibromatosis generally exhibit signs only of a palpable mass at the ileocecal junction and/or nonspecific diarrhea. This case represents an unusual presentation of localized retroperitoneal fibromatosis in which the lesion produced intestinal obstruction and death.
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10.1177/030098589503200614
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pubmed_553_3132
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A new series of analogues of the potent opiate-like peptides dermorphins (mainly tetra- and pentapeptides) were synthesized in order to better evaluate the structure-activity relationships. Relative potencies were referred to dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2), the prototype of this class of frog skin peptides. Peripheral opioid activity (guinea-pig ileum and mouse vas deferens) was determined for all the dermorphin analogues. For a selected number of them also central analgesic (hot plate and tail-flick tests) and cataleptic activities were assayed in the rat by intracerebroventricular administration.
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10.1016/0196-9781(82)90009-2
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pubmed_271_12975
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Canadian law protects people from discrimination on the grounds of sexual orientation, but our public schools do not fulfill their ethical and legal obligations where sexual and gender minority youth are concerned. This article reports on a national survey study on homophobia and transphobia in Canadian high schools. Participants (n = 3,607) were questioned about school climate, harassment, school attachment, and institutional interventions. We found that schools were neither safe nor respectful for sexual and gender minority students, and we argue that ongoing exposure to this situation undermines students' respect for the Charter of Rights and their faith in adults.
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10.1111/j.1755-618x.2011.01266.x
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pubmed_98_19472
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Atrial fibrillation (AF) is a major public health concern with a rising prevalence. Although sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown the respective favorable effects on reducing the occurrence of AF/atrial flutter (AFL), comparative protective AF/AFL effects between above 2 novel antidiabetic agents remain unavailable. Thus, we aimed to evaluate the comparative efficacy of SGLT2is and GLP-1RAs in reducing the risk of AF/AFL in patients with type 2 diabetes and estimate relative rankings of interventions. PubMed, Embase, and ClinicalTrials.gov were searched up to December 1, 2020. All available randomized controlled trials comparing SGLT2is and GLP-1RAs with one another or placebo in patients with type 2 diabetes were included. Pooled results were shown as risk ratios (RRs) with 95% confidence intervals (CIs). We used a frequentist network meta-analysis to evaluate the outcomes of interests. Thirty-six randomized controlled trials including 85,701 participants with type 2 diabetes were identified. Compared with placebo, both SGLT2is (RR: 0.82, 95% CI, 0.68-0.99) and GLP-1RAs (RR: 0.86, 95% CI, 0.76-0.97; RR long-acting ones: 0.87, 95% CI, 0.76-0.99; RR short-acting ones: 0.72, 95% CI, 0.45-1.14) significantly reduced AF/AFL risk. No significant difference between SGLT2is and GLP-1RAs was noted (RR: 0.95, 95% CI, 0.76-1.2). Compared with placebo, results from the analysis showed an RR of 0.72 (95% CI, 0.45-1.14) for short-acting GLP-1RAs and 0.87 (95% CI, 0.76-0.99) for long-acting GLP-1RAs in reducing the risk of AF/AFL. Compared with placebo, both SGLT2is and GLP-1RAs possessed favorable effects on reducing the risk of AF/AFL. However, no difference was observed when comparisons were made between them. In addition, long-acting ones may confer a more pronounced AF/AFL reduction benefit compared with placebo.
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10.1097/FJC.0000000000001197
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pubmed_454_3048
|
Empowerment of registered nurses through professional practice models inclusive of shared governance has been proposed as essential to improve quality patient care, contain costs, and retain nursing staff. The purpose of this study was to determine the relationship between perceptions of governance and empowerment among nurses working in acute care hospital units in which a shared governance model had been in place for 6 to 12 months. The 158 nurses who participated perceived themselves to be moderately empowered and in an early implementation stage of shared governance. There was a statistically significant positive relationship between perceptions of shared governance and empowerment. Recommendations for professional practice and future research are included.
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10.1097/NAQ.0b013e3181ff3845
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pubmed_358_20323
|
For a wide range of research purposes it is necessary to perform genotyping, i.e. to test which alleles, each corresponding to a particular locus, are present in the individual genome. Here we suggest a protocol of genotyping for mice with scrambler (scm) mutation. This mutation results in the aberrant splicing of the corresponding mRNA and affects the expression of mdab1 protein. Traditional approaches using genomic Southern hybridization or PCR with specific primers are not suitable for the genotyping of scm because of the lack of comprehensive information on the organization of the gene and on the presence of repetitive sequences in the known region. Here we propose a quick and highly reproducible method for genotyping scm mutant mice. The protocol consists of the following steps: isolation of genomic DNA, digestion with the restriction endonuclease, anchoring of resulting fragments with the adapter, and PCR amplification using adapter-specific primers. The final product of PCR amplification has a characteristic length which is different for the wt (wild type) and scm alleles. Thus, the characteristic pattern of bands obtained for each individual mouse specimen serves as criteria for the presence of wild type and/or scm allele. We believe that this approach could have wider application. The protocol can be easily modified and used as a convenient tool for identification of other genomic defects including those artificially introduced into genome by knockout or gene-trap techniques.
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10.1016/s1385-299x(00)00019-2
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pubmed_608_15129
|
The objective of this study was to evaluate and compare the cytotoxicity and genotoxicity on human fibroblast cell lines of sodium hypochlorite (NaOCl), chitosan and propolis as root canal irrigating solutions. Human fibroblast cells were exposed to chitosan, propolis and NaOCl for 4 and 24 h. Cell viability was assessed by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide, and oxidative DNA damage was assessed by determination of 8-hydroxydeoxyguanosine (8-OHdG) level with an ELISA kit. The data of cell cytotoxicity were analysed statistically using a test of one-way analysis of variance at a significance level of p < 0.05. In the NaOCI group, the 8-OHdG level was higher than in the chitosan group, but there was no statistical difference when compared with the other groups (p < 0.05). It was determined that the irrigation solutions were cytotoxic, depending on the dose and time. NaOCl was the most toxic solution after both 4 and 24 h of exposure (p < 0.05). Chitosan and propolis may be alternatives to NaOCl for irrigation solutions, because they are both less toxic and produce less oxidative DNA damage.
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10.1590/1807-3107bor-2018.vol32.0119
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pubmed_689_8855
|
Solar ultraviolet (UV)-induced DNA lesions are associated with skin carcinogenesis. The detection of these DNA lesions is important to understand their genotoxicity and health effects. However, sunlight exposure-relevant DNA damage measurement is still a challenge. Here, we summarize our recent progresses on the related analytical techniques, including synthesis of dimeric lesions, the optimization of procedures for ultrahigh performance liquid chromatography-coupled mass spectrometry (UHPLC-MS/MS), and the maturation of anti-T(6-4)T photoproduct antibodies and their potential applications for immunoassay.
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10.1111/php.13546
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pubmed_422_5470
|
Microbiology has a long way to go. Microbes are ubiquitous, and all other life forms in the biosphere exist solely because of them, but, as less than 1% of microorganisms can be grown in the laboratory, more than a century of research has revealed only the tip of the iceberg concerning this most crucial of life sciences. There are many intellectual challenges remaining. The flow of complete sequences of bacterial genomes is likely to spawn renewed research in answering many questions of concern to academic, medical and industrial interests. Elucidating the roles of microbes, the oldest and most vital inhabitants of the biosphere, in the evolutionary process and in the maintenance of other life forms will be the major thrust in the years to come.
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pubmed_422_5470
|
pubmed_1138_21179
|
BACKGROUND
Adozelesin, a synthetic analogue of the antitumor antibiotic CC-1065, is the first of a class of potent sequence-specific alkylating agents to be brought to clinical trial. In preclinical in vitro testing, it has demonstrated antitumor activity at picomolar concentrations.
PURPOSE
We conducted a phase I study of adozelesin to (a) determine a recommended dose for phase II testing using a 24-hour intravenous infusion, (b) characterize the toxic effects of the drug using this schedule, and (c) document any antitumor activity observed.
METHODS
Adozelesin was given as a 24-hour continuous intravenous infusion. Treatments were initially scheduled every 3 weeks, but the prolonged myelosuppression observed necessitated a final dosing interval of every 6 weeks. The starting dose of 30 micrograms/m2 was escalated using a modified Fibonacci scheme until dose-limiting toxicity was encountered.
RESULTS
Twenty-nine patients were entered in the study. Successive dose levels used were 30, 60, 100, 150, 120, and 100 micrograms/m2. Prolonged thrombocytopenia and granulocytopenia were dose limiting. No antitumor responses were observed.
CONCLUSION
We recommend that the phase II dose of adozelesin given as a continuous 24-hour intravenous infusion be 100 micrograms/m2, repeated every 6 weeks. Other potentially less myelosuppressive schedules could be pursued.
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10.1093/jnci/86.5.368
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pubmed_948_4770
|
We previously demonstrated that treatments with rIL-1 beta accelerated the onset and progression of CIA in mice. In the present study, it was observed that IL-1 also enhanced the development of CIA in rats. Like the mouse model, maximal incidence (80-100%) of arthritis occurred within 7 days after the first treatment with IL-1 in rats. Thus, the acceleration of CIA by IL-1 (IL-1 CIA) may be an improved model for the rapid screening of anti-inflammatory and/or anti-arthritic drugs. As a first step to determining the utility of the IL-1 CIA model as a drug screen, we examined the ability of various known anti-inflammatory and anti-arthritic drugs to modify the IL-1 mediated enhancement of CIA in both rats and mice. The results of these studies showed that when analyzed in the IL-1 CIA model, rats and mice exhibited differences in their responses to several of these drugs. For example, dexamethasone, cyclophosphamide, azathioprine, various non-steroidal anti-inflammatory drugs (NSAIDs) as well as methotrexate were found active in the IL-1 CIA of rats. By contrast, the NSAIDs were found to be less effective in suppressing the IL-1 accelerated disease in mice. In both rats and mice, cyclosporine A and several disease modifying anti-arthritic drugs failed to the prevent the development of CIA that was potentiated by IL-1. Thus, in the IL-1 CIA model NSAIDs appeared to be less active in mice than rats. In conclusion, because of the shorter latent period required for the development of arthritis in the IL-1 treated animals, the IL-1 accelerated CIA model in both mice and rats may be useful for screening anti-inflammatory or anti-arthritic compounds.
|
10.1007/BF01986577
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pubmed_269_18773
|
The effects of hydrothermal treatment, 0-5% KMnO4 content, and 300-400 °C pyrolysis temperature, were studied for activated carbon preparation from sugar cane leaves in comparison with non-hydrothermal treatment. The percent yield of activated carbon prepared by the hydrothermal method (20.33-36.23%) was higher than that prepared by the non-hydrothermal method (16.40-36.50%) and was higher with conditions employing the same content of KMnO4 (22.08-42.14%). The hydrothermal and pyrolysis temperatures have the effect of increasing the carbon content and aromatic nature of the synthesized activated carbons. In addition, KMnO4 utilization increased the O/C ratio and the content of C-O, Mn-OH, O-Mn-O, and Mn-O surface functional groups. KMnO4 also decreases zeta potential values throughout the pH range of 3 to 11 and the surface area and porosity of the pre-hydrothermal activated carbons. The use of the pre-hydrothermal activated carbon prepared with 3% KMnO4 and pyrolyzed at 350 °C as a filter in an aquaponic system could improve the quality of water with pH of 7.2-7.4, DO of 9.6-13.3 mg/L, and the turbidity of 2.35-2.90 NTU. It could also reduce the content of ammonia, nitrite, and phosphate with relative removal rates of 86.84%, 73.17%, and 53.33%, respectively. These results promoted a good growth of catfish and red oak lettuce.
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10.3390/ma15062133
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pubmed_146_3310
|
BACKGROUND AND AIM
A biatrial thrombus straddling a patent foramen ovale (PFO) is rare. The optimal management is controversial. This report offers an additional report and brief review of the literature.
CASE REPORT
A 72-year-old female presented with paroxysmal dyspnea. Transthoracic echocardiography showed distended right heart cavities, pulmonary artery hypertension, and a thrombus in the right atrium passing through the PFO into the left atrium. Urgent surgical embolectomy confirmed an 11.5 cm serpentine biatrial thrombus and allowed PFO closure and bilateral pulmonary embolectomy. Postoperative recovery was uneventful.
CONCLUSIONS
The risk of systemic embolization during thrombolytic or heparin treatment for biatrial thrombus makes most authors recommend surgical or interventional thrombectomy and PFO closure. Given the limited number of cases, there is no evidence that any of the treatment strategies provide a better survival.
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10.1111/j.1540-8191.2007.00542.x
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pubmed_449_8982
|
An individual each of the marine turtles, Caretta caretta and Lepidochelys kempi, were stimulated with audiofrequencies delivered directly to the skull. Startle responses were observed to underwater stimuli of .25 and .5 kc/s. Neural responses to underwater bone-conducted (bc) sound were recorded in another aquatic form, the snapping turtle, Chelydridae serpentina. The morphology of the neural response suggested the involvement of the auditory system in bc responsivity. Bc hearing appears to be a reception mechanism for marine turtles with the skull and shell acting as receiving surfaces. Turtles are capable of receiving the low-frequency spectrum of the natal beach, which may serve as one of the cues in nesting returns.
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pubmed_449_8982
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pubmed_1020_6433
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Cobb's collar is a rare intraluminal congenital cause of bulbar urethral obstruction that is commonly mislabelled congenital obstructive posterior urethral membrane (COPUM) but may be distinguished from this endoscopically as it has no connecting folds to the verumontanum. In this report, Cobb's collar is described for the first time in association with the VACTERL syndrome. The abnormality was diagnosed and treated by diathermy and dilatation at the time of endoscopic evaluation, with improvement of vesicoureteric reflux on micturating cystourethrogram and renal ultrasound.
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pubmed_1020_6433
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pubmed_779_14107
|
BACKGROUND
Controlled attenuation parameter (CAP) can evaluate hepatic steatosis in patients with chronic hepatitis B (CHB). However, prognostic implications of CAP value remain unclear. We evaluated the association between CAP and the risk of hepatocellular carcinoma (HCC) in patients with CHB under antiviral therapy and maintained virologic response.
METHODS
A total of 1823 CHB patients who were taking nucleos(t)ide analogue and showing suppressed hepatitis B virus replication were analyzed. The primary outcome was incident HCC during follow-up. Patients were grouped into those with and without advanced chronic liver disease (ACLD) (liver stiffness measurement cutoff: 10 kPa), and those with and without hepatic steatosis (CAP cutoff: 222 dB/m).
RESULTS
During 6.4 years of follow-up, 127 patients (7.0%) newly developed HCC. Among patients with ACLD (n = 382), the cumulative HCC incidence rate was lower for those with CAP ≥ 222 (11.0% at 5 years) than those with CAP < 222 (24.0% at 5 years, p = 0.002), and was an independent factor associated with HCC. When CAP value was further stratified, the cumulative HCC incidence rate decreased in dose-dependent manner according to an increase in CAP value (24.0%, 13.9%, 12.8% and 6.0% at 5 years for those with CAP < 222, 222-246, 247-273 and ≥ 274, respectively). Among patients without ACLD (n = 1441), there was no significance difference in HCC risk according to CAP value (HCC incidence rate: 3.3% and 4.0% at 5 years for those with CAP < 222 and CAP ≥ 222, p = 0.20).
CONCLUSIONS
Among CHB patients under antiviral therapy showing suppressed HBV replication, low CAP value predicted higher risk for HCC among ACLD patients, indicating that CAP value has a prognostic implication in this population.
|
10.1007/s12072-021-10205-7
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pubmed_335_21016
|
The Centers for Medicare & Medicaid Services has initiated bundled payments for hip and knee total joint replacement in an effort to decrease healthcare costs and increase quality of care. The ethical implications of this program have not been studied. This article considers the ethics of patient selection to improve outcomes; specifically, screening patients by body mass index to determine eligibility for total joint replacement. I argue that this type of screening is not ethically defensible, and that the bundled payment program as structured is likely to lead to unfair restrictions on who receives total joint replacements.
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pubmed_335_21016
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pubmed_1134_15990
|
Vibrio vulnificus is an autochthonous estuarine bacterium and a pathogen that is frequently transmitted via raw shellfish. Septicemia can occur within 24 h; however, isolation and confirmation from water and oysters require days. Real-time PCR assays were developed to detect and differentiate two 16S rRNA variants, types A and B, which were previously associated with environmental sources and clinical fatalities, respectively. Both assays could detect 10(2) to 10(3) V. vulnificus total cells in seeded estuarine water and in oyster homogenates. PCR assays on 11 reference V. vulnificus strains and 22 nontarget species gave expected results (type A or B for V. vulnificus and negative for nontarget species). The relationship between cell number and cycle threshold for the assays was linear (R(2) = >0.93). The type A/B ratio of Florida clinical isolates was compared to that of isolates from oysters harvested in Florida waters. This ratio was 19:17 in clinical isolates and 5:8 (n = 26) in oysters harvested from restricted sites with poor water quality but was 10:1 (n = 22) in oysters from permitted sites with good water quality. A substantial percentage of isolates from oysters (19.4%) were type AB (both primer sets amplified), but no isolates from overlying waters were type AB. The real-time PCR assays were sensitive, specific, and quantitative in water samples and could also differentiate the strains in oysters without requiring isolation of V. vulnificus and may therefore be useful for rapid detection of the pathogen in shellfish and water, as well as further investigation of its population dynamics.
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10.1128/AEM.01100-07
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pubmed_1128_8482
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The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Dalton's lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.
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10.1016/0378-8741(90)90095-b
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pubmed_152_9357
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Molybdenum alkynyl complexes [Mo(C identical to CR)(eta 3-allyl)(CO)2(phen)] feature long Mo-Calkynyl bond distances and propensity to undergo the cleavage of these bonds, a property that allowed their use as acetylide transfer reagents.
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10.1039/b110864f
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pubmed_1097_23868
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Severe sepsis and septic shock are an important cause of mortality and morbidity. These illnesses can be triggered by the bacterial endotoxin LPS (lipopolysaccharide) and pro-inflammatory cytokines, particularly TNF-α (tumour necrosis factor-α) and IL (interleukin)-1β. Severity and mortality of sepsis have also been associated with high concentrations of N-PCT (aminoprocalcitonin), a 57-amino-acid neuroendocrine peptide derived from ProCT (procalcitonin). Previous studies in a lethal model of porcine polymicrobial sepsis have revealed that immunoneutralization with IgG that is reactive to porcine N-PCT significantly improves short-term survival. To explore further the pathophysiological role of N-PCT in sepsis, we developed an antibody raised against a highly conserved amino acid sequence of human N-PCT [N-PCT-(44-57)]. This sequence differs by only one amino acid from rat N-PCT. First, we demonstrated the specificity of this antibody in a well-proven model of anorexia induced in rats by central administration of human N-PCT-(1-57). Next we explored further the therapeutic potential of anti-N-PCT-(44-57) in a rat model of lethal endotoxaemia and determined how this immunoneutralization affected LPS-induced lethality and cytokine production. We show that this specific antibody inhibited the LPS-induced early release of TNF-α and IL-1β and increased survival, even if treatment began after the cytokine response had occurred. In addition, anti-N-PCT-(44-57) may increase long-term survival in LPS-treated rats by up-regulating the late production of counter-regulatory anti-inflammatory mediators such as ACTH (adrenocorticotropic hormone) and IL-10. In conclusion, these results support N-PCT as a pro-inflammatory factor in both the early and the late stages of lethal endotoxaemia, and suggest anti-N-PCT as a candidate for septic shock therapy.
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10.1042/CS20100007
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pubmed_589_1446
|
We report a case of a 70-year-old woman who presented with progressively increasing intensity of lower abdominal, pelvic and rectal pain of 3-day duration. She had similar symptoms intermittently over the preceding 2 years. CT of the abdomen and pelvis revealed the presence of a 3.8×0.4 cm linear foreign body in the colorectal region. History obtained from relatives recalled inadvertent ingestion of a chicken bone 2 years prior to presentation. Trials of foreign body retrieval, both manually and via rigid and flexible sigmoidoscopy, however, were unsuccessful due to the presence of obstruction by a circumferential rectal stricture. Consequently, an exploratory laparotomy was performed, with segmental resection of 17 cm of rectum and distal sigmoid. Dissection of the strictured segment revealed the presence of a chicken bone. The patient had an uneventful postoperative course, was discharged and is to continue following up on an outpatient basis.
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pubmed_589_1446
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pubmed_851_8607
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We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively. Immunohistochemistry was used to localize GPR40/FFAR1, and the levels of free fatty acids in the hypothalamus were analyzed with liquid chromatography-tandem mass spectrometry. The repeated administration of GW1100, a GPR40/FFAR1 antagonist, exacerbated the incision-induced mechanical allodynia and significantly increased the levels of phosphorylated extracellular signal-regulated kinase in the spinal cord after low-threshold touch stimulation in the mice compared to vehicle-treated mice. The levels of long-chain free fatty acids, such as docosahexaenoic acid, oleic acid, and palmitate, which are GPR40/FFAR1 agonists, were significantly increased in the hypothalamus two days after the surgery compared to levels in the sham group. Furthermore, the incision-induced mechanical allodynia was exacerbated in the GPR40KO mice compared to the WT mice, while the response in the plantar test was not changed. These findings suggested that dysfunction of the GPR40/FFAR1 signaling pathway altered the endogenous pain control system and that this dysfunction might be associated with the development of chronic pain.
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10.1371/journal.pone.0180610
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pubmed_819_1012
|
This study investigated the possible involvement of opioid delta receptors in the modulation of morphine antinociceptive potency produced by L365,260 a CCKB antagonist. Intracerebroventricular (i.c.v.), intratheoal (i.th.) or subcutaneous (s.c.) L365,260 alone did not produce any antinociceptive actions in the mouse warm-water tail-nick test. Treatment with L365,260 by any of these routes produced a leftward shift of the corresponding morphine dose-effect curve that was blocked by pretreatment with a receptor selective dose of s.c. naltrindole, an opioid delta receptor antagonist. Pretreatment with i.c.v. antisera to [Leu5]enkephalin also blocked the leftward displacement of the i.c.v. morphine dose-effect curve resulting from L365,260 but did not directly alter the i.c.v. morphine dose-effect curve; antisera to [Met5]enkephalin did not alter the effects of morphine or the modulation of morphine antinociception produced by L365,260. Repeated pretreatment with L365,260 resulted in a progressive decrease in the magnitude of the morphine modulatory action (i.e., L365,260 "tolerance"). In these "L365,260-tolerant" mice, the dose-effect curve for i.c.v. [D-Ala2, Glu4]deltrophin (a selective delta agonist) was displaced to the right by approximately 8.2-fold. The i.c.v. administration of [Leu5]enkephalin produced a leftward displacement of the i.c.v. morphine dose-effect curve that diminished after repeated administration (i.e., [Leu5]enkephalin "tolerance"). In "[Leu5]enkephalin-tolerant" mice, L365,260 failed to produce the leftward shift of the morphine dose-effect curve seen in control animals. That is, two-way antinociceptive cross-tolerance was observed between an opioid delta agonist and a CCKB receptor antagonist. Intracerebroventricular thiorphan, a peptidase inhibitor, did not elicit antinociception directly. Co-administration of thiorphan with L365,260 elicited significant antinociception that was blocked by naltrindole or antisera to [Leu5]enkephalin; antisera to [Met5]enkephalin had no effect. Repeated administration of i.c.v. [D-Ala2, Glu4]deltorphin resulted in a progressively decreasing antinociceptive effect (i.e., [D-Ala2, Glu4]deltorphin "tolerance"). In "[D-Ala2, Glu4]deltorphin-tolerant" mice, the thiorphan/L365,260 antinociceptive effect was inhibited. Collectively, these data suggest that CCK interacts at the CCKB receptor to inhibit tonically the release and/or availability of an endogenous substance acting at opioid delta receptors. The subsequent enhancement of morphine antinociceptive potency may reflect the well-known modulation of morphine antinociception produced by opioid delta receptor agonists. In this case, the latter may be [Leu5]enkephalin or a [Leu5]enkephalin-like substance.
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pubmed_819_1012
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pubmed_402_14359
|
PURPOSE
To report the frequency of caval occlusion after Vena Tech-LGM filter placement and identify related factors and their potential clinical significance.
MATERIALS AND METHODS
The filter was inserted into 243 patients, 142 of whom met inclusion criteria for this prospective study. Follow-up examinations performed every 2 years included clinical evaluation, plain frontal radiography of the abdomen, duplex scanning of the inferior vena cava (IVC), and/or phlebocavography.
RESULTS
A progressive decrease in IVC patency was observed, reaching 66.8% at 9 years of follow-up. Complete caval occlusion occurred in 28 patients and was significantly (P < 10(-6)) associated with retraction in 24 cases. Caval occlusion was not related to age, sex, pulmonary embolism (PE), deep venous thrombosis level, underlying conditions predisposing to a thromboembolic disease before filter insertion, the level of filter placement, use of anticoagulant therapy, and death during follow-up. PE with anticoagulation failure was a predictive factor (P = .016) of subsequent filter occlusion during follow-up as compared to all other clinical indications for filter placement. Filter patency at 9 years of follow-up was 35.2% in the PE group with anticoagulation failure and 80% for other patients (odds ratio, 2.5; 95% confidence interval 1.16-5.4).
CONCLUSION
PE with anticoagulation failure was the only factor predictive of subsequent caval occlusion observed in patients after Vena Tech-LGM filter placement. Caval occlusion was also related to Vena Tech-LGM filter retraction, which usually occurred at the time of occlusion.
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10.1016/s1051-0443(99)70455-0
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pubmed_764_6817
|
OBJECTIVE
To investigate the impact of intensive lifestyle education on dietary practices, exercise and metabolic measurements in people with insulin-dependent diabetes mellitus (IDDM).
DESIGN
Sixty-one volunteer subjects with IDDM were randomised to intensive (Group 1) or standard (Group 2) education programmes for six months. During a second six month period of observation Group 1 subjects received routine surveillance for their condition and those in Group 2 were given intensive advice (phase 2). Current insulin regimens were modified to optimise glycaemic control before the start of the intervention phase. Nutrient intakes, weight, blood pressure, glycated haemoglobin (HbA1), plasma lipids, lipoproteins and maximal oxygen consumption (VO2 max) were measured at the time of recruitment and at three monthly intervals during the trial and phase 2.
SETTING
Department of Human Nutrition at the University of Otago.
RESULTS
Glycated haemoglobin decreased significantly in both groups between recruitment and randomisation, the improvement being sustained during the six months of the randomised trial and for group 1 during the six months of post trial observation. A further decrease was seen in Group 2 during the second six month period when they were given intensive advice. Comparable changes were seen with total and low density lipoprotein (LDL) cholesterol in Group 1 during the trial, but significant decreases were only seen in Group 2 in association with intensive intervention (phase 2). These changes occurred in parallel with increases in intakes of carbohydrate and monounsaturated fatty acids, a reduction in intakes of total and saturated fat, and an improvement in maximum oxygen consumption.
CONCLUSIONS
A lifestyle programme for people with IDDM results in modest changes in diet and exercise habits sufficient to improve measures of glycaemic control and lipoprotein mediated risk of coronary heart disease independent of changes in insulin regime. More innovative approaches to achieve lifestyle changes are required to meet current recommendations which in turn are likely to produce even greater beneficial changes than those observed here.
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10.1038/sj.ejcn.1600478
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pubmed_1066_14787
|
Nephrogenic diabetes insipidus (NDI) is rarely considered against more common differentials such as diabetes mellitus in patients presenting with polydipsia and polyuria. Hypokalemia and hypercalcemia are known to induce NDI, but not much is known about hypomagnesemia. Hypokalemia refractory to therapy should prompt consideration of hypomagnesemia.
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10.1002/ccr3.4564
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pubmed_959_22571
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Anoctamin 6/TMEM16F (ANO6) is a dual-function protein with Ca2+-activated ion channel and Ca2+-activated phospholipid scramblase activities, requiring a high intracellular Ca2+ concentration (e.g., half-maximal effective Ca2+ concentration [EC50] of [Ca2+]i > 10 μM), and strong and sustained depolarization above 0 mV. Structural comparison with Anoctamin 1/TMEM16A (ANO1), a canonical Ca2+- activated chloride channel exhibiting higher Ca2+ sensitivity (EC50 of 1 μM) than ANO6, suggested that a homologous Ca2+-transferring site in the N-terminal domain (Nt) might be responsible for the differential Ca2+ sensitivity and kinetics of activation between ANO6 and ANO1. To elucidate the role of the putative Ca2+-transferring reservoir in the Nt (Nt-CaRes), we constructed an ANO6-1-6 chimera in which Nt-CaRes was replaced with the corresponding domain of ANO1. ANO6- 1-6 showed higher sensitivity to Ca2+ than ANO6. However, neither the speed of activation nor the voltage-dependence differed between ANO6 and ANO6-1-6. Molecular dynamics simulation revealed a reduced Ca2+ interaction with Nt- CaRes in ANO6 than ANO6-1-6. Moreover, mutations on potentially Ca2+-interacting acidic amino acids in ANO6 Nt- CaRes resulted in reduced Ca2+ sensitivity, implying direct interactions of Ca2+ with these residues. Based on these results, we cautiously suggest that the net charge of Nt- CaRes is responsible for the difference in Ca2+ sensitivity between ANO1 and ANO6.
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10.14348/molcells.2021.2203
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pubmed_57_23445
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The Arabidopsis A1-type cyclin, CYCA1;2, also named TARDY ASYNCHRONOUS MEIOSIS (TAM), is known for its positive role in meiotic cell cycle progression, but its function in other cells has not been characterized. This paper reports the role of CYCA1;2/TAM in differentiated cells in vegetative organs. The pattern of CYCA1;2/TAM expression was investigated by promoter and protein fusions using the β-glucuronidase and the green fluorescent protein, respectively. The relevance of the promoter region used in these gene fusion constructs was verified by the effective complementation of the phenotype of the diploid null allele, tam-2 2C by a genomic fragment containing the wild-type coding region of CYCA1;2/TAM and the promoter region. CYCA1;2/TAM expression was found primarily in non-proliferating cells such as guard cells, trichomes, and mesophyll cells, and in vascular tissue. In two types of overexpression lines, one containing the CYCA1;2/TAM transgene driven by the ARABIDOPSIS SKP1-LIKE1 (ASK1) promoter and the other CYCA1;2/TAM-GFP driven by the cauliflower mosaic virus 35S promoter, the largest differences between the transgene transcript levels were approximately 72- and 45-folds, respectively, but the TAM-GFP signal levels in the mesophyll and stomata in the 35S:TAM-GFP lines only differ slightly. Furthermore, the GFP signals in the mesophyll and stomata in the TAM:TAM-GFP and 35S:TAM-GFP lines were all at similarly low levels. These results indicate that the CYCA1;2/TAM protein is likely maintained at low levels in these cells through post-transcriptional regulation. Loss of function in CYCA1;2/TAM resulted in increases in the nuclear size in both trichomes and guard cells. Surprisingly, overexpression of CYCA1;2/TAM led to similar increases. The large increases in trichome nuclear size likely reflected ploidy increases while the moderate increases in guard cell nuclear size did not justify for a ploidy increase. These nuclear size increases were not clearly correlated with trichome branch number increases and guard cell size increases, respectively. These results suggest that cellular homeostasis of the CYCA1;2/TAM protein is linked to the control of nuclear sizes in trichomes and guard cells.
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10.1007/s11103-013-0170-9
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pubmed_1136_18075
|
BACKGROUND
Esophagogastrectomy for esophageal cancer is the standard surgical treatment as a curative measure or for palliation. Esophagogastric anastomotic leakage and stricture are common life-threatening postoperative complications (more so if the leakage occurs in the chest), and the success of the anastomosis created in the reconstruction of the resected esophagus can highly influence morbidity and mortality.
METHODS
A prospective, randomized study was undertaken on 291 patients treated for carcinoma of the esophagus between January 2004 and December 2008. The study excluded 36 patients (12%) who were inoperable. Patients were assigned to 2 treatment groups that consisted of 128 patients in group A and 127 patients in group B according to a restricted, permuted block randomization plan. Patients in group A underwent an esophagogastrectomy with wrapping of the pedicle omental flap around the esophagogastric anastomosis. Group B patients underwent an esophagogastrectomy with only a stapled technique.
RESULTS
Of all 255 patients who received an esophagogastric anastomosis, 226 (89%) were discharged from the hospital within 15 days of operation. There was no significant difference between these 2 groups in regard to the incidence of pulmonary complications, abdominal or thoracic infections, and days of hospital stay. Anastomotic leaks occurred in a single patient from group A (1%) and in 7 patients from group B (6%). In group A, 33 patients underwent transhiatal esophagogastrectomy and 95 had thoracic esophagogastrectomy, which resulted in an anastomotic leakage in 1 (3%) and 0 (0%) patients, respectively. In group B, 42 patients had transhiatal esophagogastrectomy and 85 had thoracic esophagogastrectomy, which resulted in anastomotic leakage in 5 (12%) and 2 (2%) patients, respectively. The leakage ratio of group B was significant greater than that of group A (P < .05). Two patients were excluded during the evaluation of the benign stricture due to hospital mortality. Anastomotic strictures were noted in 8 patients from group A (6%) and 20 patients from group B (16%), and the difference in the incidence of anastomotic strictures between these 2 groups was statistically significant (P < .05).
CONCLUSION
Wrapping of the pedicle omental flap around the esophagogastric stapled anastomosis site decreases the incidence of anastomotic leakage and stricture rate after esophagectomy for esophageal cancer, thereby decreasing the morbidity and mortality of the procedure.
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10.1016/j.surg.2010.08.005
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pubmed_61_8144
|
Chylopericardium is a rare complication of cardiothoracic surgery, associated with significant morbidity and mortality. The presentation may be insidious in isolated chylopericardium. Early diagnosis and appropriate treatment are essential. Simultaneous chylopericardium and chylothorax postcardiac surgery has been very infrequently reported. A case of a young patient is, hereby reported, who developed simultaneous massive chylopericardium and chylothorax, after aortic valve replacement and atrial septal defect (ASD) closure, leading to significant hemodynamic compromise and prolonged hospitalization. Surgical exploration led to the correct diagnosis and a favorable outcome.
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7.2005/JCPSP.483484
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pubmed_418_1541
|
Hyperspectral data processing technique has gained increasing interests in the field of chemical and biomedical analysis. However, appropriate approaches to fusing features of hyperspectral data-cube are still lacking. In this paper, a new data fusion approach was proposed and applied to discriminate Rhizoma Atractylodis Macrocephalae (RAM) slices from different geographical origins using hyperspectral imaging. Spectral and image features were extracted from hyperspectral data in visible and near-infrared (VNIR, 435-1042 nm) and short-wave infrared (SWIR, 898-1751 nm) ranges, respectively. Effective wavelengths were extracted from pre-processed spectral data by successive projection algorithm (SPA). Meanwhile, gray-level co-occurrence matrix (GLCM) and gray-level run-length matrix (GLRLM) were employed to extract textural variables. The fusion of spectrum-image in VNIR and SWIR ranges (VNIR-SWIR-FuSI) was implemented to integrate those features on three fusion dimensions, i.e., VNIR and SWIR fusion, spectrum and image fusion, and all data fusion. Based on data fusion, partial least squares-discriminant analysis (PLS-DA) and support vector machine (SVM) were utilized to establish calibration models. The results demonstrated that VNIR-SWIR-FuSI could achieve the best accuracies on both full bands (97.3%) and SPA bands (93.2%). In particular, VNIR-SWIR-FuSI on SPA bands achieved a classification accuracy of 93.2% with only 23 bands, which was significantly better than those based on spectra (80.9%) or images (79.7%). Thus it is more rapid and possible for industry applications. The current study demonstrated that hyperspectral imaging technique with data fusion holds the potential for rapid and nondestructive sorting of traditional Chinese medicines (TCMs).
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10.3390/s19092045
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pubmed_308_9396
|
The aim of this study was to explore methods by which the ERK signaling pathway inhibitor PD98059 (PD) could be used in long-term in vivo experiments. Forty healthy New Zealand rabbits were randomly divided into blank control, model control, PD low-dose, PD high-dose, PD blank, dimethyl sulfoxide (DMSO) control, DMSO blank, and positive control groups. The corresponding treatments were administered to each experimental group over the course of four weeks, after which, total ERK1/2 and ERK5 protein levels, protein phosphorylation, and gene expression were measured in myocardial tissues. Treatment of rabbits with Adriamycin (doxorubicin) resulted in the significant overall differences in ERK1/2 and ERK5 phosphorylation (P < 0.05). Compared with the model control group, changes in phosphorylated ERK1/2 and phosphorylated ERK5 were lowest in the PD high-dose group (P < 0.05). No significant differences in total protein and mRNA levels of myocardial ERK1/2 and ERK5 were detected between the groups after four weeks (P > 0.05). Continuous intravenous injection of PD98059 significantly reduced phosphorylation of ERK1/2 and that of ERK5. In conclusion, Adriamycin-induced myocardiopathy and abnormal ERK signaling might constitute a valuable model foruse in long-term experiments. These methods may provide a theoretical basis for related in vivo studies of long duration.
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10.4238/2015.December.23.20
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pubmed_889_17694
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Several efforts aimed at discriminating between different degrees of on-road risky attitudes have been devoted to the identification of personality profiles among young drivers. However, the results are often inconsistent because of the limits of self-report measures. To overcome these limits, we tried to identify different profiles based on our study participants' driving performances in a virtual environment and to look for psychological predictors of inclusion in one of three profiles. One-hundred and fourteen inexperienced adolescents were involved in this study, which included two experimental sessions. During the first, before riding along five virtual courses on a moped simulator, participants' sensation seeking, locus of control, aggressiveness and beliefs about their peers' on-road behaviors were measured by means of self-report tools. During the second session, the participants drove the simulator along six courses that were different from those faced in the first session. A cluster analysis was run on a wide number of indexes extracted from the participants' performances to detect different riding profiles. Three profiles emerged (Imprudent, Prudent and Insecure), with specific riding patterns. The profiles also differed in terms of riding safety, assessed by means of the scores automatically given by the simulator to the participants' performances. Reporting an external locus of control, underestimating peers' on-road risky behaviors and showing less concern for fate among the possible causes of crashes are predictors that increase the risk of being included in the Imprudent profile. Low levels of dangerous thrill seeking predict inclusion in the Prudent profile, whereas high rates of self-reported anger play a role in discriminating the Insecure riders from the other profiles. The study indicates that it is possible to identify riding profiles with different degrees of on-road safety among inexperienced adolescents by means of simulated road environments. Moreover, inclusion in these profiles is predicted by different patterns of personality variables and beliefs. Further research is needed to verify the validity of these conclusions in real road conditions.
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10.3389/fpsyg.2018.02483
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pubmed_299_17304
|
This study aimed to evaluate the role of zinc (Zn)-supplemented with high cholesterol diet (HCD) on the serum and whole blood rheological properties of rabbits fed a HCD. Twenty-four New Zealand white rabbits were divided into three groups. The HCD group was fed a diet with 1.0% cholesterol and 1.0% olive oil. The HCD + Zn group was fed a diet with 1.0% cholesterol, 1.0% olive oil, and Zn. Blood viscosity, shear stress, and torque (%) were measured at shear rates ranging from 225 to 1875 s-1 for serum and 75-900 s-1 for whole blood. Serum viscosity and shear stress in HCD rabbits were significantly higher at all shear rates compared to controls; while whole blood viscosity and shear stress in HCD rabbits were significantly lower at all shear rates compared to controls. Viscosity and shear stress in both serum and whole blood from rabbits in the HCD + Zn group returned to normal values at all shear rates. The Zn supplemented to HCD rabbits, delays the progression of atherosclerosis. Changes in blood serum viscosity could reflect changes in non-clotting proteins, glucose, nutrients and trace elements; while changes in whole blood viscosity could result from changes in hematocrit, hemoglobin, and erythrocyte count. One of the factors responsible for increasing the serum viscosity values of HCD rabbits might be attributed to increase in Fe and decrease in Zn levels in the blood serum.
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pubmed_299_17304
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pubmed_509_9495
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Bisphenol-A (BPA), a toxic chemical from polycarbonate plastics, is known for behavioural and neural abnormalities. These neuro-behavioural changes reflect the changes in neural activity. However the effect of BPA on nerve action potential is not available. Therefore, present investigation was undertaken to study the effect of BPA on compound action potential (CAP) of frog sciatic nerve. Bundle containing small group of nerve fibres in a sciatic nerve was dissected and placed in a Perspex chamber perfused with Ringer solution. Suction electrodes were applied to the cut ends of the nerve for stimulating and recording purposes. The stimulation of one end (with supramaximal strength) produced CAP in the recording electrode. BPA (1-100 μM) decreased the amplitude and repolarization time of CAP in a concentration-dependent manner, without any alteration in latency, rise time and threshold. The decrease in amplitude was directly correlated with decrease in repolarization time (r=0.76). The BPA-induced decreases were absent in Ca(2+)-free medium or in presence of L-type Ca(2+)-channel antagonist (nifedipine/deltiazem). T and P type Ca(2+) channel antagonist (Ni(2+)) failed to block the BPA-induced responses. Pre-treatment with an Erα antagonist (tamoxifen) blocked the BPA-induced decrease in CAP parameters. These observations indicate that the BPA decreased the amplitude and repolarization time of CAP involving L-type Ca(2+)-channel dependent mechanisms. Further involvement of Erα in the modulation of Ca(2+) channels is a possibility.
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10.1016/j.neulet.2012.04.044
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pubmed_813_11282
|
Modern imaging of pancreatic cancer remains a daily challenge both for detection and staging. Helical CT scanning, MRI, and more recently endoscopic ultrasound (EUS) all contribute. Demonstration of local vascular anatomy for assessing resectability is increasingly performed by non-invasive methods such as CT and MR angiography avoiding the need for traditional catheter angiograms. While a variety of primary tumors can occur in the pancreas ductal adenocarcinoma is by far the most important clinically accounting for c.80% of pancreatic neoplasms. Moreover, cancer of the pancreas presents more frequent and complex diagnostic imaging problems than carcinomas of the biliary tract and will form the focus of this discussion.
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pubmed_813_11282
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pubmed_834_15677
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Chinese hamster ovary (CHO) cells transfected with the cloned human TSH receptor (CHO-R) were used to develop an assay to detect thyroid autoantibodies blocking the TSH-dependent cAMP production (TSHBAb). The study group included 38 patients with goitrous Hashimoto's thyroiditis (HT) and 47 subjects with atrophic thyroiditis (AT). In the HT group, 8 patients had subclinical hypothyroidism (HT-SH) and 30 had overt hypothyroidism (HT-H). Thirty normal subjects served as controls. Immunoglobulin G (IgG) was prepared from serum by double chromatography on DEAE-Sephadex. CHO-R cells were seeded in 96-well plates and were cultured for 48 h before the assay in RPMI-1640 medium plus 1 mmol/L glutamine, 10% fetal calf serum, and 0.4 g/L geneticin. In the assay for TSHBAb, CHO-R cells were incubated with IgG alone (0.5-2 mg/ml), TSH alone (0.2-625 mU/L), or IgG plus TSH; all samples were diluted in hypotonic medium containing 0.5 mmol/L isobutylmethylxanthine (IBMX). After 2 h of incubation at 37 degrees C in 5% CO2-95% air atmosphere, TSH-stimulation was quantified by measuring extracellular cAMP by a RIA. IgGs from normal subjects did not significantly modify the stimulation of adenylate cyclase produced by TSH, the results obtained ranging between -30% and +18% (mean +/- SD = -3 +/- 14%). All IgGs producing an inhibition greater than 2SD from the mean of controls (> 25%) were considered positive for blocking antibodies. TSHABAb were detected in 1/8 (12.5%) patients with HT-SH, in 7/30 (23.3%) with HT-H and 16/47 (34.0%) patients with AT.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1007/BF03347782
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pubmed_101_1972
|
BACKGROUND
Large outbreaks of Lassa fever (LF) occur annually in Nigeria. The case fatality rate among hospitalised cases is ~ 20%. The antiviral drug ribavirin along with supportive care and rehydration are the recommended treatments but must be administered early (within 6 days of symptom onset) for optimal results. We aimed to identify factors associated with late presentation of LF cases to a healthcare facility to inform interventions.
METHODS
We undertook a retrospective cohort study of all laboratory confirmed LF cases reported in Nigeria from December 2018 to April 2019. We performed descriptive epidemiology and a univariate Cox proportional-hazards regression analysis to investigate the effect of clinical (symptom severity), epidemiological (age, sex, education, occupation, residential State) and exposure (travel, attendance at funeral, exposure to rodents or confirmed case) factors on time to presentation.
RESULTS
Of 389 cases, median presentation time was 6 days (IQR 4-10 days), with 53% attending within 6 days. There were no differences in presentation times by sex but differences were noted by age-group; 60+ year-olds had the longest delays while 13-17 year-olds had the shortest. By sex and age, there were differences seen among the younger ages, with 0-4-year-old females presenting earlier than males (4 days and 73% vs. 10 days and 30%). For 5-12 and 13-17 year-olds, males presented sooner than females (males: 5 days, 65% and 3 days, 85% vs. females: 6 days, 50% and 5 days, 61%, respectively). Presentation times differed across occupations 4.5-9 days and 20-60%, transporters (people who drive informal public transport vehicles) had the longest delays. Other data were limited (41-95% missing). However, the Cox regression showed no factors were statistically associated with longer presentation time.
CONCLUSIONS
Whilst we observed important differences in presentation delays across factors, our sample size was insufficient to show any statistically significant differences that might exist. However, almost half of cases presented after 6 days of onset, highlighting the need for more accurate and complete surveillance data to determine if there is a systemic or specific cause for delays, so to inform, monitor and evaluate public health strategies and improve outcomes.
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10.1186/s12879-021-05822-4
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pubmed_132_6325
|
Violence against health care workers is a serious and growing problem. The objectives of this cross-sectional study were to (a) describe the frequency of workplace violence (WPV) against emergency department (ED) workers; (b) identify demographic and occupational characteristics related to WPV; and (c) identify demographic and occupational characteristics related to feelings of safety and level of confidence when dealing with WPV. Survey data were collected from 213 workers at 6 hospital EDs. Verbal and physical violence was prevalent in all 6 EDs. There were no statistically significant differences in the frequency of violence for age, job title, patient population, and hospital location. Sexual harassment was the only category of violence affected by gender with females having a greater frequency. Feelings of safety were positively related to the frequency of WPV. Females were significantly more likely to feel unsafe and have less confidence in dealing with WPV. The study findings indicate that all ED workers are at risk of violence, regardless of personal and occupational characteristics. Feelings of safety are related to job satisfaction and turnover. Violence has serious consequences for the employers, employees, and patients. It is recommended that administration, managers, and employees collaborate to develop and implement prevention strategies to reduce and manage the violence.
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10.1097/TME.0b013e3182330530
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pubmed_88_4558
|
Transcription of the bacteriophage-borne diphtheria toxin gene tox is negatively regulated, in response to intracellular Fe(2+) concentration, by the chromosomally encoded diphtheria toxin repressor (DtxR). Due to a scarcity of tools, genetic analysis of Corynebacterium diphtheriae has primarily relied on analysis of chemically induced and spontaneously occurring mutants and on the results of experiments with C. diphtheriae genes cloned in Escherichia coli or analyzed in vitro. We modified a Tn5-based mutagenesis technique for use with C. diphtheriae, and we used it to construct the first transposon insertion libraries in the chromosome of this gram-positive pathogen. We isolated two insertions that affected expression of DtxR, one 121 bp upstream of dtxR and the other within an essential region of the dtxR coding sequence, indicating for the first time that dtxR is a dispensable gene in C. diphtheriae. Both mutant strains secrete diphtheria toxin when grown in medium containing sufficient iron to repress secretion of diphtheria toxin by wild-type C. diphtheriae. The upstream insertion mutant still produces DtxR in decreased amounts and regulates siderophore secretion in response to iron in a manner similar to its wild-type parent. The mutant containing the transposon insertion within dtxR does not produce DtxR and overproduces siderophore in the presence of iron. Differences in the ability of the two mutant strains to survive oxidative stress also indicated that the upstream insertion retained slight DtxR activity, whereas the insertion within dtxR abolished DtxR activity. This is the first evidence that DtxR plays a role in protecting the cell from oxidative stress.
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10.1128/JB.184.20.5723-5732.2002
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pubmed_377_2245
|
The use of β,γ-unsaturated-α-ketoesters in the intermolecular Stetter reaction furnishes 1,2,5-tricarbonyl compounds in high yield and excellent enantioselectivity. The α,δ-diketoesters generated using this methodology serve as useful synthetic building blocks via chemo- and diastereoselective transformations.
|
10.1021/ol202040b
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pubmed_471_6831
|
Déjà vu occurs when a novel event is experienced with an erroneous sense of familiarity. Memory researchers theorise that this arises due to an error in the processes underlying the recognition memory system. Research has indicated that there may be a link between high levels of anxiety and increased frequency and intensity of déjà vu, however, there has been a comparatively little characterisation of déjà vu as experienced by individuals with clinical anxiety. We used an online questionnaire to collect data from individuals self-reporting a clinical diagnosis of anxiety, as well as from age-matched controls. The Anxiety Group reported a significantly higher frequency of déjà vu episodes over the previous month than controls. They also reported experiencing déjà vu more frequently and with higher intensity during periods of high anxiety. In addition, the Anxiety Group reported finding déjà vu episodes significantly more distressing than the Control Group. The findings indicate that there are differences in déjà vu experienced by people reporting high levels of anxiety compared to healthy controls without an anxiety diagnosis. We discuss structural and neural mechanisms thought to underpin déjà vu in relation to these results.
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10.1080/09658211.2018.1538418
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pubmed_143_25355
|
OBJECTIVE
Severe behavioural issues such as impulsive action and suicide have since long been associated with low levels of cholesterol. While it is known that cholesterol plays a role in neural development and hence low levels of serum lipids could have long-term effects on behaviour, no longitudinal studies showed the association of serum lipids levels with impulsivity. We aimed to examine the prognostic properties of serum lipid levels during childhood and adolescence on measures of impulsivity during early adulthood in a representative birth cohort sample.
METHODS
We have investigated whether serum lipid levels measured at 9, 15, 18 and 25 years of age have an association with impulsivity in 25 years old young adults. This analysis was based on data of the birth cohort representative samples of the Estonian Children Personality Behaviour and Health Study (original n = 1238). Impulsivity was self-reported with the Adaptive and Maladaptive Impulsivity Scale.
RESULTS
Total and low-density lipoprotein (LDL) cholesterol measured in boys aged 9, 15 and 18 years predicted disinhibition and thoughtlessness in 25-year-old young adults. High scores of disinhibition were associated with low total and LDL cholesterol levels in males but, while less consistently, with high total and LDL cholesterol levels in females. Cross-sectional analysis did not result in systematic outcomes.
CONCLUSIONS
Serum lipid levels could have an impact on the development of Maladaptive Impulsivity starting from an early age. This effect of cholesterol continues throughout adolescence into young adulthood.
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10.1017/neu.2019.48
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pubmed_1003_7162
|
OBJECTIVE
To investigate the effect of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, on eosinophils (EOSs) apoptosis in asthma patients.
METHODS
Peripheral blood EOSs from 10 asthma patients were cultured in the presence or absence of simvastatin (1, 5, 10, 20 micromol/L), together with or without mevalonate (100 micromol/L) for 6, 12, 24, and 48 h. Apoptosis was monitored by annexin V/PI staining and flow cytometry. Caspase-3 was measured by enzyme-linked immunosorbent assay (ELISA).
RESULTS
EOSs were particularly susceptible to apoptosis after incubated with 5 micromol/L simvastatin for 6, 12, 24, and 48 h [the rates of EOSs undergoing apoptosis were: (23 +/- 3)%, (24 +/- 3)%, (41 +/- 6)%, (70 +/- 12)% in control and (32 +/- 4)%, (47 +/- 7)%, (62 +/- 9)%, (86 +/- 14)% in simvastatin; compared with control at the same time point: P = 0.000]. EOS apoptosis occurred at doses of 1 micromol/L and was already maximal at 5 micromol/L after incubated with simvastatin for 12 h [the rates of EOSs undergoing apoptosis were: (24 +/- 3)% in control, (37 +/- 3)%, (51 +/- 3)%, (53 +/- 4)%, (52 +/- 4)% in 1, 5, 10, 20 micromol/L simvastatin, respectively; compared with control: P = 0.000]. The level of caspase-3 in EOSs was consistent with the rate of cell apoptosis [(8 +/- 3) microg/L in control, (14 +/- 4), (22 +/- 4), (24 +/- 4), (23 +/- 5) microg/L in 1, 5, 10, 20 micromol/L simvastatin, respectively; compared with control: P = 0.000 - 0.003]. However, Co-incubation of simvastatin with mevalonate (the production of HMGR) completely reversed the activity of simvastatin on EOS apoptosis even when the highest simvastatin (20 micromol/L) dose was used; the rates of EOSs undergoing apoptosis in the control, mevalonate plus simvastatin and simvastatin alone were (24 +/- 3)%, (52 +/- 4)% and (25 +/- 3)%, respectively; while the caspase-3 levels were (8 +/- 3) microg/L, (23 +/- 5) microg/L and (9 +/- 3) microg/L, respectively.
CONCLUSION
Simvastatin induces apoptosis of EOSs in asthma patients via its ability to block the synthesis of the important isoprenoid intermediates, which leads to the inhibition of small GTP-binding protein activity.
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pubmed_1003_7162
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pubmed_128_1232
|
Plant in vitro cultures are a prospective alternative for biochemicals production, for example the triterpenes oleanolic and ursolic acid present in plants and cell cultures of Salvia sp. Our objective was to develop a suitable analysis protocol for evaluation of triterpenic acid yield in plant raw material and in vitro cultures supporting selection processes. Moreover, valuable bioactive compounds had to be revealed. Thus, different strategies enhancing the separation for a sensitive and effective HPLC-UV method were investigated and the developed method was validated for linearity, precision, accuracy, limits of detection and quantification. A baseline separation of these isomers enabled detection limits of below 0.4 microg/mL and quantification limits of about 1.2 microg/mL. Over the tested concentration range a good linearity was observed (R2 > 0.9999). The variations in the method were below 6% for intra- and inter-day assays of concentration. Recoveries were between 85-98% for both compounds using ethanol as extraction solvent. Additionally, metabolite profiling of cell suspension culture extracts by GC-MS has shown the production variability of different plant metabolites and especially the presence of plant phenols and sterols. These studies provide a method suitable for screening plant and cell culture productivity of triterpenic acids and highlighted interesting co-products of plant cell cultures.
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pubmed_128_1232
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pubmed_20_10163
|
A Basidiomycetes fungus belonging to polypore family of mushrooms, Ganoderma lucidum (GL), has been known since a long time for their myriad therapeutic indications. Renowned as an invaluable resource of cardinal mycoconstituents they encompass numerous terpenoids polysaccharides and proteins. Possessing the therapeutically potent lanosteroidal skeleton, terpenoids are upheld for their invariable participation in therapeutically diverse bioactivities. Polysaccharides and proteins exhibiting distinguishable bioactivities provide this oriental mushroom with additional edges over immune function and anti-cancer potential. This review is a concerted effort to throw light upon the therapeutic versatility of the fungus, shadowed by various other natural products. An effort has been made towards conglomerating the mycoconstituents decisive for the many activities portrayed by this fungus. More importantly, this review seeks to fathom the inextricable role played by derivatives in modulating signaling cascades such as downregulation of various mitogenic pathways, inhibiting growth factors, or upregulating certain pathways enhancing cellular integrity.
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10.1007/s13277-015-4709-z
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pubmed_319_3924
|
We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternative in-frame stop codon, were observed by mass spectra analysis. The abnormal peptide peaks present in tryptic and chymotryptic LC-MS peptide mapping were confirmed by N-terminal sequencing as C-terminal light chain extension peptides. Furthermore, LC-MS/MS of Glu-C peptide mapping confirmed the stop221E mutation, which is consistent with a single base-pair mutation in TAA (stop codon) to GAA (Glu). The light chain variants were approximately 13.6% of wild type light chain as estimated by RP-HPLC analysis. DNA sequencing techniques determined a single base pair stop codon mutation, instead of a stop codon read-through, as the cause of this light chain extension. To our knowledge, the stop codon mutation has not been reported for IgGs expressed in CHO cells. These results demonstrate orthogonal techniques should be implemented to characterize recombinant proteins and select appropriate cell lines for production of therapeutic proteins because modifications could occur at unexpected locations.
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10.4161/mabs.22232
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pubmed_547_23387
|
Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.
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pubmed_547_23387
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pubmed_781_18579
|
BACKGROUND
The Schizotypal Personality Questionnaire (SPQ) is a widely used scale for measuring schizotypal characteristics modeled on DSM-III-R criteria for schizotypal personality disorder (SPD). The aim of this study was to examine the factorial structure of the Greek SPQ, its factorial invariance across gender and different age groups and possible gender and age group differences at latent mean level.
METHODS
Eight hundred sixty-five community participants completed the Greek version of the SPQ.
RESULTS
With regard to the factorial structure of the original first-order model, the results showed that a seven-factor model (sub-scales "no close friends" with "constricted affect" and "ideas of reference" with "unusual perceptual experiences" were combined) was replicated adequately. Furthermore, the second-order "paranoid" model provided also adequate fit. With regard to the factorial invariance of the SPQ across gender and age, the analysis revealed that both, the first- and second-order models showed measurement invariance (configural, metric and structural) across gender and age groups (17-35 vs. 36-70). Latent mean differences across gender and age groups were also found.
CONCLUSIONS
Based on these findings, we can conclude that the Greek version of the SPQ is a psychometrically sound instrument for measuring schizotypal characteristics and a useful screening tool for SPD across gender and age.
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pubmed_781_18579
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pubmed_713_15393
|
Several recent experiments, including our own experiments in the fission yeast, Schizosaccharomyces pombe, have characterized the motions of gene loci within living nuclei by measuring the locus position over time, then proceeding to obtain the statistical properties of this motion. To address the question of whether a population of such single-particle tracks, obtained from many different cells, corresponds to a single mode of diffusion, we derive theoretical equations describing the probability distribution of the displacement covariance, assuming the displacement itself is a zero-mean multivariate Gaussian random variable. We also determine the corresponding theoretical means, variances, and third central moments. Bolstering the theory is good agreement between its predictions and the results obtained for various simulated and measured data sets, including simulated particle trajectories undergoing simple and anomalous diffusion, and the measured trajectories of an optically trapped bead in water, and in a viscoelastic polymer solution. We also show that, for sufficiently long tracks, each covariance distribution in all of these examples is well-described by a skew-normal distribution with mean, variance, and skewness given by the theory. However, for the experimentally measured motion of a gene locus in S. pombe, we find that the first two covariance distributions are wider than predicted, although the third and subsequent covariance distributions are well-described by theory. This observation suggests that the origin of the theory-experiment discrepancy in this case is associated with localization noise, which influences only the first two covariances. Thus, we hypothesized that the discrepancy is caused by locus-to-locus heterogeneity in the localization noise, of independent measurements of the same tagged site. Indeed, simulations implementing heterogeneous localization noise revealed that the excess covariance widths can be largely recreated on the basis of heterogeneous noise. Thus, we conclude that the motion of gene loci in fission yeast is consistent with a single mode of diffusion.
|
10.1103/PhysRevE.103.032405
|
pubmed_552_21067
|
The authors describe their experience concerning silent myocardial ischemia diagnosed by Holter monitoring technique, and present an update review about this issue. The new concepts of stunned and hibernated myocardium are analyzed, as well as the concepts of ischemic cascade, total ischemic burden and variable residual coronary reserve. Diagnostic methods and therapeutic decisions are also reviewed.
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pubmed_552_21067
|
pubmed_894_2944
|
Five factors (collagen stimulating factors) have been isolated from healing murine skin wounds which stimulate prolyl hydroxylase activity and collagen synthesis in mouse fibroblasts in vitro. These factors stimulate general protein synthesis to a much smaller extent. Collagen stimulating factors are detectable in wounds three days after healing begins and disappear after six days when healing is complete. These data indicate that these factors may modulate collagen production during wound healing.
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10.1136/jcp.36.6.707
|
pubmed_827_2520
|
One disadvantage of amino acid-based chiral selectors for micellar electrokinetic chromatography (MEKC) is that either they have very low solubility or are insoluble at acidic pHs. In order to increase solubilities at lower pHs, we have synthesized a highly water-soluble achiral surfactant and copolymerized it with an amino acid-based chiral surfactant. These two surfactants were polymerized either separately or at various molar rations of binary solutions, yielding pure molecular or copolymerized surfactant (CoPS), respectively. All surfactants were characterized by use of several analytical techniques prior to using them as novel pseudostationary phases in MEKC. The chromatographic performance of the CoPS in MEKC was tested with chiral and achiral analytes. The highly soluble sulfate head group significantly increased the solubility of amino acid-based CoPS over a wide range of pH. Three chiral binaphthyl derivatives were tested and each surfactant system was found to have different selectivity.
|
10.1002/elps.200305712
|
pubmed_733_17343
|
Latex allergy in the perioperative setting presents unique challenges to the health care system. Specific needs of the latex-sensitive patient are paramount, but consideration must also include the impact on health care workers vis-a-vis latex sensitization, environmental allergen control, and barrier protection against blood-borne pathogens. It has been well documented that the greatest source of latex aeroallergen in the surgical setting is latex gloves (both sterile and nonsterile). Levels of latex aeroallergen correlate strongly with use of high-allergen and powdered gloves, total number of gloves used, and the hours of activity in a given environment. A significant reduction in aeroallergen (>10-fold) can be achieved by switching to low-allergen gloves. Ready availability of and encouragement to use nonlatex alternatives when appropriate can further reduce exposure to latex allergens. Since 1998, the Food and Drug Administration has required all medical devices (or their packaging) that contain natural rubber latex to be so labeled. In addition, industry has responded with a host of latex-free products for use in patient care. This has helped eliminate a great deal of confusion about which products are safe for use with latex-sensitive individuals. However, despite significant efforts to educate the public and the health care industry regarding latex allergies, considerable misinformation persists. Provision of a completely latex-free environment in most surgical suites may be unrealistic, but every effort should be made to minimize the unnecessary exposure of patients and health care workers to latex allergens in this high-risk arena.
|
10.1067/mai.2002.125594
|
pubmed_556_21477
|
Health reform initiatives have caused disruptive change throughout the US health care system. A key driver of change is the adoption of alternative payment models that apply financial risk on physicians and hospital systems. Success in these value-based payment models requires health care provider and payor organizations to continue developing population-based approaches, including partnerships with community-based organizations that provide services within a community setting. Community-based organizations are positioned to serve as an extension of the care continuum because they provide desired access points to upstream services that address nonclinical factors. Yet many health care providers fail to enter into sustainable contracts with community organizations. This limits their ability to treat patients' social needs and widens the clinic-to-community gap, both of which must be addressed for success in value-based contracts. Future cross-sector collaboration will require stakeholders to abandon transactional partnership arrangements primarily concerned with referral systems in favor of transformational arrangements that better align partnership aims and more equally distribute ownership in solving for capacity building, evaluation, and sustainability. The following practices are based on the experience of local YMCAs and YMCA of the USA in establishing clinic-to-community partnerships throughout the country that can influence clinical cost and quality measures.
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10.1177/1559827620910980
|
pubmed_916_6340
|
OBJECTIVES
To use blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI) to evaluate renal oxygenation in patients with primary nephrotic syndrome (PNS), and test the hypothesis that renal tissue oxygenation correlates with renal function, tubulointerstitial alterations and treatment response.
METHODS
Patients with untreated first-onset PNS and healthy control subjects underwent BOLD MRI. Blood and urine samples were obtained on the day of MRI, and patients underwent renal biopsy the day after MRI. Renal tubulointerstitial damage scores (TIDS) were determined using Katafuchi criteria. All patients received corticosteroids within 7 days after MRI and were followed up for 12 months.
RESULTS
Medullary R2* values were significantly lower in patients with PNS (n = 20) than controls (n = 18). Medullary R2* values were negatively correlated with estimated glomerular filtration rates and positively correlated with TIDS in patients with PNS. There were no significant differences in medullary or cortical R2* values when patients were classified according to treatment response.
CONCLUSIONS
The medullary oxygen concentration was higher in patients with PNS than in control subjects. BOLD MRI was a useful noninvasive method for the evaluation of renal function and tubulointerstitial impairment.
|
10.1177/0300060515579117
|
pubmed_1129_21855
|
OBJECTIVE
To evaluate the usefulness of an application when planning total knee arthroplasties (TKA), besides the accuracy when measuring the anatomical-mechanical femoral angle (AMFA), comparing, also, the time spent during planning a TKA manually and by using the application.
METHODS
An interdisciplinary team involving health and computer science areas established activities in order to develop the application. After development, 24 physicians underwent an application usability test. Each one planned a primary total knee arthroplasty (TKA) initially, in a conventional manner and then by using the application. Data concerning AMFA measurement and time spent during planning were collected, in both manners. The Mann-Whitney and Wilcoxon tests were used to evaluate statistical significance related to angle and time.
RESULTS
Users considered it important checking AMFA and drawing the bone cut lines orthogonal to the mechanical axis, when planning TKAs. They also assessed that the application could be useful for training surgeons and for specialists. There was no statistically significant difference between the AMFA, as measured by the application and by the conventional manner. The planning time was shorter when the application was used (39% of the time spent manually).
CONCLUSIONS
The application has proved to be useful in planning TKAs and has revealed accuracy when measuring the AMFA when it was compared to the manual form of preoperative planning. The application was able to reduce planning time by more than half and it demonstrated reliability in measuring the AMFA.
|
10.1016/j.rboe.2018.02.011
|
pubmed_900_10066
|
OBJECTIVE
The aim of the present study was to examine antibiotic resistant strains among the implant-associated microorganisms in vitro, first as mixed cultures and again as pure isolates for resistance to one of five antibiotics.
METHODS
Samples were taken with sterile paper points from the deepest pocket of one implant per patient (n = 24) to culture the total oral micro-flora. The samples were streaked on agar (Schaedler or BHI) and incubated for 7 d in an anaerobic atmosphere. All colonies were rinsed off the plates, aliquots were added to top-agar. Susceptibility against antibiotics (ampicillin, ampicillin + sulbactam, azithromycin and penicillin, moxifloxacin) was determined using the Etest. Resistant strains were picked, purified and characterized, and the Etests were repeated with a selection of the pure isolates.
RESULT
The majority of the mixed cultures (67 - 100 %) showed complete antibiotic resistance. No association with clinical parameters like pocket depth, bleeding on probing or insertion of implants into transplanted bone could be found. Smoking and the surface of the implant also had no influence. 23 % of the 597 resistant colonies contained only yeasts, mostly isolated from irradiated tumour patients. Of the 458 resistant bacteria, the majority were Gram-positive cocci or rods. Staphylococci and M. micros were detected occasionally. The resistance for the 138 selected pure isolates was in most cases lower than for the total micro-flora, irrespective of the antibiotic.
CONCLUSIONS
The higher resistance of the total flora might be explained by synergistic interactions between its members.
|
pubmed_900_10066
|
pubmed_731_4972
|
RATIONALE AND OBJECTIVES
To assess both the complete aorta and coronary artery disease (CAD) using low iodine contrast computed-tomography angiography before transcatheter aortic valve replacement.
MATERIALS AND METHODS
84 patients underwent computed-tomography angiography before transcatheter aortic valve replacement: 42 with standard iodine injection protocol (P1:120 mL); 42 with a low dose iodine injection protocol (P2:60 mL). Mean attenuation and subjective image quality were rated at different levels of the aorta, iliac and coronary arteries. Sensitivity, specificity, negative and positive predictive values for depiction of CAD were calculated according to the coronary angiography.
RESULTS
Mean attenuation was significantly higher in P1 for the ascending aorta (p < 0.001). No significant difference was observed regarding image quality of the aortic valve (p = 0.876), the ascending aorta (p = 0.306), or the abdominal aorta (p = 1.0). Diagnostic image quality of coronary arteries was excellent for P1 and P2 (94.6% vs 96.5%, p = 0.08). Sensitivity, specificity, negative and positive predictive values, and accuracy for depiction of CAD were excellent for P1 and P2 (100% vs 100%; 79% vs 86%, 70% vs 87%, 100% vs 100% and 86% vs 93%) without significant differences (p = 0.93; p = 0.58; p = 0.90; p = 1.0; p = 0.74), respectively.
CONCLUSION
Despite a difference in aortic mean attenuation, a reduced iodine injection protocol showed similar image quality and detection of CAD in comparison with a standard injection protocol.
|
10.1016/j.acra.2018.06.016
|
pubmed_524_19795
|
OBJECTIVES
Peri-implantitis causes dislodgement of dental implants due to inflammation in the peri-implant tissue. The microcirculation in the periodontal tissue undergoes morphological and physiological changes due to inflammation. The immune mechanism of peri-implantitis differs from that of periodontitis. In this study, we examined the changes in the microcirculation in the peri-implant tissue with experimentally induced inflammation, using morphological and physiological techniques.
METHODS
Six beagle dogs were used in the experiment. After extracting both mandibular premolars, three titanium screw implants were inserted on each side of the mandibular jaw. Dental floss was placed on the right side for 90 days in the study group but not in the control group. Microvascular resin cast models were created, and morphological changes were observed using scanning electron microscopy. Periodontal blood flow was measured using laser Doppler flowmetry.
RESULTS
Ninety days after induction of inflammation, bone resorption was observed around the implant body. Osseointegration was impaired, and a gap at the implant-bone interface was observed. The resin cast models showed that inflamed gingival blood vessels had invaded the bone marrow through the resorbed apical margin of the alveolar bone. Analysis of the physiological data obtained using laser Doppler flowmetry showed a significant increase in blood flow around the implants with experimentally induced inflammation.
CONCLUSIONS
Significant morphological and physiological changes occur in the gingival microcirculation of peri-implant tissue due to inflammation. Evaluating the vasculature and blood flow in the tissue surrounding the site of peri-implantitis may be helpful for pathologic analysis in clinical settings.
|
10.1016/j.job.2021.03.002
|
pubmed_190_11734
|
Neighborhood-focused activism is one way residents enact their vision for their community. This study examines the neighborhood socioeconomic antecedents of participation in neighborhood-focused activism in a diverse sample of residents of Chicago neighborhoods to test three theories of neighborhood socioeconomic context and participation: 1) affluence affords participation, 2) activism addresses neighborhood needs associated with disadvantage, and 3) socioeconomic inequality creates contention that necessitates participation. Measuring neighborhood socioeconomic status as two unique dimensions, neighborhood affluence and neighborhood disadvantage, and accounting for both individual and neighborhood characteristics, I find support for each theory. Neighborhood socioeconomic context matters for participation, regardless of individual socioeconomic characteristics. Only when these three perspectives are considered jointly can they fully capture the socioeconomic context of participation in neighborhood-focused activism.
|
10.1111/juaf.12013
|
pubmed_58_16999
|
Vancomycin-resistant Enterococcus faecium (VREfm) strains have become an important hospital pathogen due to their rapid spread, high mortality rate associated with infections and limited therapeutic options. Vancomycin resistance is predominantly mediated by VanA or VanB phenotypes, which differ as regards maintaining sensitivity to teicoplanin in the VanB phenotype. The majority of VREfm cases in the United States, Europe, Korea, South America and Africa are currently caused by the VanA phenotype. However, the epidemics in Australia and Singapore are chiefly brought about by the VanB phenotype. The rate of VREfm isolate spread varies greatly. The greatest percentage of VREfm is now recorded in the USA, Ireland and Australia. Supervision of VRE is implemented to varying degrees. Therefore, the epidemiological situation in some countries is difficult to assess due to limited data or lack thereof.
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pubmed_58_16999
|
pubmed_445_704
|
Lesions of seborrheic keratoses studied by transmission electron microscopy showed an unusually large number of Langerhans cells in the epidermis. The role of Langerhans cells in the development of these lesions needs further study.
|
10.1111/j.1600-0560.1978.tb00967.x
|
pubmed_207_5720
|
We studied nosocomial infection in a group of 608 pediatric surgical patients over a 14-month period. All inpatients and outpatients who received an operation with an incision by the pediatric general surgical service were entered into the study. Demographic, nutritional, clinical, and laboratory data were collected. Surveillance was conducted for wound infection, septicemia, infections of the respiratory tract, urinary tract, and abdomen, and infectious diarrhea. A total of 676 operative procedures was performed. Nosocomial infection occurred in 38 of the 608 patients (6.2%). A total of 53 infectious complications was tabulated. The number and percent risk per operation were wound 17 (2.5%), septicemia 14 (2.1%), pulmonary 10 (1.5%), urinary tract 5 (0.7%), abdominal 5 (0.7%), diarrhea 2 (0.3%). Broviac catheter sepsis occurred in 7 of 61 lines (11.5%). The highest overall occurrence of infection was in the infant group (1 mo to 1 yr), (13/161, 8.1%). The probability of septicemia was highest in neonates (4.2%) compared with infants (3.1%) or older children (1.2%) (P < .05). The most common isolates were Staphylococcus epidermidis (10/17) from septic patients, and gram-negative enteric bacteria (27/50) from organ and wound infections. Infection was associated with impaired nutrition, multiple disease processes, and multiple operations. The risk of nosocomial infection in this population was comparable to that reported in adult surgical patients. These baseline data may aid the development of strategies to lower infection risk in children.
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10.1016/0022-3468(93)90228-d
|
pubmed_954_20570
|
The antihyperglycemic activity of the extracts and preparations of solid lipid nanoparticle suspensions of two mistletoes growing in Saudi Arabia, Plicosepalus acaciae and P. curviflorus, as well as their possible antioxidant effect were investigated in a type 2 diabetic animal model. Type 2 diabetes was induced in adult male Wistar rats by a high-fat diet followed by injection of streptozotocin (STZ). The diabetic rats were treated in parallel with pioglitazone hydrochloride (PIO), non-toxic extracts of P. acaciae and P. curviflorus, as well as three different solid lipid nanoparticle (SLN) suspension formulations prepared from each of the two extracts. Blood glucose level, insulin resistance, oxidative stress parameters, and antioxidant markers were determined. The total extracts of P. acaciae and P. curviflorus as well as the SLN formulations exhibited a significant blood glucose-lowering effect associated with antioxidant effects in the diabetic rats. The SLN preparation with the highest lipid content gave the best result. Reduction of hyperglycemia and insulin resistance in the diabetic rats was, at least partly, due to the antioxidant activities of the extracts and their SLN formulations.
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10.5560/znc.2014-0047
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pubmed_570_8723
|
Fanconi anemia (FA) is an inherited disease caused by mutations in at least 13 genes and characterized by genomic instability. In addition to displaying strikingly heterogenous clinical phenotypes, FA patients are exquisitely sensitive to treatments with crosslinking agents that create interstrand crosslinks (ICL). In contrast to bacteria and yeast, in which ICLs are repaired through replication-dependent and -independent mechanisms, it is thought that ICLs are repaired primarily during DNA replication in vertebrates. However, recent data indicate that replication-independent ICL repair also operates in vertebrates. While the precise role of the FA pathway in ICL repair remains elusive, increasing evidence suggests that FA proteins function at different steps in the sensing, recognition and processing of ICLs, as well as in signaling from these very toxic lesions, which can be generated by a wide variety of cancer chemotherapeutic drugs. Here, we discuss some of the recent findings that have shed light on the role of the FA pathway in ICL repair, with special emphasis on the implications of these findings for cancer therapy since disruption of FA genes have been associated with cancer predisposition.
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10.3109/10409238.2010.502166
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pubmed_491_23220
|
Aging and bone diseases are associated with increased fracture risk. It is therefore pertinent to seek an understanding of the origins of such disease-related deterioration in bone's mechanical properties. The mechanical integrity of bone derives from its hierarchical structure, which in healthy tissue is able to resist complex physiological loading patterns and tolerate damage. Indeed, the mechanisms through which bone derives its mechanical properties make fracture mechanics an ideal framework to study bone's mechanical resistance, where crack-growth resistance curves give a measure of the intrinsic resistance to the initiation of cracks and the extrinsic resistance to the growth of cracks. Recent research on healthy cortical bone has demonstrated how this hierarchical structure can develop intrinsic toughness at the collagen fibril scale mainly through sliding and sacrificial bonding mechanisms that promote plasticity. Furthermore, the bone-matrix structure develops extrinsic toughness at much larger micrometer length-scales, where the structural features are large enough to resist crack growth through crack-tip shielding mechanisms. Although healthy bone tissue can generally resist physiological loading environments, certain conditions such as aging and disease can significantly increase fracture risk. In simple terms, the reduced mechanical integrity originates from alterations to the hierarchical structure. Here, we review how human cortical bone resists fracture in healthy bone and how changes to the bone structure due to aging, osteoporosis, vitamin D deficiency and Paget's disease can affect the mechanical integrity of bone tissue.
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10.1038/bonekey.2015.112
|
pubmed_635_19526
|
BACKGROUND
One prominent and well-cited meta-analysis published nearly 25 years ago reported that an acute or single bout of exercise reduced state anxiety by approximately ¼ standard deviation. We conducted a meta-analysis of randomized controlled trials (RCTs) published after that meta-analysis for updating our understanding of the acute effects of exercise on state anxiety.
METHODS
We searched PubMed, EBSCOHost, Medline, PsycINFO, ERIC, and ScienceDirect for RCTs of acute exercise and state anxiety as an outcome. There were 36 RCTs that met inclusion criteria and yielded data for effect size (ES) generation (Cohen's d). An overall ES was calculated using a random effects model and expressed as Hedge's g.
RESULTS
The weighted mean ES was small (Hedge's g = 0.16, standard error (SE) = 0.06), but statistically significant (P < 0.05), and indicated that a single bout of exercise resulted in an improvement in state anxiety compared with control. The overall ES was heterogeneous and post hoc, exploratory analyses using both random- and fixed-effects models identified several variables as moderators including sample age, sex and health status, baseline activity levels, exercise intensity, modality and control condition, randomization, overall study quality, and the anxiety measure (P < 0.05).
CONCLUSION
The cumulative evidence from high quality studies indicates that acute bouts of exercise can yield a small reduction in state anxiety. The research is still plagued by floor effects associated with recruiting persons with normal or lower levels of state anxiety, and this should be overcome in subsequent trials.
|
10.1002/da.22370
|
pubmed_250_15106
|
BACKGROUND & AIMS
To compare the acute effects of three fatty meals with different fat quality on postprandial thermogenesis, substrate oxidation and satiety.
METHODS
Twenty-nine healthy men aged between 18 and 30 years participated in a randomised crossover trial comparing the thermogenic effects of three isocaloric meals: high in polyunsaturated fatty acids from walnuts, high in monounsaturated fatty acids from olive oil, and high in saturated fatty acids from fat-rich dairy products. Indirect calorimetry was used to determine resting metabolic rate, respiratory quotient, 5-h postprandial energy expenditure and substrate oxidation. Satiety was estimated by using visual analogue scales and measuring caloric intake in a subsequent ad libitum meal.
RESULTS
Five-h postprandial thermogenesis was higher by 28% after the high-polyunsaturated meal (p=0.039) and by 23% higher after the high-monounsaturated meal (p=0.035) compared with the high-saturated meal. Fat oxidation rates increased nonsignificantly after the two meals rich in unsaturated fatty acids and decreased nonsignificantly after the high-saturated fatty acid meal. Postprandial respiratory quotient, protein and carbohydrate oxidation, and satiety measures were similar among meals.
CONCLUSIONS
Fat quality determined the thermogenic response to a fatty meal but had no clear effects on substrate oxidation or satiety.
|
10.1016/j.clnu.2008.10.008
|
pubmed_106_3118
|
BACKGROUND
Hereditary gingival fibromatosis (HGF) is a fibrotic enlargement of the gingiva. The mechanism that leads to the accumulation of abnormal amounts of gingival tissue in HGF is still unknown. The aim of this report was to present the clinical and histopathologic characteristics of a patient with gingival fibromatosis and to evaluate the proliferation of HGF fibroblasts.
METHODS
We examined the proliferation rate of fibroblasts in this case by using Ki-67 immunohistochemical staining and compared the rate to fibroblasts of non-fibromatosis gingival tissues from 5 healthy patients serving as controls.
RESULTS
There were no Ki-67-positive cells in the lesional tissue, and the control gingiva revealed no immunostaining. The number of Ki-67 antigen-positive epithelial cell nuclei was observed to be low in the basal cell layers of hyperplastic gingival epithelia, similar to the control group.
CONCLUSIONS
In the present case, there was no increase in the proliferation rate of lesional fibroblasts observed by Ki-67 immunohistochemical staining as a proliferation marker; only the epithelium was stained. It seems likely that the underlying mechanism of HGF may be an increase in the biosynthesis of collagen and glycosaminoglycans rather than cell proliferation.
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10.1902/jop.2003.74.6.873
|
pubmed_1032_19733
|
BACKGROUND
Colonic lipomas are rare, slow-growing benign tumors. Colonic lipomas are generally asymptomatic and are found incidentally. Although cases of cecal lipoma have been sporadically reported in the literature, the disease has not been systematically reviewed.
CASE SUMMARY
We present a 44-year-old man who underwent a routine physical check-up during which colonoscopic examination revealed an asymptomatic 1.5-cm cecal mass at the appendiceal orifice. Laparoscopic exploration was performed that also demonstrated a congested and erythematous appendix. En bloc resection of both the cecum and vermiform appendix was performed because of the suspicion of malignancy. Histopathological examination revealed a cecal lipoma composed of mature adipose tissue, and the appendix showed subclinical inflammation. Our procedures and findings were discussed, along with relevant English literature that was retrieved from the PubMed database from 2000 to 2017. Twenty-six cases, including ours, were reported. Consistent with the findings of the literature, it is difficult to obtain a definitive diagnosis by colonoscopic biopsy.
CONCLUSION
Surgery remains the treatment of choice for this condition. Intraoperative frozen pathological sectioning helped the surgeon decide the extent of surgery, and radical surgery was avoided. Excision of benign lesions occupying the appendiceal orifice may be indicated for the prevention of later development of acute appendicitis. The prognosis is generally good, with only one of the 26 reported patients complicated with acute appendicitis, who subsequently succumbed due to severe comorbidities and sepsis.
|
10.12998/wjcc.v7.i2.209
|
pubmed_1119_1793
|
Mineralocorticoid receptors in the distal nephron have no intrinsic specificity for mineralocorticoids over glucocorticoids (cortisol in humans; corticosterone in rodents), but are protected from glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase, which inactivates these steroids to cortisone and 11-dehydrocorticosterone, respectively. Recent work has demonstrated that the enzyme is expressed as multiple tissue-specific isoforms, some of which catalyse the reverse conversion of cortisone to cortisol. These isoforms may allow 11 beta-hydroxysteroid dehydrogenase to modulate access of ligands to glucocorticoid and mineralocorticoid receptors, as well as to amplify and attenuate tissue responses. 11 beta-hydroxysteroid dehydrogenase-mediated protection of mineralocorticoid receptors fails in congenital 11 beta-hydroxysteroid dehydrogenase deficiency and after inhibition of the enzyme by liquorice. In these circumstances, cortisol-dependent mineralocorticoid excess and hypertension ensue. Recent studies suggest that similar deficiencies of 11 beta-dehydrogenase activity may contribute to pathophysiology in common clinical syndromes, illustrating the potential significance of this novel mechanism for development of hypertension.
|
10.1097/00041552-199501000-00006
|
pubmed_1004_1873
|
Metabolic networks represent a set of reactions and associated metabolites that may occur in a given cell or tissue. They are frequently reconstructed from pure genomic data without thorough biochemical validation. Such genome-scale metabolic networks may thus either lack relevant or contain non-existent reactions and metabolites. Filling gaps and removing falsely predicted reactions can be a cumbersome procedure. On the other hand, using the network to build mathematical models addressing a specific problem (e.g. analyzing changes in the level of cellular ATP at substrate depletion) it may turn out that the network comprises more reactions and metabolites than actually needed or, on the contrary, that essential reactions are missing. Therefore, we propose a method to prune the whole network to a smaller sub-network which contains no dead ends and blocked reactions, i.e reactions that may neither proceed in forward nor backward direction. Inspection of this reduced network reveals its actual functional capabilities in terms of producible metabolites. We apply our method to a genome-scale metabolic network of E. coli. Depending on the choice of the exchangeable metabolites, composition of the external medium, and type of thermodynamic constraints we obtain different reduced network variants that may serve as a basis for flux balance models.
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pubmed_1004_1873
|
pubmed_378_6665
|
A multistep synthesis for 2-(2-pyridyl-N-oxide) ethylphosphonic acid 6-H2 is described along with its spectroscopic (IR, NMR) data and a single-crystal X-ray diffraction structure analysis. Combination of the ligand with Nd(OH)3 results in the formation of a complex Nd(6-H)3. Single-crystal X-ray diffraction analysis reveals a three-dimensional crystal network generated by hydrogen-bonded chains along the crystallographic c axis. The hydrogen bonds are formed between phosphonic acid anion (6-H)(-1) protons on one chain and pyridyl N-oxide oxygen atoms in neighboring chains. The asymmetric unit contains 1/3[Nd(6-H)3] and there are two unique Nd(III) atoms, each with point symmetry. As a result, each Nd(III) ion is bound to six (6-H)(-1) ligands and the symmetry about the Nd(III) ion is octahedral with each vertex occupied by a phosphonate oxygen atom. The Nd-O bond lengths are essentially identical: Nd(1)-O(3), 2.336 (1) A; Nd(2)-O(4), 2.340 (1) A. The monoanionic ligand (6-H)(-1), therefore, serves to bridge the unique Nd(III) centers.
|
10.1021/ic051937+
|
pubmed_543_12401
|
13C and 31P NMR spectroscopy were used to monitor interactions of lyso 1-palmitoylphosphatidylcholine (LPPC) in the interfacial region of egg phosphatidylcholine (PC) bilayers and determine the effect of LPPC on the phospholipid bilayer structure. 13C NMR spectroscopy of small amounts (0.5-10 mol%) of 13C carbonyl-enriched LPPC cosonicated with egg PC to form small unilamellar vesicles (SUVs) revealed separate carbonyl signals for LPPC in the inner and outer leaflets of the vesicles. The ratio of LPPC in the outer leaflet to that in the inner leaflet was > or = 3/1. Exchange of LPPC between bilayer leaflets ("flip-flop") was too slow to be measured (t1/2 > 12 h). Albumin added to the external buffer of LPPC/PC vesicles was shown by 13C NMR to extract LPPC only from the outer leaflet. LPPC was a poor detergent in egg PC multilayers and SUVs. Stable SUVs were prepared by cosonicating egg PC with up to 30 mol% LPPC, and preformed SUVs incorporated up to 40 mol % of LPPC (added as an aqueous solution) without undergoing any morphological changes as evidenced by 31P NMR spectroscopy. The presence of oleic or palmitic acid did not have observable effects on properties of LPPC in SUVs, such as the localization of the LPPC carbonyl in the interface, and the transbilayer distribution and movement of LPPC. The apparent pKa of the fatty acid (FA) carboxyl at the membrane interface (7.7) measured by 13C NMR was not affected by LPPC, but the FA carboxyl carbon resonance showed linewidth changes near the apparent pKa that were dependent on the FA/LPPC ratio. These data suggest weak interactions in the interfacial region between FA and LPPC when both lipids are present at low levels in PC vesicles.
|
10.1021/bi00016a043
|
pubmed_635_15512
|
BACKGROUND
Red blood cell (RBC) transfusion is associated with inconsistent changes in brain tissue oxygenation (PbO2). Previous studies have failed to consider alterations in cerebral autoregulation. Our objective was to investigate the effect of RBC transfusion on cerebral autoregulation, as measured by pressure reactivity index (PRx).
METHODS
Retrospective analysis of 28 severe traumatic brain injury (TBI) patients from a prospective registry between 2007 and 2014. We recorded hemoglobin (Hb) concentration, intracranial pressure, PbO2, cerebral perfusion pressure, PRx, and cerebral lactate/pyruvate ratio for 6 h before and after RBC transfusion. We also recorded body temperature, PaO2, PCO2, pH, and fraction of inspired oxygen. Subgroups of normoxia (PbO2 >20 mmHg) and hypoxia (PbO2 <20 mmHg) prior to transfusion were defined a priori.
RESULTS
The median age was 36 years [interquartile range (IQR) 27-49], 32% were female. The median admission Glasgow Coma score was 5 (IQR 4-9) and injury severity score was 16 (IQR 9-21). Overall, mean Hb concentration [80 g/L (SD 7) to 89 g/L (SD 8), p < 0.001] and PbO2 increased [23.5 mmHg (SD 8) to 25.0 mmHg (SD 9), p = 0.033] following transfusion. PRx increased post-transfusion [0.028 (SD 0.29) to 0.11 (SD 0.24), p = 0.034], indicating worsening cerebrovascular pressure reactivity. In patients with mean PbO2 >20 mmHg pre-transfusion (n = 20), the PRx increased significantly [-0.052 (SD 0.24) to 0.079 (SD 0.22), p = 0.007] but did not change in patients with PbO2 <20 mmHg: PRx [0.22 (SD 0.34) to 0.18 (SD 0.30), p = 0.36].
CONCLUSION
RBC transfusion in severe TBI patients results in worsening PRx, indicating impaired cerebral autoregulation.
|
10.1007/s12028-015-0141-x
|
pubmed_334_380
|
AIM
To study susceptibility genes which may play a potential role in the pathogenesis and etiology of inflammatory bowel disease (IBD).
METHODS
To identify potential susceptibility genes we performed global gene expression profiling in patients with IBD and control specimens. For determination of an intrinsic gene expression profile in ulcerative colitis (UC) and Crohn's disease (CD) compared to normal subjects, mucosal biopsies of non-inflamed regions of the colon and the terminal ileum were subjected to DNA microarray analysis. Real-time RT-PCR and immunohistochemistry were used for verification of selected regulated candidate genes and a genetic analysis was performed.
RESULTS
We could show that aquaporin-8 (AQP8) mRNA and protein levels were significantly increased in the colon of UC patients compared to controls. Genetic analysis of the six exons and the promoter region of AQP8, however, revealed no mutations or polymorphisms in IBD patients.
CONCLUSION
Our results suggest that upregulation of AQP8 in the colon of UC patients represents a secondary phenomenon which may, due to altered water exchange of the distal intestinal mucosa, disturb the physiologic colonic mucus barrier and thus lead to chronic inflammation and ulceration.
|
10.3748/wjg.v13.i11.1687
|
pubmed_466_4856
|
The main plasma fibrinogen species, high molecular weight fibrinogen (HMW, mw. 340,000) and LMW (mw. 305,000), displaying different in vitro properties, were examined as to half-life and incorporation into venous thrombi (DVT). Total plasma fibrinogen and relative amounts of HMW were measured pre- and postoperatively in eighteen patients undergoing total hip arthroplasty, and related to the occurrence of deep vein thrombosis, as determined by the fibrinogen uptake test (FUT). Total fibrinogen and HMW did not disclose significant differences between scan-negative and scan-positive groups. HMW and LMW, prepared from purified fibrinogen, were labelled with I125 and I131, injected simultaneously and the incorporation into thrombi registered by leg-scanning. In 5 patients demonstrating a positive FUT, HMW as well as LMW were incorporated approximately to the same extent. This result implies that neither of these fibrinogen fractions offer any advantage as compared to ordinary fibrinogen when used for FUT. The half-lives of HMW and LMW were calculated from the elimination curves of the plasma clot-radioactivity. In all the surgical patients (n = 10) as well as in the two medical DVT-patients and in two healthy volunteers the half-life of LMW was approximately 10% longer than that of HMW.
|
10.1016/0049-3848(86)90279-3
|
pubmed_391_18084
|
Cerebrospinal fluid angiotensin converting enzyme (CSF-ACE) level was measured in two patients considered to have neurosarcoidosis, three patients with possible neurosarcoidosis and in 38 control patients suffering from prolapsed intervertebral discs. Both neurosarcoidosis patients had elevated levels (1.8 and 5.4 mumol/l/min) while the possible neurosarcoidosis patients had values similar to the control patients (mean 0.59 +/- 0.42 mumol/l/min). We suggest that CSF-ACE values may be of use in some patients as a diagnostic test for neurosarcoidosis and provide a reference range of normal controls.
|
10.1177/003693309103600507
|
pubmed_20_3500
|
INTRODUCTION
Studies suggest that exposure to televised electronic cigarette (e-cigarette) advertising contributes to the recent increase in e-cigarette use among youth. This study examines the relationship between perceptions of e-cigarette advertisements and attitudes toward and intentions to use e-cigarettes among youth who had never used e-cigarettes.
METHODS
In May 2014, we conducted an online survey of 5020 youth aged 13 to 17. Participants were randomly assigned to answer questions about their attitudes toward and intentions to use e-cigarettes before or after viewing e-cigarette advertisements. Perceived effectiveness (PE) of advertisements was measured after ad exposure. Ordinary least squares models were used to assess the relationship between PE and study outcomes.
RESULTS
Among never e-cigarette users, greater PE was associated with more positive attitudes toward e-cigarettes (b = 0.74, P < .001) and intentions to use e-cigarettes (b = 0.16, P < .001). Findings suggest that PE is predictive of outcomes controlling for study condition, youth demographics, and media use variables.
CONCLUSIONS
After ad exposure, youth who have never used e-cigarettes previously perceive e-cigarettes as cooler, more fun, healthier, and more enjoyable. Youth who thought the ads were more effective were more likely to have a positive attitude toward e-cigarettes and greater intention to try e-cigarettes in the future. Restricting televised e-cigarette advertising may reduce e-cigarette initiation among youth.
IMPLICATIONS
Previous studies demonstrate that, among adults, PE is antecedent to actual ad effectiveness across a range of behaviors. To our knowledge, this is the first study to document the relationship between PE and advertising effectiveness among youth. It provides evidence that PE may be a useful tool to quantify the potential influence of advertising on youth-advertising that, in this case, is designed to market a consumer good that may be harmful to youth but that may also be used to develop public health campaigns.
|
10.1093/ntr/ntv264
|
pubmed_581_23575
|
BACKGROUND
Because most patients with small-sized non-small cell lung cancer (NSCLC) are asymptomatic, their lesions are detected by cancer screenings or routine checkups for other diseases. Incidences of multiple malignancies have been reported to be 27% in patients with stage I-III NSCLC. Some patients have treatment histories for other malignancies, and their small-sized NSCLC was incidentally detected during follow-up. There is no established report regarding the influence of multiple malignancies on small-sized NSCLC prognosis. Therefore, we investigated the correlation between multiple malignancies and surgical outcomes in patients with small-sized NSCLC.
METHODS
In total, 44 patients underwent definitive pulmonary resection for NSCLC of 1 cm or smaller between January 2003 and December 2012. Tumor size was measured by macroscopic findings of the resected specimens, and we then retrospectively investigated their clinical courses.
RESULTS
One patient had hemoptysis symptoms, whereas 43 patients were asymptomatic; among them, NSCLC was detected by examinations for other diseases in 31 patients and by cancer screening in 12 patients. In total, 20 patients (45%) had multiple malignancies. The median follow-up period was 68 months. One patient had a recurrence from current NSCLC. No patients died of current NSCLC. The overall 5-year survival rate was 90% for all patients. Patients with multiple malignancies had significantly poorer prognoses compared with those without multiple malignancies (P = 0.016). However, patients with treatment intervals of more than 5 years had prognoses equivalent to those of patients without multiple malignancies (P = 0.829). Only the presence of multiple malignancies was a significantly poor prognostic factor in univariate and multivariate analyses.
CONCLUSION
NSCLC of 1 cm or smaller showed good prognoses. The presence of multiple malignancies was a significantly poor prognostic factor, and short treatment intervals also correlated with poor prognosis.
|
10.1007/s10147-017-1185-z
|
pubmed_334_7779
|
Based on the chemiluminescence (CL) intensity generated from the potassium ferricyanide [K(3)Fe(CN)(6)]-rhodamine 6G system in sodium hydroxide (NaOH) medium, a new sensitive flow-injection chemiluminescence (FI-CL) method has been developed, validated and applied for the determination of three kinds of H(2)-receptor antagonists: cimetidine (CIMT), ranitidine (RANT) hydrochloride and famotidine (FAMT). Under the optimum conditions, the linear range for the determination was 1.0 x 10(-9)-7.0 x 10(-5) g/ml for CIMT, 1.0 x 10(-9)-5.0 x 10(-5) g/mL for RANT hydrochloride and 5.0 x 10(-9)-7.0 x 10(-5) g/mL for FAMT. During 11 repeated measurements of 1.0 x 10(-6) g/mL sample solutions, the relative standard deviations (RSDs) were all <5%. The detection limit was 8.56 x 10(-10) g/mL for CIMT, 8.69 x 10(-10) g/mL for RANT hydrochloride and 2.35 x 10(-9) g/mL for FAMT (S:N = 3). This method has been successfully implemented for the analysis of H(2)-receptor antagonists in pharmaceuticals.
|
10.1002/bio.969
|
pubmed_434_8728
|
The ileum is approximately the most distal three-fifths of the small intestine and is responsible for the digestion and the absorption of foods. The diagnosis of diseases that affects this segment can be achieved by clinical evaluation and complementary examinations. Not only does ileocolonoscopy allow macroscopical analysis, but also enables biopsies to be carried out for histological evaluation. Only three publications about the description of the endoscopic characteristics of the terminal ileum have been found in the literature. Even so, there have not been found descriptions or classifications in publications that mentioned endoscopic aspect of the terminal ileum, being reported only as normal ileum. Therefore, this strengthens the idea of the lack of knowledge or the non-acceptance of these descriptions and these classifications by the scientific community. Endoscopic aspects of this segment when affected by several diseases vary from normal endoscopically ileum to cases when the macroscopical examination demonstrate specific features of these illnesses. In the present investigation, there are doubts about the need of biopsy of this segment in patients with normal ileoscopy. Moreover, few studies with criteria for macroscopical and microscopical characterization of the ileum were found.
|
pubmed_434_8728
|
pubmed_861_6210
|
OBJECTIVE
Activating KRAS mutations are the most common drivers in the development of non-small cell lung cancer (NSCLC). However, unsuccess of treatment by direct inhibition of KRAS has been proven. Deregulation of PI3K signaling plays an important role in tumorigenesis and drug resistance in NSCLC. The activity of PI3Kα-selective inhibition against KRAS-mutated NSCLC remains largely unknown.
METHODS
Cell proliferation was detected by sulforhodamine B assay. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell signaling was assessed by Western blot and immunohistochemistry. RNA interference was used to down-regulate the expression of cyclin D1. Human NSCLC xenografts were employed to detect therapeutic efficacy in vivo.
RESULTS
CYH33 possessed variable activity against a panel of KRAS-mutated NSCLC cell lines. Although CYH33 blocked AKT phosphorylation in all tested cells, Rb phosphorylation decreased in CYH33-sensitive, but not in CYH33-resistant cells, which was consistent with G1 phase arrest in sensitive cells. Combined treatment with the CDK4/6 inhibitor, PD0332991, and CYH33 displayed synergistic activity against the proliferation of both CYH33-sensitive and CYH33-resistant cells, which was accompanied by enhanced G1-phase arrest. Moreover, down-regulation of cyclin D1 sensitized NSCLC cells to CYH33. Reciprocally, CYH33 abrogated the PD0332991-induced up-regulation of cyclin D1 and phosphorylation of AKT in A549 cells. Co-treatment with these two drugs demonstrated synergistic activity against A549 and H23 xenografts, with enhanced inhibition of Rb phosphorylation.
CONCLUSIONS
Simultaneous inhibition of PI3Kα and CDK4/6 displayed synergistic activity against KRAS-mutated NSCLC. These data provide a mechanistic rationale for the combination of a PI3Kα inhibitor and a CDK4/6 inhibitor for the treatment of KRAS-mutated NSCLC.
|
10.20892/j.issn.2095-3941.2018.0361
|
pubmed_101_12495
|
Acute pancreatitis (AP) is an inflammatory disease that can progress to severe acute pancreatitis (SAP), which increases the risk of death. AP is characterized by inappropriate activation of trypsinogen, infiltration of inflammatory cells, and destruction of secretory cells. Other contributing factors may include calcium (Ca2+) overload, mitochondrial dysfunction, impaired autophagy, and endoplasmic reticulum (ER) stress. In addition, exosomes are also associated with pathophysiological processes of many human diseases and may play a biological role in AP. However, the pathogenic mechanism has not been fully elucidated and needs to be further explored to inform treatment. Recently, the treatment guidelines have changed; minimally invasive therapy is advocated more as the core multidisciplinary participation and "step-up" approach. The surgical procedures have gradually changed from open surgery to minimally invasive surgery that primarily includes percutaneous catheter drainage (PCD), endoscopy, small incision surgery, and video-assisted surgery. The current guidelines for the management of AP have been updated and revised in many aspects. The type of fluid to be used, the timing, volume, and speed of administration for fluid resuscitation has been controversial. In addition, the timing and role of nutritional support and prophylactic antibiotic therapy, as well as the timing of the surgical or endoscopic intervention, and the management of complications still have many uncertainties that could negatively impact the prognosis and patients' quality of life. Consequently, to inform clinicians about optimal treatment, we aimed to review recent advances in the understanding of the pathogenesis of AP and its diagnosis and management.
|
10.21037/atm-20-4802
|
pubmed_724_890
|
Potassium monopersulfate (MPS) is widely used in spa and pool "shock" treatments, yet contact dermatitis associated with MPS has been rarely reported. A patient presented with a generalized scattered dermatitis from the neck down that worsened after spa use. Patch testing elicited a ++ reaction to ammonium persulfate. Contact with ammonium persulfate was ruled out; however, MPS, which can cross-react with ammonium persulfate, was found to be the active ingredient in the patient's spa shock treatments. The dermatitis cleared after the patient switched to a hydrogen peroxide-based shock treatment.
|
pubmed_724_890
|
pubmed_10_2152
|
BACKGROUND
Statins are commonly prescribed worldwide and recent evidence suggests that they may increase the risk of herpes zoster (HZ).
OBJECTIVES
To quantify the effect of statin exposure on the risk of HZ in the U.K.
METHODS
A matched case-control study was conducted using data from U.K. primary care and hospital records. Patients > 18 years with an incident diagnosis of HZ were matched to up to four controls for age, sex and general practice. Patients were included in the statin exposure group if they had ever used a statin, and the daily dosage of the most recent statin prescription and the time since the most recent statin prescription were also recorded. The primary outcome was an incident diagnosis of HZ. Odds ratios (ORs) were estimated from conditional logistic regression and adjusted for potential confounders.
RESULTS
A total of 144 959 incident cases of HZ were matched to 549 336 controls. Adjusted analysis suggested strong evidence for an increase in the risk of HZ related to statin exposure (OR 1·13, 95% confidence interval 1·11-1·15). There was also an increased risk when dosages were increased for patients who were currently or had recently been receiving statin treatment (Ptrend < 0·001), and we found an attenuation of the increased risk of HZ in previous statin users as the time since last statin exposure increased (Ptrend < 0·001).
CONCLUSIONS
These findings are consistent with the hypothesis that statin therapy leads to an increase in the risk of HZ.
|
10.1111/bjd.14815
|
pubmed_737_1092
|
Training in the primary-care child and adolescent mental health should take into consideration the local milieu, national health care education and development. It should aim to improve the mental health knowledge, competency as well as develop professional relationships between various primary, secondary and tertiary-care mental health providers to enhance outcomes. The collaborative training between the various stakeholders in the Child and Adolescent Mental Health (CAMH) should be enhanced. Currently, the favoured methods, to augment the training for practicing Primary-care Physicians, like CME and short training programs with their specific goals, settings and methodology are well documented. However, to improve the skills in CAMH for medical trainees at undergraduate and postgraduate levels, restructuring of the curriculum is essential.
|
10.1007/s12098-011-0429-6
|
pubmed_1027_19891
|
In a controlled study, 26 patients with a history of recurrent syncope were found to have increased arginine vasopressin, corticotrophin, and atrial natriuretic factor levels after 5 minutes of 60 degrees head-up tilt, long before they became hypotensive. The exaggerated neurohormonal response in these patients may indicate a greater sensitivity to central hypovolemia which may predispose to vasovagal syncope, mediated by the vasodilatory effects of atrial natriuretic factor or the sensitization of mechanoreceptors by arginine vasopressin.
|
10.1016/s0002-9149(9x)00084-9
|
pubmed_572_15561
|
Density functional theory (DFT) and time-dependent DFT calculations were performed to evaluate the influence of substituent effect of (1) R = 4-Me, (2) R = 4-OMe, and (3) R = 2,3-OC6H4 on the phenyl ring of (C∧C*)PtII(acac) (C∧C* = phenylimidazole, acac = acetylacetone), respectively, on absorption and phosphorescent spectra properties, as well as the radiative and nonradiative processes. We found that emissions of complexes 2 and 3 originate from the Kasha-like T1 state, whereas that of complex 1 originates from non-Kasha T2 state. Compared with the emission of complex 1, the emission peaks of 2 and 3 are red-shifted, which is attributed to p-π and π-π conjugation effects resulting from the electron-donating groups -OCH3 and -OC6H4 with ligand C∧C*, respectively. The radiative rate constants (κr) of 2 and 3 are larger than that of 1, namely, κr(1) < κr(2) < κr(3), indicating that κr can be efficiently increased by enlarging π-conjugation at the main ligand of (C∧C*)PtII(acac), which can cause the increase of spin-orbit coupling (SOC) matrix elements. At the same time, the activation energy barriers for the rate-limiting step can be largely raised accompanied by enlarging the ability of electron-donation of the substituent group at the main ligand of (C∧C*)PtII(acac), which can cause the decrease of the nonradiative rate constant (κnr), namely, κnr(1) > κnr(2) > κnr(3). According to ΦP = κr/(κr + κnr), the quantum yields should have the sequence ΦP(1) < ΦP(2) < ΦP(3), which is in accordance with the experiment. In addition, to guide experimental synthesis of highly efficient (C∧C*)PtII(acac), a new complex 4 through extending the π-conjugation in the C∧C* ligand of (C∧C*)PtII(acac) was theoretically designed, which has a larger quantum yield than 1-3.
|
10.1021/acs.jpca.7b04329
|
pubmed_626_6433
|
A new Coccidia species is reported from the natural population of Pied Flycatcher (Ficedula hypoleuca) in northern Germany. Sporulated oocysts were found in faeces from 6 of 8 sampled adults. The spherical oocysts of the new Isospora species have a brownish, smooth, bi-layered wall. Average size of sporulated oocysts was 19.4 x 19.3 microm (17.5-22.8 microm x 17.5-22.8 microm ) with a shape index (length/width) of 1.0. The sporulated oocysts have no micropyle or residuum, but enclose several small polar granules that often cluster into 2-3 dumbbell-shaped formations. Sporocysts are slightly elongated, rounded at the end opposite the Stieda body, 15.3 microm x 9.2 microm in size (13.8-16.1 microm x 8.5-10.3 microm ), and have a shape index of 1.7 (1.6-1.8). The Stieda body has a prominent knob-like cap, whereas the substieda body is absent. Sporocysts contain a small compact sporocyst residuum and 4 sporozoites. COI haplotypes identical to those isolated from faecal oocysts were PCR amplified from the blood of 13-day-old nestlings, suggesting that the newly described species has extra-intestinal stages in blood. This represents the first description of a new avian Isospora species supported by molecular sequence data from the same oocysts that are described morphologically.
|
10.1017/S0031182009006131
|
pubmed_527_11695
|
In this paper, a method of restoring longitudinal images is developed. By using the transfer function for longitudinal objects, and inverse filtering, a longitudinal image may be restored. The Fourier theory and sampling theorems for transverse images cannot be used directly in the longitudinal case. A modification and reasonable approximation are introduced. We have numerically established a necessary relationship between just-resolved longitudinal separation (after inverse filtering), noise level, and the taking conditions of object distance and lens diameter. An empirical formula is also found to well-fit the computed results. This formula may be of use for designing optical systems which are to image longitudinal details, such as in robotics or microscopy.
|
10.1364/AO.27.000414
|
pubmed_484_11934
|
The 5HTTLPR polymorphism in the promoter region of the human serotonin transporter (SLC6A4) gene is known to be associated with various stress-related psychological and psychiatric phenomena. We observed that a similar diallelic polymorphism in the orthologous gene of rhesus macaques (Macaca mulatta) was related to the reproductive life history of 580 males residing in the free-ranging colony of Cayo Santiago, Puerto Rico, between 1985 and 1998. At first glance, the polymorphism appeared to be selectively neutral because no difference in total reproductive output was noted between males of different 5HTTLPR genotypes. However, whereas heterozygotes were significantly more reproductive than homozygotes at intermediate age (10-13 yr), the opposite held true before and after this period (n = 682 offspring; randomization P = 0.014). This association, which explains approximately 7% of the observed variation in sire age, most likely reflects different natal dispersal patterns and represents the first reported instance of a genetic influence on reproductive timing in mammals.
|
10.1095/biolreprod.104.038059
|
pubmed_20_22458
|
This study aimed to compare the virology and epidemiology of epidemic keratoconjunctivitis (EKC), pharyngoconjunctival fever (PCF) and acute haemorrhagic conjunctivitis (AHC) outbreaks worldwide caused by the human adenovirus (HAdV) from 1953 to 2013. Eighty-three hexon sequences from 76 conjunctivitis outbreaks were analysed and subtyped using Mega 5.05, Clustal X and SimPlot software. Epidemiology was performed for the area, age and seasonal distribution. A phylogenetic analysis indicated that all the isolates could be divided into three subgenetic lineages, without a common ancestor. The major causes of the outbreaks were Ad8, Ad7 and Ad2 co-infection with enterovirus 70 (EV70) in EKC, PCF and AHC, respectively. The epidemiological findings suggested that EKC and AHC were circulating predominantly in Asia during the early winter and spring, whereas PCF was circulating mainly in China, Australia and the United States during the summer. This study suggests that EKC, AHC and PCF outbreaks have different circulating patterns throughout the world and are caused by different adenovirus serotypes. A global surveillance system should be established to monitor conjunctivitis outbreaks in the future.
|
10.1017/S0950268815003246
|
pubmed_1081_4920
|
The notion of moral exchangeability is scrutinized and its proper place in neonatal care is examined. On influential moral outlooks, the neonate is morally exchangeable. On these views, if the parents are prepared to let go of the neonate with a poor prognosis and opt instead for another child who is healthy, this may be the morally right thing for them to do, and neonatal care ought to ease their choice. The notion of moral exchangeability has a different place in different moral theories. Three theories are examined: deontological ethics (insisting on the sanctity of innocent human life), according to which there is no place for the replacement of 1 child for another. It is different, however, with utilitarianism and in the moral rights theory based on self-ownership. According to utilitarianism, we are all replaceable. According to the moral rights theory, neonates are replaceable to the extent that they have not developed personhood. Even a deontological ethicist of a Kantian bent would concur here with the moral rights theory. Because influential moral theories imply that the neonate is morally exchangeable, it is reasonable within neonatal care, as a general rule, to grant the parents a veto against any attempts to save a child with a poor prognosis. In particular, if the parents are prepared instead to have another, healthy child, this is to be recommended. However, this rule cannot be strict. In rare cases, it is necessary to yield to parents who insist that their neonate be saved despite a poor prognosis.
|
10.1542/peds.2018-0478F
|
pubmed_428_2730
|
BACKGROUND
Although male gender, aging, hypertension, dyslipidemia, and smoking are common risk factors for abdominal aortic aneurysm, diabetes mellitus is an independent negative risk factor. In aneurysm tissue, matrix metalloproteinases (MMPs) expressed by activated macrophages degrades extracellular matrix proteins. In our previous experimental study, we demonstrated that the aneurysmal formation and macrophage activity were suppressed by inhibiting mimicking hyperglycemia (HG) through upregulation of glucose-sensing nuclear receptor, Nr1h2. Here in this study, we focused on the role of HG-induced altered glucose uptake on macrophage activation.
METHODS
RAW264.7 murine macrophage cells were pretreated in cultures containing HG (HG group, 15.5 mM) or normal glucose (NG) concentrations (NG group, 5.5 mM) for 7 d. The culture medium was then changed in both groups to NG conditions, and the cells were stimulated with recombinant murine soluble receptor activator of NF-κB ligand (sRANKL). Macrophage activation was confirmed by tartrate-resistant acid phosphatase (TRAP) staining.
RESULTS
Compared with the NG group, MMP-9 expression in the HG group was significantly suppressed. Glucose uptake was increased in the NG group but not in the HG group during macrophage activation. To determine the mechanism of activation, we studied the expression and distribution of glucose transporters (Gluts) in the macrophages. Although Glut expression was unaffected by glucose pretreatment, membrane translocation of Glut-1 was significantly enhanced in macrophages in the NG group but not in the HG group during activation. Insulin receptor and insulin receptor substrate-1 (IRS-1) messenger RNA, known stimulate to membrane translocation of Gluts, were both decreased by the HG condition but not by the NG condition.
CONCLUSIONS
HG pretreatment suppressed the macrophage activation. sRANKL increased macrophage glucose uptake at NG concentrations, which was impaired by HG pretreatment through the inhibition of Glut1 membrane translocation and the insulin receptor and IRS-1 gene transcription. These data suggest that HG suppressed macrophage activation, through attenuation of glucose uptake via the suppression of the membrane translocation of Glut1 and insulin signaling.
|
10.1016/j.jss.2017.02.009
|
pubmed_1098_18912
|
Algae biomass contains various biological elements, including lipids, proteins, and carbohydrates, making it a viable feedstock for manufacturing biofuels. However, the biggest obstacle to commercializing algal biofuels is their high production costs, primarily related to an algae culture. The extraction of additional high value added bioproducts from algal biomass is thus required to increase the economic viability of producing algae biofuel. This study aims to discuss the economic benefits of a zero-carbon economy and an environmentally sustainable algae resource in decarbonizing the environment through the manufacture of algal-based biofuels from algae biomass for a range of potential uses. In addition, research on the algae biorefineries, with an emphasis on case studies for various cultivation methods, as well as the commercialization of biofuel and bioenergy. Overall, the algal biorefinery offers fresh potential for synthesizing various products.
|
10.1016/j.biortech.2022.128103
|
pubmed_75_16623
|
A microsomal activity of baby hamster kidney cells which cleaves ester-type bound fatty acids from acyl proteins in vitro has been characterized. This activity is also present in microsomal membranes from pig liver, calf kidney, and human mucous cells. Cell free deacylation is described for the Semliki Forest virus acyl proteins E1 and E2 and the precursor of E2 designated p62. Acyl chain cleavage operates with both exogenous and endogenous viral acyl protein substrates. The in vitro cleavage requires microsomes solubilized by detergents of which various kinds are equally effective (Nonidet P-40, Tween 20, sodium deoxycholate, Triton X-100, or octyl-beta-D-glucoside). If microsomes are boiled for 15 min prior to the incubation, deacylation is abolished completely and no radioactivity is released from the palmitoylated acyl proteins during incubation with either detergents or microsomes alone. No changes in the molecular structure of the deacylated Semliki Forest virus proteins were detected, and the cleavage product was identified as free fatty acid. Deacylation is time- and temperature-dependent and can be enhanced by increasing the concentration of microsomal protein in the incubation mixture. It is completely inhibited under acidic conditions (pH 5) and at low temperature (4 degrees C). Deacylation also occurs in the presence of EDTA and bivalent cations such as Mg2+, Mn2+, and Ca2+ which influence the reaction marginally. On the other hand, fatty acid release is drastically reduced with a mixture of Co2+, Zn2+, and Hg2+ ions. The activity is not identical with protein fatty acyltransferase operating in the reverse direction, since a partially purified preparation of this acyltransferase failed to cleave fatty acids from fatty acylated substrate proteins. Taken together, these data lead us to postulate an enzymatic activity which cleaves fatty acids from ester-type fatty acylated proteins, and we propose to designate this enzyme a protein fatty acylesterase.
|
pubmed_75_16623
|
pubmed_1044_8104
|
A novel method based on digital images in time domain combined with convolutional neural network (CNN) is proposed for discrimination and analysis of the adulterated mutton. For this, 195 sample images during the constant temperature heating process (about 10 min) were combined with CNN for qualitative discrimination and quantitative prediction of adulterated mutton. Furthermore, the hypothesis that temperature disturbance can improve the detection ability of adulterated mutton was confirmed by comparing the model performance of the initial heating stage and the entire heating process. The experimental results show that the performance of the latter was superior to that of the former. The accuracy of the qualitative discriminant model was increased by 7.33%, the R2 and RPD of the quantitative prediction model of the duck/pork in adulterated mutton were increased by 0.08/0.07 and 0.85/0.87 respectively, while the RMSE decreased by 0.01/0.01. Consequently, the proposed method can be used for detecting adulterated mutton effectively and accurately.
|
10.1016/j.meatsci.2022.108850
|
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