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pubmed_28_5537
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The efficacy of cancer immunotherapy is dictated by CD8+ T cell infiltration and the nature of the tumor microenvironment (TME). By inflaming the TME to favor CD8+ T cell immunity, radiation is now widely considered as a neoadjuvant for immunomodulation. Here, we observed that local irradiation enhances the infiltration of intratumoral eosinophils, and depletion of eosinophil dampens CD8+ T cell infiltration and diminishes the anti-tumor effectiveness of radiation. Retrospectively, we identified a strong correlation between eosinophilia and survival benefit in radiation-treated cancer patients. Experimentally, we further show that radiation enhances the intratumoral infiltration of adoptive transferred T cells therapy, bolstering eosinophils by intravenous interleukin-5 administration promotes the efficacy of radiation-induced abscopal effect. Together, these results suggest that eosinophil mobilization can be considered as a mechanistically relevant biomarker for predicting the effectiveness of pre-immunotherapy radiation, as well as a new strategy to enhance T cell-mediated immunotherapy against cancers.
|
10.1126/sciadv.abc7609
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pubmed_851_10164
|
Rapid DNA sequencing and analysis has been a long-sought goal in remote research and point-of-care medicine. In microgravity, DNA sequencing can facilitate novel astrobiological research and close monitoring of crew health, but spaceflight places stringent restrictions on the mass and volume of instruments, crew operation time, and instrument functionality. The recent emergence of portable, nanopore-based tools with streamlined sample preparation protocols finally enables DNA sequencing on missions in microgravity. As a first step toward sequencing in space and aboard the International Space Station (ISS), we tested the Oxford Nanopore Technologies MinION during a parabolic flight to understand the effects of variable gravity on the instrument and data. In a successful proof-of-principle experiment, we found that the instrument generated DNA reads over the course of the flight, including the first ever sequenced in microgravity, and additional reads measured after the flight concluded its parabolas. Here we detail modifications to the sample-loading procedures to facilitate nanopore sequencing aboard the ISS and in other microgravity environments. We also evaluate existing analysis methods and outline two new approaches, the first based on a wave-fingerprint method and the second on entropy signal mapping. Computationally light analysis methods offer the potential for in situ species identification, but are limited by the error profiles (stays, skips, and mismatches) of older nanopore data. Higher accuracies attainable with modified sample processing methods and the latest version of flow cells will further enable the use of nanopore sequencers for diagnostics and research in space.
|
10.1038/npjmgrav.2016.35
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pubmed_242_12498
|
BACKGROUND
Use of risk calculators for specific diseases is increasing, with an underlying assumption that they promote risk reduction as users become better informed and motivated to take preventive action. Empirical data to support this are, however, sparse and contradictory.
AIM
To explore user reactions to a cardiovascular risk calculator for people with type 2 diabetes. Objectives were to identify cognitive and emotional reactions to the presentation of risk, with a view to understanding whether and how such a calculator could help motivate users to adopt healthier behaviours and/or improve adherence to medication.
DESIGN AND SETTING
Qualitative study combining data from focus groups and individual user experience. Adults with type 2 diabetes were recruited through website advertisements and posters displayed at local GP practices and diabetes groups.
METHOD
Participants used a risk calculator that provided individualised estimates of cardiovascular risk. Estimates were based on UK Prospective Diabetes Study (UKPDS) data, supplemented with data from trials and systematic reviews. Risk information was presented using natural frequencies, visual displays, and a range of formats. Data were recorded and transcribed, then analysed by a multidisciplinary group.
RESULTS
Thirty-six participants contributed data. Users demonstrated a range of complex cognitive and emotional responses, which might explain the lack of change in health behaviours demonstrated in the literature.
CONCLUSION
Cardiovascular risk calculators for people with diabetes may best be used in conjunction with health professionals who can guide the user through the calculator and help them use the resulting risk information as a source of motivation and encouragement.
|
10.3399/bjgp15X683953
|
pubmed_749_4056
|
Crocin (CRO) and safranal (SAF) are bioactive constituents of saffron (dried stigma of Crocus sativus flower), an expensive spice with medicinal properties. Aqueous extract of saffron is known for its antigenotoxic effect against environmental genotoxins/carcinogens. However, there is need to identify saffron constituents responsible for this antigenotoxic effect. The aim of our investigation was to ascertain the role of CRO and SAF as inhibitors of in vivo genotoxic stress. For this purpose, Swiss albino mice were pretreated with CRO (50-mg/kg body weight (bw))/SAF (0.025- and 0.25-ml/kg bw) by gavage for 2 days. Thereafter, the pretreated mice were exposed to the genotoxic agents: (1) gamma radiation (GR; 2 Gy), (2) urethane (URE; 800 mg/kg) and (3) procarbazine (PCB; 60 mg/kg). In addition, CRO (50 mg/kg) was co-administered with the nitrosation reaction mixture of methylurea (MU; 300-mg/kg bw) + sodium nitrite (15 mg/kg) which can form N-nitroso-N-MU in the stomach. Genotoxic damage was measured by performing the bone marrow micronucleus test. Results obtained demonstrated significant reductions in the incidence of micronucleated polychromatic erythrocytes in the bone marrow of mice pretreated with CRO/SAF before exposure to the above DNA damaging agents, GR, URE and PCB. Co-administration of CRO with the nitrosation reaction mixture led to significant decrease in genotoxicity when compared to nitrosation reaction mixture alone. Histopathological studies revealed that these saffron constituents reduced testicular cell damage induced by the test genotoxins. The cell-free DNA-nicking assay using pBR322 DNA showed significant protective effects of CRO against hydroxyl radical-induced strand breaks.
|
10.1177/0960327116689715
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pubmed_590_1624
|
In multiobjective optimization methods, multiple conflicting objectives are typically converted into a single objective optimization problem with the help of scalarizing functions. The conic scalarizing function is a general characterization of Benson proper efficient solutions of non-convex multiobjective problems in terms of saddle points of scalar Lagrangian functions. This approach preserves convexity. The conic scalarizing function, as a part of a posteriori or a priori methods, has successfully been applied to several real-life problems. In this paper, we propose a conic scalarizing function based interactive reference point procedure where the decision maker actively takes part in the solution process and directs the search according to her or his preferences. An algorithmic framework for the interactive solution of multiple objective optimization problems is presented and is utilized for solving some illustrative examples.
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10.1155/2014/242803
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pubmed_886_6058
|
Gas-filled microbubbles are widely used in diagnostic imaging. Recent developments have greatly enhanced the potential use of microbubbles for both diagnostic and therapeutic applications. For the potential use of microbubbles in therapeutic applications, the chemical nature of the shell and its mechanical properties are crucial, and requires a tailored synthetic approach. This review describes methods of preparation, mechanism of action, in vitro and in vivo stability and structural/functional characterization of microbubbles. New mechanisms for ultrasound-enhanced local drug and gene delivery are reviewed. Different strategies used to target microbubbles to regions of disease and some of the recent experiences in ultrasound image-guided therapy are discussed.
|
10.2174/156802610791384180
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pubmed_869_1158
|
MicroRNAs (miRNAs) are a class of 20-24 nt non-coding RNAs that regulate gene expression primarily through post-transcriptional repression or mRNA degradation in a sequence-specific manner. The roles of miRNAs are just beginning to be understood, but the study of miRNA function has been limited by poor understanding of the general principles of gene regulation by miRNAs. Here we used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular system to investigate miRNA-directed regulation of VEGF and other angiogenic factors under hypoxia, and to explore the principles of gene regulation by miRNAs. Through computational analysis, 96 miRNAs were predicted as putative regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and four other VEGF-expressing cell lines, we found that only some of these miRNAs could be involved in VEGF regulation, and that VEGF may be regulated by different miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF in different cells. Some of these miRNAs also co-regulate other angiogenic factors (differential regulation and co-regulation principle). We also found that VEGF was regulated by multiple miRNAs using different combinations, including both coordinate and competitive interactions. The coordinate principle states that miRNAs with independent binding sites in a gene can produce coordinate action to increase the repressive effect of miRNAs on this gene. By contrast, the competitive principle states when multiple miRNAs compete with each other for a common binding site, or when a functional miRNA competes with a false positive miRNA for the same binding site, the repressive effects of miRNAs may be decreased. Through the competitive principle, false positive miRNAs, which cannot directly repress gene expression, can sometimes play a role in miRNA-mediated gene regulation. The competitive principle, differential regulation, multi-miRNA binding sites, and false positive miRNAs might be useful strategies in the avoidance of unwanted cross-action among genes targeted by miRNAs with multiple targets.
|
10.1371/journal.pone.0000116
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pubmed_439_5786
|
BACKGROUND
Although hypercoagulability using D-dimer levels may be a useful marker for predicting outcomes in ischemic stroke patients with cancer, other biological markers for predicting outcomes are unclear. We aimed to investigate the associations between several biological markers and short-term or long-term outcomes among ischemic stroke patients with cancer.
METHODS
Consecutive acute ischemic stroke patients with cancer (n = 309) were registered. Biological markers such as hemoglobin, albumin, C-reactive protein and D-dimer levels were assessed. Stroke outcomes, namely, a 3-month modified Rankin Scale score indicating poor functional outcome (mRS score of 3-6) and 1-year survival, were assessed.
RESULTS
Of the 277 patients who could be assessed for 3 months outcome, 131 patients (47.3%) had a poor outcome at 3 months. Multivariable analysis revealed that increased D-dimer levels and decreased albumin levels were independently associated with poor stroke outcomes (adjusted odds ratio [aOR]: 1.04, 95% confidence interval [CI]: 1.00-1.08, and aOR: 0.50, 95% CI: 0.31-0.80, respectively). Of 309 patients, 70 patients (22.7%) died during the follow-up period (median, 241 days). Multivariate Cox proportional hazard analyses showed that high D-dimer levels and hypoalbuminemia were independently associated with mortality (adjusted hazard ratio [aHR]: 2.65, 95% CI: 1.37-5.12, and aHR: 2.29, 95% CI: 1.21-4.49, respectively). The effect of each biological marker on mortality was notably observed among patients with active cancer but not among those with nonactive cancer.
CONCLUSION
Low albumin levels were independently associated with short- and long-term outcomes, as were D-dimer levels, in acute ischemic stroke patients with cancer.
|
10.1016/j.jns.2022.120246
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pubmed_726_1808
|
Concern about biodiversity loss has led to increased public investment in conservation. Whereas there is a widespread perception that such initiatives have been unsuccessful, there are few quantitative tests of this perception. Here, we evaluate whether rates of biodiversity change have altered in recent decades in three European countries (Great Britain, Netherlands and Belgium) for plants and flower visiting insects. We compared four 20-year periods, comparing periods of rapid land-use intensification and natural habitat loss (1930-1990) with a period of increased conservation investment (post-1990). We found that extensive species richness loss and biotic homogenisation occurred before 1990, whereas these negative trends became substantially less accentuated during recent decades, being partially reversed for certain taxa (e.g. bees in Great Britain and Netherlands). These results highlight the potential to maintain or even restore current species assemblages (which despite past extinctions are still of great conservation value), at least in regions where large-scale land-use intensification and natural habitat loss has ceased.
|
10.1111/ele.12121
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pubmed_937_6782
|
Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified "Myers' cocktail," which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author's clinical experiences, and discusses potential side effects and precautions.
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pubmed_937_6782
|
pubmed_607_11047
|
A short review is given about some of the data reported in the literature on dehydroepiandrosterone and its derivatives, delta 5-androstenediol (hermaphrodiol) and sexual steroid binding globulin (SHBG) in breast cancer patients. The reported results lead to hypothesis that a decreased SHBG binding activity may be found in these patients.
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pubmed_607_11047
|
pubmed_265_254
|
Recombinant adenovirus vectors (AdV) have been considered a potential vehicle for performing gene therapy in patients suffering from Duchenne muscular dystrophy but are limited by a cellular and humoral immune response that prevents long-term transgene expression as well as effective transduction after AdV readministration. Conventional immunosuppressive agents such as cyclosporine and FK506, which act by interfering with CD3-T-cell receptor-mediated signaling via calcineurin, are only partially effective in reversing these phenomena and may also produce substantial organ toxicity. We hypothesized that activation of redundant T-cell activation pathways could limit the effectiveness of these drugs at clinically tolerable doses. Therefore, we have tested the ability of immunomodulatory immunoglobulins (Ig) with different modes of action to facilitate AdV-mediated gene transfer to adult dystrophic (mdx) mice. When used in isolation, immunomodulatory Ig (anti-intercellular adhesion molecule-1, anti-leukocyte function-associated antigen-1, anti-CD2, and CTLA4Ig) were only mildly effective in mitigating cellular and/or humoral immunity against adenovirus capsid proteins and the therapeutic transgene product, dystrophin. However, the combination of FK506 plus CTLA4Ig abrogated the immune response against adenovirus proteins and dystrophin to a degree not achievable with the use of either agent alone. At 30 days after AdV injection, >90% of myofibers could be found to express dystrophin with little or no evidence of a cellular immune response against transduced fibers. In addition, the humoral immune response was markedly suppressed, and this was associated with increased transduction efficiency following vector readministration. These data suggest that by facilitating both primary and secondary transduction after AdV administration, combined targeting of CD3-T-cell receptor-mediated signaling via calcineurin and the B7:CD28 costimulatory pathway could greatly increase the potential utility of AdV-mediated gene transfer as a therapeutic modality for genetic diseases such as Duchenne muscular dystrophy that will require long-term transgene expression and repeated vector delivery.
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10.1128/JVI.72.6.4601-4609.1998
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pubmed_299_553
|
The obturator hernia is a rare type of hernia that can present a diagnostic challenge for the clinician. We report a case of an 88-year-old woman who presented with a history of right iliac fossa pain, bilious vomiting and diarrhoea. Non-specific findings on examination and blood tests made the diagnosis difficult, however, a CT scan of her abdomen revealed the site of the obstruction and the patient was taken to theatre for emergency surgery. We review the literature with focus on the diagnosis of obturator hernias and the different surgical approaches used. The authors believe that this case is of educational value to healthcare professionals, particularly those working in general practice, emergency departments and on surgical teams. It highlights to doctors that patients with incarcerated obturator hernias can present with or without overt signs of intestinal obstruction and emphasises the fact that an obturator hernia can be an important cause of intestinal obstruction in a thin, elderly woman.
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pubmed_299_553
|
pubmed_315_23408
|
The combined effect of yield stress and irreversible boundary reaction on dispersion process in a Casson fluid flowing in a conduit (pipe/channel) is studied using the generalized dispersion model proposed by Sankarasubramanian and Gill (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A 333:115-132, 1973). The study describes the development of dispersive transport following the injection of a tracer in terms of the three effective transport coefficients, viz., exchange, convection, and dispersion coefficients. The exchange coefficient does not depend on yield stress but the convection and dispersion coefficients depend on yield stress or equivalently plug flow region. For large times, when the plug flow radius is one-tenth of pipe radius, the convective coefficient is reduced by 0.41 times of the corresponding value for a Newtonian fluid at equivalent wall absorption parameter; in channel case the reduction is by 39%. It is seen that the asymptotic dispersion coefficient decreases with increase in wall absorption parameter and yield stress of the fluid. When the plug radius in pipe (channel) is 0.1, depending upon the values of wall absorption parameter, say (0.01-100) the reduction factor in dispersion coefficient is in the range (0.1-0.3) in comparison to the values of the Newtonian case. The results reduce to those of Sankarasubramanian and Gill (Sankarasubramanian, R., and W. N. Gill. Proc. R. Soc. London, Ser. A 333:115-132, 1973) when there is no yield stress for the pipe flow analysis and to those of Dash et al. (Dash, R. K., G. Jayaraman, and K. N. Mehta. Ann. Biomed. Eng. 28:373-385, 2000) when there is no interphase mass transfer. The study can be used as a starting first approximation solution for studying the dispersion in the cardiovascular system.
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10.1023/b:abme.0000030236.75826.8a
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pubmed_64_14061
|
Anesthesiology is a medical specialty that provides perioperative care for patients undergoing medical interventions requiring sedation or critical monitoring including surgery, imaging, and other diagnostic and therapeutic procedures [...].
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10.3390/children8030201
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pubmed_596_22027
|
AIM
The aim of this work was to compare the effect of intraumbilical injection of three different uterotonic solutions in the management of retained placenta.
MATERIALS AND METHODS
This study was conducted in Ain-Shams University Maternity Hospital, Cairo, Egypt. A total of 78 women with retained placenta (>30 min after delivery of the fetus) were included in the study and subdivided into three groups. Each group was injected with a different type of uterotonic into the umbilical vein after clamping it using the Pipingas technique. Uterotonics used were either 20 IU oxytocin dissolved in 30 mL saline (n=26), ergometrine 0.2 mg dissolved in 30 mL saline (n=27) or misoprostol 800 µg dissolved in 30 mL saline (n=25).
RESULTS
The overall success rate of spontaneous placental separation within 30 min after intraumbilical injection of uterotonics was 56/78 (71.79%). The success rate was higher with misoprostol when compared to oxytocin and ergometrine but the difference was not significant (20/25 [80%], 19/26 [73.08%], 17/27 [62.96%], respectively, P>0.05). The injection-to-separation interval was significantly shorter in the misoprostol group than in the oxytocin and ergometrine groups (7.0±2.2 min, 13.14±3.76 min, 22.5±4.37 min, respectively, P<0.001).
CONCLUSION
Intraumbilical injection of uterotonics, namely oxytocin, ergometrine and dissolved misoprostol in saline, are closely effective in the management of retained placenta, with misoprostol being slightly more effective. This method may have a role in minimizing the need for manual removal of the placenta and its adverse sequelae.
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10.1111/j.1447-0756.2010.01499.x
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pubmed_476_3672
|
The incidence of psoriasis in patients with rheumatoid arthritis (RA) is higher than in the general population. In addition, psoriasis may negatively affect the severity of rheumatological diseases in patients with autoinflammatory or autoimmune diseases. In this study, we evaluated the effect of psoriasis or a family history of psoriasis on the characteristics of RA. This is a cross-sectional study. We included 737 RA patients who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) RA Classification Criteria, but did not meet the CASPAR psoriatic arthritis criteria. Subsequently, we compared disease activity, the need for biologic therapy, the number of conventional synthetic disease-modifying anti-rheumatic drugs taken, the frequency of erosive disease and extra-articular involvement, glucocorticoid doses and the Stanford Health Assessment Questionnaire scores between patients with and without a history of psoriasis, and patients with and without a family history of psoriasis. Thirteen (1.8%) patients had psoriasis, while 58 (7.9%) had a family history of psoriasis in first- or seconddegree relatives. All outcome parameters were found to be similar between the groups. We show that concomitant psoriasis has no effect on the evaluated disease characteristics of RA.
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10.4081/reumatismo.2021.1453
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pubmed_34_10744
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PURPOSE
Portal vein thrombi have been observed after restorative proctocolectomy and ileal pouch-anal anastomosis, and present as a clinical spectrum of abdominal pain, fever, and leukocytosis. Anticoagulation treatment is usually associated with resolution of symptoms. However, the long-term consequences and effect on pouch function are not known. The purpose of this study was to analyze the long-term functional outcome of patients with confirmed portal vein thrombi after restorative proctocolectomy.
METHODS
A retrospective study of all patients undergoing restorative proctocolectomy from January 1997 to 2000 was performed. A case-control study was designed that matched 37 patients with confirmed portal vein thrombi in this period with 133 patients without portal vein thrombi; the groups were compared with respect to pouch function and quality of life by using the Global Cleveland Clinic Quality of Life Questionnaire for pelvic pouch patients.
RESULTS
The mean follow-up was 4.73 (range, 4.21-7.28) years. The percentage of male patients was 58.8. The most common diagnosis was ulcerative colitis (62.4 percent). There were no significant differences between portal vein thrombi patients and controls with respect to pouch function (number of bowel movements, urgency, incontinence), episodes of pouchitis, or quality of life.
CONCLUSIONS
Portal vein thrombi can be a serious complication after restorative proctocolectomy that usually resolves with anticoagulation therapy. Long-term pouch function and quality of life are not affected.
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10.1007/s10350-007-0297-3
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pubmed_236_13113
|
Immunohistochemical stains using antibody to epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF-alpha) were applied to 67 cases of renal cell carcinoma retrieved from the files of the Division of Surgical Pathology. The 64 patients (33 females, 31 males) ranged in age from 35 to 87 years (mean, 61 years). Two patients had more than one renal carcinoma included in this study. Fifty-seven cases (85%) expressed EGFR, with staining largely confined to the cell membrane. Staining intensity was directly correlated with tumor grade (P = 0.02, T test), size (P = 0.04), and stage (P = 0.01). Those cases with more intense EGFR staining also appear to have shorter patient survival than those showing less intense staining (43 mo versus 63 mo, P = 0.05). Forty-nine cases (73%) expressed TGF-alpha in a distribution similar to that of EGFR. There was no significant correlation between TGF-alpha staining intensity and tumor size, stage, or grade. When the tumor expressed either EGFR or TGF-alpha but not both proteins, average patient survival was 38 months, while the average survival of those patients whose tumors expressed both EGFR and TGF-alpha was 61 months (P = 0.04). Three of eleven cases, all of which expressed EGFR, were felt to show EGFR gene amplification using a modification of the differential polymerase chain reaction on archival, formalin-fixed, paraffin-embedded tissue. EGFR and TGF-alpha likely play a role in the progression of renal cell carcinoma, and their coexpression may have favorable prognostic implications.
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pubmed_236_13113
|
pubmed_259_9294
|
UNLABELLED
PET using (18)F-FDG is increasingly used for the diagnosis and grading of tumors. Several studies have been performed that evaluate the diagnostic and grading performance of (18)F-FDG PET for soft-tissue sarcoma, but each study has had a limited sample size. Therefore, we undertook a comprehensive meta-analysis of the evidence.
METHODS
Relevant studies were identified from MEDLINE and EMBASE. Diagnostic and grading performance were evaluated for qualitative visualization; standard uptake value (SUV, cutoffs of 2.0 and 3.0); and metabolic rate of glucose (MRG, cutoff of 6.0 micro mol/100 g/min). Quantitative data synthesis included independent weighting of sensitivity and specificity, construction of summary receiver operating characteristic curves, and pooled analyses.
RESULTS
The meta-analysis included 15 studies with 441 soft-tissue lesions (227 malignant, 214 benign). For diagnosis of malignant versus benign lesions, typical pairs of sensitivity and specificity estimates from the summary receiver operating characteristic curves were 92% and 73% for qualitative visualization; 87% and 79% for SUV 2.0; 70% and 87% for SUV 3.0; and 74% and 73% for MRG 6.0. Diagnostic performance was similar for primary and recurrent lesions. By qualitative interpretation, (18)F-FDG was positive in all intermediate/high-grade tumors (95% confidence interval [CI], 97.3%-100%), 74.4% (95% CI, 58.6%-85.9%) of low-grade tumors, and 39.3% (95% CI, 29.1%-50.3%) of benign lesions (including 11 of 12 inflammatory lesions). Using an SUV cutoff of 2.0, respective rates were 89.4% (95% CI, 79.4%-95.6%), 33.1% (95% CI, 15.6%-55.3%), and 19.1% (95% CI, 10.6%-30.5%). Limited data on comparisons with MRI and CT showed no differences against (18)F-FDG PET in diagnosing recurrent and metastatic disease.
CONCLUSION
(18)F-FDG PET has very good discriminating ability in the evaluation of both primary and recurrent soft-tissue lesions. (18)F-FDG PET may be helpful in tumor grading but offers inadequate discrimination between low-grade tumors and benign lesions.
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pubmed_259_9294
|
pubmed_1051_19362
|
BACKGROUND
The aim of this study is to determine whether regional abdominal wall nerve block is a superior to epidural anesthesia (EA) after hepatectomy.
METHODS
Patients undergoing open hepatectomy in the NSQIP targeted file (2014-2016) were identified. Those with INR > 1.5, Platelets < 100, bleeding disorders, undergoing liver ablation without resection, and spinal anesthesia were excluded. Patients with regional abdominal wall nerve block (RAB), mostly transversus abdominis plane (TAP) block, were matched (1:1) to those undergoing EA using propensity scores to adjust for baseline differences.
RESULTS
Out of 1727 patients who met our inclusion criteria, 361 (21%) had RAB. Of whom 345 were matched (1:1) to those who underwent EA. The matched cohort was well-balanced regarding preoperative characteristics, extent of hepatectomy, concurrent ablations as well as biliary reconstruction. RAB was associated with shorter hospital stay (median: 6 days vs. 5 days, p = 0.007). Overall morbidity (44.1% vs. 39.4%, p = 0.217), serious morbidity (27% vs. 25.2%, p = 0.603), and mortality (2.6% vs. 2.3%, p = 0.806) were not different between the two groups. Individual complications, readmission rate, and blood transfusion were not different between the two groups.
CONCLUSION
Regional abdominal nerve block is associated with shorter hospital stay than epidural anesthesia without an increase in overall postoperative morbidity or mortality. RAB is a viable alternative anesthesia adjunct to EA in patients undergoing hepatectomy. However, given the retrospective nature of this study further studies comparing the modalities should be considered to definitively define the utility of RAB.
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10.1007/s00464-022-09109-w
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pubmed_95_918
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PURPOSE
For treatment of lung cancer, dose heterogeneity corrections and subsequent prescription alteration remain controversial. Previous dosimetry studies based on slab geometry with a single beam geometry do not represent the clinical situation. A circumscribed tumor within lung poses a more complex problem. Energy choice also remains controversial.
METHODS AND MATERIALS
An anthropomorphic phantom was modified by replacing lung cylinders (2.5 and 5.0 cm diameters by 5.0 cm length) with muscle-equivalent cylinders. The phantom was scanned on a CT simulator. Gross, clinical, and planning target volumes (GTV, CTV, PTV1 including tumor and regional nodes, PTV2 including tumor only) were designated slice-by-slice. Three-dimensional planning was performed with large fields (AP/PA/RPO) covering PTV1 and boost fields optimized for each PTV2, for 6 and 18 MV photons. Homogeneous, Ratio-Tissue-Air-Ratio (RTAR), and convolution-adapted RTAR (CARTAR) calculation algorithms were tested. Film was placed between phantom slices at the "tumor" levels. The phantom was irradiated with monitor units corresponding to homogeneous calculations, based on a homogeneous prescription. Measured and calculated doses were compared by isodoses and dose volume histograms. Ionization chambers and TLDs were also used for some test cases.
RESULTS
The measured minimum dose covering PTV2 was within 5% of the homogeneous prescription dose of 70 Gy for 6 MV photons, while a lower dose (89% of prescription dose) was measured for 18 MV. The algorithms overpredicted the minimum dose to PTV2 by 6-18%. If the monitor units had been reduced according to simplistic heterogeneous calculations, the small PTV2 would have only been covered by 58 Gy for 18 MV irradiation. Based on this, a clinician may opt to actually increase the prescribed dose, thereby offsetting decreased monitor units. None of the algorithms predicted the diffuse penumbra associated with 18 MV photons in lung.
CONCLUSION
Before adjusting dose prescriptions based on heterogeneity corrections, realistic phantom studies must be performed. The accuracy and effect of the corrections must then be assessed. The deficient coverage of PTV2 by the 18 MV beam compares unfavorably with the slight increase (5%) in hot spots associated with 6 MV. Our studies support strong caution before reducing dose prescriptions based on simple algorithms.
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10.1016/s0360-3016(97)00110-7
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pubmed_852_23425
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The safety and efficacy of an inactivated oil-emulsion infectious coryza vaccine containing three Avibacterium paragallinarum isolates (one each of Page serovars A, B, and C) was evaluated. The safety of six batches of the vaccine was confirmed by testing with chickens vaccinated with a single large dose or vaccinated repeatedly with a normal dose. Efficacy tests were carried out on three batches of vaccine using both specific pathogen free (SPF) chickens and conventional chickens. In SPF chickens given a single vaccination at 42 days of age, the protection rate against all three serovars of Av. paragallinarum was at least 80% at 30 days post vaccination. The conventional chickens, which were immunized at 42 and 110 days of age, were challenged at 9 months post the second vaccination and the protection rate was at least 80% for all three serovars. The effect of storage on the vaccine was evaluated in SPF chickens using three batches of vaccine stored at 4-8°C for 1 year. The protection rate against challenge from all three serovars (single vaccination at 42 days of age and challenge at 30 days post-vaccination) was at least 80%.
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pubmed_852_23425
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pubmed_123_5922
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1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin. In addition, crotapotin (10 microg/paw) did not affect the release of 6-oxo-prostaglandin Fla, and TXB2 induced by ovalbumin in sensitized guinea-pig isolated lungs.5. Our results indicate that the anti-inflammatory activity of crotapotin is not due to endogenous corticosteroid release or inhibition of cyclo-oxygenase activity. It is possible that crotapotin may interact with extracellular PLA2 generated during the inflammatory process thereby reducing its hydrolytic activity.
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10.1111/j.1476-5381.1995.tb17178.x
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pubmed_916_11392
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Collective construction of topologically complex structures is one of the triumphs of social behavior. For example, many ant species construct underground nests composed of networks of tunnels and chambers. Excavation by these 'superorganisms' depends on the biomechanics of substrate manipulation, the interaction of individuals, and media stability and cohesiveness. To discover principles of robust social excavation, we used X-ray computed tomography to monitor the growth in three dimensions of nests built by groups of fire ants (Solenopsis invicta) in laboratory substrates composed of silica particles, manipulating two substrate properties: particle size and gravimetric moisture content. Ants were capable of nest construction in all substrates tested other than completely dry or fully saturated; for a given particle size, nest volume was relatively insensitive to moisture content. Tunnels were deepest at intermediate moisture content and the maximum tunnel depth correlated with measured yield force on small rod-shaped intruders (a proxy for cohesive strength). This implies that increased cohesive strength allowed creation of tunnels that were resistant to perturbation but did not decrease individual excavation ability. Ants used two distinct behaviors to create pellets composed of wetted particles, depending on substrate composition. However, despite the ability to create larger stable pellets in more cohesive substrates, pellet sizes were similar across all conditions. We posit that this pellet size balances the individual's load-carrying ability with the need to carry this pellet through confined crowded tunnels. We conclude that effective excavation of similarly shaped nests can occur in a diversity of substrates through sophisticated digging behaviors by individuals which accommodate both differing substrate properties and the need to work within the collective.
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10.1242/jeb.113795
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pubmed_91_8613
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ATP increases microtubule steady state assembly and disassembly rates in vitro in a concentration-dependent manner. Bovine brain microtubules, composed of 75% tubulin and 25% high molecular weight microtubule-associated proteins (MAPs), were purified by three cycles of assembly and disassembly in the absence of ATP. When assembled to steady state, these microtubules add dimers at one end and lose them at the other in a unidirectional assembly-disassembly process. In the presence of 1.0 mM ATP the unidirectional flow of tubulin from one end of the microtubules to the other increases as much as 20 fold, as revealed by loss of 3H-GTP from uniformly labeled microtubules under GTP chase conditions and by the rate of disassembly following addition of 50 microM podophyllotoxin. UTP, CTP and 5' adenylylimidodiphosphate (AMP-PNP) cannot substitute for ATP in producing this effect. Furthermore, the increase in steady state flow rate persists afer ATP is removed. Thus microtubules assembled in ATP and centrifuged through sucrose cushions to separate them from nucleotides continue to exhibit increased rates in the next assembly cycle in the absence of ATP. It is possible that an ATP-dependent microtubule protein kinase is responsible for the observed increase in tubulin flow rate. A kinase activity associated with brain MAPs has been reported to be cAMP-dependent (Sloboda et al., 1975). We have found an adenylate cyclase activity associated with these microtubules. Whether the adenylate cyclase is a contaminant or due to a specific microtubules-associated protein, and whether its activity is functionally linked to the increased rate of assembly and disassembly in the presence of ATP, remain to be determined.
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10.1016/0092-8674(79)90122-3
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pubmed_458_15648
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The guidelines of the German Orthopaedic Societies regarding the treatment of lateral elbow epicondylitis were analysed on the ground of recently published reviews or randomised placebo-controlled trials (RCT). For the acute phase, reviews or RCTs failed to show a clinical effect beyond placebo if follow-up was extended over 6 weeks. For the chronic phase a current Cochrane review failed to identify any controlled trial regarding surgical procedures during the last decades. Without an adequate control group, it is not possible to draw any meaningful conclusions about the value of this modality of treatment. Therefore surgery is not indicated before repetitive low-energy extracorporeal shock wave therapy (ESWT) has been applied. This novel treatment, under strictly standardized conditions, showed effects beyond placebo in independent randomised placebo-controlled trials for follow-up periods of 3 and 6 months. To date there exists no evidence-based therapeutic algorithm for the treatment of acute and chronic tennis elbow. Even medium-term effects should be regarded as either a placebo effect or natural regression to the mean.
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10.1055/s-2004-820317
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pubmed_934_24783
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Tin sulfide (SnS), as a promising absorber material in thin-film photovoltaic devices, is described. Here, it is confirmed that SnS evaporates congruently, which provides facile composition control akin to cadmium telluride. A SnS heterojunction solar cell is demons trated, which has a power conversion efficiency of 3.88% (certified), and an empirical loss analysis is presented to guide further performance improvements.
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10.1002/adma.201402219
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pubmed_694_2851
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The mdm17 mutation causes temperature-dependent defects in mitochondrial inheritance, mitochondrial morphology, and the maintenance of mitochondrial DNA in the yeast Saccharomyces cerevisiae. Defects in mitochondrial transmission to daughter buds and changes in mitochondrial morphology were apparent within 30 min after shifting cells to 37 degrees C, while loss of the mitochondrial genome occurred after 4-24 h at the elevated temperature. The mdm17 lesion mapped to MGM1, a gene encoding a dynamin-like GTPase previously implicated in mitochondrial genome maintenance, and the cloned MGM1 gene complements all of the mdm17 mutant phenotypes. Cells with an mgm1-null mutation displayed aberrant mitochondrial inheritance and morphology. A version of mgm1 mutated in a conserved residue in the putative GTP-binding site was unable to complement any of the mutant defects. It also caused aberrant mitochondrial distribution and morphology when expressed at high levels in cells that also contained a wild-type copy of the gene. Mgm1p was localized to the mitochondrial outer membrane and fractionated as a component of a high molecular weight complex. These results indicate that Mgm1p is a mitochondrial inheritance and morphology component that functions on the mitochondrial surface.
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10.1083/jcb.144.4.711
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pubmed_211_16568
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Endomorphin-1 and endomorphin-2 are newly identified endogenous peptides and have high affinity and selectivity for mu-opioid receptors. The present experiments were conducted to determine whether intracisternal injection of these peptides would produce an itch-associated response and antinociception and to compare their effects to that of morphine. Endomorphin-1 and endomorphin-2 (0.3-3 nmol/mouse) elicited facial scratching characterized by bell-shaped dose-response curves with a peak effect at endomorphin-1 at 0.3 nmol/mouse and endomorphin-2 at 1 nmol/mouse. Their peak effects were inhibited by subcutaneous pretreatment with naloxone (1 mg/kg). Morphine (0.3-30 nmol/mouse) produced facial scratching, and its dose-response curve was also bell-shaped. Scratching of the body trunk, head and ears were not elicited by these doses of endomorphins and morphine. Endomorphin-1 and -2 at doses of 0.3-3 nmol/mouse produced dose-dependent antinociception, as measured with the tail-pressure test. The potency and duration of actions of these peptides were comparable to those of morphine. The results suggest that endomorphin-1 and endomorphin-2 are involved in itch-signaling and pain-inhibiting functions of the brain.
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10.1254/jjp.78.337
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pubmed_980_13770
|
BACKGROUND
Recent experimental and clinical studies have suggested that Hwangryunhaedok-tang (HHT), an herbal formula, could improve the lipid profiles in patients with dyslipidemia. This systematic review aimed to evaluate the effectiveness and safety of HHT monotherapy or adjunctive HHT therapy with conventional lipid-lowering drugs in managing dyslipidemia.
METHODS
Twelve English, Korean, Chinese, and Japanese databases were comprehensively searched from their inception to January 2020. Randomized controlled trials (RCTs) using HHT monotherapy or adjunctive HHT therapy for dyslipidemic patients were included. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) level. Descriptive analyses of participant details, interventions, and outcomes were conducted and where appropriate data were available, a meta-analysis was performed and presented as a risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CIs). The risk of bias was assessed using the Cochrane risk of bias tool and the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
Nine RCTs with 536 participants were included. In comparison with lipid-lowering drugs alone, HHT as an adjunctive therapy to lipid-lowering drugs or as a monotherapy showed significantly superior (MD -1.15 mmol/L, 95% CI -1.25 to -1.05) or inferior results (MD 0.23 mmol/L, 95% CI 0.09 to 0.38), respectively, for LDL-C levels. The incidence of adverse events was significantly lower when HHT was used in addition to lipid-lowering drugs, in comparison to that with lipid-lowering drugs alone. No serious adverse events were reported in the HHT group. Most included studies showed a high risk of performance bias and the quality of evidence was rated generally "low" because of the high risk of bias and inconsistency or imprecision of the meta-analysis results.
CONCLUSION
Current evidence suggests that HHT may be beneficial for patients with dyslipidemia and may reduce the adverse events associated with lipid-lowering drugs. However, due to the high risk of bias of the included studies and low quality of evidence for the main findings, no definitive conclusion could be reached. Further rigorous, high-quality, and placebo-controlled RCTs should be conducted to assess the efficacy of HHT.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42020164563.
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10.1097/MD.0000000000023367
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pubmed_88_5820
|
The purpose of this study was to investigate the characteristics of female-headed households in Pakistan. "[A] sample of 680 working women will be used to analyse the economic situation of households headed by women relative to households headed by men. The paper will compare income levels, household size and composition and employment patterns in the two sets of households. Further, the study will also investigate differences in income and employment options within the subset of households headed by women." The poverty of households headed by women was generally found to reflect the disadvantaged position of women in the labor market. Comments by Nahced Aziz are included (pp. 788-90).
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pubmed_88_5820
|
pubmed_155_348
|
The activation of cellular function following the direct introduction of Ca2+ into the cytosol by the use of a Ca2+-transporting ionophore has served to confirm the widely held idea that Ca2+ has the status of a second messenger in many cell types. However, this evidence has been obtained largely from the use of a single ionophore, the antibiotic A23187; experiments with X537A, which is another ionophorous antibiotic capable of transporting Ca2+ (ref. 3), have failed to show the expected characteristics. For example, histamine release from rat mast cells mediated by X537A is neither dependent on extracellular Ca2+ nor prevented by metabolic inhibitors. Ionomycin is a recently described polyether antibiotic produced by Streptomyces conglobatus ATCC 31005, and is active against Gram-positive bacteria. The antibiotic action is presumably due to its ionophorous properties, as it extracts Ca2+ from an aqueous phase into an organic phase with a stoichiometry of 1:1 (ref. 6). The ionophore is also capable of transporting 45Ca2+ across biological membranes (our unpublished results). Here we report the application of ionomycin to rat mast cells. We show that ionomycin stimulates mast cell secretion solely through its ability to form a lipid-soluble calcium complex, and thus to convey Ca2+ across the hydrocarbon region of the cell membrane.
|
10.1038/282851a0
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pubmed_1097_22694
|
Glycosylation is a common post-translational modification of surface exposed proteins and lipids present in all kingdoms of life. Information derived from bacterial genome sequencing, together with proteomic and genomic analysis has allowed the identification of the enzymatic glycosylation machinery. Among prokaryotes, O-mannosylation of proteins has been found in the actinomycetes and resembles protein O-mannosylation in fungi and higher eukaryotes. In this review we summarize the main features of the biosynthetic pathway of O-mannosylation in prokaryotes with special emphasis on the actinomycetes, as well as the biological role of the glycosylated target proteins.
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10.1039/b916394h
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pubmed_785_15686
|
Chronic obstructive pulmonary disease is often associated with cardiovascular diseases, such as pulmonary hypertension, ischemic heart disease, arrhythmias or heart failure. These co-morbidities may cause diagnostic or therapeutic difficulties and significantly worsen the morbidity and mortality of patients with chronic obstructive pulmonary disease. In this work the author reviews special considerations for the treatment of patients with chronic obstructive pulmonary disease who have cardiovascular co-morbidities.
|
10.1556/OH.2014.29989
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pubmed_680_16048
|
BACKGROUND
Predicting disability worsening in multiple sclerosis (MS) remains an important challenge. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) seem promising biomarkers. Studies investigating blood GFAP in relation to longitudinal outcome measures in MS are scarce.
OBJECTIVE
To compare plasma-GFAP (p-GFAP) and plasma-NfL (p-NfL) levels in relation to sustained disability worsening.
METHODS
We measured baseline p-GFAP and p-NfL in a prospective cohort of 115 individuals with MS and 30 matched controls, using Single Molecule Array (Simoa). Disability worsening was defined as an increase in at least one of three measures (Expanded Disability Status Scale, Timed 25-foot walk, 9-Hole Peg test), confirmed after 6 months and persistent upon data closure.
RESULTS
In a multivariable Cox proportional-hazards model, p-GFAP was not significantly associated with sustained disability worsening after 4.40 ± 0.82 years, while p-NfL (HR = 1.046, p = 0.001), EDSS (HR = 1.24, p = 0.039), and disease duration (HR = 1.048, p = 0.017) were. Area under the curve of ROC curves in relation to worsening was 0.61 for p-GFAP (p = 0.031) and 0.63 for p-NfL (p = 0.015). Kaplan-Meier curves showed similar patterns for both proteins.
CONCLUSION
p-NfL emerged as a significant explanatory variable for worsening in Cox regression analysis, and p-GFAP did not. Both p-GFAP and p-NfL were related to worsening based on ROC curves.
|
10.1177/13524585221094224
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pubmed_754_14555
|
The synthesis of carcinoembryonic antigen (CEA) in human tumour cell cultures has been investigated at the ultrastructural level in the colon carcinoma cell line LS 174 T. By application of a CEA-specific antibody fraction, gained from goat serum which was directly coupled with horse radish peroxidase (HRP), the expression of CEA could be followed in the cell culture both intra- and extracellularly with ultra-immunohistochemical methods, utilizing the pre-embedding technique. Morphometric and ultra-immunohistochemical investigations showed the possible involvement of the Golgi systems in CEA production. The changes in the volume fraction of the Golgi apparatus related to the total cell volume showed a direct correlation with the CEA content in the cell culture supernatants. Freeze-etch control experiments revealed negligible structural changes in the cells following ethyl-dimethyl-aminopropylcarbodiimide (EDC)-and saponin permeation techniques.
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pubmed_754_14555
|
pubmed_234_8567
|
The Illness Attitudes Scale (IAS) assesses fears, beliefs and attitudes associated with hypochondriasis [Kellner, R. (1986). Somatization and hypochondriasis. New York: Praeger Publishers.]. Recent factor analytic investigations of the IAS in non-clinical samples have suggested a number of different factor solutions. In study 1, we used principal components analysis with both orthogonal and oblique rotation to better explore the structure of this measure. Using a random selection of 390 participants from a larger pool of 780, a five-factor solution was identified: (1) fear of illness, death, disease and pain, (2) effects of symptoms, (3) treatment experiences, (4) disease conviction and (5) health habits. In study 2, confirmatory factor analysis (CFA) of responses from the remaining 390 students evaluated: (a) a single-factor model, (b) Kellner's original nine-factor model, (c) a four-factor model proposed by Ferguson and Daniel [Ferguson, E. & Daniel, E. (1995). The Illness Attitudes Scale (IAS): a psychometric evaluation on a nonclinical population. Personality and Individual Differences, 18, 463-469.], (d) a different four-factor model proposed by Stewart and Watt [Stewart, S. H. & Watt, M. C. (1998). A psychometric investigation of the Illness Attitudes Scale (IAS) in a nonclinical young adult sample. Submitted for publication.] and (e) the five-factor model derived in study 1. Of these models, greatest support was obtained for our five-factor model. However, it was also clear that this model could be improved. Based on the results of the CFA, as well as previous research and theoretical considerations, we tested a revised model in which the health habits factor was deleted. Analysis of the revised model showed that it received the greatest support and could be conceptualized as either four distinct factors or as hierarchical in nature, with four lower-order factors loading on a single higher-order factor. Future directions for research as well as suggestions for scoring and using the IAS with nonclinical samples are discussed.
|
10.1016/s0005-7967(98)00159-4
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pubmed_239_15453
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Liability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1 (HSV-1), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) as well as Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174 daughters of fathers with or without SUD. Its relationships with a cognitive characteristic (IQ) in childhood and with risk for SUD in adulthood were examined using correlation, regression, survival, and path analyses. Exposure to HSV-1, EBV, and T. gondii in males and females, and CMV in males, was associated with lower IQ. Independent of that relationship, EBV in females and possibly in males, and CMV and possibly HSV-1 in females were associated with elevated risk for SUD. Therefore, childhood neurotropic infections may influence cognitive development and risk for behavior disorders such as SUD. The results may point to new avenues for alleviating cognitive impairment and SUD risk.
|
10.1017/S0954579417000529
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pubmed_1023_12137
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The concentration of lactose in plasma was determined in different sows at all phases of their reproductive cycle and related to the compositional changes in mammary secretion during lactogenesis, established lactation and weaning. Lactose was present in low concentrations (3-4 microM) in the blood of virgin sows and pregnant sows up to 107 days of gestation. From day 4 pre-partum to day 1 pre-partum circulating lactose rose gradually to 34.5 +/- 7.7 microM (mean +/- S.E. of mean). Maximal concentrations of 262 +/- 168.4 microM were reached 6 h after parturition. The concentration of lactose in plasma was correlated with the amount of lactose in mammary secretion (r = 0.88, P less than 0.01) at the beginning of farrowing. During established lactation the concentrations of lactose, Na and K in milk, and of lactose in plasma (72-86 microM), were constant. The concentration of lactose in plasma did not vary significantly during periods of suckling, or after stimulation of milk ejection by oxytocin. However, the amount of lactose in plasma rose significantly (P less than 0.02) after the administration of oxytocin if milk ejection was not accompanied by suckling. The mean plasma concentration of lactose began to rise 36 h after weaning to a peak value of 241.8 +/- 53.6 microM at 48 h; thereafter it declined to 10.2 +/- 2.0 microM by 6 days. This study has shown that lactose concentrations in the plasma vary according to the secretory activity of the mammary gland. Its plasma concentration provides an earlier temporal measure of lactogenesis in individual sows than is obtained either from observation or analysis of mammary secretion.
|
10.1113/jphysiol.1984.sp015075
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pubmed_18_24417
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The life histories of organisms can show pronounced variation in the way that the costs of reproduction are financed. To facilitate discussions of this variation, two terms are increasing in use: "capital breeding" describes the situation in which reproduction is financed using stored capital; "income breeding" refers to the use of concurrent intake to pay for a reproductive attempt. We consider the value of the capital and income typology with reference to three functions that it might serve: description, explanation, and prediction. We find that interpretations of the terms have diversified and lack rigidity, leading to subjectivity in their definition. We recognize that time frames of interest will vary among taxa, but we urge consistency of use within those taxa. We also urge consistency in the use of a single metric designed to measure the reliance of an organism on capital. The concepts of capital and income breeding have served well as proximate explanations for behavioral or physiological diversity, but efforts to explain their adaptive value have been disproportionately focused on individual taxa. Mapping cause to effect is difficult in ecology. Nevertheless, further analyses, based on consistently applied measures of reliance on stored capital, may reveal which of the putative ecological, morphological, and physiological drivers have the most consistent and widespread effects. The capital-income typology has yet to be applied to the question of prediction, and thus, it remains to be seen whether these concepts will be of use in identifying the likely responses of different populations to changes in their environment.
|
10.1890/08-1369.1
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pubmed_126_11231
|
The pharmacokinetics, biodistribution and dosimetry of 99mTc-labeled anti-human epidermal growth factor receptor (anti-hEGF-r) humanized monoclonal antibody (MAb) R3 was investigated following intravenous injection in normal Wistar rats. Serum disappearance curves were best fit by a two-compartment model having a mean distribution half-life (t 1/2alpha) of 0.250 h and a mean elimination (t 1/2beta) of 13.89 h. Among the various organs, a little accumulation of the radiolabeled antibody was found only in kidneys. Biodistribution and dosimetry studies in humans were performed by extrapolation of the animal data to humans. Absorbed dose to normal organs and the remainder of the whole body were estimated using the medical internal radiation dose formula, and dose contributions from radioactivity in transit through the gastrointestinal tract were estimated using a compartment model. Extrapolated values of radiation absorbed dose to normal organs in rads per millicurie administered were whole body, 0.0085; lower large intestine wall, 0.0898; small intestine, 0.0530; upper large intestine wall, 0.0731; and kidneys, 0.0455. The effective dose equivalent predicted was 0.0162 rem/mCi and the effective dose was found to be 0.015 rem/mCi. On the basis of the pharmacokinetics, biodistribution and internal radiation dosimetry information obtained in this study, a diagnostic phase I clinical trial with 99mTc-labeled humanized MAb R3 conjugate in patients should be supported.
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10.1016/s0969-8051(97)00139-x
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pubmed_438_8931
|
AIM
The aim of this study was to determine the shaping ability of GT Rotary Files in simulated root canals.
METHODOLOGY
Forty canals with four different shapes in terms of angle (40 degrees and 60 degrees) and position of curvature (straight section before curve: 8 and 12 mm) were prepared using a crown-down/stepback technique. Pre-operative and post-operative pictures, recorded using an image analysis system, were super-imposed and aberrations recorded. Measurements were carried out at 5 different points: at the canal orifice (0): half-way to the orifice in the straight section (HO); the beginning of the curve (BC); the apex of the curve (AC): the endpoint (EP).
RESULTS
Two instrument fractures occurred and 9 instruments were deformed. Overall, eight zips and one ledge were created. There were significant differences (P < 0.001) for the total width of the canals between the various canal shapes at AC, BC and HO. There were significant differences (P < 0.001) for the amount of resin removed from the outer aspect of the curve at AC, BC and HO; and for the amount of resin removed from the inner aspect of the curve at all five measuring points (0, AC and EP (P < 0.05) and HO and BC (P < 0.001)). Mean transportation was towards the inner aspect of the canal in canals with straight sections of 12 mm regardless the curve angle; towards the outer aspect in canals with straight sections of 8 mm and 40 degrees curves at all the five measuring points, and at AC, BC and HO when the curve was 60 degrees.
CONCLUSIONS
Under the conditions of this study, GT Rotary Files produced acceptable canal shapes. In narrow and curved canals, the length of the straight section of the canal determines the direction of transportation more than the angle of the curve. In the 60 degrees curves, a high incidence of instrument deformation was found when using the 0.04 tapered instruments.
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10.1046/j.1365-2591.2002.00540.x
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pubmed_509_21547
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Protein phosphorylation is one type of posttranslational modification, which regulates a large number of cellular processes in plant cells. As an emerging powerful biotechnology that integrates all aspects of advantages from mass spectrometry, bioinformatics, and genomics, phosphoproteomics offers us an unprecedented high-throughput methodology with high sensitivity and dashing speed in identifying a large complement of phosphoproteins from plant cells within a relatively short period of time. Needless to say, phosphoproteomics has become an integral portion of life sciences, which penetrates various research disciplines of biology, agriculture, and forestry and irreversibly changes the way by which plant scientists study biological problems.Because phosphorylation/dephosphorylation of protein is dynamic in cells and the amount of phosphoproteins is low, the preservation of a phosphor group onto phosphosite throughout protein purification as well as enrichment of these phosphoproteins during purification has become a serious technical issue. To overcome difficulties commonly associated with phosphoprotein isolation, phosphopeptides' enrichment, and mass spectrometry analysis, we have developed a urea-based phosphoprotein purification protocol for plants, which instantly denatures plant proteins once the total cell content comes into contact with the UEB solution. To measure the alteration of phosphorylation on a phosphosite using mass spectrometer, an in vivo (15)N metabolic labeling method (SILIA, i.e., stable isotope labeling in Arabidopsis) has been developed and applied for Arabidopsis differential phosphoproteomics. Thus far, hundreds of signaling-specific phosphoproteins have been identified using both label-free and (15)N-labeled differential phosphoproteomic approach. The phosphoproteomics has allowed us to identify a number of signaling components mediating plant cell signaling in Arabidopsis. It is envisaged that a huge number of phosphosites will continue to be uncovered from phosphoproteomics in the near future, which will become instrumental for the development of plant phosphor-relay networks and molecular systems biology.
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10.1007/978-1-61779-809-2_2
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pubmed_1063_1893
|
As a natural polymer with abundant sources, cellulose was one of the earliest applied electrorheological (ER) materials. However, cellulose-based ER materials have not attracted much attention because of their relatively low ER effect and sensitivity to water. In this study, cellulose rods were decorated with a urea-terminated silane, 1-(3-(trimethoxysilyl) propyl) urea, after being swelled in sodium hydroxide solution. The morphologies and structures of the cellulose particles were investigated using scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray diffraction, confirming the dramatic differences of the treated cellulose particles from the pristine cellulose. Rheological behaviors of the pristine and modified cellulose particles in silicone oil were observed using a rotational rheometer. It was found that the silane-modified cellulose showed higher ER effect and higher dielectric properties than the pristine cellulose particles, which was not only related to the grafted polar molecules but may also be associated with the porous morphologies of the treated cellulose particles.
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10.3390/polym10080867
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pubmed_756_9421
|
How organ-specific metastatic traits arise in primary tumors remains unknown. Here, we show a role of the breast tumor stroma in selecting cancer cells that are primed for metastasis in bone. Cancer-associated fibroblasts (CAFs) in triple-negative (TN) breast tumors skew heterogeneous cancer cell populations toward a predominance of clones that thrive on the CAF-derived factors CXCL12 and IGF1. Limiting concentrations of these factors select for cancer cells with high Src activity, a known clinical predictor of bone relapse and an enhancer of PI3K-Akt pathway activation by CXCL12 and IGF1. Carcinoma clones selected in this manner are primed for metastasis in the CXCL12-rich microenvironment of the bone marrow. The evidence suggests that stromal signals resembling those of a distant organ select for cancer cells that are primed for metastasis in that organ, thus illuminating the evolution of metastatic traits in a primary tumor and its distant metastases.
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10.1016/j.cell.2013.07.036
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pubmed_757_7430
|
Hypoxia typically accompanies acute inflammatory responses in patients and animal models. However, a limited number of studies have examined the effect of hypoxia in combination with inflammation (Hypo-Inf) on neural function. We previously reported that neuronal excitability in hippocampal CA1 neurons decreased during hypoxia and greatly rebounded upon reoxygenation. We attributed this altered excitability mainly to the dynamic regulation of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels and input resistance. However, the molecular mechanisms underlying input resistance changes by Hypo-Inf and reperfusion remained unclear. In the present study, we found that a change in the density of the delayed rectifier potassium current (IDR) can explain the input resistance variability. Furthermore, voltage-dependent inactivation of A-type potassium (IA) channels shifted in the depolarizing direction during Hypo-Inf and reverted to normal upon reperfusion without a significant alteration in the maximum current density. Our results indicate that changes in the input resistance, and consequently excitability, caused by Hypo-Inf and reperfusion are at least partially regulated by the availability and voltage dependence of KV channels. Moreover, these results suggest that selective KV channel modulators can be used as potential neuroprotective drugs to minimize hypoxia- and reperfusion-induced neuronal damage.
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10.1186/s13041-021-00857-9
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pubmed_639_10222
|
AIM
Our objective was to describe the impact of hyponatremia on the outcomes of COVID-19 patients [outcomes selected: intensive care unit (ICU) admission, mechanical ventilation or death].
METHODS
Two groups of COVID-19 patients were retrospectively screened on the basis of plasma sodium level at admission: hyponatremic (sodium < 135 mM, n = 92) or normonatremic (sodium ≥ 135 mM, n = 198) patients. Pearson's chi-2 (qualitative variables) and Student's T tests (quantitative variables) were used to compare the two groups. A multiple logistic regression model was used to explore the association between patients' clinical data and outcomes.
RESULTS
Hyponatremia was frequent but generally mild. There were more male patients in the hyponatremic group (p = 0.014). Pulmonary lesions on the first thoracic CT-scan performed during hospitalization were significantly more extensive in the hyponatremic group (p = 0.010). ICU admission, mechanical ventilation or death were significantly more frequent in hyponatremic compared to normonatremic patients (37 versus 14%; p < 0.001; 17 versus 6%; p = 0.003; 18 versus 9%, p = 0.042, respectively). Hyponatremia was an independent predictor of adverse outcomes (adjusted Odds-ratio: 2.77 [1.26-6.15, p = 0.011]).
CONCLUSIONS
Our study showed an independent relationship between hyponatremia at admission and transfer to ICU, use of mechanical ventilation or death in COVID-19 patients. Hyponatremia may reflect the severity of underlying pulmonary lesions. Our results support the use of sodium levels as a simple bedside screening tool for the early identification of SARS-CoV-2 infected patients at high risk of poor outcome.
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10.1007/s40620-021-01036-8
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pubmed_505_20876
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The P2X family of ATP receptors (P2XR) are ligandgated channels that have been proposed to regulate cell death of immature thymocytes. However, the nature of the P2XR subtype involved has been controversial until recently. In agreement with previous studies, we found that extracellular ATP (ATPe) induces a caspase-dependent apoptosis of BALB/c thymocytes, as observed by DNA fragmentation. Additionally, ATPe induces a predominant caspase-independent thymocytes lysis characterized by plasma membrane disruption. Both responses to ATPe can be induced by a potent P2X7R agonist, benzoylbenzoyl-ATP, whereas P2X7R antagonists, oxidized ATP and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, inhibited the effect of ATPe. These results are further supported by observations where disruption of the P2X7R gene (P2X7R(-/-) mice) completely abolishes thymocytes death induced by ATPe. Interestingly, the natural P451L mutation in the C-terminal tail of P2X7R present in C57BL/6 mice, which impairs ATPe-dependent pore formation in T lymphocytes, significantly reduces thymocytes death triggered by ATPe. Furthermore, we found that P2X7R from BW5147 thymoma cells also harbors this point mutation, accounting for their insensitivity to ATPe-induced cell death. Concentrations of ATPe effective in inducing cell death also increase phosphatidylcholine-hydrolyzing phospholipase D (PC-PLD) activity in BALB/c thymocytes through the stimulation of P2X7R. However, in contrast to ATPe-induced cell death, PC-PLD activation is totally Ca(2+)-dependent. Moreover, the stimulation of PC-PLD by ATPe is not affected by the P451L mutation present in C57BL/6 thymocytes and BW5147 cells, suggesting that cell death and PC-PLD activity are regulated through distinct domains of the P2X7R. Finally, the inhibition of ATPe-induced PC-PLD stimulation does not affect thymocytes death. Altogether, these data suggest that P2X7R-induced thymocytes death is independent of the stimulation of PC-PLD activity.
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10.1074/jbc.M313064200
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pubmed_12_9659
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Data is presented of the post-mortem macroscopic and microscopic examination of two Toy Poodles with multiple enchondromatosis (Ollier syndrome). In both animals opening and maturation disorders of the growth plates were found in several skeletal locations. Due to the dogs' age difference at necropsy (14 and 4 months), some variation was also present in occurrence and appearance of primary and secondary alterations, which gave rise to some conclusions regarding development and progression of the disease. Chondrodysplasia, a characteristic of several breeds, is considered to be the essential factor in the pathogenesis of multiple enchondromatosis in the described cases.
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pubmed_12_9659
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pubmed_741_11278
|
The development of lymphoid and nonlymphoid cells in Peyer's patches (PP) of the rat was investigated using light microscopical methods (routine histological techniques, enzyme histochemistry and immunohistochemistry). In newborn rats PP were mainly populated by T lymphocytes and Ia-positive nonlymphoid cells, which most likely are interdigitating cells. At about 12 days after birth the B and T cells were localized in defined regions, the follicular (FA) and interfollicular area (IFA), respectively. Compartmentalization within the FA started about 14 days after birth. The first signs of the development of secondary follicles were seen from about 18 days onward. PP obtained their mature structure at about 4 weeks after birth. It is suggested that after PP had developed fully, cells having cytoplasmic IgA migrate via the high endothelial venules (HEV) to the lamina propria of the intestine; cIgM and IgG cells seem to develop locally within the FA.
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10.1002/ar.1092070209
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pubmed_623_6874
|
Meta-analyses are often used to synthesize the findings of studies examining the correlational relationship between two continuous variables. When only dichotomous measurements are available for one of the two variables, the biserial correlation coefficient can be used to estimate the product-moment correlation between the two underlying continuous variables. Unlike the point-biserial correlation coefficient, biserial correlation coefficients can therefore be integrated with product-moment correlation coefficients in the same meta-analysis. The present article describes the estimation of the biserial correlation coefficient for meta-analytic purposes and reports simulation results comparing different methods for estimating the coefficient's sampling variance. The findings indicate that commonly employed methods yield inconsistent estimates of the sampling variance across a broad range of research situations. In contrast, consistent estimates can be obtained using two methods that appear to be unknown in the meta-analytic literature. A variance-stabilizing transformation for the biserial correlation coefficient is described that allows for the construction of confidence intervals for individual coefficients with close to nominal coverage probabilities in most of the examined conditions. Copyright © 2016 John Wiley & Sons, Ltd.
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10.1002/jrsm.1218
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pubmed_508_3414
|
Pulmonary vein antrum isolation offers safe and effective treatment of atrial fibrillation by eliminating the potential triggers of this arrhythmia. The pulmonary vein antra encompass, in addition to the pulmonary veins, the left atrial roof and posterior wall and, in the case of the right pulmonary vein antra, a portion of the interatrial septum. Compared with pulmonary vein ostial isolation, this technique offers a higher success rate and a lower complication rate. In patients with nonparoxysmal atrial fibrillation, extension of septal ablation to the region of the mitral annulus is associated with better outcomes. Further adjunctive strategies include ablation in the coronary sinus, atrial side of inferior mitral annulus, superior vena cava, and along the cristae terminalis, targeting complex fragmented electrograms. We usually reserve these adjunctive ablative therapies for patients with persistent or chronic atrial fibrillation and those with unsuccessful prior catheter ablation.
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10.1016/j.hrthm.2006.12.036
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pubmed_107_15374
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The QRS axis of 130 consecutive patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) were measured before balloon inflation and just before balloon deflation. Patients were divided into two groups. Group A (103) had angina pectoris and/or non-transmural old myocardial infarction with no abnormal Q waves; group B (27) had an old transmural myocardial infarction with abnormal Q waves. In group A, the QRS axis had significantly shifted to the left in patients with left anterior descending artery (LAD) occlusion (from 68.0 +/- 42.7 degrees to 40.2 +/- 44.6 degrees, P < 0.001); however in those patients without involvement of the major septal branch, significant axis changes were not observed (from 53.6 +/- 34.1 degrees to 49.8 +/- 33.1 degrees). When the right coronary artery (RCA) was occluded in group A, the QRS axis shifted to the right significantly (from 63.2 +/- 40.0 degrees to 89.8 +/- 30.1 degrees. P < 0.01); during left circumflex artery (LCX) occlusion, no significant axis shift was observed. In group B, no significant axis shift was observed either in patients with occlusion of the LAD or the RCA. It is concluded that transient left axis deviation reflects an obstructive lesion of the proximal portion of the LAD with involvement of the major septal branch, and transient right axis deviation reflects an obstructive lesion of the RCA.
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10.1093/oxfordjournals.eurheartj.a060400
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pubmed_659_19486
|
INTRODUCTION
Histone deacetylases (HDACs) have emerged as important therapeutic targets for various diseases, such as cancer and neurological disorders. Although a majority of HDAC inhibitors use hydroxamic acids as zinc binding groups, hydroxamic acid zinc-binding groups suffer from poor bioavailability and nonspecific metal-binding properties, necessitating a new zinc-binding group. Salicylic acid and its derivatives, well-known for their therapeutic value, have also been reported to chelate zinc ions in a bidentate fashion. This drew our attention towards replacing hydroxamic acid with salicylamide as a zinc-binding group.
METHODS
In this study, for the first time, compound 5 possessing a novel salicylamide zinc-binding group was synthesized and evaluated biologically for its ability to inhibit various HDAC isoforms and induce acetylation upon α-tubulin and histone H3 among MDA-MB-231 cells.
RESULTS
Compound 5 exhibits selective inhibition against class I HDAC isoforms (HDAC1, 2, and 3) over class II and IV HDAC isoforms (HDAC4, 6, and 11). The exposure of MDA-MB-231 cells to compound 5 efficiently induced the acetylation of more histone H3 than α-tubulin, suggesting that compound 5 is a class I selective HDAC inhibitor. Moreover, the molecular docking study indicated that the salicylamide zinc-binding group of compound 5 coordinates the active zinc ion of class I HDAC2 in a bidentate fashion.
CONCLUSION
Overall, salicylamide represents a novel zinc-binding group for the development of class I selective HDAC inhibitors.
GRAPHICAL ABSTRACT
(http://links.lww.com/MD/G668).
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10.1097/MD.0000000000029049
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pubmed_680_10432
|
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the data shown for the cell migration and invasion assays in Fig. 2C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 1431‑1438, 2017; DOI: 10.3892/mmr.2017.6748].
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pubmed_680_10432
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pubmed_930_1495
|
As part of a search for estradiol derivatives designed for conjugation to carboxyl or amine functions of anti-cancer agents or suitable derivatives thereof, estradiol analogs with side chains at the C-16 or -17 position were prepared for biological assay. These analogs include several which have a substituted nitrogenous function at C-17. The avidity of some of these analogs for binding to estrogen receptor was found to be of a low order.
|
10.1016/0039-128x(85)90037-6
|
pubmed_878_25784
|
Data from two studies are used to examine the proposition that excessive gambling, unlike excessive substance use, is not generally viewed as a form of dependence. In the first study, the attitudes of 100 members of the general population towards the causes of excess and towards appropriate treatments, indicated that excessive gambling was seen in more moral terms than were other addictive behaviours. In the second study, of 54 people receiving treatment for one of four forms of excessive behaviour, gamblers were just as likely to use terms such as 'addiction' or 'compulsion' to describe their behaviour but were also more likely than others to describe it in terms of moral weakness or vice. Concern is expressed at the way in which gambling may be marginalized as a form of dependence.
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10.1007/BF01013494
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pubmed_968_15004
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Entanglements are common in both natural and artificial systems and can result in both beneficial and harmful effects. Most spider webs are static structures held under constant tension and do not tangle. However, many spiders actively load tension into their webs by coiling silk threads that are released to "fire" webs at prey. Here we test whether or not tangling occurs during the rapid release of webs built by the triangle spider Hyptiotes cavatus. We use high-speed videography to examine the release of the spider's web, looking for signs of tangling both visually on the videos and on acceleration graphs. The spider tenses the web by pulling on a silken anchor line using a leg-over-leg movement, deforming the silk into permanent coils and storing excess slack in a loose bundle between the spider's legs. This 1-3cm long bundle of coils straightens during the web's release in as few as 4ms. Though the messy silk coils are pressed closely together, the web's release is never impeded by catastrophic tangling. This lack of serious tangling is perhaps due to the permanent coils preventing random movement of the silk. The coils also compact the loose silk, preventing interference with the spider's movement. The ability to coil its anchor line allows H. cavatus to permanently restructure its silk, facilitating its active web-hunting behavior. Our findings broaden our knowledge of silk manipulation by spiders and may give insights into creating tangle-free systems through structural changes.
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10.1007/s00114-021-01769-3
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pubmed_940_17129
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gamma-Hydroxybutyric acid (GHB), a naturally occurring analog of GABA, induces absence-like seizures in rats. We characterized the interaction of 3alpha-hydroxy steroids, alphaxalone and tetrahydrodeoxycorticosterone (which are potent modulators of GABAA receptors) with GHB binding sites in rat brain cortical membranes. The steroids inhibited [3H]GHB binding in a dose-dependent fashion (IC50 approximately 1 microM). Neither bicuculline nor GABA altered the dose-response of steroids in the [3H]GHB assay, suggesting that there was no GABAA component involved in the steroid-inhibition of [3H]GHB binding. Also, non 3alpha-hydroxy steroids were inactive in displacing [3H]GHB. Because GHB-induced absence seizures evolve most readily from layers I-IV of frontoparietal cortex and thalamic relay nuclei, we determined if the interaction of steroids with GHB binding sites in layers I-IV of frontoparietal cortex and thalamic relay nuclei was altered during GHB-induced absence seizures. We found that during GHB-seizures steroid-inhibition of [3H]GHB binding was increased selectively in thalamic relay nuclei but not in the layers I-IV of frontoparietal cortex or any other brain regions tested. This increase in steroid-inhibition of [3H]GHB binding in thalamus was apparent about 30 min after the onset of seizures, but not at the seizure-onset. As the seizures dissipated, the IC50 values for steroids rose to the pre-seizure level. These data suggest that the enhancement in steroid-inhibition of [3H]GHB binding in thalamic relay nuclei observed during GHB-seizures was caused by absence seizures.
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10.1016/s0006-8993(98)01036-1
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pubmed_2_18877
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Nucleoside reverse transcriptase inhibitors (NRTI) remain a cornerstone of current antiretroviral regimens in combinations usually with a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor (INI). The antiretroviral efficacy and relative safety of current NRTI results from a tight and relatively specific binding of their phosphorylated nucleoside triphosphates (NRTI-TP) with the HIV-1 reverse transcriptase which is essential for replication. The intracellular stability of NRTI-TP produces a sustained antiviral response, which makes convenient dosing feasible. Lessons learned regarding NRTI pharmacology screening, development, and use are discussed. NRTI and prodrugs currently under clinical development are outlined.
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10.1016/j.ddtec.2012.09.003
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pubmed_719_14788
|
BACKGROUND
Proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) leads to a clinical decline in the quality of life (QOL). Therefore, new treatment options are needed. We performed a multicenter, randomized, parallel-group exploratory trial to determine the efficacy of hangeshashinto (HST) in patients with PPI-refractory GERD.
METHODS
We enrolled 78 patients with PPI-refractory GERD for standard PPI regimens for at least 4 weeks and randomly assigned patients to receive either a combination of usual dose of rabeprazole (10 mg/day) + HST (7.5 g/day; HST group) or a double dose of rabeprazole (20 mg/day; double-dose PPI group). The primary end points were the extent of improvement in FSSG (Frequency Scale for the Symptoms of GERD) score and the change over time in FSSG score.
RESULTS
There was no significant difference in terms of the improvement degree of the FSSG score between the two groups. Although the total FSSG score and reflux syndrome score decreased significantly for both groups over time (p < 0.001), the acid-related dyspepsia (ARD) score decreased significantly in the HST group from 1 week after drug administration (p < 0.05), indicating an improvement in the condition earlier than in the double-dose PPI group. Moreover, in examinations concerning BMI and age, the HST group had a significantly higher improvement degree of ARD score in patients with BMI < 22 (p < 0.05) and aged < 65 years (p < 0.05) than the double-dose PPI group.
CONCLUSIONS
HST may be beneficial for patients with PPI-refractory GERD, particularly in non-obese and non-elderly patients with dyspepsia symptoms.
|
10.1007/s00535-019-01588-4
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pubmed_889_13292
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Molecular ionization in the central molecular zone of our Galaxy is enhanced over the typical galactic value by an order of magnitude or more. This cannot be easily explained for dense Galactic center molecular complexes in the absence of embedded sources of low energy cosmic rays. We provide such a source in the form of ultracompact minihalos of self-annihilating dark matter for a variety of annihilation channels that depend on the particle mass and model. Such sources are motivated for plausible inflationary power spectrum parameters, and while possibly subdominant in terms of the total dark matter mass within the Galactic bulge, might also account for, or at least not be in tension with, the Fermi Galactic center γ-ray excess.
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10.1103/PhysRevLett.121.231105
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pubmed_553_5012
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The "scarification" technique is a reliable method of healing chronic bone infection by promoting revascularisation. A wide excision of scarred or infected soft tissue is first carried out. The bone is then carefully "scarified", or petaled, with minimal removal of bone substance. A small window is made to allow drainage and curettage of the intramedullary space. Revascularisation of diseased bone is stimulated by this technique, thus encouraging the growth of granulation tissue with consequent healing. The authors claim a success rate of 93% in 86 patients.
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pubmed_553_5012
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pubmed_716_1447
|
Importance
High blood pressure (BP) in children and adolescents is becoming one of the most common health conditions worldwide and is much more widely prevalent than previously thought.
Objective
To estimate the prevalence of high BP in adolescents in India and identify associated factors.
Design, Setting, and Participants
This cross-sectional study is a secondary analysis of data from the Comprehensive National Nutrition Survey (CNNS, 2016-2018), which used a multistage, stratified, probability proportion to size cluster sampling design to enroll a nationally representative sample of households and individuals aged 10 to 19 years across all states and union territories of India. Adolescents with acute or chronic illness, physical deformity, mental illness, or cognitive disability were excluded from the survey. Because BP was measured only in children between 10 and 19 years of age, only data from children within this age group were included for secondary analyses. Data analysis was performed from March 2021 to April 2022.
Exposures
Anthropometry.
Main Outcomes and Measures
On the basis of the 2017 American Academy of Pediatrics guidelines, high BP was defined as stage 1 and 2 hypertension, with BP above the 95th percentile in children younger than 13 years and greater than 130/80 mm Hg in children 13 years or older. The association of age, sex, region, socioeconomic status, body mass index, fasting blood glucose, hemoglobin A1c, and lipid profile with high BP were examined using log binomial regression.
Results
Among 16 182 eligible children aged 10 to 19 years (mean [SD] age, 14.2 [2.8] years; 7849 [48.5%] female and 8333 [51.5%] male), 11 718 had valid BP data with 3 repeated readings. the prevalence of high BP was 35.1% (95% CI, 31.5%-38.9%) in children aged 10 to 12 years and 25.1% (95% CI, 22.5%-28.0%) in children 13 years or older. Overweight and obesity were associated with a higher risk of high BP in both younger (prevalence ratio, 1.17; 95% CI, 1.04-1.34) and older children (prevalence ratio, 1.33; 95% CI, 1.18-1.49). The prevalence of high BP in younger children with stunting was high at 40.1% (95% CI, 31.9%-48.9%) and was 21.9% (95% CI, 18.2%-26.1%) among older children with stunting. In both age groups, high BP coexisted with other cardiovascular disease risk factors, such that adolescents with high fasting blood glucose, high hemoglobin A1c, high triglyceride, and high low-density lipoprotein cholesterol levels had a higher risk of high BP.
Conclusions and Relevance
In this cross-sectional study, the prevalence of high BP, along with cardiovascular risk factors, was substantial in Indian adolescents. There is a need to screen and identify adolescents who have high BP and initiate interventions to control the burden of hypertension and its consequences in India.
|
10.1001/jamanetworkopen.2022.39282
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pubmed_72_15974
|
Morphea is an inflammatory disorder of the skin and underlying tissues characterized by an overabundance of collagen leading to fibrosis. The prevalence of this disease is estimated at around 0.4-2.7/100,000 people. When the process occurs in the gingival tissues, it induces traction, which can cause gingival recession. A 19-year-old woman was referred to the clinic for a progressive recession on teeth 11 and 12. A pale, atrophic, linear region extending from her nose to her upper lip on the right-hand side of her face was diagnosed as morphea en coup de sabre. Cone beam computed tomography, quantitative polymerase chain reaction and histologic evaluation were used to assess the pathology. Treatment with methotrexate was conducted. After 12 months, no progression of the recession could be observed.
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pubmed_72_15974
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pubmed_391_9028
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Effects of non-steroidal anti-inflammatory drugs (NSAID: amfenac sodium, diclofenac sodium, indomethacin and ketoprofen) on the generation of superoxide anion (O2-) by isolated rat polymorphonuclear leukocytes (PMN) were studied spectrophotometrically using cytochrome c. The effects of these drugs were also studied on O2- production by the xanthine-xanthine oxidase and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-NADPH oxidase systems. Amfenac sodium, at 0.1 mM, inhibited significantly O2- generation in rat PMN induced by opsonized zymosan. At 0.5 mM, diclofenac sodium and indomethacin inhibited the O2- generation in rat PMN. All of the above drugs slightly inhibited O2- production by the xanthine-xanthine oxidase system. On the other hand, O2- production by the NADPH-NADPH oxidase system was significantly inhibited by the addition of amfenac sodium, ketoprofen or indomethacin. These results suggest that non-steroidal anti-inflammatory drugs do not work as an O2- scavenger and block O2- production by the NADPH-NADPH oxidase system of rat PMN. It is concluded that amfenac sodium and the other drugs are able to inhibit granulocyte O2- production by blocking the activation of NADPH-oxidase.
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10.1248/cpb.39.1075
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pubmed_42_1872
|
In the course of idiopathic nephrotic syndrome (INS), acute renal failure (ARF) may develop. The factors, which lead to ARF appearance are not entirely defined. In 1990-1997, 1006 children suffering from INS were admitted to our Department. ARF was noticed in 8 of them (0.8%), aged 6 to 17.5 years. The aim of study was to emphasize the clinical features of ARF and to evaluate factors that may contribute to renal failure in children with INS. The following data were considered: the course of INS (disease duration, the number of relapses, the remission periods), renal histology, degree of electrolyte disorders, lipid metabolism disorders, serum albumin level, intensification of proteinuria, presence of hypertension, applied treatment. According to the analysis, it seems that considerable hypoalbuminaemia, the presence of infection and severe course of nephrotic syndrome are the factors of ARF appearance risk in the course of INS.
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pubmed_42_1872
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pubmed_452_20481
|
Aims External inquiries are carried out following specific adverse events in healthcare, many in maternity care; to identify issues and make recommendations to improve standards of care. Methods Ten publically-available national inquiry reports published between 2005-2018 relating to pregnancy loss services, were reviewed by 2 clinicians, separately, examining the content and recommendations from each report. Results A total of 258 recommendations were made in 9 reports (90%). Five inquiries (50%) clearly stated that affected families were involved and four (40%) involved affected clinical staff. In 9 reports (90%) recommendations included: increase workforce staffing and/or training, strengthen clinical governance, enhance adverse incident management and comprehensive data collection e.g. maternity outcomes. Only two inquiry reports (20%) stated that feedback was sought from key stakeholders prior to publication. Conclusion A collaborative and standardised inquiry process involving and supporting all persons affected as well as key stakeholders would ensure that all relevant issues are identified, recommendations are implemented and essential lessons are learned.
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pubmed_452_20481
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pubmed_597_24377
|
Identity by descent (IBD) can be reliably detected for long shared DNA segments, which are found in related individuals. However, many studies contain cohorts of unrelated individuals that share only short IBD segments. New sequencing technologies facilitate identification of short IBD segments through rare variants, which convey more information on IBD than common variants. Current IBD detection methods, however, are not designed to use rare variants for the detection of short IBD segments. Short IBD segments reveal genetic structures at high resolution. Therefore, they can help to improve imputation and phasing, to increase genotyping accuracy for low-coverage sequencing and to increase the power of association studies. Since short IBD segments are further assumed to be old, they can shed light on the evolutionary history of humans. We propose HapFABIA, a computational method that applies biclustering to identify very short IBD segments characterized by rare variants. HapFABIA is designed to detect short IBD segments in genotype data that were obtained from next-generation sequencing, but can also be applied to DNA microarray data. Especially in next-generation sequencing data, HapFABIA exploits rare variants for IBD detection. HapFABIA significantly outperformed competing algorithms at detecting short IBD segments on artificial and simulated data with rare variants. HapFABIA identified 160 588 different short IBD segments characterized by rare variants with a median length of 23 kb (mean 24 kb) in data for chromosome 1 of the 1000 Genomes Project. These short IBD segments contain 752 000 single nucleotide variants (SNVs), which account for 39% of the rare variants and 23.5% of all variants. The vast majority-152 000 IBD segments-are shared by Africans, while only 19 000 and 11 000 are shared by Europeans and Asians, respectively. IBD segments that match the Denisova or the Neandertal genome are found significantly more often in Asians and Europeans but also, in some cases exclusively, in Africans. The lengths of IBD segments and their sharing between continental populations indicate that many short IBD segments from chromosome 1 existed before humans migrated out of Africa. Thus, rare variants that tag these short IBD segments predate human migration from Africa. The software package HapFABIA is available from Bioconductor. All data sets, result files and programs for data simulation, preprocessing and evaluation are supplied at http://www.bioinf.jku.at/research/short-IBD.
|
10.1093/nar/gkt1013
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pubmed_691_15462
|
A criterion was established in a previous study to detect the relapse of adult acute leukemia in its early stage, i.e., when lymphocytes in peripheral blood increased over 45% of the leukocytes during the maintenance therapy, bone marrow puncture was immediately performed to examine the leukemic cells. By this criterion the relapse was detected earlier than by other criteria. To study the effect of early detection of the relapse in adult acute leukemia on the results, the second remission rate and the survival time were compared between the following groups. Group I consisted of 11 patients, whose relapse was determined by our criterion. Group II consisted of 8 patients whose relapse was determined by the appearance of leukemic cells in peripheral blood. The second remission was accomplished in 7 of 11 patients in Group I (64%) and in 1 of 8 in Group II (13%) (p less than 0.05). The mean (+/- S.D.) duration of complete remission in Group I was 9.7 +/- 7.8 months and not significantly longer than the value in Group II (5.3 +/- 3.9 months). The interval from relapse to death was 10.3 +/- 5.9 and 6.1 +/- 3.8 months in Groups I and II, respectively. The interval from relapse to death of 7 patients who accomplished the second remission in Group I was 12.5 +/- 5.5 months. This interval was significantly longer than in Group II (p less than 0.02). The mean survival time was 22.2 +/- 9.6 months in Group I and 13 +/- 2.5 months in Group II. The mean survival time of 7 patients accomplished the second remission in Group I was 26. 7 +/- 9.4 months which was significantly longer than in Group II (p less than 0.01). The results showed that our criterion to detect relapse in the early stage was effective for prolongation of the survival time in adult acute leukemia.
|
10.1620/tjem.144.77
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pubmed_460_15416
|
We investigated the clinicopathologic characteristics of and outcome after treatment for small intrahepatic cholangiocarcinomas of mass-forming type (3cm or smaller) in nine patients to study appropriate treatment. In seven of the nine patients, the cancer was detected during follow-up for hepatitis C virus-related disease. One patient was seropositive for anti-hepatitis B core antibody alone. One patient had alcoholic cirrhosis. Three patients also had hepatocellular carcinoma. Seven patients underwent liver resection and two other patients underwent microwave coagulation therapy. In the resection specimens, no vascular or lymphatic invasion, or invasion of perineural spaces, was evident pathologically. No patient had intrahepatic metastasis or lymph node metastasis; all had hepatic fibrosis. Lung metastases developed after surgery in one patient whose surgical margin was positive for cancer. In one patient with both type of carcinoma, the hepatocellular carcinoma recurred. Screening for not only hepatocellular carcinoma but also intrahepatic cholangiocarcinoma is necessary in patients with hepatic fibrosis, especially those infected with hepatitis C virus. For small intrahepatic cholangiocarcinomas of mass-forming type located peripherally in the liver, partial resection or ablation therapy with care to obtain a negative surgical margin may be appropriate.
|
10.1016/j.hepres.2004.03.010
|
pubmed_524_22964
|
BACKGROUND
Fragment-based drug discovery in recent times has been explored in the design of highly potent therapeutics.
METHODS
In this study, we explored the inhibitory dynamics of Compound 38 (Cpd38), a newly synthesized Bromodomain-containing protein 4 bromodomain 1 (BRD4-BD1) protein inhibitor derived from the synthetic coupling of Fragment 47 (Fgt47) into ABBV-075 scaffold. Using dynamic simulation methods, we unraveled the augmentative effects of chemical fragmentation on improved BRD4- BD1 inhibition.
RESULTS
Findings from this study revealed that although Fgt47 exhibited a considerable ΔGbind, its incorporation into the difluoro-phenoxy pyridine scaffold (Cpd38) notably enhanced the binding affinity. Time-based analyses of interaction dynamics further revealed that the bulkiness of Cpd38 favored its interaction at the BRD4-BD1 active site relative to the fragment. Strikingly, compared to Fgt47, Cpd38 demonstrated high mobility, which could have enabled it to bind optimally and complementarily with key residues of the active site such as Ile146, Asn140, Cys136, Tyr98, Leu94, Val87, Phe83, and Trp81.
DISCUSSION
On the contrary, the majority of these interactions were gradually lost in Fgt47, which could further indicate the essence of coupling it with the difluoro-phenoxy pyridine scaffold. Furthermore, Cpd38 had a more altering effect on BRD4-BDI relative to Fgt47, which could also be a result of its higher inhibitory activity.
CONCLUSION
Conclusively, the design of highly potent therapeutics could be facilitated by the incorporation of pharmacologically active small molecule fragments into the scaffold of existing drugs.
|
10.2174/1389201022666210322122056
|
pubmed_712_156
|
Twenty-seven thermophilic actinomycete isolates obtained from humidification systems or living-bedroom areas of individuals with suspected but unproved home environment-related respiratory disease were characterized morphologically and biochemically. All isolates were demonstrated to be members of the Thermoactinomyces genus. Two previously misidentified isolates were reclassified as a Thermoacetinomyces sp. Thus, all of our thermophilic actinomycete humidifier isolates studied to date have been identified as either Thermoactinomyces vulgaris or Thermoactinomyces sp. Large numbers of unidentified thermotolerant bacteria have also been isolated from virtually all residual humidifier water samples and their possible role in production of "humidifier-associated" respiratory disease is unknown.
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10.1016/0091-6749(76)90037-3
|
pubmed_1132_4329
|
OBJECTIVE
To examine the spatiotemporal profiles and localization of CysLT1R, CysLT2R and GPR17 in mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD).
METHODS
PD model was induced by subcutaneous injection of MPTP (25 mg/kg) for 5 d in adult male C57BL/6 mice. At d10 after MPTP injection, the expression and cellular localization of CysLT1R, CysLT2R and GPR17 in the substantia nigra were detected by immunohistochemistry and immunofluorescence.
RESULTS
CysLT1R, CysLT22 and GPR17 were normally localized in TH-positive dopaminergic neurons and microglia, while CysLT2R was also expressed in astrocytes. In dopaminergic neurons, approximately 91% co-expressed GPR17, 77% co-expressed CysLT1R and 52% co-expressed CysLT2R. Compared with the control group, TH-positive cells in the substantia nigra were significantly reduced in PD mice. CysLT1R, CysLT2R and GPR17-positive cells were significantly reduced; and CysLT1R, CysLT2R, GPR17-positive dopaminergic neurons were also significantly reduced in the PD group. In the striatum, both CysLT1R and GPR17 were normally expressed in neurons; whereas CysLT2R was expressed in astrocytes. In PD striatum, CysLT1R and GPR17-positive cells were decreased, but CysLT2R expression was significantly increased which mainly expressed in the proliferating astrocytes.
CONCLUSION
CysLT1R, CysLT2R and GPR17 may be involved in the MPTP-induced PD damage in mice.
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10.3785/j.issn.1008-9292.2013.01.009
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pubmed_730_10097
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It has been demonstrated previously that removal of acellular debris from the preimplantation mouse embryo is beneficial for subsequent development to the hatched blastocyst stage. We have studied the impact of cellular fragmentation induced in the mouse embryo during the late pronuclei and 8-cell stages on the hatching frequency and total cell number at the blastocyst stage. At the late pronuclei stage about one-quarter of the cytoplasm was removed from embryos in the experimental group, in four to six steps, thus creating four to six cytoplasts that were subsequently returned as anucleated fragments under the zona pellucida. Embryos with one-quarter of the cytoplasm removed and with intact cytoplasm after partial zona dissection (PZD) served as controls. At the 8-cell stage, embryos with their nucleoplast removed from two blastomeres served as an experimental group. Groups of embryos with part of the cytoplast removed from two blastomeres (nucleated fragments), embryos with two blastomeres removed and embryos after PZD alone served as controls. After manipulation all embryos were left in culture and analysed at about 100 h after human chorionic gonadotrophin administration. Fragments induced at the late pronuclei stage did not participate in compaction and were often spontaneously expelled from the embryo during hatching. Neither embryo hatching rate nor total cell number was affected when compared with zygotes with reduced cytoplasm. Although both nucleated and anucleated fragments induced at the 8-cell stage participated in recompaction, hatching was not compromised and there was no interference in further development as assessed by the cell number or hatching rate at the blastocyst stage, as compared with embryos with blastomeres removed. We conclude that anucleated cellular fragments formed in an otherwise healthy embryo, both before and after acquisition of the ability for compaction, are benign and that their removal provides no benefit for embryo development, at least to the hatched blastocyst stage.
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10.1093/humrep/13.5.1307
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pubmed_997_5219
|
BACKGROUND
In recent years, the mental health level and physical activity level of Chinese teenagers are not ideal, and all sectors of society are actively reversing this bad situation. The purpose of this study is to test the influence of healthy physical education curriculum model on middle school students' extracurricular sports participation based on the trans-contextual model of motivation (TCM).
METHODS
The trial adopts quasi-experimental design comparing equivalent groups. The experimental group adopted the healthy physical education curriculum model in physical education (PE), and the control group adopted the technical-traditional teaching. During the 12 weeks intervention, 327 junior school freshmen completed the test of TCM variables four times as the pre-test, test 2, test 3 and post-test of this experimental study.
RESULTS
After the intervention, students' perceived need support in PE, autonomous motivation in PE, autonomous motivation in leisure time (LT)and the amount of extracurricular sports activities in the experimental group have increased significantly. The perceived need support of experimental group students can predict autonomous motivation in PE positively (β = 0.385, P<.001); Autonomous motivation in PE can predict autonomous motivation in LT positively (β = 0.462, P<.001); Autonomous motivation in LT can predict the intention of extracurricular sports participation positively, and the direct effect was significant (β = 0.172, P<.01), the total indirect effect was significant (β = 0.382, P<.001), the indirect effect of subjective norms was not significant (P>.05); Extracurricular sports participation intention can predict the amount of extracurricular sports activities positively (β = 0.327, P<.001).
CONCLUSIONS
The structural characteristics of healthy physical education curriculum model provide need support for students' learning, improve students' autonomous motivation in and out of PE, and finally promote students' participation in extracurricular sports.
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10.1186/s12889-022-14483-0
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pubmed_432_11345
|
The coloured contact thermography may be used as an additional method for diagnosis of diseases of the abdominal aorta and its major branches. In cases with aneurysms of the abdominal aorta the coloured thermograms showed the increased skin temperature of the frontal abdominal wall over its projection. The method may be used for differential diagnosis of the aneurysm and occlusion of the abdominal aorta.
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pubmed_432_11345
|
pubmed_339_18415
|
Estimation of vitamin C (ascorbic acid) in various samples of fresh and frozen human plasma has shown that freezing in a regular freezer at -25 degrees C causes an approximately 14% loss of ascorbate in the sample. Freezing the same samples in a deep freezer at -75 degrees C causes less of an ascorbate loss amounting to about 9%. On the other hand, using the dry ice alcohol bath freezing, which shortens the freezing process to a fraction of seconds produced loss of ascorbate by 3.5% only. The storage time of previously frozen samples at -25 degrees C or -75 degrees C, from 2 to 14 days does not produce noticeable differences in the sample ascorbate concentration. Loss of ascorbate in samples frozen in the dry ice alcohol bath may be acceptable assuming analytical variability of ascorbate assay amounting to about 4% and broad biological variability of ascorbate concentration in various clinical conditions. Use of frozen plasma samples for ascorbate assays may essentially facilitate running this analysis in clinical laboratories.
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10.1016/s0009-8981(01)00577-0
|
pubmed_15_22624
|
The precise polarization and orientation of developing neurons is essential for the correct wiring of the brain. In pyramidal excitatory neurons, polarization begins with the sprouting of opposite neurites, which later define directed migration and axo-dendritic domains. We here show that endogenous N-cadherin concentrates at one pole of the newborn neuron, from where the first neurite subsequently emerges. Ectopic N-cadherin is sufficient to favour the place of appearance of the first neurite. The Golgi and centrosome move towards this newly formed morphological pole in a second step, which is regulated by PI3K and the actin/microtubule cytoskeleton. Moreover, loss of function experiments in vivo showed that developing neurons with a non-functional N-cadherin misorient their cell axis. These results show that polarization of N-cadherin in the immediate post-mitotic stage is an early and crucial mechanism in neuronal polarity.
|
10.1038/emboj.2012.41
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pubmed_397_21792
|
We assessed the relationship between sun protection policies and practices at child care centers in Massachusetts. We hypothesized that centers with sun protection policies were more likely to have regular sun protection practices in place compared to centers without these policies. We conducted a telephone survey with directors or assistant directors at 327 child care centers during the summer of 2002. The main outcome measure was sun protection practices, which included time spent outside during mid-day and the use of sunscreen, hats, and protective clothing by the majority of children assessed over the last 5 program days. The 36-item survey also inquired about the center's sun protection policy and included demographic questions. Most centers (73%) reported having a written sun protection policy. Sun protection policies were positively associated with reported sunscreen (chi squared = 14.63, p = 0.0001) and hat use (chi squared = 30.98, p < 0.0001) and inversely associated with time outside (chi squared = 10.76, p = 0.001). Seventy-seven percent of centers followed recommended sunscreen practices. However, centers were far less likely to have recommended hat use (36%) and protective clothing (1.5%) practices. A formal sun protection policy may be an effective way to increase sun protection practices in the child care setting. Further research should assess this relationship in other states. Improving and expanding existing state regulations may be a reasonable strategy to increase sun protection at child care centers.
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10.1007/s10900-005-7283-2
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pubmed_753_4725
|
OBJECTIVES
To investigate the practice patterns and clinical outcomes associated with use of rescue therapies in patients with acute lung injury.
DESIGN
Secondary analysis of multicentered, randomized, controlled trial data from the National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network.
SETTING
Intensive care units of Acute Respiratory Distress Syndrome Clinical Trials Network centers across the United States.
PATIENTS
Subjects enrolled in six Acute Respiratory Distress Syndrome Clinical Trials Network trials occurring between 1996 and 2005.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
One hundred sixty-six of 2632 (6.3%) subjects received rescue therapy, defined as prone positioning (97 of 166 [58%]), inhaled vasodilators (47 of 166 [28%]), high-frequency ventilation (12 of 166 [7%]), or extracorporeal membrane oxygenation (10 of 166 [6%]). Use of inhaled vasodilators increased whereas use of prone position decreased over time (p for trend = 0.04 and 0.0013, respectively). Multivariate predictors for use of rescue therapy included age (odds ratio per 10 yrs and 95% confidence interval: 0.88; 0.78-0.99; p = .049), positive end-expiratory pressure (odds ratio per 5-cm H2O increase: 1.33; 95% confidence interval, 1.05-1.69; p = .019), Pao2/Fio2; odds ratio per 5-cm H2O increase: 0.98; 95% confidence interval, 0.96-0.99; p = .017), peak airway pressure (odds ratio per 5-cm H2O increase: 1.11; 95% confidence interval, 1.001-1.237; p = .047), and study order (odds ratio per subsequent Acute Respiratory Distress Syndrome Clinical Trials Network study: 1.21; 95% confidence interval, 1.03-1.41; p = .02). Cox proportional hazards analysis of propensity score-matched subjects showed no difference in survival for those who received rescue therapy vs. those who did not (hazard ratio for death after rescue therapy or index date, 1.10; 95% confidence interval, 0.67-1.78; p = .72). No differences in survival were found between those who received prone positioning vs. inhaled vasodilators (propensity score-adjusted hazard ratio for prone 0.87; 95% confidence interval, 0.86-2.10; p = .76).
CONCLUSIONS
Rescue therapies are utilized in younger patients with more severe oxygenation deficits. Patterns of rescue therapy utilization appear to be changing over time. Within the limits of an observational study design, we did not find evidence of a survival benefit with use of rescue therapies in acute lung injury.
|
10.1097/CCM.0b013e3182120829
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pubmed_810_2059
|
An association of preferential X chromosome inactivation (XCI) with BRCA gene status and breast/ovarian cancer risk has been reported. We evaluated XCI in a large group of BRCA mutation carriers compared to non-carriers and investigated associations between preferential XCI (⩾90:10) and age, mutated gene, cancer development and chemotherapy. XCI was analysed by human androgen receptor (HUMARA) assay and pyrosequencing in 437 BRCA1 or BRCA2 mutation carriers and 445 age-matched controls. The distribution of XCI patterns in the two groups was compared by logistic regression analysis. The association between preferential XCI and selected variables was investigated in both univariate and multivariate fashion. In univariate analyses preferential XCI was not significantly associated with the probability of being a BRCA mutation carrier, nor with cancer status, whereas chemotherapeutic regime and age both showed a significant association. In multivariate analysis only age maintained significance (odds ratio, 1.056; 95% confidence interval, 1.016-1.096). Our findings do not support the usefulness of XCI analysis for the identification of BRCA mutation carriers and cancer risk assessment. The increasing preferential XCI frequency with ageing and the association with chemotherapy justify extending the investigation to other categories of female cancer patients to identify possible X-linked loci implicated in cell survival.
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pubmed_810_2059
|
pubmed_1085_1170
|
Six human isolates of Escherichia coli O157:H7 and E. coli (ATCC 11229) were used to determine the concentrations of free chlorine and exposure times required for inactivation. Free chlorine concentrations of 0.25, 0.5, 1.0, and 2.0 ppm at 23 degrees C were evaluated, with sampling times at 0, 0.5, 1.0, and 2.0 min. Results revealed that five of six E. coli O157:H7 isolates and the E. coli control strain were highly susceptible to chlorine, with >7 log10 CFU/ml reduction of each of these strains by 0.25 ppm free chlorine within 1 min. However, comparatively, one of the seven strains was unusually tolerant to chlorine at 23 degrees C for 1 min, with a 4-, 5.5-, 5.8-, and >5.8-log CFU/ml reduction at free chlorine concentrations (ppm) of 0.25, 0.5, 1.0, and 2.0. respectively. Based on these studies most isolates of E. coli O157:H7 have no unusual tolerance to chlorine; however, one strain was exceptional in being recovered after 1-min of exposure of 10(7) CFU/ml to 2.0 ppm of free chlorine. This isolate may be a useful reference strain for future studies on chlorine tolerance of E. coli O157:H7.
|
10.4315/0362-028x-64.10.1607
|
pubmed_840_18474
|
To elucidate the molecular mechanisms of impaired elastic fiber formation in recessive cutis laxa, we have investigated two disease-causing missense substitutions in fibulin-5, C217R and S227P. Pulse-chase immunoprecipitation experiments indicated that S227P mutant fibulin-5 was synthesized and secreted by skin fibroblasts at a reduced rate when compared with the wild-type protein. Both mutants failed to be incorporated into elastic fibers by transfected rat lung fibroblasts. Purified recombinant fibulin-5 with either mutation showed reduced affinity for tropoelastin in solid-phase binding assays. Furthermore, S227P mutant fibulin-5 also showed impaired association with fibrillin-1 microfibrils. The same mutation triggered an endoplasmic reticulum (ER) stress response, as indicated by the strong co-localization of this mutant protein with folding chaperones in the ER, including calreticulin, immunoglobulin-binding protein and protein disulfide isomerase, and by increased rates of apoptosis in patient fibroblasts. Histological analysis of skin sections from a cutis laxa patient with a homozygous S227P mutation showed a lack of fibulin-5 in the extracellular matrix and a concomitant disorganization of dermal elastic fibers. By electron microscopy, elastic fibers in the skin of this patient showed a failure of elastin globules to fuse into a continuous elastic fiber core. We conclude that recessive cutis laxa mutations in fibulin-5 result in misfolding, decreased secretion and a reduced interaction with elastin and fibrillin-1 leading to impaired elastic fiber development. These findings support the hypothesis that fibulin-5 is necessary for elastic fiber formation by facilitating the deposition of elastin onto a microfibrillar scaffold via direct molecular interactions.
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10.1093/hmg/ddl414
|
pubmed_738_16227
|
BACKGROUND
For frail patients, it may sometimes be preferable to carry out X-ray examinations at the patients' own home. The general state of such patients may worsen due to transport and change of environment when transported for examination at the hospital.
OBJECTIVE
The aim of the randomized controlled trial (RCT) was to investigate if mobile X-ray improves healthcare for fragile patients. The primary outcome was the number of hospitalizations.
DATA SOURCES
We collected all data using questionnaires and data from the Electronic Patient Record (ER).
PARTICIPANTS
Patients referred to a mobile X-ray examination living in nursing homes and homes for the elderly in the Aarhus Municipality (Denmark).
INTERVENTION
mobile X-ray examinations compared to those at the hospital. Study appraisal: Data were collected and stored using the computer programme Redcap. Stata was used for statistical calculations. One hundred and thirty-six patients were included in the RCT. We did not find significant differences between mobile X-ray (intervention) and X-ray at the hospital (control) concerning hospitalizations and number of hospital days. Challenges: We met several challenges when carrying out RCT in the planned study population. Doctors often withdraw the referral when they found out that their patient should go to the hospital instead of mobile X-ray. The nursing home staff often considered the patient too frail to allow the test person to ask questions post X-ray. We also met challenges in the randomization method resulting in bias in the first data collection, so we had to adjust the randomization method.
CONCLUSIONS
For the fragile patients in the present explorative study, mobile X-ray did not significantly reduce the number of hospitalizations compared to X-ray at the hospital. Yet, mobile X-ray may be a new important diagnostic tool for more precise treatment to the frailest patients for whom transportation to the hospital is too exhausting. We need studies with focus on this aspect. We also recommend future RCT studies in a population for which mobile X-ray has not yet been a possibility.
|
10.3390/healthcare8020118
|
pubmed_1026_3473
|
BACKGROUND
Skin cancer is a growing health concern worldwide. It is the most common malignancy in South Africa and places a large burden on the public healthcare sector. There is a paucity of published scientific data on skin cancer in South Africa.
OBJECTIVES
To report the findings of biopsies performed in patients with suspected skin cancer attending the Tygerberg Academic Hospital (TAH) Dermatology outpatient department (OPD) in the Western Cape Province of South Africa. Methodology: A retrospective chart review identified all patients who underwent a biopsy for a suspected skin cancer diagnosis between September 2015 and August 2016 at the TAH dermatology OPD.
RESULTS
A total number of 696 biopsies from 390 participants were identified, of which 460 were histologically confirmed as malignant lesions. The proportion of clinically suspected skin cancers that were histologically confirmed as cancer was 68%. The most commonly occurring malignancies were basal cell carcinoma (BCC) (54.8%), squamous cell carcinoma (SCC) (18.9%), squamous cell carcinoma in-situ (SCCI) (8.0%), Kaposi's sarcoma (KS) (6.7%), malignant melanoma (MM) (6.1%), and keratoacanthoma (KA) (4.6%). The number needed to treat (NTT) for all cancers diagnosed and for MM was 1.5 and 4 respectively. BCC (89.3%) and KS (67.7%) was the most common skin cancer in the white and black population respectively. The ratio of BCC to SCC was 2.03.
CONCLUSION
This study provides valuable scientific data on the accuracy of skin cancer diagnosis, distribution and patient demographics in the Western Cape Province of South Africa, on which further research can be based. The study highlights the burden of skin cancer on this specific population group and calls for standardised reporting methods and increased surveillance of skin cancers.
|
10.1155/2020/9061532
|
pubmed_54_22007
|
Sortase-mediated ligation (SML) is one of the most commonly used techniques for the site-specific modification of proteins. Here, a brief overview on advantages and limitations of this technology in comparison with other chemoselective protein modification techniques is provided and successful approaches that extend the application range of SML are discussed.
|
pubmed_54_22007
|
pubmed_105_13131
|
Objective
To evaluate dry eye disease and meibomian gland dysfunction among type 2 diabetes patients.
Methods
A hospital-based cross-sectional study was conducted. Parameters assessed included meibum expressibility and quality, Schirmer test 1, tear breakup time (TBUT), ocular surface staining, blink rates and Ocular Surface Disease Index (OSDI) scores. Dry eye was diagnosed based on a combination of subjective symptoms, tear function and ocular surface staining.
Results
Prevalence of DED and MGD were 72.3% and 55.3% respectively. Symptomatic dry eye (OSDI scores) was significantly associated with duration of diabetes (rs = 0.11, P = 0.028) and the presence of conjunctival disorders (OR = 2.09, P = 0.002). MGD was a risk factor for DED (OR = 1.99, P = 0.008); ocular surface damage, the presence of eye lid lesions, abnormal Schirmer test and reduced TBUT were significantly associated with MGD, the strongest predictor being ocular surface damage (OR = 3.21, P = 0.001). OSDI scores had no association with the presence of corneal lesions possibly due to reduced corneal sensitivity.
Conclusion
DED and MGD were prevalent among the patients and therefore there is the need for dry eye assessment as a routine clinical management protocol for patients with type 2 diabetes.
|
10.4314/ahs.v22i1.36
|
pubmed_738_15120
|
BACKGROUND
Radiation pneumonitis (RP) is a major pulmonary adverse event of chest radiotherapy. The PACIFIC trial that identified durvalumab as an effective subsequent-line therapy after concurrent chemoradiotherapy (CCRT) found that patients with grade 2 or higher RP may have to be excluded from treatment under certain criteria. The purpose of this study was to investigate the relationship between grade ≥2 RP and the parameters of dose-volume histograms after CCRT with cisplatin/docetaxel for stage III non-small cell lung cancer and conduct a subset analysis of severe RP that can lead to the permanent discontinuation of treatment per the PACIFIC trial criteria to help determine treatment strategy.
METHODS
We calculated the percentage of the lung volume received at least 5 Gy (V5) and 20 Gy (V20), the mean lung dose (MLD), and the lung volume spared from a 5 Gy dose (VS5) to the total lung volume. Factors affecting the incidence of grade ≥2 RP were identified; severe RP was defined as grade ≥3 as well as grade 2 RP that required ≥10 mg prednisolone for at least 12 weeks.
RESULTS
This study included 45 patients. On univariate analysis, all parameters and total lung volume were found to be significant predictors of grade ≥2 RP (P = .001, .003, .03, .004, and .02, respectively). On multivariate analysis, V20 was a significant predictive factor of grade ≥2 RP (P = .007). Severe RP developed in 6 of 37 patients (16.2%) whose V20 values were 35% or lower. On univariate analysis, only V20 was a significant predictor of severe RP in these patients (P = .01).
CONCLUSIONS
The best approach to reduce the rate of grade ≥2 RP is to maintain the V5, V20, MLD, and VS5 as low as possible during radiotherapy planning in patients receiving definitive CCRT with cisplatin/docetaxel.
|
10.1002/cam4.3093
|
pubmed_159_12558
|
Strain engineering can increase the activity and selectivity of an electrocatalyst. Tensile strain is known to improve the electrocatalytic activity of palladium electrodes for reduction of carbon dioxide or dioxygen, but determining how strain affects the hydrogen evolution reaction (HER) is complicated by the fact that palladium absorbs hydrogen concurrently with HER. We report here a custom electrochemical cell, which applies tensile strain to a flexible working electrode, that enabled us to resolve how tensile strain affects hydrogen absorption and HER activity for a thin film palladium electrocatalyst. When the electrodes were subjected to mechanically-applied tensile strain, the amount of hydrogen that absorbed into the palladium decreased, and HER electrocatalytic activity increased. This study showcases how strain can be used to modulate the hydrogen absorption capacity and HER activity of palladium.
|
10.1002/anie.202005248
|
pubmed_390_2241
|
Chemiluminescence (CL) and electron microscopy were used to study the phagocytosis of both virulent and avirulent strains of Leptospira interrogans serovar copenhageni by guinea-pig and human polymorphonuclear leukocytes (PMN). A significant CL response was observed when guinea-pig PMN were incubated with virulent leptospires in the presence but not in the absence of specific immune serum. This response was markedly enhanced by the addition of guinea-pig complement. Phagocytosis was confirmed by the observation of intracellular leptospires in guinea-pig PMN by electron microscopy. The phagocytosis of avirulent leptospires by guinea-pig PMN and of both virulent and avirulent leptospires by human PMN required the presence of both specific immune serum and complement. Thus the ability of leptospires to resist phagocytosis by PMN in the absence of immune serum does not appear to be a major determinant of virulence.
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10.3109/00313028409068531
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pubmed_936_19157
|
Histamine is the prime culprit of toxicity resulting from seafood consumption, whereas conventional detection methods are not convenient to meet the needs of rapid histamine analysis nowadays. Based on upconversion nanoparticles (UCNPs) and inner filter effects (IFE), a novel ratiometric fluorescence nanosystem was developed for the efficient detection of histamine. Through pre-treatment with solid-phase extraction (SPE) and colorific azo coupling reaction of histamine, the fluorescence of UCNPs at 548 nm was quenched, while fluorescence at 664 nm was unchanged. Thus, ratiometric fluorescence I548/I664 was inversely proportional to histamine concentration at a wide range of 10-200 mg/L. The detection limit was 7.34 mg/L, one order of magnitude lower than that of the traditional colorimetric method (25 mg/L). In addition, such a convenient and environment-friendly detection system was further employed to quantify the histamine in fish, shrimp, and shellfish samples, showing excellent application potential in seafood safety.
|
10.1016/j.foodchem.2022.133194
|
pubmed_912_9762
|
This study explored, from a public health perspective, factors that contribute to inconsistent condom use by men in Curaçao through semi-structured face-to-face interviews with 21 heterosexual men. The findings show that there is an important disconnect between what is considered culturally appropriate sexual behaviour for men and women and condom use, that diverging from prescribed notions of masculinity and femininity in order to use condoms consistently is difficult, and that condom use is particularly problematic in the context of concurrent partnerships and sexual economic exchanges. Participants further reported that Caribbean family structures, whereby mothers assume the role as primary caregiver and fathers contribute biologically but, to a much lesser extent socially, also have an impact on condom use. Additionally, consistent condom use was reported to be impeded by a cultural taboo on talking seriously about sex and sexual health. In their totality, findings provide important input from men for the development of sexual health promotion interventions that are cognizant of the cultural context in which inconsistent condom use occurs, and that are geared not only to the individual level but also to the interpersonal and structural levels.
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10.1080/13691058.2012.762119
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pubmed_207_6211
|
Dimethylsulfoxide (DMSO) is readily absorbed through skin, and relieves musculoskeletal pain when applied topically to painful areas. We studied the effects of DMSO on C-type nerve fibers, which mediate pain sensation. DMSO was applied directly to exposed cat sural nerves. C fiber conduction velocity was slowed by DMSO, even in low concentrations (5-7% v/v). Higher concentrations completely blocked C fiber conduction, with a minimum blocking concentration of 9%. Onset of nerve block was almost immediate with 15% DMSO or higher concentrations. C fiber blockade may account for analgesia with DMSO.
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10.1016/0304-3940(93)90522-m
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pubmed_608_9534
|
Heat stress, an important and damaging abiotic stress, regulates numerous WRKY transcription factors, but their roles in heat stress responses remain largely unexplored. Here, we show that pepper (Capsicum annuum) CaWRKY27 negatively regulates basal thermotolerance mediated by H2O2 signaling. CaWRKY27 expression increased during heat stress and persisted during recovery. CaWRKY27 overexpression impaired basal thermotolerance in tobacco (Nicotiana tabacum) and Arabidopsis thaliana, CaWRKY27-overexpressing plants had a lower survival rate under heat stress, accompanied by decreased expression of multiple thermotolerance-associated genes. Accordingly, silencing of CaWRKY27 increased basal thermotolerance in pepper plants. Exogenously applied H2O2 induced CaWRKY27 expression, and CaWRKY27 overexpression repressed the scavenging of H2O2 in Arabidopsis, indicating a positive feedback loop between H2O2 accumulation and CaWRKY27 expression. Consistent with this, CaWRKY27 expression was repressed under heat stress in the presence H2O2 scavengers and CaWRKY27 silencing decreased H2O2 accumulation in pepper leaves. These changes may result from changes in levels of reactive oxygen species (ROS)-scavenging enzymes, since the heat stress-challenged CaWRKY27-silenced pepper plants had significantly higher expression of multiple genes encoding ROS-scavenging enzymes, such as CaCAT1, CaAPX1, CaAPX2, CaCSD2, and CaSOD1. Therefore, CaWRKY27 acts as a downstream negative regulator of H2O2-mediated heat stress responses, preventing inappropriate responses during heat stress and recovery.
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10.3389/fpls.2018.01633
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pubmed_1041_16351
|
For the rapid and reliable detection of oxidized contaminants (i.e., nitrite, nitrate, perchlorate, dichromate) in water, a novel toxicity detection methodology based on sulfur-oxidizing bacteria (SOB) has been developed. The methodology exploits the ability of SOB to oxidize elemental sulfur to sulfuric acid in the presence of oxygen. The reaction results in an increase in electrical conductivity (EC) and a decrease in pH. When oxidized contaminants were added to the system, the effluent EC decreased and the pH increased due to the inhibition of the SOB. We found that the system can detect these contaminants in the 5-50 ppb range (in the case of NO(3)(-), 10 ppm was detected), which is lower than many whole-cell biosensors to date. At low pH, the oxidized contaminants are mostly in their acid or nonpolar, protonated form which act as uncouplers and make the SOB biosensor more sensitive than other whole-cell biosensors which operate at higher pH values where the contaminants exist as dissociated anions. The SOB biosensor can detect toxicity on the order of minutes to hours which can serve as an early warning so as to not pollute the environment and affect public health.
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10.1021/es1036892
|
pubmed_1141_13136
|
Disturbances of retinoid activated transcription mechanisms have recently been implicated as risk factors for schizophrenia. In this study we have compared the regulation of mRNAs for the nuclear orphan receptor NGFI-B, which forms a functional heterodimer with the retinoid x receptor and the related orphan nuclear receptor Nor1 with c-fos mRNA after acute and chronic treatments with haloperidol and clozapine. The antipsychotic drugs haloperidol and clozapine have different clinical profiles. Haloperidol is a typical neuroleptic giving extrapyramidal side effects (EPS), whereas the atypical compound clozapine does not. Acute haloperidol treatment increased NGFI-B, Nor1 and c-fos mRNAs in nucleus accumbens shell and core as well as medial and lateral caudate putamen. In contrast, clozapine lead to an increase of NGFI-B, Nor1 and c-fos only in the accumbens shell. No haloperidol or clozapine effect on these mRNAs was detected in cingulate, sensory or motor cortex. Chronic haloperidol lead to an increase of NGFI-B mRNA in the accumbens core. Acutely, it is possible that the increased levels of NGFI-B, Nor1 and c-fos mRNA levels in striatum and accumbens might indicate a neural activation which possibly can be used when screening for drugs that do not produce EPS. Also, the increased levels of NGFI-B, which is an important component in retinoid signaling, both after acute and chronic treatments of haloperidol suggests altered sensitivity to retinoids which could be an important component for the beneficial antipsychotic effect.
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10.1016/s0006-8993(00)02109-0
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pubmed_902_8737
|
INTRODUCTION
Neurogenic vestibular evoked potentials that are recorded from the scalp have so far been recorded in the form of N3 (click air-conducted), N5 (tone air-conducted), and P10 (bone-conducted stimulus) waveforms. The purpose of this study is to find other vestibular waveforms obtained with air-conducted sound.
METHODS
The experiments were organized into 4 parts: 1) topographic scalp mapping; 2) determining the consistency in appearance of candidate vestibular waveforms; 3) further characteristics such as their relationship to vestibular evoked myogenic potentials, sensitivity to 5-kHz tone, and threshold of activation; and (D) recording of the new vestibular waveforms in a case of hearing loss.
RESULTS
A montage was discovered, O2-P3 and O1-P4 with left and right ear stimulation respectively, that yielded a negative wave at 6 milliseconds after stimulus onset and was labeled N6. It is not a vestibular evoked myogenic potential, disappears with 5-kHz tone stimuli, has a high threshold of stimulation, and is present in a case of hearing loss.
DISCUSSION
A new vestibular waveform is discovered that probably originates at or near the midbrain based on its latency. Together with the previously mentioned waves, lesions along the vestibular pathway can now be localized further.
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10.1097/MAO.0b013e3181cdd6b7
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pubmed_777_4993
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New generation of radiation therapy accelerators requires highly accurate dose measurements with high spatial resolution patterns. IMRT is especially demanding since the positioning accuracy of all the multi-leafs should be verified for each applied field and at any incidence. A new 2-D tissue equivalent dosemeter is presented with high spatial resolution that can fulfil these tasks. A plastic scintillator sheet is sandwiched between two polystyrene cubes, and the emitted light is observed by a high-resolution camera. A patented procedure allows efficient discrimination of the scintillation proportional to the dose from the parasitic Cerenkov radiation. This extraction made on the cumulated images taken during an irradiation field at a rate of 10 images s(-1) provides high-resolution mapping of the dose rate and cumulated dose in quasi real time. The dosemeter is tissue equivalent (ICRU-44) and works both for electrons and photons without complex parameter adjustment, since phantom and detector materials are identical. The calibration is simple and independent of the irradiation conditions (energy, fluence, quality and so on). The principle of the dosemeter and its calibration procedure are discussed in this paper. The results and, in particular, the dose depth profiles are compared with standard ionisation chamber measurements in polystyrene for both photons and electrons. Finally, the detector specifications are summarised and one example of complex IMRT field is discussed.
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10.1093/rpd/ncn228
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