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pubmed_465_4062
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Thrombotic thrombocytopenic purpura is a life-threatening disorder which requires immediate therapy. Unfortunately, there are no widely accepted therapeutic recommendations for this rare disorder. The literature contains large numbers of uncontrolled and often uncomparable studies of a variety of therapies used in differing combinations. This article attempts to rationalize the therapy of thrombotic thrombocytopenic purpura based on our current understanding of its pathophysiology. The rationale of each therapeutic modality, including plasma therapy, corticosteroids, vincristine, antiplatelet agents, and splenectomy, is discussed. This is followed by an overview of the clinical results reported in the literature for these individual treatments. Finally, overall therapeutic guidelines for the therapy of thrombotic thrombocytopenic purpura are presented. It is hoped that these guidelines will clarify the treatment of this disorder until more definitive therapeutic studies are available.
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pubmed_465_4062
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pubmed_849_2312
|
The validity of spontaneous hypertensive rat (SHR) as a model of attention deficit hyperactivity disorder (ADHD) has been explored by comparing SHR with Wistar rats in a test of attention, the two-choice visual discrimination task (2-CVDT). Animals were 4-5 weeks old during the training phase of the experiment and 6-7 weeks old during the testing phase in which they were tested with D-amphetamine, a stimulant drug used for the treatment of ADHD. As compared to Wistar, SHR showed a slightly better attention performance, a slightly lower impulsivity level, and a lower general activity during the training phase, but these differences disappeared or lessened thereafter, during the testing phase. D-amphetamine (0.5, 1 mg/kg) improved attention performance in Wistar, but not in SHR, and did not modify impulsivity and activity in the two strains. In conclusion, the present study did not demonstrate that SHR represents a valid model of ADHD, since it did not show face validity regarding the behavioral symptoms of ADHD and predictive validity regarding the effect of a compound used for the treatment of ADHD. On the other hand, this study showed that the 2-CVDT may represent a suitable tool for evaluating in adolescent Wistar rats the effect on attention of compounds intended for the treatment of ADHD.
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10.1007/s00213-015-3974-2
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pubmed_258_2053
|
Optical coherence tomography (OCT) has changed the standard of care for diagnosis and management of macular diseases in adults. Current commercially available OCT systems, including handheld OCT for pediatric use, have a relatively narrow field of view (FOV), which has limited the potential application of OCT to retinal diseases with primarily peripheral pathology, including many of the most common pediatric retinal conditions. More broadly, diagnosis of all types of retinal detachment (exudative, tractional, and rhegmatogenous) may be improved with OCT-based assessment of retinal breaks, identification of proliferative vitreoretinopathy (PVR) membranes, and the pattern of subretinal fluid. Intraocular tumors both benign and malignant often occur outside of the central macula and may be associated with exudation, subretinal and intraretinal fluid, and vitreoretinal traction. The development of wider field OCT systems thus has the potential to improve the diagnosis and management of myriad diseases in both adult and pediatric retina. In this paper, we present a case series of pediatric patients with complex vitreoretinal pathology undergoing examinations under anesthesia (EUA) using a portable widefield (WF) swept-source (SS)-OCT device.
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10.3389/fmed.2022.860371
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pubmed_910_7415
|
INTRODUCTION
Patients who develop intensive care unit (ICU) acquired delirium stay longer in the ICU, and hospital, and are at risk of long-term mental and physical health problems. Despite guidelines for patient assessment, risk limitation, and treatment in the ICU population, delirium and associated delusions remain a relatively common occurrence on the ICU. There is considerable information in the literature describing the incidence, suspected causes of, and discussion of the benefits and side-effects of the various treatments for delirium in the ICU. But peer-reviewed patient-focused research is almost non-existent. There is therefore a very limited understanding of the reality of delusions in the intensive care unit from the patient's point of view.
METHOD
A secondary analysis of the original interviews conducted by the University of Oxford Health Experiences Research Group was undertaken to explore themes relating specifically to sleep and delirium.
RESULTS
Patients describe a liminal existence on the ICU. On the threshold of consciousness their reality is uncertain and their sense of self is exposed. Lack of autonomy in an unfamiliar environment prompts patients to develop explanations and understandings for themselves with no foothold in fact.
CONCLUSION
Patients on the ICU are perhaps more disoriented than they appear and early psychological intervention in the form of repeated orientation whilst in the ICU might improve the patient experience and defend against development of side-effects.
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10.1371/journal.pone.0153775
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pubmed_1098_15856
|
PURPOSE
Deep endometriosis (DE) is defined by the presence of ectopic endometrial glands, with rectal involvement ranging from 5.3 to 12%. The prevalence of low anterior resection-like syndrome (LARS) in patients with DE, how it affects quality of life (QoL), and its evolution after surgery is unclear. The objective of this study was to assess the gastrointestinal functional outcomes and QoL in patients who underwent surgery for DE.
PATIENTS AND METHODS
A prospective study was conducted from 2017 to 2019, recruiting patients who underwent DE surgery with and without rectal resection. Patients completed LARS and SF-36 questionnaires before, at 6 months and at 1 year after surgery.
RESULTS
Eighty-two patients were enrolled. Rectal segmental resection was required in 16 (19.5%) patients, shaving in 16 (19.5%) and discoid resection in 8 (9.8%). All 8 domains of the SF-36 questionnaire showed improvement during follow-up, reflecting improved QoL after surgery (p ≤ 0.05) in all patients. Mean LARS scores for patients without rectal surgery were 7.5 ± 10.4 before and 13.7 ± 14.2 1 year after surgery; rectal surgery was 13.6 ± 13.6 and 14.6 ± 13.1, respectively (p = 0.17). No significant differences were found in the rectal surgery patients' postoperative LARS score among the 3 rectal DE surgical techniques (p = 0.97), and the SF-36 scores improved independent of the technique performed.
CONCLUSIONS
Patients with DE present a LARS-like syndrome before surgery that does not appear to be negatively affected after rectal surgery, independent of the technique performed. Rectal surgery improves the QoL of patients with DE patients as measured by the SF-36 questionnaire at 1 year of follow-up.
|
10.1007/s00423-022-02705-3
|
pubmed_425_2054
|
Industrial enzymes are the "chip" of modern bio-industries, supporting tens- and hundreds-fold of downstream industries development. Elucidating the relationships between enzyme structures and functions is fundamental for industrial applications. Recently, with the advanced developments of protein crystallization and computational simulation technologies, the structure-function relationships have been extensively studied, making the rational design and de novo design become possible. This paper reviews the progress of structure-function relationships of industrial enzymes and applications, and address future developments.
|
10.13345/j.cjb.190222
|
pubmed_1030_6693
|
BACKGROUND
Earthing is a body contact with earth without insulator. In previous studies, grounding revealed anti-inflammatory effect, immunity enhancement, anticoagulation, and rising blood oxygenation.
AIM
To investigate the role of earthing in treatment and prevention of COVID-19 infection.
METHODS
An observational and interventional study included 71 cases with COVID-19 infection. Earthing was applied as preventive and treatment measures. All participants conducted earthing through direct contact with the earth or connecting apparatus for about 15 min to 6 h/day.
RESULTS
Sixty-nine patients were fully improved within 2 h-11 days after commencement of earthing (mean: 2.9 days, SD ± 2, median: 2 days), while the mean illness duration was 8.9 days (SD ± 4.6) and the median was 9 days. Two patients with many risk factors died where earthing was carried out insufficiently and too late. Nine people contracted mild or short-lived illness (mean: 6.3 days, SD ± 5.5) as a consequence of performing prophylactic earthing. There was a spectacular response in a critically ill patient who was unable to speak due to severe dyspnea with blood oxygen level 38% on continuous oxygen supply. On the second day, after two sessions of 3 h daily earthing, his oxygen level raised to 95% with oxygen supply and 77% without oxygen supply. The following symptoms were improved after implementing earthing: fever, dyspnea, cough, weakness, headache, chest pain, taste and smell sensation loss, anorexia, and body pain.
CONCLUSIONS
Earthing revealed significant curing and preventive effects with a shorter illness duration.
|
10.1016/j.bj.2022.08.002
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pubmed_556_19169
|
Poly(N-isopropyl acrylamide) grafted heparin and chondroitin sulfate were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The copolymers were characterized by NMR, IR, SEC, DLS, SLS and NTA methods. High grafting densities were reached for both glycosaminoglycans. The temperature, pH and polymer concentration affected the low critical solution temperatures values. The increased pNIPAAm chain length, grafting density and concentration led to the sharp phase transition at 35 °C. Spherical nanogels were formed around this temperature. Terminal dodecyl trithiocarbonate groups of the copolymers were reduced to thiols that allowed formation of sensitive nanogels with sharp phase transitions induced by pNIPAAm chains. The copolymers showed no toxicity to the ocular cells and they provided the prolonged release of dexamethasone phosphate at 37 °C. These copolymers are interesting alternatives for ocular drug delivery.
|
10.1016/j.carbpol.2020.116764
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pubmed_592_23109
|
The analysis of lickometer data is often rendered prohibitively tedious by the large volume of data generated by the typical experiment. TongueTwister is an integrated program for the rapid and automatic analysis, presentation, and summary of long- and medium-access data collected by lickometers or of brief-access data collected by multi-bottle lickometers such as the DiLog Instruments MS80. The program was written in C+2 for Macintosh computers, and analyzes data collected by MS-DOS PCs. It takes advantage of the Macintosh user interface to provide quick and convenient output from all the files of a single experimental session, and to export the data to third-party statistical software or other documents. It can batch-process data files by automatically opening and analyzing all the files in a directory; thus, the user can employ directories as a simple database for organizing experimental groups. When a lickometer data file is opened, a textual summary, a raster plot of the lick pattern, the cumulative licks, the lick rate, a histogram of inter-lick intervals, and a breakdown of the session by fractions are automatically calculated and displayed. When an MS80 brief-access file is opened, the lick pattern for each tube presentation and a textual summary of the mean values derived for each tube are automatically displayed. If a directory of files is opened, the mean values derived across all the individual files are calculated and graphed. Analysis parameters can be tailored to the investigator's liking. Tables or graphs can be saved to disk, or copied and pasted into other Macintosh programs for additional analysis. The program may also be used for general-purpose analysis of periodic event records.
|
10.1016/s0031-9384(96)00252-1
|
pubmed_28_10972
|
The gas-to-liquid (GTL) process generates considerable amounts of wastewater that are highly acidic and characterized by its high chemical oxygen demand (COD) content, due to the presence of several organic pollutants, such as alcohols, ketones, aldehydes, and fatty acids. The presence of these organics in the process water may lead to adverse effect on the environment and aquatic life. Thus, it is necessary to reduce the COD content of GTL process water to an acceptable limit before discharging or reusing the treated water. Due to several advantages, biological treatment is often utilized as the main step in GTL process water treatment plants. In order to have a successful biotreatment process, it is required to choose effective and suitable bacterial strains that have the ability to degrade the organic pollutants in GTL process water. In this work, bacterial strains were isolated from the GTL process water, identified by 16S rRNA gene sequencing and then used in the biodegradation process. The detailed identification of the strains confirmed the presence of three organics-degrading bacteria identified as Alcaligenes faecalis, Stenotrophomonas sp., and Ochrobactrum sp. Furthermore, biodegradation experiments were carried out and confirmed that the pure culture as well as the mixed culture consortium of the bacterial strains has the ability to reduce the organic pollutants in GTL process water. However, the growth rate and biodegradation efficiency depend on the type of strains and the initial COD content. Indeed, the removal percentage and growth rate were enhanced after 7 days for all cultures and resulted in COD reduction up to 60%. Moreover, the mixed culture of bacterial strains can tolerate and treat GTL process water with a variety of ranges of COD contents.
|
10.3389/fbioe.2020.603305
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pubmed_767_11030
|
OBJECTIVE
To evaluate the accuracy and safety of freehand pedicle screw placement in surgical correction for thoracolumbar kyphosis caused by ankylosing spondylitis (AS).
METHODS
We retrospectively reviewed 266 consecutive patients with AS who underwent osteotomy for kyphosis correction with freehand screw insertion from January 1998 to April 2015 at our institution. A total of 2314 pedicle screws in 158 patients with AS with postoperative computed tomography scans were included in the study. Postoperative computed tomography was performed to classify accuracy of screws, using the established Gertbein classification (grade 0: no perforation, grade 1: perforation <2 mm, grade 2: perforation between 2 and 4 mm, and grade 3: perforation >4 mm). Patients were divided into 2 groups according to coronal Cobb angle: group A (n = 21, Cobb angle ≥10°), group B (n = 137, Cobb angle <10°).
RESULTS
Among the 2314 pedicle screws, 2168 pedicle screw placements were categorized as grade 0, 71 were grade 1, 51 were grade 2, and 24 were grade 3. Breaches occurred more frequently in L1-S1 than the thoracic spine (7.1% and 5.4%, respectively). T5 (25.0%) and S1 (17.7%) experienced the greatest breach rate, whereas T8, L1, and L3 had the lowest breach rate. The breach rate of group A was greater than that of group B (7.9% vs. 6.1%). None of the breaches resulted in either neurologic deficits or vascular complications.
CONCLUSIONS
Freehand pedicle screw placement can be performed safely with acceptable breach rate in patients with AS and thoracolumbar kyphosis.
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10.1016/j.wneu.2018.05.116
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pubmed_713_4392
|
To assess the efficacy and safety of endoscopic versus conventional surgery for benign parotid tumor.
We searched the electronic databases including PubMed, Embase, Web of Science, CNKI and Wanfang Data for studies published before January, 2021. A meta-analysis was performed using Rev Man 5.3 software.
We retrieved 8 eligible studies involving a total of 532 patients, and 4 of the studies were RCT. The results of meta-analysis showed that endoscopic surgery was better than conventional surgery in terms of incision length (WMD=- 5.73; 95% CI: - 6.84--4.62), intraoperative bleeding volume (WMD=-34.50; 95% CI: -49.09--19.91), postoperative drainage volume (WMD=- 21.72; 95% CI: - 29.31--14.12), subjective satisfaction with incision scar(WMD=2.23; 95%CI: 1.11-3.34), and temporary facial paresis (OR=0.37; 95%CI: 0.17-0.78). There were no significant differences in the operation time, salivary fistula, Frey's syndrome or tumor recurrence between the two groups.
For treatment of benign parotid tumor, endoscopic surgery is a safe surgical procedure and is superior to conventional surgery in terms of incision length, operative bleeding volume, postoperative drainage volume, subjective satisfaction with incision scar, and temporary facial paresis.
|
10.12122/j.issn.1673-4254.2021.03.22
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pubmed_113_18942
|
Background: As preventive measures to curb coronavirus disease 2019 (COVID-19)transmission, Indonesia, Malaysia and Singapore had imposed web-accessible regulations where the popularity of relative internet search volume can be obtained from Google Trends(GT). This research aimed to seek the relationship between public search interest and countries policies, furthermore to observe whether the GT data could be utilized as a tool to make a risk communication during this pandemic. Methods: This retrospective study used GT to analyze the relative search volume (RSV) of keywords large-scale social restrictions (Pembatasan Sosial Berskala Besar - PSBB ), MovementControl Order (MCO) or Perintah Kawalan Pergerakan (PKP) and Circuit Breaker (CB) for Indonesia, Malaysia and Singapore respectively. Daily number of COVID-19 confirmed cases were collected and analyzed using Pearson correlation and time-lag with P<0.05. Every search interest peak and mobility trends changes were qualitatively analyzed. Results: The results exhibited the relationship between the government containment policy, the peaks of analyzed RSV keywords and the mobility trends. The containment policy has significant relationships with COVID-19 daily cases (P<0.05). Conclusion: These results indicated that the government could use GT RSV as a strategy of crisis and risk communication to intervene public behavior towards the pandemic.
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10.34172/hpp.2021.46
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pubmed_873_10154
|
OBJECTIVES
The use of medical foods (MFs) specifically for non-inborn errors of metabolism (non-IEM) is rising. Concomitantly, evidence for the safety and efficacy of these non-IEM MFs is lacking. We examined the current use and costs of non-IEM MFs and determined whether the scientific evidence supporting their effectiveness and medical utility is adequate to warrant public reimbursement.
STUDY DESIGN
We employed a qualitative literature review analysis.
METHODS
PubMed and MEDLINE databases were searched for all years using relevant keywords, including names of non-IEM MFs identified in the California Workers' Compensation System (CAWCS) claims dataset from 2011 to 2013. The quality of extracted data was scored with the Delfini Evidence Tool Kit.
RESULTS
Only 2 (3.2%) of 62 studies were conducted with scientific rigor. These 2 studies were for dietary management of Alzheimer disease, which does not have a distinctive nutritional requirement necessitating an MF. Seventy-one percent of the studies of MFs used by patients in the CAWCS were considered to have uncertain validity.
CONCLUSIONS
Most reviewed non-IEM MFs lack evidence to support their safety and efficacy. These non-IEM MFs do not abide by FDA draft guidance, as they do not address a distinct nutritional requirement for a disease and yet often have a National Drug Code or "Rx only" label. Consequently, these products do not meet the statutory definition of an MF. We recommend that CAWCS and other payers not provide insurance coverage for non-IEM MFs until more scientific evidence supports their safety, efficacy, and use for nutritional need of a disease.
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pubmed_873_10154
|
pubmed_839_13360
|
Mice lacking superoxide dismutase-2 (SOD2 or MnSOD) die during embryonic or early neonatal development, with diffuse superoxide-induced mitochondrial damage. Although stem and progenitor cells are exquisitely sensitive to oxidant stress, they have not been well studied in MnSOD2-manipulated mouse models. Patterns of proliferation and differentiation of cultured myoblasts (muscle progenitor cells), PI3-Akt signaling during differentiation, and the maintenance of mitochondrial mass with aging using myoblasts from young (3-4 week old) and aged (27-29 months old) MnSOD2-overexpressing (Sod2-Tg) and heterozygote (Sod2(+/-)) mice were characterized by us. Overexpression of MnSOD2 in myoblasts had a protective effect on mitochondrial DNA abundance and some aspects of mitochondrial function with aging, and preservation of differentiation potential. Sod2 deficiency resulted in defective signaling in the PI3-Akt pathway, specifically impaired phosphorylation of Akt at Ser473 and Thr308 in young myoblasts, and decreased differentiation potential. Compared with young myoblasts, aged myoblast Akt was constitutively phosphorylated, unresponsive to mitogen signaling, and indifferent to MnSOD2 levels. These data suggest that specific sites in the PI3K-Akt pathway are more sensitive to increased superoxide levels than to the increased hydrogen peroxide levels generated in Sod2-transgenic myoblasts. In wild-type myoblasts, aging was associated with significant loss of mitochondrial DNA relative to chromosomal DNA, but MnSOD2 overexpression was associated with maintained myoblast mitochondrial DNA with aging.
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10.1111/j.1474-9726.2009.00477.x
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pubmed_315_4487
|
Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is an inherited disorder of homocysteine transsulfuration, which manifests by neurological, vascular and connective tissue involvement. So far, 130 pathogenic mutations have been recognized in the CBS gene. We examined 10 independent alleles in Polish patients suffering from CBS deficiency, and we detected four already described mutations (c.1224-2A>C, c.684C>A, c.833T>C, and c.442G>A) and two novel mutations (c.429C>G and c.1039+1G>T). The pathogenicity of the novel mutations was demonstrated by expression in E.coli. This is the first published communication on mutations leading to CBS deficiency in Poland.
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10.1002/humu.9249
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pubmed_923_9043
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Hardiness, social support, perceived health, functional independence, and use of health care facilities were compared in this descriptive study of 45 elderly women with osteoarthritis living in three different environments--urban, rural, and frontier. All participants were between the ages of 65 and 75 years and were residing in their own homes. Statistical differences were found between groups in overall perceived health and functional independence; the frontier sample perceived their health as better and themselves as more functionally independent than the urban or the rural sample. No statistical differences were found in levels of hardiness or perceived social support between the three groups. Use of health care facilities varied among participant groups by environmental context; the urban group made more use of facilities than the rural or frontier group, and the rural group used more facilities than the frontier group.
|
10.1002/art.1790060107
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pubmed_872_4183
|
Treatment of hyperlipidemic patients with the thiol compound N-acetylcysteine (NAC) was previously shown to cause a significant dose-related increase in the high-density lipoprotein (HDL)-cholesterol serum level, suggesting the possibility that its disease-related decrease may result from a diminished thiol concentration and/or thiol/disulfide redox status (REDST) in the plasma. We therefore investigated plasma thiol levels and REDST in normo-/hyperlipidemic subjects with and without coronary heart disease (CHD). The thiol level, REDST, and amino acid concentrations in the plasma and intracellular REDST of peripheral blood mononuclear cells (PBMC) have been determined in 62 normo- and hyperlipidemic subjects. Thirty-three of these subjects underwent coronary angiography, because of clinical symptoms of CHD. All groups of hyperlipidemic patients under test and those normolipidemic individuals with documented coronary stenoses showed a marked decrease in plasma thiol concentrations, plasma and intracellular REDST of PBMCs, and a marked increase in plasma taurine levels. Individual plasma thiol concentrations and plasma REDST were strongly negatively correlated with the serum LDL-cholesterol and positively correlated with the serum HDL-cholesterol level. Together with the earlier report about the effect of NAC on the HDL-cholesterol serum level, our findings suggest strongly that lower HDL-cholesterol serum levels may result from a decrease in plasma thiol level and/or REDST possibly through an excessive cysteine catabolism into taurine.
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10.1016/j.freeradbiomed.2003.07.001
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pubmed_263_5954
|
Advances in our understanding of the complex mechanisms of immune regulation and the interactions between tumor cells and the immune system have provided a solid foundation for advancing cancer immunotherapy and have inspired novel therapeutic strategies. Optimizing the effectiveness of immunotherapy will require targeting the antitumor immune response at multiple levels, and this may be achieved through synergistic combinations. Examples include combining two cancer vaccines to achieve a "prime and boost" effect, combining two immune checkpoint inhibitors, combining immunotherapy with targeted agents, or combining immunotherapy with low-dose chemotherapy or radiation. Immune checkpoint inhibitors, such as ipilimumab and nivolumab, will likely play an important role in the future of immunotherapy. The ability to block key pathways by which tumor cells seek to evade or suppress the immune response is critical to realizing the potential of cancer immunotherapy. Other exciting advances include recombinant oncolytic viruses and adoptive transfer of chimeric antigen receptor T cells. However, many challenges remain if durable tumor eradication with minimal toxicity is to be achieved in a broader population of cancer patients.
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pubmed_263_5954
|
pubmed_442_19820
|
A 32-year-old male presented to Dermatology outpatient Department with complaints of a single nonhealing ulcer on his right thigh. This lesion was there for the last 1 months. It had begun as a small nodule and increased up to the present size of 3 cm with an oozing and ulcerated surface and thickened everted margins. The systemic investigations were normal which included hemogram, biochemistry, including liver and renal function tests, chest X-ray, ultrasonography of abdomen, computed tomography of the thorax, and abdomen. Skin biopsy revealed multiple rounds to oval spores with surrounding halo intracellularly as well as extracellularly. A diagnosis of deep fungal infection as histoplasmosis was made and confirmed on culture.
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10.4103/0019-5154.185748
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pubmed_456_13233
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Pentameric ligand-gated ion channels (pLGICs) are important neuroreceptors, embedded in neuronal membranes, that mediate fast synaptic transmission. The molecular details of their working mechanisms have still to be fully unravelled due to their complexity and limited structural information available. Here we focus on a potential molecular switch in a prototypical pLGIC, the serotonin-activated 5-HT3 receptor, consisting of the trans- cis isomerization of a proline at the interface between the extracellular and transmembrane domain. Mutagenesis electrophysiology experiments previously showed that if such isomerization could not take place, the channel would not open, but the hypothetical role of this mechanism as key to channel gating is still debated. We investigate this switch within the receptor with molecular dynamics and enhanced sampling simulations. We analyze how the isomerization free energy landscape is affected by the receptor environment in comparison to simplified models. Moreover, we reveal how the isomerization, in turn, affects the structural and electrostatic properties of the receptor at the extracellular-transmembrane domain interface, e.g., by tuning the ion selectivity filter.
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10.1021/acs.jpclett.8b03431
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pubmed_635_5099
|
The accelerated failure time (AFT) model is a well-known alternative to the Cox proportional hazard model for analyzing time-to-event data. In this paper we consider fitting an AFT model to right censored data when a predictor variable is subject to measurement errors. First, without measurement errors, estimation of the model parameters in the AFT model is a challenging task due to the presence of censoring, especially when no specific assumption is made regarding the distribution of the logarithm of the time-to-event. The model complexity increases when a predictor is measured with error. We propose a non-parametric Bayesian method for analyzing such data. The novel component of our approach is to model (1) the distribution of the time-to-event, (2) the distribution of the unobserved true predictor, and (3) the distribution of the measurement errors all non-parametrically using mixtures of the Dirichlet process priors. Along with the parameter estimation we also prescribe how to estimate survival probabilities of the time-to-event. Some operating characteristics of the proposed approach are judged via finite sample simulation studies. We illustrate the proposed method by analyzing a data set from an AIDS clinical trial study.
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10.1177/0962280215580668
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pubmed_60_21061
|
Innate immunity and nutrient metabolism are complex biological systems that must work in concert to sustain and preserve life. The effector cells of the innate immune system rely on essential nutrients to generate energy, produce metabolic precursors for macromolecule biosynthesis and tune their responses to infectious agents. Thus disruptions to nutritional status have a substantial impact on immune competence and can result in increased susceptibility to infection in the case of nutrient deficiency, or chronic inflammation in the case of over-nutrition. The traditional, reductionist methods used in the study of nutritional immunology are incapable of exploring the extremely complex interactions between nutrient metabolism and innate immunity. Here, we review a relatively new analytical approach, systems biology, and highlight how it can be applied to nutritional immunology to provide a comprehensive view of the mechanisms behind nutritional regulation of the innate immune system.
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10.1016/j.mam.2011.10.013
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pubmed_499_3418
|
BACKGROUND
Understanding the mechanisms of implementation of public health interventions in community settings is a key aspect of programme assessments. To determine core components and establish a programme theory are important tools to improve functioning and support dissemination of programme models to new locations. An extended early childhood home visiting intervention has been developed on-site in a socioeconomically disadvantaged area of Sweden since 2013 with the aim of reducing persisting health inequities in the population. This study aimed at investigating the core programme components and how the intervention was perceived to contribute towards health equity from early childhood.
METHODS
Qualitative framework method was applied in a document analysis and subsequent semi-structured interviews with 15 key actors involved in the programme.
RESULTS
The intervention was found to be constituted of five core components centred around the situation-based, parental strengthening work method delivered by a qualified team of child health care nurse and social worker. The programme theory foresaw positive effects on child and parental health, responsive parenting practices, families' use of welfare services according to need and increased integration and participation in society. The principles of Proportionate Universalism were recognised in the programme theory and the intervention was perceived as an important contribution to creating conditions for improved health equity for the families. Still, barriers to health equity were identified on the structural level which limit the potential impact of the programme.
CONCLUSIONS
The core components of the Extended home visiting programme in Rinkeby correspond well to those of similar evidence-based home visiting interventions. Combining focus on early childhood development and responsive parenting with promoting access to the universal welfare services and integration into society are considered important steppingstones towards health equity. However, a favourable macro-political environment is required in the endeavour to balance the structural determinants' influence on health inequities. Improved availability and accessibility to welfare services that respond to the needs of the families regarding housing, education and employment are priorities.
TRIAL REGISTRATION
The study was retrospectively registered on 11/08/2016 in the ISRCTN registry ( ISRCTN11832097 ).
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10.1186/s12889-022-13492-3
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pubmed_460_21986
|
INTRODUCTION
In the management of dysphagic stroke patients, percutaneous endoscopic gastrostomies (PEGs) are frequently sited early due to the failure of nasogastric tube (NGT) feeding, with NGTs becoming displaced in over 58% of cases. PEG insertion is a procedure with significant mortality and morbidity. We adapted a novel technique of securing NGTs (a nasal loop) which is non-invasive, allows successful NG feeding and may avoid the need for PEG placement.
AIMS
To show that nasal loops result in improved delivery of enteral nutrition. To compare the outcome and complication rate of nasal loop fed patients with those undergoing PEG feeding.
METHODS
A 6 month prospective audit of dysphagic stroke patients who were referred for PEG. All patients who were referred with failed NG feeding within 28 days of presentation were offered a nasal loop. Patients who were 28 days post-stroke had a PEG placed if appropriate. The daily feed intake was monitored before and after nasal loop placement. Complication rates and patient outcomes were documented at 2 week and 3 month follow-up.
RESULTS
Nasal loop group: 14 patients had a nasal loop for a median of 15 days. The median daily feed provided was 0% before nasal loop and 100% after. Four patients went on to recover normal swallowing, 4 patients died and 6 later proceeded to PEG. PEG group: Seven patients proceeded direct to PEG, 1 died and 6 were alive and PEG fed at 3 months. There were 6 complications from PEG insertion. No patients recovered normal swallowing.
CONCLUSIONS
Nasal loops are safe, well tolerated, and effective at delivering full enteral nutrition. Nasal loops allow time for patients who may recover normal swallowing to do so, and thus avoid a PEG. Nasal loops avoid unnecessary PEG insertion in those with a poor prognosis who will not ultimately survive their initial stroke.
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10.1016/j.clnu.2003.09.008
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pubmed_1096_7890
|
BACKGROUND
The application of alcohol-containing medicinal products to children has been a subject of discussion for many years. A safety threshold of 0.125‰ blood alcohol concentration following the administration of a single dose has been recommended by the European Medicines Agency.The aim of this clinical study was to prove the safety of administering a fixed combination of thyme herb and primrose root fluid extract (Bronchicum(®) Elixir) containing 4.9% ethanol.
METHODS
The herbal drug was administered for a period of 7-9 days to 16 children (ages 1-12 years) suffering from acute bronchitis for ≤ 48 h. After 3-5 days, a blood sample was taken 45 min (children ≥ 5 years: also 0 and 90 min) after application of the drug. The efficacy was assessed using the Bronchitis Severity Score. Global efficacy and tolerability were rated by the investigator and patients.
RESULTS
All measured blood ethanol concentrations were below the threshold (mean value after 45 min: 0.0029 ± 0.0057‰ and after 90 min: 0.0051 ± 0.0078‰). The Bronchitis Severity Score decreased from 6.6 ± 1.0 to 0.9 ± 1.6 points. Global efficacy was assessed as "very good" and "good" in 60% (investigator) and 80% (patients) of cases. Global tolerability was rated as "very good" and "good" in more than 90% of cases.
CONCLUSION
In conclusion, oral administration of the drug containing 4.9% ethanol to children (age 1-12 years) demonstrated a favourable risk/benefit ratio of the drug.
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10.1055/s-0034-1398543
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pubmed_1113_18235
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Accidental ingestion of foreign bodies is a common pediatric problem. Non-sharp items like coins, jewelry, pieces of toys are most frequently found among swallowed objects. They usually pass through a child's digestive system without health consequences (40-90% of reported cases). Approximately 10% of children require endoscopic intervention and 1-3% undergoes a surgical treatment. Authors present a unique health hazard caused by multiple magnet ingestion and general management in these cases of this specific foreign body presence. A 6 y.o. boy, in excellent health has been admitted G.I. Dept. presenting a history of accidental ingestion of two magnets (size 1.5 x 0.5 cm) 4 days prior to hospitalization. On admission patient presented no symptoms of foreign body in GI tract, however his WBC was 15000/mm3, ESR-22mm. Foreign bodies have been removed under general anesthesia using endoscopic technique. Endoscopic view of the esophagus region from which magnet has been removed at first might have been identify as a perforation of the esophageal wall. Chest X-ray has not revealed symptoms of pneumothorax, as well as the contrast radiologic study showed symptoms of upper GI tract perforation. Conservative treatment has been administered. Patient has been discharged home with no complaints in general and local good condition. Ingestion of more than one magnets is an strong indication for an immediate endoscopic intervention. Such an algorithm is strongly advocated to prevent of lesion formation in the soft tissues located between two objects with paramagnetic properties which may cause ischemic necrosis and perforation of the GI tract wall.
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pubmed_1113_18235
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pubmed_20_13081
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The fact that many chemotherapeutic drugs cause chemoresistance and side effects during the course of colorectal cancer treatment necessitates development of novel cytotoxic agents aiming to attenuate new molecular targets. Here, we show that Astragalus membranaceus (Fischer) Bge. var. mongolicus (Bge.) Hsiao (AM), a traditional Chinese medicine, can inhibit tumor growth in vivo and elucidate the underlying molecular mechanisms. The antitumor effect of AM was assessed on the subcutaneous tumors of human colorectal cancer cell line HCT116 grafted into nude mice. The mice were treated with either water or 500 mg/kg AM once per day, before being sacrificed for extraction of tumors, which were then subjected to microarray expression profiling. The gene expression of the extraction was then profiled using microarray analysis. The identified genes differentially expressed between treated mice and controls reveal that administration of AM suppresses chromosome organization, histone modification, and regulation of macromolecule metabolic process. A separate analysis focused on differentially expressed microRNAs revealing involvement of macromolecule metabolism, and intracellular transport, as well as several cancer signaling pathways. For validation, the input of the identified genes to The Library of Integrated Network-based Cellular Signatures led to many chemopreventive agents of natural origin that produce similar gene expression profiles to that of AM. The demonstrated effectiveness of AM suggests a potential therapeutic drug for colorectal cancer.
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10.3892/or.2015.4441
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pubmed_386_14348
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There is a soft consensus on what the health system's characteristics should be, the firmer view on the recurring barriers to change, and how all of this, save for the digital backbone element, could have been written 30 years ago. It is this chronic system stasis when change is urgently needed that casts doubt on the public administration of health services.
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10.1016/j.hcmf.2014.08.012
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pubmed_830_13230
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BACKGROUND
There is a growing problem of physical inactivity in America, and approximately a quarter of the population report being completely sedentary during their leisure time. In the U.S., TV viewing is the most common leisure-time activity. Stepping in place during TV commercials (TV Commercial Stepping) could increase physical activity. The purpose of this study was to examine the feasibility of incorporating physical activity (PA) into a traditionally sedentary activity, by comparing TV Commercial Stepping during 90 min/d of TV programming to traditional exercise (Walking).
METHODS
A randomized controlled pilot study of the impact of 6 months of TV Commercial Stepping versus Walking 30 min/day in adults was conducted. 58 sedentary, overweight (body mass index 33.5 ± 4.8 kg/m2) adults (age 52.0 ± 8.6 y) were randomly assigned to one of two 6-mo behavioral PA programs: 1) TV Commercial Stepping; or 2) Walking 30 min/day. To help facilitate behavior changes participants received 6 monthly phone calls, attended monthly meetings for the first 3 months, and received monthly newsletters for the last 3 months. Using intent-to-treat analysis, changes in daily steps, TV viewing, diet, body weight, waist and hip circumference, and percent fat were compared at baseline, 3, and 6 mo. Data were collected in 2010-2011, and analyzed in 2011.
RESULTS
Of the 58 subjects, 47 (81%) were retained for follow-up at the completion of the 6-mo program. From baseline to 6-mo, both groups significantly increased their daily steps [4611 ± 1553 steps/d vs. 7605 ± 2471 steps/d (TV Commercial Stepping); 4909 ± 1335 steps/d vs. 7865 ± 1939 steps/d (Walking); P < 0.05] with no significant difference between groups. TV viewing and dietary intake decreased significantly in both groups. Body weight did not change, but both groups had significant decreases in percent body fat (3-mo to 6-mo), and waist and hip circumference (baseline to 6-mo) over time.
CONCLUSIONS
Participants in both the TV Commercial Stepping and Walking groups had favorable changes in daily steps, TV viewing, diet, and anthropometrics. PA can be performed while viewing TV commercials and this may be a feasible alternative to traditional approaches for increasing daily steps in overweight and obese adults.
TRIAL REGISTRATION
This study is registered at ClinicalTrials.gov, NCT01342471.
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10.1186/1479-5868-9-95
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pubmed_463_20022
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This study was performed to clarify the morphologic characteristics of two layers of the posterior tibiotalar ligament (PTT) and two bands of the deep PTT (dPTT), and to correlate the dissection findings with MR images. Sixty-four ankles from 42 cadavers were examined. The origin and insertion sites of the superficial PTT (sPTT) and the two bands of the dPTT were identified, and their length, width, and thickness were measured. MRI was performed on four ankles before serial sectioning or dissection. The serial sections were taken at a thickness of 2 mm. The sPTT was observed in 50 out of 60 dissected specimens (83.3%), taken from 64 ankles of 42 cadavers. The dPTT was observed in all specimens. The sPTT, superficial band of the dPTT (sdPTT), and deep band of the dPTT (ddPTT) arose from the inferior surface of the medial malleolus. The sPTT attached to the posterior process of the talus, and the sdPTT and ddPTT attached to the depression below the articular facet for the medial malleolus. The sPTT and two bands of the dPTT could be distinguished on coronal MR images, where the sPTT appeared as a thin string superficial to the two bands of the dPTT, which were separated as two thick, low-density strings. In the coronal plane of frozen sections, the outermost sPTT appeared as a thin, white bundle attached to the sdPTT. The PTT is composed of superficial and deep layers, and the dPTT is composed of superficial and deep bands.
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10.1002/ca.22302
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pubmed_728_7593
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A comparative study of individuals exhibiting the trisomy 21 syndrome (Down's) and a normal group has shown statistically significant differences in cranial shape (norma lateralis). These differences illustrate the departure from normal growth seen in individuals displaying the trisomy 21 syndrome. Fourier analysis is a preferred method since it is more efficient than conventional techniques in the analysis of complex shapes. Fourier analysis is also attractive because the series terms are orthogonal, hence independent; further, the Fourier approach allows for the control of size differences. A three-way analysis of variance was used to test for significant differences between mean Fourier coefficients. The results showed significant difference between individuals with trisomy 21 and controls. Age differences were also significant, only sex differences tended to be non-significant. Finally, the trisomy 21 sample is twice as variable as the controls.
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pubmed_728_7593
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pubmed_1119_16316
|
Type II oculocutaneous albinism (OCA2) is an autosomal recessive disorder in which the biosynthesis of melanin pigment is reduced in the skin, hair, and eyes. OCA2, which results from mutations of the P gene, is the most frequent type of albinism in African and African-American patients. OCA2 is especially frequent in Tanzania, where it occurs with an incidence of approximately 1/1,400. We have identified abnormalities of the P gene in each of 13 unrelated patients with OCA2 from Tanzania. One of these, a deletion of exon 7, is strongly predominant, accounting for approximately 77% of mutant alleles in this group of patients.
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pubmed_1119_16316
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pubmed_196_763
|
INTRODUCTION
The purpose of this study was to determine the effectiveness and harms of periprostatic block compared with other interventions in patients with clinically suspected prostate cancer who underwent transrectal biopsy to diminish pain.
MATERIAL AND METHODS
We included only clinical trials which involved male adults older than 18 years-old suspected of having prostate cancer. The intervention performed was a periprostatic block and the comparators were topical anesthetics, sedatives, placebo/no intervention or combined therapies. The primary outcome was perianal or perineal pain and serious adverse effects (SAE). Literature search was conducted in MEDLINE, EMBASE, LILACS, CENTRAL and non-published literature from inception to March 2019. We performed a network meta-analysis in R.
RESULTS
We included 43 studies in the meta-analysis. Thirteen studies compared periprostatic block vs. placebo/no intervention (the most frequent). Most of the studies had an unclear risk of bias for selection, performance and detection bias and low risk for attrition, reporting and other bias. Periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) vs. periprostatic block (lidocaine) showed an RR -0.9 (95%CI - 1.9 to 0.074); intrarectal gel (lidocaine) vs. periprostatic block (lidocaine) had a RR 0.77 (95%CI 0.14 to 1.4); placebo/no intervention vs. periprostatic block (lidocaine) + intrarectal gel (lidocaine+prilocaine) RR 3 (95%CI 1.9 to 4); intrarectal gel (lidocaine) versus periprostatic block (lidocaine) + intrarectal gel (lidocaine + prilocaine) RR 1.7 (95%CI 0.64 to 2.7).
CONCLUSIONS
The blockage of the periprostatic plexus in the performance of a transrectal ultrasound-guided prostatic biopsy, alone or in combination with intrarectal analgesia or sedation, is an effective method to reduce pain.
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10.5173/ceju.2019.1874
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pubmed_1063_11662
|
Type 2 diabetes (T2D) is known as a disease caused by gene alterations characterized by insulin resistance, thus the insulin-responsive tissues are of great interest for T2D study. It's of great relevance to systematically investigate commonalities and specificities of T2D among those tissues. Here we establish a multi-level comparative framework across three insulin target tissues (white adipose, skeletal muscle, and liver) to provide a better understanding of T2D. Starting from the ranks of gene expression, we constructed the 'disease network' through detecting diverse interactions to provide a well-characterization for disease affected tissues. Then, we applied random walk with restart algorithm to the disease network to prioritize its nodes and edges according to their association with T2D. Finally, we identified a merged core module by combining the clustering coefficient and Jaccard index, which can provide elaborate and visible illumination of the common and specific features for different tissues at network level. Taken together, our network-, gene-, and module-level characterization across different tissues of T2D hold the promise to provide a broader and deeper understanding for T2D mechanism.
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10.3389/fgene.2019.00252
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pubmed_260_14243
|
The introduction of oxygen in electrochemical oxidation at relatively high temperature and pressure as a promoter resulting in synergetic effects, greatly improves the mineralization of high-concentrated organic pollutants.
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10.1039/b702198d
|
pubmed_801_15183
|
BACKGROUND
Many studies have reported significant behavioral impact of physical activity interventions. However, few have examined changes in potential mediators of change preceding behavioral changes, resulting in a lack of information concerning how the intervention worked. Our purpose was to examine mediation effects of changes in psychosocial variables on changes in physical activity in type 2 diabetes patients.
METHODS
Ninety-two patients (62 ± 9 years, 30, 0 ± 2.5 kg/m(2), 69% males) participated in a randomized controlled trial. The 24-week intervention was based on social-cognitive constructs and consisted of a face-to-face session, telephone follow-ups, and the use of a pedometer. Social-cognitive variables and physical activity (device-based and self-reported) were collected at baseline, after the 24-week intervention and at one year post-baseline. PA was measured by pedometer, accelerometer and questionnaire.
RESULTS
Post-intervention physical activity changes were mediated by coping with relapse, changes in social norm, and social modeling from family members (p ≤ 0.05). One-year physical activity changes were mediated by coping with relapse, changes in social support from family and self-efficacy towards physical activity barriers (p ≤ 0.05)
CONCLUSIONS
For patients with type 2 diabetes, initiatives to increase their physical activity could usefully focus on strategies for resuming regular patterns of activity, on engaging family social support and on building confidence about dealing with actual and perceived barriers to activity.
TRIAL REGISTRATION
NCT00903500, ClinicalTrials.gov.
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10.1186/1479-5868-8-105
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pubmed_512_8343
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Rachel Wright qualified as a veterinary nurse in England and volunteered extensively in developing countries before setting up an animal hospital in Rajasthan in India.
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10.1136/vr.i1222
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pubmed_952_81
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53 patients presenting with post-prostatectomy obstructive complications above the verumontanum were treated in a single session by means of guided dilatation of the stricture followed by transurethral resection of the stenosing fibrotic tissue. The results obtained in cases of vesical neck stenosis were very encouraging. Unsatisfactory results were observed in cases of cervicoprostatic fibrosclerosis where resection was insufficient for resolution of the obstruction. No failures or complications with the guided dilatation technique have been observed.
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10.1055/s-0028-1098478
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pubmed_286_15452
|
Purpose To evaluate the association between Breast Imaging Reporting and Data System (BI-RADS) mammographic and magnetic resonance (MR) imaging features and breast cancer recurrence risk in patients with estrogen receptor-positive breast cancer who underwent the Oncotype DX assay. Materials and Methods In this institutional review board-approved and HIPAA-compliant protocol, 408 patients diagnosed with invasive breast cancer between 2004 and 2013 who underwent the Oncotype DX assay were identified. Mammographic and MR imaging features were retrospectively collected according to the BI-RADS lexicon. Linear regression assessed the association between imaging features and Oncotype DX test recurrence score (ODxRS), and post hoc pairwise comparisons assessed ODxRS means by using imaging features. Results Mammographic breast density was inversely associated with ODxRS (P ≤ .05). Average ODxRS for density category A was 24.4 and that for density category D was 16.5 (P < .02). Both indistinct mass margins and fine linear branching calcifications at mammography were significantly associated with higher ODxRS (P < .01 and P < .03, respectively). Masses with indistinct margins had an average ODxRS of 31.3, which significantly differed from the ODxRS of 18.5 for all other mass margins (P < .01). The average ODxRS for fine linear branching calcifications was 29.6, whereas the ODxRS for all other suspicious calcification morphologies was 19.4 (P < .03). Average ODxRS was significantly higher for irregular mass margins at MR imaging compared with spiculated mass margins (24.0 vs 17.6; P < .02). The presence of nonmass enhancement at MR imaging was associated with lower ODxRS than was its absence (16.4 vs 19.9; P < .05). Conclusion The BI-RADS features of mammographic breast density, calcification morphology, mass margins at mammography and MR imaging, and nonmass enhancement at MR imaging have the potential to serve as imaging biomarkers of breast cancer recurrence risk. Further prospective studies involving larger patient cohorts are needed to validate these preliminary findings. © RSNA, 2017 Online supplemental material is available for this article.
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10.1148/radiol.2017162333
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pubmed_471_10824
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Troxerutin (TX), a bioflavonoid widely present in various fruits and vegetables, has shown to exhibit numerous pharmacological properties including anti-neoplastic and anti-cancer activities. Nrf2 and NF-κB are the key transcription factors that regulate oxidative stress and inflammation, therefore we assessed whether TX modulate these pathways and its downstream proteins in HuH-7 hepatocarcinoma cells. TX induced apoptotic cellular and nuclear changes were examined by fluorescence staining techniques, agarose gel electrophoresis and flow cytometry. Oxidative stress was determined through biochemical analysis of antioxidant enzymes and lipid peroxidation profile. The protein expressions of NF-κB and Nrf2 pathway regulators, cell proliferation markers and apoptotic pathway mediators were evaluated by performing immunoblotting, immunocytochemistry and molecular docking. Our results revealed that TX inhibits the growth of HuH-7 cells in a concentration and time-dependent manner. TX treated HuH-7 cells exhibited increased heme oxygenase (HO)-1 protein expression, augmented nuclear translocation of Nrf2, and reduced oxidative stress. Furthermore, TX suppressed the expression of IKKβ which subsequently inhibited the nuclear translocation of NF-κB (p65 subunit), and thus downregulated NF-κB mediated inflammatory responses, proliferation and cell survival. Collectively, our results indicate that TX exerts anti-cancer effect in HuH-7 hepatocarcinoma cells possibly through simultaneous regulation of the molecular signalling pathways, Nrf2 and NF-κB.
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10.1016/j.tiv.2018.10.018
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pubmed_239_4226
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Reflecting on Storeng and Béhague ("Lives in the balance": the politics of integration in the Partnership for Maternal, Newborn and Child Health. Health Policy and Planning Storeng and Béhague (2016).) historical ethnography of the Partnership for Maternal, Newborn and Child Health (PMNCH), this commentary provides a more current account of PMNCH's trajectory since its inception in 2005. It highlights PMNCH's distinct characteristics and how it is positioned to play an instrumental role in the current global health landscape.
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10.1093/heapol/czx018
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pubmed_738_18926
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Constructing biocompatible soft materials via supramolecular approaches remains an important challenge for in vivo applications. Substantial efforts have been made to develop biocompatible non-polymeric materials allowing sustained release of biomolecules and/or drugs in vivo. Herein, we introduce disulfide based low molecular weight gels (LMWGs) allowing the in vitro selective sustained release of proteins containing thiol residues. The novel glycosylated nucleoside based bola-amphiphile (GNBA), which features a disulfide bond inserted in the hydrophobic segment, self-assembles to stabilize the resulting hydrogel. Rheological studies show the dominant elastic character and thixotropic properties of the disulfide LMWG demonstrating its injectability. In vitro and in vivo biodegradation investigations reveal that the disulfide LMWG is stable for several weeks. Importantly, disulfide bonds can be cleaved through the thiol-disulfide exchange reactions with small redox molecules such as dithiothreitol (DTT). The disulfide LMWG loaded with a thiol-containing protein (bovine serum albumin) features sustained release in vitro, whereas a dextran of the same molecular weight, lacking a thiol biomolecule, shows quick release. The disulfide GNBA is the first example of a LMWG allowing selective long term sustained release in vitro via a disulfide reshuffling mechanism.
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10.1039/d0bm00508h
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pubmed_1001_4281
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We consider a random network of nonlinear maps exhibiting a wide range of local dynamics, with the links having normally distributed interaction strengths. The stability of such a system is examined in terms of the asymptotic fraction of nodes that persist in a nonzero state. Scaling results show that the probability of survival in the steady state agrees remarkably well with the May-Wigner stability criterion derived from linear stability arguments. This suggests universality of the complexity-stability relation for random networks with respect to arbitrary global dynamics of the system.
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10.1103/PhysRevE.71.020902
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pubmed_265_276
|
Expression of retroviral Gag polyproteins is sufficient for morphogenesis of virus-like particles with a spherical immature protein shell. Proteolytic cleavage of Gag into the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains (in the case of human immunodeficiency virus [HIV]) leads to condensation to the mature cone-shaped core. We have analyzed the formation of spherical or cylindrical particles on in vitro assembly of purified HIV proteins or inside Escherichia coli cells. CA protein alone yielded cylindrical particles, while all N-terminal extensions of CA abolished cylinder formation. Spherical particles with heterogeneous diameters or amorphous protein aggregates were observed instead. Extending CA by 5 amino acids was sufficient to convert the assembly phenotype to spherical particles. Sequences C-terminal of CA were not required for sphere formation. Proteolytic cleavage of N-terminally extended CA proteins prior to in vitro assembly led to the formation of cylindrical particles, while proteolysis of in vitro assembly products caused disruption of spheres but not formation of cylinders. In vitro assembly of CA and extended CA proteins in the presence of cyclophilin A (CypA) at a CA-to-CypA molar ratio of 10:1 yielded significantly longer cylinders and heterogeneous spheres, while higher concentrations of CypA completely disrupted particle formation. We conclude that the spherical shape of immature HIV particles is determined by the presence of an N-terminal extension on the CA domain and that core condensation during virion maturation requires the liberation of the N terminus of CA.
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10.1128/JVI.72.6.4798-4810.1998
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pubmed_650_15825
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Endo-beta-glucanase I (EGI) of Trichoderma reesei was produced in laboratory and pilot scale using recombinant strains of "bottom-fermenting" Saccharomyces cerevisiae. The gene eg/1 was integrated in the chromosome or an expression cassette was inserted on a multicopy plasmid. Expression levels were compared in a laboratory scale bioreactor. The best EGI-producing strain was cultivated in pilot scale. Adsorbent treatment was used to remove endogenous yeast proteins and other impurities from the culture filtrate during concentration. Effective pilot scale one-step purification of the EGI protein was obtained using DEAE-Sepharose, on which EGI was weakly bound. The purified enzyme reacted with antibodies prepared against T. reesei EGI and catalyzed the hydrolysis of both insoluble and soluble substrates.
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10.1016/0168-1656(91)90004-f
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pubmed_1142_9034
|
BACKGROUND
Scrub typhus is a neglected rickettsial disease in India. Every year, we are facing outbreaks of Scrub typhus after Monsoon season. Patients present with a wide clinical spectrum ranging from pyrexia of unknown origin to multiple organ dysfunction. Some of these clinical features overlap with presentation of other tropical infections prevalent in Indian subcontinent, which leads to diagnostic dilemma and delay in diagnosis. Hence, we planned this study to know the demographic, clinical and biochemical profile of scrub typhus patients.
METHODS
This was an observational study conducted in department of Medicine, King George's Medical University Lucknow, India a leading tertiary care hospital of Northern India. All scrub typhus patients were evaluated by detailed history, examination and laboratory tests.
RESULTS
We enrolled 52 patients in our study. The mean age of the patients was 35.17 ± 16.90 years with majority (82.7%) of patients from rural background. All the patients had fever with an average duration of 9.6 ± 2 days. Most of the patients developed hepatitis (69.2%) followed by acute encephalitis syndrome (47%), acute kidney injury (23.1%) and acute respiratory failure (19.2%). Eschar was found in 11 patients (21.2%).
CONCLUSION
Scrub typhus is often misdiagnosed or diagnosed late due to its wide clinical spectrum overlapping with clinical presentation of other commonly prevalent tropical diseases. One should always consider the differential diagnosis of scrub typhus while evaluating a young febrile patient of rural background, with features of single or multiple organ dysfunction and laboratory findings of leucocytosis, thrombocytopenia and elevation of transaminases.
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10.4103/jfmpc.jfmpc_1162_20
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pubmed_63_19832
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Few studies have evaluated human seizure occurrence over the 24-hour day, and only one group has employed intracranial electrocorticography monitoring to record seizures. Circadian patterns in seizures may have important implications in diagnosis and therapy and provide opportunities in research. We have analyzed spontaneous seizures in 33 consecutive patients with long-term intracranial EEG and video monitoring. Several aspects of seizures were noted, including time of day, origin, type, and behavioral state (sleeping/awake). We recorded 450 seizures that showed an uneven distribution over the day, depending on lobe of origin: temporal lobe seizures occurred preferentially between 1100 and 1700 hours, frontal seizures between 2300 and 0500 hours, and parietal seizures between 1700 and 2300 hours. In the awake state, larger proportions of clinical seizures were seen from 0500 to 1100 hours and from 1700 to 2300 hours. During sleep, larger proportions occurred from 1100 to 1700 hours and from 2300 to 0500 hours. Our results suggest that seizures from different brain regions have a strong tendency to occur in different diurnal patterns.
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10.1016/j.yebeh.2009.01.020
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pubmed_298_24404
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Globally, abortion has emerged as a critical determinant of maternal morbidity and mortality. The Ghana government amended the country's abortion law in 1985 to promote safe abortion. This article discusses the findings of a qualitative study that explored the decision-making experiences of 28 female abortion seekers aged between 15 and 30 years in Ghana. Key findings from the study are that individuals claimed autonomy in their abortion decisions; underlying the abortion decisions were pragmatic concerns such as economic difficulties, child spacing, and fear of parental reaction. In conclusion, we examine the health implications of Ghanaian women's abortion decisions.
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10.1080/07399332.2014.914941
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pubmed_636_7734
|
BACKGROUND
Dengue, a mosquito-borne viral infection caused by one of the four dengue virus (DENV) serotypes (DENV-1 to 4), replicate alternately on the mosquito vector and human host and are responsible for infections throughout tropical and subtropical regions of the world. In Brazil, the disease has become a major public health problem and the introduction of DENV-3 in 2000 in Rio de Janeiro (RJ) was associated with severe dengue epidemics. The potential emergence of strains associated with severe disease highlights the need for the surveillance of DENV in human host and vectors.
METHODS
Aiming to contribute for DENV phylogenetic and vector-virus-human host studies, we sequenced the entire genome of one DENV-3 isolated from naturally infected Aedes aegypti from RJ in 2001 and characterized the 3' UTR from strains isolated from mosquitoes and humans. Mosquitoes were pooled and submitted to virus isolation in Ae. albopictus C6/36 cells and the infecting serotype was identified by immunofluorescence using type-specific monoclonal antibody. Sequence analysis was performed using BioEdit software, the multiple alignments were performed using CLUSTAL W and the phylogenetic analysis by MEGA 5, using the Neighbor-joining method. Secondary structure prediction was performed by using the MFOLD program.
RESULTS
Exclusive substitutions and a substitution leading to a stop codon on the NS5 gene were observed in the DENV-3 isolated from a naturally infected Ae. aegypti and fully sequenced. As an 8- nucleotides deletion was observed within the 11- nucleotides (nts) insertion on the variable region (VR) from the 3'UTR in this isolate, we further sequenced other DENV-3 from both mosquitoes and humans. The majority of DENV-3 from RJ analyzed were characterized by the 11-nts insertion in the VR of the 3'UTR, despite the observation of strains carrying the 8-nts deletion. The latter presented similar secondary structures, however not all strains presenting the 11-nts insertion were similar in the predicted secondary structure.
CONCLUSIONS
The phylogeny based on the analysis of the complete genome and 3'UTR characterized the DENV-3 isolated from both vector and human host as belonging to Genotype III (GIII), despite the differences observed on the 3' UTR. Further studies are needed to address the role of those mutations in the transmission of the different viral populations and vector competence.
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10.1186/1743-422X-10-3
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pubmed_699_13416
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In mammals, odor information detected in the olfactory epithelium is converted to a topographic map of activated glomeruli in the olfactory bulb. Odor signals are then conveyed by projection neurons to the olfactory cortex for decision making. Odor information is processed by two distinct pathways, one is innate and the other is learned, which are separately activated during exhalation and inhalation, respectively. There are two types of odor signals, exteroceptive and interoceptive, which are also processed in different phases of respiration. Exteroceptive sensory information whether attractive/pleasant or aversive/stressful, is evaluated by the valence regions in the amygdala. Stress is an alert signal telling the body to take an action so that the normal condition can be recovered. When the odor quality is negative, the brain sets up a behavioral strategy to avoid the danger or to improve the situation. In this review article, we will describe the recent progress in the study of olfactory perception focusing on stress responses to external and internal odors.
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10.3389/fnbeh.2022.943647
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pubmed_403_3902
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Despite recent close attention to issues related to the reliability of psychological research (e.g., the replication crisis), issues of the validity of this research have not been considered to the same extent. This paper highlights an issue that calls into question the validity of the common research practice of studying samples of individuals, and using sample-based statistics to infer generalizations that are applied not only to the parent population, but to individuals. The lack of ergodicity in human data means that such generalizations are not justified. This problem is illustrated with respect to two common scenarios in psychological research that raise questions for the sorts of theories that are typically proposed to explain human behavior and cognition. The paper presents a method of data analysis that requires closer attention to the range of behaviors exhibited by individuals in our research to determine the pervasiveness of effects observed in sample data. Such an approach to data analysis will produce results that are more in tune with the types of generalizations typical in reports of psychological research than mainstream analysis methods.
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10.3389/fpsyg.2020.594675
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pubmed_594_16423
|
BACKGROUND
We carried out a descriptive analysis of the mortality in a Catalonian rural town (Canet d'Adri, 12 km from Girona) for the period 1872-1900. The knowledge of the main mortality causes, especially those non-transmissible, could be very illustrative. The objective was to show the distribution of the mortality by age and cause, and to compare mortality due to infections with mortality consequence of the rest of the causes.
METHOD
Three aspects were analysed: the distribution of the deaths by age and sex; the temporal and seasonal evolution; and the distribution by cause-specific.
RESULTS
49.3% of the deaths corresponded to women and 50.7% to men. Younger than one-year old were the most important group, 35.6% of the total mortality, followed by older than 65, 23.7%. Respiratory diseases were responsible for 33.4% of deaths; infectious diseases 31.1%, circulatory diseases 13.4% and digestive diseases 2.6%. Amongst younger than 45 year old the main cause of mortality was infectious diseases, above all in women. Respiratory diseases were the main cause of mortality in women older than 45 and in men older than 65 year old. Deaths because circulatory diseases were a very important cause amongst men older than 65.
CONCLUSIONS
Besides of the importance of the infectious diseases as the main cause of death, it is surprising the importance of circulatory diseases (the third cause of mortality).
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pubmed_594_16423
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pubmed_33_10919
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We report an 11 year old boy with IgA nephropathy developing chronic myeloid leukemia on follow-up. This association suggests that a B cell defect might be involved in the pathogenesis of these two conditions.
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pubmed_33_10919
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pubmed_345_6945
|
Previous abdominal surgery (PAS) is an important factor for postoperative adhesion. It is considered to be the most common complication of gastrointestinal and pelvic surgery. Both an Internet based and a manual search were used to acquire relevant studies about this topic. Parameters have been compared such as, Operating time in PAS versus Non PAS, Blood loss, Perioperative blood transfusion, Conversion to open, Anastomotic leakage and overall complications. Results of this study suggest that laparoscopy is too safe and effective in the treatment of colorectal disease for patients with previous abdominal surgery as it is for those without surgical backgrounds. However sufficient large-volume study is necessary to validate the long-term outcomes in previous abdominal surgical patients.
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pubmed_345_6945
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pubmed_1052_2424
|
UNLABELLED
Covering a cough can be useful in reducing the transmission of airborne infectious diseases. However, no simple method is available in the literature for predicting the exhaled airflow from a cough with the mouth covered. This investigation used smoke to visualize the airflow exhaled by 16 human subjects. Their mouths were covered by a tissue, a cupped hand, a fist, and an elbow with and without a sleeve. This study then developed simplified models for predicting the airflow on the basis of the smoke visualization data. In addition, this investigation performed numerical simulations to assess the influence of mouth coverings on the receptor's exposure to exhaled particles. It was found that covering a cough with a tissue, a cupped hand, or an elbow can significantly reduce the horizontal velocity and cause the particles to move upward with the thermal plumes generated by a human body. In contrast with an uncovered cough, a covered cough or a cough with the head turned away may prevent direct exposure.
PRACTICAL IMPLICATIONS
This study developed simplified models for predicting the exhaled airflow from a cough with the mouth covered. The proposed models can easily be used to investigate the risk of transmission of airborne infectious diseases in enclosed environments.
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10.1111/ina.12109
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pubmed_302_19180
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Studying the cellular physiology of human detrusor muscle obtained from patients with normally functioning bladders and comparing it with that of detrusor muscle from patients with unstable bladders may help identify potential targets for drug therapy in patients with abnormal bladder function. Considerable advances have been made in the understanding of the cellular processes that result in contraction and relaxation of detrusor smooth muscle, particularly in the role and modulation of calcium. Several changes in these cellular mechanisms that impair normal function have been observed in detrusor muscle from patients with unstable bladders. Whether these changes represent primary causes of bladder dysfunction or whether they are secondary to bladder dysfunction remains to be determined. Nevertheless, the identification of specific cellular lesions in bladder dysfunction presents a novel approach to identification of drug targets and potential treatment modalities.
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10.1016/s0090-4295(01)01632-6
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pubmed_651_2015
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A double-blind study was conducted to compare topical erythromycin 1.5 percent solution (Staticin solution) with oral tetracycline (250 mg) twice a day in fifty-four patients with Grades II and III acne vulgaris. Although both therapies produced a statistically significant reduction in the number and severity of the acne lesions, the topical preparation usually showed an effect earlier and to a greater degree than the oral medication. By the end of the study, some of these differences were statistically significant. After twelve weeks of treatment, topical erythromycin therapy produced a 58 percent reduction in the overall lesion count, as opposed to the 38 percent reduction produced by oral tetracycline therapy. In addition, the Propionibacterium acnes counts were reduced with erythromycin by over 90 percent and with tetracycline treatment by over 80 percent. Two patients treated with tetracycline developed vaginal candidiasis and therapy had to be discontinued. During topical treatment with erythromycin only mild adverse experiences were reported and none resulted in withdrawal from the study.
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pubmed_651_2015
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pubmed_213_420
|
Three to four months' PUVA treatment is a widely-adopted procedure to induce psoriasis remission and for the purpose of this study is called "medium-term". The 32 psoriatic patients considered revealed a statistically significant baseline decrease in OKT3+ (p less than 0.001), OKT4+ (p less than 0.001) and OKT8+ (p less than 0.001) as compared with 40 healthy controls, while OKT4/OKT8 was normal. Variance analysis within the psoriatic group failed to reveal further significant variation in the immunological parameters during the 3 months under study. Nevertheless, there was a marked trend towards a reduction in OKT4+ cells and OKT4/OKT8 as compared with baseline values after 3 months. These results suggest that "medium-term" PUVA therapy does not statistically restore the pre-existing baseline changes in T-lymphocyte subsets of the psoriatic patients. The non-statistically significant effects as regards OKT4+ may be due to the small number of patients who reached 3 months' treatment (9 patients) but could be regarded as the first step towards the significant changes described here in long-term PUVA-treated psoriatic patients.
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pubmed_213_420
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pubmed_341_13780
|
Course-based undergraduate research experiences (CUREs) have the potential to improve undergraduate biology education by involving large numbers of students in research. CUREs can take a variety of forms with different affordances and constraints, complicating the evaluation of design features that might contribute to successful outcomes. In this study, we compared students' responses to three different research experiences offered within the same course. One of the research experiences involved purely computational work, whereas the other two offerings were bench-based research experiences. We found that students who participated in computer-based research reported at least as much interest in their research projects, a higher sense of achievement, and a higher level of satisfaction with the course compared with students who did bench-based research projects. In open-ended comments, similar proportions of students in each research area expressed some sense of project ownership as contributing positively to their course experiences. Their comments also supported the finding that experiencing a sense of achievement was a predictor of course satisfaction. We conclude that both computer-based and bench-based CUREs can have positive impacts on students' attitudes. Development of more computer-based CUREs might allow larger numbers of students to benefit from participating in a research experience.
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10.1187/cbe.18-07-0112
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pubmed_246_3952
|
In order to avoid amputation, which does not seem to improve survival in osteosarcoma, we have initiated a limb-preservation program using intra-arterial radiosensitization. Eleven osteosarcomas with soft tissue involvement and six other bone malignancies were prospectively treated according to the following protocol: (a) surgical insertion of an intra-arterial catheter through a Dacron patch, (b) intra-arterial infusion of 15 mg/kg BUDR on days 1-2 every 5 days for 40 days, (c) 600 rads flash irradiation on day 3 every 5 days, X 8. Median follow-up time has been 36 months. In the osteosarcoma group, median survival has been 12 months. Four of the five osteosarcoma patients who died had received prophylactic HD methotrexate-vincristine-adriamycin systemic chemotherapy; one patient refused.
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10.1007/978-3-642-82025-0_34
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pubmed_169_8177
|
The prophylactic effect of calcitonin, somatostatin and cimetidine on stress ulcer formation in rats was investigated in two stress models: restraint + ketamin (4 h) and hypovolemia (4 h). The basis of the comparative study was a 70% inhibition of acid secretion for 4 h in pyloric ligated animals. This was achieved with 1000 microgram/kg somatostatin s.c., 10 microgram/kg calcitonin s.c., and 2 X 100 mumol/kg cimetidine s.c. In restraint stress and ketamin with calcitonin and cimetidine a significantly lower frequency of gastric lesions was found than with somatostatin. The most potent substance in hypovolemia was calcitonin, with a significant difference in the frequency of mucosal lesions to the groups with cimetidine and somatostatin.
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pubmed_169_8177
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pubmed_170_6828
|
New glycidyl-based (epoxide-based) poly(aminoester) (EPAE) containing hydroxyl and amino groups in the backbone and side chain was synthesized. EPAE self-assembled readily with the plasmid DNA(pCMV-betagal) in HEPES buffer and was characterized by dynamic light scattering, Zeta-potential, fluorescence images, and XTT cell viability assays. To evaluate the effect of molecular weight of EPAE system on transfection, EPAE polymers with three different molecular weights (EPAE22k, EPAE18k, and EPAE8k) were also prepared. This study found that all EPAE polymers were able to bind plasmid DNA and yielded positively charged complexes with a nano-sized particles (200 nm). The EPAE22k/DNA and EPAE18k/DNA complexes were able to transfect COS-7 cell in vitro with higher transfection efficiency than other EPAE8k/DNA. These results demonstrated that molecular weight of EPAE system had a significant effect on transferring ability. Examination of the cytotoxicity of PEI25k and EPAEs system revealed that EPAEs system had lower cytotoxicity. In this article, EPAEs seemed to be a novel cationic poly(aminoester) for gene delivery and an interesting candidate for further study.
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10.1016/j.ijpharm.2010.04.024
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pubmed_471_21470
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Pulmonary artery sling is a rare congenital cardiac anomaly, in which the left pulmonary artery originates from the right pulmonary artery and courses leftward between the trachea and the esophagus. Tetralogy of Fallot associated with pulmonary artery sling is even rarer, and only a few cases have been reported in the literature. We present a case of tetralogy of Fallot associated with pulmonary artery sling that was repaired successfully.
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10.5090/kjtcs.2018.51.5.360
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pubmed_792_3621
|
Exposure to hostile conditions initiates the secretion of several hormones, including corticosterone/cortisol, catecholamines, prolactin, oxytocin, and renin, as part of the survival mechanism. Such conditions are often referred to as "stressors" and can be divided into three categories: external conditions resulting in pain or discomfort, internal homeostatic disturbances, and learned or associative responses to the perception of impending endangerment, pain, or discomfort ("psychological stress"). The hormones released in response to stressors often are referred to as "stress hormones" and their secretion is regulated by neural circuits impinging on hypothalamic neurons that are the final output toward the pituitary gland and the kidneys. This review discusses the forebrain circuits that mediate the neuroendocrine responses to stressors and emphasizes those neuroendocrine systems that have previously received little attention as stress-sensitive hormones: renin, oxytocin, and prolactin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABAA, histamine, and serotonin receptors alter the neuroendocrine stress response. The effects of these drugs are discussed in relation to their effects on forebrain neural circuits that regulate stress hormone secretion. For psychological stressors such as conditioned fear, the neural circuits mediating neuroendocrine responses involve cortical activation of the basolateral amygdala, which in turn activates the central nucleus of the amygdala. The central amygdala then activates hypothalamic neurons directly, indirectly through the bed nucleus of the stria terminalis, and/or possibly via circuits involving brainstem serotonergic and catecholaminergic neurons. The renin response to psychological stress, in contrast to those of ACTH and prolactin, is not mediated by the bed nucleus of the stria terminalis and is not suppressed by benzodiazepine anxiolytics. Stressors that challenge cardiovascular homeostasis, such as hemorrhage, trigger a pattern of neuroendocrine responses that is similar to that observed in response to psychological stressors. These neuroendocrine responses are initiated by afferent signals from cardiovascular receptors which synapse in the medulla oblongata and are relayed either directly or indirectly to hypothalamic neurons controlling ACTH, prolactin, and oxytocin release. In contrast, forebrain pathways may not be essential for the renin response to hemorrhage. Thus current evidence indicates that although a diverse group of stressors initiate similar increases in ACTH, renin, prolactin, and oxytocin, the specific neural circuits and neurotransmitter systems involved in these responses differ for each neuroendocrine system and stressor category.
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10.1006/frne.1998.0172
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pubmed_832_16718
|
It is estimated that over 60% of out-of-hospital cardiac arrest (OHCA) patients with a shockable rhythm are refractory to current treatment, never achieve return of spontaneous circulation, or die before they reach the hospital. Therefore, we aimed to identify whether field resuscitation time is associated with survival rate in refractory OHCA (rOHCA) with a shockable initial rhythm. This cross-sectional retrospective study extracted data of emergency medical service (EMS)-treated patients aged ≥ 15 years with OHCA of suspected cardiac etiology and shockable initial rhythm confirmed by EMS providers from the OHCA registry database of Korea. A multivariable logistic regression analysis was conducted for survival to discharge and good neurological outcomes in the scene time interval groups. The median scene time interval for the non-survival and survival to discharge patients were 16 (interquartile range (IQR) 13-21) minutes and 14 (IQR 12-16) minutes, respectively. In this study, for rOHCA patients with a shockable rhythm, continuing CPR for more than 15 min on the scene was associated with a decreased chance of survival and good neurological outcome. In particular, we found that in the patients whose transport time interval was >10 min, the longer scene time interval was negatively associated with the neurological outcome.
|
10.3390/ijerph18020496
|
pubmed_387_13499
|
The role of estrogens in the development of skin cancer is controversial. Sex steroids have a profound effect on the epidermis and epidermal appendages. Estradiol in pharmacologic doses has been reported to stimulate basal cell carcinoma in an animal model. Sex hormones act by means of a specific protein receptor. In this study we used a specific, highly sensitive monoclonal antibody to evaluate sex steroid receptors in human basal cell carcinoma. No estrogen or progesterone receptor protein was detected in the basal cell tumor, despite clear positive control tissues. We conclude that these sex steroid receptors are not present in significant amounts to mediate a direct effect in basal carcinoma.
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10.1016/s0190-9622(88)70101-2
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pubmed_111_15180
|
The intercapsular segment of the oviduct in the golden hamster is not a simple duct which has constant outer and inner diameters. After penetrating the bursa ovarica the ICS has a circular constriction and the corresponding oviductal lumen is narrowed.
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10.1007/BF02004509
|
pubmed_895_10607
|
PURPOSE
Participation in physical activity (PA) is reported to decline in adolescence, particularly for girls. However, we do not know if this decline in PA is consistent across modes and settings or whether there are transfers of participation between modes and settings. Nor do we understand the changes in specific types of PA or the interaction between types of participation and different modes/settings. This study investigated contexts of PA participation for female adolescents at two life transition points.
METHOD
A survey of 489 Year 7 and 243 Year 11 adolescent girls was conducted, incorporating a measure of overall PA level and participation rates in seven modes/settings and in specific types of sport and PA.
RESULTS
Less than half of the respondents met or exceeded the recommended level of moderate or vigorous PA--60 min or more--on the previous day, and there was no statistically significant difference in the proportions in Years 7 and 11 (39.5% vs. 45.9%; p > .05). However, older adolescents shifted their participation away from organized, competitive modes and settings toward nonorganized and noncompetitive modes and settings and individual types of PA.
CONCLUSIONS
An understanding of the changes in PA modes and settings identified here can inform the planning of policies and implementation of programs for the promotion of PA by adolescent girls.
|
10.1080/02701367.2013.784846
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pubmed_144_1297
|
N-Nitrosodialkylamines are known to be potent indirect-acting mutagens/carcinogens, which are activated by cytochrome P450. The reaction product of N-nitroso-N-methylbutylamine (NMB) with modified Fenton's reagent supplemented with copper salt (Fe²(+)-Cu²(+)-H₂O₂) was reported to be mutagenic in Salmonella typhimurium TA1535 without S9 mix. In this study, the NMB activation mechanism was investigated by ESR spectroscopy with radical trapping agents to detect radical species and also by observing changes in mutagenic potency with a Salmonella strain in the Ames assay in the presence of radical trapping agents. In ESR spectroscopy experiments, the hydroxyl radical generated from the modified Fenton's reagent was detected using the hydroxyl radical trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Since the amount of the DMPO-OH adduct decreased with the addition of NMB, hydroxyl radical was presumed to react with NMB followed by the generation of nitric oxide (NO), which was detected as CarboxyPTI through reaction with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (CarboxyPTIO). The mutagenicity of the reaction extract decreased following the addition of DMPO or CarboxyPTIO. Furthermore, the mutagenicity of the reaction product in the presence of DMPO was enhanced by the addition of NO. The reaction product from NMB with Fe²(+)-Cu²(+)-NO in the absence of H₂O₂ was mutagenic, and this activity increased with the introduction of additional NO. These findings suggest that hydroxyl radical takes part in the generation of NO from NMB and that NO plays an important role in NMB activation in the presence of Fe²(+) and Cu²(+).
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10.1016/j.bmc.2010.10.002
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pubmed_367_19735
|
We present a case of expansive CSF collection in the cerebellar convexity. The patient was a 74 years old lady who one month before had suffered a cerebellar infarct complicated with acute hydrocephalus. She had good evolution after decompressive craniectomy without shunting. Fifteen days after surgery, the patient started with new positional vertigo, nausea and vomiting and a wound CSF fistula that needed ventriculoperitoneal shunt (medium pressure) because conservative treatment failed. After shunting, the fistula closed, but the patient symptoms worsened. The MRI showed normal ventricular size with a cerebellar hygroma, extending to the posterior interhemispheric fissure. The collection had no blood signal and expanded during observation. A catheter was implanted in the collection and connected to the shunt. The patient became asymptomatic after surgery, and the hygromas had disappeared in control CT at one month. This case shows an infrequent problem of CSF circulation at posterior fossa that resulted in vertigo of central origin. A higroma-ventricle-peritoneal shunt solved the symptoms of the patient.
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10.1016/s1130-1473(09)70146-0
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pubmed_787_5700
|
Nosema ceranae is a microsporidian parasite described from the Asian honey bee, Apis cerana. The parasite is cross-infective with the European honey bee, Apis mellifera. It is not known when or where N. ceranae first infected European bees, but N. ceranae has probably been infecting European bees for at least two decades. N. ceranae appears to be replacing Nosema apis, at least in some populations of European honey bees. This replacement is an enigma because the spores of the new parasite are less durable than those of N. apis. Virulence data at both the individual bee and at the colony level are conflicting possibly because the impact of this parasite differs in different environments. The recent advancements in N. ceranae genetics, with a draft assembly of the N. ceranae genome available, are discussed and the need for increased research on the impacts of this parasite on European honey bees is emphasized.
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10.1016/j.jip.2009.06.017
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pubmed_362_26825
|
OBJECTIVE
To determine the effect of blocking the obturator nerve in addition to performing femoral nerve and sciatic nerve blocks on intraoperative nociception in dogs undergoing unilateral tibial plateau levelling osteotomy (TPLO) surgery.
STUDY DESIGN
Prospective, blinded, randomized, placebo-controlled, clinical comparison.
ANIMALS
A total of 88 client-owned dogs undergoing unilateral TPLO surgery (100 procedures).
METHODS
Dogs were randomly assigned to either group FSO (femoral, sciatic and obturator nerve blocks) [n = 50; ropivacaine 0.75% (0.75 mg kg-1)] or group FSP (femoral, sciatic and placebo) [n = 50; ropivacaine 0.75% (0.75 mg kg-1) femoral and sciatic nerve blocks plus saline solution 0.9% (0.1 mL kg-1) as a placebo injection around the obturator nerve]. The anaesthetic protocol was standardized. Data collection included intraoperative cardiopulmonary variables and opioid consumption. Rescue analgesia consisted of an intravenous bolus of fentanyl (2 μg kg-1) and was administered when a change in cardiopulmonary variables (20% increase in mean arterial pressure or heart rate) was attributed to a sympathetic stimulus. Data were analysed using generalized linear mixed models, cross tables and multivariable binary logistic regression. Results were expressed as adjusted odds ratios with 95% confidence intervals and Wald p values (α = 0.05).
RESULTS
There were no clinically relevant differences between groups in intraoperative cardiopulmonary variables and need for rescue analgesia. The requirement for rescue analgesia was significantly higher in dogs with a body weight >34 kg.
CONCLUSIONS AND CLINICAL RELEVANCE
Anaesthesia of the obturator nerve in addition to the femoral and sciatic nerves was not associated with clinically significant differences in cardiopulmonary variables or a reduced need for rescue analgesia. Therefore, the clinical benefit of an additional obturator nerve block for intraoperative antinociception in dogs undergoing unilateral TPLO surgery using the described anaesthetic regimen is low.
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10.1016/j.vaa.2021.09.021
|
pubmed_30_11348
|
Limited digestion of filamentous myosin with chymotrypsin at 0 degrees C in the absence of divalent cations generates two forms of subfragment 1 (S1), with heavy chains of 95 kDa and 98 kDa. The difference is at the C-terminal end of the chain. The 98 kDa form prevails, in contrast to the preparations obtained by digestion at room temperature which consist of the shorter species and only traces of the longer one. The results support the idea of a temperature-dependent conformational transition at the head-rod junctional region of the myosin heavy chain.
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10.1016/0014-5793(89)81211-6
|
pubmed_484_1881
|
Copper tolerant fungi are known for more than 60 years but the complete mechanisms of copper tolerance by these fungi are still not fully understood. Copper tolerance has previously been linked to oxalic acid excretion by copper tolerant brown rot fungi. The oxalic acid then reacts with copper in the wood to form an insoluble and therefore less toxic copper oxalate. It has been suggested that copper tolerance could be due to lowering of the pH of the medium rather than the low solubility of copper oxalate. In order to elucidate this presumption, copper/chromium/boron (CCB) treated wood specimens were acidified with organic (oxalic, acetic, lactic, formic) and inorganic (sulphuric) acids and exposed to copper tolerant (Antrodia vaillantii, Leucogyrophana pinastri) and copper sensitive (Poria monticola, Gloeophyllum trabeum) brown rot fungal strains according to the mini block procedure. After eight weeks of exposure, the wood specimens were isolated and their mass losses determined. Additionally, electron paramagnetic resonance (EPR) measurements on the exposed specimens were performed. The EPR spectra of the specimens decayed by A. vaillantii were very similar to the EPR spectra of the specimens acidified with oxalic acid. Additionally, acidification of the CCB impregnated specimens made them significantly more susceptible to decay by both the copper tolerant and copper sensitive brown rot fungi.
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10.1016/j.chemosphere.2004.09.031
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pubmed_774_14561
|
Skin is exposed to various physico-chemical cues. Keratinocytes, a major component of the skin epidermis, directly interact with the surrounding extracellular matrix, and thus, biochemical and biophysical stimulations from the matrix regulate the function of keratinocytes. Although it was reported that inflammatory responses of skin were altered by an applied mechanical force, understanding how the keratinocytes sense the mechanical stimuli and regulate a cytokine secretion remains unclear. Here, we designed a device that is able to apply chemo-mechanical cues to keratinocytes and assess their proinflammatory cytokine IL-6 production. We showed that when chemical stimuli were applied with mechanical stimuli simultaneously, the IL-6 production markedly increased compared to that observed with a single stimulus. Quantitative structural analysis of cellular components revealed that the applied mechanical stretch transformed the cell morphology into an elongated shape, increased the cell size, and dictated the distribution of focal adhesion complex. Our results suggest that the mechanical cue-mediated modulation of focal adhesion proteins and actin cytoskeleton translates into intracellular signaling associated with the IL-6 production particularly in skin sensitization. Our study can be applied to understand proinflammatory responses of skin under altered biophysical environments of the skin.
|
10.1038/s41598-019-41480-y
|
pubmed_780_10852
|
Genetic information and technologies are increasingly important in health care, not only in technologically advanced countries, but world-wide. Several global factors promise to increase future demand for morally conscious genetic health services and research. Although they are the largest professional group delivering health care world-wide, nurses have not taken the lead in meeting this challenge. Insights from feminist analysis help to illuminate some of the social institutions and cultural obstacles that have impeded the integration of genetics technology into the discipline of nursing. An alternative model is suggested--the transdisciplinary model--which was developed initially by a nurse and introduced in the 1970s into the delivery of health care and social services for children with developmental disabilities. This holistic model enables all health care professionals to have an equal voice in determining how genetic health care will be globalized.
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10.1177/096973300000700302
|
pubmed_317_8272
|
PURPOSE
To evaluate the visual outcomes of pseudophakic patients who underwent supplementary toric intraocular lens (IOL) implantation to correct astigmatic refractive errors.
METHODS
Pseudophakic patients referred for the implantation of a supplementary toric IOL (Sulcoflex Toric 653T) were evaluated. Uncorrected and corrected distance visual acuities (UDVA and CDVA, respectively), spherical equivalent (SE) refraction, rotational stability, higher order aberrations (HOA), and photopic glare and no-glare contrast sensitivity (CSV-1000, VectorVision) were evaluated.
RESULTS
A total of 10 eyes of 10 patients were included. The mean age was 56.42 ± 5.9 years (range 45-65 years). Mean follow-up was 6.99 ± 5.1 months (6-18 months). Postoperatively, UDVA improved to 0.10 ± 0.12 (0.3 to -0.1) (p = 0.004) and CDVA to 0.07 ± 0.12 (0.3 to -0.1) (p = 0.021). Mean SE was -0.30 ± 0.56 D (-1.00 to +0.75) (p = 0.001). Mean toric IOL axis rotation at 6-month follow-up was 3.0° ± 2.45° (0-6). Ocular aberrometry values decreased after surgery (for average HOA root mean square, p = 0.008). Photopic contrast sensitivity (for all spatial frequencies) showed a trend for improvement after surgery; however, this was not borne out from the analysis (p>0.05).
CONCLUSIONS
The implantation of the Sulcoflex Toric IOL to correct astigmatism in pseudophakic patients provided excellent visual outcomes, predictability of refractive results, rotational stability, and optical performance. The implantation of this IOL is a safe and effective technique to correct pseudophakic cylindrical refractive errors and reduce spectacle dependence in these patients.
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10.5301/ejo.5000564
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pubmed_955_6339
|
Pituitary hormones are released in pulses as a result of episodic patterns of electrical activity in neuroendocrine neurons. The mechanisms underlying such pulsatility have, however, been difficult to elucidate. For example, the luteinizing hormone-releasing hormone neurons regulating reproductive functioning have a sparse and scattered distribution within the hypothalamus which has made definitive electrophysiological investigation impracticable. Little is known not only of their electrical characteristics, but also of the critical neural components with which they interact to form the so-called "luteinizing hormone-releasing hormone pulse generator". We have used here a neural modelling approach, based on the FitzHugh-Nagumo model of a single neuron, to provide a simple dynamical network model of this neuroendocrine pulse generator. We have found that the minimal components required to generate pulsatile luteinizing hormone secretion arise from combining luteinizing hormone-releasing hormone neurons with reciprocally connected inhibitory interneurons and an external stimulatory input. Local GABA neurons and ascending noradrenergic and/or adrenergic inputs have been used as the biological basis for these respective components. The network displays a wide repertoire of behaviours comparable with experimental observations, including some thought previously to be paradoxical. The capacity of this model network to display complex behavioural features interpretable against experimental evidence suggests that this type of modelling may become a necessary adjunct to empirical studies of pulsatile neuroendocrine systems.
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10.1016/0306-4522(94)90531-2
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pubmed_122_11092
|
Cutaneous melanoma is an aggressive form of skin cancer that causes death worldwide. Although much has been learned about the molecular basis of melanoma genesis and progression, there is also increasing appreciation for the continuing discovery of melanoma genes to improve the genetic understanding of this malignancy. In the present study, melanoma candidate genes were identified by analysis of the common network from cancer type-specific RNA-Seq co-expression data and protein-protein interaction profiles. Then, an integrated network containing the known melanoma-related genes represented as seed genes and the putative genes represented as linker genes was generated using the subnetwork extraction algorithm. According to the network topology property of the putative genes, we selected seven key genes (CREB1, XPO1, SP3, TNFRSF1B, CD40LG, UBR1, and ZNF484) as candidate genes of melanoma. Subsequent analysis showed that six of these genes are melanoma-associated genes and one (ZNF484) is a cancer-associated gene on the basis of the existing literature. A signature comprising these seven key genes was developed and an overall survival analysis of 461 cutaneous melanoma cases was carried out. This seven-gene signature can accurately determine the risk profile for cutaneous melanoma tumors (log-rank P=3.27E-05) and be validated on an independent clinical cohort (log-rank P=0.028). The presented seven genes might serve as candidates for studying the molecular mechanisms and help improve the prognostic risk assessment, which have clinical implications for melanoma patients.
|
10.1097/CMR.0000000000000525
|
pubmed_4_25190
|
Warning signal variation is ubiquitous but paradoxical: low variability should aid recognition and learning by predators. However, spatial variability in the direction and strength of selection for individual elements of the warning signal may allow phenotypic variation for some components, but not others. Variation in selection may occur if predators only learn particular colour pattern components rather than the entire signal. Here, we used a nudibranch mollusc, Goniobranchus splendidus, which exhibits a conspicuous red spot/white body/yellow rim colour pattern, to test this hypothesis. We first demonstrated that secondary metabolites stored within the nudibranch were unpalatable to a marine organism. Using pattern analysis, we demonstrated that the yellow rim remained invariable within and between populations; however, red spots varied significantly in both colour and pattern. In behavioural experiments, a potential fish predator, Rhinecanthus aculeatus, used the presence of the yellow rims to recognize and avoid warning signals. Yellow rims remained stable in the presence of high genetic divergence among populations. We therefore suggest that how predators learn warning signals may cause stabilizing selection on individual colour pattern elements, and will thus have important implications on the evolution of warning signals.
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10.1098/rspb.2017.0926
|
pubmed_339_14703
|
From July 1996 to March 2000, 391 patients with intraoperative cardiac low-output syndrome who underwent surgery with heart-lung bypass and had an intra-aortic balloon pump (IABP) implanted were analyzed in a prospective study. Of these 391 patients, 153 (39%) were operated on in an emergency situation, and 238 (61%) patients had elective surgeries. The perioperative mortality was 34% (133 patients). Clinical parameters were analyzed 1 hour after IABP support began. Statistical multivariate analysis showed that patients with an adrenaline requirement higher than 0.5 microg/kg/min, a left atrial pressure higher than 15 mmHg, output of less than 100 mL/hour, and mixed venous saturation (SvQ2) of less than 60% had poor outcomes. Using this data, we developed an IABP score to predict survival early after IABP implantation in cardiac surgery. We conclude that the success or failure of perioperative IABP support can be predicted early after implantation of the balloon pump. In patients with low-output syndrome despite IABP support, implantation of a ventricular assist system should be considered.
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10.1111/j.1540-8191.2001.tb00486.x
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pubmed_768_19822
|
BACKGROUND
Multiple limb loss from combat injuries has increased as a proportion of all combat-wounded amputees. Bilateral lower-extremity limb loss is the most common, with bilateral transfemoral amputations being the most common subgroup followed by bilateral amputations consisting of a single transfemoral amputation and a single transtibial amputation (TFTT). With improvements in rehabilitation and prostheses, we believe it is important to ascertain how TFTT amputees from the present conflicts compare to those from the Vietnam War.
QUESTIONS/PURPOSES
We compared self-reported (1) health status, (2) quality of life (QoL), (3) prosthetic use, and (4) function level between TFTT amputees from the Vietnam War and Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF).
METHODS
As part of a larger survey, during 2007 to 2008, servicemembers with a diagnosis of amputation associated with battlefield injuries from the Vietnam War and OIF/OEF were identified from the Veterans Affairs and military databases. Participants were asked to respond to a questionnaire to determine their injuries, surgical history, presence of other medical problems, health status, QoL, function, and prosthetic use. We assessed QoL and health status using single-item questions and function using seven categories of physical activity. Thirteen of 298 (4.3%) participants in the Vietnam War group and 11 of 283 (3.8%) in the OIF/OEF group had sustained TFTT amputations. Mean age ± SD at followup was 61 ± 2 years and 28 ± 5 years for the Vietnam War and OIF/OEF groups, respectively.
RESULTS
Excellent, very good, and good self-reported health (85% versus 82%; p = 0.85) and QoL (69% versus 72%; p = 0.85) were similar between the Vietnam War and OIF/OEF groups, respectively. Level of function was higher in the OIF/OEF group, with four of 11 reporting participation in high-impact activities compared to none in the Vietnam War group (p = 0.018).
CONCLUSIONS
Participants with TFTT limb loss from both conflicts reported similar scores for QoL and health status, although those from OIF/OEF reported better function and use of prosthetic devices. It is unclear whether the improved function is from age-related changes or improvements in rehabilitation and prosthetics. Some areas of future research might include longitudinal studies of those with limb loss and assessments of physical function of older individuals with limb loss as the demographics shift to where this group of individuals becomes more prominent.
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10.1007/s11999-014-3534-9
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pubmed_434_14011
|
This article explores immersive virtual reality as a potential educational strategy for nursing education and describes an immersive learning experience now being developed for nurses. This pioneering project is a virtual reality application targeting speed and accuracy of nurse response in emergency situations requiring cardiopulmonary resuscitation. Other potential uses and implications for the development of virtual reality learning programs are discussed.
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pubmed_434_14011
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pubmed_601_5784
|
Serial physiological responses were examined for 150 min from captive collared peccaries during immobilization with ketamine hydrochloride. Rectal temperatures decreased significantly (P less than 0.01) during anesthesia. Serum concentrations of total proteins, albumin, cholesterol, alanine aminotransferase, and calcium declined significantly (P less than 0.05) during the first 45 min post-immobilization before stabilizing. Concentrations of lactate dehydrogenase and alkaline phosphatase in sera showed similar but nonsignificant (P greater than 0.05) trends. Inorganic phosphorus and aspartate aminotransferase concentrations increased significantly (P less than 0.05) throughout the trial. Concentrations of serum glucose and glucocorticoid during the immobilization period were highly variable between individuals. Serum electrolytes, urea nitrogen, creatinine, gammaglutamyl transferase and progesterone were not significantly (P greater than 0.05) affected by immobilization. Elevations in serum testosterone were noted. Results indicated appropriate sampling times relative to immobilization for assay of particular serum biochemicals and steroid hormones during investigations of the physiology of the collared peccary.
|
10.7589/0090-3558-21.4.417
|
pubmed_517_24009
|
Lysophosphatidic acid (LPA; monoacyl-glycerol-3-phosphate) is a lipid mediator that functions as a mitogen and motility factor for many cell types. LPA signals through six specific G protein-coupled receptors, named LPA(1-6), which trigger both overlapping and distinct signaling pathways. LPA is produced from extracellular lysophosphatidylcholine by a secreted lysophospholipase D, named autotaxin (ATX), originally identified as an "autocrine motility factor" for tumor cells. ATX-LPA signaling is vital for embryonic development and promotes tumor formation, angiogenesis, and experimental metastasis in mice. Elevated expression of ATX and/or aberrant expression of LPA receptors are found in several human malignancies, while loss of LPA(6) function has been implicated in bladder cancer. In this review, we summarize our present understanding of ATX and LPA receptor signaling in cancer.
|
10.1007/s10555-011-9319-7
|
pubmed_177_2148
|
Humans have selectively bred and used dogs over a period of thousands of years, and more recently the dog has become an important model animal for studies in ethology, cognition and genetics. These broad interests warrant careful descriptions of the senses of dogs. Still there is little known about dog vision, especially what dogs can discriminate in different light conditions. We trained and tested whippets, pugs, and a Shetland sheepdog in a two-choice discrimination set-up and show that dogs can discriminate patterns with spatial frequencies between 5.5 and 19.5 cycle per degree (cpd) in the bright light condition (43 cd m-2). This is a higher spatial resolution than has been previously reported although the individual variation in our tests was large. Humans tested in the same set-up reached acuities corresponding to earlier studies, ranging between 32.1 and 44.2 cpd. In the dim light condition (0.0087 cd m-2) the acuity of dogs ranged between 1.8 and 3.5 cpd while in humans, between 5.9 and 9.9 cpd. Thus, humans make visual discrimination of objects from roughly a threefold distance compared to dogs in both bright and dim light.
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10.1371/journal.pone.0188557
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pubmed_936_8602
|
(1) The objective of this socio-epidemiologic cross-sectional study was to investigate caries burdens in Ghanaian children aged 3 to 13 years. The main focus was the analysis of urban-rural disparities and associating socio-demographic and behavioural factors. (2) Standardized caries examination with documentation of decayed, missing, filled deciduous (dmft) and permanent teeth (DMFT) was conducted in 11 school facilities according to WHO guidelines. A parental questionnaire gathered data considering associating factors. Descriptive statistics were used to evaluate their influence on caries prevalence and experience using mean dmft+DMFT, Significant Caries Index (SiC), and Specific Affected Caries Index (SaC). (3) In total, 313 study participants were included (mean age 7.7 ± 3.8 years; 156 urban, 157 rural). The urban region showed slightly higher caries prevalence (40.4% vs. 38.9%). The rural region had higher caries experience in mean dmft+DMFT (1.22 ± 2.26 vs. 0.96 ± 1.58), SiC (3.52 ± 2.73 vs. 2.65 ± 1.71), and SaC (3.15 ± 2.68 vs. 2.37 ± 1.68). Lower education and occupation level of parents and rural residence were associated to higher caries values. Sugary diet showed an inverse relation with caries prevalence and oral hygiene practices supported the generally known etiologic correlation. (4) This study highlights the importance of targeting children vulnerable to caries due to social inequality with adequate preventive means. The implementation of regular dental screening and education, e.g. in schools, may be helpful.
|
10.3390/ijerph19095771
|
pubmed_509_788
|
BACKGROUND
Aerosolized chemotherapy has been recognized as a potential treatment for lung cancer. The challenge of providing sufficient therapeutic effects without reaching dose-limiting toxicity levels hinders the development of aerosolized chemotherapy. This could be mitigated by increasing drug-delivery efficiency with a noninvasive drug-targeting delivery method. The purpose of this study is to use direct numerical simulations to study the resulting local enhancement of deposition due to magnetic field alignment of high aspect ratio particles.
METHODS
High aspect ratio particles were approximated by a rigid ellipsoid with a minor diameter of 0.5 μm and fluid particle density ratio of 1,000. Particle trajectories were calculated by solving the coupled fluid particle equations using an in-house micro-macro grid finite element algorithm based on a previously developed fictitious domain approach. Particle trajectories were simulated in a morphologically realistic geometry modeling a symmetrical terminal bronchiole bifurcation. Flow conditions were steady inspiratory air flow due to typical breathing at 18 L/min. Deposition efficiency was estimated for two different cases: [1] particles aligned with the streamlines and [2] particles with fixed angular orientation simulating the magnetic field alignment of our previous in vitro study.
RESULTS
The local enhancement factor defined as the ratio between deposition efficiency of Case [1] and Case [2] was found to be 1.43 and 3.46 for particles with an aspect ratio of 6 and 20, respectively.
CONCLUSIONS
Results indicate that externally forcing local alignment of high aspect ratio particles can increase local deposition considerably.
|
10.1089/jamp.2011.0921
|
pubmed_989_19760
|
AIM
Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.
METHODS
The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate.
RESULTS
Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P < 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P < 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively).
CONCLUSION
The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities.
CLINICAL TRIAL REGISTRATION
NCT02256800.
|
10.1016/j.ejca.2020.05.031
|
pubmed_412_3016
|
Expression of the NF-kappaB-dependent gene A20 in endothelial cells (EC) inhibits tumor necrosis factor (TNF)-mediated apoptosis in the presence of cycloheximide and acts upstream of IkappaBalpha degradation to block activation of NF-kappaB. Although inhibition of NF-kappaB by IkappaBalpha renders cells susceptible to TNF-induced apoptosis, we show that when A20 and IkappaBalpha are coexpressed, the effect of A20 predominates in that EC are rescued from TNF-mediated apoptosis. These findings place A20 in the category of "protective" genes that are induced in response to inflammatory stimuli to protect EC from unfettered activation and from undergoing apoptosis even when NF-kappaB is blocked. From a therapeutic perspective, genetic engineering of EC to express an NF-kappaB inhibitor such as A20 offers the mean of achieving an anti-inflammatory effect without sensitizing the cells to TNF-mediated apoptosis.
|
pubmed_412_3016
|
pubmed_886_10952
|
The necessity of integrated approach to age dating of injuries implies the search for new diagnostic criteria. Shock may be one of them. Analysis of shock-related morphological changes in the affected and intact tissues along with concomitant inflammatory reactions permits to more accurately determine the length of the post-trauma period.
|
pubmed_886_10952
|
pubmed_409_19875
|
Corrinoids were extracted with hot ethanol from human plasma and faeces and separated by high-performance liquid chromatography. The corrinoids (cobalamin and cobalamin analogues) were quantified in the eluted fractions by a dual radioisotope assay using as binders intrinsic factor and haptocorrin to detect cobalamin and total corrinoids, respectively. Recoveries ranged from 37.7 +/- 5.1% for hydroxycobalamin to 75.0 +/- 9.1% for cyanocobalamin. In plasma, the main forms of cobalamin were the coenzymes methylcobalamin and 5'-deoxyadenosylcobalamin (32.1 +/- 13.4 and 28.4 +/- 12.3%, respectively, of total corrinoids). The cobalamin analogue fraction of plasma was eluted with a retention time close to that of cobinamide and of deoxyadenosylcobalamin. In the faeces, most of the corrinoids separated were detected better by the haptocorrin assay than by the intrinsic factor assay. One corrinoid peak was eluted with the same retention time as cobinamide. This peak was detected by haptocorrin assay but not by intrinsic factor assay. It could therefore correspond to cobinamide.
|
10.1016/s0378-4347(00)83809-8
|
pubmed_100_5088
|
PURPOSE
The first aim of this study was to compare the detectability of metastasis of postoperative differentiated thyroid cancer (DTC) among (131)I whole body scintigraphy (IWBS), fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), and diffusion-weighted magnetic resonance imaging (DWI). The second aim was to clarify the association between the image pattern and prognosis.
MATERIALS AND METHODS
We evaluated 70 postoperative DTC patients on both a patient basis and an organ basis (lymph nodes, lung, bone), and we analyzed the correlation between the image pattern and the prognosis.
RESULTS
For the patient-basis analysis, the detectability by IWBS, PET/CT, and DWI was 67.1%, 84.2%, and 57.6%, respectively. IWBS provided complementary information to that provided by PET/CT in 11 of 70 (15.7%) cases. For the organ-basis analysis, IWBS was the best detector for lymph node metastasis (72.4%). PET/CT was superior to IWBS for detecting metastasis of bone (85.7% vs. 71.4%) and lung (94.1% vs. 62.7%). For the correlation analysis, PET and DWI positivity were the factors predicting a poor prognosis.
CONCLUSION
PET/CT was the best modality for detecting metastases in postoperative DTC patients, although IWBS provided complementary information. Because PET/CT and DWI gave similar information (e.g., positivity) suggesting poor prognoses, the combination of IWBS and DWI might be the method of choice for monitoring postoperative DTC.
|
10.1007/s11604-011-0572-z
|
pubmed_592_8391
|
Uroepithelial defense has ben suggested to contribute to the local host resistance against ascending urinary tract infection. The cellular mechanism, however, is not known. In this study, bacterial growth was measured under the direct and indirect influence of uroepithelial cells. To study if a specific ligand-receptor interaction is required for uroepithelial cell (UEC) activation, isogenic Escherichia coli mutants expressing either mannose-sensitive, mannose-resistant (p), or mannose resistant (s) pili were tested for their capacity to induce the UEC defense mechanism. The antibacterial effect of UEC was abolished either by performing coculture in chambers with a fluid-permeable membrane which separates UEC from bacteria or by inhibiting membrane contact using the antiadherence factor pentosane polysulfate. No difference between the various types of pili could be shown. All E. coli strains adhered comparably to the UEC and were subsequently suppressed in their growth. Even a "naked" mutant without expression of common pili showed a similar behavior. In conclusion, bacterial growth suppression depends on direct contact between the UEC and bacteria, but is independent of common pili expressed on E. coli.
|
10.1007/s004670050162
|
pubmed_103_22919
|
Articular cartilage injuries lead to progressive degeneration of the joint with subsequent progression to osteoarthritis, which currently becomes a serious health and economic issue. Due to limited capability for self-regeneration, cartilage repair remains a challenge for the present-day orthopedics. Currently, available therapeutic methods fail to provide satisfactory results. A search for other strategies that could regenerate a hyaline-like tissue with a durable effect and adequate mechanical properties is underway. Tissue engineering strategies comprise the use of an appropriately chosen scaffold in combination with seeding cells. Mesenchymal stem cells (MSC) provide an interesting new option in regenerative medicine with solid preclinical data and first promising clinical results. They act not only through direct cartilage formation, but also due to paracrine effects, such as releasing trophic factors, anti-inflammatory cytokines, and promoting angiogenesis. The MSC can be applied in an allogeneic setting without eliciting a host immune response. Out of the various available sources, MSC derived from Wharton's jelly of an umbilical cord seem to have many advantages over their counterparts. This article details a novel, single-staged, and minimally invasive technique for cartilage repair that involves dry arthroscopic implantation of scaffold-embedded allogenic mesenchymal stem cells isolated from umbilical cord Wharton's jelly.
|
10.1007/5584_2017_9
|
pubmed_412_11943
|
Identification of eicosanoids which are metabolites of arachidonic acid in red algae Gracilaria asiatica, one of the popular seaweeds in Japan, was carried out using high-performance liquid chromatography (HPLC) interfaced with electrospray ionization mass spectrometry. Prostaglandin (PG) E2, 15-keto-PGE2, and 8-hydroxyeicosatetraenoic acid (HETE) were detected as major eicosanoids and PGA2, leukotriene B4 as minor ones in G. asiatica. 8- and 12-HETE had the same retention time in HPLC analysis, but using this analytical method, we were able to identify them.
|
10.1016/s0021-9673(97)00943-6
|
pubmed_689_3452
|
The current epidemic proportions of infections caused by Staphylococcus aureus strains and especially by methicillin-resistant S. aureus (MRSA) are one of today's many threats to global public health, particularly in underdeveloped countries where significant gaps on the subject exist. The rapid spread and diversification of pandemic clones that exhibit remarkably increasing virulence and antimicrobial resistance pose a risk to the effective prevention and treatment of a wide range of infections. Undoubtedly, the remarkable versatility involving the pathogenesis and resistance of these bacteria is perpetuated through geographic and temporal factors inherent to clonal evolution and is reflected in the dramatic epidemiological changes of MRSA which, after decades prevailing in healthcare settings, have emerged in the community. Denominated community-associated [CA]-MRSA, these strains are particularly prevalent in some population groups, facilitating the spread of successful clones that are potentially capable of triggering severe community-acquired infections. Therefore, a broad approach to local epidemiological aspects in less studied regions, but nonetheless at latent risk of endemic spread that may reach global proportions, is necessary. In Brazil, despite limited molecular epidemiology data, CA-MRSA strains predominantly characterized as SCCmec IV, often classified as CC30-ST30, CC5-ST5 and CC8-ST8, seem to be spreading across different population groups in different regions of the country. Another important fact addressed in this review is the identification of the ST398-MRSA-IV/V clone and methicillin-susceptible S. aureus (MSSA) in healthy individuals from the community. Although susceptible to methicillin, the ST398 clone is associated with severe infections in humans and animals, denominated livestock-associated MRSA. It is therefore important to encourage assertive actions by all government sectors and by society, with a reassessment of current public health measures in light of the new perspectives arising from the scientific and epidemiological data on MRSA.
|
10.1016/j.bjid.2021.101636
|
pubmed_731_10871
|
Retinoblastoma is the most common intraocular malignancy in children with poor prognosis. The progression of retinoblastoma is dependent on a robust angiogenic response. Targeting both retinoblastoma cells and angiogenesis may therefore provide an alternative therapeutic strategy in retinoblastoma. Here, we demonstrated the inhibitory effects of tigecycline, a FDA-approved antibiotic, in retinoblastoma and angiogenesis in vitro and in vivo. We showed that tigecycline significantly inhibited growth and induced caspase-dependent apoptosis of multiple retinoblastoma cell lines. Tigecycline also effectively inhibited angiogenesis through suppressing capillary network formation, migration, proliferation and survival of human retinal microvascular endothelial cell (HREC). Mechanistically, tigecycline acts on both retinoblastoma cells and HREC via inhibiting mitochondrial protein translation, resulting in mitochondrial dysfunction, energy crisis, and oxidative damage. Importantly, we demonstrated the in vivo efficacy of tigecycline in inhibiting retinoblastoma and angiogenesis, and inducing oxidative stress on xenograft mouse model. In addition, ATP levels and growth rates were largely affected in retinoblastoma ρ0 cells that lacked mitochondrial respiration. Our work provides systematic pre-clinical evidence for repurposing tigecycline from its traditional use for retinoblastoma treatment. Our work demonstrates the essential roles of mitochondrial metabolism in both retinoblastoma and its angiogenesis.
|
10.1038/s41598-018-29938-x
|
pubmed_572_4612
|
PURPOSE OF STUDY
To examine change in balance-related fall risk and daily functional abilities in the first 2 post-operative weeks and up to 6 weeks after gynecologic surgery.
MATERIALS AND METHODS
Prospective cohort study in gynecologic surgery patients age 65 and older. Balance confidence (Activities-specific Balance Confidence Scale) and functional status (basic and instrumental activities of daily living) were recorded pre- and post-operatively daily for 1 week and twice the second week. Physical performance balance and functional mobility were measured pre- and 1 week post-operatively using the Tinetti Fall Risk Scale, Timed Up and Go, and 6-Minute Walk test. Measures were repeated 6 weeks after surgery. Non-parametric tests for paired data were used comparing scores baseline to post-operative (POD) 7 and to POD 42.
RESULTS
Median age was 72 years (range 65-88). Fall risk was elevated during the first 2 post-operative weeks, greatest on the median discharge day, POD 2 (p<0.01). Balance performance and functional mobility at 1 week were significantly lower than baseline (p<0.01). Functional abilities declined, including new dependence in medication management at home in 22% of these independent and cognitively intact women.
CONCLUSIONS
After gynecologic surgery, older women's fall risk is highest on POD 2 and remains elevated from baseline for 2 weeks. Functional limitations in the early home recovery period include the anticipated (bathing, cooking, etc.) and some unanticipated (medication management) ones. This information may help with post-operative discharge planning.
|
10.1016/j.archger.2017.07.006
|
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