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pubmed_919_3067 | The objective of this study was to investigate the adsorption of Basic Yellow 28 that is a cationic dye on clinoptilolite and amberlite XAD-4. Both equilibrium and batch rate adsorption in aqueous solutions of the dyestuff were investigated. Adsorption rate data were analysed using the pseudo-first order kinetic model of Lagergren and the pseudo-second order model to determine adsorption rate constants at 20, 30 and 40 degrees C. The adsorption equilibrium data were analysed using various adsorption isotherm models and the results have shown that adsorption behaviour of Basic Yellow 28 by clinoptilolite and amberlite could be described by either Langmuir or Freundlich models. Langmuir adsorption isotherm constants corresponding to adsorption capacity, Q(0), were found to be 59.6, 52.9 and 56.7 mg/g for clinoptilolite at 20, 30 and 40 degrees C, respectively. Lower adsorption capacities for Basic Yellow 28 on amberlite were obtained. The increase of adsorption rate constants with an increase in temperature for BY 28 adsorption on amberlite indicated chemisorption with dissociation and increased availability of sites due to higher penetration of adsorbing molecules into the pores. | 10.1016/j.jcis.2005.07.040 |
pubmed_1121_1852 | The triazole ring system has emerged as an exciting prospect in the optimization studies of promising lead molecules in the quest for new drugs for clinical usage. Several marketed drugs possess these versatile moieties that are used in a wide range of medical indications. This stems from the unique intrinsic properties of triazoles, which impart stability to the basic pharmacophoric unit with an added advantage of being a bioisostere of different chemical functionalities. In the last decade, the use of triazoles as bioisosteres and linkers in the development of microtubule targeting agents has been extensively investigated. The present review highlights the advances in this promising area of drug discovery and development. | 10.1039/c9md00458k |
pubmed_704_23676 | BACKGROUND
People who use drugs problematically are consistently left out of consultations and deliberation on drug policy. This article explores how people who formerly used drugs problematically and service providers view Ireland's current drug policy and if alternative policies could be successful in an Irish context.
METHODS
Semi-structured interviews were conducted with eight people who used drugs problematically and six practitioners working with people who use drugs in Cork city, Ireland. All people who used drugs problematically had at least one year of abstinence and had been criminalised because of their drug use, all but one had served at least one custodial sentence. Participants were asked their opinions on safe injecting facilities, heroin assisted treatment, decriminalisation of drugs for personal use, depenalisation of cannabis and, the relationships between economic deprivation and problematic drug use.
RESULTS
Respondents stressed that, in Cork city, problematic drug use is closely linked with economic deprivation and social exclusion. There was a near consensus that criminalisation and penalisation do not deter consumption and produce unintended consequences. All participants supported safe injecting facilities and the decriminalisation of drugs for personal use. Participants were less certain about the utility of heroin assisted treatment and depenalisation of cannabis. Many discussions drifted away from alternatives policies towards the need for improved treatment provision.
CONCLUSION
Several participants were clear that none of the alternative policies discussed are silver bullets. Participates felt that, while they could reduce the harms caused by drugs and drug policies, the government's longer-term objectives should be increased treatment provision and, reduced social exclusion and economic deprivation. | 10.1016/j.drugpo.2020.102891 |
pubmed_852_13706 | Exposure of the respiratory tract during surgical interventions is an important topic of occupational medicine, which has only rarely been investigated. Based on a literature search, relevant information on the possible health risk is summarised. Within the operating room, an exposure of the respiratory tract to gas (volatile anaesthetics) and aerosols (smoking gas by coagulation) can occur. This exposure needs to be considered as a potential health risk if safety measures are not sufficient. Health risks comprise possible disturbances of gravidity and fertility, neurotoxicity and cancer generation. Such health risks can be prevented with primary preventive measures and can be early recognised/diagnosed by preventive investigations of occupational medicine (secondary prevention). Safety measures are developed according to the STOP principle (substitution, technical, organisatory and personal measures). Assessment of the potential danger begins with an appropriate description of the working procedure and detection of the toxic features of the drugs and medical products, which helps to determine individual exposure and to estimate risk potential. Required occupational safety measures can be derived from this and, subsequently, the work organisation can be optimised. In addition, employees in the operating room are to be instructed about the indicated preventive mode of behaviour. Due to better implementation of the above-mentioned basic principles, introduction of novel narcotics and technological developments, potential exposure of the respiratory tract within the operating room has been reduced over the last 10 years. Thus, risks for gravidity and possible disturbances of fertility by exposure to volatile narcotics are currently assessed to be low. However, available data on health risks of the chronic exposure to smoking gases are still deficient although toxic and cancerogenic organic pyrolysis products are generated. The protection effect of modern air conditioning (e.g., laminar air flow) is only insufficiently investigated. Therefore, further studies on these problems are required. | 10.1055/s-0032-1328179 |
pubmed_529_15604 | OBJECTIVES
Renal replacement therapy may be required for acute kidney injury treatment in neonates with complex cardiac conditions. Continuous veno-venous hemofiltration is applied safely in this population but no published recommendations for dose prescription in neonates currently exist. The aim of our study was to evaluate the effects of a relatively small dialysis dose on critically ill neonates.
DESIGN
Retrospective analysis of clinical charts.
SETTING
Pediatric Cardiac ICU.
PATIENTS
Ten critically ill neonates with severe acute kidney injury were analyzed. The primary indication for continuous veno-venous hemofiltration initiation was severe fluid overload with oligoanuria.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
The median (range) age and weight were 3 days (1-12 d) and 2.6 kg (2.1-4.2 kg), respectively, whereas the median continuous veno-venous hemofiltration duration was 17 days (3-63 d). Median prescribed blood flow rate, replacement fluid rate, and net ultrafiltration rate were 12 mL/min (9-50 mL/min), 100 mL/hr (40-200 mL/hr), and 20 mL/hr (5-45 mL/hr), respectively. The median effluent-based continuous veno-venous hemofiltration dose was 35 mL/kg/hr (11-66 mL/kg/hr), whereas the median delivered daily Kt/V per session (24 hr) was 0.5 (0.01-1.8). However, for treatment sessions lasting less than or equal to 12 versus greater than or equal to 12 hours per session, the median prescribed effluent dose was 41 (11-66) and 32 (17-60) mL/kg/hr, respectively (p = 0.06), whereas the delivered creatinine daily Kt/V values were 0.3 (0.01-0.9) and 0.9 (0.5-1.8), respectively (p < 0.0001). An inverse correlation was found between delivered daily Kt/V and the blood concentration differences of both creatinine (r = -0.3; p = 0.0093) and urea (r = -0.3; p = 0.0028) measured at the end and the beginning of a 24-hour treatment. The decrease of creatinine concentration was significantly greater during 24-hour treatment sessions with a delivered daily Kt/V greater than 0.9 than during those with daily Kt/V less than 0.9.
CONCLUSIONS
Based on these findings, we propose on a provisional basis the use of daily Kt/V as a measure of continuous renal replacement therapy adequacy for critically ill neonates. | 10.1097/PCC.0000000000001177 |
pubmed_42_6206 | Using 500 MHz NMR, we have carried out a stable ion protonation and model nitration study of the methoxy-substituted hydrocarbon 6, its 15-ol 7, and the dimer 10, in order to evaluate OMe substituent effects on directing electrophilic attack and on charge delocalization mode/conformational aspects in the resulting carbocations. It is found that the C-11 methoxy group directs the electrophilic attack to C-12 and C-14. Thus protonation of 6 with FSO(3)H/SO(2)ClF gives a 4:1 mixture of monoarenium ions 6H(+)()/6aH(+)(). Prolonged reaction times and increased temperature induced fluorosulfonylation at C-14 (6(+)-SO(2)()F), whereas ambient nitration with NO(2)(+)BF(4)(-) occurred at C-12. The 15-ol derivative 7 is cleanly ionized to 11(+)(), providing the first example of an alpha-phenanthrene-substituted carbocation from phenanthrene C-1 position. Contrasting behavior of the D-ring methyl-substituted 9 and the C-11 methoxy-substituted 10 dimers is remarkable in that unlike 9 which is readily cleaved to produce the monomeric arenium ion 3H(+)(), 10 is diprotonated at the two C-12 sites and at C-12/C-14 in each unit. The latter dication-dimer exists as a mixture of diastereomers. Reactivity of 7 underscores the importance of 11(+)(). Attack at the C-14 ring junction is in concert with the proposal that electrophilic oxygen would attack at C-14/C-15 (epoxidation) followed by ring opening to give the biologically active 15-ol as a major metabolite. | 10.1021/jo000534i |
pubmed_1066_20161 | BACKGROUND
Anxiety, mood, and substance use disorders have significant social and economic impacts, which are largely attributable to their early age of onset and chronic disabling course. Therefore, it is critical to intervene early to prevent chronic and debilitating trajectories.
OBJECTIVE
This paper describes the study protocol of a CONSORT (Consolidated Standards of Reporting Trials)-compliant randomized controlled trial for evaluating the effectiveness of the Mind your Mate program, a mobile health (mHealth) peer intervention that aims to prevent mental health (focusing on anxiety and depression) and substance use problems in adolescents.
METHODS
Participants will consist of approximately 840 year 9 or year 10 students (60 students per grade per school) from 14 New South Wales high schools in Sydney, Australia. Schools will be recruited from a random selection of independent and public schools across the New South Wales Greater Sydney Area by using publicly available contact details. The intervention will consist of 1 introductory classroom lesson and a downloadable mobile app that will be available for use for 12 months. Schools will be randomly allocated to receive either the mHealth peer intervention or a waitlist control (health education as usual). All students will be given web-based self-assessments at baseline and at 6- and 12-month follow-ups. The primary outcomes of the trial will be the self-reported use of alcohol and drugs, anxiety and depression symptoms, knowledge about mental health and substance use, motives for not drinking, and willingness to seek help. Secondary outcomes will include positive well-being, the quality of life, and the impact of the COVID-19 pandemic. Analyses will be conducted using mixed-effects linear regression analyses for normally distributed data and mixed-effects logistic regression analyses for categorical data.
RESULTS
The Mind your Mate study was funded by an Australian Rotary Health Bruce Edwards Postdoctoral Research Fellowship from 2019 to 2022. Some of the development costs for the Mind your Mate intervention came from a seed funding grant from the Brain and Mind Centre of the University of Sydney. The enrollment of schools began in July 2020; 12 of 14 schools were enrolled at the time of submission. Baseline assessments are currently underway, and the first results are expected to be submitted for publication in 2022.
CONCLUSIONS
The Mind your Mate study will generate vital new knowledge about the effectiveness of a peer support prevention strategy in real-world settings for the most common mental disorders in youth. If effective, this intervention will constitute a scalable, low-cost prevention strategy that has significant potential to reduce the impact of mental and substance use disorders.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry ACTRN12620000753954; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379738&isReview=true.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/26796. | 10.2196/26796 |
pubmed_343_11089 | Hierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural strategy into advanced digital manufacturing like three-dimensional (3D) printing remains a technical challenge. This work presents a 3D printing technique with silk fibroin to address this challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and robust mechanical features. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. The manufacturing capability is exemplified by the single-step construction of perfusable microfluidic chips which eliminates the use of supporting or sacrificial materials. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds. This work also provides insights into the recapitulation of solvent-directed hierarchical molecular assembly for artificial manufacturing. | 10.1002/mabi.201900191 |
pubmed_804_19375 | BACKGROUND
It is unclear whether germline breast cancer susceptibility gene mutations affect breast cancer related outcomes. We wanted to evaluate mutation patterns in 20 breast cancer susceptibility genes and correlate the mutations with clinical characteristics to determine the effects of these germline mutations on breast cancer prognosis.
METHODS
The study cohort included 480 ethnic Chinese individuals in Taiwan with at least one of the six clinical risk factors for hereditary breast cancer: family history of breast or ovarian cancer, young age of onset for breast cancer, bilateral breast cancer, triple negative breast cancer, both breast and ovarian cancer, and male breast cancer. PCR-enriched amplicon-sequencing on a next generation sequencing platform was used to determine the germline DNA sequences of all exons and exon-flanking regions of the 20 genes. Protein-truncating variants were identified as pathogenic.
RESULTS
We detected a 13.5% carrier rate of pathogenic germline mutations, with BRCA2 being the most prevalent and the non-BRCA genes accounting for 38.5% of the mutation carriers. BRCA mutation carriers were more likely to be diagnosed of breast cancer with lymph node involvement (66.7% vs 42.6%; P = 0.011), and had significantly worse breast cancer specific outcomes. The 5-year disease-free survival was 73.3% for BRCA mutation carriers and 91.1% for non-carriers (hazard ratio for recurrence or death 2.42, 95% CI 1.29-4.53; P = 0.013). After adjusting for clinical prognostic factors, BRCA mutation remained an independent poor prognostic factor for cancer recurrence or death (adjusted hazard ratio 3.04, 95% CI 1.40-6.58; P = 0.005). Non-BRCA gene mutation carriers did not exhibit any significant difference in cancer characteristics or outcomes compared to those without detected mutations. Among the risk factors for hereditary breast cancer, the odds of detecting a germline mutation increased significantly with having bilateral breast cancer (adjusted odds ratio 3.27, 95% CI 1.64-6.51; P = 0.0008) or having more than one risk factor (odds ratio 2.07, 95% CI 1.22-3.51; P = 0.007).
CONCLUSIONS
Without prior knowledge of the mutation status, BRCA mutation carriers had more advanced breast cancer on initial diagnosis and worse cancer-related outcomes. Optimal approach to breast cancer treatment for BRCA mutation carriers warrants further investigation. | 10.1186/s12885-018-4229-5 |
pubmed_76_2532 | OBJECTIVE
In essential hypertension, captopril attenuates forearm vasoconstriction reflexly induced by deactivation of cardiopulmonary and arterial baroreceptors, thus exerting a sympathomoderating effect. We investigated whether this is a common effect of angiotensin converting enzyme (ACE) inhibitors.
METHODS AND DESIGN
Cardiopulmonary and arterial baroreceptors were deactivated by progressively reducing central venous pressure (CVP) through progressively greater lower body negative pressures in eight untreated mild essential hypertensives on a moderately low-sodium diet (50 mmol/l per day). This deactivation was performed after oral administration of the non-sulphidrylic ACE inhibitor benazepril (10 mg) and placebo according to a double-blind randomized crossover experimental design.
RESULTS
After placebo, the reduction in CVP increased forearm vascular resistance (FVR; mean arterial pressure: plethysmographic forearm blood flow ratio). After benazepril, baseline blood pressure (beat-to-beat finger pressure) and FVR were significantly reduced whilst plasma angiotensin II was suppressed and PRA increased (both measured by radioimmunoassay). The FVR increases induced by progressive CVP reduction were less than after placebo administration, and the overall difference was statistically significant. Benazepril did not affect the reflex FVR reduction observed by increasing CVP through leg raising, nor the reflex changes in plasma norepinephrine measured by high-performance liquid chromatography accompanying the changes in FVR.
CONCLUSIONS
Benazepril attenuates sympathetic vasoconstriction as does captopril. This effect (which is mainly operative during an increased sympathetic drive and exerted through a reduction of adrenoceptor responsiveness) is thus likely to be a class- rather than a compound-related feature. | 10.1097/00004872-199204000-00009 |
pubmed_1108_1323 | Interest in the presence and management of synchronous multiple ipsilateral breast cancer has been reported since the early 1920s. The demonstration of multiple foci of breast cancer has been reported in 9-75% of breast cancer related specimens. The large difference in reported incidence is multifactorial and related to the definitions applied, mode of detection and pathological assessment. However, randomised clinical trials comparing total mastectomy and segmental mastectomy with or without radiation over many years have shown no difference in distant disease-free survival or overall survival in patients with synchronous multiple ipsilateral breast cancer compared with unifocal breast cancer. This review examines the current definitions, incidence, pathological assessment, staging and surgical options of synchronous multiple ipsilateral breast cancer. | 10.1080/00313020802563502 |
pubmed_625_22447 | Epiretinal membrane over macula secondary to toxoplasmosis compromises vision. We describe the outcome of pars plana vitrectomy and epiretinal membrane removal after adequate treatment of acute infection. The average age of all four male patients was 36 years (range 20-60 years). Following surgery there was an average three or more lines visual acuity improvement, restoration of foveal contour with reduction in central macular thickness. One patient developed choroidal neovascular membrane postsurgery and was effectively treated with intravitreal bevacizumab. Surgery for ERM secondary to healed toxoplasmosis infection has good anatomical outcome and reasonable visual improvement, when the surgery is done in a quiet eye. | 10.4103/ijo.IJO_364_18 |
pubmed_1006_8549 | The main directions in the research and study of industrial microclimate are represented in the article. Evaluation of the microclimate based on thermophysiology, studies of correlation between the environmental temperature and the human functional status helped to establish the normal parameters, measures of the overheating and the overcooling prophylaxis. New data about the immediate and late effect of single microclimate parameters on the human functional status necessitate the creation of new methodic approaches to the evaluation and control of microclimate conditions. | pubmed_1006_8549 |
pubmed_399_9258 | This study of colorectal polyps is based on 129 patients in whom 241 colorectal polyps were diagnosed and excised by colonoscopy in the Gastroenterology Unit of a hospital in the Upper Galilee, Israel, between 1 July 1984 and 30 June 1987. The male:female ratio was 2:1. Anemia was demonstrated in 7% and positive Hemoccult II test (Smith Kline, USA) in 64%. The types of polyp were 58% adenomatous, 25% hyperplastic and 15% inflammatory. Adenomatous polyps were larger than the other types (chi 2 = 13.24, P less than 0.01), and were more frequent in the left colon than inflammatory polyps (chi 2 = 4.67, P less than 0.05). The annual incidence of colorectal polyps and the percentage of colonoscopies that revealed polyps were highest for Jews of European/American origin (5.3/10,000, 26%) compared with Jews of Israeli and Asian/African origin and Arabs (2/10,000, 6%; 1.3/10,000, 12%; and 1/10,000, 9%, respectively). These data confirm findings of other investigators showing a higher incidence of colorectal polyps in European/American Jews than in other ethnic Israeli groups. | pubmed_399_9258 |
pubmed_1111_6043 | Chronic heart failure often results in catabolic muscle wasting, exercise intolerance, and death. Oxidative muscles, which have greater expression of the metabolic master gene peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and its target genes, are more resistant to catabolic wasting than are glycolytic muscles; however, the underlying mechanism is unknown. To determine the functional role of PGC-1α in oxidative phenotype-associated protection, skeletal muscle-specific PGC-1α transgenic mice were crossbred with cardiac-specific calsequestrin transgenic mice, a genetic model of chronic heart failure. PGC-1α overexpression in glycolytic muscles significantly attenuated catabolic muscle wasting induced by chronic heart failure. In addition to inactivation of forkhead transcription factor signaling through enhanced Akt/protein kinase B expression, in glycolytic muscles, PGC-1α overexpression led to enhanced expression of inducible nitric oxide synthase and endothelial nitric oxide synthase, production of nitric oxide, and expression of antioxidant enzyme including superoxide dismutases (SOD1, SOD2, and SOD3) and catalase, and reduced oxidative stress. These findings suggest that PGC-1α protects muscle from catabolic wasting in chronic heart failure through enhanced nitric oxide antioxidant defenses and inhibition of the forkhead transcription factor signaling pathways. | 10.1016/j.ajpath.2011.01.005 |
pubmed_886_981 | OBJECTIVES
Although the ileal conduit is the most well-established urinary diversion, the optimal technique for ureteroileal anastomosis remains controversial. Here, we present a technique for anastomosis of the ureters from within the lumen of the ileal conduit, under direct visualization. We examine the rate of ureteral stricture using this method, and review the literature regarding ureteroenteric anastomotic complications with various techniques.
METHODS
An intraluminal technique for ureteroenteric anastomsosis was performed by opening the conduit on the antimesenteric border to allow direct visualization of the ureteroileal anastomosis. Using our prospectively collected database, we investigated the prevalence of anastomotic stricture in patients undergoing urinary diversion using this method for anastomosis.
RESULTS
One-hundred eighteen patients underwent ileal conduit diversion with ureteroileal anastomoses performed as described. Median postoperative follow-up was 15 months. Ureteral strictures were identified in 5/118 patients (4.2%). Of the patients with strictures, one was successfully treated with endoscopic balloon dilatation, three were managed with chronic ureteral stents, and one was managed with a chronic percutaneous nephrostomy. Review of the recent literature reveals stricture rates up to 10% with current techniques.
CONCLUSIONS
We conclude from these results that during ileal conduit creation, intraluminal anastomosis of the ureters to the ileal segment under direct vision represents a viable alternative to other techniques, with complication rates that compare favorably with other reported series. | 10.1016/j.urology.2010.01.035 |
pubmed_422_1081 | Electron microscope autoradiography was used to study glycoprotein synthesis in cellular trophoblast (cytotrophoblast) and syncytial trophoblast of term human placental villi incubated in vitro with D-[1-3H]galactose ([3H]gal). Autoradiographs were analyzed using the hypothetical grain analysis of Blackett and Parry (1973. J. Cell Biol. 57:9-15). The results of this study indicated that [3H]gal incorporation into term placental villi was predominantly localized to cytotrophoblast. Utilization of [3H]gal by term syncytial trophoblast was extremely low and yielded too few grains for a quantitative grain analysis. This result is in striking contrast to that found in the preceding study of [3H]leucine incorporation (Nelson, D. M., A. C. Enders, and B. F. King. 1978). Within cytotrophoblast, the rough endoplasmic reticulum incorporated the most [3H]gal into glycoprotein. The Golgi apparatus was another site of [3H]gal incorporation. The vast majority of the [3H]gal incorporated into cytotrophoblast during the pulse incubation remained intracellular through the duration of the experiment. There was little autoradiographic evidence for secretion of tritiated macromolecules. Cytotrophoblast incubated for the longest time period studied (4 h+) showed a substantial concentration of tritiated macromolecules in the Golgi complex and in the ground plasm but not in the rough endoplasmic reticulum. | 10.1083/jcb.76.2.418 |
pubmed_35_4195 | In this paper, the traditional snake model and gradient vector flow (GVF) snake model are studied, which are believed to be quite slow due to the need to compute inverse matrix. Actually, the GVF in the latter snake model is formed by a biased linear diffusion procedure, and there would be oscillations around the edge of the object. Based on GVF generated through non-linear diffusion, we present a fast GVF (FGVF) snake model which is much faster than the traditional snake model and GVF snake model, and would cause no degradation of stability and flexibility, meanwhile, it could reduce the oscillations around the edges. The segmentation results using FGVF and error analysis on simulated images are presented. Finally, the demonstration of FGVF applied to Computed Tomography and Magnetic Resonance images are shown, the segmentation results are satisfactory visually with much less computation time in comparison with former snakes. | 10.1016/j.compmedimag.2003.12.002 |
pubmed_774_5567 | BACKGROUND
Although feeding difficulties are commonly described amongst children with chronic diseases, those admitted to a paediatric intensive care unit (PICU) represent a mix of previously healthy children as well as those with pre-existing diseases. There is, however, a lack of evidence describing the prevalence and type of feeding difficulties amongst healthy children who survive a period of critical illness and the subsequent impact on growth and family life. The aim of this work was to complete a scoping review of evidence describing feeding difficulties amongst PICU-survivors.
METHOD
Six electronic databases were searched from January 2000-October 2018. NICE Healthcare Databases Advanced Search website (https://hdas.nice.org.uk/) was used as a tool to complete multiple searches within multiple databases, including the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and Medline. Any studies considering feeding difficulties amongst previously healthy children following discharge from PICU or those which explored the parental/caregiver experiences were included.
RESULTS
As the initial search yielded only one study which fulfilled the inclusion criteria, the criteria was extended to include studies relating to feeding difficulties (post-discharge) amongst otherwise healthy ex-preterm infants (born < 37 weeks gestational age) and infants/children with chronic diseases where feeding difficulties were described following a PICU admission. A review team screened and extracted the data of published qualitative and quantitative studies, using content analysis techniques. Of the 9622 articles identified from the searches, 22 full-text studies were reviewed with seven studies included. Four overarching categories represented the results: prevalence of feeding difficulties; risk factors and predictors for developing feeding difficulties; parental/carer experience and emotional response to feeding difficulties; and challenges in accessing feeding support.
CONCLUSIONS
The results of this scoping review suggest there are gaps in the research, particularly those exploring the prevalence of feeding difficulties amongst previously healthy children and the negative impact this may have on family life. Future research should focus on addressing the extent of the problem and identifying risk factors, in addition to the potential development of toolkits for health care professionals to better support parents. | 10.1016/j.clnesp.2019.01.013 |
pubmed_920_653 | AIM OF THE STUDY
To describe bacterial infections in injection drug users (IDUs) hospitalized at Montpellier University Hospital, France, and to identify factors that might influence the development of local or systemic infections.
METHODS
This cross-sectional observational monocentric study prospectively included bacterial infections in IDUs hospitalized at Montpellier University Hospital between 2012 and 2018. Types of infection (local or systemic) were described and compared to identify specific features (injection practices).
RESULTS
The study included 144 bacterial infections (56% of local infections and 44% of systemic infections) concerning 117 IDUs. The most common infection types were abscesses (50%), skin and soft tissue infections (33%), bacteremia/sepsis (20%), endocarditis (17%), and bone and joint infections (16%). Patients were mainly men (n=94; 80%), and the median age was 40 years [IQR25-75: 34-47]. Four deaths related to systemic infection were reported. The most frequent injected substances were cocaine, opioid maintenance treatments (OMT), and opioids. According to the multivariate analysis, factors associated with the occurrence of systemic infections were number of injection (OR 2.59 [1.07-6.27]; P=0.034) and injection of at least one opioid (OR 3.52 [1.28-9.72]; P=0.015).
CONCLUSION
Different types of bacterial infections, local or systemic, are observed in IDUs. Skin infections are quite common, but other infection types also are reported, with sometimes serious consequences. It is already known that injection practices are contributing factors in infection development, but the type of injected psychoactive substance(s) also may have an influence. | 10.1016/j.therap.2021.05.008 |
pubmed_920_26152 | BACKGROUND
Little information is available regarding the effect of religiosity and spirituality on medication adherence in patients with schizophrenia.
AIM
This study aimed to evaluate the association of medication adherence with different aspects of religiosity and spirituality in patients with schizophrenia.
MATERIALS AND METHODS
One hundred patients with schizophrenia were evaluated on religiousness measure scale and Duke Religion Index (DUREL); Brief Religious Coping Scale (Brief RCOPE); World Health Organization Quality of Life Spirituality, Religiosity, and Personal Beliefs (WHOQoL-SRPB); and Brief Adherence Rating Scale (BARS).
RESULTS
A higher level of religiosity as assessed by the religiousness measure scale, private religious activities and intrinsic religiosity as per DUREL, positive religious coping, and all the domains of WHOQOL-SRPB was associated with better medication compliance as assessed by the percentage of doses of medications consumed in the last 1 month as evaluated by using BARS.
CONCLUSION
The present study suggests that a higher level of religiosity and spirituality were associated with better medication compliance. | 10.4103/psychiatry.IndianJPsychiatry_413_20 |
pubmed_791_20210 | AIM AND PATIENTS
The aim of the present study was to assess the effects of dipyridamole on stress and rest peak filling rate in consecutive patients who showed perfusion and, or function abnormalities at Gated-SPECT. Were enrolled 96 patients (73 males (76%); mean age 71.7 ± 9.57). Forty patients (41.7%) had an history of myocardial infarction and fifty-seven (59.4%) of previous cardiac revascularization. All patients underwent a 2-day 99mTc-SestaMIBI gated perfusion SPECT protocol.
RESULTS
Twenty-nine (30.2%) patients showed fixed perfusion defects, 54 (56.2%) showed partially or completely reversible ones, while 13 (13.5%) showed normal perfusion but reduced LVEF. SSS was significantly higher than SRS (9.55 ± 9.29 vs. 7.10 ± 8.48; P = 0.0001). Stress peak filling rate was not significantly higher than rest peak filling rate (1.73 EDV/s ± 0.69 EDV/s vs. 1.67 EDV/s ± 0.56 EDV/s; P = 0.62). At a multivariate regression analysis, only stress peak filling rate, as independent variable, was directly correlated with myocardial ischemia (SDS) (P = 0.018). We divided patients according to SDS in those with mild (SDS < 5) and severe (SDS ≥ 5) ischemia. Stress peak filling rate was the only parameter significantly different between groups.
CONCLUSION
Stress PFR showed a better correlation with the degree of ischemia compared to the remaining perfusion and functional parameters. The direct correlation between SDS and stress PFR leads us to speculate that dipyridamole could improve diastolic function in ischemic patients. | 10.1097/MNM.0000000000001303 |
pubmed_11_23485 | While most drug policy researches paid attention to the financial impact of expensive drugs, the market situation of low-priced drugs in a country was seldom analyzed. We used the nationally representative claims datasets to explore the status within the National Health Insurance (NHI) in Taiwan. In 2007, a total of 12,443 distinct drug items had been prescribed 853,250,147 times with total expenditure of 105,216,950,198 new Taiwan dollars (NTD). Among them, 7,366 oral drug items accounted for 701,353,383 prescribed items and 68,133,988,960 NTD. Besides, 2,887 items (39.2% of oral drug items) belonged to cheap drugs with the unit price ≤ 1 NTD (about 0.03 of US dollar). While the top one item among all oral drugs had already a market share of 5.0%, 30 items 30.3% and 107 items 50.0%, the cheap drugs with aggregate 332,893,462 prescribed items (47.5% of all prescribed oral drug items) only accounted for 2,750,725,433 NTD (4.0% of expenditure for oral drugs and 2.6% of total drug expenditure). The drug market of Taiwan's NHI was abundant in cheap drugs. The unreasonably low prices of drugs might not guarantee the quality of pharmaceutical care and the sustainability of a healthy pharmaceutical industry in the long run. | 10.1155/2014/234941 |
pubmed_1129_11250 | BACKGROUND
Glycopeptide antibiotics inhibit bacterial cell-wall synthesis, and are important for the treatment of infections caused by multi drug-resistant strains of enterococci, streptococci and staphylococci. The main mechanism by which bacteria resist the action of glycopeptides is by producing a modified cell-wall in which the dipeptide D-Alanine-D-Alanine is substituted by D-Alanine-D-Lactate or D-Alanine-D-Serine. Recently, it has been shown that inorganic phosphate (Pi) induces hypersensitivity to vancomycin in Streptomyces coelicolor (which is highly resistant to the antibiotic in low-Pi media). This finding was surprising because the bacterium possesses the entire set of genes responsible for vancomycin resistance (VR); including those coding for the histidine kinase/response regulator pair VanS/VanR that activates the system.
RESULTS
This work shows that high Pi amounts in the medium hamper the activation of the van promoters and consequently inhibit VR in S. coelicolor; i.e. the repression effect being stronger when basic or acidic forms of the nutrient are used. In addition, this work shows that lysozyme resistance is also highly regulated by the Pi concentration in the medium. At least five different mutations contribute to the overcoming of this repression effect over VR (but not over lysozyme resistance). Therefore, the interconnection of VR and lysozyme resistance mechanisms might be inexistent or complex. In particular, two kinds of mutant in which Pi control of VR has been lost (one class expresses the van genes in a constitutive manner; the other retains inducibility by vancomycin) have been isolated and further characterized in this study. Sequencing revealed that the first class of mutation conferred a single amino acid substitution in the second transmembrane helix of the VanS protein; whereas the other class hampered the expression or activity of a putative homolog (SCO1213) to the staphylococcal GatD protein. Complementation, phenotypic and bioinformatics analyses identified SCO1213, and its upstream gene (i.e. murT), as relevant genetic determinants involved with VR in S. coelicolor.
CONCLUSION
The genomic approach of this study together with other genetic and phenotypic analyses has allowed the identification of the uncharacterized murT-gatD Streptomyces genes and the characterization of their involvement with the Pi control of VR in S. coelicolor. | 10.1186/s12864-018-4838-z |
pubmed_667_1952 | The risks during pregnancy from commonly prescribed psychopharmacological agents are summarized in this article. Psychotropic agents included in this discussion are antidepressants, antianxiety agents, and antipsychotic agents. The focus of this review is to describe the association between these medications and the incidence of congenital malformations. Epidemiological studies, cohort studies, case reports, and animal studies are discussed. | 10.1016/s0146-0005(97)80059-6 |
pubmed_151_18980 | The threat from invasive meningococcal disease (IMD) remains a serious source of concern despite the licensure and availability of vaccines. A limitation of current serogroup B vaccines is the breadth of coverage afforded, resulting from the capacity for extensive variation of the meningococcus and its huge potential for the generation of further diversity. Thus, the continuous search for candidate antigens that will compose supplementary or replacement vaccines is mandated. Here, we describe successful efforts to utilize the reverse vaccinology 2.0 approach to identify novel functional meningococcal antigens. In this study, eight broadly cross-reactive sequence-specific antimeningococcal human monoclonal antibodies (hmAbs) were cloned from 4 ml of blood taken from a 7-month-old sufferer of IMD. Three of these hmAbs possessed human complement-dependent bactericidal activity against meningococcal serogroup B strains of disparate PorA and 4CMenB antigen sequence types, strongly suggesting that the target(s) of these bactericidal hmAbs are not PorA (the immunodominant meningococcal antigen), factor-H binding protein, or other components of current meningococcal vaccines. Reactivity of the bactericidal hmAbs was confirmed to a single ca. 35 kDa protein in western blots. Unequivocal identification of this antigen is currently ongoing. Collectively, our results provide proof-of-principle for the use of reverse vaccinology 2.0 as a powerful tool in the search for alternative meningococcal vaccine candidate antigens. | 10.3389/fimmu.2018.01621 |
pubmed_1017_12208 | Using experience sampling methods we examined how group size and context-specific drinking norms corresponded to alcohol consumption and compliance with drinking offers during natural social drinking events. For 30 days, 397 college students reported daily on their alcohol consumption during social events, the size of the group they were with, the average alcohol consumption of its' members, and the number of drinks they accepted that came directly from the group they were with during these social drinking events. Larger groups corresponded with greater alcohol consumption, but only when context-specific norms were high. Furthermore, larger groups increased compliance with drinking offers when context-specific norms were high, but decreased compliance with drinking offers when context-specific norms were low. Thus, subtle features of the social-context may influence not only overall consumption behavior, but also compliance with more overt forms of social influence. | 10.1080/01973533.2012.693341 |
pubmed_485_8889 | Hypothermia and hyperthermia related cases recorded for the period 1973 to 1984 were collected from the files of the Department of Forensic Medicine, University of Oulu, and the necropsy protocols including toxicological results were analyzed. The fact that similar alcohol concentrations were found in both types of fatalities points to the poikilothermic effect of alcohol in humans, as found in animal studies. Both types of deaths seem to be associated with the alcohol elimination phase. Antidepressants and neuroleptics were most often found in the hypothermia cases, but benzodiazepines were also quite frequently present. In spite of the diminished use of barbiturates, these still appear in hypothermia fatalities. Certain other drugs that affect thermoregulation were also noted in solitary cases. Extended toxicological analysis was seldom made in the cases of hyperthermia deaths, and no firm conclusions on the poikilothermic effect of psychotropic drugs could be reached, for example. Therapeutic drug concentrations did not alone predispose the subjects to hypothermia, but appeared in connection with alcohol consumption or chronic diseases. | pubmed_485_8889 |
pubmed_1110_3916 | Telomere biology disorders, which are characterized by telomerase activity haploinsufficiency and accelerated telomere shortening, most commonly manifest as degenerative diseases. Tissues with high rates of cell turnover, such as those in the hematopoietic system, are particularly vulnerable to defects in telomere maintenance genes that eventually culminate in bone marrow (BM) failure syndromes, in which the BM cannot produce sufficient new blood cells. Here, we review how telomere defects induce degenerative phenotypes across multiple organs, with particular focus on how they impact the hematopoietic stem and progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and differentiation. We also discuss how both the increased risk of myelodysplastic syndromes and other hematological malignancies that is associated with telomere disorders and the discovery of cancer-associated somatic mutations in the shelterin components challenge the conventional interpretation that telomere defects are cancer-protective rather than cancer-promoting. | 10.1016/j.diff.2018.01.001 |
pubmed_817_24271 | In brief
Post-ovulatory ageing of oocytes leads to poor oocyte and embryo quality as well as abnormalities in offspring. This review provides an update on the contributions of oxidative stress to this process and discusses the current literature surrounding the use of antioxidant media to delay post-ovulatory oocyte ageing.
Abstract
Following ovulation, the metaphase II stage oocyte has a limited functional lifespan before succumbing to a process known as post-ovulatory oocyte ageing. This progressive demise occurs both in vivo and in vitro and is accompanied by a deterioration in oocyte quality, leading to a well-defined sequelae of reduced fertilisation rates, poor embryo quality, post-implantation errors, and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been characterised, less is known regarding the molecular mechanisms that drive this process. This review presents an update on the established relationships between the biochemical changes exhibited by the ageing oocyte and the myriad of symptoms associated with the ageing phenotype. In doing so, we consider the molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We highlight the mounting evidence that oxidative stress acts as an initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to disrupt mitochondrial function and directly damage multiple intracellular components of the oocyte such as lipids, proteins, and DNA. Finally, this review addresses emerging strategies for delaying post-ovulatory oocyte ageing with emphasis placed on the promise afforded by the use of selected antioxidants to guide the development of media tailored for the preservation of oocyte integrity during in vitro fertilisation procedures. | 10.1530/REP-22-0206 |
pubmed_718_13153 | Cytokines produced by immune system cells infiltrating pancreatic islets are candidate mediators of islet beta-cell destruction in insulin-dependent diabetes mellitus. In this study, we examined the role of nitric oxide (NO) as a mediator of cytokine-induced islet beta-cell destruction in a rat insulinoma cell line (RINm5F). The cytokine combination of interleukin-1 beta (IL-1 beta; 10 U/ml), tumor necrosis factor-alpha (10(3) U/ml), and interferon-gamma (10(3) U/ml) induced DNA fragmentation (first detected at 6 h), mitochondrial damage (by 12 h), and death (by 24 h) of RIN cells, whereas the individual cytokines did not have these destructive effects. Also, the cytokine combination of IL-1 beta, tumor necrosis factor-alpha, and interferon-gamma induced a 10-fold increase in NO production by RIN cells, and L-NG-monomethyl arginine, an inhibitor of NO synthase, produced a dose-dependent inhibition of cytokine-induced NO production, DNA fragmentation, and cell destruction. However, IL-1 beta, acting alone, induced a 7-fold increase in NO production without causing DNA fragmentation, mitochondrial damage, or cell destruction. In addition, nicotinamide, a known inhibitor of ADP ribosylation and scavenger of oxygen free radicals, inhibited cytokine-induced DNA fragmentation and cell destruction without affecting NO production. We conclude that stimulation of NO production may be a necessary, but not sufficient, condition for cytokine-induced destruction of islet beta-cells. | 10.1210/endo.134.3.8119136 |
pubmed_1029_11049 | The rabbit iris-ciliary body contains 78 +/- 6 ng/gm serotonin (5-HT) while the amine content in the aqueous humor is less than 0.01 ng/100 microliter. The low levels of endogenous 5-HT in the iris-ciliary body could not be directly detected by immunocytochemistry. However, pretreatment in vivo and in vitro with L-tryptophan and pargyline resulted in the localization of a sparse population of 5-HT fibers. These fibers could not be studied by exposing the tissue to exogenous 5-HT since the amine was taken up by noradrenergic fibers as well. This was confirmed in studies involving superior cervical ganglionectomy. It is concluded that 5-HT is taken up by both serotonergic and adrenergic fibers of the iris-ciliary body. In the presence of lithium, 5-HT stimulated an increase in the 3H-inositol phosphate accumulation in a dose-dependent manner in tissue where the phosphoinositide pool was labeled with 3H-inositol. A variety of agonists and antagonists were used to show that the 5-HT response is mediated, at least partly, by 5-HT2 receptors. The 5-HT-mediated effect on inositol phosphates is unaffected by superior cervical ganglionectomy. The effect of noradrenaline, which also stimulates inositol phosphate accumulation (but via alpha 1-adrenergic receptors in the iris-ciliary body), was elevated following superior cervical ganglionectomy. | pubmed_1029_11049 |
pubmed_588_6927 | The Bordetella adenylate cyclase toxin-hemolysin (CyaA) targets phagocytes expressing the alpha(M)beta2 integrin (CD11b/CD18), permeabilizes their membranes by forming small cation-selective pores, and delivers into cells a calmodulin-activated adenylate cyclase (AC) enzyme that dissipates cytosolic ATP into cAMP. We describe here a third activity of CyaA that yields elevation of cytosolic calcium concentration ([Ca2+]i) in target cells. The CyaA-mediated [Ca2+]i increase in CD11b+ J774A.1 monocytes was inhibited by extracellular La3+ ions but not by nifedipine, SK&F 96365, flunarizine, 2-aminoethyl diphenylborinate, or thapsigargin, suggesting that influx of Ca2+ into cells was not because of receptor signaling or opening of conventional calcium channels by cAMP. Compared with intact CyaA, a CyaA-AC- toxoid unable to generate cAMP promoted a faster, albeit transient, elevation of [Ca2+]i. This was not because of cell permeabilization by the CyaA hemolysin pores, because a mutant exhibiting a strongly enhanced pore-forming activity (CyaA-E509K/E516K), but unable to deliver the AC domain into cells, was also unable to elicit a [Ca2+]i increase. Further mutations interfering with AC translocation into cells, such as proline substitutions of glutamate residues 509 or 570 or deletion of the AC domain as such, reduced or ablated the [Ca2+]i-elevating capacity of CyaA. Moreover, structural alterations within the AC domain, because of insertion of various oligopeptides, differently modulated the kinetics and extent of Ca2+ influx elicited by the respective AC- toxoids. Hence, the translocating AC polypeptide itself appears to participate in formation of a novel type of membrane path for calcium ions, contributing to action of CyaA in an unexpected manner. | 10.1074/jbc.M609979200 |
pubmed_1109_19724 | Vibrio cholerae O1 biotype El Tor producing Haitian variant Cholera Toxin (HCT) and showing reduced susceptibility to ciprofloxacin caused a cholera outbreak associated with a high case fatality rate (4.5) in India. HCT-secreting strains responsible for severe cholera epidemics in Orissa (India), Western Africa and Haiti were associated with increased mortality. There is a pressing need for an integrated multidisciplinary approach to combat further spread of newly emerging variant strains. The therapeutic effect of ciprofloxacin was diminished whereas use of doxycycline in moderate to severe cholera patients was found to be effective in outbreak management. | 10.1111/1469-0691.12393 |
pubmed_919_20043 | The term visual field corresponds to the angular field of view that is seen by the eyes when they are fixed on a point straight-ahead. In neurological patients--e.g. stroke, trauma, or tumour patients--visual field function can be restricted, depending on lesion site and size. In contrast, the term "functional visual field" describes the area of visual field responsiveness under more ordinary viewing conditions. The visual exploration, i.e. the capacity to explore and analyze our visual world, is dependent on the integrity of the visual system and the oculomotor system which has to move the fovea from one object of interest to the next. In this paper, we present a new method to assess the functional visual field, conceptualized as the area that a patient actively scans with eye movements to detect predefined targets placed on everyday scenes. This method allows us to compare three levels of visual field function: (a) the spatial distribution of successful search (hits, i.e. which targets did the patient find?), (b) the spatial distribution of fixations (i.e. where did the patient preferentially search for targets?), and (c) the retinotopic level (i.e. the visual field assessed by perimetry). By integrating these three levels, one can evaluate functional outcomes of visual field disorders. Of particular importance is the question of how a patient compensates for a visual field loss with appropriate eye movements. A further clinical application of this method is the comparison of pre- with post-treatment data. Patients with visual field disorders usually undergo specific exploration trainings, aimed at enhancing the number and amplitude of saccades towards the region of the visual field deficit. The first experiences and clinical application with this method are presented here. | 10.1016/s0035-3787(05)85085-4 |
pubmed_36_11072 | Quantitative detection of BCR-ABL1 transcript is essential in monitoring residual disease of Philadelphia chromosome positive B lymphoblastic leukemia (Ph+ B-LL). We studied the kinetics of BCR-ABL1 transcript in 41 Ph+ B-LL patients in correlation with their clinical outcome. A total of 23 patients achieved complete molecular remission at 6 months post-treatment. This was associated with a lower relapse risk and better overall survival. Likewise, sustainable complete molecular remission in 27 patients was associated with superior clinical outcome. Sporadic low level BCR-ABL1 was detected in 12 of 27 patients who had attained complete molecular remission. The relapse rate was significantly higher in non-transplant patients with persistent positive BCR-ABL1 than patients transplanted when BCR-ABL1 was detectable. All eight patients harboring ABL1 kinase domain mutations died of disease or were transferred to hospice care. We concluded that monitoring the level of BCR-ABL1 transcript after hematologic remission has predictive value to the long-term outcome. | 10.3109/10428194.2014.1003059 |
pubmed_671_6934 | Hyperpyrexia, followed rapidly by multiple organ failure and death, developed in a previously healthy man. Postmortem examination indicated disseminated tuberculosis with adrenal involvement, but also evidence compatible with heat stroke. Mycobacterium tuberculosis was isolated from a routine blood culture. The patient's symptoms may have been the result of his bacillemia or the result of unapparent tuberculous chronic adrenocortical insufficiency that made him unusually sensitive to heat. | pubmed_671_6934 |
pubmed_177_19315 | The Asiatic blue tick, Rhipicephalus microplus, a known vector of bovine babesiosis and bovine anaplasmosis, is of great concern in the cattle industry. For this reason, detailed knowledge of the distribution of R. microplus is vital. Currently, R. microplus is believed to be associated mainly with the northern and eastern Savanna and Grassland vegetation in South Africa. The objective of the study was to record the distribution of R. microplus, and the related endemic Rhipicephalus decoloratus, in the central-western region of South Africa that comprises Albany Thicket, Fynbos and Savanna vegetation. In this survey, ticks were collected from 415 cattle in four provinces (Eastern Cape, Northern Cape and Western Cape and Free State provinces) and from the vegetation in the Eastern Cape province of South Africa between October 2013 and September 2015. More than 8000 ticks were collected from cattle at 80 localities of which R. microplus was present at 64 localities and R. decoloratus at 47 localities. A total of 7969 tick larvae were recorded from the vegetation at 20 localities of which 6593 were R. microplus and 1131 were R. decoloratus. Rhipicephalus microplus was recorded in each of the regions that were sampled. Rhipicephalus microplus is now present throughout the coastal region of the Eastern Cape province and at multiple localities in the north-eastern region of the Northern Cape province. It was also recorded in the western region of the Western Cape province and one record was made for the Free State province. The observed range changes may be facilitated by the combined effects of environmental adaptability by the tick and the movement of host animals. | 10.4102/jsava.v88i0.1482 |
pubmed_772_624 | BACKGROUND
Recent genome sequence analysis in the red flour beetle Tribolium castaneum indicated that this highly crepuscular animal encodes only two single opsin paralogs: a UV-opsin and a long wavelength (LW)-opsin; however, these animals do not encode a blue (B)-opsin as most other insects. Here, we studied the spatial regulation of the Tribolium single LW- and UV-opsin gene paralogs in comparison to that of the five opsin paralogs in the retina of Drosophila melanogaster.
RESULTS
In situ hybridization analysis reveals that the Tribolium retina, in contrast with other insect retinas, constitutes a homogenous field of ommatidia that have seven LW-opsin expressing photoreceptors and one UV-/LW-opsin co-expressing photoreceptor per eye unit. This pattern is consistent with the loss of photoreceptors sensitive to blue wavelengths. It also identifies Tribolium as the first example of a species in insects that co-expresses two different opsins across the entire retina in violation of the widely observed "one receptor rule" of sensory cells.
CONCLUSION
Broader studies of opsin evolution in darkling beetles and other coleopteran groups have the potential to pinpoint the permissive and adaptive forces that played a role in the evolution of vision in Tribolium castaneum. | 10.1186/1742-9994-4-24 |
pubmed_655_13489 | Following the setting up by the Government of their project for the management of drug addicts, and under the guidance of the CEIP (Centre d'Evaluation et d'Information sur les Pharmacodépendances [Centre for Evaluation and Information on Drug Addiction]) in Marseille, a survey of prescriptions written on controlled-drug prescription pads was performed. The aims were threefold: to study the medicines prescribed, to follow up the legislation and to inform doctors and pharmacists. Copies of the prescriptions, dated between 1 January 1996 and 30 June 1996, which were sent by 81 per cent of the 216 pharmacies contacted in 15 towns in the Provence-Alpes-Côte d'Azur (PACA) region were studied. Various criteria, relating to writing of the prescriptions and distribution of the medicines to the patients, were coded and analysed. This survey showed that of 4 prescriptions, 3 were prescribed for maintenance and one for analgesic therapy. The patients receiving maintenance therapy were male in three-quarters of the cases, and were around 30 years old. Analgesics were prescribed in equal proportions for patients of both sexes, who were around 65 years old. Since it was put on the market, Subutex has been quickly prescribed. | pubmed_655_13489 |
pubmed_680_13747 | BACKGROUND
The duodenal «diverticulization» is a surgical technique described by Berne and colleagues in 1968 for the treatment of combined duodenal pancreatic injuries. It consisted of closure of the duodenal injury by suture and tube duodenostomy, gastric antrectomy with end-to-side isoperistaltic Billroth II gastrojejunostomy, and abdominal drainage. As evidenced from the literature in few reports, this technique has also been adopted for lateral duodenal lacerations in non traumatic conditions. Most biliary disease may be responsible for duodenal injury.
CASE PRESENTATION
Herein, we describe the application of this emergency technique for the treatment of a wide lateral duodenal laceration discovered intra-operatively during laparoscopic cholecystectomy for acute cholecystitis. A comprehensive critical review of the different surgical methods proposed for duodenal protection in case of severe duodenal lesions has been performed and discussed.
CONCLUSION
Duodenal injuries represent a challenging condition, especially for surgeons with limited experience in this field. The key-message of this report is to consider emergency surgical techniques in difficult unexpected intra-operative situations which may occur during routine surgical practice.
KEY WORDS
Duodenal diverticulization, Duodenal fistula, Laparoscopic cholecystectomy, Surgical repair. | pubmed_680_13747 |
pubmed_457_18144 | To understand medication use prior to suicide in relation to patterns, polypharmacy, and adherence. A total of 1,371 suicide cases were coded and latent class analysis used to identify combinations of medications prescribed prior to death. Two thirds had been prescribed medication with 30.7% prescribed 3 or more. Latent class analysis revealed three classes: Mixed medication use, primarily mental medication use, and baseline/low medication use. There are potentially high rates of medication non-adherence. Not only medication use but also non-adherence rates were high in this sample of individuals who died by suicide. Potential implications and areas for future research are discussed. | 10.1080/13811118.2017.1289870 |
pubmed_957_603 | Color is an essential criterion for assessing the freshness, quality, and acceptability of red meat and certain fish with red muscle. Myoglobin (Mb), one of the significant pigment substances, is the uppermost reason to keep the color of red meat. Their oxidation and browning are easy to occur throughout the storage and processing period. Natural antioxidants are substances with antioxidant activity extracted from plants, such as plant polyphenols. Consumers prefer natural antioxidants due to safety concerns and limitations on the use of synthetic antioxidants. In recent years, plant polyphenols have been widely used as antioxidants to slow down the deterioration of product quality due to oxidation. As natural antioxidants, it is necessary to strengthen the researches on the antioxidant mechanism of plant polyphenols to solve the discoloration of red meat and certain fish. A fundamental review of the relationship between Mb oxidation and color stability is discussed. The inhibiting mechanisms of polyphenols on lipid and Mb oxidation are presented and investigated. Meanwhile, this review comprehensively outlines applications of plant polyphenols in improving color stability. This will provide reference and theoretical support for the rational application of plant polyphenols in green meat processing. | 10.1080/10408398.2022.2122922 |
pubmed_77_16715 | Three mouse monoclonal antibodies, Act I, Act II, and Act IV, against actin from the cellular slime mold Dictyostelium discoideum, have been made and characterized. All three antibodies are IgG1 and share the following properties: They form stable complexes with monomeric Dictyostelium actin, which prevents polymerization of the actin into filaments. On addition to preformed actin filaments, they cause a reduction in filament size and in the viscosity of the actin solution. They cross-react strongly with actins from the lower eucaryotes Physarum and Acanthamoeba, but not with alpha-actins from rabbit and human muscle or beta- and gamma-actins from human erythrocytes and a human B lymphoid cell line. Act II and Act IV recognize a similar antigenic determinant that is topographically distinct from that identified by Act I. In protein immunoblotting, only Act I bound strongly to Dictyostelium actin. Analysis of actin fragments with this technique showed that amino acids 13 to about 50 are required for Act I binding to actin. A comparison of the amino acid sequences of actins from lower eucaryotes and higher vertebrates implicates threonine 41 as a critical residue in the Act I antigenic site. The properties of Act II and Act IV suggest that they recognize antigenic sites involving the NH2-terminal six residues. | 10.1083/jcb.99.1.287 |
pubmed_531_8342 | The platelet aggregation capability of whole cells of Enterococcus faecalis, E. faecium and E. avium was tested. The optimum ratios of bacteria to platelets in E. faecalis (strain SMU-37), E. faecium (strain SMU-138) and E. avium (strain SMU-197) were 1.0, 1.2 and 2.0, respectively. During the platelet aggregation induced by the three strains of enterococci, 65-69% of total serotonin was released. The aggregation was totally inhibited by ethylenediaminetetraacetate (10 mM) and apyrase (1 mg/ml), while no effect was shown by aspirin (10 mM), indomethacin (10 mM) and quinacrine (1 mM). By pretreatment of platelet-poor plasma with heat (56 C, 30 min) or zymosan, the reactivities with platelets of each strain of species were markedly diminished. These results suggest that enterococci-induced platelet aggregation was an ion-dependent, cyclooxygenase-insensitive event, and plasma component(s) was (were) required for the reaction. | 10.1111/j.1348-0421.1991.tb01615.x |
pubmed_603_15972 | Scant information is available regarding the effects of cisplatin on the expression profile of tachykinin NK(1) receptors and downstream signaling during cisplatin-induced emesis. Cisplatin causes peak early- and delayed-phase emesis in the least shrew at 1-2 and 33 h post-injection. To investigate the expression profile of NK(1) receptor during both emetic phases, we cloned the cDNA corresponding to a ~700 base pairs of mRNA flanked by two stretches of nucleotides conserved among different species and demonstrated that the shrew NK(1) receptor nucleotide sequence shares ~90% sequence identity with the human NK(1) receptor. Of the 12 time-points tested, significant increases in expression levels of NK(1) receptor mRNA in the shrew brainstem occurred at 2 and 28 h post-cisplatin injection, whereas intestinal NK(1) receptor mRNA was increased at 28 h. Shrew brainstem and intestinal substance P mRNA levels also tended to increase during the two phases. Furthermore, expression levels of NK(1) receptor protein were significantly increased in the brainstem at 2, 8, and 33 h post-cisplatin. No change in brainstem 5-HT(3) receptor protein expression was observed. The temporal enhancements in NK(1) receptor protein expression were mirrored by significant increases in the phosphorylation status of the brainstem ERK1/2 at 2, 8, and 33 h post-cisplatin. Phosphorylation of PKA significantly increased at 33rd and 40th hour. Our results indicate associations between cisplatin's peak immediate- and delayed-phase vomiting frequency with increased: (1) expression levels of NK(1) receptor mRNA and its protein level, and (2) downstream NK(1) receptor-mediated phosphorylation of ERK1/2 and PKA signaling. | pubmed_603_15972 |
pubmed_729_18748 | Complement (C) activation is believed to play an adverse role in several chronic degenerative disease processes, including atherosclerosis, myocardial infarction and Alzheimer's disease. We developed several in vitro quantitative assays to evaluate processes which activate C in human serum, and to assess candidates which might block that activation. Binding of C-reactive protein (CRP) to immobilized cell surfaces was used as a tissue-based method of activation, while immunoglobulin G in solution was used as a surrogate antibody method. Activation was assessed by deposition of C fragments on fixed cell surfaces, or by capture of C5b-9 from solution. We observed that several cell lines, including SH-SY5Y, U-937, THP-1 and ECV304, bound CRP and activated C following attachment of cells to a plastic surface by means of air drying. Treatment of human neuroblastoma SH-SY5Y cells with the reactive oxygen intermediates generated by xanthine (Xa) - xanthine oxidase (XaOx) prior to air drying or by hydrogen peroxide solutions after air drying, enhanced C activation, possibly through oxidation of the cell lipid membrane. Several C inhibitors were tested for their effectiveness in blocking these systems. Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1-1000 microg/ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor. | 10.1046/j.1365-2567.2002.01425.x |
pubmed_149_6986 | INTRODUCTION
The Helicobacter pylori(H. pylori) infection leads to intensification of symptoms and calenture of autoimmune diseases. This study aimed to evaluate the relationship between H. pylori infection and clinical outcomes in rheumatoid arthritis (RA) patients.
METHODOLOGY
This study was performed on 100 RA patients. Blood samples were collected for measuring Anti-H. pylori IgG antibodies and cytotoxin-associated gene A (CagA) protein. Fresh fecal samples were also collected and the fecal H. pylori antigen was extracted. Clinical condition as well as severity and type of RA symptoms in both groups of H. pylori positive and H. pylori negative were also compared.
RESULTS
Serum levels of rheumatoid factor (RF), ESR, CRP, anti-cyclic citrullinated peptide (Anti-CCP), and anti-mutated citrullinated vimentin (Anti-MCV) were significantly higher in H. pylori positive patients than in H. pylori negative patients (P < 0.05). Serum RF, ESR, CRP and Anti-MCV levels were significantly higher in CagA positive patients than in CagA negative patients (P < 0.05). There were no significant differences in DAS-28 scores between H. pylori positive and H. pylori negative patients (P = 0.064) as well as between patients with positive and negative fecal H. pylori antigen (P = 0.237). However, DAS-28 score was significantly higher in CagA positive patients than in CagA negative patients (P < 0.001). Furthermore, mean VAS score was significantly higher in H. pylori positive patients (P = 0.031) and CagA positive patients (P = 0.004); however, there were no significant differences in VAS scores between patients with positive and negative fecal H. pylori antigen (P = 0.310).
CONCLUSION
Follow-up and examination of RA patients in terms of infection with serum and fecal H. pylori organism and CagA seems necessary that will contribute to better and further control and treatment of the patients. | 10.1016/j.imlet.2019.05.014 |
pubmed_994_9683 | Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails due to an incomplete delineation of the epileptogenic zone. Brain networks in epilepsy can be studied with resting-state functional connectivity analysis, yet previous investigations using functional magnetic resonance imaging or electrocorticography have produced inconsistent results. Magnetoencephalography allows non-invasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the epileptogenic zone. In magnetoencephalography recordings from presurgical epilepsy patients, we examined: (i) global functional connectivity maps in patients versus controls; and (ii) regional functional connectivity maps at the region of resection, compared to the homotopic non-epileptogenic region in the contralateral hemisphere. Sixty-one patients were studied, including 30 with mesial temporal lobe epilepsy and 31 with focal neocortical epilepsy. Compared with a group of 31 controls, patients with epilepsy had decreased resting-state functional connectivity in widespread regions, including perisylvian, posterior temporo-parietal, and orbitofrontal cortices (P < 0.01, t-test). Decreased mean global connectivity was related to longer duration of epilepsy and higher frequency of consciousness-impairing seizures (P < 0.01, linear regression). Furthermore, patients with increased regional connectivity within the resection site (n = 24) were more likely to achieve seizure postoperative seizure freedom (87.5% with Engel I outcome) than those with neutral (n = 15, 64.3% seizure free) or decreased (n = 23, 47.8% seizure free) regional connectivity (P < 0.02, chi-square). Widespread global decreases in functional connectivity are observed in patients with focal epilepsy, and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning. | 10.1093/brain/awv130 |
pubmed_751_14555 | Doxycycline (D) is often administered during respiratory infections to asthmatic patients, many of them treated by theophylline (T) as well. We therefore investigated a possible interaction between D and T. Steady-state basal T levels were measured on two successive days before and after three and four days of D administration in ten stable asthmatic patients. Mean T levels before D were 9.9 +/- 3.1 micrograms/mL and after D 10.1 +/- 2.9 micrograms/mL, which are not significantly different. But T levels in four patients increased and in two patients, T levels decreased. We conclude that in some patients, T concentrations may be affected by D. This may require determination of T blood levels and T dose adjustment in some patients treated by T and D. | pubmed_751_14555 |
pubmed_948_8821 | Patients with prosthetic valves were investigated by Doppler echocardiography in 902 cases between November 1987 and February 1990. The parameters of 209 of 344 mitral and 258 of 299 aortic prosthetic valves were evaluated. No significant correlation was found between the type of aortic or mitral prosthetic valves and the measured gradient. As concerns the size of the valve and the measured gradient, a close correlation for aortic valve replacement was detected. For a normally functioning mitral prosthetic valve, a maximum early diastolic velocity of less than 2 m/s (16 mm Hg gradient) and a pressure half-time of less than 130 ms (mitral valve area 1.8 cm2) were characteristic. In cases of aortic valve replacements, the maximum velocity was less than 3 m/s (36 mm Hg gradient), except for the small-diameter valves. More than 95% of the cases met these criteria. (Even if small-diameter valves were included, a maximum velocity of more than 3 m/s occurred only in 8.9%.) Doppler echocardiography is a suitable tool for detecting normal prosthetic valve function, while colour Doppler allows the optimal alignment of jet direction and Doppler beam. | pubmed_948_8821 |
pubmed_982_23722 | Being awake, alert, and able to function in our 24-7 world is a challenge in the face of the fatigue and sleepiness engendered by long work hours, unusual work schedules, sickness, and other factors. Development of effective treatments to combat fatigue and sleepiness requires an understanding of the neurobiology of wakefulness. In this brief review, we examine the neuroanatomical, neurochemical, and molecular basis of the wakeful state to provide a framework for understanding current and future pharmacologic approaches to modification of wakefulness. The spontaneously awake state can be defined as a natural state of vigilance or arousal differing from natural sleep in both behavior and neural activity. These differences have long intrigued researchers and largely have been characterized in the brain areas and neurochemical systems affecting the sleep and wake states. Many of the strategies for promoting the awake condition involve manipulation or modulation of specific neurochemical systems with the ultimate goal of enhancing wakefulness, diminishing sleepiness, or both. Wakefulness is an important cortical function that depends on the coordinated effort of multiple brain areas including the thalamus, hypothalamus, and basal forebrain to integrate and relay information from the brainstem to the cortex. Norepinephrine and serotonin-long considered arousal-enhancing transmitters as well as glutamate, acetylcholine, histamine, and the neuromodulators hypocretin-orexins and adenosine, are known to affect the signal transduction in these brain areas and initiate, promote, or enhance wakefulness. Use of molecular tools to evaluate the awake, asleep, and sleep-deprived state has revealed novel insights concerning the gene expression events associated with wakefulness. Understanding wakefulness at this level undoubtedly will contribute to the development of pharmacologic approaches to promote or enhance the wakeful state. We caution, however, that sleep may have a necessary, restorative function for the brain; therefore, prolonging wakefulness for long periods through artificial means could have unexpected and perhaps detrimental consequences on brain health. | 10.1016/j.metabol.2006.07.007 |
pubmed_439_19279 | BACKGROUND
Intra-articular injections of human mesenchymal stromal cells (hMSCs) have shown promise in slowing cartilage degradation in posttraumatic osteoarthritis (PTOA). Clinical use of cell therapies for osteoarthritis has accelerated in recent years without sufficient scientific evidence defining best-use practices. Common recommendations advise patients to avoid nonsteroidal anti-inflammatory drug (NSAID) use before and after cell injection over concerns that NSAIDs may affect therapeutic efficacy. Recommendations to restrict NSAID use are challenging for patients, and it is unclear if patients are compliant.
HYPOTHESIS
NSAIDs will reduce the efficacy of hMSC therapy in treating a preclinical model of PTOA.
STUDY DESIGN
Controlled laboratory study.
METHODS
Lewis rats underwent medial meniscal transection (MMT) surgery to induce PTOA or a sham (sham group) surgery that did not progress to PTOA. Rats received naproxen solution orally daily before (Pre-NSAID group) or after (Post-NSAID group) hMSC treatment, throughout the course of the experiment (Full-NSAID group), or received hMSCs without NSAIDs (No NSAID). Cartilage morphology and composition were quantified using contrast-enhanced micro-computed tomography and histology. Pain (secondary allodynia) was measured using a von Frey filament.
RESULTS
Injection of hMSCs attenuated cartilage degeneration associated with MMT. hMSCs prevented proteoglycan loss, maintained smooth cartilage surfaces, reduced cartilage lesions, reduced mineralized osteophyte formation, and reduced pain by week 7. The Pre-NSAID group had decreased proteoglycan levels compared with the hMSC group, although there were no other significant differences. Thus, pretreatment with NSAIDs had minimal effects on the therapeutic benefits of hMSC injections. The Post-NSAID and Full-NSAID groups, however, exhibited significantly worse osteoarthritis than the hMSC-only group, with greater proteoglycan loss, surface roughness, osteophyte volume, and pain.
CONCLUSION
Use of NSAIDs before hMSC injection minimally reduced the therapeutic benefits for PTOA, which included preservation of cartilage surface integrity as well as a reduction in osteophytes. Use of NSAIDs after injections, however, substantially reduced the therapeutic efficacy of cellular treatment.
CLINICAL RELEVANCE
Our data support the clinical recommendation of avoiding NSAID use after hMSC injection but suggest that using NSAIDs before treatment may not substantially diminish the therapeutic efficacy of cell treatment. | 10.1177/03635465221083610 |
pubmed_904_1856 | BACKGROUND
MicroRNAs (miRNAs) are short regulatory RNAs that derive from hairpin precursors. Important for understanding the functional roles of miRNAs is the ability to predict the messenger RNA (mRNA) targets most responsive to each miRNA. Progress towards developing quantitative models of miRNA targeting in Drosophila and other invertebrate species has lagged behind that of mammals due to the paucity of datasets measuring the effects of miRNAs on mRNA levels.
RESULTS
We acquired datasets suitable for the quantitative study of miRNA targeting in Drosophila. Analyses of these data expanded the types of regulatory sites known to be effective in flies, expanded the mRNA regions with detectable targeting to include 5' untranslated regions, and identified features of site context that correlate with targeting efficacy in fly cells. Updated evolutionary analyses evaluated the probability of conserved targeting for each predicted site and indicated that more than a third of the Drosophila genes are preferentially conserved targets of miRNAs. Based on these results, a quantitative model was developed to predict targeting efficacy in insects. This model performed better than existing models, and it drives the most recent version, v7, of TargetScanFly.
CONCLUSIONS
Our evolutionary and functional analyses expand the known scope of miRNA targeting in flies and other insects. The existence of a quantitative model that has been developed and trained using Drosophila data will provide a valuable resource for placing miRNAs into gene regulatory networks of this important experimental organism. | 10.1186/s13059-018-1504-3 |
pubmed_1140_7861 | Revealing the free radical mechanism by which the anticancer drug tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide) induces hypoxia-selective cytotoxicity, is seen as a way forward to develop clinically useful bioreductive drugs against chemo- and radiation-resistant hypoxic tumor cells. Our previous studies point to the formation of an active benzotriazinyl radical following the one-electron reduction of tirapazamine and its elimination of water from the initial reduction intermediate, and have suggested that this species is a cytotoxin. In this paper we have used pulse radiolysis to measure the one-electron reduction potentials of the benzotriazinyl radicals E(B*,H(+)/B) of 30 analogues of tirapazamine as well as the one-electron reduction potentials of their two-electron reduced metabolites, benzotriazine 1-oxides E(B/B*-). The redox dependencies of the back-oxidation of the one-electron reduced benzotriazine 1,4-dioxides by oxygen, their radical prototropic properties and water elimination reactions were found to be tracked in the main by the one-electron reduction potentials of the benzotriazine 1,4-dioxides E(A/A*-). Multiple regression analysis of published aerobic and hypoxic clonogenic cytotoxicity data for the SCCVII murine tumor cell line with the physical chemistry parameters measured in this study, revealed that hypoxic cytotoxicity is dependent on E(B*, H(+)/B) thus providing strong evidence that the benzotriazinyl radicals are the active cytotoxic species in hypoxia, while aerobic cytotoxicity is dependent on E(B/B*-). It is concluded that maximizing the differential ratio between these two controlling parameters, in combination with necessary pharmacological aspects, will lead to more efficacious anticancer bioreductive drugs. | 10.1039/b502586a |
pubmed_744_14608 | Solid tumors are not static entities but are constantly responding to environmental signals as they grow and develop. One mechanism by which they respond to the adverse conditions of the tumor microenvironment is through coordinated changes in gene expression. The synchronized turning of genes on and off leads to biologic adaption to the adverse oxygen-poor environment. Because tumor hypoxia can be found in almost every solid tumor, it represents one of the most pervasive microenvironmental stresses that can impact malignant progression and therapeutic response. Interestingly, tumors that exhibit robust induction of hypoxia-responsive gene expression networks show a clinically more aggressive natural history. The contribution of hypoxia-responsive gene networks to malignant response is currently under investigation. An understanding of the coordinated functions of hypoxia induced and repressed genes can lead to a better understanding of the clinical significance of the hypoxic tumor phenotype. | 10.1016/j.semradonc.2004.04.007 |
pubmed_743_15553 | DNA methyltransferase 1 (Dnmt1) is crucial for cell maintenance and preferentially methylates hemimethylated DNA. Recently, a study revealed that Dnmt1 is timely and site-specifically activated by several types of two-mono-ubiquitinated histone H3 tails (H3Ts). However, the molecular mechanism of Dnmt1 activation has not yet been determined, in addition to the role of H3T. Based on experimental data, two-mono-ubiquitinated H3Ts activate Dnmt1 by binding, with different binding affinities. In contrast, ubiquitin molecules unlinked with H3T do not bind to Dnmt1. Despite the existence of experimental data, it is unclear why the binding affinities for Dnmt1 are different. To obtain new insights into the activation mechanism of Dnmt1, we performed all-atom molecular dynamics (MD) simulations on three systems: (1) K14/K18, (2) K14/K23 mono-ubiquitinated H3Ts, and (3) two ubiquitin molecules unlinked with H3T. As an analysis of our MD trajectories, these ubiquitylation patterns modulated ubiquitin-ubiquitin intermolecular interactions. More specifically, the intermolecular contacts between a pair of ubiquitin molecules linked with H3T became weak in the presence of H3T, indicating that H3T makes a cleft between them to inhibit their intermolecular interactions. For these three systems, the intermolecular interactions between the ubiquitin molecules calculated by our MD simulations are in good agreement with the binding affinities for Dnmt1 experimentally measured in a previous study. Therefore, we conclude that H3T acts as a spacer to inhibit ubiquitin-ubiquitin intermolecular interactions, enhancing binding to Dnmt1. | 10.1016/j.jmb.2021.167371 |
pubmed_365_6260 | STUDY OBJECTIVE
To evaluate the effects of alfentanil or lidocaine on the excitatory phenomena (myoclonus, cough, hiccough) caused by methohexital anesthesia and on the hemodynamic changes induced by retrobulbar block.
DESIGN
Prospective, randomized, placebo-controlled, double-blind study.
SETTING
University-affiliated, tertiary-care hospital.
PATIENTS
60 ASA physical status II and III patients who were admitted for elective cataract extractions and intraocular lens implantations.
INTERVENTIONS
Patients were randomly assigned to one of three groups. After adequate preoxygenation in the holding area, Group 1 received alfentanil 5 micrograms/kg intravenously (i.v.), Group 2 received lidocaine 1 mg/kg i.v. and Group 3 received the placebo (saline) i.v. Immediately after the bolus injection of the study solution, sodium methohexital 1.5 mg/kg was injected i.v. over 30 seconds. As soon as the eyelid reflex was lost, the retrobulbar block was placed over 5 seconds.
MEASUREMENTS AND MAIN RESULTS
Occurrences of excitatory phenomena were recorded by an independent observer who was blinded as to treatment allocation. Other side effects such as oculocardiac reflex, nausea, vomiting, itching, or chest wall rigidity were recorded. Vital signs were recorded at baseline and 1, 3, and 5 minutes after placement of the block. In the alfentanil group, the incidence of myoclonus or cough was significantly less than in the lidocaine or placebo groups. Alfentanil also decreased systolic and diastolic blood pressure significantly at 1, 3, and 5 minutes after retrobulbar block. Changes in heart rate were not significantly different from baseline.
CONCLUSION
A small dose of alfentanil (5 micrograms/kg i.v.) decreases myoclonus and cough induced by sodium methohexital anesthesia i.v., resulting in improved quality of induction of anesthesia. Alfentanil also attenuates the cardiovascular responses caused by placement of a retrobulbar block. | 10.1016/s0952-8180(98)00072-5 |
pubmed_969_2816 | The heart is a target organ of anaphylaxis. In isolated perfused hearts, an anaphylactic reaction is characterized by arrhythmias, coronary constriction and severe impairment of ventricular contractile force. Various mediators such as PAF, thromboxane A2 and leukotrienes are responsible for anaphylactic coronary constriction and negative inotropic effects. The cardiac effects of anaphylactic histamine release are related to the stimulation of two antagonistic receptor types. Histamine induces atrioventricular conduction delay and constriction of the epicardial coronary vessels via H1-receptor stimulation. H2-receptors, however, mediate coronary vasodilation and an increase in heart rate and myocardial contractility. It may therefore be concluded that administration of histamine H2-receptor antagonists is disadvantageous. During anaphylactic states, the cardiodepressive effects of the other mediators of anaphylaxis are unmasked, resulting in a sustained coronary constriction and impairment of myocardial contractility. To verify this speculation, we investigated the effects of H1- and H2-receptor antagonists on cardiovascular function of guinea pigs during systemic anaphylaxis. In guinea pigs, sensitization was produced by subcutaneous application of ovalbumin. Fourteen days after sensitization, the effects of an intravenous infusion of ovalbumin were tested in the anesthetized artificially ventilated guinea pigs. The renewed administration of the antigen induced severe cardiac dysfunction. Within a few minutes, cardiac output markedly decreased and left ventricular end-diastolic pressure increased significantly, indicating left ventricular pump failure. In the same time range, ECG recordings uniformly showed signs of acute myocardial ischemia. In addition, arrhythmias occurred in terms of an atrioventricular block.(ABSTRACT TRUNCATED AT 400 WORDS) | 10.1007/BF01980881 |
pubmed_586_1658 | 1 The overall functional capacity of the liver was evaluated using [35S]-bromosulphophthalein (BSP, 100 mg/kg, i.v.) in biliary fistulated adult rats pretreated orally with different doses of paracetamol (APAP) for varying time intervals. 2 The maximal hepatic damage occurred between 12-18 h after single doses of APAP (0.5 or 1 g/kg); hepatic excretory function returned to control levels by 48-72 hours. 3 Administration of either 0.5 or 1 g/kg APAP 18 h before BSP caused a dose-dependent inhibition of the choleretic effect of BSP and of the 60 min cumulative excretion of the dye, but conversely, produced a significant increase in the liver and plasma concentrations of 35S. 4 Following acute (0.25 g/kg), or subacute (0.5 g/kg, twice daily for 7 days) treatment with APAP, the total excretion of 35S in bile and the retention of 35S in the liver or plasma remained essentially the same as that for the controls. 5 In rats given single doses of 1 g/kg APAP, the hepatic uptake of the dye was significantly increased during the early stages of intoxication, while the opposite effect was observed at late periods. 6 The bile flow appeared to be inversely related to the excretion of unchanged BSP, and directly related to the excretion of the major BSP conjugate in bile. 7 The hepatic clearance of BSP was more rapid in rats treated subacutely with 0.5 or 1 g/kg APAP, than in those treated acutely with equal doses, suggesting that the intensity of APAP-induced hepatotoxicity became less severe after the repeated administration of this drug. 8 It is concluded that the hepatic uptake, metabolism and excretion of BSP are reversibly impaired following APAP-induced liver injury. | 10.1111/j.1476-5381.1976.tb07437.x |
pubmed_396_9074 | Hydroperoxides are the primary oxygenated products of polyunsaturated fatty acids and were determined spectrophotometrically based on their reaction with an excess of Fe2+ at low pH in the presence of the dye Xylenol Orange. Triphenylphosphine-mediated hydroxide formation was used to authenticate the signal generated by the hydroperoxides. The method readily detected lipid peroxidation in a range of plant tissues including Phaseolus hypocotyls (26 +/- 5 nmol.g of fresh weight(-1); mean +/- S.D.), Alstroemeria floral tissues (sepals, 66+/-13 nmol.g of fresh weight(-1); petals, 49+/-6 nmol.g of fresh weight(-1)), potato leaves (334+/-75 nmol.g of fresh weight(-1)), broccoli florets (568+/-68 nmol.g of fresh weight(-1)) and Chlamydomonas cells (602+/-40 nmol.g of wet weight(-1)). Relative to the total fatty acid content of the tissues, the percentage hydroperoxide content was within the range of 0.6-1.7% for all tissue types (photosynthetic and non-photosynthetic) and represents the basal oxidation level of membrane fatty acids in plant cells. Leaves of transgenic potato with the fatty acid hydroperoxide lyase enzyme expressed in the antisense orientation were elevated by 38%, indicating a role for this enzyme in the maintenance of cellular levels of lipid hydroperoxides. | pubmed_396_9074 |
pubmed_56_5750 | Despite widespread clinical application of melatonin, several unanswered questions remain regarding the pharmacokinetics of this drug. This lack of knowledge may contribute to the inconsistency of results in previous clinical studies. Currently, a t max value of 30-45 min and a t ½elimination of 45 min are well established. Several questions relate to what constitutes a clinically effective plasma concentration, the choice of ideal administration route, and the optimal method of analysis. Furthermore, investigations of melatonin metabolites in humans are urgently needed in order to characterize their biological functions and the metabolic fates of these derivatives. Finally, pharmacokinetics in patients should be investigated further in order to reduce the risk of potential adverse effects, such as daytime sleepiness or unintended sedation. | 10.1007/s40262-016-0386-3 |
pubmed_889_7983 | OBJECTIVE
The aim of study was to evaluate the influence of pharmacist intervention based on "CMO model", to improve activation in HIV-patients.
METHODS
Longitudinal, prospective, single-center study. Eligible patients were HIV-infected, taking antiretroviral treatment. The collected data included demographic characteristics, clinical and HIV-related and pharmacotherapeutic variables. The primary outcome was the variation of patient activation measured by Spanish adapted patient activation measure questionnaire. This questionnaire assesses people's knowledge, skills and confidence in managing their own health care. The assessment was performed at the beginning and 6 months after the program start, which consisted of individualized interventions planned in the stratification model, a motivational interview and a specific pharmacotherapeutic follow-up.
RESULTS
A total of 140 patients were included. The most common regimens prescribed were based on non-nucleoside plus nucleoside reverse transcriptase inhibitor (44.0%) and more than half of the patients had chronic concomitant medication. The patients who achieved the highest activation level increased from 28.1% to 68.3% (p<0.0005). The relationship between this increase in patient activation and the stratification level that occurs in largest increases in patients with a low need level, where it was observed an improvement in the percentage of patients with high activation from 28.3% to 74.3% (p<0.001) after intervention. The percentage of patients with adequate adherence to concomitant treatment increased by 18.4% (p = 0.035). Baseline PAM values showed high activation for 28.6% (40 patients), intermediate for 43.6% (61) and low for 27.9% (39).
CONCLUSIONS
CMO model has an important role for patient activation, improving adherence and health outcomes for HIV+ patients. | pubmed_889_7983 |
pubmed_256_5476 | The National Health Service reforms have placed public health medicine centre stage in controversies over the internal market, rationing of health care, and issues of equity in access to care. One of the key determinants of the need for reform in health services internationally is the demographic transition of post-industrial countries into an ageing population. This paper considers some of the implications of ageing and how public health medicine might respond to these new challenges. | pubmed_256_5476 |
pubmed_405_7547 | The balance between bone formation by osteoblasts and destruction of mineralized bone matrix by osteoclasts is important for bone homeostasis. The increase of osteoclast differentiation by RANKL induces bone diseases such as osteoporosis. Recent studies have shown that insulin is one of main factors mediating the cross-talk between bone remodeling and energy metabolism. However, the systemic examination of insulin-induced differential gene expression profiles in osteoclasts has not been extensively studied. Here, we investigated the global effects of insulin on osteoclast precursors at the level of gene transcription by microarray analysis. The number of genes that were up-regulated by ≥ 1.5 fold after insulin treatment for 6 h, 12 h, or 24 h was 76, 73, and 39; and 96, 83, and 54 genes were down-regulated, respectively. The genes were classified by 20 biological processes or 24 molecular functions and the number of genes involved in 'development processes' and 'cell proliferation and differentiation' was 25 and 18, respectively, including Inhba, Socs, Plk3, Tnfsf4, and Plk1. The microarray results of these genes were verified by real-time RT-PCR analysis. We also compared the effects of insulin and RANKL on the expression of these genes. Most genes had a very similar pattern of expressions in insulin- and RANKL-treated cells. Interestingly, Tnfsf4 and Inhba genes were affected by insulin but not by RANKL. Taken together, these results suggest a potential role for insulin in osteoclast biology, thus contributing to the understanding of the pathogenesis and development of therapeutics for numerous bone and metabolic diseases. | 10.14348/molcells.2014.0223 |
pubmed_81_18537 | Sodium strontium pentaborate, Na(3)SrB(5)O(10), maintains the same, previously unobserved, structure type at 200, 250 and 293 K. The fundamental building units are anionic [B(5)O(10)](5-) groups distorted from mm2 point symmetry. The Sr atoms are eightfold coordinated by O atoms, forming trigonal dodecahedra. The Na atoms appear in three crystallographically different environments. The present single-crystal results correct a previous report in which a monoclinic cell was deduced for this compound on the basis of powder diffraction data. The structure of the title compound is discussed in the crystalochemical context of other borates with the same formula type. Although the unit cell of the present compound is similar to that determined in a previous study of the analogous Ca-containing compound, this study demonstrates that the structures of the two are different. These novel alkali-alkaline earth borates are considered as potential host materials for optical applications (fluorescence materials or phosphors). | 10.1107/S0108270108016909 |
pubmed_10_19453 | Mutations in the GJB2 gene encoding connexin 26 are the main cause of hereditary hearing impairment. These mutations generate mainly autosomal recessive and rarely autosomal dominant deafness. Dominant mutations in GJB2 can be responsible for isolated deafness as well as syndromic hearing loss associated with various skin abnormalities. Until now few papers discuss dominant mutations in the GJB2 gene. In this work we report a rare case about a Moroccan family with a compound heterozygous mutation (the dominant p.R75Q and the recessive c.35delG alleles) in the GJB2 gene with intra-familial phenotypic variability. This study reinforces the involvement of p.R75Q mutation of GJB2 in syndromic deafness associated with dermatological diseases the palmoplantar keratoderma. | pubmed_10_19453 |
pubmed_718_21336 | Although primates have been the craniofacial growth models of choice, recent circumstances have stimulated the search for nonprimate models. In a series of studies we have described changes in various regions of the craniofacial complex for seven commonly used animal models. The present study examined the bony nasal cavity. One hundred and forty-four serial and cross-sectional lateral head x-rays were obtained for unoperated controls from previous growth studies. The sample consisted of data from 26 rats, 21 rabbits, 21 domestic cats, 23 domestic dogs, 17 baboons, 16 rhesus monkeys, and 20 chimpanzees. Comparative human data was taken from the Bolton Standards. The samples were divided into three age categories based on dental and somatic development. Midsagittal nasal cavity measurements included length, height, shape index, and area. Analysis was based on the percent increase in measures from the infant condition. Three major shapes were discerned at adulthood (1) vertical quadrangles (humans and cats); (2) triangles (chimpanzees, rhesus monkeys, and baboons), and (3) horizontal quadrangles (rabbits, rats, and dogs). Results showed that overall shape was best modeled by the chimpanzee and, as a nonprimate model, the laboratory cat. Rabbits and rats also showed similar percent changes for length or height dimensions at different ages, suggesting that these animals may be acceptable, inexpensive alternatives to primates in some experimental situations. | 10.1597/1545-1569_1994_031_0017_ccsonc_2.3.co_2 |
pubmed_1129_7262 | SEC23B is a component of coat protein complex II (COPII) vesicles that transport secretory proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. Loss-of-function SEC23B mutations cause a rare form of anemia, resulting from decreased SEC23B levels. We recently identified germline heterozygous SEC23B variants as potentially cancer-predisposing. Mutant SEC23B associated with ER stress-mediated tumorigenesis, without decreased SEC23B expression. However, our understanding of the processes behind these observations remain limited. Here, we show mutant SEC23B exists within nucleoli, in addition to classical distribution at the ER/Golgi. This occurs independent of other COPII proteins and does not compromise secretory function. Mutant cells have increased ribosomal protein and translation-related gene expression, and enhanced translational capacity, in the presence of ER stress. We show that mutant SEC23B binds to UBF transcription factor, with increased UBF transcription factor binding at the ribosomal DNA promoter. Our data indicate SEC23B has potential non-canonical COPII-independent function, particularly within the ribosome biogenesis pathway, and that may contribute to the pathogenesis of cancer-predisposition. | 10.1093/hmg/ddy226 |
pubmed_852_8525 | This paper describes the design of a front-end circuit consisting of an integrated preamplifier with a Sallen-Key Butterworth filter for very-high-frequency ultrasonic transducers and a low-power handheld receiver. This preamplifier was fabricated using a 0.18-μm 7WL SiGe bi-polar complementary metal oxide semiconductor (BiCMOS) process. The Sallen-Key filter is used to increase the voltage gain of the front-end circuit for high-frequency transducers which are generally low in sensitivity. The measured peak voltage gain of the frontend circuits for the BiCMOS preamplifier with the Sallen-Key filter was 41.28 dB at 100 MHz with a-6-dB bandwidth of 91%, and the dc power consumption of the BiCMOS preamplifier was 49.53 mW. The peak voltage gain of the front-end circuits for the CMOS preamplifier with the Sallen-Key filter was 39.52 dB at 100 MHz with a-6-dB bandwidth of 108%, and the dc power consumption of the CMOS preamplifier was 43.57 mW. Pulse-echo responses and wire phantom images with a single-element ultrasonic transducer have been acquired to demonstrate the performance of the front-end circuit. | 10.1109/TUFFC.2011.2127 |
pubmed_265_13375 | A macaque model was employed to explore staphylococcal enterotoxin B (SEB) superantigen-driven T lymphocyte responses. The SEB-reactive Vbeta+ cell subpopulations demonstrated a striking tri-phase response in rhesus monkeys following an SEB challenge in vivo. The hyperacute down-regulation, seen as early as 2 h through 2 days after SEB injection, was characterized by a disappearance of the reactive Vbeta-restricted PBL subpopulations from the circulation and decreased expression of these cell subpopulations in lymphoid tissues. Following this, a dominant expansion of reactive Vbeta-expressing CD4+ cell subpopulations occurred in lymph nodes and spleens, whereas in the peripheral blood a preferential expansion of reactive Vbeta-expressing CD8+ cell subpopulations was seen. An exhaustion of this response was then seen, with a prolonged decrease in the number of the reactive Vbeta+ CD4+ lymphocyte subpopulations. Interestingly, monoclonal or oligoclonal dominance was seen in the reactive Vbeta+ cell subpopulations in the period of the transition from the polyclonal cellular expansion to the exhaustion of the response, suggesting that some Vbeta+ cell clones may be more resistant than others to superantigen-mediated depletion. These results indicate that in vivo SEB superantigen-mediated effect on lymphocyte subpopulations in macaques is complex, suggesting that profound dynamics in the TCR repertoires may in part account for the susceptibility of higher primates to SEB-induced diseases. | pubmed_265_13375 |
pubmed_81_10294 | INTRODUCTION
Increasing age is associated with reduced numbers of circulating endothelial progenitor cells (EPCs). It is unclear whether this relates to depletion or impairment of bone marrow progenitors, or to deficient mobilization signals from aging tissues. In cardiac transplant patients, one previous study has reported an association between circulating EPCs and the risk of cardiac allograft vasculopathy (CAV). We investigated whether increased donor heart age, a strong risk factor for CAV, was associated with reduced circulating EPC numbers in a group of cardiac transplant recipients matched for factors which influence EPC numbers, but with maximally discordant donor heart ages.
METHODS
We identified 32 patient pairs, matched for factors known to influence EPC numbers, but who had discordant donor heart ages by at least 20 years. EPCs were quantified using flow cytometry for absolute counts of cells expressing all the combinations of CD45, CD34, CD133 and the kinase domain receptor (KDR).
RESULTS
There were no significant differences in the numbers of circulating EPCs between patients with old or young donor heart age. There was no association between the presence of CAV and circulating EPC numbers.
CONCLUSIONS
We suggest that the increased susceptibility to CAV of older donor hearts is not mediated via circulating EPCs. Our results are consistent with the theory that the normal age-related decline in EPC numbers relates to bone marrow aging rather than failure of target tissues to induce EPC mobilization. | 10.1016/j.atherosclerosis.2008.05.020 |
pubmed_44_5203 | The tumor vasculature and extracellular matrix make attractive targets for distinguishing solid tumors from normal cells. In solid tumors, the processes of angiogenesis and metastasis potentially give rise to unique epitopes not usually accessible in homeostatic organs. Specific targeting of solid tumors for radioimmunotherapy requires that the targeting agent accumulate rapidly and at high levels at the tumor site. This study involved the selection of scFvs that recognize laminin-1 in vitro from the Tomlinson I and J phage display libraries. Selected, purified scFvs were radioiodinated and injected in tumor-bearing mice. One of these, scFv 15-9, exhibited preferential accumulation at subcutaneous tumors when compared to other antilaminin scFvs or to a control scFv. Autoradiographic analysis indicated that scFv15- 9 also displayed a higher vessel:parenchyma ratio than did two other antilaminin scFvs, scFv 15-6 and scFv 15-1, indicating a preferential accumulation of scFv 15-9 around vessel structures. Immunohistochemistry confirmed that scFv 15-9 accumulated at sites of endothelial cells lining vessel structures where significant levels of laminin were present. These data demonstrate that scFv 15-9 binds to a specific epitope on laminin and has potential for tumor endoradiotherapy in subcutaneous tumors. | 10.1089/cbr.2005.20.524 |
pubmed_227_16572 | OBJECTIVE
Our objectives were to develop the population pharmacokinetic (PK) for pertuzumab and examine the variability of steady-state trough serum concentrations (C(SS,trough)) and exposure after fixed, body-weight-based, or body-surface area (BSA)-based dosing methods in cancer patients.
METHODS
Pertuzumab was administered by i.v. infusion (every 3 weeks) either as a weight-based dose (0.5-15 mg/kg) or a fixed dose (420 or 1050 mg). Data from three clinical studies, comprising 153 patients and 1458 concentration-time points, were pooled for this analysis using NONMEM.
RESULTS
A linear two-compartment model best described the data. Body weight and BSA were significant covariates affecting clearance (CL) and distribution volume (Vc), respectively. However, weight and BSA only explained small percentage of interpatient variability for CL and Vc, respectively. Simulation results indicated that PK profiles were very similar after the three dosing methods. Compared to fixed dosing, weight- and BSA-based dosing only reduced the population variability of C(SS,trough) moderately.
CONCLUSION
A population PK model was developed for pertuzumab, the first monoclonal IgG1 antibody in a new class of agents known as HER dimerization inhibitors. In addition, our analyses demonstrate the feasibility of administering pertuzumab using a fixed dose in women with ovarian and breast cancers. | 10.1007/s11095-006-0205-x |
pubmed_911_12187 | Free energies and dynamics of electron-transfer reactions for a diatomic donor-acceptor complex in ambient and supercritical water are studied via molecular dynamics computer simulations using a two-state electronic description. The free energy perturbation method is employed to examine diabatic electronic curves relevant to charge separation and recombination and electron self-exchange. It is found that the diabatic curves are anharmonic and vary with the charge distributions of the donor-acceptor complex, consonant with earlier studies under ambient conditions. Nonetheless, the extent of their anharmonicity and dependence on charge distributions grows with decreasing solvent density so that the Marcus free energy relationship breaks down in low-density supercritical water. The influence of solvent dynamics associated with activation, deactivation, and adiabatic barrier crossing on reaction kinetics is analyzed. Although the transition state theory generally provides a reasonable framework to describe electron-transfer kinetics in a wide range of thermodynamic conditions, the deviation of the reaction rate from the transition state theory predictions increases as the water density decreases. | 10.1021/jp075270j |
pubmed_1065_10521 | Directed evolution uses a combination of powerful search techniques to generate proteins with improved properties. Part of the success is due to the stochastic element of random mutagenesis; improvements can be made without a detailed description of the complex interactions that constitute function or stability. However, optimization is not a conglomeration of random processes. Rather, it requires both knowledge of the system that is being optimized and a logical series of techniques that best explores the pathways of evolution (Eigen et al., 1988). The weighing of parameters associated with mutation, recombination, and screening to achieve the maximum fitness improvement is the beginning of rational evolutionary design. The optimal mutation rate is strongly influenced by the finite number of mutants that can be screened. A smooth fitness landscape implies that many mutations can be accumulated without disrupting the fitness. This has the effect of lowering the required library size to sample a higher mutation rate. As the sequence ascends the fitness landscape, the optimal mutation rate decreases as the probability of discovering improved mutations also decreases. Highly coupled regions require that many mutations be simultaneously made to generate a positive mutant. Therefore, positive mutations are discovered at uncoupled positions as the fitness of the parent increases. The benefit of recombination is twofold: it combines good mutations and searches more sequence space in a meaningful way. Recombination is most beneficial when the number of mutants that can be screened is limited and the landscape is of an intermediate ruggedness. The structure of schema in proteins leads to the conclusion that many cut points are required. The number of parents and their sequence identity are determined by the balance between exploration and exploitation. Many disparate parents can explore more space, but at the risk of losing information. The required screening effort is related to the number of uphill paths, which decreases more rapidly for rugged landscapes. Noise in the fitness measurements causes a dramatic increase in the required mutant library size, thus implying a smaller optimal mutation rate. Because of strict limitations on the number of mutants that can be screened, there is motivation to optimize the content of the mutant library. By restricting mutations to regions of the gene that are expected to show improvement, a greater return can be made with the same number of mutants. Initial studies with subtilisin E have shown that structurally tolerant positions tend to be where positive activity mutants are made during directed evolution. Mutant fitness information is produced by the screening step that has the potential to provide insight into the structure of the fitness landscape, thus aiding the setting of experimental parameters. By analyzing the mutant fitness distribution and targeting specific regions of the sequence, in vitro evolution can be accelerated. However, when expediting the search, there is a trade-off between rapid improvement and the quality of the long-term solution. The benefit of neutrality has yet to be captured with in vitro protein evolution. Neutral theory predicts the punctuated emergence of novel structure and function, however, with current methods, the required time scale is not feasible. Utilizing neutral evolution to accelerate the discovery of new functional and structural solutions requires a theory that predicts the behavior of mutational pathways between networks. Because the transition from neutral to adaptive evolution requires a multi-mutational switch, increasing the mutation rate decreases the time required for a punctuated change to occur. By limiting the search to the less coupled region of the sequence (smooth portion of the fitness landscape), the required larger mutation rate can be tolerated. Advances in directed evolution will be achieved when the driving forces behind such proce | 10.1016/s0065-3233(01)55003-2 |
pubmed_268_13579 | The purpose of this paper is to encourage the development of women's health as a multidisciplinary specialty. The idea for such a specialty arose from the grass roots women's health movement of the 1960s, whose tenets were rapidly embraced by physicians sympathetic to its ideals, especially members of the American Medical Women's Association. Women's health would be a multidisciplinary specialty offering service to a specific patient population, analogous to geriatric medicine. It would blend primary care, ambulatory obstetrics-gynecology, and psychiatry with additional training in endocrinology, nutrition, sports medicine, and orthopaedics. Suggestions for residency training and specialty certification are included. | pubmed_268_13579 |
pubmed_987_10087 | Molecular orientation plays a pivotal role in defining the functionality and chemistry of interfaces, yet accurate measurements probing this important feature are few, due, in part, to technical and analytical limitations in extracting information from molecular monolayers. For example, buried liquid/liquid interfaces, where a complex and poorly understood balance of inter- and intramolecular interactions impart structural constraints that facilitate the formation of supramolecular assemblies capable of new functions, are difficult to probe experimentally. Here, we use vibrational sum-frequency generation spectroscopy, numerical polarization analysis, and atomistic molecular dynamics simulations to probe molecular orientations at buried oil/aqueous interfaces decorated with amphiphilic oligomers. We show that the orientation of self-assembled oligomers changes upon the addition of salts in the aqueous phase. The evolution of these structures can be described by competitive ion effects in the aqueous phase altering the orientations of the tails extending into the oil phase. These specific anionic effects occur via interfacial ion pairing and associated changes in interfacial solvation and hydrogen-bonding networks. These findings provide more quantitative insight into orientational changes encountered during self-assembly and pave the way for the design of functional interfaces for chemical separations, neuromorphic computing applications, and related biomimetic systems. | 10.1021/acs.jpcb.2c01148 |
pubmed_665_9530 | Charging mechanisms of trapped, element-selectively excited free SiO2 nanoparticles by soft x rays are reported. The absolute charge state of the particles is measured and the electron emission probability is derived. Changes in electron emission processes as a function of photon energy and particle charge are obtained from the charging current. This allows us to distinguish contributions from primary photoelectrons, Auger electrons, and secondary electrons. Processes leading to no change in charge state after absorption of x-ray photons are identified. O 1s-excited SiO2 particles of low charge state indicate that the charging current follows the inner-shell absorption. In contrast, highly charged SiO2 nanoparticles are efficiently charged by resonant Auger processes, whereas direct photoemission and normal Auger processes do not contribute to changes in particle charge. These results are discussed in terms of an electrostatic model. | 10.1103/PhysRevLett.96.066801 |
pubmed_729_8221 | OBJECTIVE
To analyse agreement between patients' and GPs' perceptions of risk factors and overall risk of ischaemic heart disease (IHD).
DESIGN
Cross-sectional study based on paired information from patients and GPs.
SETTING
Twenty-six GPs in the County of Ringkøbing, Denmark, participating in a medical audit during 3 weeks in May 1999.
SUBJECTS
252 patients with IHD and 1239 without IHD.
MAIN OUTCOME MEASURES
GPs and patients were asked about specific risk factors for IHD and their perception of overall risk. Their agreement was evaluated by Kappa statistics.
RESULTS
Agreement between GPs and patients varied from 70% to 97%. Disagreement was observed most often for patients with IHD and patients listed with elderly GPs ( > 50 years). Generally, patients perceived the overall risk of IHD lower than their doctors, and for most patients with a perception of low risk the GP estimated the risk as high.
CONCLUSIONS
Patients and GPs have different perceptions of the risk of [HD. This may be due to different perceptions of the importance of specific risk factors and different reference frames for risk perception. GPs have an important role in communicating the meaning of risk factors and interventions should be considered to improve risk communication in general practice. | 10.1080/028134302317282680 |
pubmed_217_22325 | The adult mammalian forebrain contains neural stem/progenitor cells (NSCs) that generate neurons throughout life. As in other somatic stem cell systems, NSCs are proposed to be predominantly quiescent and proliferate only sporadically to produce more committed progeny. However, quiescence has recently been shown not to be an essential criterion for stem cells. It is not known whether NSCs show differences in molecular dependence based on their proliferation state. The subventricular zone (SVZ) of the adult mouse brain has a remarkable capacity for repair by activation of NSCs. The molecular interplay controlling adult NSCs during neurogenesis or regeneration is not clear but resolving these interactions is critical in order to understand brain homeostasis and repair. Using conditional genetics and fate mapping, we show that Notch signaling is essential for neurogenesis in the SVZ. By mosaic analysis, we uncovered a surprising difference in Notch dependence between active neurogenic and regenerative NSCs. While both active and regenerative NSCs depend upon canonical Notch signaling, Notch1-deletion results in a selective loss of active NSCs (aNSCs). In sharp contrast, quiescent NSCs (qNSCs) remain after Notch1 ablation until induced during regeneration or aging, whereupon they become Notch1-dependent and fail to fully reinstate neurogenesis. Our results suggest that Notch1 is a key component of the adult SVZ niche, promoting maintenance of aNSCs, and that this function is compensated in qNSCs. Therefore, we confirm the importance of Notch signaling for maintaining NSCs and neurogenesis in the adult SVZ and reveal that NSCs display a selective reliance on Notch1 that may be dictated by mitotic state. | 10.1523/JNEUROSCI.0455-12.2012 |
pubmed_308_18237 | Abnormal expression of metastasis-associated in colon cancer 1 (MACC1) was found to be closely associated with several types of malignant tumors. The present study aimed to verify the relationship between MACC1 and cisplatin resistance in ovarian cancer cells and the possible mechanisms, which was implemented by inhibition of the expression of MACC1 in cisplatin-resistant human ovarian cancer cell lines A2780/DDP and COC1/DDP. MACC1 shRNA eukaryotic plasmids and negative control plasmids were transfected into A2780/DDP and COC1/DDP cells, respectively, while A2780/DDP and COC1/DDP cells were used as blank controls. Western blotting and sqRT-PCR were used to detect the expression of MACC1 in the different cell groups. Different concentrations of cispaltin (0, 10, 20, 30, 40, 50 and 60 µmol/l) were used to treat the cell groups, respectively, and then the chemosensitivity of cisplatin and cell apoptosis were examined by MTT and flow cytometry, respectively. The activity of caspase-3 was determined by spectrophotometry. Expression levels of p-ERK1/2, permeability glycoprotein (P-gp), B-cell lymphoma 2 (Bcl-2), Bcl-XL, Bax and Bad protein were detected in the different ovarian cancer cells by western blotting. After MACC1 knockdown, the chemosensitivity of cisplatin in the ovarian cancer cells was enhanced, and the cell growth inhibition and apoptosis rates were increased. The expression levels of Bax and Bad were upregulated, the activity of caspase-3 was increased, while the expression levels of p-ERK1/2, P-gp, Bcl-2 and Bcl-XL were downregulated as a result of MACC1 inhibition. These results indicate that inhibition of MACC1 improves the chemosensitivity of cisplatin in epithelial ovarian cancer cells, through the regulation of the ERK1/2 signaling pathway on P-gp and its downstream apoptosis proteins. | 10.3892/or.2016.4585 |
pubmed_1004_6590 | This article provides a review of literature both to identify the effects of yoga-based therapy on the management of type 2 diabetes mellitus and to examine the social context of physical activity. Findings from the review indicate that yoga has a positive short-term effect on multiple diabetes-related outcomes; however, long-term effects of yoga therapy on diabetes management remain unclear. The context of the social environment, including interpersonal relationships, community characteristics, and discrimination, influences the adoption and maintenance of health behaviors such as physical activity, including yoga practice. Further research is necessary to determine the extent of this influence. | 10.1097/01.FCH.0000324480.40459.20 |
pubmed_1124_7105 | We propose that the fit between an action's strategic orientation and the actor's regulatory state can influence the amount of enjoyment the action provides. In two studies using different methods of manipulating regulatory states and of gauging action evaluations, high regulatory fit increased participants' anticipations of action enjoyability. In a third study, high regulatory fit increased participants' enjoyment of perceived success at, and willingness to repeat a novel laboratory task, and these effects were independent of participants' actual success on the task. Across the three studies, participants in a regulatory state oriented toward accomplishment experienced eagerness-related actions more favorably than vigilance-related actions, whereas participants in a regulatory state oriented toward responsibility experienced vigilance-related actions more favorably than eagerness-related actions. These findings' implications for understanding task interest and motivation are discussed. | 10.1111/1467-9280.00401 |
pubmed_382_17985 | OBJECTIVE
To evaluate caregiver knowledge and delivery of a prescription medication (albuterol) for children.
DESIGN
Prospective convenience sample.
PARTICIPANTS
Caregivers listing albuterol as one of their child's medications.
SETTING
Two urban, university-affiliated pediatric emergency departments.
INTERVENTIONS
Caregivers were asked about their knowledge of the medication, the child's dose, frequency, duration of use, and where it was prescribed. In a mock scenario, they measured and demonstrated medication delivery to their child. Common measuring devices and formulations were offered.
RESULTS
Forty-one caregivers were enrolled. Thirty-six (88%) were high school educated and 39 (95%) had a primary care provider. Twenty-six (63%) were out of medication, 7 (17%) stated an incorrect dose, 18 (44%) reported an incorrect frequency, and 10 (24%) stated an inadequate duration of use. Formulations chosen were liquid (n = 15, 37%), nebulizers (n= 15, 37%), and inhalers (n = 11, 27%). Metered dosing (metered-dosing inhaler or premixed solution) were chosen by 22 caregivers (54%), calibrated measuring tools (droppers, syringes) by 15 (37%), and noncalibrated delivery devices (teaspoon) by 4 (10%). An improper dose was measured by 9 (22%), and the dose intended was inaccurately measured by 7 (17%). All caregivers using a teaspoon inaccurately measured their intended dose of the liquid formulation.
CONCLUSIONS
Metered dosing and calibrated measuring devices aided in the accurate delivery of this prescription medication. However, considerable concern exists with the use of noncalibrated measuring devices (teaspoons), improper frequency, and duration of use. Refilling of medication was also a concern since 63% were out of albuterol. Caregiver education on use, delivery, and refilling of medications must be stressed and assessed at all emergency department and primary care visits. In addition, metered dosing and the use of calibrated measuring devices should be encouraged. | 10.1001/archpedi.153.6.615 |
pubmed_73_23396 | Detecting a change in sound duration is important in language processing. The cerebral reactivity to a duration deviant in oddball paradigm has been reflected as a mismatch negativity (MMN). This study aimed to see cerebral responses to several duration-varying sounds presented with equal probability. Magnetoencephalographic (MEG) and behavior responses to equi-probable sounds (25-50-75-100-125 ms or 50-75-100-125-150 ms tones) were recorded in 10 healthy adult volunteers. By subtracting the average of the responses to 4 longer tones from the response to the shortest tone, a clear deflection peaking at 100-200 ms from stimulus onset was identified. This activity was called as sub-standard MMNm, and its amplitude tended to increase with the increment of duration deviance within a stimulation paradigm. The source of sub-standard MMNm was localized in superior temporal area, with 5-6 mm more anterior to the generator of N100m response. Behavioral tests also showed best performance in the recognition of the shortest tone than longer tones. In conclusion, the preferential response to the shortest tone in an equiprobable paradigm suggests an asymmetrical processing in the auditory cortex for duration-varying sounds. | 10.1016/j.heares.2010.06.009 |
pubmed_741_977 | Twenty-three normal male subjects received 900 mg of acetaminophen and 750 mg of chlorzoxazone as an oral suspension. Analysis of plasma samples indicated a rapid absorption and rapid elimination of chlorzoxazone. Average values of the elimination half-life and plasma clearance were 1.12 +/- 0.48 hr and 148.0 +/- 39.9 ml/min, respectively. Analysis of urine samples showed that chlorzoxazone was eliminated from the body as the glucuronide conjugate of the intermediate metabolite 6-hydroxychlorzoxazone, to the extent of 74% of the dose. The plasma and the urinary excretion data were fitted to theoretical equations, and excellent fits were obtained using a five-parameter pharmacokinetic model. | 10.1002/jps.2600720905 |
pubmed_897_116 | BACKGROUND
The prevalence of knee osteoarthritis is traditionally based on radiographic findings, but magnetic resonance imaging is now being used to provide better visualization of bone, cartilage, and soft tissues as well as the patellar compartment. The goal of this study was to estimate the prevalences of knee features defined on magnetic resonance imaging in a population and to relate these abnormalities to knee osteoarthritis severity scores based on radiographic findings, physical functioning, and reported knee pain in middle-aged women.
METHODS
Magnetic resonance images of the knee were evaluated for the location and severity of cartilage defects, bone marrow lesions, osteophytes, subchondral cysts, meniscal and/or ligamentous tears, effusion, and synovitis among 363 middle-aged women (724 knees) from the Michigan Study of Women's Health Across the Nation. These findings were related to Kellgren-Lawrence osteoarthritis severity scores from radiographs, self-reported knee pain, self-reported knee injury, perception of physical functioning, and physical performance measures to assess mobility. Radiographs, physical performance assessment, and interviews were undertaken at the 1996 study baseline and again (with the addition of magnetic resonance imaging assessment) at the follow-up visit during 2007 to 2008.
RESULTS
The prevalence of moderate-to-severe knee osteoarthritis changed from 3.7% at the baseline assessment to 26.7% at the follow-up visit eleven years later. Full-thickness cartilage defects of the medial, lateral, and patellofemoral compartments were present in 14.5% (105 knees), 4.6% (thirty-three knees), and 26.2% (190 knees), respectively. Synovitis was identified in 24.7% (179) of the knees, and joint effusions were observed in 70% (507 knees); 21.7% (157) of the knees had complex or macerated meniscal tears. Large osteophytes, marked synovitis, macerated meniscal tears, and full-thickness tibial cartilage defects were associated with increased odds of knee pain and with 30% to 40% slower walking and stair-climbing times.
CONCLUSIONS
Middle-aged women have a high prevalence of moderate-to-severe knee osteoarthritis corroborated by strong associations with cartilage defects, complex and macerated meniscal tears, osteophytes and synovitis, knee pain, and lower mobility levels. | 10.2106/JBJS.I.00667 |
pubmed_842_13561 | Wild birds are rarely found with active arbovirus infections, and relatively little is known about the patterns of viremia they exhibit under field conditions or how infection varies with date, bird age, or other factors that potentially affect transmission dynamics. Buggy Creek virus (BCRV; Togaviridae, Alphavirus) is an arbovirus associated with colonially nesting Cliff Swallows (Petrochelidon pyrrhonota) and transmitted by its vector, the hematophagous swallow bug (Oeciacus vicarius), an ectoparasite of the Cliff Swallow. Introduced House Sparrows (Passer domesticus) that have occupied swallow nests at colony sites in peridomestic settings are also exposed to BCRV when fed upon by swallow bugs. We used data from 882 nestling House Sparrows in western Nebraska from 2006 to 2008 to examine seasonal variation and age-related correlates of virus infection in the field. Over 17% of nestling House Sparrows had active infections. Prevalence was higher in 2007 than in 2008 when birds from all colony sites were analyzed, but there was no significant difference between years for sites sampled in both seasons. Buggy Creek virus prevalence was similar in early and late summer, with a peak in midsummer, coinciding with the greatest swallow bug abundance. Nestlings 10 days of age and younger were most commonly infected, and the likelihood of BCRV infection declined for older nestlings. Average viremia titers also declined with age (but did not vary with date) and were high enough at all nestling ages to likely infect blood-feeding arthropods (swallow bugs). Length of viremia for nestlings in the field was ≥4 days, in agreement with an earlier study of BCRV. Nestling birds offer many advantages for field studies of arbovirus amplification and transmission. | 10.7589/0090-3558-48.1.138 |
pubmed_1093_3169 | Pitched battles over aspects of the law will continue, but the fundamental reality is that stakeholders are fully engaged, and implementation will move ahead. | 10.1377/hlthaff.2012.1279 |
pubmed_383_21344 | BACKGROUND
The muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor-blocking activity but causes cholinergic adverse events. Trospium is a peripherally restricted muscarinic receptor antagonist that reduces peripheral cholinergic effects of xanomeline. The efficacy and safety of combined xanomeline and trospium in patients with schizophrenia are unknown.
METHODS
In this double-blind, phase 2 trial, we randomly assigned patients with schizophrenia in a 1:1 ratio to receive twice-daily xanomeline-trospium (increased to a maximum of 125 mg of xanomeline and 30 mg of trospium per dose) or placebo for 5 weeks. The primary end point was the change from baseline to week 5 in the total score on the Positive and Negative Syndrome Scale (PANSS; range, 30 to 210, with higher scores indicating more severe symptoms of schizophrenia). Secondary end points were the change in the PANSS positive symptom subscore, the score on the Clinical Global Impression-Severity (CGI-S) scale (range, 1 to 7, with higher scores indicating greater severity of illness), the change in the PANSS negative symptom subscore, the change in the PANSS Marder negative symptom subscore, and the percentage of patients with a response according to a CGI-S score of 1 or 2.
RESULTS
A total of 182 patients were enrolled, with 90 assigned to receive xanomeline-trospium and 92 to receive placebo. The PANSS total score at baseline was 97.7 in the xanomeline-trospium group and 96.6 in the placebo group. The change from baseline to week 5 was -17.4 points with xanomeline-trospium and -5.9 points with placebo (least-squares mean difference, -11.6 points; 95% confidence interval, -16.1 to -7.1; P<0.001). The results for the secondary end points were significantly better in the xanomeline-trospium group than in the placebo group, with the exception of the percentage of patients with a CGI-S response. The most common adverse events in the xanomeline-trospium group were constipation, nausea, dry mouth, dyspepsia, and vomiting. The incidences of somnolence, weight gain, restlessness, and extrapyramidal symptoms were similar in the two groups.
CONCLUSIONS
In a 5-week trial, xanomeline-trospium resulted in a greater decrease in the PANSS total score than placebo but was associated with cholinergic and anticholinergic adverse events. Larger and longer trials are required to determine the efficacy and safety of xanomeline-trospium in patients with schizophrenia. (Funded by Karuna Therapeutics and the Wellcome Trust; ClinicalTrials.gov number, NCT03697252.). | 10.1056/NEJMoa2017015 |
pubmed_882_7473 | The small GTPase DiRas1 has tumor-suppressive activities, unlike the oncogenic properties more common to small GTPases such as K-Ras and RhoA. Although DiRas1 has been found to be a tumor suppressor in gliomas and esophageal squamous cell carcinomas, the mechanisms by which it inhibits malignant phenotypes have not been fully determined. In this study, we demonstrate that DiRas1 binds to SmgGDS, a protein that promotes the activation of several oncogenic GTPases. In silico docking studies predict that DiRas1 binds to SmgGDS in a manner similar to other small GTPases. SmgGDS is a guanine nucleotide exchange factor for RhoA, but we report here that SmgGDS does not mediate GDP/GTP exchange on DiRas1. Intriguingly, DiRas1 acts similarly to a dominant-negative small GTPase, binding to SmgGDS and inhibiting SmgGDS binding to other small GTPases, including K-Ras4B, RhoA, and Rap1A. DiRas1 is expressed in normal breast tissue, but its expression is decreased in most breast cancers, similar to its family member DiRas3 (ARHI). DiRas1 inhibits RhoA- and SmgGDS-mediated NF-κB transcriptional activity in HEK293T cells. We also report that DiRas1 suppresses basal NF-κB activation in breast cancer and glioblastoma cell lines. Taken together, our data support a model in which DiRas1 expression inhibits malignant features of cancers in part by nonproductively binding to SmgGDS and inhibiting the binding of other small GTPases to SmgGDS. | 10.1074/jbc.M115.696831 |
pubmed_56_2311 | We aimed to examine the potential relationship between season of birth (SOB) and clinical characteristics in Korean patients with unipolar non-psychotic major depressive disorder (MDD). Using data from the Clinical Research Center for Depression (CRESCEND) study in South Korea, 891 MDD patients were divided into two groups, those born in spring/summer (n=457) and those born in autumn/winter (n=434). Measurement tools comprising the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Brief Psychiatric Rating Scale, Scale for Suicidal Ideation, Clinical Global Impression of severity, Social and Occupation Functional Assessment Scale, WHO Quality of Life assessment instrument-abbreviated version, Alcohol Use Disorder Identification Test, and Temperament and Character Inventory were used to evaluate depression, anxiety, overall symptoms, suicidal ideation, global severity, social function, quality of life, drinking, and temperament and character, respectively. Using independent t-tests for continuous variables and χ² tests for discrete variables, the clinical characteristics of the two groups were compared. MDD patients born in spring/summer were on average younger at onset of first depressive episode (t=2.084, p=0.038), had greater loss of concentration (χ²=4.589, p=0.032), and were more self-directed (t=2.256, p=0.025) than those born in autumn/winter. Clinically, there was a trend for the MDD patients born in spring/summer to display the contradictory characteristics of more severe clinical course and less illness burden; this may have been partly due to a paradoxical effect of the 5-HT system. | 10.3349/ymj.2016.57.3.784 |
pubmed_21_5460 | BACKGROUND AND PURPOSE
ATP-sensitive K(+)(K(ATP)) channels, which are composed of K(IR)6.x associated with sulphonylurea receptor (SUR) subunits, have been detected in native smooth muscle cells, but it is currently not known which of these is expressed in mouse vas deferens myocytes.
EXPERIMENTAL APPROACH
Pharmacological and electrophysiological properties of K(ATP) channels in mouse vas deferens myocytes were investigated using patch clamp techniques. Molecular biological analyses were performed to examine the properties of these K(ATP) channels.
KEY RESULTS
During conventional whole-cell recording, pinacidil elicited an inward current that was suppressed by glibenclamide, a sulfonylurea agent, and by U-37883A, a selective K(IR)6.1 blocker. When 0.3 mM ATP was added to the pipette solution, the peak amplitude of the pinacidil-induced current was much smaller than that recorded in its absence. When 3 mM UDP, GDP or ADP was included in the pipette solution, an inward current was elicited after establishment of the conventional whole-cell configuration, with potency order being UDP > GDP > ADP. These nucleoside diphosphate-induced inward currents were suppressed by glibenclamide. MCC-134, a SUR modulator, induced glibenclamide-sensitive K(ATP) currents that were similar to those induced by 100 μM pinacidil. In the cell-attached configuration, pinacidil activated channels with a conductance similar to that of K(IR)6.1. Reverse transcription PCR analysis revealed the expression of K(IR)6.1 and SUR2B transcripts and immunohistochemical studies indicated the presence of K(IR)6.1 and SUR2B proteins in the myocytes.
CONCLUSIONS AND IMPLICATIONS
Our results indicate that native K(ATP) channels in mouse vas deferens myocytes are a heterocomplex of K(IR)6.1 channels and SUR2B subunits. | 10.1111/bph.12437 |
pubmed_380_17942 | PURPOSE
Although rituximab is now routinely used in the treatment of B-cell non-Hodgkin's lymphoma, the mechanism of its antitumor effect is not clear. One potential mechanism of action involves antibody-dependent cellular cytotoxicity (ADCC). Two aspects of ADCC influence the effectiveness of this process: the susceptibility of tumor cells and the activation of effector cells via their immunoglobulin G fragment C receptors (Fc gamma Rs). Several Fc gamma R polymorphisms have been identified that may affect the killing function of natural killer cells and macrophages.
PATIENTS AND METHODS
The pretreatment tumor cells from 43 patients with follicular lymphoma were tested for their intrinsic susceptibility to rituximab-mediated ADCC. In addition, the Fc gamma RIIIa (CD16) and Fc gamma RIIa (CD32) polymorphisms were determined in an expanded group of 87 patients. The results were then correlated with clinical outcome of these patients.
RESULTS
No difference was found between the susceptibility of tumors from patients who clinically responded to rituximab versus those who did not respond. Conversely, both the Fc gamma RIIIa 158 valine/valine and the Fc gamma RIIa 131 histidine/histidine genotypes were found to be independently associated with the response rate and freedom from progression.
CONCLUSION
These data support the hypothesis that ADCC plays an important role in the clinical effect of rituximab at the level of the effector cell. It will be important to include information on Fc receptor polymorphisms in future trials of rituximab therapy. | 10.1200/JCO.2003.05.013 |
pubmed_949_6692 | A pilot project was implemented involving students from three disciplines: dental hygiene, physical therapy, and physician assistant. The purpose was to prepare students to work together in multidiscipline teams utilizing concepts of problem-based learning (PBL) on both simulated and real patients. The project was divided into three phases. Phase I introduced discipline specific information, team concepts, and PBL concepts. Phase II involved students working in multidisciplinary teams solving a simulated patient case in the PBL format. Phase III consisted of students working in small groups and on real patients, performing an extraoral/intraoral and periodontal examination, a problem oriented physical examination, and a neuromuscular assessment. Pre and posttest evaluation of Phase I revealed no difference in knowledge among the three disciplines. Of those students evaluating Phase II and III, 100% felt PBL was an effective means of presenting multidisciplinary material; 93% reported enhanced problem-solving; 98% indicated improvements in working in groups; and 98% felt they had learned more about each other's discipline. This model may provide a viable means to prepare interdisciplinary teams to work effectively together. | pubmed_949_6692 |
pubmed_678_11722 | BACKGROUND
Prior reviews of geriatrics curricula for internal medicine (IM) and family medicine (FM) residents have not evaluated study quality or assessed learning objectives or specific IM or FM competencies.
OBJECTIVE
This review of geriatrics curricula for IM and FM residents seeks to answer 3 questions: (1) What types of learning outcomes were measured? (2) How were learning outcomes measured? and (3) What was the quality of the studies?
METHODS
We evaluated geriatrics curricula that reported learning objectives or competencies, teaching methods, and learning outcomes, and those that used a comparative design. We searched PubMed and 4 other data sets from 2003-2015, and assessed learning outcomes, outcome measures, and the quality of studies using the Medical Education Research Study Quality Instrument (MERSQI) and Best Evidence Medical Education (BEME) methods.
RESULTS
Fourteen studies met inclusion criteria. Most curricula were intended for IM residents in the inpatient setting; only 1 was solely dedicated to FM residents. Median duration was 1 month, and minimum geriatrics competencies covered were 4. Learning outcomes ranged from Kirkpatrick levels 1 to 3. Studies that reported effect size showed a considerable impact on attitudes and knowledge, mainly via pretests and posttests. The mean MERSQI score was 10.5 (range, 8.5-13) on a scale of 5 (lowest quality) to 18 (highest quality).
CONCLUSIONS
Few geriatrics curricula for IM and FM residents that included learning outcome assessments were published recently. Overall, changes in attitudes and knowledge were sizeable, but reporting was limited to low to moderate Kirkpatrick levels. Study quality was moderate. | 10.4300/JGME-D-16-00037.1 |
pubmed_271_20600 | Multiple DNA polymerases are involved in the generation of somatic mutations during Ig gene hypermutation. Mice expressing a catalytically inactive REV1 (REV1AA) exhibit reduction of both C to G and G to C transversions and moderate decrease of A/T mutations, whereas DNA polymerase η (POLH) deficiency causes greatly reduced A/T mutations. To investigate whether REV1 and POLH interact genetically and functionally during Ig gene hypermutation, we established REV1AA Polh(-/-) mice and analyzed Ig gene hypermutation in the germinal center (GC) B cells. REV1AA Polh(-/-) mice were born at the expected ratio and developed normally with no apparent gross abnormalities. B-cell development, maturation, Ig gene class switch and the GC B-cell expansion were not affected in these mice. REV1AA Polh(-/-) B cells also exhibited relatively normal sensitivity to etoposide and ionizing radiation. Analysis of somatic mutations in the J(H)4 intronic region revealed that REV1AA Polh(-/-) mice had a further decrease of overall mutation frequency compared with REV1AA or Polh(-/-) mice, indicating that the double deficiency additively affected the generation of mutations. Remarkably, REV1AA Polh(-/-) mice had nearly absent C to G and G to C transversions, suggesting that POLH is essential for the generation of residual C to G and G to C transversions observed in REV1AA mice. These results reveal genetic interactions between REV1 catalytic activity and POLH and identify an alternative pathway, mediated by non-catalytic REV1 and POLH, in the generation of C to G and G to C transversions. | 10.1093/intimm/dxr109 |
pubmed_1056_1241 | Manganese is growth inhibitory for Escherichia coli. The manganese concentration required for inhibition is dependent upon the magnesium concentration of the medium. Mutants have been isolated which are partially resistant to manganese inhibition in both liquid and solid media. From conjugation experiments, the genetic locus for manganese-resistance, mng, appears to be between 34 and 37 min on the E. coli genetic map. Experiments with radioactive (28)Mg lead to the tentative conclusion that the mng mutants are altered in the inhibition constant for manganese as a competitive inhibitor for the mangnesium accumulation system. Once high manganese enters the cells, it displaces internal magnesium and leads to a net cellular loss and hence growth inhibition. The mng mutants are somewhat less subject to manganese-induced magnesium loss under comparable conditions than are manganese-sensitive wild-type cells. | 10.1128/jb.110.1.186-195.1972 |
pubmed_807_23392 | The RpoS sigma factor in proteobacteria regulates genes in stationary phase and in response to stress. Although of conserved function, the RpoS regulon may have different gene composition across species due to high genomic diversity and to known environmental conditions that select for RpoS mutants. In this study, the distribution of RpoS homologs in prokaryotes and the differential dependence of regulon members on RpoS for expression in two gamma-proteobacteria (Escherichia coli and Pseudomonas aeruginosa) were examined. Using a maximum-likelihood phylogeny and reciprocal best hits analysis, we show that the RpoS sigma factor is conserved within gamma-, beta-, and delta-proteobacteria. Annotated RpoS of Borrelia and the enteric RpoS are postulated to have separate evolutionary origins. To determine the conservation of RpoS-dependent gene expression across species, reciprocal best hits analysis was used to identify orthologs of the E. coli RpoS regulon in the RpoS regulon of P. aeruginosa. Of the 186 RpoS-dependent genes of E. coli, 50 proteins have an ortholog within the P. aeruginosa genome. Twelve genes of the 50 orthologs are RpoS-dependent in both species, and at least four genes are regulated by RpoS in other gamma-proteobacteria. Despite RpoS conservation in gamma-, beta-, and delta-proteobacteria, RpoS regulon composition is subject to modification between species. Environmental selection for RpoS mutants likely contributes to the evolutionary divergence and specialization of the RpoS regulon within different bacterial genomes. | 10.1007/s00239-010-9352-0 |
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