Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective inhibition of warfarin metabolism by diltiazem in humans.

Healthy men were administered i.v. racemic warfarin, S-warfarin or R-warfarin on two occasions, once in the drug-free state and once during concomitant administration of oral diltiazem 120 mg three times daily. Blood samples for determination of plasma warfarin and diltiazem concentrations, the prothrombin time and complete urine collections were obtained for determination of urinary excretion of dehydrowarfarin, 4'-hydroxywarfarin, 6-hydroxywarfarin, 7-hydroxywarfarin, 8-hydroxywarfarin and unchanged parent drug for 216 h after each dose. Concurrent diltiazem administration decreased total racemic warfarin clearance (+/- S.D.) [3.60 +/- 0.99 (control) versus 3.19 +/- 0.86 (diltiazem) ml/min; P less than . 05]. Disposition of the more potent anticoagulant S-warfarin was not altered by diltiazem treatment. In contrast total clearance of R-warfarin was decreased [3.47 +/- 1.10 (control) versus 2.77 +/- 0.92 ml/min; P less than . 05]. No change in the area under the prothrombin time versus time after warfarin administration curve was associated with diltiazem treatment for any warfarin trial. Inhibition of R-warfarin by diltiazem was regioselective for metabolites as determined by fractional clearance of urinary metabolites. R-6-hydroxywarfarin clearance (+/- S.E.) [29.5 +/- 7.2 (control) versus 15.7 +/- 2.8 ml/h; P less than 0.05] and R-8-hydroxywarfarin clearance [21.1 +/- 3.6 (control) versus 11.2 +/- 2.0 ml/h; P less than . 05] were selectively decreased with no significant change in the urinary clearance of R-dehydro, R-4-hydroxy and R-7-hydroxywarfarin. Urinary clearance of unchanged R-warfarin was also decreased during diltiazem administration. Diltiazem inhibits warfarin disposition in humans in a stereospecific and regiospecific manner.
Breast masses: removal of all US evidence during biopsy by using a handheld vacuum-assisted device--initial experience.

PURPOSE To assess the effects of removal of all ultrasonographic (US) evidence of breast lesions by using a vacuum-assisted biopsy (VAB) device. MATERIALS AND METHODS Thirty-four women with breast masses underwent US-guided biopsy with an 11-gauge VAB device, with which removal of all evidence of the lesion was attempted. Histologic findings were compared with results of surgery and follow-up imaging. Patient tolerance and perceptions of the procedure and the ability of the procedure to eliminate a palpable finding were evaluated with questionnaires and findings at follow-up physical examination. RESULTS The biopsy protocol was completed in all cases. Twenty-six benign lesions (76%) and eight malignancies (24%) were diagnosed. After VAB, 10 patients (29%) underwent surgery on the basis of histologic findings of invasive carcinoma (n = 7), ductal carcinoma in situ (n = 1), lobular neoplasia (n = 1), or atypical ductal hyperplasia (n = 1). VAB resulted in complete excision of four of 10 lesions: two of eight malignancies and two of two benign lesions. Among 21 patients with benign lesions who underwent 6-month follow-up imaging, eight (38%) had a definite residual mass. At 6-month follow-up examination, VAB was seen to have eliminated the palpable abnormality in seven (88%) of eight patients with initially palpable benign masses. Thirty-two patients (94%) described no or mild pain during biopsy, and 33 patients (97%) rated care as excellent. CONCLUSION After removal of all US evidence of breast masses with a VAB device, there was a substantial probability that residual lesion that was not visualized during the procedure would later be found at surgery or follow-up imaging. A palpable mass (< or =1.2 cm in mean diameter) was eliminated in 88% of cases, and patient tolerance and perceptions of the procedure were favorable.
Psoriasis patients with nail disease have a greater magnitude of underlying systemic subclinical enthesopathy than those with normal nails

Objective Enthesopathy is a major feature of psoriatic arthritis (PsA), which is supported by imaging studies. Given that nail disease often predates PsA and that the nail is directly anchored to entheses, the authors asked whether nail involvement in psoriasis equates with a systemic enthesopathy. Methods Forty-six patients with psoriasis (31 with nail disease) and 21 matched healthy controls (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an ultrasonographer blinded to clinical details. Results Psoriasis patients had higher enthesitis scores than HC (median (range) 21 (0–65) vs 11 (3–39), p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0–65)) than in patients without nail disease (15 (5–26), p=0.02) and HC (11 (3–39), p=0.003). Inflammation scores of patients with nail disease (13 (0–34)) were higher than patients without nail disease (8 (2–15), p=0.02) and HC (5 (0–19), p<0.001). Modified nail psoriasis severity index scores were correlated to both inflammation (r2=0.45, p=0.005) and chronicity scores (r2=0.35, p=0.04). No link between the psoriasis area and severity index and enthesitis was evident. Conclusion The link between nail disease and contemporaneous subclinical enthesopathy offers a novel anatomical basis for the predictive value of nail psoriasis for PsA evolution.
Effects of RFamide‐Related Peptide (RFRP)‐1 and RFRP‐3 on Oxytocin Release and Anxiety‐Related Behaviour in Rats

RFamide‐related peptides (RFRP‐1 and RFRP‐3) are localised in neurones of the dorsomedial hypothalamus in rats. The dorsomedial hypothalamus plays an essential role in neuroendocrine and behavioural stress responses. In the present study, we examined the role of RFRP in the control of neuroendocrine and behavioural responses in rats. Stressful stimuli increased expression of Fos protein in RFRP‐immunoreactive neurones of the dorsomedial hypothalamus, suggesting that stressful stimuli activate RFRP neurones. Intracerebroventricular injection of RFRPs increased the expression of Fos protein in oxytocin neurones in the hypothalamus and plasma concentrations of adrenocorticotrophic hormone and oxytocin. The hypothalamic paraventricular and supraoptic nuclei expressed mRNA of GPR147, the putative RFRP receptor, and application of RFRPs to isolated supraoptic nuclei facilitated oxytocin release, suggesting that RFRPs activate oxytocin neurones directly. Furthermore, the administration of RFRPs induced anxiety‐related behaviour in rats in open‐field tests. All these data taken together suggest that RFRPs play a role in the control of neuroendocrine and behavioural stress responses in rats.
Methodological guidance documents for evaluation of ethical considerations in health technology assessment: a systematic review

Despite the advances made in the development of ethical frameworks for health technology assessment (HTA), there is no clear agreement on the scope and details of a practical approach to address ethical aspects in HTA. This systematic review aimed to identify existing guidance documents for incorporation of ethics in HTA to provide an overview of their methodological features. The review identified 43 conceptual frameworks or practical guidelines, varying in their philosophical approach, structure, and comprehensiveness. They were designed for different purposes throughout the HTA process, ranging from helping HTA-producers in identification, appraisal and analysis of ethical data to supporting decision-makers in making value-sensitive decisions. They frequently promoted using analytical methods that combined normative reflection with participatory approaches. The choice of a method for collection and analysis of ethical data seems to depend on the context in which technology is being assessed, the purpose of analysis, and availability of required resources.
Chondrogenic differentiation of murine embryonic stem cells: Effects of culture conditions and dexamethasone

Pluripotent embryonic stem (ES) cells have the capability to differentiate to various cell types and may represent an alternative cell source for the treatment of cartilage defects. Here, we show that differentiation of ES cells toward the chondrogenic lineage can be enhanced by altering the culture conditions. Chondrogenesis was observed in intact embryoid body (EB) cultures, as detected by an increase in mRNA levels for aggrecan and Sox9 genes. Collagen IIB mRNA, the mature chondrocyte‐specific splice variant, was absent at day 5, but appeared at later time points. Dexamethasone treatment of alginate‐encapsulated EB cultures did not have a strong chondrogenic effect. Nor was chondrogenesis enhanced by alginate encapsulation compared to simple plating of EBs. However, disruption of day 5 EBs and culture as a micromass or pelleted mass, significantly enhanced the expression of the cartilage marker gene collagen type II and the transcription factor Sox9 compared to all other treatments. Histological and immunohistochemical analysis of pellet cultures revealed cartilage‐like tissue characterized by metachromatically stained extracellular matrix and type II collagen immunoreactivity, indicative of chondrogenesis. These findings have potentially important implications for cartilage tissue engineering, since they may enable the increase in differentiated cell numbers needed for the in vitro development of functional cartilaginous tissue suitable for implantation. © 2004 Wiley‐Liss, Inc.
Effects of supplementation level and particle size of alfalfa hay on growth characteristics and rumen development in dairy calves.

The aim of this study was to assess the effects of particle size (PS) of alfalfa hay on growth characteristics and rumen development in dairy calves at two levels of alfalfa supplementation. Fifty newborn dairy calves (42.7 ± 2.2 kg BW) were used in a 2 × 2 factorial arrangement with the factors supplementation level (low, 8%; or high, 16% on DM basis) and PS (medium, 2.92 mm; or long, 5.04 mm as geometrical means) of alfalfa hay. In addition, a control group without alfalfa hay was used. Hence, treatments were: control (C); low level with medium PS (LM); low level with long PS (LL); high level with medium PS (HM) or high level with long PS (HL). Growth performance of alfalfa-fed calves did not differ from control calves, but alfalfa supplementation decreased corneum thickness of the rumen wall. In alfalfa-fed calves, post-weaning starter intake was greater for LL calves than for LM calves. During the entire rearing period, starter intake was 26-32% higher for LL and HM calves than for LM calves. Pre-weaning average daily gain was higher for LL and HM calves than for HL calves, but this effect was not persistent over the entire rearing period. Final body weight decreased from 86 to 79 kg when the level of long PS alfalfa hay increased from 8 to 16%, but increased from 78 to 87 kg when the level of medium PS alfalfa increased from 8 to 16%. Regardless of PS and level, morphometric characteristics of rumen wall were generally similar among alfalfa feeding groups, but corneum thickness decreased from 8.7 to 6.1 μm with greater PS at the low level. These results indicate that adequate, but not excessive, physical stimulation is required for appropriate rumen development and growth performance of dairy calves.
Comparison of Acute and Chronic Pain after Open Nephrectomy versus Laparoscopic Nephrectomy

AbstractWe evaluated postoperative pain intensity and the incidence of chronic pain in patients with renal cell carcinoma undergoing laparoscopic or open radical nephrectomy.In this prospective study, 27 laparoscopic nephrectomy (Group LN) and 25 open nephrectomy (Group ON) patients were included. All patients received paracetamol infusion and intramuscular morphine 30 minutes before the end of the operation and intravenous patient controlled analgesia with morphine postoperatively. Data including patients’ demographics, visual analog scale (VAS) pain scores at postoperative 0.5, 1, 2, 4, 6, 12, and 24 hours, postoperative morphine consumption, analgesic demand, analgesic delivery, number of patients requiring rescue analgesics, side effects because of analgesic medications, and overall patient satisfaction were recorded and compared between the two groups. Two and 6 months after the operation, patients were evaluated for chronic postsurgical pain (CPSP). Postoperative average VAS pain scores were not different between the two groups. However, only at 2 hours postoperatively, pain score was significantly higher in Group ON than in Group LN. In both groups, the highest pain scores were recorded at 30 minutes and 1 hour after surgery. Ninety-six percent of group ON patients and 88% of group LN patients required additional analgesia in the early postoperative period (P = 0.33). Postoperative morphine consumption and analgesic demand were found to be similar between the two groups. CPSP at 2 months after surgery was observed in 4 out of 25 patients (16%) in the ON group and 3 out of 27 patients (11.1%) in the LN group (P = 0.6). Chronic pain at 6 months after surgery was observed in 1 ON patient (4%) and 1 LN patient (3.7%, P = 0.9). This study demonstrated that postoperative acute pain scores were not different after laparoscopic or open nephrectomy and patients undergoing laparoscopic or open nephrectomy were at equal risk of developing CPSP. Pain control should be carefully planned in order to reduce early postoperative pain and also potentially prevent CPSP.
A first approach on the failure mechanisms of IGBT inverters for aeronautical applications: Effect of humidity-pressure combination

Comparing to the most common reliability tests this work presents a new approach of accelerated testing, by combining temperature, humidity and pressure cycling with voltage stress. A design of experiments methodology has been proposed to test IGBT inverters and understand environmental factors effect. The humidity-pressure combination effect is studied for various IGBT inverter packaging materials.
Inactivation of bad by site‐specific phosphorylation: The checkpoint for ischemic astrocytes to initiate or resist apoptosis

Bcl‐2‐associated death protein (Bad), a member of the Bcl family, directs astrocytes in primary cultures to enter or resist apoptosis during ischemia in vitro. Under ischemia, Bad was the only Bcl family member whose expression was upregulated significantly during the early stages of an ischemic insult. Increased endogenous Bad was translocated from the cytoplasm to mitochondria to induce apoptosis in astrocytes. Concurrently, ischemia also induced Bad phosphorylation specifically on Ser112 to promote survival. This site‐specific phosphorylation of Bad was mediated by an early activation of the mitogen‐activated protein kinase/extracellular signal‐regulated protein kinase (MAPK/ERK) intracellular signaling pathway. This study demonstrates that ischemia‐induced Bad plays a dual role in determining whether astrocytes enter or resist apoptosis after an ischemic insult. © 2005 Wiley‐Liss, Inc.
High miR‐21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer

Colon cancer (CC) is a leading cause of cancer mortality. Novel biomarkers are needed to identify CC patients at high risk of recurrence and those who may benefit from therapeutic intervention. The aim of this study is to investigate if miR‐21 expression from RNA isolated from formalin‐fixed paraffin‐embedded (FFPE) tissue sections is associated with prognosis and therapeutic outcome for patients with CC. The expression of miR‐21 was measured by quantitative reverse transcriptase‐polymerase chain reaction in a Japanese cohort (stage I‐IV, n = 156) and a German cohort (stage II, n = 145). High miR‐21 expression in tumors was associated with poor survival in both the stage II/III Japanese (p = 0.0008) and stage II German (p = 0.047) cohorts. These associations were independent of other clinical covariates in multivariable models. Receipt of adjuvant chemotherapy was not beneficial in patients with high miR‐21 in either cohort. In the Japanese cohort, high miR‐21 expression was significantly associated with poor therapeutic outcome (p = 0.0001) and adjuvant therapy was associated with improved survival in patients with low miR‐21 (p = 0.001). These results suggest that miR‐21 is a promising biomarker to identify patients with poor prognosis and can be accurately measured in FFPE tissues. The expression of miR‐21 may also identify patients who will benefit from adjuvant chemotherapy.
Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians' transfusion practices.

BACKGROUND Transfusion services have used various techniques to reduce blood product utilization. Given the potential adverse effects of transfusions and the resources consumed in implementing strategies to reduce transfusions, there is a need to understand their effectiveness. Therefore, we performed a systematic review of the literature to examine the effectiveness of behavioral interventions to reduce blood product utilization. METHODS We identified all relevant articles through the use of electronic searches of MEDLINE and EMBASE, as well as hand searches of review articles and personal files. The electronic searches included articles published between January 1966 and May 2003. The searches included the terms blood transfusion, plasma exchange, guidelines, education, practice patterns, and professional practice. The outcomes of interest were the number of units transfused and the proportion of patients who received transfusions. RESULTS Nineteen studies examining the effectiveness of single (guidelines, prospective audits, retrospective audits, and reminders) or multifaceted interventions in reducing red blood cell, platelet, plasma, cryoprecipitate, and albumin transfusions met the inclusion criteria. Eighteen studies demonstrated a relative reduction in the number of units given (range, 9%-77%) or the proportion of patients receiving transfusions (range, 17%-79%). The reported reductions were qualitatively similar for the different blood products studied. No particular intervention or combination of interventions appeared more effective in reducing utilization. CONCLUSIONS Behavioral interventions, including simple interventions, appear to be effective in changing physician transfusion practices and reducing blood utilization. Appropriately designed clinical trials are still needed to determine the relative effectiveness of different interventions to change practices.
NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase‐4 and caspase‐5

Humans encode two inflammatory caspases that detect cytoplasmic LPS, caspase‐4 and caspase‐5. When activated, these trigger pyroptotic cell death and caspase‐1‐dependent IL‐1β production; however the mechanism underlying this process is not yet confirmed. We now show that a specific NLRP3 inhibitor, MCC950, prevents caspase‐4/5‐dependent IL‐1β production elicited by transfected LPS. Given that both caspase‐4 and caspase‐5 can detect cytoplasmic LPS, it is possible that these proteins exhibit some degree of redundancy. Therefore, we generated human monocytic cell lines in which caspase‐4 and caspase‐5 were genetically deleted either individually or together. We found that the deletion of caspase‐4 suppressed cell death and IL‐1β production following transfection of LPS into the cytoplasm, or in response to infection with Salmonella typhimurium. Although deletion of caspase‐5 did not confer protection against transfected LPS, cell death and IL‐1β production were reduced after infection with Salmonella. Furthermore, double deletion of caspase‐4 and caspase‐5 had a synergistic effect in the context of Salmonella infection. Our results identify the NLRP3 inflammasome as the specific platform for IL‐1β maturation, downstream of cytoplasmic LPS detection by caspase‐4/5. We also show that both caspase‐4 and caspase‐5 are functionally important for appropriate responses to intracellular Gram‐negative bacteria.
Tobacco use and baccalaureate nursing students: a study of their attitudes, beliefs and personal behaviours.

AIM To report findings about student nurses' attitudes, beliefs and personal behaviour in relation to tobacco issues. RATIONALE Nurses have the potential to influence clients' behaviours and public policy concerning tobacco use. However, a review of the literature suggests that this is not happening. Further understanding of nursing students' attitudes, beliefs and behaviours regarding tobacco use is needed in order to develop strategies which can positively impact on their future health promotion role. METHODS A cross-sectional survey of the total population of baccalaureate nursing students in one Canadian province was employed. Students were asked to complete a self-administered questionnaire, which included questions related to their smoking history; stage of behavioural change, and beliefs and attitudes towards tobacco. Students also completed the Health Promotion Lifestyle Profile (HPLP) and the Fagerström Nicotine Tolerance Scale. FINDINGS Two hundred and seventy-two students (61.9%) responded. Sixty (22.1%) indicated that they smoked daily or in social situations. These smokers were found to have a fairly low level of nicotine dependence and although 91.4% said they wanted to quit, few were actively engaged in the quitting process (16.9%). When comparing the beliefs and attitudes of smoking and non-smoking students, proportionally more of the non-smokers agreed that smokers will need close family/friends to help them quit; that the health of society should be protected by laws against smoking; and that nurses should set a non-smoking example. Non-smokers indicated more health promoting behaviours on items in the HPLP especially on the variables of physical activity, nutrition and stress management. CONCLUSIONS Nurses have the potential to influence clients' behaviours and public policy concerning tobacco use. Developing future nurses with the knowledge and skill to do so needs to be an important emphasis of nursing curricula.
[Effect of Bushenhuoxue Yin on cerebral levels of nitric oxide, tumor necrosis factor-α and interferon-γ in a mouse model of Parkinson disease].

OBJECTIVE To observe the effects of Bushenhuoxue Yin (BSHXY), a compound traditional Chinese herbal medicine, on nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) levels in the brain of a mouse model of Parkinson disease (PD). METHODS Forty-five C57BL/6 mice were randomized into MPTP-induced PD model group, BSHXY treatment group and normal control group. The contents of NO and the two cytokines in the brain tissue of the mice were determined by spectroscopy and enzyme-linked immunosorbent assay, respectively. RESULTS The concentration of NO in the brain tissue of the PD model group was 5.93 ∓ 0.79 µmol/g.protein, significantly higher than that in BSHXY group (P<0.01) and normal control group (P<0.01). The levels of TNF-α and IFN-γ in the PD model group were 0.36 ∓ 0.11 ng/L and 0.83 ∓ 0.25 ng/L, respectively, also higher than those in the other two groups (P<0.01 or 0.001). But BSHXY group and the normal control group showed no significant differences in the levels of NO, TNF-α and IFN-γ (P>0.05). CONCLUSION The therapeutic effect of BSHXY on PD is partially attributed to decreased content of NO, TNF-α and IFN-γ in the brain.
Medicare Expenditures Associated with Alzheimer Disease

This study uses 4 years of data from the Medicare Current Beneficiary Survey to compare the use of Medicare covered services for persons who report having a diagnosis of dementia or Alzheimer disease with those who do not, adjusting for the prevalence of comorbidities and functional limitations. Although overall rates of Medicare spending are higher for demented persons, when other factors such as functional status are included in the predictive model, there is no consistent relation between the presence of dementia and higher Medicare spending. In some years, dementia was associated with higher adjusted expenditures for community living persons, whereas nursing home residents with Alzheimer disease have lower Medicare expenditures.