Miracle-dz/UniFAR-FTUs huggingface dataset:
The combination of CYP3A4*22 and CYP3A5*3 single-nucleotide polymorphisms determines tacrolimus dose requirement after kidney transplantation

Introduction Tacrolimus (Tac) has a narrow therapeutic window and shows large between-patient pharmacokinetic variability. As a result, over-immunosuppression and under-immunosuppression are frequently encountered in daily clinical practice. Unraveling the impact of genetic polymorphisms on Tac pharmacokinetics may help to refine therapy. In this study, the associations of single-nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes (CYP3A) with Tac pharmacokinetics were investigated in renal transplant recipients. Participants and methods In a cohort of 272 kidney transplant recipients, associations between functional genetic variants (CYP3A4*22 and CYP3A5*3) and dose-adjusted predose Tac concentrations (C0) and daily doses of Tac at days 5–7 and 15 and 1, 3, 6 and 12 months after renal transplantation were evaluated. Patients were genotyped and clustered according to both CYP3A4*22 and CYP3A5*3 allelic status: poor (PM) (CYP3A4*22 carriers with CYP3A5*3/*3), intermediate (IM) (CYP3A4*1/*1 with CYP3A5*3/*3 or CYP3A4*22 carriers with CYP3A5*1 carriers) and extensive CYP3A-metabolizers (EM) (CYP3A4*1/*1 and CYP3A5*1 carriers). Results EM had an 88% lower dose-adjusted C0 compared with IM. PM had a 26% higher dose-adjusted C0 compared with IM. The percentage of patients with supratherapeutic Tac exposure (C0>15 ng/ml) was significantly higher in PM (43.5%) compared with EM (0%) at days 5–7 after transplantation (P=0.01). About 30% of EM had subtherapeutic exposure (C0<5 ng/ml) at days 5–7 after transplantation (P=0.001). Conclusion The combined CYP3A4 and CYP3A5 genotype of renal transplant recipients has a major influence on the Tac dose required to reach the target exposure.
Decreased Plasma Antioxidants in Schizophrenia

An aberration in the level of antioxidants has been suggested in schizophrenia. Therefore, this study examined the difference in the antioxidant level between patients with schizophrenia and healthy controls, as well as the difference between the drug-naïve schizophrenic patients with a first episode (FSPR) and the risperidone-treated chronic schizophrenia (RCSPR) patients. The plasma albumin, bilirubin and uric acid levels were determined in 47 FSPR and 55 chronic schizophrenia patients who met the DSM-IV criteria for schizophrenia, and in 68 controls. The albumin and bilirubin levels were significantly lower in the schizophrenic patients compared to the controls, although there was no significant difference between the FSPR and RCSPR patients. The bilirubin level was significantly lower in the negative subgroup of the patient group. This study supports the hypothesis that an aberration in the antioxidant levels may be involved in schizophrenia. In addition, this study suggests that the antioxidant level may be associated with the clinical symptomatology as well as the treatment implications in schizophrenia, particularly the negative symptoms.
Alvarado score for the acute appendicitis in a provincial hospital.

OBJECTIVE To assess the accuracy of Alvarado Score in predicting acute appendicitis in Chachoengsao Hospital. MATERIAL AND METHOD The prospective study involved 1, 000 patients with suspected acute appendicitis. It was carried out between April 2008 and March 2010. The patients were given specific scores according to variables of Alvarado Scoring System. The signs, symptoms, laboratory values and pathology reports of each patient were collected and evaluated. The diagnosis was confirmed by operative findings and histopathological examination of specimens. The sensitivity, specificity, positive and negative predictive values and receiver operator characteristic (ROC) curves of each indicator were also calculated. RESULTS Out of total 1,000 patients (407 males, 593 females), 838 underwent surgery (352 males, 486 females) and specimens of 715 patients (313 males, 402 females) were confirmed by histopathological examination, thus giving negative appendectomy rate of 14.7% (11.08% males, 17.28% females). The overall sensitivity of Alvarado Score was 87.41% and the specificity was 74.39%, while the positive predictive value was 83.7%. The area under the curve was 0.74. CONCLUSION Though the diagnosis of acute appendicitis remains mainly clinical evaluation, Alvarado Score can be recommended as a helpful tool for the admission criteria and further management in order to reduce unnecessary admission, morbidity and mortality, length of stay, and cost of treatment.
What is Wrong With Cardiac Conditioning? We May be Shooting at Moving Targets

Early recanalization of the occluded culprit coronary artery clearly reduces infarct size in both animal models and patients and improves clinical outcomes. Unfortunately, reperfusion can seldom be accomplished before some myocardium infarcts. As a result there has been an intensive search for interventions that will make the heart resistant to infarction so that reperfusion could salvage more myocardium. A number of interventions have been identified in animal models, foremost being ischemic preconditioning. It protects by activating signaling pathways that prevent lethal permeability transition pores from forming in the heart’s mitochondria at reperfusion. Such conditioning can be accomplished in a clinically relevant manner either by staccato reperfusion (ischemic postconditioning) or by pharmacological activation of the conditioning signaling pathways prior to reperfusion. Unfortunately, clinical trials of ischemic postconditioning and pharmacologic conditioning have been largely disappointing. We suggest that this may be caused by inappropriate use as models intended to mimic the clinical scenario of young healthy animals that receive none of the many drugs currently given to our patients. Patients may be resistant to some forms of conditioning because of comorbidities, for example, diabetes, or they may already be conditioned by adjunct medications, for example, P2Y12 inhibitors or opioids. Incremental technological improvements in patient care may render some approaches to cardioprotection redundant, and thus the clinical target may be continually changing, while our animal models have not kept pace. In remote conditioning, a limb is subjected to ischemia/reperfusion prior to or during coronary reperfusion. Its mechanism is not as well understood as that of ischemic preconditioning, but the results have been very encouraging. In the present article, we will review ischemic, remote, and pharmacologic conditioning and possible confounders that could interfere with their efficacy in clinical trials in 2 settings of myocardial ischemia: (1) primary angioplasty in acute myocardial infarction and (2) elective angioplasty.
Adrenal ganglioneuromas: experience from a retrospective study in a Chinese population.

PURPOSE Ganglioneuromas (GNs) are benign neoplasms of combined neural crest, schwannian,and connective tissue origin, occurring rarely in the adrenal glands. The present study is to share our experience regarding diagnostic and therapeutic management of these tumors. MATERIALS AND METHODS Adrenal GNs of 15 patients were found incidentally with ultrasonography and were evaluated subsequently with computed tomography (CT) scan. Clinical data as well as follow-up data were collected retrospectively. All the patients received operative resection. RESULTS The mean age of the patients was 38.4 years (range, 25-52 years; male to female ratio, 2:1). Of study subjects 11 patients had unilateral GN on the right side, and the remaining 4 on the left side. All but 1 patient were asymptomatic. No hormonal secretion was apparent. Mean size of the tumors in CT scan was 6.27 cm (range, 2.5-14 cm), while 10 were larger than 5 cm. Eight patients underwent open adrenalectomy and the remaining 7 underwent laparoscopic anterior adrenalectomy. Histologically, all 15 neoplasms were completely differentiated,mature GN. We had no mortality or significant morbidity. Mean duration of hospitalization was 5.5 days (range, 3-7 days). There was no recurrence, during a mean followup of 5.4 years (range, 1-10 years). CONCLUSION Pre-operative diagnosis of adrenal GNs remains difficult merely according to physical examination. Therefore, we recommend complete operative resection once malignancy cannot be excluded by pre-operative analyses. Laparoscopic adrenalectomy is a reasonable option, at least for tumors ≤ 5 cm.
Endotoxin exposure and symptoms in asthmatic children

Endotoxins (ET) are pro‐innammatory substances present in hou.sc dust which may increase non‐specific bronchial reactivity in asthmatic patients. Endotoxins (EU/g) and Der p I levels were compared in the homes often asthmatic and ten control children, aged 6‐16 years, living in Sao Paulo, Brazil. The houses were visited once a month from February 1993 lo February 1994 and dust samples were collected from the bedding and floor of each subject's house. No significant differences were observed in ET and Derp 1 levels in the homes of asthmatics and controls. The highest ET levels were detected in January and November, whereas the lowest levels were detected in April and August (p < 0.05). demonstrating a distinct seasonal distribution. The highest Der p I levels in bedding were observed in July and the lowest in February (p < 0.05). while Derp I levels in floor did not show significant differences throughout the year. Symptom and medication scores were evaluated monthly in the group of asthmatic children. There was a significant correlation (p < 0.05. r = 0.63) between clinical symptom scores and ET exposure, however no significant correlation was found for mite exposure (p > 0.05. r = 0.19). The results suggest that ET exposure exacerbates asthmatic symptoms in mite allergic, asthmatic children.
Differential Effects of the Volume and Diversity of Communication Network Ties on Knowledge Workers' Performance

Research problem: For knowledge workers, such as IT professionals, the ties within their social network are a major channel for communicating the requisite knowledge and information. While prior studies tended to favor higher network centrality (i.e., larger volume of network ties), in this study, the researchers argue that centrality can reduce communication efficiency if the diversity of the ties is low. Research question: Which characteristic of communication ties, volume or diversity, has more influence on knowledge workers' performance? Literature review: Using social network analysis (SNA) as the theoretical framework, a review of the literature shows that social network ties have important performance implications because they can enhance an individual's access to valued resources. Studies have also examined the performance impact of “hindrance network centrality,” or how frequently a person is described by other network members as a hindrance to their performance. However, current research has overlooked the possible negative communication consequences of centrality in regards to redundant information, which may negatively affect job performance. Methodology: The current study employs a quantitative approach, using the standard SNA method of a “name generator” questionnaire to collect network data. Participants were 98 people in the IT department at a large defense company. We identified 3905 relationships and analyzed them with the UCINET software. Subsequently, social network variables, as well as performance and human capital variables were analyzed in logistic regressions. Results and discussion: Results showed a significant relationship between constraint, a measure of tie diversity, and performance. Centrality, the measure of tie volume, however, was not significantly related to performance. Our findings about the volume versus diversity of communication ties have important implications for professional communicators in the age of fast-growing social network media. A limitation of our study is that we approximated communication ties with social network links. We suggest that future studies further validate our findings by using a more direct measure of communication ties.
Evaluation of orthodontic treatment after 1 year of retention--a randomized controlled trial.

The aim of this study was to use a randomized controlled trial methodology to evaluate and compare three different retention methods. The capacity of the retention methods to retain orthodontic treatment results was in this first phase analysed on a short-term basis, i.e. after 1 year of retention. The subjects were recruited from adolescents undergoing fixed appliance treatment at an orthodontic clinic in the National Health Service (NHS) in Sweden between 2001 and 2007. Seventy-five patients (45 girls and 30 boys with a mean age of 14.4 years at the start of retention) were randomized into three retention systems; a vacuum-formed retainer in the maxilla and bonded canine-to-canine retainer in the mandible (group V-CTC), a vacuum-formed retainer in the maxilla combined with stripping of the 10 proximal surfaces of the lower mandibular anterior teeth (group V-S), and a prefabricated positioner covering the teeth in the maxilla and mandible (group P). The main outcome measures were: Little's irregularity index (LII), intercanine and intermolar width, arch length, overjet, and overbite. Registrations were made before orthodontic treatment, when the fixed orthodontic appliance was removed, and after 12 months in retention. Differences in means between groups were tested by one-way analysis of variance. After 1 year of retention, no clinically significant difference in retention capacity was found between the three retention methods. Small but significant differences (P < 0.05) were observed between the V-CTC and V-S groups regarding mandibular canine width, mandibular arch length, and overbite. In group P, two patients failed to co-operate.
Antibodies against Adhesion Molecules Reduce Apoptosis after Transient Middle Cerebral Artery Occlusion in Rat Brain

We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery. Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction (p < 0.01) and a decline in the absolute (p < 0.001), and normalized (to the ischemic area, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group (p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.
Predictors of Immediate and 6‐Month Outcomes in Hospitalized Elderly Patients

This article presents results of a prospective multivariate study of hospitalized elderly patients at an acute‐care Veterans Administration (VA) hospital to identify factors on hospital admission predictive of several short‐ and long‐term outcomes: in‐hospital and 6‐month mortality, immediate and delayed nursing home admission, length of hospital stay, and 6‐month rehospitalization. All patients aged 70 years and over admitted to acute‐care beds on the medical service wards during a 1‐year period were included in the study (N = 396). Factors most predictive of 6‐month mortality (using logistic regression) were decreased functional status, admitting diagnosis, and de creased mental status. Factors most predictive of nursing home admission were decreased functional status, living location, and decreased mental status. Functional status was a stronger predictor of length of stay, mortality, and nursing home placement than was principal admitting diagnosis — of relevance to the current emphasis on diagnosis‐related groups (DRGs). These data may be helpful in improving discharge planning, in resource allocation, and in targeting patients for different specialized geriatric programs.
Nonsteroidal Anti-Inflammatory Drugs for Low Back Pain: A Systematic Review Within the Framework of the Cochrane Collaboration Back Review Group

Study Design. A systematic review of randomized and double-blind controlled trials was performed. Summary of Background Data. Nonsteroidal anti-inflammatory drugs are the most frequently prescribed medications worldwide and are widely used for patients with low back pain. Objectives. To assess the effects of nonsteroidal anti-inflammatory drugs in the treatment of nonspecific low back pain with or without radiation, and to assess which type of nonsteroidal anti-inflammatory drug is most effective. Methods. For this study, the Cochrane Controlled Trials Register, Medline and Embase, and reference lists of articles were searched. Two reviewers blinded with respect to authors, institution, and journal independently extracted data and assessed the methodologic quality of the studies. If data were considered clinically homogeneous, a meta-analysis was performed. If data were considered clinically heterogeneous, a qualitative analysis was performed using a rating system with four levels of evidence: strong, moderate, limited, and no evidence. Results. This review involved 51 trials and 6057 patients. Of these trials, 16 (31%) were of high quality. The pooled relative risk for global improvement after 1 week was 1.24 (95% confidence interval [CI] = 1.10–1.41), and for additional analgesic use was 1.29 (95% CI = 1.05–1.57), indicating a statistically significant but small effect in favor of nonsteroidal anti-inflammatory drugs as compared with a placebo. The results of the qualitative analysis showed that there is conflicting evidence (Level 3) that nonsteroidal anti-inflammatory drugs are more effective than paracetamol for acute low back pain, and that there is moderate evidence (Level 2) that nonsteroidal anti-inflammatory drugs are not more effective than other drugs for acute low back pain. There is strong evidence (Level 1) that various types of nonsteroidal anti-inflammatory drugs are equally effective for acute low back pain. Conclusions. The evidence from the 51 trials included in this review suggests that nonsteroidal anti-inflammatory drugs are effective for short-term symptomatic relief in patients with acute low back pain. Furthermore, there does not seem to be a specific type of nonsteroidal anti-inflammatory drug that is clearly more effective than others. Sufficient evidence on chronic low back pain still is lacking.
Manometric tests of anorectal function in healthy adult Thai subjects.

BACKGROUND AND OBJECTIVES Diseases of the distal gastrointestinal tract are becoming more common among Thai people especially in the elderly. Manometry is a new and useful technique in the diagnosis and management of anorectal disorders. This cross-sectional study aimed to measure anorectal manometric parameters in normal Thai subjects. MATERIAL AND METHOD Thirty healthy Thai subjects (17 males and 13 females) were studied. They completed a questionnaire assessing their bowel function. A water-perfused manometric system with non-pull-through technique was used to monitor pressure in the rectum and anus. All subjects were asked to squeeze the anal sphincters, bear down, then blow up a party balloon. Rectal sensation and recto-anal inhibitory reflex were also assessed by intermittent phasic balloon distention. Simulated defecation or balloon expulsion test was also performed. RESULT The study revealed the following anorectal manometric parameters. The mean with standard deviation of the resting, squeezed, and sustained squeezed pressures were 55.4 +/- 15.3, 170.3 +/- 81.7 and 109.3 +/- 54.4 mm Hg respectively. Men had a longer anal sphincter (p = 0.01) and higher squeezed, and sustained squeezed pressures (p < 0. 001) compared to women, while their resting sphincter pressures were similar. Threshold volumes for rectal sensation and desire to defecate were not different among male and female subjects, but the threshold for urgency to defecate was higher in men. The study yielded normal anorectal manometric parameters in Thai subjects. Some parameters vary with gender. It is difficult to compare these normal ranges in Thai subjects to those in Caucasians, as the number of subjects is rather small and the details of instruments and techniques always vary from lab to lab. The manometric findings in these Thai subjects create more understanding in anorectal physiology and can be used as a guideline for the investigation of anorectal function in a symptomatic Thai population in a motility clinic.
Sheep pulmonary adenomatosis: characterization of two pathological forms associated with jaagsiekte retrovirus.

Pathological and immunohistochemical studies were performed on the lungs of 10 sheep with lesions of "classical" sheep pulmonary adenomatosis (SPA) and six sheep with "atypical" lung tumours. Lung tumour samples and other tissues from the same 16 animals were tested for the presence of jaagsiekte retrovirus (JSRV) by a polymerase chain reaction (PCR) that amplified a portion of the U3 long terminal repeat. The differences in the gross appearance of the classical and atypical forms paralleled the histopathological differences. The latter mainly concerned the stroma of the tumours which in the atypical cases was more heavily infiltrated by inflammatory cells and connective tissue fibres. JSRV major capsid protein was detected immunohistochemically in the epithelial transformed cells of both classical and atypical tumours, but the immune reactivity was slightly milder in atypical SPA. Proviral U3 sequences of JSRV were detected by specific PCR in all the tumour samples. Furthermore, the sequences of amplimers obtained from the two different pathological forms of the tumour were very similar. However, the dissemination of JSRV to other organs was greater in sheep with classical SPA than in those with atypical SPA. The pathological and virological features of these two forms of tumour are compared in an attempt to clarify whether classical and atypical SPA are two separate diseases or different expressions of a single disease spectrum.