Miracle-dz/UniFAR-FTUs huggingface dataset:
Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis.

OBJECTIVE Melatonin is involved in the regulation of the sleep-wake cycle and exhibits multiple interactions with the neuroendocrine and the immune system. Melatonin secretion in healthy individuals follows a stable circadian rhythm. Critical illness, continuous administration of drugs, and loss of external zeitgeber might impair the circadian rhythm of melatonin secretion in the intensive care unit (ICU), thereby compromising the physiologic stress-induced immune response. DESIGN Prospective, controlled clinical study. SETTING Medical intensive care unit in a university hospital. PATIENTS Seventeen septic, sedated ICU patients (group A); 7 nonseptic ICU patients (group B); and 21 control patients (group C) were studied. MEASUREMENTS AND MAIN RESULTS 6-Sulfatoxymelatonin (aMT6s) was determined from urine samples taken at 4-hr intervals over a total period of 24 hrs. aMT6s was measured by enzyme-linked immunosorbent assay. Circadian mesors, phase amplitudes, and timing of the acrophase were assessed by cosinor analysis. Differences between groups were calculated by contingency data analysis and by analysis of variance. Circadian mesors of urinary aMT6s were 3904 +/- 1597, 2622 +/- 927, and 3183 +/- 1514 ng/4 hrs in groups A, B, and C, respectively (p = NS). aMT6s exhibited significant circadian periodicity in only 1/17 (6%) patients of group A but in 6/7 (86%) patients of group B and in 18/23 (78%) patients of group C (group A vs. groups B and C: p = .0001) Phase amplitudes were markedly lower in group A (1071 +/- 1005 ng/4 hrs) compared with group B (2284 +/- 581 ng/4 hrs, p = .009) and C (2838 +/- 2255 ng/4 hrs, p = .006). The acrophase was significantly delayed in patients of group A (10:35 am +/- 255 mins) compared with group B (05:43 am +/- 114 mins, p = .01) and group C (4:20 am +/- 107 mins, p < .0001). In sepsis survivors, aMT6s excretion profiles tended to normalize, but still lacked a significant circadian rhythm at ICU discharge. CONCLUSION The present study revealed striking abnormalities in urinary aMT6s excretion in septic ICU patients. In contrast, circadian rhythm was preserved in nonseptic ICU patients, indicating that impaired circadian melatonin secretion in septic patients is mainly related to the presence of severe sepsis and/or concomitant medication. Further investigations are required to examine the underlying pathophysiologic mechanism and the clinical implications of this finding.
Pharmacotherapy of Alzheimer Disease

Objective: To systematically review published clinical trials of the pharmacotherapy of Alzheimer disease (AD). Method: We searched MEDLINE for published English-language medical literature, using Alzheimer disease and treatment as key words. No other search engine was used. Our review focused on randomized clinical trials (RCTs) and corresponding metaanalyses. Results: Although there are many RCTs for the treatment of mild cognitive impairment (MCI), none have been successful in their primary analysis. The cholinesterase inhibitors donepezil, rivastigmine, and galantamine have demonstrated efficacy in 3- to 12-month placebo-controlled RCTs assessing cognitive, functional, behavioural, and global outcomes in patients with mildly to moderately severe AD. Recent data from patients with severe stages of AD demonstrate the efficacy of donepezil on cognitive and functional measures but not on behaviour. The N-methyl-D-aspartate receptor antagonist memantine has been demonstrated to be effective in 6-month, placebo-controlled RCTs of 6 months duration assessing cognitive, functional, and global outcomes of inpatients with moderate-to-severe AD (defined as a Mini Mental State Examination score below 20). Post hoc analyses have demonstrated a benefit in regard to agitation and (or) aggression, but this needs to be confirmed in a prospective RCT across Canada. Disease-modifying treatments are being tested in mild stages of AD in 18-month RCTs with cognitive and global outcomes as primary efficacy outcomes, primarily with drugs reducing amyloid synthesis or aggregation. Successful treatment in mild stages of AD could lead to RCTs in MCI and, possibly, in genetically high-risk asymptomatic individuals. Conclusion: The significant advances in the symptomatic pharmacotherapy of AD may be followed by disease-modification treatments.
M1 Receptor-Mediated Nitric Oxide-Dependent Relaxation Unmasked in Stomach Fundus from M3 Receptor Knockout Mice

Muscarinic receptors can mediate both contractile and relaxant responses in smooth muscle. The stomach fundus from wild-type mice possesses a neuronal M1 receptor that mediates relaxation to carbamylcholine and (4-hydroxy-2-butynyl)-1-trimethylammonium-3-chlorocarbanilate chloride (McN-A-343) but is masked by M3 receptor-mediated contraction to both agonists. When the M3 receptor was deleted, cholinergic-induced relaxation was unmasked. M1receptor antagonism with pirenzepine, nitric oxide (NO) synthase inhibition withN ω-nitro-l-arginine methyl ester hydrochloride, and inhibition of neuronal activation with tetrodotoxin abolished relaxation to McN-A-343 in tissues from M3 receptor knockout mice, supporting the neuronal localization of an M1 receptor that activated NO release to effect relaxation. However, the cyclooxygenase inhibitor indomethacin did not affect contraction or relaxation to carbamylcholine in stomach fundus from wild-type or M3 receptor knockout mice, indicating that cyclooxygenase products played no role in these responses. The neuronal M1 receptor modulated relaxation induced by carbamylcholine and McN-A-343 but not relaxation induced by electric field stimulation of the stomach fundus. These data support the presence of M1 receptor-mediated relaxation in the stomach and suggest that when the M3 receptor is eliminated or blocked, M1 receptor-mediated gastric relaxation may be enhanced, possibly leading to alterations in gastric emptying and subsequent effects on body weight.
Regression of left ventricular hypertrophy with echocardiography: some lessons from the LIVE study

Objective Large trials on left ventricular hypertrophy (LVH) regression are indispensable to allow accurate evaluation of the different classes of treatments. Such a trial, the LIVE study, gave us the opportunity to examine the influence of the mode of reading of the echo tracings on results and to underline the value of two initial recordings performed at entry. Methods The LIVE study was designed to compare 1.5 mg indapamide SR with 20 mg enalapril on the regression of LVH evaluated echocardiographically. M-mode tracings of the left ventricle were performed at selection and after a 2 week placebo run-in. Recordings were read by investigators and by three experts all through the study, and finally read again by the three experts blind to treatment and sequence. Results The two initial examinations produced an estimate of the reproducibility of the measurement of the left ventricular mass (LVM) that can be proposed as an indicator of overall quality provided no patients are excluded. The standard deviation of the differences between these two estimates of LVM was 52 g. These two examinations may also help quantify regression to the mean, which was not significant for the whole group. Knowledge of the sequence of examinations overestimates the change in LVM with treatment, as shown by comparison of measurements carried out during quality control with the measurements made blind (−19 ± 52 versus −6 ± 53 g, P < 0.01). Conclusions The comparison of two initial echoes at entry allow one to define a quality criteria for such trials and to quantify a possible regression to the mean. The reading of recordings with knowledge of sequence significantly overestimates LVM variations on treatment.
RRT-A* Motion planning algorithm for non-holonomic mobile robot

The RRT algorithm can deal with the motion planning problems in consideration of non-holonomic differential constraints, but it does not taken into consideration the optimal path problem in planning process. Random selection of nodes leads to every planning cost relatively different because of only use of metric function in new node selection. In this paper, an improved heuristic RRT-A* algorithm is proposed for robot motion planning with non-holonomic constraints. In this algorithm, the cost function of A-Star(A*) is introduced into the RRT algorithm to optimize the performance. Meanwhile, several metric functions are used as the heuristic information functions respectively to measure the performance of different metric function. The simulation results shown that the Manhattan heuristic information function based RRT-A* planning algorithm is better than the other improved RRT algorithms in optimization path and computational cost.
Histological and clinical evaluation of 3 different grafting materials for sinus lifting procedure based on 8 cases.

BACKGROUND The reconstruction of edentulous patients with adequate bone volume and density by using dental implants has become a viable treatment option with high predictability. However, initial stabilization is difficult to achieve in the posterior maxillary regions where cortical bone is thin or absent due to severely resorbed alveolar ridges. Maxillary sinus lift procedures applied with various grafting materials enable clinicians to place implant-supported prostheses even in cases with increased pneumatization of the maxillary sinus. METHODS The purpose of this study was to evaluate histologically and clinically different grafting materials used in maxillary sinus floor augmentation. Deproteinized bovine bone granules (DBBG), demineralized freeze-dried bone powder (DFBP), and porous hydroxyapatite (PHA) were used as grafting materials. A total of 19 implants in 8 patients were placed into grafted sites. In 3 patients, a 2-stage approach was used wherein implants were inserted after a 6-month healing period following a sinus lift procedure. Specimens were taken with a trephine drill, and the site of the specimen was enlarged to accept an implant. For the remaining cases, a 1-stage approach, which included sinus lifting and implant placement, was used and bone biopsies were taken during the uncovering stage. After 6 months of healing, fixed prosthetic restorations were fabricated. RESULTS The healing period progressed without any complications, and all implants were loaded. The mean functioning time was 12 months, varying from 9 to 24 months. CONCLUSION The results indicate that DFBP resorbs earlier than PHA and DBBG in sinus lift procedures.
Imbalance of T-Cell Subsets in Angiotensin II–Infused Hypertensive Rats With Kidney Injury

Abstract—Blockade of angiotensin (Ang) II is efficient in various renal diseases. Although interest has focused on the hemodynamic changes and reduction of proteinuria, recent studies emphasize the nonhemodynamic effects of Ang II on kidney injury. The aim of this study was to clarify the mechanisms of Ang II on the immune system that alter the balance of helper T-cell (Th) subsets. We used a continuous, Ang II infusion model of rats that develop hypertension, proteinuria, and tubulointerstitial damage, including de novo expression of &agr;-smooth muscle actin and loss of endothelial cells. We isolated T cells from the spleen and measured cytokine levels by ELISA systems. Ang II–infused rats showed an increase in the Th1 cytokine &ggr;-interferon and a decrease in the Th2 cytokine interleukin-4. The same change in cytokine mRNA expression in the spleen and kidney was confirmed by quantitative polymerase chain reaction analysis. Our ELISPOT assay showed an increase in the number of &ggr;-interferon–secreting T cells by Ang II. To investigate whether these changes were specific effects of Ang II, we treated the model rats with the Ang II receptor blocker (ARB) olmesartan or the nonspecific vessel dilator hydralazine. Administration of the ARB ameliorated disease manifestations and the imbalance in Th subsets, whereas hydralazine did not, despite comparable effects on blood pressure. These results demonstrate a direct role of Ang II in the modification of Th balance. The imbalance of Th subsets was associated with hypertensive kidney injury induced by Ang II. Some of the beneficial effects of ARBs might be explained by their immunomodulatory reactions.
State of the art of short dental implants: a systematic review of the literature.

BACKGROUND Short implants (≤8 mm) are manufactured for use in atrophic regions of the jaws. As implant length in many studies has been proven to play a major role in implant survival it is indicated to evaluate survival of short implants in the present literature. PURPOSE The purpose of this study was systematically to evaluate publications concerning short dental implants defined as an implant with a length of ≤8 mm installed in the maxilla or in the mandible with special reference to implant type, survival rate, location of implant site, and observation time. MATERIALS AND METHODS A Medline and a hand search were conducted to identify studies concerning short dental implants of length ≤8 mm published between 1992 and October 2009. The articles included in this study report data on implant length ≤8 mm, implant surface, registered region of installment, observation time, single tooth restorations, supporting overdentures, splinted implants, and implants used for prostheses. RESULTS The 27 included studies represent zero randomized clinical trial studies, 15 prospective nonrandomized, noncontrolled clinical trials, 11 retrospective nonrandomized, noncontrolled clinical trials, and one review. Data on 6-mm implants were few and most frequent represented was manufactured Straumann implants representing 441 out of 549 implants. Brånemark implants, 7 mm in length, comprised 1607 implants out of 1808. Straumann implants, 8 mm in length, comprised 2040 out of 2352 implants. Failures varied between 0 and 14.5%, 0 and 37.5% and 0 and 22.9% of the 6-, 7-, and 8-mm-long implants, respectively. CONCLUSION Short implant length was not related to observation time, installment region, failures, and dropouts were not specified, subsequently a meta-analysis was not possible to perform.
A Longitudinal Study of Radiation-Induced Changes in Tumor Vasculature by Contrast-Enhanced Magnetic Resonance Imaging

Abstract Yu, H. , Su, M-Y. , Wang, Z. and Nalcioglu O. , A Longitudinal Study of Radiation-Induced Changes in Tumor Vasculature by Contrast-Enhanced Magnetic Resonance Imaging. Radiat. Res. 158, 152–158 (2002). Dynamic contrast-enhanced MRI with two different-sized contrast agents, Gd-DTPA and Gadomer-17, was used to study the effects of radiation on the pharmacokinetics of the paramagnetic enhancement of water relaxation in the rat R3230 AC adenocarcinoma tumor model. The kinetics of enhancement was analyzed by a two-compartment pharmacokinetic model to derive parameters related to vascular volume (Vb) and permeability (K2). Rats implanted with tumors were divided into two groups; one received 5 Gy and the other received 20 Gy 137Cs γ rays. Sequential dynamic contrast-enhanced MRI studies were performed, one before irradiation, one at day 1 after irradiation, and another at day 3 after irradiation, to investigate the effect of the radiation dose and the changes that occurred over time. The analysis was performed on a pixel-by-pixel basis to study the heterogeneity within the tumor. The pixel distribution profiles of Vb and K2 from each tumor were obtained to assess the regional radiation-induced effects on vascular volume and permeability. No significant change in vascular volume was detected with either Gd-DTPA or Gadomer-17 after irradiation of the tumor; however, a small dependence of K2 on the radiation dose was observed. After low-dose (5 Gy) irradiation, the mean value of K2 decreased by 46% at day 1 compared to the baseline, presumably due to cell swelling, and decreased further by 67% from the baseline on day 3. When the dose was increased to 20 Gy, the mean value of K2 measured with Gadomer-17 did not show any significant changes at either day 1 or day 3 after irradiation. The value of K2 measured with Gd-DTPA did not show any significant changes after either the low or the high radiation dose.
Costs and benefits of a United Kingdom exit from the European Union

Is it possible to take part in the economic advantages of the European project without having to bear the associated political costs of relinquishing sovereignty? Proponents of the United Kingdom leaving the European Union – the Brexit (“British Exit”) – believe that the answer to this question is yes.2 Opponents see economic unification above all as a means for creating a political community in Europe. And many pragmatists think that true, deep economic integration without a minimum of common political institutions is impossible. Therefore, the idea of gaining economic advantages without sacrificing a certain amount of political leeway is simply fiction. You can’t have your cake and eat it, too. We can’t have both things at the same time - the benefits of deep economic integration and complete political flexibility.
Credit, Financial Conditions and the Business Cycle in China

This paper presents empirical evidence of the role of financial conditions in China’s business cycle. We estimate a Bayesian-VAR for the Chinese economy, incorporating a financial conditions index for China that captures movements across a range of financial variables, including interest rates and interbank spreads, bond returns, and credit and equity flows. We impose sign restrictions on the impulse response functions to identify shocks to financial conditions and shocks to monetary policy. The model suggests that monetary policy, credit and financial conditions have played an important role in shaping China’s business cycle. Using conditional scenarios, we examine the role of credit in shaping economic outcomes in China over the past decade. Those scenarios underscore the important role of credit growth in supporting activity during the past decade, particularly the surge in credit following the global financial crisis in 2008. The financial tightening since the end of 2016 has contributed to a modest slowing of credit growth and activity. JEL Classification: E32, E44, E51, E17
The Use of Videogames as Complementary Therapeutic Tool for Cognitive Behavioral Therapy in Bulimia Nervosa Patients

Although cognitive behavioral therapy (CBT) has been demonstrated to be the most effective approach for the treatment of bulimia nervosa (BN), there is lack of studies showing whether a combination with a serious video game (SVG) might be useful to enhance patients' emotional regulation capacities and general outcome. The aims of this study were (a) to analyze whether outpatient CBT + SVG, when compared with outpatient CBT - SVG, shows better short-term outcome; (b) to examine whether the CBT + SVG group is more effective in reducing emotional expression and levels of anxiety than CBT - SVG. Thirty-eight patients diagnosed as having BN according to DSM-5 criteria were consecutively assigned to two outpatient group therapy conditions (that lasted for 16 weekly sessions): 20 CBT + SVG versus 18 CBT - SVG. Patients were assessed before and after treatment using not only a food and binging/purging diary and clinical questionnaires in the field of eating disorders but also additional indexes for measuring anger expression and anxiety. Regarding the post-treatment psychometric measures, most of the mean differences (Eating Disorder Inventory-2, Symptom Checklist-Revised, State-Trait Anxiety Index, and partially State-Trait Anger Expression Inventory) achieved moderate to high effect size (d > 0.5), in the sense that CBT + SVG obtained the best results compared with the CBT - SVG group. Regarding therapy outcome (dropout, partial remission, and total remission), CBT + SVG showed better results and a moderate effect size emerged for the comparison of the risk of dropout during the treatment, being higher for CBT - SVG compared with CBT + SVG (44.1 percent versus 20.0 percent, d = 0.54). Although the sample size in our study was low, and consequently results should be considered with caution, we have obtained promising findings suggesting that in the short-term CBT + SVG might be a good option not only for improving emotional dysregulation and approaching the current limitations of CBT - SVG in BN but also for enhancing the therapy adherence of patients.
CYP3A5 Polymorphism and the Ethnic Differences in Cyclosporine Pharmacokinetics in Healthy Subjects 1

To determine the relationship between CYP3A5 polymorphism and cyclosporine pharmacokinetic parameters among healthy volunteers, an oral cyclosporine (CsA) pharmacokinetic study was performed in 16 healthy subjects. Blood CsA concentrations were measured by high-performance liquid chromatography. Concentration-versus-time data were analyzed by a noncompartmental method using WinNonLin, and the blood samples were genotyped for the CYP3A5 using the polymerase chain reaction and pyrosequencing. CsA pharmacokinetic parameters were dichotomized and compared using the 1-way ANOVA test according to the CYP3A5*3C genotype. There were 6 homozygous A/A (wild type), 6 homozygous G/G (variant), and 4 heterozygous A/G genotypes for CYP3A5*3 C in these 16 healthy volunteers. All whites were G/G group, and all African Americans except 1 were either A/A or A/G group. The mean AUC (ng·h/mL) of CsA for the 3 genotype groups were 4962 ± 1074 (A/A), 6677 ± 1153 (G/G), and 5416 ± 1817 (A/G), (A/A versus G/G, P = 0.03), and the mean CL/F (mL/min/kg) were 15.6 ± 3.1 (A/A), 12.0 ± 2.3 (G/G), and 14.7 ± 5.9 (A/G), (A/A versus G/G, P = 0.04). None of the other parameters were significantly different among the 3 genotypes. In conclusion, the CYP3A5*3C polymorphism appears to affect AUC and CL/F of oral CsA significantly in healthy subjects, which may partly explain some of the differences of pharmacokinetics in CsA between African Americans and whites.
Is real depreciation or more government deficit expansionary? The case of Macedonia

The paper finds that real depreciation of the denar reduces real GDP and that more government deficit spending as a percent of GDP raises real GDP. In addition, a lower world real interest rate, a higher lagged world real income, a lower real oil price or a lower expected inflation would increase real GDP. It suggests that the negative impact of real depreciation such as higher import costs and domestic inflation and less international capital inflows dominates the positive impact of real depreciation such as more exports.
Neutrophil to lymphocyte ratio: a novel marker for predicting hospital mortality of patients with acute type A aortic dissection

Introduction: The inflammatory process has been reported to be associated with aortic dissection (AD) from the development to the prognosis. The aim of the study was to investigate a relationship between the neutrophil to lymphocyte ratio (NLR) and in-hospital outcomes in patients with acute aortic dissection (AAD) who underwent surgical repair. Methods: One hundred and eighty-four patients who were admitted with the diagnosis of type A AAD who underwent surgical repair at two large tertiary hospitals. According to their NLR, 91 patients had high NLR (>6.0) and 93 patients had low NLR (⩽6.0). Results: The frequency of major bleeding, hospital-related infection, multi-organ dysfunction and mortality in hospital were higher in the high NLR group compared to the low NLR group. NLR, WBC count and operation duration were found to be independent predictors for in-hospital mortality. Conclusions: The novel inflammatory marker NLR may be used to predict worse outcomes and hospital mortality in patients with AAD treated by surgical repair.
Association of Obesity‐Related Hemodilution of Prostate‐Specific Antigen, Dihydrotestosterone, and Testosterone

Prostate‐specific antigen (PSA) hemodilution is the leading theory for lower PSA values in obese men. However, testosterone and dihydrotestosterone (DHT), which are necessary for PSA production, are reduced in obese men. We assessed the relationship of body mass index (BMI) and PSA, taking into consideration the effect of testosterone and DHT.