Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of different therapeutic strategies in hypertension: a low-dose combination of perindopril/indapamide versus a sequential monotherapy or a stepped-care approach

Objective To compare the efficacy and the tolerability of three different strategies in the treatment of hypertension (low-dose combination, sequential monotherapy and stepped-care). Design Hypertensive patients were randomized to a 9-month treatment with the aim to lower blood pressure below 140/90 mmHg. Treatment adjustments were allowed at months 3 and 6. The study was discontinued for patients with normal blood pressure at month 6. In the ‘low-dose combination’ group, perindopril (2 mg) and indapamide (0.625 mg) were first administered with the possibility to increase the doses in two steps up to respectively, 4 and 1.25 mg. In the ‘sequential monotherapy’ group, the treatment was initiated with atenolol (50 mg), replaced if necessary by losartan (50 mg), and then by amlodipine (5 mg). In the ‘stepped-care’ group, valsartan, was given first at a 40 mg dose, then at a 80 mg dose, to be co-administered finally if needed with hydrochlorothiazide, 12.5 mg. All study tablets were encapsulated to conceal their identity and had to be taken once a day. Patients Patients with uncomplicated essential hypertension were recruited (n = 180 in the ‘low-dose combination’ group, n = 176 in the ‘sequential monotherapy’ group and n = 177 in the ‘stepped-care’ group). Results The percentage of patients having achieved the target blood pressure was significantly greater in the ‘low-dose combination’ group (62%) than in the ‘sequential monotherapy’ (49%, P = 0.02) and the ‘stepped-care’ group (47%, P = 0.005). The percentage of patients having normalized their blood pressure without experiencing drug-related adverse events was also significantly higher in the ‘low-dose combination’ group (56%) than in the ‘sequential monotherapy’ (42%, P = 0.002) and the ‘stepped-care’ group (42%, P = 0.004). Conclusions A first line management of hypertension based on a low-dose combination of perindopril and indapamide allows the normalization of blood pressure in significantly more patients than a ‘sequential monotherapy’ strategy involving atenolol, losartan and amlodipine, and a ‘stepped-care’ strategy involving valsartan and hydrochlorothiazide. These better blood pressure results were not obtained at the expense of a worsening of tolerability.
Randomized efficacy and safety trial of once‐daily remogliflozin etabonate for the treatment of type 2 diabetes

The sodium‐dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12‐week, double‐blind, randomized, placebo‐ and active‐controlled, parallel‐group study. A total of 252 newly diagnosed and drug‐naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0–≤9.5% (53–80 mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000 mg once daily or 250 mg twice daily), placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose–response relationship for change from baseline in HbA1c at week 12 (p < 0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed.
Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy

Mutations in the GABAA receptor γ2 subunit are associated with childhood absence epilepsy and febrile seizures. To understand better the molecular basis of absence epilepsy in man, we developed a mouse model harboring a γ2 subunit point mutation (R43Q) found in a large Australian family. Mice heterozygous for the mutation demonstrated behavioral arrest associated with 6-to 7-Hz spike-and-wave discharges, which are blocked by ethosuximide, a first-line treatment for absence epilepsy in man. Seizures in the mouse showed an abrupt onset at around age 20 days corresponding to the childhood nature of this disease. Reduced cell surface expression of γ2(R43Q) was seen in heterozygous mice in the absence of any change in α1 subunit surface expression, ruling out a dominant-negative effect. GABAA-mediated synaptic currents recorded from cortical pyramidal neurons revealed a small but significant reduction that was not seen in the reticular or ventrobasal thalamic nuclei. We hypothesize that a subtle reduction in cortical inhibition underlies childhood absence epilepsy seen in humans harboring the R43Q mutation.
Therapeutic Relationships and Boundary Maintenance: The Perspective of Forensic Patients Enrolled in a Treatment Program for Violent Offenders

To extend current knowledge about therapeutic relationships and boundary maintenance with the incarcerated forensic patient, the focus of this naturalistic inquiry was the exploration of the perspectives of forensic patients enrolled in a treatment program for violent offenders. Twelve male participants were interviewed three times. Eight of the twelve participants were interviewed a fourth time for the purpose of soliciting their feedback regarding the researcher's analysis of the data. Analysis of the data collected revealed a core process--the development of "therapeutic" relationships--indicating that the development of relationships was a complex process. Consistent with the participants' tendency to use terms analogous to a house to describe their experiences, the analogy of a house was used to describe the five interrelated themes that emerged from the data. If the interpersonal relationship is the heart of nursing then forensic mental health nurses need to understand the complexity of therapeutic relationships from the perspective of their patients.
Helicobacter pylori induces apoptosis in gastric mucosa through an upregulation of Bax expression in humans.

BACKGROUND Maintenance of gastric mucosal integrity depends on the balance between cell loss due to apoptosis and cell proliferation. Helicobacter pylori induces apoptosis in gastric epithelial cells, but the regulation of this process has been little studied. The Bcl-2 proteins are the best-studied family of proteins involved in the mechanism of apoptotic death. Some members of this family, such as Bcl-2, inhibit apoptosis, whereas others, such as Bax, induce it. The present study was performed to determine the apoptosis rate and mRNA and protein expression for Bax and Bcl-2 in the gastric mucosa of duodenal ulcer (DU) patients with H. pylori infection before and after H. pylori eradication. We recruited 8 H. pylori-negative control subjects and 20 DU patients (H. pylori-positive) given a 1-week triple therapy to eradicate H. pylori. The apoptosis was analyzed by means of terminal deoxyribonucleotide transferase-mediated digoxigenin-11-deoxyuridine triphosphate biotin nick-end labeling (TUNEL) staining, and the expression of mRNA for Bax and Bcl-2 by reverse transcription polymerase chain reaction (RT-PCR) and Southern blot. In all patients gastritis was assessed histologically on the basis of the Sydney classification, the presence of H. pylori, and analysis of cagA status. RESULTS All 20 DU patients were H. pylori-positive, and 18 (90%) were CagA-positive. The apoptotic cells were infrequently identified in gastric surface epithelium by TUNEL histochemistry in H. pylori-negative controls. In DU patients infected with H. pylori, apoptotic cells were more numerous and seen deep in the gastric glands. The infection was associated with significantly upregulated expression of mRNA and protein for Bax and suppressed mRNA and protein expression for Bcl-2, as determined using RT-PCR and Western blot analysis. The Bax overexpression was significantly stronger in the antrum than in the corpus of H. pylori-infected patients. Four weeks after the eradication a marked decrease of neutrophil infiltration, an improvement of the grade of gastritis (mononuclear infiltration), and significant reduction in apoptosis rate were observed. After eradication the Bax mRNA expression was still at an increased level, whereas the Bcl-2 mRNA expression remained suppressed. CONCLUSIONS 1) H. pylori induces apoptosis in the gastric epithelium, at least in part, due to an upregulation of proapoptotic Bax and downregulation of antiapoptotic Bcl-2, and 2) Bax mRNA and protein expression was higher in the antrum than in the corpus, and this was probably due to greater inflammatory changes observed in the antrum than in the corpus.
Effect of negative-pressure wound therapy on open fractures of the lower limb.

INTRODUCTION Early debridement and coverage has long been regarded as the standard of care for open fractures of the lower limb, as infection is a serious complication. However, the best time for wound closure remains controversial. Negative-pressure wound therapy (NPWT) is thought to result in reduced flap infection and failure. To determine the effect of NPWT, we reviewed patients with open fractures of the lower limb and compared the rates of infection and flap failure in two time-based cohorts. METHODS Two cohorts of patients (periods 2003-2004 and 2008-2009) with Gustilo type IIIB open tibial fractures were recruited and their outcomes were compared. In the 2003-2004 cohort, wounds were dressed with occlusive dressing. In the 2008-2009 cohort, all patients underwent NPWT. Data was retrospectively analysed with regard to infection, failure, age, type of flap, comorbidities and defect size. The incidences of infection and flap failure were further analysed for any statistical difference between the different treatment protocols. RESULTS In the 2003-2004 cohort, 33% of patients developed infection and 11% had flap failure. However, in the 2008-2009 cohort, 10% of patients developed infection and 6% had flap failure. The difference in the incidence of infection was statistically significant between the two cohorts (p = 0.029). CONCLUSION Patients in the 2008-2009 cohort had better outcomes, and we are of the opinion that performing NPWT may have contributed to this result.
Transcriptional Induction of Collagenase-1 in Differentiated Monocyte-like (U937) Cells is Regulated by AP-1 and an Upstream C/EBP-β Site*

In this report, we demonstrate that the AP-1 site and a distal promoter element regulate transcriptional induction of collagenase-1 during monocytic differentiation. Chloramphenicol acetyltransferase expression constructs containing regions of the human collagenase-1 promoter were stably or transiently transfected into U937 cells, and reporter activity was assessed at various times after the onset of phorbol 12-myristate 13-acetate (PMA)-mediated differentiation. Rapid and strong induction of promoter activity was lost in constructs with a mutant AP-1 element; however, at 16–96 h post-PMA, the mutant collagenase-1 promoter displayed AP-1 independent PMA-mediated transactivation. The AP-1 mutant constructs also showed delayed transcriptional activation in PMA-treated fibroblasts. Western and supershift analyses indicated that functional Jun and Fos proteins were present in nuclear extracts of PMA-differentiated U937 cells. Promoter deletion constructs demonstrated the potential role of distal promoter sequences in regulating collagenase-1 transcription. In particular, Western, supershift, and promoter deletion analyses suggested a role for CCAAT/enhancer-binding protein-β (C/EBP-β) binding site between −2010 and −1954 in regulating transcription of collagenase-1 in monocytic cells. Our findings suggest that distinct regulatory elements, acting somewhat independently of each other, control expression of collagenase-1. In addition, our data suggests that the rapid PMA-mediated induction of collagenase-1 transcription is controlled by a mechanism distinct from that regulating the sustained expression of this proteinase in activated macrophages.
Association of Quality Physical Education Teaching with Students’ Physical Fitness

USA Abstract This study examined the extent to which four essential dimensions of quality physical education teaching (QPET) were associated with healthy levels of physical fitness in elementary school students. Participants were nine elementary PE teachers and 1, 201 fourth- and fifth-grade students who were enrolled in nine elementary schools. The students’ physical fitness were assessed using four FITNESSGRAM tests. The PE teachers’ levels of QPET were assessed using the Assessing Quality Teaching Rubrics (AQTR). The AQTR consisted of four essential dimensions including Task Design, Task Presentation, Class Management, and Instructional Guidance. Codes were confirmed through inter-rater reliability (82.4% and 84.5%). Data were analyzed through descriptive statistics, multiple R-squared regression models, and independent sample t -tests. The four essential teaching dimensions of QPET were significantly associated with the students’ cardiovascular endurance, muscular strength and endurance, and flexibility. However, they accounted for relatively low percentage of the total variance in PACER test, followed by Curl-up test, while explaining very low por-tions of the total variance in Push-up and Trunk Lift tests. This study indicated that the students who had experienced high level of QPET were more physically fit than their peers who did not have this experience in PACER and Curl-up tests, but not in Push-up and Trunk lift tests. In addition, the significant contribution of the four essential teaching dimensions to physical fitness components was gender-specific. It was concluded that the four teaching dimensions of QPET were significantly associated with students’ health-enhancing physical
The Underlying Structure of Adaptation under Strong Selection in 12 Experimental Yeast Populations

ABSTRACT The aims of this study were to determine (i) whether adaptation under strong selection occurred through mutations in a narrow target of one or a few nucleotide sites or a broad target of numerous sites and (ii) whether the programs of adaptation previously observed from three experimental populations were unique or shared among populations that underwent parallel evolution. We used archived population samples from a previous study, representing 500 generations of experimental evolution in 12 populations under strong selection, 6 populations in a high-salt environment and 6 populations in a low-glucose environment. Each set of six populations included four with sexual reproduction and two with exclusively asexual reproduction. Populations were sampled as resequenced genomes of 115 individuals and as bulk samples from which frequencies of mutant alleles were estimated. In a high-salt environment, a broad target of 11 mutations within the proton exporter, PMA1, was observed among the six populations, in addition to expansions of the ENA gene cluster. This pattern was shared among populations that underwent parallel evolution. In a low-glucose environment, two programs of adaptation were observed. The originally observed pattern of mutation in MDS3/MKT1 in population M8 was a narrow target of a single nucleotide, unique to this population. Among the other five populations, the three mutations were shared in a broad target, sensing/signaling genes RAS1 and RAS2. RAS1/RAS2 mutations were not observed in the high-salt populations; PMA1 mutations were observed only in a high-salt environment.
D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina

Activation of D2-like dopamine receptors in rods with quinpirole stimulates L-type calcium currents (ICa). This result appears inconsistent with studies showing that D2-like dopamine receptor activation diminishes rod signals in second-order retinal neurons. Since small reductions in [Cl−]i can inhibit photoreceptor ICa, we tested the hypothesis that enhancement of ICa with the D2/D4 receptor agonist, quinpirole, increases calcium-activated chloride currents (ICl(Ca)) causing an efflux of Cl− from rods that would provide a negative feedback inhibition of ICa. In agreement with studies from Xenopus, quinpirole reduced rod input to second-order neurons of tiger salamander retina without significantly altering rod voltage responses. Quinpirole also diminished the amplitude of depolarization-evoked increases in [Ca2+]i measured with Fura-2 in rods, a finding consistent with inhibition of synaptic transmission from rods. Electrophysiological and Cl−-imaging experiments indicated ECl in rods is ∼ −20 mV. Quinpirole enhanced ICl(Ca) and elicited an efflux of Cl− at the resting potential. A similar Cl− efflux was produced by extracellular replacement of 24 mM Cl− with CH3SO4− and this low Cl− solution inhibited Ca2+responses to a similar degree as quinpirole did. When ICl(Ca) was inhibited with niflumic acid, quinpirole enhanced both ICa and depolarization-evoked increases in [Ca2+]i. Furthermore, with niflumic acid, quinpirole no longer inhibited rod inputs into horizontal and bipolar cells. These results suggest an initial enhancement of ICa by quinpirole is followed by a stimulation of Cl− currents, including ICl(Ca). The net result is a Cl− efflux that inhibits depolarization-evoked increases in [Ca2+]i and synaptic transmission from rods.
Cost-effectiveness analysis of quadrivalent versus trivalent influenza vaccine in Taiwan: A lifetime multi-cohort model

ABSTRACT A government-funded trivalent influenza vaccine (TIV) program to prevent seasonal influenza was implemented in Taiwan since 1998. However, mismatch between the vaccine and circulating strains may occur. Alternatively, a quadrivalent influenza vaccine (QIV) includes all 4 influenza lineages could minimize the risk of mismatches. Therefore, QIV could be considered as an alternative strategy to enhance protection against seasonal influenza. The objective of the study was to analyze, from a governmental perspective, the cost-effectiveness of using QIV vs. TIV as a vaccination strategy in Taiwan. A lifetime multi-cohort, static Markov model was constructed with 9 age groups to assess the costs and effectiveness of QIV vs. TIV. Direct costs were obtained from a database released by the Ministry of Health and Welfare. Outcomes included life-years gained, quality-adjusted life years (QALYs) gained, influenza cases avoided and incremental cost-effectiveness ratios (ICERs). The discount rate of costs and effectiveness was set at 3.5% and the time horizon used in the model was 100 y. Results show that a vaccination strategy utilizing QIV instead of TIV would bring an additional 10,557 QALYs at an extra cost of US$39.4 million, yielding an ICER of US$3,015.07 per QALY gained. When setting the willingness-to-pay threshold at US$10,000, compared to TIV, the probability that QIV would be cost-effective was 98%. Sensitivity analyses show that ICER was sensitive to the changes of circulation of influenza virus subtypes and vaccine mismatch. From a governmental perspective, the QIV vaccination could be considered as a cost-effective strategy within the context of public health in Taiwan.
Extramammary Paget's Disease of the Perianal Region: A Review of the Literature Emphasizing Management

BACKGROUD Perianal Paget's disease is a rare malignant condition affecting the epidermal apocrine gland that is usually complicated, with a confusing clinical picture, and diagnosis is therefore often delayed. Although, more than 100 years has gone by since its first description by Darier and Coulillaud in 1893, proper treatment guidelines have yet to be established. OBJECTIVE To review the available literature, emphasizing various current treatment strategies and aiming to increase clinicians' awareness of this rare disease, along with its management, for better practice and improvement of patient prognosis. METHODS The review of the concerned literature was done by searching and compiling data available on PubMed, Medline, and other databases using the key words “perianal Paget's disease,” “extramammary Paget's disease,” “intraepithelial adenocarcinoma,” and “apocrine glands. ” CONCLUSIONS Surgery is the mainstay of treatment. Some noninvasive therapeutic modalities were also reported to be effective, such as photodynamic therapy, imiquimod, radiotherapy, chemotherapy, anti‐androgen therapy, and carbon dioxide. Management of perianal Paget's disease remains difficult, and large controlled, multicentric studies should be performed to compare the effectiveness of current thera‐peutic modalities.
Anger and aggression in psychiatric outpatients.

BACKGROUND This study sought to evaluate the degree of anger and aggression experienced by psychiatric outpatients and to determine whether anger is as prominent an emotional state in these patients as are depression and anxiety. We also sought to determine which Axis I and Axis II disorders were associated with increased rates of subjective anger and aggressive behavior. METHOD 1300 individuals presenting to a psychiatric outpatient practice underwent semistructured interviews to evaluate current DSM-IV Axis I (N = 1300) and Axis II disorders (N = 687). Levels of subjective anger and aggression during the preceding week were assessed in each patient, and the odds ratios were calculated for each disorder. A multiple regression analysis was performed to determine which psychiatric disorders independently contributed to the presence of subjective anger and aggressive behavior. RESULTS Approximately one half of our sample reported currently experiencing moderate-to-severe levels of subjective anger, and about one quarter had demonstrated aggressive behavior in the preceding week. This level of anger was found to be comparable to the levels of depressed mood and psychic anxiety reported by our sample. Major depressive disorder, bipolar I disorder, intermittent explosive disorder, and cluster B personality disorders independently contributed to the presence of both anger and aggression. CONCLUSION Anger and aggression are prominent in psychiatric outpatients to a degree that may rival that of depression and anxiety; it is therefore important that clinicians routinely screen for these symptoms.
Contribution of Calcium Channel Subtypes to the Intracellular Calcium Signal in Sensory Neurons: The Effect of Injury

Background:Although the activation-induced intracellular Ca2+ signal is disrupted by sensory neuron injury, the contribution of specific Ca2+ channel subtypes is unknown. Methods:Transients in dissociated rat dorsal root ganglion neurons were recorded using fura-2 microfluorometry. Neurons from control rats and from neuropathic animals after spinal nerve ligation were activated either by elevated bath K+ or by field stimulation. Transients were compared before and after application of selective blockers of voltage-activated Ca2+ channel subtypes. Results:Transient amplitude and area were decreased by blockade of the L-type channel, particularly during sustained K+ stimulation. Significant contributions to the Ca2+ transient are attributable to the N-, P/Q-, and R-type channels, especially in small neurons. Results for T-type blockade varied widely between cells. After injury, transients lost sensitivity to N-type and R-type blockers in axotomized small neurons, whereas adjacent small neurons showed decreased responses to blockers of R-type channels. Axotomized large neurons were less sensitive to blockade of N- and P/Q-type channels. After injury, neurons adjacent to axotomy show decreased sensitivity of K+-induced transients to L-type blockade but increased sensitivity during field stimulation. Conclusions:All high-voltage–activated Ca2+ current subtypes contribute to Ca2+ transients in sensory neurons, although the L-type channel contributes predominantly during prolonged activation. Injury shifts the relative contribution of various Ca2+ channel subtypes to the intracellular Ca2+ transient induced by neuronal activation. Because this effect is cell-size specific, selective therapies might potentially be devised to differentially alter excitability of nociceptive and low-threshold sensory neurons.