Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and Characterization of Recombinant Rat Acyl-CoA Synthetases 1, 4, and 5

Inhibition by triacsins and troglitazone of long chain fatty acid incorporation into cellular lipids suggests the existence of inhibitor-sensitive and -resistant acyl-CoA synthetases (ACS, EC 6.2.1.3) that are linked to specific metabolic pathways. In order to test this hypothesis, we cloned and purified rat ACS1, ACS4, and ACS5, the isoforms present in liver and fat cells, expressed the isoforms as ACS-Flag fusion proteins in Escherichia coli, and purified them by Flag affinity chromatography. The Flag epitope at the C terminus did not alter the kinetic properties of the enzyme. Purified ACS1-, 4-, and 5-Flag isoforms differed in their apparent K m values for ATP, thermolability, pH optima, requirement for Triton X-100, and sensitivity to N-ethylmaleimide and phenylglyoxal. The ACS inhibitor triacsin C strongly inhibited ACS1 and ACS4, but not ACS5. The thiazolidinedione (TZD) insulin-sensitizing drugs and peroxisome proliferator-activated receptor γ (PPARγ) ligands, troglitazone, rosiglitazone, and pioglitazone, strongly and specifically inhibited only ACS4, with an IC50 of less than 1.5 μm. Troglitazone exhibited a mixed type inhibition of ACS4. α-Tocopherol, whose ring structure forms the non-TZD portion of troglitazone, did not inhibit ACS4, indicating that the thiazolidine-2,4-dione moiety is the critical component for inhibition. A non-TZD PPARγ ligand, GW1929, which is 7-fold more potent than rosiglitazone, inhibited ACS1 and ACS4 poorly with an IC50 of greater than 50 μm, more than 100-fold higher than was required for rosiglitazone, thereby demonstrating the specificity of TZD inhibition. Further, the PPARα ligands, clofibrate and GW4647, and various xenobiotic carboxylic acids known to be incorporated into complex lipids had no effect on ACS1, -4, or -5. These results, together with previous data showing that triacsin C and troglitazone strongly inhibit triacylglycerol synthesis compared with other metabolic pathways, suggest that ACS1 and ACS4 catalyze the synthesis of acyl-CoAs used for triacylglycerol synthesis and that lack of inhibition of a metabolic pathway by triacsin C does not prove lack of acyl-CoA involvement. The results further suggest the possibility that the insulin-sensitizing effects of the thiazolidinedione drugs might be achieved, in part, through direct interaction with ACS4 in a PPARγ-independent manner.
Colorimetric Indicator Based on Gold Nanoparticles and Sodium Alginate for Monitoring Fish Spoilage

In this work, a colorimetric indicator based on gold nanoparticles (AuNP) and a biodegradable and eco-friendly polymer (sodium alginate, Alg.), was developed for the real-time detection of fish spoilage products. The AuNPs and the colorimetric indicator were characterized using UV-VIS, FTIR spectroscopies, TGA, DSC, XRD, TEM, and colorimetry. The UV-VIS spectrum and TEM showed the successful synthesis, the spherical shape, and the size of AuNPs. The results indicated color changes of the indicator in packaged fish on day 9 of storage at a refrigerated temperature (5 °C. These results showed the successful application of the colorimetric indicator in the detection of TVB-N in packaged fish.
Trapidil (Triazolopyrimidine), a Platelet‐Derived Growth Factor Antagonist, Reduces Restenosis After Percutaneous Transluminal Coronary Angioplasty: Results of the Randomized, Double‐Blind STARC Study

BackgroundTrapidil is an antiplatelet drug with specific platelet- derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty. Methods and ResultsThe Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P < .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%; P = .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P < .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group. ConclusionsTrapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.
Mitochondrial DNA sequence context in the penetrance of mitochondrial t-RNA mutations: A study across multiple lineages with diagnostic implications

Mitochondrial DNA (mtDNA) mutations are well recognized as an important cause of inherited disease. Diseases caused by mtDNA mutations exhibit a high degree of clinical heterogeneity with a complex genotype-phenotype relationship, with many such mutations exhibiting incomplete penetrance. There is evidence that the spectrum of mutations causing mitochondrial disease might differ between different mitochondrial lineages (haplogroups) seen in different global populations. This would point to the importance of sequence context in the expression of mutations. To explore this possibility, we looked for mutations which are known to cause disease in humans, in animals of other species unaffected by mtDNA disease. The mt-tRNA genes are the location of many pathogenic mutations, with the m.3243A>G mutation on the mt-tRNA-Leu(UUR) being the most frequently seen mutation in humans. This study looked for the presence of m.3243A>G in 2784 sequences from 33 species, as well as any of the other mutations reported in association with disease located on mt-tRNA-Leu(UUR). We report a number of disease associated variations found on mt-tRNA-Leu(UUR) in other chordates, as the major population variant, with m.3243A>G being seen in 6 species. In these, we also found a number of mutations which appear compensatory and which could prevent the pathogenicity associated with this change in humans. This work has important implications for the discovery and diagnosis of mtDNA mutations in non-European populations. In addition, it might provide a partial explanation for the conflicting results in the literature that examines the role of mtDNA variants in complex traits.
Endometrial pathology in breast cancer patients: Effect of different treatments on ultrasonographic, hysteroscopic and histological findings

Breast cancer patients have an increased risk of endometrial pathology. To investigate whether the incidence of endometrial abnormalities and their clinicopathological features were affected by receiving tamoxifen (TAM), non-steroidal aromatase inhibitors (AIs) or no treatment (NT), 333 peri/postmenopausal breast cancer patients, who were referred to the Department of Gynecological, Obstetrical Sciences and Reproductive Medicine for gynecological assessment, were reviewed retrospectively. Transvaginal ultrasonographic (TVUS), hysteroscopic and histological findings were investigated. Endometrial histological findings included: atrophy in 61, 94.3 and 55.6% of cases in the TAM, AIs and NT groups, respectively; polyps in 30.9, 31.4 and 42.2% of cases in the TAM, AIs and NT groups, respectively; hyperplasia in 3% of patients in the TAM group and 11.1% of patients in the NT group; and cancer in 3.8% of cases in the TAM group and 11.1% of cases in the NT group. There was a significant correlation between the duration of TAM treatment and the severity of endometrial pathology. In all groups, there was a significant correlation between hysteroscopic and histological findings with regard to the diagnosis of endometrial atrophy, polyps, hyperplasia and cancer (P<0.001). In conclusion, these data revealed that there was a higher incidence of endometrial pathology in the NT group compared with the TAM group, which was significant for endometrial hyperplasia and cancer. The chance of developing high-risk histological subtypes of endometrial cancer was independent of TAM use. Lastly, although there was no significant difference in recurrent vaginal bleeding and mean endometrial thickness between the TAM and AIs groups, patients receiving AIs did not exhibit hyperplastic, dysplastic or neoplastic changes in the endometrium. This study indicates that breast cancer patients require screening for endometrial pathology; TVUS alone is useful in asymptomatic patients, however, in patients where the endometrial line is irregular or its thickness is >3 mm, hysteroscopy with directed biopsy is the appropriate diagnostic method.
The genus Catapyrenium s. lat. (Verrucariaceae) in the Iberian Peninsula and the Balearic Islands

Abstract A taxonomic treatment of the genera included in Catapyrenium s. lat. in the Iberian Peninsula and the Balearic Islands is provided, based on study of c. 2000 specimens from both herbaria and fresh material collected by the authors from 2005 to 2009 in numerous localities. A total of 33 species belonging to six of the eight genera included in Catapyrenium s. lat. are present in the region, which correspond to c. 80% of species from Europe. The genera are Anthracocarpon Breuss, Catapyrenium Flot. (Catapyrenium s. str.), Heteroplacidium Breuss, Involucropyrenium Breuss, Neocatapyrenium H. Harada and Placidium A. Massal. The genus Neocatapyrenium is reported for the first time from this region. Clavascidium liratum, the only representative of the genus Clavascidium in the region, has been reduced to synonymy with Anthracocarpon virescens. Heteroplacidium acervatum, H. congestum and Neocatapyrenium cladonioideum are new to Europe. Involucropyrenium pusillum, only previously known from Austria, I. waltheri, an arctic-alpine species, and Neocatapyrenium latzelii, known from Croatia and Greece, are cited for the first time in the Iberian Peninsula. Placidium subrufescens and P. tenellum, two mainly Mediterranean species, are also new records from the Iberian Peninsula. Placidium boccanum is here for the first time cited in Spain, and Anthracocarpon virescens, Heteroplacidium contumescens, Placidium imbecillum and P. michelii are new to Portugal. Most of the remaining species showed a considerable expansion of their known ranges. Placidium pyrenaicum is reduced to synonymy with P. velebiticum. Keys to genera and species occurring in the Iberian Peninsula and the Balearic Islands are presented.
Endoscopic Ultrasound-Guided Biliary Drainage Using a Fully Covered Metallic Stent after Failed Endoscopic Retrograde Cholangiopancreatography

Background and Study Aims. Endoscopic ultrasound- (EUS-) guided biliary drainage (EUS-BD) is an alternative treatment for biliary obstruction after failed endoscopic retrograde cholangiopancreatography (ERCP). In this study, we present the outcomes of inpatients with obstructive jaundice treated with EUS-BD using a fully covered metallic stent after failed ERCP. Patients and Methods. A total of 21 patients with biliary obstruction due to malignant tumors and prior unsuccessful ERCP underwent EUS via an intra- or extrahepatic approach with fully covered metallic stent between March 2014 and October 2015. A single endoscopist performed all procedures. Results. Seven patients underwent hepatogastrostomy (HGS) and 14 underwent choledochoduodenostomy (CDS). The technical and clinical success rates were both 100%. There was no difference in efficacy between HGS and CDS. Adverse events occurred in three patients, including two in the HGS group (1 bile leakage and 1 sepsis) and one in the CDS group (sepsis). Four patients died as a result of their primary tumors during a median follow-up period of 13 months (range: 3–21 months). No patient presented with stent migration. Conclusion. EUS-BD using a fully covered metallic stent appears to be a safe and effective method for the treatment of obstructive jaundice.
UHI Research Database pdf download summary A Website to promote physical activity in people with type 2 diabetes living in remote and rural locations: A feasibility pilot randomized controlled trial

Background: Research supports the use of Web-based interventions to promote physical activity in diabetes management. However, previous interventions have found poor levels of engagement or have not included health professionals and people with diabetes in the design of the tool. Objective: To develop and explore the feasibility and indicative effect of a Web-based physical activity promotion intervention in people diagnosed with type 2 diabetes living in remote or rural locations. Methods: A qualitative approach using focus groups that included patients with diabetes and health professionals were run to identify key concepts, ideas, and features, which resulted in the design of a physical activity website. This site was tested using a quantitative approach with a qualitative 6-month pilot study that adopted a three-armed approach. Participants were randomized into three groups: a control group who received written diabetes-specific physical activity advice; an information Web group, a Web-based group who received the information online; and an intervention Web group, an interactive Web-based group who received online information plus interactive features, such as an activity log, personalized advice, and goal setting. Results: A website was designed based on patient and health professional ideas for effective physical activity promotion. This website was tested with 31 participants, 61% (19/31) male, who were randomized into the groups. Website log-ins decreased over time: 4.5 times in month 1, falling to 3 times in month 6. Both the information Web group—mean 134.6 (SD 123.9) to mean 154.9 (SD 144.2) min—and the control group—mean 118.9 (SD 103.8) to mean 126.1 (SD 93.4) min, d=0.07—increased time spent in moderate-to-vigorous physical activity, but this decreased in the intervention Web group—mean 131.9 (SD 126.2) to mean 116.8 (SD 107.4) min. Conclusions: Access to online diabetes-specific physical information was effective in promoting physical activity in people with type 2 diabetes; access to interactive features was not associated with increases in activity. Trial Registration: International Standard Randomised Controlled Trial Number (ISRCTN): 96266587; http://www.isrctn. com/ISRCTN96266587 (Archived by WebCite at http://www.webcitation.org/6tzX6YesZ) (JMIR Diabetes 2017;2(2):e26) doi:10.2196/diabetes.6669
Interventions before consultations to help patients address their information needs by encouraging question asking: systematic review

Objective To assess the effects on patients, clinicians, and the healthcare system of interventions before consultations to help patients or their representatives gather information in consultations by question asking. Design Systematic review with meta-analysis. Data sources Electronic literature searches of seven databases and hand searching of one journal and bibliographies of relevant articles. Review methods Inclusion criteria included randomised controlled trials. Main outcome measures Primary outcomes were question asking; patients’ anxiety, knowledge, and satisfaction; and length of consultation. Results 33 randomised trials of variable quality involving 8244 patients were identified. A few studies showed positive effects. Meta-analyses showed small and statistically significantly increases in question asking (standardised mean difference 0.27, 95% confidence interval 0.19 to 0.36) and patients’ satisfaction (0.09, 0.03 to 0.16). Non-statistically significant changes occurred in patients’ anxiety before consultations (weighted mean difference −1.56, −7.10 to 3.97), patients’ anxiety after consultations (standardised mean difference −0.08, −0.22 to 0.06), patients’ knowledge (−0.34, −0.94 to 0.25), and length of consultation (0.10, −0.05 to 0.25). Interventions comprising written materials had similar effects on question asking, consultation length, and patients’ satisfaction as those comprising the coaching of patients. Interventions with additional training of clinicians had little further effect than those targeted at patients alone for patients’ satisfaction and consultation length. Conclusions Interventions for patients before consultations produce small benefits for patients. This may be because patients and clinicians have established behaviours in consultations that are difficult to change. Alternatively small increases in question asking may not be sufficient to make notable changes to other outcomes.
Development of Eczema Vaccinatum in Atopic Mouse Models and Efficacy of MVA Vaccination against Lethal Poxviral Infection

Smallpox vaccine based on live, replicating vaccinia virus (VACV) is associated with several potentially serious and deadly complications. Consequently, a new generation of vaccine based on non-replicating Modified vaccinia virus Ankara (MVA) has been under clinical development. MVA seems to induce good immune responses in blood tests, but it is impossible to test its efficacy in vivo in human. One of the serious complications of the replicating vaccine is eczema vaccinatum (EV) occurring in individuals with atopic dermatitis (AD), thus excluding them from all preventive vaccination schemes. In this study, we first characterized and compared development of eczema vaccinatum in different mouse strains. Nc/Nga, Balb/c and C57Bl/6J mice were epicutaneously sensitized with ovalbumin (OVA) or saline control to induce signs of atopic dermatitis and subsequently trans-dermally (t.d.) immunized with VACV strain Western Reserve (WR). Large primary lesions occurred in both mock- and OVA-sensitized Nc/Nga mice, while they remained small in Balb/c and C57Bl/6J mice. Satellite lesions developed in both mock- and OVA-sensitized Nc/Nga and in OVA-sensitized Balb/c mice with the rate 40–50%. Presence of mastocytes and eosinophils was the highest in Nc/Nga mice. Consequently, we have chosen Nc/Nga mice as a model of AD/EV and tested efficacy of MVA and Dryvax vaccinations against a lethal intra-nasal (i.n.) challenge with WR, the surrogate of smallpox. Inoculation of MVA intra-muscularly (i.m.) or t.d. resulted in no lesions, while inoculation of Dryvax t.d. yielded large primary and many satellite lesions similar to WR. Eighty three and 92% of mice vaccinated with a single dose of MVA i.m. or t.d. , respectively, survived a lethal i.n. challenge with WR without any serious illness, while all Dryvax-vaccinated animals survived. This is the first formal prove of protective immunity against a lethal poxvirus challenge induced by vaccination with MVA in an atopic organism.
Measuring Real-World Accuracies and Biases in Modeling Password Guessability

Parameterized password guessability--how many guesses a particular cracking algorithm with particular training data would take to guess a password--has become a common metric of password security. Unlike statistical metrics, it aims to model real-world attackers and to provide per-password strength estimates. We investigate how cracking approaches often used by researchers compare to real-world cracking by professionals, as well as how the choice of approach biases research conclusions. We find that semi-automated cracking by professionals outperforms popular fully automated approaches, but can be approximated by combining multiple such approaches. These approaches are only effective, however, with careful configuration and tuning; in commonly used default configurations, they underestimate the real-world guessability of passwords. We find that analyses of large password sets are often robust to the algorithm used for guessing as long as it is configured effectively. However, cracking algorithms differ systematically in their effectiveness guessing passwords with certain common features (e.g., character substitutions). This has important implications for analyzing the security of specific password characteristics or of individual passwords (e.g., in a password meter or security audit). Our results highlight the danger of relying only on a single cracking algorithm as a measure of password strength and constitute the first scientific evidence that automated guessing can often approximate guessing by professionals.
Pharmacokinetics of Multiple Doses of Valsartan in Patients With Heart Failure

Angiotensin II has adverse actions in heart failure including vasoconstriction, aldosterone secretion, and activation of the sympathetic nervous system. Valsartan, a potent specific angiotensin II type 1 receptor blocker, may produce beneficial effects in heart failure. The purpose of this study was to evaluate the steady-state pharmacokinetics of valsartan 40, 80, and 160 mg each given every 12 h for 7 days in heart failure patients. Eighteen patients with chronic stable heart failure and left ventricular ejection fractions ≤ 40% received each dosing regimen starting with the 40-mg dose. On day 7 of each dosing period, serial blood samples were obtained over 12 h for pharmacokinetic assessment. Results showed that the mean area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased in a linear and nearly proportional manner with valsartan dose. A dose-proportionality assessment, based on a statistical power model, showed that doubling the dose increased the AUC and Cmax 1.8 times. The pharmacokinetics of valsartan are predictable in heart failure patients within the dose range of 40–160 mg BID. Age did not appear to have influenced the valsartan clearance in heart failure patients. The pharmacokinetic values were higher in heart failure patients than in healthy volunteers. All doses were generally safe and well tolerated.