Miracle-dz/UniFAR-FTUs huggingface dataset:
Bispyridinium Compounds Inhibit Both Muscle and Neuronal Nicotinic Acetylcholine Receptors in Human Cell Lines

Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs. Here, we have investigated the structural requirements for antagonism and compared inhibitory potency of these compounds at muscle and neuronal nicotinic receptors and acetylcholinesterase. A series of compounds was synthesised, in which the length of the polymethylene linker between the two pyridinium moieties was increased sequentially from one to ten carbon atoms. Their effects on nicotinic receptor-mediated calcium responses were tested in muscle-derived (CN21) and neuronal (SH-SY5Y) cells. Their ability to inhibit acetylcholinesterase activity was tested using human erythrocyte ghosts. In both cell lines, the nicotinic response was inhibited in a dose-dependent manner and the inhibitory potency of the compounds increased with greater linker length between the two pyridinium moieties, as did their inhibitory potency for human acetylcholinesterase activity in vitro. These results demonstrate that bispyridinium compounds inhibit both neuronal and muscle nicotinic receptors and that their potency depends on the length of the hydrocarbon chain linking the two pyridinium moieties. Knowledge of structure-activity relationships will aid the optimisation of molecular structures for therapeutic use against the nicotinic effects of organophosphorus poisoning.
Exact Spectral Dimension of the Random Surface

We propose a new method of the analytical computation of the spectral dimension which is based on the equivalence of the random walk and the q-state Potts model with non-zero magnetic field in the limit $q\to 0$. Calculating the critical exponent of the magnetization of this model on the dynamically triangulated random surface by means of a matrix model technique we obtain that the spectral dimension of this surface is equal to two.
Are Adverse Events of Nevirapine and Efavirenz Related to Plasma Concentrations?

Objective The relationships between adverse events (AEs) and plasma concentrations of nevirapine (NVP) and efavirenz (EFV) were investigated as part of the large, international, randomized 2NN study. Methods Treatment-naive, HIV-1-infected patients received NVP (once or twice daily), EFV or their combination, each in combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Concentrations of NVP and EFV were quantitatively assessed by a validated HPLC assay. Individual Bayesian estimates of the area under the plasma concentration–time curve over 24 h (AUC24h), and minimum and maximum plasma concentrations (Cmin and Cmax) as measures for drug exposure of NVP and EFV, were generated using a previously developed population pharmacokinetic model. Pharmacokinetic parameters were compared for patients with and without central nervous system (CNS) and psychiatric AEs, hepatic events, liver enzyme elevations (LEEs) and rash. Furthermore, it was investigated whether a clear cut-off for a pharmacokinetic parameter could be identified above which the incidence of AEs was clearly increased. AEs were also related to demographic parameters and baseline characteristics. Results In total, from 1077 patients, NVP (3024 samples) and EFV (1694 samples) plasma concentrations and AE data (825 observations) were available. For all patients Cmin, Cmax and AUC24h were determined. When corrected for known covariates of gender, CD4 cell count at baseline, region, hepatitis coinfection and possible interactions between these factors, no significant associations between AEs and any tested exposure parameter of NVP was observed. Also, no target Cmin value, above which patients were at increased risk for AEs, could be established. On the other hand, geographical region, hepatitis coinfection, CD4 cell count and gender were found to be significantly related with the incidence of CNS and psychiatric AEs, hepatic events, LEEs and rash during the treatment with NVP. The occurrence of elevated liver enzymes during the first 6 weeks in the EFV-containing arm was significantly (P=0.036) correlated to the exposure of EFV (Cmin). Only hepatitis coinfection impacted on LEEs during the first 6 weeks of treatment. With an EFV Cmin above 2.18 mg/l during the induction phase, patients were 4.4 (range 1.3–15.5) times more at risk for elevated liver enzymes. No other correlations between AEs and EFV pharmacokinetics or patient characteristics could be identified. Conclusions Pharmacokinetic parameters of NVP did not have a relationship to AEs in the 2NN trial when corrected for known covariates. The value of periodical drug monitoring of NVP as a way to prevent toxicity is therefore limited. Treating physicians should instead focus on factors that are more predictive of AEs (gender, CD4 count and hepatitis coinfection). High EFV Cmin levels resulted in elevated liver enzyme values during the first 6 weeks of treatment. Regular measurement of EFV levels and liver enzymes at the start of therapy may therefore be advised.
Simplified Configuration of Brillouin Optical Correlation-Domain Reflectometry

We develop a simple and cost-efficient configuration of Brillouin optical correlation-domain reflectometry (BOCDR), the setup of which does not include an additional reference path used in standard BOCDR systems. The Fresnel-reflected light from an open end of a sensing fiber is used as reference light. The limitations of spatial resolution, measurement range, and their ratio are theoretically clarified, and then, a distributed strain measurement with a <; 100-mm spatial resolution and a 4.1-m measurement range is demonstrated with a high signal-to-noise ratio.
Canine Myocardial Reperfusion Injury: Its Reduction by the Combined Administration of Superoxide Dismutase and Catalase

Therapy directed against the toxic effects of reactive oxygen species may reduce the final extent of ischemic injury in otherwise viable tissue irreversibly injured by the abrupt reoxygenation of reperfusion. In four groups of dogs, superoxide dismutase plus catalase (groups I—III) or saline (controls) (group IV) was infused into the left atrium. Group I received the infusion for 2 hours, beginning 15 minutes before occlusion of the left circumflex coronary artery (90 minutes) and ending 15 minutes after reperfusion. Group II received the infusion for 1 hour starring 15 minutes before reperfusion. Group III received the infusion for 1 hour beginning 40 minutes after reperfusion. Dogs were killed the next day, and infarct size was determined by dissection and weighing, and confirmed histologically. Infarct size expressed as percent of the anatomic area at risk was: group I, 19.4 ± 5.0; group II, 21.8 ± 3.3; group III, 47.6 ± 10.3; group IV, 43.6 ± 3.5 (mean ± sem). Analysis of variance followed by Duncan's multiple range test showed that ultimate infarct size as assessed in groups I and II differed significantly (P < 0.05) from that observed in the control animals in group IV, whereas infarct size between groups III and IV did not differ significantly (P > 0.05). The percent of left ventricle at risk did not differ between the four groups. The beneficial effects of superoxide dismutase plus catalase could not be explained by hemodynamic differences. Similar protection of jeopardized myocardium in groups I and II suggest that potentially viable tissue is salvaged by scavenging free radicals during early reperfusion. Lack of protection in group III suggests that injury has occurred within the first 40 minutes of reperfusion. The results of this investigation demonstrate that the ‘primary’ myqcardial cellular damage due to ischemia is additive to the cardiac cell damage during the phase of reperfusion, and that the “secondary” effects are mediated by toxic metabolites of oxygen.
Optimal Planning of Loop-Based Microgrid Topology

In microgrid planning, topological design is a critical concern for ensuring certain features such as high reliability in islanded operation. This paper proposes a graph partitioning and integer programming integrated methodology for the optimal loop-based microgrid topology planning while considering the distributed energy resources in the microgrid. The proposed methodology is applied to a microgrid test system and the planning results are discussed. The results demonstrate that the proposed planning methodology is able to accurately and efficiently determine an optimal loop structure for microgrids, and exhibit the potentials for applying the proposed planning methodology in practical microgrid applications.
[Ramadan fasting in type 2 diabetes mellitus].

This study was designed to assess the effects of fasting during Ramadan on weight, blood pressure, metabolic control and plasma lipoproteins in diabetic patients. This study was conducted in December 2000 (Ramadan 1421) when the length of fasting was 12 hours a day. It included 38 type 2 diabetic patients (20 males and 18 females). Mean patient age was 51.410. 5 years and mean body mass index (BMI) 28.94. 7kg/m2. Three patients were treated with diet and 35 with oral hypoglycemic agents. Clinical and biochemical parameters were evaluated during three periods: three weeks before Ramadan (T0), at the fourth week of Ramadan (T1) and three weeks after the end of Ramadan (T2). During the month of Ramadan, a decrease in weight (0.52kg) and no change in blood pressure were observed. No metabolic complication occurred in our patients. A significant effect of Ramadan fasting was observed on glycemic control and lipoprotein levels. In patients whose fructosamine level before Ramadan was higher than 340micromol/l, plasma fasting glucose and serum fructosamine increased during Ramadan (p<0.003) and returned to initial levels at the end of Ramadan T2; in these patients also, a decrease of HDL-cholesterol (p<0.01) associated with an increase of LDL-cholesterol (p<0.003) were observed at T1 and disappeared at T2. But, in patients whose fructosamine level at T0 was lower than 340micromol/l, no effect on glycemic control and no significant effect on serum lipoprotein levels were found during Ramadan month. Ramadan fasting in type 2 diabetic patients seems to cause slight effects on glycemia and lipoprotein levels when previous metabolic control is quite good; but fasting induces more deterioration when previous control is poor.
Perceived Prejudice and the Mental Health of Chinese Ethnic Minority College Students: The Chain Mediating Effect of Ethnic Identity and Hope

As a multinational country incorporating 56 officially recognized ethnic groups, China is concerned with the mental health of members of minority ethnic groups, with an increasing focus on supporting Chinese ethnic minority college students. Nevertheless, in daily life, members of minority ethnic groups in China often perceive prejudice, which may in turn negatively influence their mental health, with respect to relative levels of ethnic identity and hope. To examine the mediating effects of ethnic identity and hope on the relationship between perceived prejudice and the mental health of Chinese ethnic minority college students, 665 students (18–26 years old; 207 males, 458 females; the proportion of participants is 95.38%) from nine colleges in the Guangxi Zhuang autonomous region and Yunnan and Guizhou provinces of China took part in our study, each completing adapted versions of a perceived prejudice scale, a multiethnic identity measure, an adult dispositional hope scale, and a general health questionnaire. Analysis of the results reveals that perceived prejudice negatively influences mental health through both ethnic identity and hope in Chinese ethnic minority college students. The total mediation effect was 54.9%. Perceived prejudice was found to negatively predict ethnic identity and hope, suggesting that perceived prejudice brings about a negative reconstruction of ethnic identity and hope mechanisms within the study's Chinese cultural context. The relationship between perceived prejudice and mental health was fully mediated by hope and the chain of ethnic identity and hope. Ethnic identity partially mediated the relationship between perceived prejudice and hope. The relationship between perceived prejudice and mental health mediated by ethnic identity was not significant, which suggests that the rejection–identification model cannot be applied to Chinese ethnic minority college students. This paper concludes by considering the limitations of our study and discussing the implications of its results for researchers and practitioners.
In-depth analysis of HIV-1 drug resistance mutations in HIV-infected individuals failing first-line regimens in West and Central Africa

Objective:In resource-limited countries, antiretroviral therapy (ART) has been scaled up, but individual monitoring is still suboptimal. Here, we studied whether or not ART had an impact on the frequency and selection of drug resistance mutations (DRMs) under these settings. We also examined whether differences exist between HIV-1 genetic variants. Design:A total of 3736 sequences from individuals failing standard first-line ART (n = 1599, zidovudine/stavudine + lamivudine + neviparine/efavirenz) were analyzed and compared with sequences from reverse transcriptase inhibitor (RTI)-naive individuals (n = 2137) from 10 West and Central African countries. Methods:Fisher exact tests and corrections for multiple comparisons were used to assess the significance of associations. Results:All RTI-DRM from the 2015 International Antiviral Society list, except F227C, and nine mutations from other expert lists were observed to confer extensive resistance and cross-resistance. Five additional independently selected mutations (I94L, L109I, V111L, T139R and T165L) were statistically associated with treatment. The proportion of sequences with multiple mutations and the frequency of all thymidine analog mutations, M184V, certain NNRTIS, I94L and L109I showed substantial increase with time on ART. Only one nucleoside and two nonnucleoside RTI-DRMs differed by subtype/circulating recombinant form. Conclusion:This study validates the global robustness of the actual DRM repertoire, in particular for circulating recombinant form 02 predominating in West and Central Africa, despite our finding of five additional selected mutations. However, long-term ART without virological monitoring clearly leads to the accumulation of mutations and the emergence of additional variations, which limit drug options for treatment and can be transmitted. Improved monitoring and optimization of ART are necessary for the long-term effectiveness of ART.
The Complete Genome Sequence of Cupriavidus metallidurans Strain CH34, a Master Survivalist in Harsh and Anthropogenic Environments

Many bacteria in the environment have adapted to the presence of toxic heavy metals. Over the last 30 years, this heavy metal tolerance was the subject of extensive research. The bacterium Cupriavidus metallidurans strain CH34, originally isolated by us in 1976 from a metal processing factory, is considered a major model organism in this field because it withstands milli-molar range concentrations of over 20 different heavy metal ions. This tolerance is mostly achieved by rapid ion efflux but also by metal-complexation and -reduction. We present here the full genome sequence of strain CH34 and the manual annotation of all its genes. The genome of C. metallidurans CH34 is composed of two large circular chromosomes CHR1 and CHR2 of, respectively, 3,928,089 bp and 2,580,084 bp, and two megaplasmids pMOL28 and pMOL30 of, respectively, 171,459 bp and 233,720 bp in size. At least 25 loci for heavy-metal resistance (HMR) are distributed over the four replicons. Approximately 67% of the 6,717 coding sequences (CDSs) present in the CH34 genome could be assigned a putative function, and 9.1% (611 genes) appear to be unique to this strain. One out of five proteins is associated with either transport or transcription while the relay of environmental stimuli is governed by more than 600 signal transduction systems. The CH34 genome is most similar to the genomes of other Cupriavidus strains by correspondence between the respective CHR1 replicons but also displays similarity to the genomes of more distantly related species as a result of gene transfer and through the presence of large genomic islands. The presence of at least 57 IS elements and 19 transposons and the ability to take in and express foreign genes indicates a very dynamic and complex genome shaped by evolutionary forces. The genome data show that C. metallidurans CH34 is particularly well equipped to live in extreme conditions and anthropogenic environments that are rich in metals.
Influence of resistant starch alone or combined with wheat bran on gastric emptying and protein digestion in healthy volunteers

Objective. Resistant starch (RS) is not absorbed in the small intestine, but is partly fermented in the colon and may positively influence putative risk factors for colon cancer. The purpose of the study was to investigate the influence of RS type 3 (retrograded amylose) alone or combined with wheat bran on gastric emptying (GE) and protein assimilation. Material andmethods. GE and protein assimilation were investigated by means of breath-test technology in 20 healthy volunteers who were randomly divided into two groups, each subject performing two tests. In each test, the volunteers received a labelled test meal either as such or in combination with, respectively, 15 g RS3 or 15 g RS3 combined with 6 g wheat bran (WB). Breath samples were collected during the 6 h after administration of a test meal containing egg proteins, intrinsically labelled with 13C-leucine, to measure protein digestion and sodium-14C-octanoate for measurement of GE. Results. Intake of RS3 +WB did not influence GE time compared to baseline values, whereas intake of RS3 seemed to hasten GE: from 93±32 min to 55±15 min (p=0.012). The overall protein assimilation parameters at baseline were not significantly different from those obtained after simultaneous intake of RS3 +WB, whereas RS3 significantly shortened the time of maximum excretion compared to baseline, but the extent of protein digestion after RS3 intake was not affected (12.54±3.60% versus 13.43±3.40%). Conclusions. The presence of RS3 alone or in combination with wheat bran demonstrates that there are no adverse effects on protein digestion and no influence on the nitrogen supply to the colon.
Effect of Vinpocetine (Cognitol™) on Cognitive Performances of a Nigerian Population

Background: Chronic medical disorders are often complicated by cognitive impairments, making medical intervention that can alleviate cognitive disturbances desirable. Vinpocetine enhances cerebral utilization of oxygen and glucose and consequently improves cerebral functions including memory. Aim: This study assessed the efficacy of vinpocetine (Cognitol™) in improving memory and concentration in cognitively impaired patients. Subjects and Methods: A prospective analytical study of 56 cognitively impaired patients compared with age, sex and level of education matched 56 controls. Cognitive performance was assessed with the Short Blessed Test, which was pilot-tested. Baseline cognitive performances of the patients and controls were obtained and thereafter cognitive performances of the patients were assessed at 6 and 12 weeks after administration of vinpocetine at a dose of 5 mg twice-a-day. Comparative analysis of their performances at baseline was done using the Student t-test, while the improvement in patients′ performances and effect of disease variables on cognitive performances were analyzed with one-way analysis of variance and likelihood ratio analysis respectively. Results: The mean (standard deviation) [SD] ages of the cognitively impaired patients (56/112) and controls (56/112) were 49.5 (18.9) and 53.8 (15.8) years respectively (P = 0.19; 95% confidence interval [CI]: 2.2-10.8). The pilot study yielded an optimal cut-off error score of 6 with a sensitivity of 71.4%, specificity of 96.4% and accuracy of 83.9%. Patients performed significantly worse than the controls (P < 0.001; 95% CI 6.7-11.4). There were significant improvements in memory and concentration with vinpocetine therapy (P < 0.05). The clinical variables of the patients had no effect on the trend of cognitive performances. Conclusions: Vinpocetine was effective in improving memory and concentration of patients with epilepsy and dementia although the efficacy was minimal in demented patients.
Optimal management of common acquired melanocytic nevi (moles): current perspectives

Although common acquired melanocytic nevi are largely benign, they are probably one of the most common indications for cosmetic surgery encountered by dermatologists. With recent advances, noninvasive tools can largely determine the potential for malignancy, although they cannot supplant histology. Although surgical shave excision with its myriad modifications has been in vogue for decades, the lack of an adequate histological sample, the largely blind nature of the procedure, and the possibility of recurrence are persisting issues. Pigment-specific lasers were initially used in the Q-switched mode, which was based on the thermal relaxation time of the melanocyte (size 7 μm; 1 μsec), which is not the primary target in melanocytic nevus. The cluster of nevus cells (100 μm) probably lends itself to treatment with a millisecond laser rather than a nanosecond laser. Thus, normal mode pigment-specific lasers and pulsed ablative lasers (CO2/erbium [Er]:yttrium aluminum garnet [YAG]) are more suited to treat acquired melanocytic nevi. The complexities of treating this disorder can be overcome by following a structured approach by using lasers that achieve the appropriate depth to treat the three subtypes of nevi: junctional, compound, and dermal. Thus, junctional nevi respond to Q-switched/normal mode pigment lasers, where for the compound and dermal nevi, pulsed ablative laser (CO2/Er:YAG) may be needed. If surgical excision is employed, a wide margin and proper depth must be ensured, which is skill dependent. A lifelong follow-up for recurrence and melanoma is warranted in predisposed individuals, although melanoma is decidedly uncommon in most acquired melanocytic nevi, even though histological markers may be seen on evaluation.