Patterns of Genetic Diversity and the Invasion of Commercial Starters in Saccharomyces cerevisiae Vineyard Populations of Santorini Island.
Autochthonous Saccharomyces cerevisiae vineyard populations are important components of the grape/wine system. Besides their direct impact on winemaking, they also constitute an untapped reservoir of genotypes with special technological attributes for the wine industry. Research so far on S. cerevisiae populations has focused on spatial distribution on large scales, yet little is known about the genetic variability of populations within viticultural zones and their temporal genotypic variation. Here, S. cerevisiae populations from different vineyards in Santorini, a small Aegean island, were genotyped and their genetic diversity was assessed within and between vineyards during two consecutive years. Despite the relative geographical isolation of the island, a relatively high genetic diversity was uncovered. The vast majority of genotypes were vineyard-specific, while in one of the vintages, significant differences in the genotypic composition of vineyards were detected. Overall, higher differences were detected between vintages rather than among vineyards. Notably, only four genotypes were common for the two vintages, three of which were commercial S. cerevisiae strains, probably "escapees" from wineries. Nevertheless, the populations of the two vintages were not genetically distinct. Present results highlight the magnitude of genetic diversity in natural wine yeast populations on a small spatial scale, yet the invasion of commercial starters may constitute a potential risk for loss of local yeast biodiversity. However, present results show that industrial strains do not necessarily dominate over the natural strains or their high abundance may be temporary.


Biased agonism of the angiotensin II type 1 receptor.
G protein-coupled receptors (GPCRs) can be activated by multiple ligands and exhibit the capacity to couple to numerous intracellular signal transduction pathways. This property allows GPCRs to be modulated by biased agonists that selectively activate specific subsets of GPCR-regulated cellular signaling proteins. The angiotensin II type 1 receptor (AT1R) is a GPCR that endogenously binds to the peptide ligand angiotensin II. More recently it has been demonstrated that a modified peptide, [Sar1I-le4-Ile8]-angiotensin II (SII) acts as a biased agonist towards the AT1R. SII binds to the AT1R without promoting heterotrimeric G protein-coupling, but serves to link the receptor to the beta-arrestin-dependent activation of the mitogen activated protein kinase pathway. The present mini-review summarizes current knowledge regarding the role of biased agonists in stimulating biased AT1R signaling.


Concern for dental appearance among Norwegian young adults in region with low uptake of orthodontic treatment.
The purpose of the present study was to examine orthodontic concern among orthodontically untreated young adults living in an area where the relative number of children receiving treatment was only 15-20% and to compare orthodontic concern among these individuals with that of untreated persons from an area with a higher treatment frequency. All the subjects were clinically examined and impressions for dental study casts, radiographs and photographs were taken. The subject's occlusion was classified according to two methods: 1) allocation to one of four groups according to the national Need for Orthodontic Treatment Index (NOTI), and 2) allocation to one of three groups according to presence or absence of six Anterior Occlusal Traits (AOT). Frequencies of NOTI scores demonstrated that in the study group more individuals were in need of treatment relative to the comparison group. Reported concern was at the same level in both groups, and significantly related to NOTI and AOT scores. The individuals in the area with the low treatment frequency were generally less aware of their anterior traits compared to the individuals in the area with a higher treatment frequency. The results indicated that a long-term low uptake of orthodontic treatment among children in the particular area was not accompanied by a similar increase in concern about own dental appearance in early adulthood.


Epidemiology and variables involved in dental abscess: survey of dental emergency unit in Trieste.
The objective of this epidemiologic study was to estimate the healing time of acute dental abscesses and to evaluate the main variables involved in the healing process itself. Among a sample of over 24 000 patients visited at the emergency dental unit, 688 subjects were diagnosed with dental abscess and enrolled in the study. Case histories of all patients were collected to investigate the clinical course and healing time of dental abscess according to anamnestic and diagnostic data and therapeutic management. A multiple logistic regression model was performed to evaluate the association of each variable with the healing time required for dental abscess. Variables associated with increased healing time were spring seasonality at admission, pyretic state, trismus, involvement of multiple anatomic spaces, and spontaneous drainage. Moreover, administration of some, but not all, classes of antibiotics was also associated with an increased healing time. The knowledge of variables involved in healing time for dental abscess is crucial in the optimization of managing such infections in terms of cost-benefit ratio. This would represent a valuable way to ensure a shortened and more effective healing.


The diagnosis of exocrine pancreatic disease: the present position reviewed.
In this paper, recent advances in the diagnosis of pancreatic disease are reviewed, together with older methods currently in use. The clinical role of these techniques in the diagnosis of pancreatic disease is discussed with particular reference to symptomatology and prognosis of the various pancreatic disorders. Likely future developments in this field are considered.


Biochemical characterization and crystallographic structure of an Escherichia coli protein from the phosphotriesterase gene family.
Phosphotriesterase homology protein (PHP) is a member of a recently discovered family of proteins related to phosphotriesterase, a hydrolytic, bacterial enzyme with an unusual substrate specificity for synthetic organophosphate triesters and phosphorofluoridates, which are common constituents of chemical warfare agents and agricultural pesticides. No natural substrate has been identified for phosphotriesterase, and it has been suggested that the enzyme may have evolved the ability to hydrolyze synthetic compounds in bacteria under selective pressure to meet nutritional needs. PHP, which has 28% sequence identity with phosphotriesterase, may belong to the family of proteins from which phosphotriesterase evolved. Here we report the cloning, expression, initial characterization, and high-resolution X-ray crystallographic structure of PHP. Biochemical analysis shows that PHP is monomeric and binds two zinc ions per monomer. Unlike phosphotriesterase, PHP does not catalyze the hydrolysis of nonspecific phosphotriesters. The structure, similar to that of phosphotriesterase, consists of a long, elliptical alpha/beta barrel and has a binuclear zinc center in a cleft at the carboxy end of the barrel at the location of the presumptive active site.


A Metagenomic Approach to Evaluating Surface Water Quality in Haiti.
The cholera epidemic that occurred in Haiti post-earthquake in 2010 has resulted in over 9000 deaths during the past eight years. Currently, morbidity and mortality rates for cholera have declined, but cholera cases still occur on a daily basis. One continuing issue is an inability to accurately predict and identify when cholera outbreaks might occur. To explore this surveillance gap, a metagenomic approach employing environmental samples was taken. In this study, surface water samples were collected at two time points from several sites near the original epicenter of the cholera outbreak in the Central Plateau of Haiti. These samples underwent whole genome sequencing and subsequent metagenomic analysis to characterize the microbial community of bacteria, fungi, protists, and viruses, and to identify antibiotic resistance and virulence associated genes. Replicates from sites were analyzed by principle components analysis, and distinct genomic profiles were obtained for each site. Cholera toxin converting phage was detected at one site, and Shiga toxin converting phages at several sites. Members of the Acinetobacter family were frequently detected in samples, including members implicated in waterborne diseases. These results indicate a metagenomic approach to evaluating water samples can be useful for source tracking and the surveillance of pathogens such as Vibrio cholerae over time, as well as for monitoring virulence factors such as cholera toxin.


Involvement of information professionals in patient- and family-centered care initiatives: a scoping review.
The goal of this scoping review was to collect data on patient- and family-centered care (PFCC) programs and initiatives that have included the direct involvement of librarians and information professionals to determine how librarians are involved in PFCC and highlight opportunities for librarians to support PFCC programs. Systematic literature searches were conducted in seven scholarly databases in the information, medical, and social sciences. Studies were included if they (1) described initiatives presented explicitly as PFCC programs and (2) involved an information professional or librarian in the PFCC initiative or program. Based on the definition of PFCC provided by the Institute for Patient- and Family-Centered Care, the authors developed a custom code sheet to organize data elements into PFCC categories or initiatives and outcomes. Other extracted data elements included how the information professional became involved in the program and a narrative description of the initiatives or programs. All included studies (n=12) identified patient education or information-sharing as an integral component of their PFCC initiatives. Librarians were noted to contribute to shared decision-making through direct patient consultation, provision of health literacy education, and information delivery to both provider and patient with the goal of fostering collaborative communication. The synthesis of available evidence to date suggests that librarians and information professionals should focus on patient education and information-sharing to support both patients or caregivers and clinical staff. The burgeoning efforts in participatory care and inclusion of patients in the decision-making process pose a unique opportunity for librarians and information professionals to offer more personalized information services.


Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme.
To evaluate the effect of an antifibrotic treatment by a combination of pentoxifylline (PTX) and tocopherol (vitamin E) in patients with a thin endometrium who were enrolled in an oocyte donation programme. Eighteen oocyte recipients who failed to develop a pre-ovulatory endometrial thickness of at least 6 mm after receiving vaginal micronized estradiol were enrolled in the study. The patients received a combination of PTX (800 mg/day) and vitamin E (1000 IU/day) for 6 months. The main outcome measurements were the change in endometrial thickness and the pregnancy and delivery rates after treatment. Endometrial thickness increased significantly (P <0.001), with a mean of (+/-SD) 4.9 +/-0.6 mm before and 6.2 +/- 1.4 mm after treatment, with 72% (13/18) of patients being good responders. Five patients either did not respond to the treatment or responded only slightly. Three patients, of which two had received previous radiotherapy, became spontaneously pregnant, and two became pregnant after embryo transfer. Three patients did not have embryo transfer. A total of four babies were delivered. The pregnancy rate was thus 33% and the delivery rate 27%. Treatment by combination of PTX and vitamin E appears to improve the pregnancy rate in patients with a thin endometrium by increasing the endometrial thickness and improving ovarian function. This was especially noticeable in patients who had previously received total body irradiation.


Development of the bioadhesive tetracaine gels for enhanced local anesthetic effects.
To develop the new local anesthetic formulations with a suitable bioadhesive property, hydroxypropyl methylcellulose (HPMC)-based gel was formulated. As the drug concentration in the gels, and the temperature of surrounding solutions increased, the drug release increased. The activation energy of tetracaine permeation was 4.47 kcal/mol. The effects of permeation enhancers on the permeation rate of drug through skin were studied using various enhancers, such as the glycols, the nonionic surfactants, and the bile salts. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest enhancing effects on drug permeation through skin. The analgesic activity was examined using a tail-flick analgesimeter. In the AUEC (area under the efficacy curve) of the rat-tail flick test, tetracaine gel containing polyoxyethylene 2-oleyl ether showed about 3.2-fold increase in analgesic activity compared with the control. The results of this study support that the tetracaine gels with efficient anesthetic effects could be developed using HPMC and poloxamer with combination of enhancer and vasoconstrictor.


Effect of tumor promote phorbol esters on the in vitro keratinization of rat epidermal cells in normal, premalignant and malignant stages.
The effect of skin tumor promote, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related phorbol esters on primary diploid and four established, i.e. two aneuploid premalignant and two malignant, lines of fetal rat epidermal cells wee analyzed. TPA quantitatively or qualitatively affected the keratinization processes of cultured epidermal cells in the concentration range of 10 - 1,000 ng/ml. Its inhibitory effect on keratinization was obvious in the lamellar keratinization processes of aneuploid premalignant epidermal cells. With a few exceptions, the inhibition was reversible. However, TPA lethally damaged the primary diploid epidermal cells in this range of concentration. TPA did not inhibit the keratinization of malignant epidermal cells but destroyed the polarity in their keratinization processes.


African Swine Fever in the Russian Far East (2019-2020): Spatio-Temporal Analysis and Implications for Wild Ungulates.
African swine fever (ASF) is an emerging viral contagious disease affecting domestic pigs (DP) and wild boar (WB). ASF causes significant economic damage to the pig industry worldwide due to nearly 100% mortality and the absence of medical treatments. Since 2019, an intensive spread of ASF has been observed in the Russian Far East region. This spread raises concerns for epidemiologists and ecologists given the potential threat to the WB population, which is an essential member of the region's wild ungulates and provides a notable share of food resources for predatory species. This study aims to determine the genotype of ASF virus circulating in the region, reveal the spatio-temporal patterns of the ASF outbreaks' emergence, and assess the potential reduction of the regional fauna because of expected depopulation of WB. The first historical case of ASF in the study region was caused by an African swine fever virus (ASFV) isolated from DPs and belonging to Genotype 2, CVR1; IGR-2 (TRS +). Sequencing results showed no significant differences among ASFV strains currently circulating in the Russian Federation, Europe, and China. The spatiotemporal analysis with the space-time permutations model demonstrated the presence of six statistically significant clusters of ASF outbreaks with three clusters in DPs and one cluster in WBs. DP outbreaks prevail in the north-west regions of the study area, while northern regions demonstrate a mixture of DP and WB outbreaks. Colocation analysis did not reveal a statistically significant pattern of grouping of one category of outbreaks around the others. The possible damage to the region's fauna was assessed by modeling the total body mass of wild ungulates before and after the wild boars' depopulation, considering a threshold density of WB population of 0.025 head/km2, according to the currently in force National Plan on the ASF Eradication in Russia. The results suggest the total mass of ungulates of the entire study region will likely decrease by 8.4% (95% CI: 4.1-13.0%), while it may decrease by 33.6% (19.3-46.1%) in the Primorsky Krai, thereby posing an undeniable threat to the predatory species of the region.


Multi-faceted functions of secretory IgA at mucosal surfaces.
Secretory IgA (SIgA) plays an important role in the protection and homeostatic regulation of intestinal, respiratory, and urogenital mucosal epithelia separating the outside environment from the inside of the body. This primary function of SIgA is referred to as immune exclusion, a process that limits the access of numerous microorganisms and mucosal antigens to these thin and vulnerable mucosal barriers. SIgA has been shown to be involved in avoiding opportunistic pathogens to enter and disseminate in the systemic compartment, as well as tightly controlling the necessary symbiotic relationship existing between commensals and the host. Clearance by peristalsis appears thus as one of the numerous mechanisms whereby SIgA fulfills its function at mucosal surfaces. Sampling of antigen-SIgA complexes by microfold (M) cells, intimate contact occurring with Peyer's patch dendritic cells (DC), down-regulation of inflammatory processes, modulation of epithelial, and DC responsiveness are some of the recently identified processes to which the contribution of SIgA has been underscored. This review aims at presenting, with emphasis at the biochemical level, how the molecular complexity of SIgA can serve these multiple and non-redundant modes of action.


First case of pneumonia caused by Cupriavidus pauculus in an infant in the Gulf Cooperation Council.
Cupriavidus pauculus is an emerging organism causing infections in immunocompromised and immunocompetent patients. We report a C.pauculus pneumonia case susceptible to cefepime in an infant with end-stage renal failure. To our knowledge, this is the first case report of C. pauculus causing respiratory infections in the Gulf Cooperation Council.


Atorvastatin Effectively Inhibits Ancestral and Two Emerging Variants of SARS-CoV-2 in vitro.
This article evaluated the in vitro antiviral effect of atorvastatin (ATV) against SARS-CoV-2 and identified the interaction affinity between this compound and two SARS-CoV-2 proteins. The antiviral activity of atorvastatin against this virus was evaluated by three different treatment strategies [(i) pre-post treatment, (ii) pre-infection treatment, and (iii) post-infection treatment] using Vero E6 and Caco-2 cells. The interaction of atorvastatin with RdRp (RNA-dependent RNA polymerase) and 3CL protease (3-chymotrypsin-like protease) was evaluated by molecular docking. The CC50s (half-maximal cytotoxic concentrations) obtained for ATV were 50.3 and 64.5 μM in Vero E6 and Caco-2, respectively. This compound showed antiviral activity against SARS-CoV-2 D614G strain in Vero E6 with median effective concentrations (EC50s) of 15.4, 12.1, and 11.1 μM by pre-post, pre-infection, and post-infection treatments, respectively. ATV also inhibited Delta and Mu variants by pre-post treatment (EC50s of 16.8 and 21.1 μM, respectively). In addition, ATV showed an antiviral effect against the D614G strain independent of the cell line (EC50 of 7.4 μM in Caco-2). The interaction of atorvastatin with SARS-CoV-2 RdRp and 3CL protease yielded a binding affinity of -6.7 kcal/mol and -7.5 kcal/mol, respectively. Our study demonstrated the in vitro antiviral activity of atorvastatin against the ancestral SARS-CoV-2 D614G strain and two emerging variants (Delta and Mu), with an independent effect of the cell line. A favorable binding affinity between ATV and viral proteins by bioinformatics methods was found. Due to the extensive clinical experience of atorvastatin use, it could prove valuable in the treatment of COVID-19.


1 alpha,25-Dihydroxyvitamin D3 inhibits gamma-interferon synthesis by normal human peripheral blood lymphocytes.
1 alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D3, inhibited synthesis of gamma-interferon (IFN-gamma) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-gamma protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)2D3 concentration (0.1 nM). 1,25-(OH)2D3 also inhibited accumulation of IFN-gamma mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)2D3 to modulate IFN-gamma protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-gamma synthesis by PBLs was specific for 1,25-(OH)2D3; the potencies of other vitamin D3 metabolites were correlated with their affinities for the cellular 1,25-(OH)2D3 receptor. The time course of 1,25-(OH)2D3 receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)2D3-mediated inhibition of IFN-gamma synthesis. In selected experiments, T-lymphocyte-enriched cell preparations were utilized. In these experiments, 1,25-(OH)2D3 was equally active as in PBL preparations. Finally, we examined the effects of 1,25-(OH)2D3 on the constitutive IFN-gamma production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-gamma synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)2D3, whereas IFN-gamma synthesis by Ab-VDR cells was not altered by 1,25-(OH)2D3. The data presented in this study provide further evidence for a role of 1,25-(OH)2D3 in immunoregulation.


[Functional status of neutrophils in patients with autoimmune thyroiditis].
The paper discusses the functional activity of peripheral neutrophilic granulocytes in 25 patients with autoimmune thyroiditis (AIT). The course of the latter is shown to be attended by a reduction in serum lactoferrin levels with simultaneous increases in the production of active oxygen forms and in the blood count of CD95+ granulocytes.


Clinical functional tests help identify elderly women highly concerned about falls.
BACKGROUND/STUDY CONTEXT: Limited research exists on functional tests in the discrimination of elderly individuals with high concern about falls from individuals with low concern about falls. The purpose of this study was to determine which functional test best discriminates between elderly women with low and high concern about falls. One hundred thirty-five elderly women (72.6 ± 4.8 years) were divided into two groups based on their Falls Efficacy Scale-International score: low concern (n = 56) and high concern (n = 79) about falls. Five functional tests were applied: Timed Up and Go test (TUG), unipodal stance test, five-repetition sit-to-stand test (5-STS), gait velocity, and grip strength. Factorial analysis and discriminant analysis were used. Factorial analysis resulted in three factors that explained 83.8% of the total variance. Factor 1, with 49.5% of total variance explanation, was represented by the TUG, 5-STS, and gait velocity tests and was the only factor to discriminate between the groups, classifying correctly 68.9% of the observations. Among the original variables of Factor 1, the Fisher linear coefficient showed that the TUG was the most discriminant of the tests. The TUG test best discriminates elderly women with low and high concern about falls; therefore, it is an important test that should be performed during the assessment of elderly individuals afraid of falling.


Effects of benzalkonium chloride- or polyquad-preserved fixed combination glaucoma medications on human trabecular meshwork cells.
We investigated the potential short and long-term effects in cultured human trabecular meshwork (TM) cells of various topical glaucoma formulations containing different preservatives. We tested the fixed combination medications 0.004% travoprost plus 0.5% timolol preserved with either 0.015% benzalkonium chloride (BAK; DuoTrav®), or with 0.001% polyquad (PQ; DuoTrav(®) BAK-free); and 0.005% latanoprost plus 0.5% timolol preserved with 0.020% BAK (Xalacom(®)). Also tested was a range of BAK concentrations (0.001%-0.020%) in balanced salt solution (BSS). Cells were treated for 25 min at 37 °C with solutions diluted 1:10 and 1:100 to mimic the reduced penetration of topical preparations to the anterior chamber. The percentage of live cells was determined immediately after treatment through the uptake of the fluorescent vital dye calcein-AM. To determine any long-term effects, we assayed release of matrix metalloproteinase 9 (MMP-9) and apoptosis 24 h after treatments. BAK demonstrated a dose-dependent reduction in TM cell viability, ranging from 71±5% live cells at 0.001% BAK (diluted 1:10) to 33±3% live cells at 0.020% BAK (diluted 1:10). Travoprost (0.004%) plus 0.5% timolol preserved with 0.015% BAK had statistically fewer live TM cells (79±7%) than the same preparation preserved with 0.001% polyquad® (PQ; 93±1%; p<0.001). Latanoprost plus timolol preserved with 0.020% BAK (29±9% live cells) was similar to the 0.020% BAK (33±3%) treatment. However, travoprost plus timolol preserved in 0.015% BAK had significantly more live cells (83±12%) than the 1:10 dilution of 0.015% BAK (49±10%). We also found 0.020% BAK (diluted 1:100) resulted in elevated levels of extracellular MMP-9 at 24 h. These results demonstrate that the substitution of the preservative BAK from topical ophthalmic drugs results in greater in vitro viability of TM cells. Travoprost with timolol, but not latanoprost with timolol, countered some of the toxic BAK effects. BAK treatment appeared to cause elevated levels of MMP-9, a matrix metalloproteinase implicated in the pathogenesis of glaucoma.


Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder: A Randomized Clinical Trial.
The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine. Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo. clinicaltrials.gov Identifier: NCT02009163.


Synthesis of 3-selena-1-dethiacephems and selenazepines via iodocyclization.
A convenient approach to synthesize novel selenium-beta-lactams, 3-selena-1-dethiacephems and selenazepines, was accomplished via the regioselective iodocyclization reaction. The substituent of allenyl moieties dramatically influenced the regiochemical outcome in the iodocyclization of allene-selenourea derivatives.


Accuracy of caries diagnosis in digital images from charge-coupled device and storage phosphor systems: an in vitro study.
To evaluate the diagnostic accuracy of carries detection with four intra-oral digital radiographic systems in vitro and to investigate the impact of image compression. 116 extracted human premolars and molars mounted three in a line with approximal contacts were radiographed with four digital systems (Digora, RVG, Sens-A-Ray, and Visualix) and imported into a Windows-based program. Sixteen images from each system were compressed (JPEG, irreversible compression). The total of 528 images was assessed by six radiologists using a 5-point confidence scale for the detection of approximal and occlusal caries. Caries was validated histologically. The disease threshold was caries in enamel for approximal surfaces and in dentine for occlusal surfaces. Mean ROC curve areas for approximal surfaces were 0.611 (DIG), 0.572 (RVG), 0.594 (SAR), and 0.596 (VIX), and for occlusal surfaces 0.794 (DIG), 0.819 (RVG), 0.751 (SAR), and 0.761 (VIX). There were no significant differences between the areas under the ROC curves (p > 0.05); nor were there any significant differences between the compressed and uncompressed images (p > 0.05). The four digital systems performed almost equally well for detection of caries in vitro, and compressed images were as accurate as uncompressed.


[Holter monitoring in patients with focal cerebral ischaemic attacks (author's transl)].
One hundred patients with focal cerebral ischaemic attacks of suspected embolic origin were investigated by Holter monitoring to determine whether paroxysmal arrhythmia may have been responsible for the episodes. There were 57 men and 43 women aged from 16 to 79 years (mean 50 years). Ninety-seven had residual focal neurological deficits and 3 had transient ischaemic attacks. The neurological lesions were verified by cerebral angiography in 68. Twenty-one had arterial hypertension and 9 had old myocardial infarction or angina. Nine had a history of palpitations. None had cardiac valve disease. All patients were in sinus rhythm, 4 had ventricular extrasystoles on routine ECG, and 4 had supraventricular extrasystoles. None of the patients were receiving anti-arrythmic drugs at the time of investigation. Holter monitoring was performed for 18 hours in 91 cases and for 24-54 hours in the remaining ones. The interval between the cerebral ischaemic attack and the monitoring was less than one month (mean 20 days) for 50 patients and longer for the others. Cardiac arrythmias were found in 36 patients. Sixteen had more than 10 supraventricular extrasystoles per hour, 13 had runs of 3 to 8 beats of supraventricular tachycardia, 1 had an episode of atrial fibrillation. Eighteen subjects had more than 5 ventricular extrasystoles per hour, 1 had accelerated ventricular rhythm, 2 had runs of 4 to 7 beats of ventricular tachycardia. Two patients had second degree A.V. block. None had palpitations during monitoring. Arrythmias were increasingly frequent with age. Our findings are similar to those obtained with monitoring in ambulatory asympatomatic subjects of the same age without apparent heart diseases reported by other authors. On the other hand, the frequency of arrythmia was unrelated to the time elapsed between the ischaemic attack and Holter monitoring. In conclusion, Holter monitoring performed several weeks after suspected cerebral embolism failed to reveal arrythmias likely to be responsible for a focal cerebral ischaemic attack.


[Long-term functional outcome of Laccourreye hemipharyngectomy-hemilaryngectomy with reference to oncologic outcome].
Various techniques for the treatment of hypopharyngeal malignancies are used to achieve disease control while preserving laryngeal function. This study details the long-term results of 22 patients (ages 39-80; average age 57 years) following hemipharyngo-hemilaryngectomy (described by Laccourreye) for unilateral hypopharyngeal squamous cell carcinomas (G2-G3; T1-T4; N0-N3). Follow-up was 16-83 months (average 43) and included extensive speech and swallowing assessment. From 1989-1994 the procedure was performed in 26 patients. Two died within one year postoperatively, two were lost for follow-up, and 22 were included in this study. One patient developed recurrent disease with liver metastasis; two patients were successfully treated for recurrent disease. Two patients developed second primary tumors, while all others had no signs of recurrent disease. Fourteen patients had no difficulties eating or drinking. Six patients could only eat soft foods, and two patients required a gastrostomy feeding tube. Nineteen patients had a useful but hoarse voice, and three patients had severe difficulties when communicating. Modulation of voice was decreased because the supraglottic structures (mainly false cord and scar tissue) were used for phonation. Eighteen patients were completely satisfied with their voice. The tracheotomy was closed in 18 patients within six months, while four patients required a tracheostoma for more than two years. These data show that function-preserving surgical techniques can be successfully used in hypopharyngeal carcinomas even for patients with advanced disease. Useful functional results for swallowing, voice, and airway were achieved in most patients undergoing this procedure.


Gender and leg-dominance differences in shoe properties and foot injuries in badminton: a cross-sectional survey.
While the roles of injury prevention and performance enhancement have increasingly been investigated for badminton footwear, there is a lack of research on gender-specific badminton footwear. The purpose of this study was to examine the gender differences in footwear demands and foot injuries in badminton. The study was a cross-sectional survey, in which 326 recreational badminton players were recruited. The questionnaire was divided into four sections enquiring about the characteristics of (1) participant profiles, (2) importance of shoe properties (3) shoe complaints (4) and pain or discomfort in different foot regions. The Mann-Whitney U test and Wilcoxon Signed Ranks test were performed to determine the differences between genders and the differences between leg dominance, respectively. The significance level was set at 0.05. Both males and females rated shoe fit as the most important features, followed by the overall comfort and injury protection. Females considered the shoe forefoot cushioning, comfort, breathability and colour as more important compared with the other properties, which showed distinct pattern differences from males. The shoe problem results indicated that plantar pain of the non-dominant foot was considered the most commonly reported footwear problem by both males and females. The problem of excessive arch-support on the dominant and non-dominant sides of male participants was significantly higher than females (p < 0.05). Occasional pain or frequent pain were mainly distributed in the forefoot, followed by the rearfoot and midfoot regions. There were small differences in footwear demand between the dominant and non-dominant sides, but several differences existed between females and males. The results from gender differences suggested that female shoes prefer a specific shoe last for better fit, rather than a modified version of male shoes. In the future, the design of badminton shoes should consider footwear demands and foot discomfort profiles in respective male and female badminton players.


Porous Functionalized Self-Standing Carbon Fiber Paper Electrodes for High-Performance Capacitive Energy Storage.
A facile and cost-efficient approach to functionalize raw carbon fiber paper (CFP) used for a self-standing capacitive electrode has been proposed here. Benefiting from the improved specific surface area and surface functional groups, the functionalized CFP (F-CFP) showed much enhanced capacitive performance, 3 orders of magnitude higher than that of the raw CFP. It delivered the areal capacitance of 1275 mF cm-2 at 5 mA cm-2 with a rather wide voltage window of 1.4 V (-0.4 to 1 V vs Ag/AgCl) in 0.5 M H2SO4. However, in a neutral 1 M Na2SO4 aqueous solution, although the areal capacitance of 1115 mF cm-2 at 3 mA cm-2 is slightly smaller, the potential window is much wider (2 V, -1 to 1 V vs Ag/AgCl), indicating a high overpotential of hydrogen evolution. The areal capacitance was still as high as 722 mF cm-2 at a very fast charge-discharge current density of 50 mA cm-2, and about 66% of the initial capacitance (at 3 mA cm-2) was remained in Na2SO4, indicating considerable rate capability.


The growth and recovery of vibrotactile TTs caused by hand-transmitted repetitive shocks of various waveforms.
The effect of shock repetition rate on the temporary threshold shifts (TTSs) in vibrotactile perception at the fingers has been studied with shocks having exponential decays and hanning waveforms. The repetition rate of shocks delivered at the hand varied from 2 shocks per second up to 64 shocks per second. Subjects were exposed to vertical hand-transmitted repetitive shock vibration of equal energy contents. The magnitudes of the stimuli were adjusted to 2.8 ms-2 r.m.s. so that they were all equally severe according to current standards for assessing the severity of hand-transmitted vibration (e.g. International Standard 5349, 1986). It was found that the TTS in vibrotactile perception decreased with decreasing shock repetition rate for both waveforms. The relation between the TTS, the logarithm of exposure time, and the logarithm of the ratio between the frequency-weighted r.m.s. acceleration and the peak amplitude was described by the relation TTS = 16.1 + 3.9log10T + 17.9log10 (RMS/PEAK), where TTS is the temporary threshold shift (in decibels), T is the exposure time, and RMS is the frequency-weighted r.m.s. acceleration according to BS 6842 and ISO 5349, and PEAK is the peak amplitude of the frequency-weighted acceleration. This shows that current standards are not appropriate for the prediction of the changes in vibrotactile perception produced by shocks such as those on many hand-held percussive tools.


Reduction of 9-nitrocamptothecin-triggered apoptosis in DU-145 human prostate cancer cells by ectopic expression of 14-3-3zeta.
A promising family of anticancer agents, the camptothecins, is noted for their ability to induce apoptosis specifically in malignant cells. However, a major obstacle for successful cancer treatment by these and other chemotherapeutic agents is the intrinsic or acquired resistance to drug treatment. Resistance to 9NC6, a camptothecin derivative, has been modeled in vitro using a human prostate cancer cell line. To elucidate the mechanism for acquired 9NC resistance, we have used a subtractive cloning approach to identify genes whose altered expression level is reflective of 9NC resistance or susceptibility. Differential gene expression was compared between wild-type human prostate cancer cell line, DU-145, and a 9NC-resistant subline, RC1. Results were confirmed by Northern and Western blot analyses. In this report, we focus on one gene, 14-3-3zeta. An expression vector of a full-length myc-epitope-tagged 14-3-3zeta cDNA was constructed and used for transfection into DU-145 cells. We consistently observed that 14-3-3zeta message and protein levels were dramatically increased in 9NC resistant cells. The expression levels of other 14-3-3 family members were unaffected. Strikingly, ectopic overexpression of 14-3-3zeta in wild-type 9NC-susceptible prostate cancer cells decreased 9NC-induced apoptosis. Our results suggest a novel direct or indirect role of 14-3-3zeta in mediating resistance of DU-145 cells to the topoisomerase I inhibitor, 9NC. We are currently exploring whether this represents a more general pathway for drug resistance as well.


AAA Proteases: Guardians of Mitochondrial Function and Homeostasis.
Mitochondria are dynamic, semi-autonomous organelles that execute numerous life-sustaining tasks in eukaryotic cells. Functioning of mitochondria depends on the adequate action of versatile proteinaceous machineries. Fine-tuning of mitochondrial activity in response to cellular needs involves continuous remodeling of organellar proteome. This process not only includes modulation of various biogenetic pathways, but also the removal of superfluous proteins by adenosine triphosphate (ATP)-driven proteolytic machineries. Accordingly, all mitochondrial sub-compartments are under persistent surveillance of ATP-dependent proteases. Particularly important are highly conserved two inner mitochondrial membrane-bound metalloproteases known as m-AAA and i-AAA (ATPases associated with diverse cellular activities), whose mis-functioning may lead to impaired organellar function and consequently to development of severe diseases. Herein, we discuss the current knowledge of yeast, mammalian, and plant AAA proteases and their implications in mitochondrial function and homeostasis maintenance.


Soluble CD23 reliably reflects disease activity in B-cell chronic lymphocytic leukemia.
This study was initiated to evaluate whether soluble CD23 (sCD23) reflects disease activity and tumor load in B-cell chronic lymphocytic leukemia (B-CLL) and to determine its prognostic potential for this disease. The concentration of sCD23 was measured in the serum of 45 B-CLL patients, 50 patients with other lymphoproliferative disorders, and 41 healthy donors (HD). sCD23 serum levels from B-CLL patients were correlated with parameters of disease activity and total tumor mass (TTM) score. In selected cases, sCD23 was measured repeatedly over a 24-month period. Expression, density, and calculated total amount of membrane CD23 on peripheral-blood B-CLL cells, as well as its correlation to sCD23 levels in serum and supernatants, were determined. sCD23 in B-CLL patients serum was highly elevated as compared with other lymphoproliferative disorders, with the exception of immunocytoma (IC). Both advanced Rai stages and active forms of B-CLL were associated with higher levels of sCD23. There was a highly significant reciprocal relationship between sCD23 and lymphocyte count doubling time (LCDT). Serum sCD23 correlated positively with serum deoxythymidine kinase activity and TTM score, but not with absolute lymphocyte counts. The repetitive measurement of serum sCD23 showed the usefulness of this marker in monitoring disease progression in B-CLL. The total amount of membrane CD23 on in vitro-cultured B-CLL cells correlated significantly with sCD23 levels in the supernatant, whereas correlation between serum sCD23 and membrane CD23 on freshly isolated B-CLL cells was absent. Our results indicate that sCD23 is a highly sensitive and specific parameter with prognostic potential for B-CLL, which may be used as a tumor marker and may help to assess disease activity.


H2O2-dependent substrate oxidation by an engineered diiron site in a bacterial hemerythrin.
The O2-binding carboxylate-bridged diiron site in DcrH-Hr was engineered in an effort to perform the H2O2-dependent oxidation of external substrates. A His residue was introduced near the diiron site in place of a conserved residue, Ile119. The I119H variant promotes the oxidation of guaiacol and 1,4-cyclohexadiene upon addition of H2O2.


Hippo Pathway: An Emerging Regulator of Craniofacial and Dental Development.
The evolutionarily conserved Hippo signaling pathway is a vital regulator of organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A number of important studies have revealed critical roles of Hippo signaling and its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator with PDZ binding motif) in tissue development, homeostasis, and regeneration, as well as in tumorigenesis. In addition, recent studies have shown evidence of crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt signaling, that not only regulates developmental processes but also contributes to disease pathogenesis. In this review, we summarize the major discoveries in the field of Hippo signaling and what has been learned about its regulation and crosstalk with other signaling pathways, with a particular focus on recent findings involving the Hippo-Yap pathway in craniofacial and tooth development. New and exciting studies of the Hippo pathway are anticipated that will significantly improve our understanding of the molecular mechanisms of human craniofacial and tooth development and disease and will ultimately lead to the development of new therapies.


Retrospective evaluation of the clinical characteristics associated with Corynebacterium species bacteremia.
Corynebacterium spp. are becoming recognized as pathogens that potentially cause various infections. We aimed to evaluate the clinical characteristics associated with Corynebacterium spp. bacteremia. We retrospectively reviewed the medical records of all adult patients who had positive blood cultures for Corynebacterium spp. in a single university hospital between January 2014 and December 2016. Patients were divided into a bacteremia group and a contamination group based on microbiological test results and clinical characteristics. Patients' characteristics, antimicrobial susceptibility of isolated species, antimicrobials administered, and patient outcomes were evaluated. Corynebacterium spp. were isolated from blood samples of 63 patients; Corynebacterium striatum was the predominant isolate. Twenty-eight patients were determined to have bacteremia. Younger age (p=0.023), shorter time to positivity (p=0.006), longer hospital stay (p=0.009), and presence of an indwelling vascular catheter (p=0.002) were observed more often in the bacteremia group compared to the contamination group. The source of infection in most patients with bacteremia was an intravenous catheter. All tested strains were susceptible to vancomycin. Four of the 27 patients with bacteremia died, despite administration of appropriate antimicrobial therapy. We found that younger age, shorter time to positivity, and presence of an indwelling catheter were related to bacteremia caused by Corynebacterium spp. Appropriate antimicrobials should be administered once Corynebacterium spp. are isolated from the blood and bacteremia is suspected.


Antimicrobial Resistance Patterns In Community Acquired Urinary Tract Infections.
Urinary tract infection (UTI) is the most frequent disease for which patients seek medical care. The antimicrobial agents causing UTI and their sensitivity patterns have remarkably changed throughout the world over the past few years. Hence, the present study was designed to explore the uropathogens and their susceptibility to various molecules in our region. This descriptive cross sectional study was conducted at Medical C Unit of Ayub Teaching Hospital, Abbottabad from January 2015 to January 2016. Patients with clinical features of UTI were evaluated using Urine R/E and Urine culture and sensitivity. Ten antibiotics were checked for susceptibility. Results were analysed using SPSS 17. A total of 630 patients presented with urinary complaints. Of these, 236 patients had more than 8-10 pus cells on urine R/E. They were further evaluated using culture and sensitivity and positive culture was obtained in 75 patients. Of these 34 (45.3%) were males and 41 (54.7%) were females. E Coli was the predominant isolate being present in 49 (65.3%) patients. This was followed by Klebsiella in 9 (12%) patients. Tazobactam-piperacillin and cefoperazone-sulbactam were the most sensitive drugs having overall sensitivity of 96% and 93.3% respectively. The isolates were highly resistant to Fluoroquinolones 77.3% followed by Penicillins 72% and TMP-SMX 69.3%. Antibiotic sensitivity patterns have enormously changed over the past decade. Newer agents are quite efficacious but their use should be highly judicious to prevent the development of resistance to these molecules.


Comparative Anatomy of Trunk Musculature in Salamandridae with Different Habitats.
The diversity of trunk muscle morphology of Salamandridae occupying different habitats (aquatic: Pachytriton labiatus; terrestrial: Tylototriton kweichowensis and Salamandra salamandra salamandra) was examined. Trunk muscles were dissected, and muscle weight ratios were quantified. The terrestrial species have larger abdominal trunk muscles than the aquatic species do. In contrast, the lateral hypaxial muscles are larger in the aquatic species. The M. rectus abdominis profundus is located subjacent to the M. rectus abdominis in the terrestrial species. In the aquatic species, the ventral muscle is composed of the M. rectus abdominis alone. The lateral hypaxial muscles in the aquatic species are suited to lateral bending during underwater locomotion in the denser aquatic medium. Larger abdominal muscles may be used in supporting body weight against gravity in the terrestrial species. The function of the M. rectus abdominis profundus may be to support the M. rectus abdominis in the terrestrial species. These findings suggest a divergent evolution of trunk muscle characteristics within the Salamandridae, which correlate with both habitats and modes of locomotion.


GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells.
Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the "empty slots" corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts.


Cross-Dehydrogenative C-H Amination of Indoles under Aerobic Photo-oxidative Conditions.
A novel cross-dehydrogenative C(sp2)-H amination catalyzed by an organic photocatalyst is reported. The reaction is mediated by 2-tert-butylanthraquinone as a photocatalyst, harmless visible light, and aerobic oxygen as the sole oxidant without a transition-metal catalyst and or external oxidant.


Metabolism of androstenedione by Sertoli cell enriched preparations and purified Leydig cells from boar testes in relation to estrogen formation.
The metabolism of [3H]androstenedione in relation to estrogen formation was studied in incubations of Sertoli cell-enriched preparations (30-40% Sertoli cells) and purified Leydig cells (greater than 98%) from testes of mature male pigs. Radioactive metabolites were partitioned by countercurrent distribution (CCD) into unconjugated and 'conjugated' (water-soluble) fractions. Both unconjugated and solvolysed metabolites were separated into neutral and phenolic fractions by CCD with toluene and NaOH. The distribution of radioactivity was examined subsequently for each fraction by partition chromatography on celite columns. Major differences were noted in the products of metabolism from the two cell types. More than half of the radioactivity appeared in the conjugate fraction for Leydig cell incubations, but little or no conjugation occurred in Sertoli cell preparations. Metabolism of androstenedione to other neutral substances was extensive only for Leydig cells, with approx 2% remaining unchanged. No clear evidence of estrogen formation was observed with Sertoli cells; however, both unconjugated and conjugated phenolic for Leydig cell products showed radioactivity corresponding to estrone and estradiol-17 beta on chromatography. About 2-5% of androstenedione was converted to these two estrogens, whereas most of the phenolic material was present as compounds more polar than estradiol.


Expression of the secreted form of clusterin protein in renal cell carcinoma as a predictor of disease extension.
To evaluate the significance of clusterin expression in surgically resected renal cell carcinoma (RCC) specimens. Normal kidney and RCC specimens were obtained from 131 patients who had radical surgery. The expression of clusterin protein was analysed by immunohistochemical staining with an antibody recognizing all isoforms of clusterin. Cell proliferative activities and apoptotic features in these specimens were investigated using Ki-67 immunostaining and the terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling assay, respectively. Findings were evaluated in relation to several clinicopathological factors. There were various levels of clusterin expression in 128 of the 131 RCC specimens, while 37 of 131 normal kidney tissues (28.2%) had no clusterin staining. Clusterin protein was present in the cytoplasm of both normal and cancer cells, but there was no nuclear staining identified in either type of cell. The expression level of clusterin protein in RCC tissues was significantly related to tumour stage and grade, but not to age, gender or histological cell type. Cell proliferative activity in RCC specimens was significantly associated with clusterin expression, while the apoptotic index was inversely related to clusterin expression. Furthermore, recurrence-free survival in patients with strong clusterin expression was significantly lower than that in those with weak expression. These findings suggest that the secreted form of clusterin may be involved in the progression of RCC, and that overexpression of clusterin could be a useful prognostic variable after radical surgery in patients with RCC.


Adoption of Robot-Assisted Partial Nephrectomies: A Population-Based Analysis of U.S. Surgeons from 2004 to 2013.
Urological surgeries have contributed to the increasing prevalence of minimally invasive robotic procedures. Although factors influencing the adoption of robot-assisted radical prostatectomy have previously been identified, the explanation for the rapid rise in robotic partial nephrectomies remains unknown. Using a retrospective population-based sample, we attempt to determine hospital and surgeon-specific factors influencing a surgeon's decision to utilize robotic assistance for partial nephrectomies. A nationally representative weighted sample of all men who underwent a partial nephrectomy in the United States between 2003 and 2014 was identified within the Premier Hospital Database. Hospital, surgeon, and patient characteristics for each operation were analyzed. Descriptive statistics and a multivariate regression model stratified according to the Law of Diffusion of Innovation were performed. A weighted sample of 14,890 nephrectomies was included in the study. Patient demographics were similar between the two groups. The adoption of robotic technology followed the Law of Diffusion of Innovation with the percentage of partial nephrectomies with robotic assistance increasing yearly, reaching 64.1% by 2013. Surgical volume was a significant factor driving the use of robotic assistance, with high volume surgeons (>5 partial nephrectomies/year) performing 23.2% more robotic partial nephrectomies per year than their low volume colleagues (< = 5 partial nephrectomies/year) from 2009 to 2013 (p < 0.001). This retrospective population-based study examines key factors influencing the diffusion of robotic technology for partial nephrectomies. Surgical volume and year of surgery were found to be the most significant factor in robotic adoption, with other patient and hospital-specific characteristics playing a minor role. Future studies are needed to correlate adoption rates with the clinical or cost-effectiveness of novel technologies within the medical field to determine whether rapid adoption is a patient-centered vs a clinician-centered decision point.


A Gaussian Model-Based Probabilistic Approach for Pulse Transit Time Estimation.
In this paper, we propose a new probabilistic approach to pulse transit time (PTT) estimation using a Gaussian distribution model. It is motivated basically by the hypothesis that PTTs normalized by RR intervals follow the Gaussian distribution. To verify the hypothesis, we demonstrate the effects of arterial compliance on the normalized PTTs using the Moens-Korteweg equation. Furthermore, we observe a Gaussian distribution of the normalized PTTs on real data. In order to estimate the PTT using the hypothesis, we first assumed that R-waves in the electrocardiogram (ECG) can be correctly identified. The R-waves limit searching ranges to detect pulse peaks in the photoplethysmogram (PPG) and to synchronize the results with cardiac beats--i.e., the peaks of the PPG are extracted within the corresponding RR interval of the ECG as pulse peak candidates. Their probabilities of being the actual pulse peak are then calculated using a Gaussian probability function. The parameters of the Gaussian function are automatically updated when a new pulse peak is identified. This update makes the probability function adaptive to variations of cardiac cycles. Finally, the pulse peak is identified as the candidate with the highest probability. The proposed approach is tested on a database where ECG and PPG waveforms are collected simultaneously during the submaximal bicycle ergometer exercise test. The results are promising, suggesting that the method provides a simple but more accurate PTT estimation in real applications.


Modulation of the immune response to tetanus toxoid by polylactide-polyglycolide microspheres.
The cellular and antibody responses in mice to tetanus toxoid (TT), alone or adsorbed to aluminium hydroxide TT were compared to those obtained with TT incorporated in polylactide-polyglycolide (PLGA) microspheres, a candidate single dose vaccine. After subcutaneous injection, the serum IgM antibody to TT followed similar overall patterns for all preparations although the highest levels were achieved with the alum-adsorbed material. A similar pattern was observed with the overall IgG antibody responses. The isotype distribution of antibodies was broadly similar for all types of preparation although considerable qualitative differences were observed. IgG1 antibodies predominated although IgG2a and IgG2b made a substantial contribution, especially at three months in the case of the two adjuvanted preparations. The IgG3 responses to each type of vaccine were very low. Both alum and microsphere vaccines induced proliferative responses to TT in splenic lymphocytes at three months after vaccination. Each type of vaccine was much less effective in inducing proliferative responses in lymph node cells. There was evidence of induction of IL2, IL4 and interferon-gamma genes by microsphere vaccines in splenic but not lymph node cells. There were indications that PLGA microspheres alone exerted a modulating effect on cellular responses after immunization. These results suggest that TT encapsulated in microspheres induces a pattern of cellular and antibody responses qualitatively similar to those induced by conventional TT vaccines.


Overproduction of the epsilon subunit of DNA polymerase III counteracts the SOS mutagenic response of Escherichia coli.
It has been found that the mutator phenotype of the recA441 and recA730 strains that express the SOS response constitutively is suppressed by pIP1, a high-copy plasmid carrying the dnaQ gene encoding the 3'----5' exonuclease subunit (epsilon) of DNA polymerase III. We have constructed plasmid pIP11, in which the dnaQ gene is fused to the strong tac (trp-lac) promoter. Enhanced synthesis of the epsilon subunit stimulated by isopropyl beta-D-thiogalactopyranoside, the inducer of tac, prevents expression of the mutator phenotype of recA441 and markedly decreases the frequency of UV-induced mutations. These results strongly suggest that a loss of editing capacity by the epsilon subunit of DNA polymerase III holoenzyme plays a crucial role in generation of mutations during the SOS response.


Cholesterol Biosynthesis and Uptake in Developing Neurons.
Brain cholesterol biosynthesis, a separate and distinct process from whole-body cholesterol homeostasis, starts during embryonic development. To gain a better understanding of the neuronal and glial contributions to the brain cholesterol pool, we studied this process in control, Dhcr7-/-, and Dhcr24-/- cell cultures. Our LC-MS/MS method allowed us to measure several different sterol intermediates and cholesterol during neuronal differentiation. We found that developing cortical neurons rely on endogenous cholesterol synthesis and utilize ApoE-complexed cholesterol and sterol precursors from their surroundings. Both developing neurons and astrocytes release cholesterol into their local environment. Our studies also uncovered that developing neurons produced significantly higher amounts of cholesterol per cell than the astrocytes. Finally, we established that both neurons and astroglia preferentially use the Bloch sterol biosynthesis pathway, where desmosterol is the immediate precursor to cholesterol. Overall, our studies suggest that endogenous sterol synthesis in developing neurons is a critical and complexly regulated homeostatic process during brain development.


Systematic Handling of Environmental Fate Data for Model Development-Illustrated for the Case of Biodegradation Half-Life Data.
The assessment of environmental hazard indicators such as persistence, mobility, toxicity, or bioaccumulation of chemicals often results in highly variable experimental outcomes. Persistence is particularly affected due to a multitude of influencing environmental factors, with biodegradation experiments resulting in half-lives spanning several orders of magnitude. Also, half-lives may lie beyond the limits of reliable half-life quantification, and the number of available data points per substance may vary considerably, requiring a statistically robust approach for the characterization of data. Here, we apply Bayesian inference to address these challenges and characterize the distributions of reported soil half-lives. Our model estimates the mean, standard deviation, and corresponding uncertainties from a set of reported half-lives experimentally obtained for a single substance. We apply our inference model to 893 pesticides and pesticide transformation products with experimental soil half-lives of varying data quantity and quality, and we infer the half-life distribution for each compound. By estimating average half-lives, their experimental variability, and the uncertainty of the estimations, we provide a reliable data source for building predictive models, which are urgently needed by regulatory authorities to manage existing chemicals and by industry to design benign, nonpersistent chemicals. Our approach can be readily adapted for other environmental hazard indicators.


[Interaction of both hypertriglyceridemic waist and impaired fasting glucose on the incidence of diabetes mellitus].
To study the use of hypertriglyceridemic waist (HTGW) to predict the occurrence of diabetes. Also to independently study whether there was an interaction between HTGW and impaired fasting glucose impaired fasting glucose (IFG) on the cause of diabetes. We undertook a cohort study based on data from the "Prevention of Multiple Metabolic Disorders and Metabolic Syndrome (MS) Study in Jiangsu Province, China". We used the logistic regression model to analyze the relations between both HTGW, IFG and diabetes mellitus and to evaluate the multiplied interaction between HTGW and IFG to include product terms method. Counting additive interaction was carried out under the Excel Calculation Sheet, compiled by Anderson and his colleagues. After adjusted for general risk factors and baseline fasting plasma glucose (FPG), results showed that subjects with HTGW had a 2.10 (95% CI: 1.36 - 3.25) adjusted relative risk (HR) of developing a diabetes when compared with those individuals without HTGW at the baseline study. When IFG was stratified, participants with HTGW were significantly associated with diabetes, regardless of IFG. The multi-adjusted HRs of diabetes were 3.09 (1.70 - 5.61) and 2.09 (1.08 - 4.02), respectively. Compared to the participants with non-HTGW and their FPG level below the threshold, those having HTGW and their FPG level was above the threshold, had the highest adjusted HR values [12.05 (95% CI: 6.89 - 21.07)]. Data from the additive interaction analysis showed that RERI as 7.00 (95% CI: 0.49 - 13.51), AP as 0.57 (95% CI: 0.32 - 0.82) and SI as 2.66 (95% CI: 1.36 - 5.21). HTGW could predict the occurrence of diabetes, independent from IFG while the presence of HTGW with IFG could have an additive interaction on the cause of diabetes.


Crosstalk of CREB and Fos/Jun on a single cis-element: transcriptional repression of the steroidogenic acute regulatory protein gene.
Transcriptional regulation of the steroidogenic acute regulatory (StAR) protein gene by cAMP-dependent mechanisms occurs in the absence of a consensus cAMP-response element (CRE; TGACGTCA) and is mediated by several sequence-specific transcription factors. We previously identified three CRE-like sites (within the -151/-1 bp cAMP-responsive region of the mouse StAR gene), of which the CRE2 site overlaps with an activator protein-1 (AP-1) motif (TGACTGA, designated as CRE2/AP-1) that can bind both CRE and AP-1 DNA-binding proteins. The present studies were aimed at exploring the functional crosstalk between CREB (CRE-binding protein) and cFos/cJun (AP-1 family members) on the CRE2/AP-1 element and its role in regulating transcription of the StAR gene. Using MA-10 mouse Leydig tumor cells, we demonstrate that the CRE and AP-1 families of proteins interact with the CRE2/AP-1 sequence. CREB, cFos, and cJun proteins were found to bind to the CRE2/AP-1 motif but not the CRE1 and CRE3 sites. Treatment with the cAMP analog (Bu)(2)cAMP augmented phosphorylation of CREB (Ser(133)), cFos (Thr(325)), and cJun (ser(73)). Chromatin immunoprecipitation studies revealed that the induction of CREB, cFos, and cJun by (Bu)(2)cAMP was correlated with protein-DNA interactions and recruitment of the coactivator CREB-binding protein (CBP) to the StAR promoter. EMSA studies employing CREB and cFos/cJun proteins demonstrated competition between these factors for binding to the CRE2/AP-1 motif. Transfection of cells containing the -151/-1 StAR reporter with CREB and cFos/cJun resulted in trans-repression of the StAR gene, an event tightly associated with CBP, demonstrating that both CREB and Fos/Jun compete with each other for binding with limited amounts of intracellular CBP. Overexpression of adenovirus E1A, which binds and inactivates CBP, markedly suppressed StAR gene expression. Ectopic expression of CBP eliminated the repression of the StAR gene by E1A and potentiated the activity of CREB and cFos/cJun on StAR promoter responsiveness. These findings identify molecular events involved in crosstalk between CREB and cFos/cJun, which confer both gain and loss of function on a single cis-element in fine-tuning of the regulatory events involved in transcription of the StAR gene.


N-(p-isothiocyanatophenethyl)spiperone, a selective and irreversible antagonist of D2 dopamine receptors in brain.
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible and nonselective protein-modifying reagent, has been used extensively in studies involving inactivation of receptors. Here, we present N-(p-isothiocyanatophenethyl)spiperone (NIPS), a novel and highly selective irreversible inactivator of D2 but not D1 receptors. In in vitro studies, NIPS exhibited an apparent Ki of 10 nM for [3H]methylspiperone binding to D2 receptors in rat striatum. Preincubation of the striatal membranes with NIPS followed by extensive washing resulted in up to an 80% reduction of the D2 receptor maximum binding (Bmax). Coincubation with the D2 receptor antagonist domperidone could protect against this reduction. NIPS was additionally shown to irreversibly inactivate D2 receptor binding activity in cultured cells expressing the D2 receptor protein. In in vivo administration studies, using [3H]SCH 23390 and [3H]spiperone to assay D1 and D2 receptors in vitro, 24 hr after injection (s.c.) with 5 to 40 mg/kg of NIPS D2 receptor, Bmax was decreased by 58 to 76%, without a change in D2 receptor affinity. In contrast, there was no effect on D1 receptor Bmax or affinity. There was also a small (24%) reduction in frontal cortex 5-hydroxytryptamine2 receptors by 20 mg/kg of NIPS. However, there was no effect on alpha-1 or alpha-2 adrenergic receptors in the frontal cortex, or on muscarinic cholinergic or 5-hydroxytryptamine1A receptors in the hippocampus. After single doses of either 20 mg/kg of NIPS or 10 mg/kg of EEDQ, the D2 receptor recovery rate was much slower after NIPS (half-time of receptor recovery = 170 hr) than after EEDQ (half-time of receptor recovery = 76.7 hr).(ABSTRACT TRUNCATED AT 250 WORDS)


Templated Synthesis of End-Functionalized Graphene Nanoribbons through Living Ring-Opening Alkyne Metathesis Polymerization.
Atomically precise bottom-up synthesized graphene nanoribbons (GNRs) are promising candidates for next-generation electronic materials. The incorporation of these highly tunable semiconductors into complex device architectures requires the development of synthetic tools that provide control over the absolute length, the sequence, and the end groups of GNRs. Here, we report the living chain-growth synthesis of chevron-type GNRs (cGNRs) templated by a poly-(arylene ethynylene) precursor prepared through ring-opening alkyne metathesis polymerization (ROAMP). The strained triple bonds of a macrocyclic monomer serve both as the site of polymerization and the reaction center for an annulation reaction that laterally extends the conjugated backbone to give cGNRs with predetermined lengths and end groups. The structural control provided by a living polymer-templated synthesis of GNRs paves the way for their future integration into hierarchical assemblies, sequence-defined heterojunctions, and well-defined single-GNR transistors via block copolymer templates.


Characterization of VdASP F2 Secretory Factor from Verticillium dahliae by a Fast and Easy Gene Knockout System.
The vascular wilt fungus Verticillium dahliae produces persistent resting structures known as microsclerotia, which enable long-term survival of this plant pathogen in soil. The completed genome sequence of V. dahliae has facilitated large-scale investigations of individual gene functions using gene-disruption strategies based on Agrobacterium tumefaciens-mediated transformation. However, the construction of gene-deletion vectors and screening of deletion mutants have remained challenging in V. dahliae. In this study, we developed a fast and easy gene knockout system for V. dahliae using ligation-independent cloning and fluorescent screening. We identified secretory factor VdASP F2 in a T-DNA insertion library of V. dahliae and deleted the VdASP F2 gene using the developed knockout system. Phenotypic analysis suggests that VdASP F2 is not necessary for V. dahliae growth on potato dextrose agar under various stress conditions. However, on semisynthetic medium or under limited nutrient conditions at lower temperatures, the VdASP F2 deletion mutant exhibited vigorous mycelium growth, less branching, and a significant delay in melanized microsclerotial formation. Further assessment revealed that VdASP F2 was required for the expression of VDH1 and VMK1, two genes involved in microsclerotial formation. Cotton inoculated with the VdASP F2 deletion mutant wilted, demonstrating that VdASP F2 is not associated with pathogenicity under normal conditions. However, after inducing microsclerotial formation and incubation at low temperatures, cotton infected with the VdASP F2 deletion mutant did not exhibit wilt symptoms. In conclusion, our results show that VdASP F2 plays an important role in the response of V. dahliae to adverse environmental conditions and is involved in a transition to a dormant form for prolonged survival.


Perovskite-based electrocatalysts for oxygen evolution reaction in alkaline media: A mini review.
Water electrolysis is one of the attractive technologies for producing clean and sustainable hydrogen fuels with high purity. Among the various kinds of water electrolysis systems, anion exchange membrane water electrolysis has received much attention by combining the advantages of alkaline water electrolysis and proton exchange membrane water electrolysis. However, the sluggish kinetics of the oxygen evolution reaction, which is based on multiple and complex reaction mechanisms, is regarded as a major obstacle for the development of high-efficiency water electrolysis. Therefore, the development of high-performance oxygen evolution reaction electrocatalysts is a prerequisite for the commercialization and wide application of water electrolysis systems. This mini review highlights the current progress of representative oxygen evolution reaction electrocatalysts that are based on a perovskite structure in alkaline media. We first summarize the research status of various kinds of perovskite-based oxygen evolution reaction electrocatalysts, reaction mechanisms and activity descriptors. Finally, the challenges facing the development of perovskite-based oxygen evolution reaction electrocatalysts and a perspective on their future are discussed.


Idiopathic palmar fasciitis with polyarthritis syndrome.
A 31-yr-old Korean woman was presented with 4-month history of bilateral hand swelling and stiffness. On clinical examination, she had a painful synovitis of both hands, wrists, knees and ankles. The radiologic and histological examinations confirmed it with palmar fasciitis and polyarthritis syndrome (PFPAS). PFPAS is an uncommon disorder characterized by progressive flexion contractures of both hands, inflammatory fasciitiis, fibrosis, and a generalized inflammatory arthritis. Although most reported cases of PFPAS have been associated with various malignancies, our patient have not been associated with malignancy during 24 months follow up period from her first symptom onset. Her symptoms were improved with moderate dose of corticosteroid and she is currently taking prednisone 5 mg daily without any evidence for internal malignancy. We present here in a young Korean patient with idiopathic PFPAS who was successfully treated with administration of corticosteroid.


Structure and rheology of SiO2 nanoparticle suspensions under very high shear rates.
High shear rate experiments have been performed with capillary microviscometers onto SiO2 nanoparticles dispersed in alcohol (so-called nanofluids). The aim of these experiments was to investigate the processes of aggregation and dislocation of the nanoparticles in a shear flow under perikinetic and orthokinetic conditions. Shear rates as high as 2x10(5) s-1 were obtained in pressure-driven microchannels laminar flows. All the nanofluids under test have displayed a Newtonian behavior but with a strong enhanced viscosity, that is, the consequence of an effective volume concentration higher than the real one. It was possible to determine the average size of the aggregates and to find a correlation between their structure and the range of the hydrodynamic Peclet number at which experiments were performed. These results display a strong evidence of the role of aggregates and support the recent conclusions about the controversy of the thermal properties of nanofluids.


Preferences Of Doctors For Working In Rural Islamabad Capital Territory, Pakistan: A Qualitative Study.
Developing countries are faced with acute shortages of human resources in rural/remote areas. Decisions of human resources for health to work in rural areas are influenced by many financial and non-financial factors. This study focused on preferences of doctors for working in rural and resource constrained areas of Pakistan. The study was based on qualitative research techniques. Focus group discussions (FGDs) were conducted with final year medical students and house officers and In-depth Interviews (IDIs) with senior health managers of Islamabad Capital Territory (ICT). Results were analyzed using qualitative content analysis technique to present the findings. The results showed that quality of facilities; career development, lack of incentives, quality of life, and lack of connectivity between rural and urban health facilities, transportation services and governance issues are some of the main factors identified by young doctors of ICT that contribute in their decision of choosing a certain job or not in rural areas. Study results show the indepth detail of deciding factors for attracting and retaining health workforce in rural areas. These can be used for designing DCE (Discrete Choice Experiment) questionnaire to further analyze the preference incentive packages for attracting doctors to work in rural Islamabad.


Changes in high-sensitivity C-reactive protein levels and metabolic indices according to grip strength in Korean postmenopausal women.
This study aimed to investigate the changes in high-sensitivity C-reactive protein (hs-CRP) level and metabolic indices such as blood pressure, serum lipid level and serum glucose level according to grip strength in postmenopausal women. Data from participants (postmenopausal women) in the Seventh Korea National Health and Nutrition Examination Survey 2018 were analyzed. Absolute handgrip strength was the sum of the maximal grip strength of both hands, and relative handgrip was calculated as absolute handgrip divided by the body mass index. We performed linear regression analysis after adjusting for confounders to assess the influence of grip strength on hs-CRP level and metabolic indices. Linear regression analysis showed that after adjusting for confounders, with an increased absolute grip strength, systolic blood pressure and hs-CRP levels were decreased; however, the changes were not significant for the remaining indices. Relative grip strength was associated with hs-CRP levels and metabolic indices. With a high relative grip strength, hs-CRP, blood pressure, fasting blood glucose, hemoglobin A1c and triglyceride levels were decreased, while the high-density lipoprotein cholesterol level was increased. Our study evaluated the overall health status using grip strength in postmenopausal women. The grip strength adjusted by body size was suitable in evaluating the overall health status, including inflammatory and metabolic indices. Additionally, increased grip strength was associated with a better health status in postmenopausal women.


Hot-Water Extracts from Roots of Vitis thunbergii var. taiwaniana and Identified ε-Viniferin Improve Obesity in High-Fat Diet-Induced Mice.
In this study, hot-water extracts (HW) from roots of Vitis thunbergii var. taiwaniana (VTT-R) were shown to lower levels of lipid accumulation significantly (P < 0.01 or 0.001) compared to the control in 3T3-L1 adipocytes. The VTT-R-HW (40 mg/kg) interventions concurrent with a high-fat (HF) diet in C57BL/6 mice over a 5 eek period were shown to reduce body weights significantly (P < 0.05) compared to those of mice fed a HF diet under the same food-intake regimen. The (+)-ε-viniferin isolated from VTT-R-HW was shown to reduce the size of lipid deposits significantly compared to the control (P < 0.05 or 0.001) in 3T3-L1 adipocytes, and dose-dependent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitions showed that the 50% inhibitory concentration was calculated to be 96 μM. The two-stage (+)-ε-viniferin interventions (10 mg/kg, day 1 to day 38; 25 mg/kg, day 39 to day 58) were shown to lower mice body weights significantly (P < 0.05 or 0.001), the weight ratio of mesenteric fat, blood glucose, total cholesterol, and low-density lipoprotein compared to that of the HF group under the same food-intake regimen but without concurrent VTT-R-HW interventions. It might be possible to use VTT-R-HW or (+)-ε-viniferin as an ingredient in the development of functional foods for weight management, and this will need to be investigated further.


Assessment of Antimicrobial Agents, Analgesics, and Epidermal Growth Factors-Embedded Anti-Adhesive Poly(Lactic-Co-Glycolic Acid) Nanofibrous Membranes: In vitro and in vivo Studies.
Postoperative tissue adhesion is a major concern for most surgeons and is a nearly unpreventable complication after abdominal or pelvic surgeries. This study explored the use of sandwich-structured antimicrobial agents, analgesics, and human epidermal growth factor (hEGF)-incorporated anti-adhesive poly(lactic-co-glycolic acid) nanofibrous membranes for surgical wounds. Electrospinning and co-axial electrospinning techniques were utilized in fabricating the membranes. After spinning, the properties of the prepared membranes were assessed. Additionally, high-performance liquid chromatography and enzyme-linked immunosorbent assays were utilized in assessing the in vitro and in vivo liberation profiles of the pharmaceuticals and the hEGF from the membranes. The measured data suggest that the degradable anti-adhesive membranes discharged high levels of vancomycin/ceftazidime, ketorolac, and hEGF in vitro for more than 30, 24, and 27 days, respectively. The in vivo assessment in a rat laparotomy model indicated no adhesion in the peritoneal cavity at 14 days post-operation, demonstrating the anti-adhesive capability of the sandwich-structured nanofibrous membranes. The nanofibers also released effective levels of vancomycin, ceftazidime, and ketorolac for more than 28 days in vivo. Histological examination revealed no adverse effects. The outcomes of this study implied that the anti-adhesive nanofibers with sustained release of antimicrobial agents, analgesics, and growth factors might offer postoperative pain relief and infection control, as well as promote postoperative healing of surgical wounds.


The grounded nature of psychological perspective-taking.
Psychological perspective-taking is a powerful social cognition that helps us to understand other people. It creates feelings of closeness and sympathy, motivates us to help others, and is important for positive social relationships. In contrast to the impressive knowledge about its consequences, relatively little is known about how exactly people achieve them. The present paper addresses this question from a grounded cognition perspective, drawing on recent findings on the embodiment of visuospatial perspective-taking. Visuospatial perspective-taking involves a mental transformation of one's body schema into the physical location of another person. We argue that when people psychologically "put themselves in another person's shoes," this simulation of physical proximity happens, too, and is one source of perceived closeness. In five experiments (total N = 1067), participants completed a visuospatial perspective-taking task. During half of the trials, angular disparity between the target person and the participant was high and participants had to adopt the target's visual perspective (which involves an embodied simulation). During the remaining trials, angular disparity was low and participants could solve the task egocentrically. Taking another's perspective led participants to adopt the thoughts of the target person more strongly (Experiments 1-3) and increased the perceived similarity of that person to the self (Experiment 4) and participants' liking of that person (Experiment 5). These effects were independent of task difficulty (Experiment 2), and only present during trials where an embodied transformation happened (i.e., at high angular disparities; Experiment 3). Implications for psychological and visuospatial perspective-taking research and related phenomena are discussed. (PsycINFO Database Record


[Tolerability of oral bisphosponates in patients with osteoporosis and other osteopathies].
Oral nitrogen containing bisphosphonates (NCB) are effective drugs to inhibit bone metabolism turnover in osteoporosis and other bone diseases. Notwithstanding, some digestive disturbances create concern on the long term acceptance of the oral route. Side effects are mainly caused by low absorption and poor solubility in digestive content. Therefore the compound may precipitate and irritate the mucosas. Furthermore, the administered amount of a particular molecule, its intrinsic potency to irritate digestive walls and the degree of exposition to such sensitive tissue are other facts that combined, may determine the clinical tolerability. Thus, a single factor cannot predict the clinical tolerability. Pamidronate, alendronate and olpadronate are the main NCB under clinical usage. Alendronate is 10 times more potent than pamidronate but possesses a similar slight solubility (2.4 vs 3.0% W/V respectively). It also seems to be more (3 times fold) ulcerogenic in experimental assays. The current available pamidronate formulation protects from esophagus and gastric exposition. Up to now and until randomized clinical trials be performed the selection of the most tolerated aminobisphosphonate in clinical practice will depend on the interplay of many factors (table 1 shows a hypothetical view). Moreover, different patients may react dissimilarly depending on their sensitivity to a particular factor. Olpadronate is free-soluble (24% W/V), almost equipotent with alendronate (figure 1) and seems to lack relevant irritation potential, but clinical data is on its early phases and is still not available. Micronization of the bisphosphonate preparation may be of help to improve tolerability as shown with newer pamidronate oral formulations. The current clinical published data shows more or less the same safety profile for pamidronate (only when enteric coated capsules are used) as alendronate, with more than 90% of patients complying with long term treatments. Anyway the trials are not entirely comparable as said before. Some other pamidronate formulations proved to be intolerable and have not been accepted. Identifying the many factors of oral NCB's digestive tolerability may help with their clinical management. And in those countries where the two compounds are available they may alternatively be used in the sensitive patients. Finally, extra-digestive side effects, not commented in this article, should also be weighted when selecting a bisphosphonate.


A Perovskite Photovoltaic Mini-Module-CsPbBr3 Photoelectrochemical Cell Tandem Device for Solar-Driven Degradation of Organic Compounds.
Recently, halide perovskites have been widely explored for high-efficiency photocatalysis or photoelectrochemical (PEC) cells. Here, in order to make an efficient photoanode electrode for the degradation of pollutants, concretely 2-mercaptobenzothiazole (MBT), nanoscale cesium lead bromide (CsPbBr3) perovskite was directly formed on the surface of mesoporous titanium dioxide (meso-TiO2) film using a two-step spin-coating process. This photoelectrode recorded a photocurrent of up to 3.02 ± 0.03 mA/cm2 under standard AM 1.5G (100 mW/cm2) illumination through an optimization process such as introducing a thin aluminum oxide (Al2O3) coating layer. Furthermore, to supply high voltage for efficient oxidation of MBT without an external bias, we developed a new photovoltaic/PEC tandem system using a methylammonium lead iodide (MAPbI3) based mini-module consisting of three solar cells interconnected in series and confirmed its successful operation. This approach looks very promising due to its applicability to various PEC reactions.


[Placing two parallel catheters by Seldinger's approach through the femoral artery for CT angiography and CT during arterioportography: evaluation of efficacy and safety].
The purpose of this study was to evaluate the efficacy and safety of placing two parallel catheters by Seldinger's approach through the femoral artery for CT angiography (CTA) and CT during arterioportography (CTAP). We performed an analysis of 30 patients. Two introducers were successfully placed in all cases. Only one minor complication was observed, a localized inguinal hematoma. The CTA/CTAP procedures were successful in all patients except six who had anatomical variations of the hepatic arterial supply. Our methods proved to be useful and safe for patients with standard hepatic arterial supply.


Effects of lutein and docosahexaenoic Acid supplementation on macular pigment optical density in a randomized controlled trial.
We studied the macular pigment ocular density (MPOD) in patients with early age macular degeneration (AMD) before and 1 year after nutritional supplementation with lutein and docosahexaenoic acid (DHA). Forty-four patients with AMD were randomly divided into two groups that received placebo (n = 21) or a nutritional supplement (n = 23, 12 mg of lutein and 280 mg of DHA daily). Heterochromatic flicker photometry was used to determine the MPOD. At baseline, the MPOD in AMD patients with placebo was 0.286 ± 0.017 meanwhile in AMD patients with supplementation it was 0.291 ± 0.016. One year later, the mean MPOD had increased by 0.059 in the placebo group and by 0.162 in patients receiving lutein and DHA. This difference between groups was significant (p < 0.05). Lutein and DHA supplementation is effective in increasing the MPOD and may aid in prevention of age related macular degeneration.


Postoperative Quality of Life in Oculoplastic Patients.
To conduct a literature review on postoperative quality of life in oculoplastic patients. The authors conducted a database search to evaluate the evidence available for the change in quality of life after oculoplastic surgery. There was a wide disparity of evidence available for different oculoplastic conditions. Certain conditions, such as nasolacrimal duct obstruction, were well-researched while other conditions, such as epiblepharon, had little to no research supporting improvement in quality of life after surgery. The scales used to measure quality of life displayed heterogeneity. There is a lack of published evidence concerning postoperative quality of life in patients with certain oculoplastic conditions such as brow ptosis, entropion, ectropion, epiblepharon, and orbital wall fracture. There is a need to standardize the quality of life data collection tools and scoring systems to allow better comparison and scrutiny of the current literature.


An international perspective on Japanese mental health law: ethics and policy.
The challenge remains in international mental health legislation trends to find appropriate balances between specific cultural norms and appropriate international mental health standards for assessment, treatment, and release of persons suffering from mental disorders. It is important that cultural norms not be used as an excuse for inaction or substandard delivery of services. Furthermore, the international community of experts must agree upon a course of action to produce a set of guidelines which can become the point of reference for accelerating a timely delivery of improved services both in and outside hospital. Criteria for admission and release should not be compromised by short-term economic considerations nor by the local limitations imposed by the accepted corporate structures in place. It may be necessary for major re-thinking to occur, in order to link the hospital and the community in an interchange of services that will be to the benefit of patients and their families. To this end community treatment orders, intensive community treatment teams, and special follow-up procedures of care have to be applied and then monitored by responsible government agencies. After years of questionable applications of law reform in Japan it is imperative that critical self-assessment be done to give proper meaning to both the spirit and rule of mental health law in Japan.


IKKbeta inhibition protects against bone and cartilage destruction in a rat model of rheumatoid arthritis.
The IKK complex regulates NF-kappaB activation, an important pathway implicated in the rheumatoid arthritis (RA) disease process. This study was undertaken to assess the efficacy of N-(6-chloro-7-methoxy-9H-beta-carbolin-8-yl)-2-methylnicotinamide (ML120B), a potent and selective small molecule inhibitor of IKKbeta. Polyarthritis was induced in rats by injection of Freund's complete adjuvant into the hind footpad. ML120B was administered orally twice daily, either prophylactically or therapeutically. Paw volumes and body weights were measured every 2-3 days throughout the study. We assessed bone erosions by several methods: histologic evaluation, quantitative micro-computed tomography (micro-CT) imaging analysis, and measurement of type I collagen fragments in the serum. Quantitative polymerase chain reaction was used to evaluate expression of messenger RNA for genes related to inflammation and to bone and cartilage integrity. Oral administration of ML120B inhibited paw swelling in a dose-dependent manner (median effective dosage 12 mg/kg twice daily) and offered significant protection against arthritis-induced weight loss as well as cartilage and bone erosion. We were able to directly demonstrate that NF-kappaB activity in arthritic joints was reduced after ML120B administration. Also, we observed that down-regulation of the NF-kappaB pathway via IKKbeta inhibition dampened the chronic inflammatory process associated with rat adjuvant-induced arthritis. The results of the present study suggest that IKKbeta inhibition is an effective therapeutic approach to treat both the inflammation and the bone/cartilage destruction observed in RA. Methods for the determination of serum markers for bone and cartilage destruction, as well as micro-CT analysis, may aid in predicting and evaluating the therapeutic efficacy of IKKbeta inhibition therapy in humans.


Premenstrual syndrome and atopy: a double-blind clinical evaluation of treatment with a gamma-globulin/histamine complex.
The relationship between atopy and premenstrual syndrome was studied in 138 women, aged between 20 and 39-years' old, who had suffered from symptoms for at least 6 months. The results showed that there was a high incidence of a personal or familial history of allergy, immediate positive skin test reactions to conventional allergens, eosinophilia, low titre of histamine latex test and high levels of IgE in the premenstrual syndrome patients compared with the normal controls. A preliminary study in 40 patients showed that a course of treatment using a gamma-globulin/histamine complex by subcutaneous injection produced a satisfactory response in 70%. A follow-on double-blind, placebo-controlled study was carried out using the same drug in 42 out of 86 women. Very effective or effective symptomatic relief was significantly higher in the group receiving active treatment. The best results were obtained in patients who had high IgE levels.


From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local Transport Region Formation.
Current models of tissue electroporation either describe tissue with its bulk properties or include cell level properties, but model only a few cells of simple shapes in low-volume fractions or are in two dimensions. We constructed a three-dimensional model of realistically shaped cells in realistic volume fractions. By using a 'unit cell' model, the equivalent dielectric properties of whole tissue could be calculated. We calculated the dielectric properties of electroporated skin. We modeled electroporation of single cells by pore formation on keratinocytes and on the papillary dermis which gave dielectric properties of the electroporated epidermis and papillary dermis. During skin electroporation, local transport regions are formed in the stratum corneum. We modeled local transport regions and increase in their radii or density which affected the dielectric properties of the stratum corneum. The final model of skin electroporation accurately describes measured electric current and voltage drop on the skin during electroporation with long low-voltage pulses. The model also accurately describes voltage drop on the skin during electroporation with short high-voltage pulses. However, our results indicate that during application of short high-voltage pulses additional processes may occur which increase the electric current. Our model connects the processes occurring at the level of cell membranes (pore formation), at the level of a skin layer (formation of local transport region in the stratum corneum) with the tissue (skin layers) and even level of organs (skin). Using a similar approach, electroporation of any tissue can be modeled, if the morphology of the tissue is known.