Kidney Stone Disease: An Update on Current Concepts.
Kidney stone disease is a crystal concretion formed usually within the kidneys. It is an increasing urological disorder of human health, affecting about 12% of the world population. It has been associated with an increased risk of end-stage renal failure. The etiology of kidney stone is multifactorial. The most common type of kidney stone is calcium oxalate formed at Randall's plaque on the renal papillary surfaces. The mechanism of stone formation is a complex process which results from several physicochemical events including supersaturation, nucleation, growth, aggregation, and retention of urinary stone constituents within tubular cells. These steps are modulated by an imbalance between factors that promote or inhibit urinary crystallization. It is also noted that cellular injury promotes retention of particles on renal papillary surfaces. The exposure of renal epithelial cells to oxalate causes a signaling cascade which leads to apoptosis by p38 mitogen-activated protein kinase pathways. Currently, there is no satisfactory drug to cure and/or prevent kidney stone recurrences. Thus, further understanding of the pathophysiology of kidney stone formation is a research area to manage urolithiasis using new drugs. Therefore, this review has intended to provide a compiled up-to-date information on kidney stone etiology, pathogenesis, and prevention approaches.


Seasonal Body Composition Variation Amongst Elite European Professional Soccer Players: An Approach of Talent Identification.
The primary aim of the investigation was to study the seasonal changes in body composition in elite European soccer players and identify key playing positional differences. Twenty-two players (age = 24 ± 3.7 years, body height = 180.45 ± 5.12 cm, body mass = 76.66 ± 5.34 kg) were tested. Players' mass (kg), lean body mass (LBM), fat free mass (FFM), fat mass (FM), muscle girths (MG) and sum of 8 skinfolds (mm) were measured across 5 time points (T0 = Start of pre-season training; T1 = End of pre-season training; T2 = Mid-season; T3 = End of mid-season break; T4 = End of season). Players were divided into their tactical positional roles for analysis. The specific positions they were divided into included defenders (n = 8), midfielders (n = 8) and forwards (n = 6). Assessment of training and matchplay exposure were also recorded. Sites-4, Sites-7, Sites-8 and Fat Mass decreased dramatically from T0 to T1 and T2 in all playing positions (p < 0.01), while no remarkable differences were found between T2, T3 and T4. Except for defenders, calf girth and lean mass were higher in T2, T3 and T4 compared to T0 and T1 (p < 0.01). Midfielders were found to be leaner than forwards and defenders in all data collection time point sessions. Defenders showed higher values in calf girth and lean body mass than midfielders and forwards. It can be concluded from this investigation that there are large variances n positional body composition profiles amongst professional European soccer players. Furthermore, significant changes are prevalent and occur across the season from LBM, FFM, MG and skinfold assessment amongst European elite level soccer players.


Ultrasonic synthesis of Oct. trans-Br2Cu(N ∩ N)2 Jahn-Teller distortion complex: XRD-properties, solvatochromism, thermal, kinetic and DNA-binding evaluations.
Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr2(N ∩ N)2]·3H2O complex with N ∩ N = 2,2-dimethylpropane-1,3-diamine was obtained. The structure of the desired complex was characterized by UV-Vis. spectroscopy, FT-IR, EDX, MS, SEM, TG/DTA and CHN-analysis. The octahedral-structure of the desired Cu(II) complex was proven via XRD single-crystal diffraction and its molecular interactions were computed by Hirschfeld surface analysis. Alcohol (as solvent) and short ultrasonic vibration dose period played a critical role in sonochemistry synthesis of octahedral neutral trans-CuBr2(N ∩ N)2 complex instead of trigonal bi-pyramidal monocation [CuBr(N ∩ N)2]Br one. Due to the Jahn-Teller effect, the complex exhibited a trans bonds elongation along Br-Cu-Br axis originating a distorted-octahedral Cu(II), as revealed by the XRD measurements (Br-Cu = 3.04 Å). Therefore, the Solvatochromic behavior of the complex was successfully performed since the trans di-bromide ions are loosely coordinated to Cu(II) center, the change in complex solutions colors by using different solvents which can be detected even by naked-eye supported atypical Jahn-Teller elongation effect formation. TG/DTA and Flynn Wall Ozawa (FWO) isoconversional kinetic methods were applied for the complex to figure out the thermal behavior, kinetic of the ligands de-structured and estimate its Ea/α relation. The complex binding mode to the CT-DNA was examined by UV-vis. spectroscopic, melting curve, CV and viscosity tests. The complex exhibited very strong DNA binding via an intercalation mode of coordination with Kb = 6.5 × 105 value.


An empirical study of the wound effect on sap flux density measured with thermal dissipation probes.
The insertion of thermal dissipation (TD) sensors on tree stems for sap flux density (SFD) measurements can lead to SFD underestimations due to a wound formation close to the drill hole. However, the wound effect has not been assessed experimentally for this method yet. Here, we propose an empirical approach to investigate the effect of the wound healing on measured sap flux with TD probes. The approach was performed for both, diffuse-porous (Fagus sylvatica (Linnaeus)) and ring-porous (Quercus petraea (Lieblein)) species. Thermal dissipation probes were installed on different dates along the growing season to document the effects of the dynamic wound formation. The trees were cut in autumn and additional sensors were installed in the cut stems, therefore, without potential effects of wound development. A range of water pressures was applied to the stem segments and SFDs were simultaneously measured by TD sensors as well as gravimetrically in the laboratory. The formation of wounds around sensors installed in living tree stems led to underestimation of SFD by 21.4 ± 3 and 47.5 ± 3.8% in beech and oak, respectively. The differences between SFD underestimations of diffuse-porous beech and ring-porous oak were, however, not statistically significant. Sensors with 5-, 11- and 22-week-old wounds also showed no significant differences, which implies that the influence of wound formation on SFD estimates was completed within the first few weeks after perforation. These results were confirmed by time courses of SFD measurements in the field. Field SFD values decreased immediately after sensor installation and reached stable values after ~2 weeks with similar underestimations to the ones observed in the laboratory. We therefore propose a feasible approach to correct directly field observations of SFD for potential underestimations due to the wound effect.


Antibodies to Candida after operations on the heart.
The occurrence of yeasts and antibodies to yeasts was studied in patients undergoing open-heart surgery without antifungal prophylaxis, and in a similar group receiving antifungal prophylaxis. An association was demonstrated between the occurrence of commensal yeasts and the appearance of antibodies. None of the patients developed overt systemic or superficial yeast infection. The antigenic stimulus for the post-operative production of antibodies appeared to be the increase in the yeast flora that occurred shortly after operation. When the commensal yeast population was suppressed by antifungal antibiotics, the antibody response was also reduced. The implications of these findings in the interpretation of serological tests for diagnosis of systemic yeast infections are discussed.


A novel 3D liver organoid system for elucidation of hepatic glucose metabolism.
Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two-dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three-dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Employing this new method of culturing cells within a hollow fiber reactor, hepatocytes were observed to self-assemble into 3D spherical organoids with preservation of tight junctions and display increased liver-specific functions. Compared to both monolayer culture and sandwich culture, the hepatocyte organoids displayed higher intracellular glycogen content, glucose consumption, and gluconeogenesis and approached the in vivo values, as also confirmed by gene expression of key enzymes. Moreover, hepatocyte organoids demonstrated more realistic sensitivity to hormonal challenges with insulin, glucagon, and dexamethasone. Finally, the exposure to high glucose demonstrated toxicities including alteration of mitochondrial membrane potential, lipid accumulation, and reactive oxygen species formation, similar to the in vivo responses, which was not captured by monolayer cultures. Collectively, hepatocyte organoids mimicked the in vivo functions better than hepatocyte monolayer and sandwich cultures, suggesting suitability for applications such as antihyperglycemic drugs screening.


Identification of essential outstanding questions for an adequate European laboratory response to Ebolavirus Zaire West Africa 2014.
On August 8 2014, the World Health Organization (WHO) declared the outbreak of Ebola Virus Disease (EVD) evolving in West Africa since December 2013, a Public Health Emergency of International Concern (PHEIC). It is expected that the outbreak of Ebolavirus Disease (EVD) in West Africa will lead to increased testing of individuals in Europe for EVD. The severity of the situation in West Africa warranted a critical appraisal of the laboratory preparedness and response for EVD, with a focus on information needs for laboratories involved in diagnostics of rare viral diseases associated with the European Network for the Diagnostics of "Imported" Viral Diseases", ENIVD. Essential knowledge and knowledge gaps for an adequate laboratory response focusing on virus properties, infection kinetics, tests specifics and field performances were identified. An inventory of the laboratory capacity for EVD diagnostics among ENIVD laboratories was made.


[Intensity of intravascular microcoagulation in chronic obstructive pulmonary disease with atherotrombosis and thrombophilia].
The growing occurrence of thrombophilic conditions in recent years, the discovery of new forms of thrombophilia, the involvement of intravascular microcoagulation in the development of many diseases make their study of primary importance especially in patients with chronic obstructive pulmonary disease and atherothrombosis. Such investigations would facilitate a deeper understanding of the detailed mechanisms of thrombosis in these patients and thereby contribute to the optimization of their treatment and prevention.


Air pollution and the heart.
Despite legislation, leading to dramatic decreases in levels of air pollution since the time of the great smogs, a large body of epidemiological evidence has demonstrated that pollution continues to have adverse effects on human health. One striking finding from the epidemiological data is that patients with cardiovascular disease are susceptible to acute rises in ambient pollutants. Mortality and hospital admissions for myocardial infarction, congestive cardiac failure and cardiac arrhythmia all increase with a rise in the concentration of both particulate and gaseous pollutants. Before concluding that this association is a causal one, plausible pathophysiological mechanisms are required. Evidence is accumulating in support of two mechanistic hypotheses: inhalation of pollutants might provoke a local inflammatory response with the consequent release into the circulation of pro-thrombotic and inflammatory cytokines. A systemic response of this nature would put individuals with coronary atheroma at increased risk of cardiac events; exposure to pollutants may have an adverse effect on cardiac autonomic control, leading to an increased risk of arrhythmia in susceptible patients. Clarification of the pollutants involved and the precise mechanisms of action is essential in designing measures by which susceptible individuals might be protected from the adverse cardiovascular effects of air pollution.


Long-term survival of Stanmore total hip replacements inserted with radiolucent bone cement.
Radio-opacifiers in bone cements are an accepted part of every-day practice. They have, however, been shown to be a potential cause of an increase in third body wear and to excite bone resorption in in vitro and in vivo studies. We reviewed the results of 228 consecutive Stanmore total hip replacements performed between 1981 and 1985 in 211 patients. All were inserted with radiolucent bone cement. Information regarding whether the prosthesis had been revised was available for all patients. Seventy-three patients (83 hips) were still alive and 41 patients (44 hips) were sufficiently healthy to attend clinic. Information regarding pain level was obtained from the remaining 32 patients. When revision of the implant was taken as the end-point, there was 95% ten-year survival, 91% fifteen-year survival and 75% eighteen-year survival. These long-term results of Stanmore THRs, performed in a district general hospital, with radiolucent bone cement, compare favourably with the other published series for this implant. We did not find the inability to see the bone cement a particular disadvantage when reviewing radiographs for signs of loosening. (Hip International 2002; 12: 274-80).


Serotyping of cell culture-adapted subgroup 2 human rotavirus strains by neutralization.
Nine human rotavirus strains from stools of infants with gastroenteritis were serially propagated in MA-104 cell cultures. All strains were identified as subgroup 2 rotaviruses by RNA gel electrophoresis, complement fixation, and enzyme-linked immunosorbent assay. The human rotavirus strains were propagated for 15 to 20 passages and then used for immunization of guinea pigs and rabbits. Animal antisera were also raised against a subgroup 1 human strain purified from stools and against the cell culture-adapted Wa strain, a reference subgroup 2 rotavirus of human origin. Cross-neutralization studies revealed the existence of two distinct serotypes within the cell culture-adapted subgroup 2 human rotaviruses: strains related and unrelated to strain Wa were classified as serotypes 1 and 3, respectively. Results with convalescent-phase sera from infants with primary rotavirus infections confirmed the existence of two serotypes within subgroup 2, and the serotypes responsible for primary subgroup 2 infections could be determined on the basis of the neutralizing reactivity of convalescent sera.


Factors affecting filamentation in Candida albicans: relationship of the uptake and distribution of proline to morphogenesis.
When glucose was present in high concentration, Candida albicans formed filaments in a phosphate-buffered medium, regardless of the nitrogen source. In lower concentrations of glucose, filamentation occurred only when various members of the glutamate, succinyl, or acetoacetyl-coenzyme A families of amino acids were used as sole nitrogen sources. Yeast morphology could be maintained either by replacing the amino acids in the medium with ammonium chloride or by making the medium high in phosphate or biotin. Studies using [U-14C]proline indicated that proline was catabolized in a manner consistent with the generation of increased cellular reducing potential and that the proline label entered into the Kreb's cycle. A reduction in Kreb's cycle activity was evidenced by an initial increase and then a rapid drop of the total organic acid content of the cells as well as in specific Kreb's cycle intermediates. Filamentation under conditions of low phosphate, high glucose, and increased cellular reduction potential, accompanied by a decrease in Kreb's cycle activity, suggests that morphogenesis in C. albicans is correlated with a Crabtree-like effect, i.e., repression of mitochondrial activity.


Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans.
The heterotrimeric motor protein, kinesin-II, and its presumptive cargo, can be observed moving anterogradely at 0.7 microm/s by intraflagellar transport (IFT) within sensory cilia of chemosensory neurons of living Caenorhabditis elegans, using a fluorescence microscope-based transport assay (Orozco, J.T., K.P. Wedaman, D. Signor, H. Brown, L. Rose, and J.M. Scholey. 1999. Nature. 398:674). Here, we report that kinesin-II, and two of its presumptive cargo molecules, OSM-1 and OSM-6, all move at approximately 1.1 microm/s in the retrograde direction along cilia and dendrites, which is consistent with the hypothesis that these proteins are retrieved from the distal endings of the cilia by a retrograde transport pathway that moves them along cilia and then dendrites, back to the neuronal cell body. To test the hypothesis that the minus end-directed microtubule motor protein, cytoplasmic dynein, drives this retrograde transport pathway, we visualized movement of kinesin-II and its cargo along dendrites and cilia in a che-3 cytoplasmic dynein mutant background, and observed an inhibition of retrograde transport in cilia but not in dendrites. In contrast, anterograde IFT proceeds normally in che-3 mutants. Thus, we propose that the class DHC1b cytoplasmic dynein, CHE-3, is specifically responsible for the retrograde transport of the anterograde motor, kinesin-II, and its cargo within sensory cilia, but not within dendrites.


Differential effects of prenylation and s-acylation on type I and II ROPS membrane interaction and function.
Prenylation primarily by geranylgeranylation is required for membrane attachment and function of type I Rho of Plants (ROPs) and Gγ proteins, while type II ROPs are attached to the plasma membrane by S-acylation. Yet, it is not known how prenylation affects ROP membrane interaction dynamics and what are the functional redundancy and specificity of type I and type II ROPs. Here, we have used the expression of ROPs in mammalian cells together with geranylgeranylation and CaaX prenylation-deficient mutants to answer these questions. Our results show that the mechanism of type II ROP S-acylation and membrane attachment is unique to plants and likely responsible for the viability of plants in the absence of CaaX prenylation activity. The prenylation of ROPs determines their steady-state distribution between the plasma membrane and the cytosol but has little effect on membrane interaction dynamics. In addition, the prenyl group type has only minor effects on ROP function. Phenotypic analysis of the CaaX prenylation-deficient pluripetala mutant epidermal cells revealed that type I ROPs affect cell structure primarily on the adaxial side, while type II ROPs are functional and induce a novel cell division phenotype in this genetic background. Taken together, our studies show how prenyl and S-acyl lipid modifications affect ROP subcellular distribution, membrane interaction dynamics, and function.


Association between 5,10-methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and conotruncal heart defects.
Reports related some polymorphisms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) to folate-dependent neural tube defects. In view of the common origin of the cells involved both in neural tube closure and heart septation, we analyzed the MTHFR C677T and A1298C polymorphisms in mothers of children with conotruncal heart defect (CD) and in their offspring to evaluate the association between the MTHFR genotype and the risk of CD. We genotyped 103 Italian mothers with CD offspring, 200 control mothers, 103 affected children and their fathers by restriction fragment length polymorphism analysis. No increased risk was observed for the prevalence of the 677TT genotype by itself in affected children and in their mothers. The combined maternal 677TT/1298AA and 677CC/1298CC genotypes have odds ratio of 1.73 and 1.85, respectively. The prevalence of 1298CC genotype in the affected children gives odds ratio of 1.90, that becomes 2.31 for the 677CC/1298CC genotype. However, none of the odds ratios was statistically significant. We observed a higher frequency of the 677T allele in Italy than in other European countries. No association has been demonstrated between the 677TT MTHFR genotype and CD.


Assays of dioxins and dioxin-like compounds in actually contaminated soils using transgenic tobacco plants carrying a recombinant mouse aryl hydrocarbon receptor-mediated β-glucuronidase reporter gene expression system.
The transgenic tobacco plant XD4V-26 carrying the recombinant mouse aryl hydrocarbon receptor XD4V-mediated β-glucuronidase (GUS) reporter gene expression system was used for assay of dioxins and dioxin-like compounds consisting of polychlorodibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls (Co-PCBs) in actually contaminated soils. The transgenic tobacco plant XD4V-26 showed a significant dose-dependent induced GUS activity when cultured on MS medium containing PCB126 [toxic equivalency factor (TEF) = 0.1]. In contrast, PCB169 and PCB180, which have 0.03 of TEF and unassigned TEF values, respectively, did not significantly induce GUS activity under the same conditions as with PCB126. When the tobacco plants were cultivated for up to 5 weeks on actually contaminated soils with dioxins and dioxin-like compounds collected from the periphery of an incinerator used for disposal of life and industrial wastes, GUS activity in the leaves was dose-dependently increased. The plants clearly detected 360 pg-TEQ g(-1) of dioxins and dioxin-like compounds in this assay. There was a positive correlation between GUS activity and TEQ value of dioxins and dioxin-like compounds in the plants. This assay does not require any extraction and purification processes for the actually contaminated soil samples.


Tonic dopamine and biases in value learning linked through a biologically inspired reinforcement learning model.
A hallmark of various psychiatric disorders is biased future predictions. Here we examined the mechanisms for biased value learning using reinforcement learning models incorporating recent findings on synaptic plasticity and opponent circuit mechanisms in the basal ganglia. We show that variations in tonic dopamine can alter the balance between learning from positive and negative reward prediction errors, leading to biased value predictions. This bias arises from the sigmoidal shapes of the dose-occupancy curves and distinct affinities of D1- and D2-type dopamine receptors: changes in tonic dopamine differentially alters the slope of the dose-occupancy curves of these receptors, thus sensitivities, at baseline dopamine concentrations. We show that this mechanism can explain biased value learning in both mice and humans and may also contribute to symptoms observed in psychiatric disorders. Our model provides a foundation for understanding the basal ganglia circuit and underscores the significance of tonic dopamine in modulating learning processes.


Large multicentre hypertension trials.
The earlier large multicentre trials in hypertensive patients addressed questions of whether mild to moderate hypertension should be treated and whether similar approaches would be effective in elderly hypertensive patients or those with isolated systolic hypertension. The research focus of recent trials has now shifted to how rather than whether such patients should be treated. Trials such as the Hypertension Optimal Treatment study attempted to discern optimal targets for long-term blood pressure control. Although unsuccessful in this primary aim, they have established the safety of aggressive blood pressure lowering to diastolic targets of less than 80 mmHg as well as the safety and efficacy of a calcium entry blocker as a first line antihypertensive approach. The Captopril Prevention Project study and Swedish Trial in Old Patients with Hypertension-2 trial focussed on whether there might be specific antiatherosclerotic advantages of the newer agents (angiotensin converting enzyme inhibitors and calcium entry blockers) over conventional therapy in comparison studies with beta blockers and diuretics. Similar efficacy for cardiovascular outcomes appears to be emerging for each of the major classes of drugs with the degree of blood pressure lowering of prime importance in cardiovascular disease prevention.


Daily Technology Interruptions and Emotional and Relational Well-Being.
The current abundance of technology in daily life creates opportunities for interruptions in couple interactions, termed technoference or phubbing. The current study examined reports from both partners in 173 romantic relationships who completed daily surveys on technoference and relational well-being measures across 14 days. By using daily diary data, we were able to examine within-person associations and more closely approximate everyday life. Utilizing multilevel modeling, we found that on days when participants rated more technoference than usual, they felt worse about their relationship, perceived more conflict over technology use, rated their face-to-face interactions as less positive, and experienced more negative mood. These relationships existed even after controlling for general feelings of relationship dissatisfaction, depression, and attachment anxiety, and there were no significant differences between women and men in these associations. This suggests that regardless of an individual's or a couple's current level of well-being, if individuals perceive technology use as interfering in their interactions with their partner, these perceptions may affect their daily assessments of their relationship and mood.


MDCT, MR and interventional radiology in biliary atresia candidates for liver transplantation.
The multi-detector computed tomography (MDCT) scan and magnetic resonance (MR) of the abdomen play a key role in the work-up to liver transplantation (LT) by identifying congenital anomalies or cirrhosis-related modifications, conditions that can require changes in surgical technique. Moreover, the MDCT and MR scans allow identification of cirrhotic liver hepatic masses, extrahepatic porto-systemic shunts, eventual thrombosis of portal system and radiological signs of portal hypertension associated with biliary atresia (BA). The aim of this paper is to review MDCT, MR imaging and interventional radiology procedures performed to evaluate morphological changes and degree of portal hypertension in pediatric patients with end-stage liver disease secondary to BA, who are candidates for LT. Advances in the field of MR, MDCT and in percutaneous minimally invasive techniques have increased the importance of radiology in the management of pediatric patients with BA who are candidates for LT.


Rural-urban disparities in nutritional status among ever-married women in Bangladesh: A Blinder-Oaxaca decomposition approach.
This study aims to investigate socioeconomic disparities in nutritional status among ever-married women in Bangladesh and to break down urban-rural differences in the underlying causes of undernutrition. We utilized data from the Bangladesh Demographic and Health Survey 2017-18, a sample size of 18328 ever-married women, including 5170 from urban residences, and 13159 from rural residences. To explore socioeconomic inequality, we employed a concentration indexing measure, while a multiple binary logistic regression model was carried out to identify the determinants associated with the outcome variable. A Blinder-Oaxaca decomposition analysis was performed to decompose the urban-rural gap in women's nutritional status using associated factors. The prevalence of undernutrition among ever-married women in Bangladesh was 12 percent. Notably, this percentage varied by region, with urban residents accounting for 8.6% and rural residents accounting for 13.3%. Our findings confirmed that undernutrition was more prevalent among women with lower wealth indexes in Bangladesh, as indicated by the concentration index (CIX = -0.26). The multivariable analysis investigating the determinants of undernutrition status among ever-married women, with a focus on residence revealed significant associations with respondent age, education, marital status, mass media access, wealth status, and division. According to the Blinder-Oaxaca decomposition and its extension, the prevalence was significantly higher in rural residences of Bangladesh than in urban residences, and the endowment effect explained 86 percent of the total urban-rural difference in undernutrition prevalence. The results of this study indicate that the factors that influence women's nutritional status in rural areas play a significant role in the gap, and the majority of the gap is caused by education and economic position. In order to effectively promote maternal health policies in Bangladesh, intervention techniques should be created that are aimed at the population, that is, the poorest and least educated.


The types of Osteoglossum formosum Müller & Schlegel, 1840 (Teleostei, Osteoglossidae).
The designation of a neotype for Scleropages formosus (Müller & Schlegel, 1840) by Pouyaud et al. (2003) triggered a search for the type specimens of the species, which were found in the collections of the Naturalis Biodiversity Center, Leiden (RMNH) and the Natural History Museum, London (BM(NH)). The publication date of the species is corrected. Moreover, detailed data on the day of capture and the type locality were uncovered. An English translation of the major part of the original Dutch description is provided, and a number of neglected colour descriptions and figures of S.formosus are discussed. Lastly, a lectotype is designated.


Patients with Congenital Limb Anomaly Show Short Telomere, Shutdown of Telomerase and Deregulated Expression of Various Telomere-Associated Proteins in Peripheral Blood Mononuclear Cells-A Case Series.
Congenital limb anomalies are outcome of improper bone formation during embryonic development when cells divide, differentiate with high rate. So, telomerase activity is essential to maintain telomere length for such highly dividing cells. Here, we report four cases of congenital limb anomalies with detailed structures of limbs along with other clinical manifestations of age less than two years. We compared telomere length, expression of telomerase and telomere-associated genes of Peripheral Blood Mononuclear Cells (PBMC) in patient and four age-matched normal individual. Patient-1 was diagnosed with congenital limb hypogenesis ectrodactyly sequence, an autosomal dominant disorder, showing absence of digits and fibula in upper and lower limb respectively. Both mother and grandmother of Patient-1 showed similar hypogenesis of limbs. Patient-2 showed bilateral clenched hand with arthrogryposis, microcephaly and holoprosencephaly. Both Patient-3 and Patient-4 has no radius in upper limb. Additionally, Paient-3 showed right sided orbital Space Occupying Lesion (SOL) and Paranasal Sinuses (PNS) whereas Patient-4 showed fused kidney with fanconi anaemia. Furthermore, all the patients showed shorter telomere length, inactive telomerase and de-regulated expression of telomere-associated proteins in PBMC compared with age-matched control group. So, we can conclude that congenital limb anomalies may be linked with telomeropathy and a study with large number of samples is required to firmly establish such association.


Canine model for investigating the impact of oral enrofloxacin on commensal coliforms and colonization with multidrug-resistant Escherichia coli.
A model was developed in dogs to determine the impact of oral enrofloxacin administration on the indigenous coliform population in the gastrointestinal tract and subsequent disposition to colonization by a strain of multidrug-resistant Escherichia coli (MDREC). Dogs given a daily oral dose of 5 mg enrofloxacin kg(-1) for 21 consecutive days showed a significant decline in faecal coliforms to levels below detectable limits by 72 h of administration. Subsequently, faecal coliforms remained suppressed throughout the period of enrofloxacin dosing. Upon termination of antibiotic administration, the number of excreted faecal coliforms slowly returned over an 8-day period, to levels comparable to those seen prior to antibiotic treatment. Enrofloxacin-treated dogs were more effectively colonized by MDREC, evidenced by a significantly increased count of MDREC in the faeces (7.1 +/- 1.5 log(10) g(-1)) compared with non-antibiotic-treated dogs (5.2 +/- 1.2; P = 0.003). Furthermore, antibiotic treatment also sustained a significantly longer period of MDREC excretion in the faeces (26.8 +/- 10.5 days) compared with animals not treated with enrofloxacin (8.5 +/- 5.4 days; P = 0.0215). These results confirm the importance of sustained delivery of an antimicrobial agent to maintain and expand the colonization potential of drug-resistant bacteria in vivo, achieved in part by reducing the competing commensal coliforms in the gastrointestinal tract to below detectable levels in the faeces. Without in vivo antimicrobial selection pressure, commensal coliforms dominated the gastrointestinal tract at the expense of the MDREC population. Conceivably, the model developed could be used to test the efficacy of novel non-antibiotic strategies aimed at monitoring and controlling gastrointestinal colonization by multidrug-resistant members of the Enterobacteriaceae that cause nosocomial infections.


Interprofessional ethics rounds concerning dialysis patients: staff's ethical reflections before and after rounds.
To evaluate whether ethics rounds stimulated ethical reflection. Philosopher-ethicist-led interprofessional team ethics rounds concerning dialysis patient care problems were applied at three Swedish hospitals. The philosophers were instructed to stimulate ethical reflection and promote mutual understanding between professions but not to offer solutions. Questionnaires directly before and after rounds were answered by 194 respondents. The analyses were primarily content analysis with Boyd's framework but were also statistical in nature. Seventy-six per cent of the respondents reported a moderate to high rating regarding new insights on ethical problem identification, but the ethics rounds did not seem to stimulate the ethical reflection that the respondents had expected (p < 0.001). Dominant new insights did not seem to fit into traditional normative ethics but were instead interpreted as hermeneutic ethics. This was illustrated in the extended perspective on the patient and increased awareness of relations to other professions. Regarding insights into how to solve ethical problems, the request for further interprofessional dialogue dominated both before and after rounds. The findings show the need for interprofessional reflective ethical practice but a balance between ethical reflection and problem solving is suggested if known patients are discussed. Further research is needed to explore the most effective leadership for reflective ethical practice.


Fluorescent small molecules with alternating triarylamine-substituted selenophenothiophene and triarylborane: synthesis, photophysical properties and anion sensing studies.
Two novel D-π-A fluorophores based on selenopheno[3,2-b]thiophene, possessing triphenylamine and 4,4'-dimethoxytriphenylamine units as donors and dimesitylborane as an acceptor, linked through a π-conjugated thiophene spacer (BTPAST and BOMeTPAST, respectively) were synthesized. Their photophysical properties were investigated in both solution and the state of aggregation and compared to those of their corresponding donor parts, having no dimesitylborane units (TPAST and OMeTPAST). All the compounds displayed large Stokes shifts between 100 and 140 nm with positive solvatochromism in solvents having different polarities. While BTPAST displayed both aggregation induced emission (AIE) and twisted intramolecular charge transfer (TICT) characteristics, the others preponderated with TICT effects. The sensing abilities of BTPAST and BOMeTPAST towards different anions were studied. Both exhibited chromogenic and fluorogenic responses to small anions such as fluoride and cyanide, for which the detection limits were found to be 0.12 and 2.43 ppm with BTPAST and 0.59 and 0.92 ppm with BOMeTPAST, respectively. These results provide guidance for the development of novel fused selenophenothiophene sensors in the field of anion sensing.


Access to institutional delivery care and reasons for home delivery in three districts of Tanzania.
Globally, health facility delivery is encouraged as a single most important strategy in preventing maternal and neonatal morbidity and mortality. However, access to facility-based delivery care remains low in many less developed countries. This study assesses facilitators and barriers to institutional delivery in three districts of Tanzania. Data come from a cross-sectional survey of random households on health behaviours and service utilization patterns among women and children aged less than 5 years. The survey was conducted in 2011 in Rufiji, Kilombero, and Ulanga districts of Tanzania, using a closed-ended questionnaire. This analysis focuses on 915 women of reproductive age who had given birth in the two years prior to the survey. Chi-square test was used to test for associations in the bivariate analysis and multivariate logistic regression was used to examine factors that influence institutional delivery. Overall, 74.5% of the 915 women delivered at health facilities in the two years prior to the survey. Multivariate analysis showed that the better the quality of antenatal care (ANC) the higher the odds of institutional delivery. Similarly, better socioeconomic status was associated with an increase in the odds of institutional delivery. Women of Sukuma ethnic background were less likely to deliver at health facilities than others. Presence of couple discussion on family planning matters was associated with higher odds of institutional delivery. Institutional delivery in Rufiji, Kilombero, and Ulanga district of Tanzania is relatively high and significantly dependent on the quality of ANC, better socioeconomic status as well as between-partner communication about family planning. Therefore, improving the quality of ANC, socioeconomic empowerment as well as promoting and supporting inter-spousal discussion on family planning matters is likely to enhance institutional delivery. Programs should also target women from the Sukuma ethnic group towards universal access to institutional delivery care in the study area.


Using Bayes' rule to model multisensory enhancement in the superior colliculus.
The deep layers of the superior colliculus (SC) integrate multisensory inputs and initiate an orienting response toward the source of stimulation (target). Multisensory enhancement, which occurs in the deep SC, is the augmentation of a neural response to sensory input of one modality by input of another modality. Multisensory enhancement appears to underlie the behavioral observation that an animal is more likely to orient toward weak stimuli if a stimulus of one modality is paired with a stimulus of another modality. Yet not all deep SC neurons are multisensory. Those that are exhibit the property of inverse effectiveness: combinations of weaker unimodal responses produce larger amounts of enhancement. We show that these neurophysiological findings support the hypothesis that deep SC neurons use their sensory inputs to compute the probability that a target is present. We model multimodal sensory inputs to the deep SC as random variables and cast the computation function in terms of Bayes' rule. Our analysis suggests that multisensory deep SC neurons are those that combine unimodal inputs that would be more uncertain by themselves. It also suggests that inverse effectiveness results because the increase in target probability due to the integration of multisensory inputs is larger when the unimodal responses are weaker.


Assessment of the right ventricle in donation after circulatory death hearts.
In donation after circulatory death heart transplantation, the donor heart is exposed to circulatory load. The right ventricle, due to its structure, has high compliance for volume load but is particularly vulnerable to increased pressure load. This study used a porcine model to conduct a functional assessment of the hemodynamics of the heart, with a focus on the right ventricle. Six pigs weighing 24.6 ± 1.4 kg were used. Circulatory death was induced by asphyxiation after median sternotomy. After 30 minutes in the state of global warm ischemia, the ascending aorta was clamped, followed by a 20-minute reperfusion of the heart with a 20°C blood cardioplegia solution. Systemic circulation was established by cardiopulmonary bypass after aortic cross-clamping. After initial reperfusion, the blood cardioplegia solution was replaced with blood. The blood was then rewarmed while the heart was still in a non-working state. Cardiac function was assessed twice in situ, first by the thermodilution method, and then, by the pressure-volume measurement both at preischemia and at three hours after initiation of reperfusion. The recovery rate of cardiac output was 75%. End-systolic elastance (P = .02) and pulmonary arterial elastance significantly increased (P = .03), but the ratio of arterial elastance to end-systolic elastance was preserved (P = .91) in the right ventricle. Despite a decrease in cardiac output after reperfusion from warm ischemia, the right ventricle had a potential to respond the elevated afterload. It is important that donations after circulatory death heart transplantation should be performed with attention to avoiding right ventricular distension.


An automatic 2D CAD algorithm for the segmentation of the IMT in ultrasound carotid artery images.
Common carotid intima-media thickness (IMT) is a reliable measure of early atherosclerosis - its accurate measurement can be used in the process of evaluating the presence and tracking the progression of disease. The aim of this study is to introduce a novel unsupervised Computer Aided Detection (CAD) algorithm that is able to identify and measure the IMT in 2D ultrasound carotid images. The developed technique relies on a suite of image processing algorithms that embeds a statistical model to identify the two interfaces that form the IMT without any user intervention. The proposed image segmentation scheme is based on a spatially continuous vascular model and consists of several steps including data preprocessing, edge filtering, model selection, edge reconstruction and data refinement. To conduct a quantitative evaluation each image was manually segmented by clinical experts and performance metrics between the segmentation results obtained by the proposed method and the ground truth data were calculated. The experimental results show that the proposed CAD system is robust in accurately estimating the IMT in ultrasound carotid data.


SREBP-dependent triazole susceptibility in Aspergillus fumigatus is mediated through direct transcriptional regulation of erg11A (cyp51A).
As triazole antifungal drug resistance during invasive Aspergillus fumigatus infection has become more prevalent, the need to understand mechanisms of resistance in A. fumigatus has increased. The presence of two erg11 (cyp51) genes in Aspergillus spp. is hypothesized to account for the inherent resistance of this mold to the triazole fluconazole (FLC). Recently, an A. fumigatus null mutant of a transcriptional regulator in the sterol regulatory element binding protein (SREBP) family, the ΔsrbA strain, was found to have increased susceptibility to FLC and voriconazole (VCZ). In this study, we examined the mechanism engendering the observed increase in A. fumigatus triazole susceptibility in the absence of SrbA. We observed a significant reduction in the erg11A transcript in the ΔsrbA strain in response to FLC and VCZ. Transcript levels of erg11B were also reduced but not to the extent of erg11A. Interestingly, erg11A transcript levels increased upon extended VCZ, but not FLC, exposure. Construction of an erg11A conditional expression strain in the ΔsrbA strain was able to restore erg11A transcript levels and, consequently, wild-type MICs to the triazole FLC. The VCZ MIC was also partially restored upon increased erg11A transcript levels; however, total ergosterol levels remained significantly reduced compared to those of the wild type. Induction of the erg11A conditional strain did not restore the hypoxia growth defect of the ΔsrbA strain. Taken together, our results demonstrate a critical role for SrbA-mediated regulation of ergosterol biosynthesis and triazole drug interactions in A. fumigatus that may have clinical importance.


Classification of Protein Structure Classes on Flexible Neutral Tree.
Accurate classification on protein structural is playing an important role in Bioinformatics. An increase in evidence demonstrates that a variety of classification methods have been employed in such a field. In this research, the features of amino acids composition, secondary structure's feature, and correlation coefficient of amino acid dimers and amino acid triplets have been used. Flexible neutral tree (FNT), a particular tree structure neutral network, has been employed as the classification model in the protein structures' classification framework. Considering different feature groups owing diverse roles in the model, impact factors of different groups have been put forward in this research. In order to evaluate different impact factors, Impact Factors Scaling (IFS) algorithm, which aim at reducing redundant information of the selected features in some degree, have been put forward. To examine the performance of such framework, the 640, 1189, and ASTRAL datasets are employed as the low-homology protein structure benchmark datasets. Experimental results demonstrate that the performance of the proposed method is better than the other methods in the low-homology protein tertiary structures.


Intimate partner violence and maternal depression during the perinatal period: a longitudinal investigation of Latinas.
This study assessed the course of perinatal depression among 210 Latinas who were and were not affected by intimate partner violence (IPV) and identified associated psychosocial factors. Peak depression prevalence occurred prenatally among 45.7% of IPV-exposed and 24.6% of non-IPV-exposed Latinas. At each assessment, depression was significantly higher for IPV-exposed compared to non-IPV-exposed mothers. Mastery and social support were associated with lower depression, whereas history of IPV, perceived stress, and avoidant coping behaviors were associated with higher depression. Findings support recommendations for routine depression and IPV screening of Latinas in perinatal clinical settings.


Synthesis of reblastatin, autolytimycin, and non-benzoquinone analogues: potent inhibitors of heat shock protein 90.
A full account of an asymmetric synthesis of reblastatin (1) and the first total synthesis of autolytimycin (2) and related structural compounds is described. The syntheses expand the utility of a highly regio- and diastereoselective hydrometalation aldehyde addition sequence to assemble the fully functionalized ansa chain of the natural products. Also documented is an intramolecular copper-mediated amidation reaction to close the 19-membered macrolactams. The amidation reaction was also employed for the generation of structural derivatives (6-9) of phenolic ansamycins. Ansamycin natural products and selected structural analogues were evaluated in a competitive binding assay to breast cancer cell lysate and a cytotoxicity assay. Both reblastatin (1) and autolytimycin (2) were shown to bind the heat shock protein 90 with enhanced binding activity (approximately 25 nM) than 17-allylamino-17-demethoxygeldanamycin (17-AAG, 4), a geldanamycin (3) derivative currently under evaluation for treatment of cancer (approximately 100 nM).


Cloning, expression, purification and preliminary X-ray diffraction studies of a novel AB₅ toxin.
AB₅ toxins are key virulence factors found in a range of pathogenic bacteria. AB₅ toxins consist of two components: a pentameric B subunit that targets eukaryotic cells by binding to glycans located on the cell surface and a catalytic A subunit that disrupts host cellular function following internalization. To date, the A subunits of AB₅ toxins either have RNA-N-glycosidase, ADP-ribosyltransferase or serine protease activity. However, it has been suggested that a novel AB₅ toxin produced by clinical isolates of Escherichia coli and Citrobacter freundii has an A subunit with metalloproteinase activity. Here, the expression, purification and crystallization of this novel AB₅ toxin from E. coli (EcxAB) and the collection of X-ray data to 1.9 Å resolution are reported.


Endoscopic Extended Sinus Surgery for Patients with Severe Chronic Rhinosinusitis with Nasal Polyps, the Choice of Mucoplasty: A Systematic Review.
The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these patients towards personalized and precision medicine. Surgery has been positioned as a suitable alternative in patients who do not achieve control with appropriate medical treatment, but polypoid recurrences remain a constraint. The emergence of new surgical approaches based on patient phenotyping and the poor disease control associated with type 2 inflammatory phenotype makes it necessary to review the role of personalized and precision surgery in managing the disease. Surgical approaches based on wide resection of bony sinus structures and the treatment of mucosa lining the sinonasal cavity have been analyzed and compared with other techniques and seem to offer more favorable surgical outcomes and improved quality of life (QoL), in addition to lower relapse rates. The innovations with new complementary surgical techniques, such as reboot surgery adding an extended autologous mucosal graft from the nasal floor (mucoplasty), may benefit endoscopic and QoL outcomes in the most severe CRSwNP patients with type 2 phenotype. Using bilateral endonasal mucoplasty as a complementary technique to reboot surgery is a suitable technical choice that has improved short- and medium-term QoL and endoscopic outcomes for patients with severe CRSwNP. These results are likely due to a combination of the extension of reboot and the inherent inflammatory and healing properties of mucoplasty. We propose this technique as a valuable surgical resource, although more robust clinical studies are needed to evaluate its long-term benefits comprehensively.


MicroRNA-21 promotes cell metastasis in cervical cancer through modulating epithelial-mesenchymal transition.
MicroRNA (miR)-21 is known to act as an oncogene in cervical cancer by promoting cell proliferation and migration; however, the underlying molecular mechanisms have remained to be fully elucidated. The present study revealed that the gene expression levels of miR-21 and epithelial-mesenchymal transition (EMT)-associated transcription factor Zinc finger E-box-binding homeobox 1 (ZEB1), in cervical cancer and lymphatic metastatic carcinoma tissues were significantly higher than those in normal tissues (P<0.05). Furthermore, the gene expression levels of miR-21 and ZEB1 were positively associated with muscular infiltration depth, parametrical invasion and lymph node metastasis in patients with cervical cancer. Immunohistochemistry assays indicated that the expression levels of ZEB1 and the mesenchymal cell marker Vimentin in cervical cancer tissues were significantly higher than those in normal cervical tissues (P<0.05). Overexpression of miR-21 in HeLa and SiHa cells caused the upregulation of the mesenchymal cell markers Vimentin and N-cadherin, and downregulation of the epithelial cell marker E-cadherin at the proteins level. In addition, overexpression of miR-21 enhanced the invasiveness of HeLa and SiHa cells. These results demonstrated that miR-21 was upregulated in cervical cancer tissues and promoted cell metastasis through modulating EMT. A better understanding of the role of miR-21 and EMT may lead to the development of more effective therapies for patients with cervical cancer.


Graves' disease in DiGeorge syndrome: patient report with a review of endocrine autoimmunity associated with 22q11.2 deletion.
DiGeorge syndrome, which falls within a wider phenotypic spectrum associated with deletions of 22q11.2, is associated with a number of endocrine disorders. These include hypoparathyroidism, hypothyroidism and growth hormone deficiency. We report an unusual case of autoimmune hyperthyroidism (Graves' disease) presenting in a 3 year-old male with DiGeorge syndrome. The development of endocrine specific autoimmune disease in a syndrome associated with immune deficiency and the spectrum of endocrine autoimmunity associated with deletions of 22q11.2 are described. Paediatricians and patients with 22q11.2 deletions should be particularly aware of the risks of developing disorders of thyroid function.


[The winter seasonality of intestinal infections].
On the basis of various publications and his own researches the author analyses the possible causes of winter seasonal intestinal infections. It was found out that typical summer-autumn seasonal rate of bacterial intestinal infections turned into morbidity upgrowth in cold periods of year because of serious violations of hygienic regulations and sanitary rules of water supplies. The winter seasonal character of viral intestinal infections is basically connected with water-borne transmission due to high chlorine resistance of causative agents, especially at low temperatures. As for water-borne transmission, no principal differences were disclosed in seasonal characteristic features of typhoid and hepatitis A in the same social and natural conditions.


Eastern North America as an independent center of plant domestication.
The status of eastern North America as an independent center of plant domestication has recently been called into question by a number of genetic and archaeological studies, which suggest that the region may not have witnessed the independent domestication of local crop plants, but rather may have been on the receiving end of domesticated crop plants introduced from Mexico. Here, I provide a synthesis of the currently available archaeological and genetic evidence from both eastern North America and Mexico regarding the spatial and temporal context of initial domestication of the four plant species identified as potential eastern North American domesticates: marshelder (Iva annua), chenopod (Chenopodium berlandieri), squash (Cucurbita pepo), and sunflower (Helianthus annuus). Genetic and archaeological evidence provides strong support for the independent domestication of all four of these plant species in the eastern United States and reconfirms the region as one of the world's independent centers of domestication.


FI: The Fecobiome Initiative.
Animal husbandry has been key to the sustainability of human societies for millennia. Livestock animals, such as cattle, convert plants to protein biomass due to a compartmentalized gastrointestinal tract (GIT) and the complementary contributions of a diverse GIT microbiota, thereby providing humans with meat and dairy products. Research on cattle gut microbial symbionts has mainly focused on the rumen (which is the primary fermentation compartment) and there is a paucity of functional insight on the intestinal (distal end) microbiota, where most foodborne zoonotic bacteria reside. Here, we present the Fecobiome Initiative (or FI), an international effort that aims at facilitating collaboration on research projects related to the intestinal microbiota, disseminating research results, and increasing public availability of resources. By doing so, the FI can help mitigate foodborne and animal pathogens that threaten livestock and human health, reduce the emergence and spread of antimicrobial resistance in cattle and their proximate environment, and potentially improve the welfare and nutrition of animals. We invite all researchers interested in this type of research to join the FI through our website: www.fecobiome.com.


A technological assessment of the current and future status of hemodialysis.
The principles of hemodialysis and the technology of hemodialysis, as currently practiced, have been described in some detail. Future trends in the development of these devices have been considered briefly. For the immediate future, the trend that is expected to have the greatest influence is the trend towards shorter durations of treatment. Patient preference and economic pressures have already set this trend in motion.


Guanine nucleotide and cation regulation of mu, delta, and kappa opioid receptor binding: evidence for differential postnatal development in rat brain.
A study of the onset of cation and guanine nucleotide regulation of delta, mu, and kappa rat brain opioid receptors during postnatal development was undertaken. Site-specific binding assays were utilized for each receptor type and the effects of 0.5 mM MnCl2, 100 mM NaCl, and/or 50 microM guanosine-5'-(beta, gamma-imido) triphosphate [Gpp(NH)p] were assessed. The most pronounced changes of opioid binding were seen in the presence of Mn2+. In adults, agonist binding to delta sites was stimulated by Mn2+, whereas that to mu sites was not affected and kappa binding was inhibited. The postnatal development of Mn2+ regulation for the three receptor subtypes was distinctly different. The largest effects were seen on delta sites detected in the early neonatal period, Mn2+ eliciting a 68% stimulation of binding over controls at day 1. Significant inhibition of kappa site binding by Mn2+ was detected only after the third postnatal week. Mn2+ caused a significant reversal of Gpp(NH)p inhibition of delta binding in the early neonatal period, exceeding that in the absence of regulators. Inhibition of mu and delta receptor binding by Na+ was greater, and the Mn2+ reversal of this effect was smaller, in the first 2 postnatal weeks than in adults. Gpp(NH)p + Na+ regulation did not change appreciably during the postnatal period. However, Mn2+ reversal of the considerable inhibition elicited by the combination of Na+ and Gpp(HN)p was developmental time-dependent. The data are discussed in terms of multiple sites of interaction for guanine nucleotides and cations.(ABSTRACT TRUNCATED AT 250 WORDS)


Longevous Cycling of Rechargeable Zn-air Battery Enabled by "raisin-bread" Cobalt Oxynitride/Porous Carbon Hybrid Electrocatalysts.
Developing commercially viable electrocatalyst lies at the research hotspot of rechargeable Zn-air batteries, but it is still challenging to meet the requirements of energy efficiency and durability in realistic applications. Strategic material design is critical to addressing its drawbacks in terms of sluggish kinetics of oxygen reactions and limited battery lifespan. Herein, a "raisin-bread" architecture is designed for a hybrid catalyst constituting cobalt nitride as the core nanoparticle with thin oxidized coverings, which is further deposited within porous carbon aerogel. Based on synchrotron-based characterizations, this hybrid provides oxygen vacancies and Co-Nx -C sites as the active sites, resulting from a strong coupling between CoOx Ny nanoparticles and 3D conductive carbon scaffolds. Compared to the oxide reference, it performs enhanced stability in harsh electrocatalytic environments, highlighting the benefits of the oxynitride. Furthermore, the 3D conductive scaffolds improve charge/mass transportation and boost durability of these active sites. Density functional theory calculations reveal that the introduced N species into hybrid can synergistically tune the d-band center of cobalt and improve its bifunctional activity. As a result, the obtained air cathode exhibits bifunctional overpotential of 0.65 V and a battery lifetime exceeding 1350 hours, which sets a new record for rechargeable Zn-air battery reported so far. This article is protected by copyright. All rights reserved.


Unique DNA methylation loci distinguish anatomic site and HPV status in head and neck squamous cell carcinoma.
We have used a genome-wide approach to identify novel differentially methylated CpG dinucleotides that are seen in different anatomic sites of head and neck squamous cell carcinoma (HNSCC), as well as those that might be related to HPV status in the oropharynx. We conducted genome-wide DNA methylation profiling of primary tumor samples and corresponding adjacent mucosa from 118 HNSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY, using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M-value). When datasets were individually analyzed by anatomic site of the primary tumor, we identified 293 differentially methylated CpG loci in oral cavity squamous cell carcinoma (SCC), 219 differentially methylated CpG loci in laryngeal SCC, and 460 differentially methylated in oropharyngeal SCC. A subset of these differentially methylated CpG loci was common across all anatomic sites of HNSCC. Stratification by HPV status revealed a significantly higher number of differentially methylated CpG loci in HPV+ patients. Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used as molecular classifiers of this disease, revealing many new avenues of investigation for this disease.


Aspirin induces apoptosis in vitro and inhibits tumor growth of human hepatocellular carcinoma cells in a nude mouse xenograft model.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to induce apoptosis in a variety of cancer cells, including colon, prostate, breast and leukemia. Among them, aspirin, a classical NSAID, shows promise in cancer therapy in certain types of cancers. We hypothesized that aspirin might affect the growth of liver cancer cells since liver is the principal site for aspirin metabolism. Therefore, we investigated the effects of aspirin on the HepG2 human hepatocellular carcinoma cell line in vitro and the HepG2 cell xenograft model in BALB/c nude mice. We found that treatment with aspirin inhibited cell growth and induced apoptosis involving both extrinsic and intrinsic pathways as measured by DNA ladder formation, alteration in the Bax/Bcl-2 ratio, activation of the caspase activities and related protein expressions. In vivo antitumor activity assay also showed that aspirin resulted in significant tumor growth inhibition compared to the control. Oral administration of aspirin (100 mg/kg/day) caused a significant reduction in the growth of HepG2 tumors in nude mice. These findings suggest that aspirin may be used as a promising anticancer agent against liver cancer.


Targeting peptides and positron emission tomography.
Biologically active peptides have during the last decades made their way into conventional nuclear medicine diagnosis using single photon emission computed tomography (SPECT) and gamma-camera. Several clinical trails are also investigating the role of radiolabeled peptides for targeting radionuclide therapy. This has raised the question as to whether positron emission tomography (PET) can be used in order to obtain better quantitative information of the peptide distribution in tumor and healthy organs, i.e., to get a better dosimetry. Positron emitting analogs of the therapeutic radionuclides used have been produced and successfully applied in peptide pharmacokinetic measurements with PET. But the recent boom in (18)FDG-PET ((18)FDG = [(18)F]2-deoxy-2-fluoro-D-glucose), and with this a worldwide increasing number of PET systems, has also inspired several research groups to hunt for alternative labels to be used for peptide diagnostics and PET. The rapid kinetic of short peptides agrees well with the short half-lives of standard PET nuclides like (11)C and (18)F. Especially, (18)F appears to be excellent for labeling bioactive peptides due to its favorable physical and nuclear characteristics. However, with present techniques labeling peptides with (18)F is laborious and time-consuming, and is not yet a clinical alternative. Other halogens like (75, 76)Br and (124)I are, from the chemical point of view, easier to apply. But an even better labeling alternative may be positron emitting metal ions like (55)Co, (68)Ga, and (110m)In since they tend to give better intracellular retention and thus a better signal-to-background ratio than the halogen labels. The main drawback with these radionuclides is that they are not readily available. Some of these radionuclides also emit gamma in their decay that may affect the measuring properties of the PET equipment. This article reviews mainly the present situation of production and use of nonconventional positron emitters for peptide labeling.


ABCA1 69C>T Polymorphism and the Risk of Type 2 Diabetes Mellitus: A Systematic Review and Updated Meta-Analysis.
The ATP-binding cassette transporter A1 (ABCA1) is likely associated with the risk of type 2 diabetes mellitus (T2DM) via β cell function modification, but the evidence on the association remains unclear. This study aimed to investigate the relationship between the ABCA1 69C>T polymorphism and the risk of T2DM through a systematic review and meta-analysis. The PubMed, Web of Science, and Embase databases were searched for qualified studies published until August 2020. Studies that included the association between the ABCA1 69C>T polymorphism and the risk of T2DM were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated. We analyzed data from a total of 10 studies involving 17,742 patients. We found that the CC or CT genotype was associated with increased risk of T2DM than the TT genotype (OR, 1.41; 95% CI, 1.02-1.93). In the Asian population, the C allele carriers had a higher risk of T2DM than those with the TT genotype; the ORs of the CC and CT genotypes were 1.80 (95% CI, 1.21-2.68) and 1.61 (95% CI, and 1.29-2.01), respectively. This meta-analysis confirmed that the ABCA1 69C>T genotype showed a decrease risk of T2DM compared to the CC or CT genotypes.


Mean Blood Pressure Difference among Adolescents Based on Dyssomnia Types.
Dyssomnia is the most frequent sleep disturbance and associated with increased blood pressure. There has been no study determining the difference in mean blood pressure based on dyssomnia types among adolescents. To determine the difference in mean blood pressure among adolescents based on dyssomnia types. Cross-sectional study was conducted in SMP Negeri 1 Muara Batang Gadis in April 2016. Samples were students having sleep disturbance based on Sleep Disturbance Scale for Children (SDSC) questionnaire. Stature and blood pressure data were collected along with demographic data and sleep disorder questionnaire. Analyses were done with Kruskal-Wallis test and logistic regression. P - value < 0.05 was considered significant. Seventy-six samples were obtained with mean age 13.9 (SD 1.14) years - old. Dyssomnia proportion and hypertension were 72/76 and 20/76 respectively. Mean systolic (SBP) and diastolic blood pressure (DBP) was 111.1 (SD 16.46) mmHg and 70.3 (SD 11.98) mmHg respectively. Mean SDSC score was 49.7 (SD 8.96), and the most frequent dyssomnia type was disorders of initiating and maintaining sleep. Age and sex were not the risk factors of hypertension in dyssomnia. There was a significant difference in mean SBP (P = 0.006) and DBP (P = 0.022) based on dyssomnia types. Combination dyssomnia type had the highest mean blood pressure among dyssomnia types. There is a significant difference in mean blood pressure among adolescents based on dyssomnia types.


The glycerophosphocholine acyltransferase Gpc1 contributes to phosphatidylcholine biosynthesis, long-term viability, and embedded hyphal growth in Candida albicans.
Candida albicans is a commensal fungus, opportunistic pathogen, and the most common cause of fungal infection in humans. The biosynthesis of phosphatidylcholine (PC), a major eukaryotic glycerophospholipid, occurs through two primary pathways. In Saccharomyces cerevisiae and some plants, a third PC synthesis pathway, the PC deacylation/reacylation pathway (PC-DRP), has been characterized. PC-DRP begins with the acylation of the lipid turnover product, glycerophosphocholine (GPC), by the GPC acyltransferase, Gpc1, to form Lyso-PC. Lyso-PC is then acylated by lysolipid acyltransferase, Lpt1, to produce PC. Importantly, GPC, the substrate for Gpc1, is a ubiquitous metabolite available within the host. GPC is imported by C. albicans, and deletion of the major GPC transporter, Git3, leads to decreased virulence in a murine model. Here we report that GPC can be directly acylated in C. albicans by the protein product of orf19.988, a homolog of ScGpc1. Through lipidomic studies, we show loss of Gpc1 leads to a decrease in PC levels. This decrease occurs in the absence of exogenous GPC, indicating that the impact on PC levels may be greater in the human host where GPC is available. A gpc1Δ/Δ strain exhibits several sensitivities to antifungals that target lipid metabolism. Further, loss of Gpc1 results in both a hyphal growth defect in embedded conditions, and a decrease in long-term cell viability. These results demonstrate for the first time the importance of Gpc1 and this alternative PC biosynthesis route (PC-DRP) to the physiology of a pathogenic fungus.


Excessive dose requirements of local anaesthetic for epidural analgesia. How far should an epidural catheter be inserted?
On two separate occasions, a 78-year-old obese man suffering from congestive cardiac failure and peripheral vascular disease, required epidural anaesthesia for surgery to his leg. The dosage requirement on the first occasion was large and much greater than on the second occasion. Reasons for the difference in dosage are discussed. We suggest an epidural catheter should be inserted 3 cm into the epidural space.


MAP2 expression and neuritic outgrowth and branching are coregulated through region-specific neuro-astroglial interactions.
Embryonic neurons from the rat striatum and mesencephalon were plated on mesencephalic or striatal astrocytes in 4 possible combinations. It was found that specific traits are expressed by the neurons when they are grown on homotopic astrocytes (neurons and astrocytes from the same region). These traits are the following: 1. The number of cells stained with an antibody raised against the microtubule-associated protein 2 (MAP2) is higher in homotopic than in heterotopic cocultures. This is true for both mesencephalic and striatal neurons. 2. In homotopic conditions, there is an increase in the number of cells having more primary neurites and branching points. This effect is observed for both neuronal populations but is more pronounced in mesencephalic neurons. 3. The intensity of MAP2 staining was correlated with the branching ability of the neurons. First, on comparing MAP2-positive and MAP2-negative cells, it was found that, in any combination (homotopic and heterotopic cocultures), the number of primary neurites and branching points was much higher in MAP2-positive cells. In fact, almost no branching activity was found in MAP2-negative neurons. Second, within the MAP2-positive neuronal population, the higher number of branching points observed under homotopic neuro-astroglial conditions was mostly due to the neuritic compartment, which was strongly and homogeneously stained with the anti-MAP2 antibody. These observations strongly suggest that the astrocytic environment regulates the synthesis and/or intracellular distribution of MAP2, as well as the morphology of the neurons, and that this regulation is region specific.


Natural Products in Renal-Associated Drug Discovery.
The global increase in the incidence of kidney failure constitutes a major public health problem. Kidney disease is classified into acute and chronic: acute kidney injury (AKI) is associated with an abrupt decline in kidney function and chronic kidney disease (CKD) with chronic renal failure for more than three months. Although both kidney syndromes are multifactorial, inflammation and oxidative stress play major roles in the diversity of processes leading to these kidney malfunctions. Here, we reviewed various publications on medicinal plants with antioxidant and anti-inflammatory properties with the potential to treat and manage kidney-associated diseases in rodent models. Additionally, we conducted a meta-analysis to identify gene signatures and associated biological processes perturbed in human and mouse cells treated with antioxidants such as epigallocatechin gallate (EGCG), the active ingredient in green tea, and the mushroom Ganoderma lucidum (GL) and in kidney disease rodent models. We identified EGCG- and GL-regulated gene signatures linked to metabolism; inflammation (NRG1, E2F1, NFKB1 and JUN); ion signalling; transport; renal processes (SLC12A1 and LOX) and VEGF, ERBB and BDNF signalling. Medicinal plant extracts are proving to be effective for the prevention, management and treatment of kidney-associated diseases; however, more detailed characterisations of their targets are needed to enable more trust in their application in the management of kidney-associated diseases.


[Mesenteric fibromatosis as the cause of a single abdominal mass].
We present a mesenteric desmoid tumor in a man without associated diseases. Characteristics of this tumor are reviewed and the need to perform total exeresis of the mass for diagnosis is emphasized. Although surgery is the treatment of choice, alternative treatments are recommended when surgery cannot be performed, has been incomplete, or in cases of repeated recurrence.


Demographic and public health characteristics explain large part of variability in COVID-19 mortality across countries.
The numbers of coronavirus disease 2019 (COVID-19) deaths per million people differ widely across countries. Often, the causal effects of interventions taken by authorities are unjustifiably concluded based on the comparison of pure mortalities in countries where interventions consisting different strategies have been taken. Moreover, the possible effects of other factors are only rarely considered. We used data from open databases (European Centre for Disease Prevention and Control, World Bank Open Data, The BCG World Atlas) and publications to develop a model that could largely explain the differences in cumulative mortality between countries using non-interventional (mostly socio-demographic) factors. Statistically significant associations with the logarithmic COVID-19 mortality were found with the following: proportion of people aged 80 years and above, population density, proportion of urban population, gross domestic product, number of hospital beds per population, average temperature in March and incidence of tuberculosis. The final model could explain 67% of the variability. This finding could also be interpreted as follows: less than a third of the variability in logarithmic mortality differences could be modified by diverse non-pharmaceutical interventions ranging from case isolation to comprehensive measures, constituting case isolation, social distancing of the entire population and closure of schools and borders. In particular countries, the number of people who will die from COVID-19 is largely given by factors that cannot be drastically changed as an immediate reaction to the pandemic and authorities should focus on modifiable variables, e.g. the number of hospital beds.


Contact angle hysteresis on superhydrophobic stripes.
We study experimentally and discuss quantitatively the contact angle hysteresis on striped superhydrophobic surfaces as a function of a solid fraction, ϕS. It is shown that the receding regime is determined by a longitudinal sliding motion of the deformed contact line. Despite an anisotropy of the texture the receding contact angle remains isotropic, i.e., is practically the same in the longitudinal and transverse directions. The cosine of the receding angle grows nonlinearly with ϕS. To interpret this we develop a theoretical model, which shows that the value of the receding angle depends both on weak defects at smooth solid areas and on the strong defects due to the elastic energy of the deformed contact line, which scales as ϕS(2)lnϕS. The advancing contact angle was found to be anisotropic, except in a dilute regime, and its value is shown to be determined by the rolling motion of the drop. The cosine of the longitudinal advancing angle depends linearly on ϕS, but a satisfactory fit to the data can only be provided if we generalize the Cassie equation to account for weak defects. The cosine of the transverse advancing angle is much smaller and is maximized at ϕS ≃ 0.5. An explanation of its value can be obtained if we invoke an additional energy due to strong defects in this direction, which is shown to be caused by the adhesion of the drop on solid sectors and is proportional to ϕS(2). Finally, the contact angle hysteresis is found to be quite large and generally anisotropic, but it becomes isotropic when ϕS ≤ 0.2.


4-Octyl Itaconate Alleviates Airway Eosinophilic Inflammation by Suppressing Chemokines and Eosinophil Development.
4-Octyl itaconate (4-OI) is a derivative of the Krebs cycle-derived metabolite itaconate and displays an array of antimicrobial and anti-inflammatory properties through modifying cysteine residues within protein targets. We have found that 4-OI significantly reduces the production of eosinophil-targeted chemokines in a variety of cell types, including M1 and M2 macrophages, Th2 cells, and A549 respiratory epithelial cells. Notably, the suppression of these chemokines in M1 macrophages was found to be NRF2-dependent. In addition, 4-OI can interfere with IL-5 signaling and directly affect eosinophil differentiation. In a model of eosinophilic airway inflammation in BALB/c mice, 4-OI alleviated airway resistance and reduced eosinophil recruitment to the lungs. Our findings suggest that itaconate derivatives could be promising therapeutic agents for the treatment of eosinophilic asthma.


The JAK/STAT3 pathway is a common inducer of astrocyte reactivity in Alzheimer's and Huntington's diseases.
Astrocyte reactivity is a hallmark of neurodegenerative diseases (ND), but its effects on disease outcomes remain highly debated. Elucidation of the signaling cascades inducing reactivity in astrocytes during ND would help characterize the function of these cells and identify novel molecular targets to modulate disease progression. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is associated with reactive astrocytes in models of acute injury, but it is unknown whether this pathway is directly responsible for astrocyte reactivity in progressive pathological conditions such as ND. In this study, we examined whether the JAK/STAT3 pathway promotes astrocyte reactivity in several animal models of ND. The JAK/STAT3 pathway was activated in reactive astrocytes in two transgenic mouse models of Alzheimer's disease and in a mouse and a nonhuman primate lentiviral vector-based model of Huntington's disease (HD). To determine whether this cascade was instrumental for astrocyte reactivity, we used a lentiviral vector that specifically targets astrocytes in vivo to overexpress the endogenous inhibitor of the JAK/STAT3 pathway [suppressor of cytokine signaling 3 (SOCS3)]. SOCS3 significantly inhibited this pathway in astrocytes, prevented astrocyte reactivity, and decreased microglial activation in models of both diseases. Inhibition of the JAK/STAT3 pathway within reactive astrocytes also increased the number of huntingtin aggregates, a neuropathological hallmark of HD, but did not influence neuronal death. Our data demonstrate that the JAK/STAT3 pathway is a common mediator of astrocyte reactivity that is highly conserved between disease states, species, and brain regions. This universal signaling cascade represents a potent target to study the role of reactive astrocytes in ND.


Seed-mediated co-reduction in a large lattice mismatch system: synthesis of Pd-Cu nanostructures.
Metal nanoparticles (NPs) are of interest for applications in catalysis, electronics, chemical sensing, and more. Their utility is dictated by their composition and physical parameters such as particle size, particle shape, and overall architecture (e.g., hollow vs. solid). Interestingly, the addition of a second metal to create bimetallic NPs adds multifunctionality, with new emergent properties common. However, synthesizing structurally defined bimetallic NPs remains a great challenge. One synthetic pathway to architecturally controlled bimetallic NPs is seed-mediated co-reduction (SMCR) in which two metal precursors are simultaneously co-reduced to deposit metal onto shape-controlled metal seeds, which direct the overgrowth. Previously demonstrated in a Au-Pd system, here SMCR is applied to a system with a larger lattice mismatch between the depositing metals: Pd and Cu (7% mismatch for Pd-Cu vs. 4% for Au-Pd). Through manipulation of precursor reduction kinetics, the morphology and bimetallic distribution of the resultant NPs can be tuned to achieve eight-branched Pd-Cu heterostructures with Cu localized at the tips of the Pd nanocubes as well as branched Pd-Cu alloyed nanostructures and polyhedra. Significantly, the symmetry of the seeds can be transferred to the final nanostructures. This study expands our understanding of SMCR as a route to structurally defined bimetallic nanostructures and the synthesis of multicomponent nanomaterials more generally.


Effects of progressive reduction in coronary blood flow on regional and global left ventricular contraction and relaxation during normal and increased afterload: a roentgen videometric study.
The effects of step-wise reduction in left circumflex coronary blood flow on: 1) posteroinferior wall dynamics; 2) normally-perfused anterior wall dynamics; and 3) cavity function were assessed simultaneously by roentgen videometric analysis of left ventricular angiograms in open-chest dogs during normal and increased afterload. At control coronary flow with normal afterload, peak rates of systolic thickening and diastolic thinning of the posteroinferior and anterior walls were similar. Step-wise reduction in circumflex coronary flow resulted in a progressive fall in systolic and diastolic posteroinferior wall dynamics. Increased LV afterload resulted in a decrease in posteroinferior wall dynamics even at control coronary flow, and reduction in flow resulted in even greater deterioration than occurred with normal afterload. The decrease in posteroinferior wall dynamics with reduction in circumflex coronary flow was accompanied by an increase in peak rates of systolic thickening and diastolic thinning of the normally perfused anterior wall. The level of coronary blood flow at which this increase in anterior wall dynamics occurred, varied with LV loading conditions, occurring earlier when afterload was increased. There was no earlier or greater decrease in diastolic than systolic wall dynamics with progressive reduction in coronary flow with either normal or increased afterload. Left ventricular end-diastolic volume, end-diastolic pressure and ejection fraction changed little until coronary blood flow was reduced to 50% of control; by contrast, stroke-work was exquisitely sensitive to changes in coronary flow. There was no correlation between changes in regional and cavity systolic or diastolic function. The delay in onset of LV cavity dysfunction with ischemia may have been partly due to the "compensatory increase" in anterior wall dynamics, counterbalancing the impaired posteroinferior wall dynamics.


Halogen bond catalysis of the [4+2] cycloaddition reaction of 2-alkenylindoles: catalytic modes and stereoselectivity.
Halogen bond donor catalysts have been widely used in organic reactions because they are environmentally friendly, inexpensive and recyclable. The [4+2] cycloaddition reaction is a key reaction in organic synthesis because of its ease of use, fast speed, and wide range of applications. In this work, halogen bond catalysis in the [4+2] cycloaddition reaction between 2-alkenylindoles was investigated based on DFT calculations. There are two modes of I⋯π halogen bond catalysis: either on the ethenyl of 2-alkenylindole (mode A) or on the five-membered ring of 2-alkenylindole (mode B). Both modes involve two steps: the formation of carbon-carbon bonds and the formation of six-membered rings. Gibbs free energy barriers were determined to investigate the stereoselectivity of the endo pathway and exo pathway. For mode A, the exo products were more easily generated when the substituent R = H, and the N-H⋯π interaction promoted high endo selectivity in the case of the substituent R = Ph. For mode B, an increasing proportion of endo products can be obtained in the order of catalyst I2, IBr and ICl. The π⋯π interaction of the substituent R = Ph promotes the [4+2] cycloaddition reaction, which is consistent with the experimental observation that R = Ph has a higher yield than R = H. The study of different catalytic modes and stereoselectivity would provide new ideas for the further study of the [4+2] cycloaddition reaction.


[Atypical antipsychotics in the elderly].
Central criteria for the definition of atypical antipsychotics are antipsychotic efficacy and minimal or none extrapyramidal symptoms (EPS). This last criterium is of importance in the differentiation with the traditional antipsychotics. Of the four atypical antipsychotics which are discussed here, clozapine is the most atypical. The best proof is its good efficacy in the treatment of Parkinson psychosis with minimal adverse effects on motor function. Clozapine is the best choice for this indication. At this moment there is not enough evidence available concerning quetiapine. Risperidon and olanzapine give more Dopamine2-occupancy with higher doses and can evoke EPS, but this is still less compared to the traditional antipsychotics. All four atypical drugs cause less tardive dyskinesia. Atypical antipsychotics are not well studied in the treatment of elderly patients with functional psychosis. However the available information and the literature on the treatment of young adults makes it probable that the atypical antipsychotics are at least as effective in the elderly as the traditional antipsychotics. The median daily doses are lower for elderly than for younger patients. Risperidon has been proven effective in the treatment of agressive behaviour in dementia. Atypical antipsychotics have their 'own' adverse effects. Those which have the most impact in the elderly are discussed.


Role of l-Ca(2+) channels in intestinal pacing in wild-type and W/W(V) mice.
Rhythmic contractions generating transit in the digestive tract are paced by a network of cells called interstitial cells of Cajal (ICC) found in the myenteric plexus (MP). ICC generate cyclic depolarizations termed "slow waves" that are passively transmitted to the smooth muscle to initiate contractions. The opening of l-Ca(2+) channels are believed to be primarily responsible for the influx of calcium generating a contraction in smooth muscle. However, l-Ca(2+) channels are not thought to be important in generating the pacing current found in ICC. Using intact segments of circular (CM) and longitudinal (LM) muscle from wild-type mice and mice lacking c-kit kinase (W/W(V)), we found that l-Ca(2+) channel currents are required for pacing at normal frequencies to occur. Application of 1 muM nicardipine caused a significant decrease in contraction amplitude and frequency in LM and CM that was successfully blocked with BAY K 8644. Nicardipine also abolished the pacing gradient found throughout the intestines, resulting in a uniform contraction frequency of 30-40/minute. Stimulating l-Ca(2+) channels with BAY K 8644 neither removed nor recovered the pacing gradient. W/W(V) mice, which lack ICC-MP, also exhibited a pacing gradient in LM. Application of nicardipine to LM segments of W/W(V) mouse intestine did not reduce pacing frequency, and in jejunum, resulted in a slight increase. BAY K 8644 did not affect pacing frequency in W/W(V) tissue. In conclusion, we found that l-Ca(2+) channel activity was required for normal pacing frequencies and to maintain the pacing frequency gradient found throughout the intestines in wild-type but not in W/W(V) mouse intestine.


Do statin medications impact renal functional or oncologic outcomes for robot-assisted partial nephrectomy?
To evaluate if statin medications (3-hydroxyl-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors) improve either oncologic or renal functional outcomes for patients undergoing robot-assisted partial nephrectomy (RPN). Patients undergoing RPN between March 2008 and October 2013 were evaluated from a prospectively maintained database for statin usage. The rate of perioperative acute kidney injury (AKI), as defined according to the RIFLE criteria, and the progression of chronic kidney disease (CKD) were compared between users and nonusers. Oncologic outcomes and rate of progression were compared between users and nonusers. One hundred four (31%) of 339 patients were on statin therapy preoperatively and continued this medication peri- and postoperatively. Statin patients were older and had higher rates of comorbidities, including coronary artery disease, diabetes, and hypertension (p<0.0001 for all).The rate of AKI in the statin (16%) and nonstatin patients (14%) (p=0.60) and CKD progression based on Kaplan-Meier estimates (p=0.57) were similar between both the groups. Subgroup analysis of the 271 (80%) patients with hilar clamping also had similar rates of AKI, in statin users 10% vs 12% in nonusers (p=0.50). Multivariate analysis of factors affecting CKD progression confirmed these findings. Oncologic progression was not affected by statin therapy (p=0.90). Statin medications do not appear to influence perioperative renal function following RPN, in either clamped or unclamped procedures. Continuation of these medications may be continued perioperatively, but any effect on renal functional or oncologic outcomes was not elucidated in this study.


Epigenetically altered miR-1247 functions as a tumor suppressor in pancreatic cancer.
Altered expression of microRNAs has been strongly implicated in human cancers, and growing evidence is emerging that a number of miRNAs are downregulated in cancer associated with CpG island hypermethylation. Although pancreatic cancer is one of the most malignant human cancers, the roles of miRNAs underlying the tumorigenesis of pancreatic cancer are still poorly understood. In the present study, we explored the molecular functional role of microRNA-1247 as tumor suppressor associated with epigenetic alteration in pancreatic cancer. CpG islands methylation of miR-1247 is frequently observed in various pancreatic cancer cell lines and in primary pancreatic tumors, but not in normal pancreatic tissue. Ectopic expression of miR-1247 in five pancreatic cancer cell lines results in suppressing of cell growth, proliferation, migration, and invasion in vitro and tumorigenicity of pancreatic cancer cells in vivo. Interestingly, we found one putative target gene of miR-1247, regulator of chromosome condensation 2 (RCC2), harbored miR-1247 target sequences in the 3' UTR of its mRNA. In functional studies in vitro to understand the interaction between miR-1247 and RCC2, decreasing of RCC2 gene expression by miR-1247 was observed by immunoblotting and immunohistochemistry at both mRNA and protein levels. Moreover, luciferase reporter assay confirmed that RCC2 was a direct target of miR-1247. Taken together, our data suggest that CpG island hypermethylation of miR-1247 is responsible for its downregulation in pancreatic cancer, and ectopic expression of miR-1247 functions as a potential tumor suppressor targeting RCC2 in pancreatic cancer cells.


Natural History of Serviceable Hearing During Active Surveillance of Nongrowing Sporadic Vestibular Schwannoma Supports Consideration of Initial Wait-and-Scan Management.
The treatment paradigm of vestibular schwannoma (VS) focuses on preservation of neurologic function, with small tumors increasingly managed with active surveillance. Often, tumor size and hearing outcomes are poorly correlated. The aim of the current work was to describe the natural history of hearing among patients with nongrowing VS during observational management. Historical cohort study. Adults with sporadic VS. Wait-and-scan management. Maintenance of serviceable hearing (SH) after diagnosis. Among 228 patients with nongrowing VS, 157 patients had SH at diagnosis. Rates of maintaining SH (95% CI; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (89-98; 118), 81% (74-89; 65), and 78% (71-87; 42), respectively. Poorer hearing at diagnosis (hazard ratio [HR] per 10 dB hearing level increase in pure-tone average of 2.51, p < 0.001; HR per 10% decrease in word recognition score of 1.70, p = 0.001) was associated with increased likelihood of developing non-SH during observation. When controlling for baseline hearing status, tumors measuring 5 mm or greater in the internal auditory canal or with cerebellopontine angle extension were associated with significantly increased risk of developing non-SH (HR, 4.87; p = 0.03). At 5 years after diagnosis, 95% of patients with nongrowing intracanalicular VS measuring less than 5 mm maintained SH. Hearing worsens during periods of nongrowth in sporadic VS. Patients with small (<5 mm) intracanalicular tumors demonstrate robust maintenance of SH over time, reinforcing the consideration of initial observation in this patient subset.


Timing of solid food introduction is associated with urinary F2-isoprostane concentrations in childhood.
Timing of solid food introduction in infancy has been associated with several chronic diseases. To explore potential mechanisms, we investigated the relationship between timing of solid food introduction and F2-isoprostanes-a marker of oxidative stress. Urinary F2-isoprostanes were assessed in 336 healthy children aged less than 11.5 y with 1,266 clinic visits (mean = 3.8 visits per child) in the Diabetes Autoimmunity Study in the Young. We analyzed the association between F2-isoprostane concentrations and infant diet exposures using linear mixed models adjusted for age, age(2), HLA-DR3/4,DQB1*0302 genotype, first-degree relative with type 1 diabetes, maternal age, maternal education, sex, and exposure to in utero cigarette smoke. Later solid food introduction was associated with lower F2-isoprostane concentrations in childhood (on average, 0.10 ng/mg per month of age at introduction; estimate: -0.10 (95% confidence interval (CI): -0.18, -0.02) P value = 0.02). Moreover, childhood F2-isoprostane concentrations were, on average, 0.24 ng/mg lower in individuals breastfed at solid food introduction (estimate: -0.24 (95% CI: -0.47, -0.01) P value = 0.04) compared with those who were not. Associations remained significant after limiting analyses to F2-isoprostanes after 2 y of age. Our results suggest a long-term protective effect of later solid food introduction and breastfeeding at solid food introduction against increased F2-isoprostane concentrations throughout childhood.


[What strategy after three trabeculectomy failures?].
Three trabeculectomy failures raises the delicate problem of refractory glaucoma with unresponsive ocular hypertony. The therapeutic strategy requires first a careful assessment of the reasons for the previous failures (internal or external obstacles to filtration which might have responded to preventive treatment), then, depending on the patient's age, type of glaucoma, anatomic status of the ocular structures and the visual potential of the eye, a choice has to be made between different surgical techniques aimed at favoring aqueous humor evacuation (trabeculectomy associated with antimetabolites or drainage implant) or destruction of the ciliary body to reduce intraocular pressure by limiting the production of aqueous humor. Choosing between these two possibilities is not an easy task as success rates are highly variable on such eyes and complications are frequent, leading to lower visual acuity in 30 % of the cases. These salvage procedures recall that first line trabeculectomy must be optimized in all cases.


Feasibility and safety of balloon-expandable transcatheter aortic valve implantation with moderate or without predilatation.
Aortic valve preparation by performing balloon aortic valvuloplasty (BAV) has always been considered mandatory during transcatheter aortic valve implantation (TAVI) procedures. We aimed to investigate the feasibility and safety of performing balloon-expandable TAVI with moderate or with no predilatation (PD). Overall, 121 patients underwent TAVI with no PD and 392 with moderate PD. TAVI endpoints and adverse events were considered according to the Valve Academic Research Consortium (VARC)-2 definitions. Device success for the entire cohort was 95.1%. Post-dilatation was performed in nine patients in the no PD group (7.4%) and in 40 patients in the moderate PD group (10.2%) (p=0.06). Total fluoroscopy time and the amount of contrast used were lower in the no PD group. All-cause mortality up to 30 days was 3.3% in the no PD group vs. 3.6% in the moderate PD group (p=0.89). VARC-2 defined complication rates at 30 days including cerebrovascular accident (CVA)/transient ischaemic attack (TIA) were similar between groups. Overall, there was no significant difference in survival rates between the two groups (HR 1.33, 95% CI: 0.75-2.35; p=0.34). Balloon-expandable TAVI with moderate or without balloon PD is feasible and safe. The omission of PD in appropriate cases was associated with reduced fluoroscopy time without affecting procedural success.