Cross-Modal Plasticity in Higher-Order Auditory Cortex of Congenitally Deaf Cats Does Not Limit Auditory Responsiveness to Cochlear Implants.
Congenital sensory deprivation can lead to reorganization of the deprived cortical regions by another sensory system. Such cross-modal reorganization may either compete with or complement the "original" inputs to the deprived area after sensory restoration and can thus be either adverse or beneficial for sensory restoration. In congenital deafness, a previous inactivation study documented that supranormal visual behavior was mediated by higher-order auditory fields in congenitally deaf cats (CDCs). However, both the auditory responsiveness of "deaf" higher-order fields and interactions between the reorganized and the original sensory input remain unknown. Here, we studied a higher-order auditory field responsible for the supranormal visual function in CDCs, the auditory dorsal zone (DZ). Hearing cats and visual cortical areas served as a control. Using mapping with microelectrode arrays, we demonstrate spatially scattered visual (cross-modal) responsiveness in the DZ, but show that this did not interfere substantially with robust auditory responsiveness elicited through cochlear implants. Visually responsive and auditory-responsive neurons in the deaf auditory cortex formed two distinct populations that did not show bimodal interactions. Therefore, cross-modal plasticity in the deaf higher-order auditory cortex had limited effects on auditory inputs. The moderate number of scattered cross-modally responsive neurons could be the consequence of exuberant connections formed during development that were not pruned postnatally in deaf cats. Although juvenile brain circuits are modified extensively by experience, the main driving input to the cross-modally (visually) reorganized higher-order auditory cortex remained auditory in congenital deafness. In a common view, the "unused" auditory cortex of deaf individuals is reorganized to a compensatory sensory function during development. According to this view, cross-modal plasticity takes over the unused cortex and reassigns it to the remaining senses. Therefore, cross-modal plasticity might conflict with restoration of auditory function with cochlear implants. It is unclear whether the cross-modally reorganized auditory areas lose auditory responsiveness. We show that the presence of cross-modal plasticity in a higher-order auditory area does not reduce auditory responsiveness of that area. Visual reorganization was moderate, spatially scattered and there were no interactions between cross-modally reorganized visual and auditory inputs. These results indicate that cross-modal reorganization is less detrimental for neurosensory restoration than previously thought.


Accuracy of child morbidity data in demographic and health surveys.
The Demographic and Health Surveys (DHSs) have been used throughout the developing world for the last 20 years to provide data on the distribution of disease in order to inform planning. Data on child illness and death are reported by mothers and are susceptible to error. We conducted an in-depth study of the Iranian DHS carried out in 2000-2001 and reviewed 110 DHS carried out around the world to check for bias by assessing the social gradient in reported child morbidity and mortality. We found that the reported under-5 child morbidity and mortality rates for the 28 Iranian provinces were inversely correlated (r = -0.592, P < 0.001) and that the adjusted social gradient of child morbidity implied increased illness in those who had literate vs illiterate mothers (OR = 1.26, 95% CI 1.20-1.32) compared with a decrease in mortality with increased literacy (OR = 0.52, 95% CI 0.46-0.59). Many of the other DHSs also show increased rates of reported child diarrhoea in households with higher levels of maternal education, access to piped water and urban (vs rural) dwellings, the reverse of what is found with mortality rates. This suggests that there may be significant recall and reporting bias in under-5 childhood morbidity in DHSs. Caution should be used in the interpretation and use of data from DHSs and the survey methods should be reviewed.


Tuning activity-based probe selectivity for serine proteases by on-resin 'click' construction of peptide diphenyl phosphonates.
Activity-based probes (ABPs) are powerful tools for functional proteomics studies. Their selectivity can be influenced by modification of a recognition element that interacts with pockets near the active site. For serine proteases there are a limited number of simple and efficient synthetic procedures for the development of selective probes. Here we describe a new synthetic route combining solid and solution phase chemistries to generate a small library of diphenyl phosphonate probes. Building blocks carrying a P1 recognition element and an electrophilic phosphonate warhead were prepared in solution and 'clicked' on-resin onto a tripeptide. We show the ability to modulate the activity and selectivity of diphenyl phosphonate ABPs and demonstrate activity-dependent labeling of endogenous proteases within a tissue proteome. The herein described synthetic approach therefore serves as a valuable method for rapid diversification of serine protease ABPs.


A method for the simultaneous analysis of mRNA levels of multiple cardiac ion channels with a multi-probe RNase protection assay.
Various pathological conditions can alter cardiac electrophysiological properties not only by physiological responses but also by modifying the gene expression of ion channels (electrical remodelling). To investigate the underlying mechanisms of the latter, electrophysiological alterations would require a simultaneous and comprehensive analysis of the mRNA level of the ion channel genes. We designed 19 cardiac ion channel cDNA templates to analyse the corresponding mRNAs and classified them into three template sets. Those sets were a voltage-dependent K(+) channel series (rat erg, KvLQT1, Kv4.3, Kv4.2, Kv2.1, Kv1.5, Kv1.4, Kv1.2), an inwardly rectifying K(+) channel series (rat Kir6.2, SUR2A/B, Kir3.4, Kir3.1, Kir2.2, Kir2.1), and an inward cationic ion channel series (rat SCN5A, alpha1C, beta2, alpha2delta2 of cardiac L-type Ca(2+) channel and alpha1G). These cDNA templates were used to synthesize antisense digoxigenin-labelled RNA probes. An amount of the total RNA of 25 microg was adequate to analyse simultaneously the mRNA levels of the ion channel genes with the use of multi-probe RPA, and these three multi-probe template sets enabled us to evaluate the profile of the spatial and temporal transcripts of the cardiac ion channels. The newly developed ion channel multi-probe RPA templates provide an aid in the comprehensive analysis of the electrical remodelling of the heart.


A modification of the scale illusion into a detection task for assessment of binaural streaming.
Binaural streaming by frequency-proximity was investigated without subjective listener-feedback by modifying the scale illusion of Deutsch [J. Acoust. Soc. Am. 57, 1156-1160 (1975)] into a detection-task. Nineteen listeners had to detect one deviation within a repeating melody stream, while simultaneously presented with a randomized distractor stream. Every second note in each stream was presented to the opposite ear, requiring binaural streaming to detect the deviant. Listeners performed well in this test but adding interaural delay or timbre-difference let the listeners group by lateralization instead. This confirms the grouping by frequency-proximity. The method could be used to investigate binaural streaming in hearing-impaired patients, where interaural percepts might differ.


Patterns of Human Respiratory Viruses and Lack of MERS-Coronavirus in Patients with Acute Upper Respiratory Tract Infections in Southwestern Province of Saudi Arabia.
We undertook enhanced surveillance of those presenting with respiratory symptoms at five healthcare centers by testing all symptomatic outpatients between November 2013 and January 2014 (winter time). Nasal swabs were collected from 182 patients and screened for MERS-CoV as well as other respiratory viruses using RT-PCR and multiplex microarray. A total of 75 (41.2%) of these patients had positive viral infection. MERS-CoV was not detected in any of the samples. Human rhinovirus (hRV) was the most detected pathogen (40.9%) followed by non-MERS-CoV human coronaviruses (19.3%), influenza (Flu) viruses (15.9%), and human respiratory syncytial virus (hRSV) (13.6%). Viruses differed markedly depending on age in which hRV, Flu A, and hCoV-OC43 were more prevalent in adults and RSV, hCoV-HKU1, and hCoV-NL63 were mostly restricted to children under the age of 15. Moreover, coinfection was not uncommon in this study, in which 17.3% of the infected patients had dual infections due to several combinations of viruses. Dual infections decreased with age and completely disappeared in people older than 45 years. Our study confirms that MERS-CoV is not common in the southwestern region of Saudi Arabia and shows high diversity and prevalence of other common respiratory viruses. This study also highlights the importance and contribution of enhanced surveillance systems for better infection control.


Influence of a carbohydrate-electrolyte solution ingested during running on muscle glycogen utilisation in fed humans.
This study investigated whether the ingestion of a carbohydrate-electrolyte solution during running would influence muscle glycogen utilisation in subjects who had consumed a carbohydrate meal 3 hours before exercise. Eight men completed two 60-min treadmill runs at 70% VO(2)max. Before each run they consumed a carbohydrate meal (183 +/- 7 g) 3 hours before exercise and either 1) a carbohydrate-electrolyte solution during the run (46 +/- 1 g) (M+C), or 2) water during the run (M + W). Biopsy samples were obtained from the vastus lateralis muscle at rest and after 60 min of running. Serum insulin concentrations were higher (p < 0.01) in both trials at the start of exercise compared with fasting values, whereas blood glucose concentrations were higher (p < 0.01) after 60 min of running in the M+C trial. Pre-exercise muscle glycogen concentrations were similar in both trials (M+C: 321.9 +/- 27.2 vs M+W: 338.8 +/- 32.8 mmol x kg x dry weight (-1) [dw]; NS). There was no difference in the amount of glycogen used during exercise (M+C: 96.1 +/- 22.1 vs M+W: 77.9 +/- 11.7 mmol x kg x dw (-1); NS). In conclusion, a carbohydrate-electrolyte solution ingested during treadmill running at 70 % VO(2)max does not influence muscle glycogen use during the first hour of exercise when a carbohydrate meal is consumed 3 hours before exercise.


Multiplex digital PCR: a superior technique to qPCR for the simultaneous detection of duck Tembusu virus, duck circovirus, and new duck reovirus.
Duck Tembusu virus (DTMUV), duck circovirus (DuCV), and new duck reovirus (NDRV) have seriously hindered the development of the poultry industry in China. To detect the three pathogens simultaneously, a multiplex digital PCR (dPCR) was developed and compared with multiplex qPCR in this study. The multiplex dPCR was able to specifically detect DTMUV, DuCV, and NDRV but not amplify Muscovy duck reovirus (MDRV), Muscovy duck parvovirus (MDPV), goose parvovirus (GPV), H4 avian influenza virus (H4 AIV), H6 avian influenza virus (H6 AIV), and Newcastle disease virus (NDV). The standard curves showed excellent linearity in multiplex dPCR and qPCR and were positively correlated. The sensitivity results showed that the lowest detection limit of multiplex dPCR was 1.3 copies/μL, which was 10 times higher than that of multiplex qPCR. The reproducibility results showed that the intra- and interassay coefficients of variation were 0.06-1.94%. A total of 173 clinical samples were tested to assess the usefulness of the method; the positive detection rates for DTMUV, DuCV, and NDRV were 18.5, 29.5, and 14.5%, respectively, which were approximately 4% higher than those of multiplex qPCR, and the kappa values for the clinical detection results of multiplex dPCR and qPCR were 0.85, 0.89, and 0.86, indicating that the two methods were in excellent agreement.


Biofilms: Microbial Cities Wherein Flow Shapes Competition.
The phenotypic diversity in biofilms allows bacteria to adapt to changing environmental conditions. Stochastic gene expression and structural differentiation are believed to confer phenotypic diversity. However, two recent publications demonstrate how hydrodynamic flow and substrate topography can also alter the competitive outcomes of different bacterial phenotypes, increasing biofilm phenotypic variation.


Outcomes of Multi-Trauma Road Traffic Crashes at a Tertiary Hospital in Oman: Does attendance by trauma surgeons versus non-trauma surgeons make a difference?
Trauma surgeons are essential in hospital-based trauma care systems. However, there are limited data regarding the impact of their presence on the outcome of multi-trauma patients. This study aimed to assess the outcomes of multi-trauma road traffic crash (RTC) cases attended by trauma surgeons versus those attended by non-trauma surgeons at a tertiary hospital in Oman. This retrospective study was conducted in December 2015. A previously published cohort of 821 multi-trauma RTC patients admitted between January and December 2011 to the Sultan Qaboos University Hospital, Muscat, Oman, were reviewed for demographic, injury and hospitalisation data. In-hospital mortality constituted the main outcome, with admission to the intensive care unit, operative management, intubation and length of stay constituting secondary outcomes. A total of 821 multi-trauma RTC cases were identified; of these, 60 (7.3%) were attended by trauma surgeons. There was no significant difference in mortality between the two groups (P = 0.35). However, patients attended by trauma surgeons were significantly more likely to be intubated, admitted to the ICU and undergo operative interventions (P <0.01 each). The average length of hospital stay in both groups was similar (2.6 versus 2.8 days; P = 0.81). No difference in mortality was observed between multi-trauma RTC patients attended by trauma surgeons in comparison to those cared for by non-trauma surgeons at a tertiary centre in Oman.


Studies on the metabolism and toxicological detection of the new designer drug 4'-methyl-alpha-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry.
4'-Methyl-alpha-pyrrolidinopropiophenone (MPPP) is a new designer drug which has appeared on the illicit drug market. The aim of our study was to identify the MPPP metabolites and to develop a toxicological detection procedure in urine using solid-phase extraction, ethylation and GC-MS. In urine samples of rats treated with MPPP, MPPP was found to be completely metabolized by oxidative desamination, hydroxylation of the 4'-methyl group followed by oxidation finally to the corresponding carboxy compound and/or by hydroxylation of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam. The carboxy groups were found to be partly conjugated. Based on these data, MPPP could be detected in urine via its metabolites by GC-MS using mass chromatography for screening and library search for identification.


Direct Investment from Russia Abroad: Changes since 2018.
The article considers the specifics of Russian foreign direct investment outflows in 2018-the first half of 2020. Three main reasons for the new stagnation of Russian foreign investment expansion are identified: 1) the strengthening of "sanctions war" with the West after the election of Vladimir Putin for the 4th presidential term; 2) the slowdown in the global economy in 2018-2019 against the background of relatively low prices for hydrocarbons and other raw materials exported from Russia; and 3) the crisis caused by the coronavirus pandemic in 2020. These factors resulted in a reduction of both outward foreign direct investment stocks by Russian MNEs (partially due to revaluation of their assets after the collapse of the ruble rate), and a decrease in investments of wealthy Russians in foreign real estate as well as pseudo-foreign investment because of the regular attempts to conduct de-offshorization. Based on a study conducted at INION within the framework of the international program for studying MNEs from emerging markets, a list of leading Russian non-financial MNEs by the end of 2019 is presented. Further prospects of Russian direct investment are shown at the end of the article.


A comparative study of heat shock protein 70 in normal and PSE (pale, soft, exudative)-like muscle from broiler chickens.
This study investigated the level and location of heat shock protein 70 (HSP70) in pale, soft, and exudative (PSE)-like and normal chicken breast muscle (Pectoralis major [PM]) so as to identify HSP70 interacting proteins by immunoprecipitation. We found that HSP70 level in the PSE-like meat group was significantly lower than in the normal group (P < 0.05). Immuno-fluorescence indicated that HSP70 was present in the cytoplasm and on surface membranes of PM muscle fibers in the normal muscle group, while HSP70 was present on surface membranes and extracellular matrix, but was barely visible in the sarcoplasm of the PSE-like muscle group. According to HSP70-associated protein analysis, most of the proteins were glycolytic pathway enzymes, structural proteins, and molecular chaperones. The HSP70-interacted protein of heat shock protein 90 and 6-phosphofructokinase were clearly different between the two groups. Our research suggested that HSP70 may be associated with an unknown mechanism that leads to such variation in meat quality; the abundance and activity of HSP70 binding proteins may play a significant role in this process.


Recurrent spontaneous miscarriage is still a challenging diagnostic and therapeutic quagmire.
Recurrent spontaneous miscarriage (RSM), affecting 1-2% of women of reproductive age seeking pregnancy, has been a clinical quagmire and a formidable challenge for the treating physician. There are many areas of controversy in the definition, aetiology, investigations and treatment of RSM. This review will address the many factors involved in the aetiology of RSM which is multifactorial in many patients, with antiphospholipid syndrome (APS) being the most recognized aetiological factor. There is no identifiable cause in about 40-60% of these patients, in which case the condition is classified as idiopathic or unexplained RSM. The RSM investigations are extensive and should be undertaken in dedicated, specialized, well-equipped clinics/centres where services are provided by trained specialists. The challenges faced by the treating physician are even more overwhelming regarding the decision of what should be the most appropriate therapy offered to patients with RSM. Our review will cover the diverse modalities of therapy available including the role of preimplantation genetic testing using recent microarray technology, such as single nucleotide polymorphism and comparative genomic hybridization, as well as preimplantation genetic diagnosis; the greatest emphasis will be on the treatment of APS, and there will be important comments on the management of patients presenting with idiopathic RSM. The controversial areas of the role of natural killer cells in RSM, the varied modalities in the management of idiopathic RSM and the need for better-planned studies will be covered as well.


No adverse lung effects of 7- and 28-day inhalation exposure of rats to emissions from petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without particulate filter - the FuelHealth project.
Increased use of biofuels raises concerns about health effects of new emissions. We analyzed relative lung health effects, on Fisher 344 rats, of diesel engine exhausts emissions (DEE) from a Euro 5-classified diesel engine running on petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without diesel particulate filter (DPF). One group of animals was exposed to DEE for 7 days (6 h/day), and another group for 28 days (6 h/day, 5 days/week), both with and without DPF. The animals (n = 7/treatment) were exposed in whole body exposure chambers. Animals breathing clean air were used as controls. Genotoxic effects of the lungs by the Comet assay, histological examination of lung tissue, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury, and mRNA markers of inflammation and oxidative stress were analyzed. Our results showed that a minor number of genes related to inflammation were slightly differently expressed in the exposed animals compared to control. Histological analysis also revealed only minor effects on inflammatory tissue markers in the lungs, and this was supported by flow cytometry and ELISA analysis of cytokines in BALF. No exposure-related indications of genotoxicity were observed. Overall, exposure to DEE with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF. Overall, exposure to DEE from a modern Euro 5 light vehicle engine run on B20 fuel with or without DPF technology produced no adverse effects in the endpoints analyzed in the rat lung tissue or the BALF.


[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension].
Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.


Structure and dynamics of perfluoroalkane/beta-cyclodextrin inclusion compounds as studied by solid-state 19F MAS and 1H -->19F CP/MAS NMR spectroscopy.
The molecular structure and dynamics of novel inclusion compounds (ICs) consisting of n-perfluoroalkane (PFA) guests and beta-cyclodextrin (beta-CD) host (PFA/beta-CD) have been investigated using 19F magic angle spinning (MAS) and 1H-->19F cross polarization (CP)/MAS NMR spectroscopy with the aid of thermal analyses, FT-IR spectroscopy, and X-ray diffraction method. The ICs of C9F20/beta-CD and C20F42/beta-CD were successfully obtained as precipitates from mixtures of respective PFAs and saturated aqueous solution of beta-CD. The wide-angle X-ray diffraction (WAXD) revealed that C9F20/beta-CD forms a channel-type crystallite, while C20F42/beta-CD is nearly amorphous at room temperature. The structural orders in both ICs increase at elevated temperatures. The 19F NMR signals obtained by the direct polarization (DP) method for PFA/beta-CD are resonated at higher frequencies than those for original PFA. This can be ascribed to the lower dielectric environment of the beta-CD cavity. Above 80 degrees C, 1H-->19F CP/MAS NMR technique revealed that C9F20 molecules undergo vigorous molecular motion and partly come out of the beta-CD channel. However, the guests hardly degrade or evaporate unless the host is pyrolytically decomposed above ca. 300 degrees C. The spin-lattice relaxation times in the laboratory frame for 19F (T1F) are almost identical for all the fluorines in PFA/beta-CD at each temperature, while significantly different values were observed for fluorines in neat PFA. This indicates that effective intramolecular spin diffusion occurs within a PFA molecule included in beta-CD.


[Predictive value of the markers of inflammation in acute coronary syndromes].
This prospective study aims to establish the association between markers of inflammation (CRP and fibrinogen) and the severity of coronary lesions in patients with acute coronary syndromes. For this purpose, Plasma CRP, fibrinogen and troponin I were measured upon admission in 143 consecutive patients presenting with an acute coronary syndrome who underwent subsequently coronarography . Mean age is 55.5+/-11.6 years. Sex Ratio is 3.61 in favour of men; 68% of our patients presented with acute myocardial infarction with ST segment elevation; 23% with an unstable angina and 9% with an acute myocardial infarction without ST segment elevation. 31 patients (24.4%) have not any significant coronary lesion. Mean CRP level in these patients is (6.82+/-8.2 mg/l) lower than that measured in patients with significant lesions (17.4+/-26.9 mg/l; p=0.02). In patients with pathologic coronarogram, we demonstrated that the mean CRP level is higher in patients heaving one or more lesion of at least 70% of diameter stenosis than that in patients with no significant lesions (21.28+/-30.45 mg/l vs 11+/-14.2 mg/l; p=0.05). The mean CRP level grows with the number of proximal and significant stenoses. (CRP level in patients with one significant stenosis: 11+/-14.2 mg/l vs 27.45+/-39.67 mg/l in patients heaving 3 lesions; p=0.02. CRP level in patients with one proximal lesion: 14.35+/-19.8 mg/l vs 50.33+/-65 mg/l in patients heaving 3 proximal lesions; p=0.007). Fibrinogen levels measured upon admission in patients having significant lesions are higher than those measured in patients with normal coronary arteries (4.7+/-1.81 mg/l vs 3.93+/-1.69 mg/l; p=0.02). Compared with that measured in patients having distal lesions, the fibrinogen level is higher in case of proximal and multiple coronary lesions. There is a significant gradual increase in fibrinogen levels with increasing of the number of proximal coronary lesions and the degree of diameter stenosis. Multivariate logistic regression analysis showed that a CRP level higher than 10 mg/l is an independent predictive factor of the presence of the presence of significant coronary lesions (p=0.006; OR = 8.62; CI=0.7 to 7.4). We conclude that high CRP and fibrinogen plasma levels are associated with extended, severe and proximal coronary lesions.


Exposure modeling of engineered nanoparticles in the environment.
The aim of this study was to use a life-cycle perspective to model the quantities of engineered nanoparticles released into the environment. Three types of nanoparticles were studied: nano silver (nano-Ag), nano TiO2 (nano-TiO2), and carbon nanotubes (CNT). The quantification was based on a substance flow analysis from products to air, soil, and water in Switzerland. The following parameters were used as model inputs: estimated worldwide production volume, allocation of the production volume to product categories, particle release from products, and flow coefficients within the environmental compartments. The predicted environmental concentrations (PEC) were then compared to the predicted no effect concentrations (PNEC) derived from the literature to estimate a possible risk. The expected concentrations of the three nanoparticles in the different environmental compartments vary widely, caused by the different life cycles of the nanoparticle-containing products. The PEC values for nano-TiO2 in water are 0.7--16 microg/L and close to or higher than the PNEC value for nano-TiO2 (< 1 microg/L). The risk quotients (PEC/PNEC) for CNT and nano-Ag were much smaller than one, therefore comprising no reason to expect adverse effects from those particles. The results of this study make it possible for the first time to carry out a quantitative risk assessment of nanoparticles in the environment and suggest further detailed studies of nano-TiO2.


Genetic variants of DNA repair gene XPC modulating susceptibility to cervical cancer in North India.
The objective of the study was to investigate the association of Xeroderma Pigmentoum group C (XPC) Lys939Gln (A > C) and poly (AT) insertion deletion (PAT -/+) gene polymorphism with the risk of cervical cancer. We enrolled 220 cervical cancer patients and 237 healthy individuals. Polymorphism for XPC gene (Lys939Gln, PAT -/+) was genotyped by polymerase chain reaction and restriction fragment length polymorphism method. XPC Lys939Gln CC genotype was associated with elevated risk of cervical cancer (OR = 2.15, p = 0.036). CC genotype of Lys939Gln (OR = 3.68; p = 0.02) and +/+ genotype of PAT (OR = 7.99; p = 0.01) were observed to have statistically significant elevated risk in stage IV of cervical cancer. Among tobacco users, carriers of the +/+ genotype of PAT showed a borderline significance (OR = 3.72, p = 0.032). Haplotypes A+ and C- (A > C of Lys939Gln, --> + of PAT) were significantly associated with higher susceptibility to cervical cancer (OR = 2.01, p = 0.005 and OR = 1.76, p = 0.002, respectively). Polymorphisms and haplotypes in XPC appear to influence cervical cancer risk and may modify risk attributable to tobacco usage.


Copper-Catalyzed Ring-Opening Radical Trifluoromethylation of Cycloalkanone Oximes.
The copper-catalyzed ring-opening C-trifluoromethylation of cycloalkanone oximes with Zn(CF3)2 complexes is described. The reaction proceeds in dichloromethane under mild conditions, providing an efficient and general entry to γ- or δ-CF3-substituted nitriles via tandem N-O and C(sp2)-C(sp3) bond cleavage and C(sp3)-CF3 bond formation. The protocol exhibits a broad substrate scope and wide functional group compatibility. A radical mechanism involving the CF3 transfer from Cu(II)-CF3 complexes to alkyl radicals is proposed.


Effects of copper-bearing montmorillonite on growth performance, digestive enzyme activities, and intestinal microflora and morphology of male broilers.
Avian commercial male broiler chicks (n = 240), 1 d of age, were used to investigate the effects of copper-bearing montmorillonite (Cu-MMT) on growth performance, digestive enzyme activities, and intestinal microflora and morphology. The chicks were allocated to 4 treatments, each of which had 5 pens of 12 chicks per pen. The 4 treatments were basal diet only (control group), basal diet + 1.5 g/kg montmorillonite (MMT), basal diet + 36.75 mg/kg Cu, in the form of CuSO4, and basal diet + 1.5 g/kg Cu-MMT. The results showed that supplementation with Cu-MMT significantly improved growth performance compared with the control diet, and that chicks fed with Cu-MMT had higher average daily gain (ADG) than those fed with MMT or CuSO4. Supplementation with Cu-MMT significantly reduced the total viable counts of Escherichia coli and Clostridium in the small intestine and cecum. Supplementation with MMT or CuSO4 had no influence on intestinal microflora. Chicks fed with Cu-MMT had lower viable counts of E. coli in cecal contents than those fed with MMT or CuSO4. The addition of either MMT or Cu-MMT to the diet improved the activities of total protease, amylase, and lipase in the small intestinal contents but had no effect on those in the pancreas. Morphological measurements of the small intestinal mucosa of chicks indicated that dietary addition of MMT or Cu-MMT improved intestinal mucosal morphology.


Molar-incisor-hypomineralisation (MIH). Retrospective clinical study in Greek children. I. Prevalence and defect characteristics.
This was to evaluate the prevalence and the clinical characteristics of MIH in a group of Greek children. During the years 2003--2005, all MIH cases diagnosed according to the recently set criteria were selected from the new patients clinic of a Community Dental Centre for Children (Athens). Age, gender and teeth involved were recorded. The severity of MIH was determined collectively by dividing the affected teeth in two groups; a) mild defect (demarcated opacities) and b) moderate/severe defect (enamel breakdown and atypical restorations). Evaluation of the distribution of the affected teeth within MIH cases was performed in a separate group of 225 affected children aged 8-12 years with their entire 12 'index' teeth erupted. From the 3,518, 5.5 to 12 year old children that were examined, there were 360 (10.2%) children with MIH, 211 (58.6%) females and 149 (41.4%) males, with 1,926 affected teeth, 1,231 molars and 695 incisors. In the molars group, maxillary molars were more frequently affected (87.8/90.3%) than mandibular (81.7/82.2%). In the central incisor group, maxillary teeth were also more frequently affected (50/55%) than mandibular (24.4/25%), while laterals were the least affected. In all there were 37.9% molars with moderate/severe defects as compared with 4.9% incisors, the remaining 62.1% and 95.1% respectively being mild. The various associations between the affected teeth were evaluated in the sub-group of 225 MIH children with all 'index' teeth erupted (1,286 affected teeth, 776 molars and 510 incisors), with mean number of affected teeth per child being 5.7; separately for molars 3.4 and for incisors 2.2. In these cases 28.4% of the children had only molars affected and 71.6% had both molars and incisors. In descending order the associations of affected teeth more frequently found were: 4 molars/2 incisors (23.5%), 4 molars/4 incisors (16.8%), 4 molars alone (15.1%) and 2 molars alone (9.7%), the remaining being much less. As age increased the clinical severity of the affected teeth became more prevalent (p=0.0001), and when the total number of affected teeth was assessed the likelihood of having severe defect was also increased (p=0.001). The prevalence of the defect in the present study was 10.2% with maxillary teeth being more frequently affected. Severity increased with age. Mild defects were much more frequent, particularly in incisors. The total number of teeth affected and the most frequently found associations were, 4 molars/2 incisors, 4 molars/4 incisors, 4 molars alone and 2 molars alone.


Cloning of influenza cDNA ino M13: the sequence of the RNA segment encoding the A/PR/8/34 matrix protein.
A strategy has been developed for sequencing the single-stranded RNA genes of influenza virus. Restriction fragments derived from double-stranded cDNA copies of total influenza RNA were cloned into the bacteriophage M13mp2 and sequenced by the dideoxy technique. Sequences were extended and overlapped by using the virion RNA as template and priming with small restriction fragments. In the course of this strategy, the nucleotide sequence of segment 7 (1027 nucleotides) was completed and provides the primary structure of the matrix protein (27, 861 daltons). In addition, there is a second long reading frame which partly overlaps the reading frame of the matrix protein.


Association between serum calcium, serum phosphate and aortic stenosis with implications for prevention.
Background Aortic stenosis is the most common cause of valvular heart disease with no means of prevention. Lowering serum levels of calcium or phosphate are potential preventive strategies but observational studies on the associations with aortic stenosis are inconsistent. Design and methods A case-control study was conducted in 132 individuals undergoing echocardiography (63 with aortic stenosis and 69 without) and the results combined with three other comparable studies (914 individuals overall) to provide a summary odds ratio of aortic stenosis for a 0.1 mmol/L increase (approximately one standard deviation) in calcium and phosphate respectively. The relationship between calcium and phosphate and the severity of aortic stenosis, according to peak trans-aortic velocity, was also examined in the case-control study using linear regression. Results Both calcium and phosphate were positively associated with aortic stenosis. The summary odds ratio for a 0.1 mmol/L increase in calcium was 1.79 (95% confidence interval 1.07-2.99), p = 0.027 and for phosphate it was 1.47 (1.08-2.01), p = 0.015. Peak trans-aortic velocity increased with phosphate levels, 9% (4%-14%) per 0.1 mmol/L, p = 0.001, but not with calcium, p = 0.089. Conclusions If the associations are causal and reversible, these results indicate that a small reduction in calcium or phosphate levels, within the physiological rage, would translate into a clinically significant reduction in the risk of aortic stenosis. Randomised trials of calcium and phosphate lowering therapies in aortic stenosis are needed.


Pediatric splanchnic arterial occlusive disease: clinical relevance and operative treatment.
Splanchnic arterial occlusive disease is rare in childhood. The purpose of this study was to review the clinical relevance and operative treatment of these lesions in a unique experience from a single institution. Seventeen children (11 boys and 6 girls) from 2 years to 17 years in age with critical narrowings of the celiac artery (CA) and superior mesenteric artery (SMA) underwent treatment at the University of Michigan from 1974 to 2000. Etiologic factors included embryologic fusion abnormalities of the fetal aortae during formation of the splanchnic arteries (n = 15), inflammatory aortoarteritis (n = 1), and radiation-induced arterial fibrosis (n = 1). Individual lesions included CA occlusions (n = 6) and stenoses (n = 7), SMA occlusions (n = 3) and stenoses (n = 11), and inferior mesenteric artery stenosis (n = 1). Fourteen children had abdominal aortic coarctations, and 15 had renal artery stenoses. Two patients had postprandial abdominal discomfort and food aversion, consistent with intestinal angina. Small stature affected five others, perhaps attributable to severe renovascular hypertension and failure to thrive. Ten children underwent intestinal revascularization, at the time of an aortoplasty or thoracoabdominal bypass for aortic coarctation (n = 7) or at the time of renal artery revascularization (n = 8). Primary splanchnic revascularization procedures included SMA-aortic implantation (n = 3), aorto-SMA and CA bypass with an internal iliac artery graft (n = 3) or a saphenous vein graft (n = 1), CA-aortic implantation at a stenotic SMA origin (n = 2), and CA and SMA intimectomy (n = 1). Secondary operations included SMA-aortic implantation (n = 2). All 10 children who underwent splanchnic revascularization have thrived, gained weight, and are free of abdominal pain, with follow-up periods averaging 9 years. No intestinal ischemic manifestations occurred in the seven children who did not undergo operation. Pediatric splanchnic arterial occlusive disease is a rare illness appropriately treated with operation in properly selected children.


Genetic counseling and testing for hereditary hemorrhagic telangiectasia.
Genetic counseling is an important means of identifying a patient's genetic risk of hereditary hemorrhagic telangiectasia (HHT) and assisting patients in making informed decisions about their health. With an increase in understanding of the genetic mechanisms underlying HHT over the last decade, genetic counseling is increasingly being incorporated into the care of patients affected by HHT. In addition to refining the diagnosis of symptomatic patients, genetic testing can help to distinguish asymptomatic, at-risk patients from those who are unaffected by HHT. The purpose of this review article is to summarize the current knowledge regarding the role of genetic counseling and genetic testing in identifying and managing HHT in at-risk populations. This article also reviews the guidelines, outcomes, risks, and challenges of genetic counseling and testing for HHT in various patient populations, and provides an algorithm for the use of genetic counseling in symptomatic and asymptomatic patients.


[Patients with heart failure in the last year of their life: the primary care perspective].
The care of end-stage patients with heart failure (HF) represents a substantial cost and a relevant workload for health professionals and caregivers. Studies performed in out-of-hospital settings are limited. We aimed to provide data about management in primary care and professional needs of general practitioners (GPs). One hundred fifty-one GPs provided information about patients with HF who died (whatever the cause) in the previous 365 days: a) where they died, b) cause of death, c) number and cause of hospital admission, d) who was mainly in charge of the patient during the year preceding death, e) place where patients were mainly cared for, f) relevant diseases other than HF. GPs were also requested to express their personal opinion about their professional needs. GPs identified 245 patients (mean age 83.8 ± 8.76 years, range 48-103, 53.9% female). The place of death was hospital (46.5%), home (42.9%), nursing home (4.9%), hospice (1.6%). Fifty percent of patients died of worsening HF, 14% of sudden death, 23% of noncardiovascular diseases. In the last year of life, 193 (78.8%) patients were hospitalized, 149 (60.8%) for HF. GPs were responsible for care in the majority of patients. Total number of hospitalizations was the only variable significantly associated with death in hospital. GPs reported clinical or organizational problems in 58.4% of cases. The care of HF patients is mostly home-based and provided by families and GPs. GPs often need simple and inexpensive cardiological and organizational support.


[Liver deiodase activity in rats of different body weight and fat contents following high or low fat diet. Comparison of enzymatic deiodination with T4-clearance rate and thyroid activity in animals].
Weanling male wistar rats were fed 4 weeks a standard diet and separated into 2 groups, which received a high fat diet (50% w fat; HFD) or a low fat diet (3% w fat; LFD). These diets were fed 6-8 weeks and the animals then separated into light and heavy animals in each group. T4 deiodination in liver homogenates was investigated in all groups and compared with T4 clearance rate and thyroidal activity of these animals. The HFD-rats showed independently of weight and body fat content significantly higher liver deiodinase activity than LFD-rats. In light and heavy HFD-rats with great differences in body fat content the liver deiodinase activity was equal. T4 deiodination in liver, contrary to the T4 clearance rate, depends on fat content of diet and not of body. The thyroidal radioiodine uptake and PBI-131-values in some weight groups of HFD-rats were significantly higher than in some LFD-weight-groups, but a dependence of the thyroidal activity from fat content of diet or of body was not clearly evident. The results indicate however, that the thyroidal activity is likely not responsible for the increase of liver deiodinase activity after high fat diet. The apparent discrepancy between the results of higher liver T4 deiodination and equal or lower T4 clearance rate or equal T3 serum concentrations is discussed.


Bacterial endophyte communities in the foliage of coast redwood and giant sequoia.
The endophytic bacterial microbiome, with an emerging role in plant nutrient acquisition and stress tolerance, is much less studied in natural plant populations than in agricultural crops. In a previous study, we found consistent associations between trees in the pine family and acetic acid bacteria (AAB) occurring at high relative abundance inside their needles. Our objective here was to determine if that pattern may be general to conifers, or alternatively, is more likely restricted to pines or conifers growing in nutrient limited and exposed environments. We used 16S rRNA pyrosequencing to characterize the foliar endophyte communities of two conifers in the Cupressaceae family: Two coast redwood (CR; Sequoia sempervirens) populations and one giant sequoia (GS; Sequoiadendron giganteum) population were sampled. Similar to the pines, the endophyte communities of the giant trees were dominated by Proteobacteria, Firmicutes, Acidobacteria, and Actinobacteria. However, although some major operational taxonomic units (OTUs) occurred at a high relative abundance of 10-40% in multiple samples, no specific group of bacteria dominated the endophyte community to the extent previously observed in high-elevation pines. Several of the dominating bacterial groups in the CR and GS foliage (e.g., Bacillus, Burkholderia, Actinomycetes) are known for disease- and pest suppression, raising the possibility that the endophytic microbiome protects the giant trees against biotic stress. Many of the most common and abundant OTUs in our dataset were most similar to 16S rRNA sequences from bacteria found in lichens or arctic plants. For example, an OTU belonging to the uncultured Rhizobiales LAR1 lineage, which is commonly associated with lichens, was observed at high relative abundance in many of the CR samples. The taxa shared between the giant trees, arctic plants, and lichens may be part of a broadly defined endophyte microbiome common to temperate, boreal, and tundra ecosystems.


Does alcohol advertising affect overall consumption? A review of empirical studies.
This article reviews the empirical warrant for the assertion that alcohol advertising affects overall alcohol consumption. Econometric, exposure, experimental studies and advertising bans are examined. The evidence indicates that advertising bans do not reduce alcohol sales, total advertising expenditures have no reliable correlation with sales of alcoholic beverages, and that experimental studies typically show no effect of advertising on actual consumption. However, one set of studies does show that drinkers are exposed to more television alcohol advertisements, without making the causal connection clear. In general, the evidence indicates little impact of alcohol advertising on alcohol sales or drinking. However, some results are suggestive and there is a need for more sophisticated econometric, exposure and experimental studies that take into account a wider range of variables.


Carbenylative Amination and Alkylation of Vinyl Iodides via Palladium Alkylidene Intermediates.
Most palladium-catalyzed reactions involving insertion of alkylidenes with α-hydrogens undergo β-hydride elimination from alkylpalladium(II) intermediates to form alkenes. Vinyl iodides were shown to generate η(3)-allylpalladium intermediates that resist β-hydride elimination, preserving the sp(3) center adjacent to the carbene moiety. Acyclic stereocontrol (syn/anti) for carbenylative amination and alkylation reactions was low, suggesting a lack of control in the migratory insertion step. Highly hindered carbene precursors inexplicably led to formation of Z-alkenes with high levels of stereocontrol.


Nuclear hormone receptor corepressor promotes esophageal cancer cell invasion by transcriptional repression of interferon-γ-inducible protein 10 in a casein kinase 2-dependent manner.
Aberrant expression of casein kinase 2 (CK2) is associated with tumor progression; however, the molecular mechanism by which CK2 modulates tumorigenesis is incompletely understood. In this paper, we show that CK2α phosphorylates the C-terminal domain of the nuclear receptor corepressor (NCoR) at Ser-2436 to stabilize the NCoR against the ubiquitin-dependent proteasomal degradation pathway. Importantly, NCoR promoted the invasion of esophageal cancer cells in a CK2-dependent manner. By using cyclic DNA microarray analysis, we identified CXCL10/IP-10 as a novel CK2α-NCoR cascade-regulated gene. The depletion of both NCoR and HDAC3 commonly derepressed IP-10 transcription, demonstrating the functional engagement of the NCoR-HDAC3 axis in IP-10 transcriptional repression. Furthermore, chromatin immunoprecipitation assays showed that c-Jun recruits NCoR-HDAC3 corepressor complexes to the (AP1 site of IP-10, leading to histone hypoacetylation and IP-10 down-regulation. Collectively these data suggest that the CK2α-NCoR cascade selectively represses the transcription of IP-10 and promotes oncogenic signaling in human esophageal cancer cells.


Tunable Lifshitz Transitions and Multiband Transport in Tetralayer Graphene.
As the Fermi level and band structure of two-dimensional materials are readily tunable, they constitute an ideal platform for exploring the Lifshitz transition, a change in the topology of a material's Fermi surface. Using tetralayer graphene that host two intersecting massive Dirac bands, we demonstrate multiple Lifshitz transitions and multiband transport, which manifest as a nonmonotonic dependence of conductivity on the charge density n and out-of-plane electric field D, anomalous quantum Hall sequences and Landau level crossings that evolve with n, D, and B.


Myogenic Heartbeat in the Primitive Crustacean Triops longicaudatus.
Pacemaker mechanisms in the heart of the primitive crustacean Triops longicaudatus were examined electrophysiologically. The heart is tubular and the heart wall consists of a single layer of myocardial cells. No nerve cells were found in the heart, either with methylene blue vital staining or by light microscopy of serial sections. The heart beats rhythmically at a frequency of 120 to 240 beats/min, and each beat is associated with a slow membrane potential change in the heart muscle. The amplitude of the slow potential varies widely and no spikes appear on it. The heart muscle cells are electrically coupled with each other and generate synchronous slow potentials. No localized portion of the heart exhibited a frequency that always preceded the others. The muscle activity could be phase-shifted by injection of a single brief current pulse and could be entrained to a lower or higher frequency by repeated brief current pulses injected into the muscle cell. The frequency of muscle activity could be changed by the injection of DC current into the muscle cell, and the change in frequency was linearly related to the intensity of the current. When the intensity of hyperpolarizing DC current exceeded a certain value, the muscle activity disappeared abruptly, and the heart stopped beating completely. These results show clearly that the heartbeat of Triops is myogenic. The heart is diffusely myogenic and should be regarded as a single muscle oscillator.


N-silyl protecting groups for labile aziridines: application toward the synthesis of N-H aziridinomitosenes.
Hindered N-silylamines were examined for their utility to serve as protecting groups for the labile aziridine nitrogen found within the highly sensitive aziridinomitosene framework. tert-Butyldiphenylsilyl and modified tert-butyldiphenylsilyl groups were the most resistant to nitrogen-silicon bond cleavage under various reaction conditions and were thus employed in transformations relevant to aziridinomitosene synthesis. The N-silylaziridines 7a, 21a, and 21b underwent azomethine ylide cycloaddition and afforded, upon deprotection, the N-H aziridine 24 in 18-32% overall yield for the three steps.


Tuberculosis in adults.
Tuberculosis (TB) in Malaysia is rising due to multiple factors and issues related to its management are addressed in the updated evidence-based clinical practice guidelines. Screening for active TB should be considered in high risk groups. Light emitting diode-based fluorescence microscopy and nucleic acid amplification tests are recommended investigations. Health education and standardised 6-month daily antituberculosis (antiTB) regimen are among important elements for successful treatment. Latent TB infection screening should only be performed on high risk individuals. AntiTB regimen offered to HIV-positive adults should be the same as for HIV-negative adults and timing to initiate highly active antiretroviral therapy in patients with TB is based on CD4 count. All patients on antiTB treatment should be monitored to assess their response to treatment and to identify problems associated with it.


Spatio-temporal characterization of the pleiotrophinergic system in mouse cerebellum: evidence for its key role during ontogenesis.
The development of the central nervous system requires an appropriate micro-environment that is conditioned by a combination of various extracellular components. Most of the known signaling factors, such as neurotransmitters or neuropeptides, are soluble and diffuse into the extracellular matrix. However, other secreted molecules like proteoglycans or glycosaminoglycans anchor in the extracellular matrix to influence cerebral ontogenesis. As such, pleiotrophin (PTN), which binds the proteoglycans syndecan-3 (SDC3) and protein tyrosine phosphatase zeta (PTPζ), has been described as a pro-migratory and a pro-differentiating secreted cytokine on cortical neurons. In rat cerebellum, PTN is highly expressed during the first postnatal week, suggesting that this cytokine could participate to the development of the cerebellar cortex. According to this hypothesis, our spatio-temporal cartography of PTN, PTPζ and SDC3 indicated that, in mouse, the PTNergic system was present in the cerebellum at least from the first postnatal day (P0). Until P12, PTN was mainly expressed by granule cell precursors and located in the extracellular matrix, while SDC3 was expressed by Purkinje cells, Golgi cells and granule cell precursors, and PTPζ was present on Purkinje cells and Bergmann fibers. In vitro studies confirmed the presence of SDC3 on immature granule cells and demonstrated that PTN could stimulate directly their velocity in culture. In contrast, subarachnoidal injection of PTN in the cerebellum significantly reduced the rate of migration of granule cells, exacerbated their apoptosis and induced an atrophy of the Purkinje cell dendritic tree. Since differentiated granule cells did not express SDC3 or PTPζ, the PTN effect observed on migration and apoptosis may be indirectly mediated by Purkinje and/or Bergmann cells. From P21 to adulthood, the distribution of PTN, SDC3 and PTPζ changed and their expression dramatically decreased even if they were still detectable. PTN and SDC3 immunolabeling was restricted around Purkinje cell bodies and Golgi cells, whereas PTPζ was located around interneurons. These data suggested that, in the cerebellum of adult mice, PTN participates to the perineuronal nets that control neuronal plasticity. To conclude, the present work represents the first spatio-temporal characterization of the PTNergic system in the mouse cerebellum and indicates that PTN may contribute to cerebellum ontogenesis during the postnatal development as well as to neuronal plasticity at adulthood.


An overview of nanomedicines for neuron targeting.
Medical treatments of neuron-related disorders are limited due to the difficulty of targeting brain cells. Major drawbacks are the presence of the blood-brain barrier and the lack of specificity of the drugs for the diseased cells. Nanomedicine-based approaches provide promising opportunities for overcoming these limitations. Although many previous reviews are focused on brain targeting with nanomedicines in general, none of those are concerned explicitly on the neurons, while targeting neuronal cells in central nervous diseases is now one of the biggest challenges in nanomedicine and neuroscience. We review the most relevant advances in nanomedicine design and strategies for neuronal drug delivery that might successfully bridge the gap between laboratory and bedside treatment in neurology.


Grading of Urothelial Carcinoma and The New "World Health Organisation Classification of Tumours of the Urinary System and Male Genital Organs 2016".
In the management of urothelial carcinoma, determination of the pathological grade aims at stratifying tumours into different prognostic groups to allow evaluation of treatment results, and optimise patient management. This article reviews the principles behind different grading systems for urothelial bladder carcinoma discussing their reproducibility and prognostic value. This paper aims to show the evolution of the World Health Organisation (WHO) grading system, discussing their reproducibility and prognostic value, and evaluating which classification system best predicts disease recurrence and progression. The most optimal classification system is robust, reproducible, and transparent with comprehensive data on interobserver and intraobserver variability. The WHO published an updated tumour classification in 2016, which presents a step forward, but its performance will need validation in clinical studies. Medline and EMBASE were searched using the key terms WHO 1973, WHO/International Society of Urological Pathology 1998, WHO 2004, WHO 2016, histology, reproducibility, and prognostic value, in the time frame 1973 to May 2016. The references list of relevant papers was also consulted, resulting in the selection of 48 papers. There are still inherent limitations in all available tumour classification systems. The WHO 1973 presents considerable ambiguity for classification of the G2 tumour group and grading of the G1/2 and G2/3 groups. The 2004 WHO classification introduced the concept of low-grade and high-grade tumours, as well as the papillary urothelial neoplasm of low malignant potential category which is retained in the 2016 classification. Furthermore, while molecular markers are available that have been shown to contribute to a more accurate histological grading of urothelial carcinomas, thereby improving selection of treatment for a given patient, these are not (yet) part of standard clinical practice. The prognosis of patients diagnosed with urothelial carcinoma greatly depends on correct histological grading of the tumour. There is still limited data regarding intraobserver and interobserver variability differences between the WHO 1973 and 2004 classification systems. Additionally, reproducibility remains a concern: histological differences between the various types of tumour may be subtle and there is still no consensus amongst pathologists. The recent WHO 2016 classification presents a further improvement on the 2004 classification, but until further data becomes available, the European Association of Urology currently recommends the use of both WHO 1973 and WHO 2004/2016 classifications. Bladder cancer, when treated in time, has a good prognosis. However, selection of the most optimal treatment is largely dependent on the information your doctor will receive from the pathologist following evaluation of the tissue resected from the bladder. It is therefore important that the classification system that the pathologist uses to grade the tissue is transparent and clear for both urologists and pathologists. A reliable classification system will ensure that aggressive tumours are not misinterpreted, and less aggressive cancer is not overtreated.


Oxyntomodulin suppresses appetite and reduces food intake in humans.
Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg.min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 +/- 0.9 kg/m(2)) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 +/- 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 +/- 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 +/- 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.


Cytochemical evaluation of C-heterochromatic-DNA in metaphase chromosomes.
A method is proposed to evaluate the amount of DNA resistant to the C-banding pretreatments (C-heterochromatic-DNA) in metaphase chromosomes. Measurements were performed by microfluorometry on propidium iodide stained metaphases of man, gorilla and mouse; in these species, C-heterochromatin exhibits significant differences of both base composition and distribution along the chromosomes. The amount of C-heterochromatic-DNA was found to be about 16%, 28% and 58% of the total DNA content (genome size) in man, gorilla and mouse, respectively. The areas of C-bands after Giemsa staining were also assessed by microdensitometry, and corresponded to about 8%, 15% and 14% of the total karyotype area of man, gorilla and mouse respectively. No direct relation thus exists between C-band areas and the amount of DNA resistant to the C-banding pretreatments. In man and gorilla, the amount of C-heterochromatic-DNA accounts for the differences observed in genome size.


MoS₂ nanosheet phototransistors with thickness-modulated optical energy gap.
We report on the fabrication of top-gate phototransistors based on a few-layered MoS(2) nanosheet with a transparent gate electrode. Our devices with triple MoS(2) layers exhibited excellent photodetection capabilities for red light, while those with single- and double-layers turned out to be quite useful for green light detection. The varied functionalities are attributed to energy gap modulation by the number of MoS(2) layers. The photoelectric probing on working transistors with the nanosheets demonstrates that single-layer MoS(2) has a significant energy bandgap of 1.8 eV, while those of double- and triple-layer MoS(2) reduce to 1.65 and 1.35 eV, respectively.


Ustekinumab pharmacokinetics after subcutaneous administration in swine model.
Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.


Combatting Social Isolation, Anxiety, and Loneliness in Hospitalized Patients: A Quasi-Experimental Study.
The objective of this study was to determine the effectiveness of an intervention related to social isolation and loneliness among hospitalized patients by improving: 1) social connectedness; 2) anxiety; and 3) loneliness and to evaluate experiences of the connection intervention. Social isolation and loneliness can lead to detrimental effects on morbidity/mortality and health indices. A connection intervention was developed by investigators using key strategies to promote connectedness, providing in-person contact for hospitalized patients to meet individual and self-care needs. This quasi-experimental study was conducted in a Midwest adult academic health center. Social connectedness, anxiety, and loneliness were evaluated at baseline and postintervention using a paired-sample t test. Experience responses were analyzed using content analysis. There were no significant differences in social connectedness, anxiety, or loneliness when comparing baseline with postintervention. Experience themes included sharing personal stories back and forth, treating me as a person, mitigating loneliness, and finding benefit. Despite nonsignificant findings, participants found benefit in filling the social void of being an inpatient. Clinicians should ensure that holistic care is delivered to hospitalized inpatients. Inclusive patient-centered strategies targeted to decrease social isolation and loneliness among acute care inpatients should continue to be developed and tested.


A human choriocarcinoma xenograft in nude mice; a model for the study of antibody localization.
The successful development of the concept of linking cell-killing agents to tumour-specific antibodies will be largely determined by the extent to which the antibodies are preferentially localized in the malignant tissue. A xenograft of human choriocarcinoma (CC3) has been established in nude mice, and the relative distribution of affinity-purified specific antibodies to human chorionic gonadotrophin has been compared with that of nonspecific antibodies from the same species. Treatment of the nonspecific antibodies with ammonium thiocyanate appeared to be important to ensure that the distributions in normal nude mice were equivalent. Specificity indices, derived from the comparative distributions of isotope activity in the tumour and lung of labelled specific and nonspecific antibodies, ranged between 1.3 and 2.0.


Dissociation in major depressive disorder: a pilot study.
The principal objective of this study was to evaluate the occurrence of various dissociative phenomena in patients with major depressive disorder (MDD) and their possible implications in manifestation and course of depression. We administered the Dissociative Experiences Scale (DES) and a self-questionnaire of life events to 27 patients with MDD and to 40 healthy participants in order to collect information on traumatic events. Patients who scored >or= 20 on the DES were also assessed to determine the presence of dissociative disorder. Patients with MDD reported a significantly higher mean score on the DES than the comparison healthy participants. In all, 12 out of 27 patients with MDD reported childhood trauma, and their mean score on the DES representing absorption and imaginative involvement was significantly higher than that of participants without childhood trauma. Also, 7% of our MDD patients were diagnosed with dissociative disorder during this study. The principal limitations of the study were its small sample size and the use of a nonstandardized trauma measure. These findings indicate that dissociative phenomena should not be overlooked in MDD. Screening methods and structured interview for dissociative disorders are useful in psychiatric and psychological practice. Further studies should analyze the role and clinical consequence of different forms of dissociation experiences.


Combiphore (Structure and Ligand Based Pharmacophore) - Approach for the Design of GPR40 Modulators in the Management of Diabetes.
Pharmacophore mapping and molecular docking can be synergistically integrated to improve the drug design and discovery process. A rational strategy, combiphore approach, derived from the combined study of Structure and Ligand based pharmacophore has been described to identify novel GPR40 modulators. DISCOtech module from Discovery studio was used for the generation of the Structure and Ligand based pharmacophore models which gave hydrophobic aromatic, ring aromatic and negative ionizable as essential pharmacophoric features. The generated models were validated by screening active and inactive datasets, GH scoring and ROC curve analysis. The best model was exposed as a 3D query to screen the hits from databases like GLASS (GPCR-Ligand Association), GPCR SARfari and Mini-Maybridge. Various filters were applied to retrieve the hit molecules having good drug-like properties. A known protein structure of hGPR40 (pdb: 4PHU) having TAK-875 as ligand complex was used to perform the molecular docking studies; using SYBYL-X 1.2 software. Clustering both the models gave RMSD of 0.89. Therefore, the present approach explored the maximum features by combining both ligand and structure based pharmacophore models. A common structural motif as identified in combiphore for GPR40 modulation consists of the para-substituted phenyl propionic acid scaffold. Therefore, the combiphore approach, whereby maximum structural information (from both ligand and biological protein) is explored, gives maximum insights into the plausible protein-ligand interactions and provides potential lead candidates as exemplified in this study.


Correlated mass spectrometry and confocal microscopy imaging verifies the dual-targeting action of an organoruthenium anticancer complex.
An addressable single cell imaging strategy combining ToF-SIMS and confocal fluorescence microscopy imaging has been developed, and sucessfully applied to visualize the subcellular distribution of an organoruthenium anticancer complex, [(η6-benzene)Ru(N,N-L)Cl]+ (1; L: 4-anilinoquinazoline ligand), showing its accumulation in both cell membrane and nuclei, and verifying its dual-targeting feature.


The cytological study of the hypophysis pars anterior in the Indian grey mongoose, Herpestes edwardsi (Geoffroy).
The pituitary gland of the Herpestes edwardsi has been studies with special reference to the cytology of the pars anterior. In addition to the agranular chromophobic cells, six morphologically distinct chromophilic cell types have been observed in the pars anterior on the basis of selective histochemical and cytochemical staining techniques which can be classified into various groups such as STH, LTH, TSH, FSH, LH/ICSH and ACTH. The mucoid cells TSH, FSH and LH are much more concentrated in the centro-median region of the pars anterior. Highly concentrated colloid material appears in the acini or follicles which are scattered throughout the pars anterior. A relationship between the distribution of colloid material and any particular type of cell could not be established. The double intermedia layer surrounds almost completely the entire pars nervosa.


Endoscopic submucosal dissection for gastric adenomyoma: A rare entity of 15 cases among 571 patients with gastric submucosal eminence lesions.
Gastric adenomyoma (GA) is a kind of rare gastric submucosal eminence lesions. As the malignant transformation cannot be ruled out, surgery and laparoscopic resection are usually considered. The aim of this study is to evaluate the therapeutic effect and safety of endoscopic submucosal dissection (ESD) for GA.All of the patients with gastric submucosal eminence lesions who underwent ESD from June 2008 to June 2015 in General Hospital, Tianjin Medical University, China, were identified, and patients with GA, which was confirmed by pathological evaluation, were enrolled for further analysis.Among the 571 patients who received ESD, 15 cases with uncertain diagnosis before the procedure were finally confirmed as GA. The mean age of these 15 patients was 46.93 ± 15.56 years (range: 18-73). Most of the lesions were located in antrum (12/15 patients), with 2 in the body of stomach and 1 in cardia, respectively. The mean size of the lesions was 1.47 ± 0.67 cm (range: 0.4-3.0). According to the endoscopic ultrasonography, the lesions of 14 patients originated from submucosa and 1 originated from superficial muscularis, totally with mixed echoes changes. En bloc complete resection was achieved in all of the lesions. No perforation, intraoperative bleeding, delayed bleeding, and mortalities occurred. No recurrence or metastasis was found during 1 to 67 months.ESD appears to be a feasible, safe, and effective treatment for GA with clinical presentation of gastric submucosal eminence lesions.


More than Meets the Eye: Hidden Structures in the Proteome.
A central dogma of molecular biology is that the sequence of a protein dictates its particular fold and the fold dictates its function. Indeed, the sequence → structure → function hypothesis has been a guiding principle by which scientists approach molecular biology. Every student knows that the genome encodes information for the progression from primary sequence to secondary, tertiary, and ultimately quaternary structure. Yet with a growing number of proteins, a fifth level has been identified: rearrangement of existing structures into distinct forms. Recent observations indicate that replication of Ebola virus depends on this fifth level. We believe other viruses with compact genomes and rapid evolution under selective pressure will be a rich source of examples of polypeptides that rearrange to gain added functions. In this review, we describe mechanisms by which viral, prokaryotic, and eukaryotic polypeptides have adopted alternate structures to control or gain function.


Vicarious retribution: the role of collective blame in intergroup aggression.
We provide a new framework for understanding 1 aspect of aggressive conflict between groups, which we refer to as vicarious retribution. Vicarious retribution occurs when a member of a group commits an act of aggression toward the members of an outgroup for an assault or provocation that had no personal consequences for him or her but which did harm a fellow ingroup member. Furthermore, retribution is often directed at outgroup members who, themselves, were not the direct causal agents in the original attack against the person's ingroup. Thus, retribution is vicarious in that neither the agent of retaliation nor the target of retribution were directly involved in the original event that precipitated the intergroup conflict. We describe how ingroup identification, outgroup entitativity, and other variables, such as group power, influence vicarious retribution. We conclude by considering a variety of conflict reduction strategies in light of this new theoretical framework.


Giant yolk sac tumor operated under percutaneous cardiopulmonary support (PCPS) and aspiration device.
We here report the case of an 18-year-old man with a giant yolk sac tumor that is resected under percutaneous cardiopulmonary support (PCPS). Because this patient had severe dyspea when he lay in a supine position, we resected the tumor. We used PCPS during the operation for the induction and maintenance of ventilation because his trachea and left main bronchus were collapsed by the tumor. Also, we used a vacuum aspiration device that is commonly used for facilitating difficult vaginal deliveries. We propose that several devices, such as a PCPS and vacuum aspiration device, are useful for the operation of a mediastinal tumor with dyspnea.


Hepatic metastases of primary jejunal carcinoid tumor: A case report with radiological findings.
Carcinoid tumors represent a group of well-differentiated tumors originating from the diffuse endocrine system outside the pancreas and thyroid. The overall prevalence of carcinoid tumors in the United States is estimated to be one to two cases per 100,000 persons. Various sites of origin of this neoplasm are appendix - 30-45%, small bowel - 25-35% (duodenum 2%, jejunum 7%, ileum 91%, multiple sites 15-35%), rectum 10-15%, caecum - 5%, and stomach - 0.5%. Liver metastases from jejunal and ileal carcinoids are generally hypervascular. Here we report a case of primary jejunal carcinoid tumor in a 66-year-old woman metastasizing to liver with ultrasonography, computed tomography, and diffusion-weighted magnetic resonance imaging (DWI) findings. Primary jejunal carcinoid tumor is a rare entity. DWI can help in the differential diagnosis of hepatic hypervascular metastatic mass lesions from benign ones, as well as in the diagnosis of carcinoid tumor.


Protocol of the Budapest sleep, experiences, and traits study: An accessible resource for understanding associations between daily experiences, individual differences, and objectively measured sleep.
Sleep is both a neurophysiological state and a biologically necessary behavior that performs a variety of indispensable roles for human health, development, and cognitive functioning. Despite this, comparatively little is known about the relationships between daily experiences and sleep features. Importantly, these relationships are bidirectional in nature, may be differently associated with subjectively and objectively assessed sleep, and may also be modulated by individual differences To address this challenge, we created the Budapest Sleep, Experiences, and Traits Study (BSETS), a multidisciplinary observational sleep study utilizing novel remote EEG devices. BSETS was designed to establish a dataset for future use in investigating the relationships between sleep features and daily experiences. In this paper we describe the protocol of the currently ongoing BSETS, which examines a community-dwelling sample of over 250 healthy participants who are studied in a naturalistic setting using a large questionnaire assessing psychological, demographic, and anthropometric information, as well as evening/morning diaries of sleep and daily experiences, and mobile EEG recordings over a period of 7 days. This dataset will become an accessible resource to the wider scientific community and can be utilized to investigate the complex multidirectional relationships between objectively and subjectively measured sleep, daily experiences, and individual differences, bestowing it with significant value for sleep researchers as well as practitioners working in clinical settings with patients suffering from disordered sleep.


Liposomal phospholipid preparations of chloramphenicol for ophthalmic applications.
Since their discovery by Bangham and coworkers almost four decades ago, liposomes have become models for biomembranes and vehicles for pharmaceutical, diagnostic, and cosmetic agents. One of the advantages of using liposomes as a drug vehicle is their ability for slow release, thus reducing dosage, localizing a drug, and minimizing its side-effects. Antibiotic resistance is a growing global problem, including for ocular bacterial infection by Staphylococcus aureus, where time is an important parameter that determines the severity of infection. This situation has prompted the pursuit of ways to prepare drug-encapsulating liposomes that enable bulk release of the drug chloramphenicol (CAP) once the liposomal structure is perturbed. Our approach is a two-step process: first, to characterize the interaction of CAP with model biomembranes of dimyristoylphosphatidylcholine (DMPC) used to prepare CAP-liposomes by different formulations; second, to test the efficiency of these formulation against S. aureus. Solid-state NMR, differential scanning calorimetry, and infrared spectroscopy were used to study the interaction of CAP with DMPC bilayers. The minimum inhibitory concentrations and time-kill curves for S. aureus using different liposomal preparations were compared. Evidence of conformational changes in the DMPC molecules and the effectiveness of the CAP encapsulated in liposomes are reported.


Contributory factors to postoperative spinal fusion complications for children with myelomeningocele.
This is a retrospective review of all children with myelomeningocele (MMC) who were undergoing surgery for scoliosis at our institution. Our aim was to investigate possible correlations between poor nutritional indexes and/or positive urinary cultures before surgery to perioperative infection risk. Patients who have scoliosis secondary to MMC have been shown to have a high rate of infectious complications. Many children with MMC have been found to have asymptomatic urinary tact infections due to their neurogenic bladder. There is little literature on risk factors for and ways to prevent postoperative infections for these patients. We reviewed a comprehensive database for the outcome for spinal fusion surgeries of 59 patients with MMC treated at our institution over the past 45 years. Perioperative infections were correlated to preoperative nutritional status (measured by patient hematocrit [Hct]) and presence of active infection using Fisher Exact Probability Test. A total of 84 different spinal fusion operations for 59 patients were recorded. Patients presenting with poor preoperative nutrition (Hct<or=33) and positive preoperative urinary cultures demonstrated the highest risk for perioperative wound infection (P=0.001). Patients with preoperative poor nutrition without a positive urinary culture as well as those with adequate nutritional status but a preoperative positive urinary culture showed an increased risk of wound infection respectively (P=0.03) and (P=0.002). Positive urine cultures obtained before spinal surgery for children with MMC significantly increased the risk for perioperative wound (P=0.002). Urinary tract infections can be easily detected and treated. We believe urinary culture, protein deficiencies, or Hct<or=33, should be treated and corrected before surgery.


Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.
From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).


Selectivity of cyclooxygenase isoform activity and prostanoid production in normal and diseased Han:SPRD-cy rat kidneys.
Renal prostanoids are important regulators of normal renal function and maintenance of renal homeostasis. In diseased kidneys, renal cylooxygenase (COX) expression and prostanoid formation are altered. With the use of the Han:Sprague-Dawley-cy rat, the aim of this study was to determine the relative contribution of renal COX isoforms (protein, gene expression, and activity) on renal prostanoid production [thromboxane B(2) (TXB(2), stable metabolite of TXA(2)), prostaglandin E(2) (PGE(2)), and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha), stable metabolite of PGI(2))] in normal and diseased kidneys. In diseased kidneys, COX-1-immunoreactive protein and mRNA levels were higher and COX-2 levels were lower compared with normal kidneys. In contrast, COX activities were higher in diseased compared with normal kidneys for both COX-1 [0.05 +/- 0.02 vs. 0.45 +/- 0.11 ng prostanoids x min(-1) x mg protein(-1) (P < 0.001)] and COX-2 [0.64 +/- 0.10 vs. 2.32 +/- 0.22 ng prostanoids x min(-1).mg protein(-1) (P < 0.001)]. As the relative difference in activity was greater for COX-1, the ratio of COX-1/COX-2 was higher in diseased compared with normal kidneys, although the predominant activity was still due to the COX-2 isoform in both genotypes. Endogenous and steady-state in vitro levels of prostanoids were approximately 2-10 times higher in diseased compared with normal kidneys. The differences between normal and diseased kidney prostanoids were in the order of TXB(2) > 6-keto-PGF(1alpha) > PGE(2), as determined by higher renal prostanoid levels and COX activity ratios of TXB(2)/6-keto-PGF(1alpha), TXB(2)/PGE(2), and 6-keto-PGF(1alpha)/PGE(2). This specificity in both the COX isoform type and for the prostanoids produced has implications for normal and diseased kidneys in treatments involving selective inhibition of COX isoforms.


Nuclear Quantum Effects on Aqueous Electron Attachment and Redox Properties.
Nuclear quantum effects (NQEs) on the reduction and oxidation properties of small aqueous species (CO2, HO2, and O2) are quantified and rationalized by first-principles molecular dynamics and thermodynamic integration. Vertical electron attachment, or electron affinity, and detachment energies (VEA and VDE) are strongly affected by NQEs, decreasing in absolute value by 0.3 eV going from a classical to a quantum description of the nuclei. The effect is attributed to NQEs that lessen the solvent response upon oxidation/reduction. The reduction of solvent reorganization energy is expected to be general for small solutes in water. In the thermodynamic integral that yields the free energy of oxidation/reduction, these large changes enter with opposite sign, and only a small net effect (0.1 eV) remains. This is not obvious for CO2, where the integrand is strongly influenced by NQEs due to the onset of interaction of the reduced orbital with the conduction band of the liquid during thermodynamic integration. We conclude that NQEs might not have to be included in the computation of redox potentials, unless high accuracy is needed, but are important for VEA and VDE calculations.


Longitudinal displacement in viscoelastic arteries: a novel fluid-structure interaction computational model, and experimental validation.
Recent in vivo studies, utilizing ultrasound contour and speckle tracking methods, have identified significant longitudinal displacements of the intima-media complex, and viscoelastic arterial wall properties over a cardiac cycle. Existing computational models that use thin structure approximations of arterial walls have so far been limited to models that capture only radial wall displacements. The purpose of this work is to present a simple fluid-struture interaction (FSI) model and a stable, partitioned numerical scheme, which capture both longitudinal and radial displacements, as well as viscoelastic arterial wall properties. To test the computational model, longitudinal displacement of the common carotid artery and of the stenosed coronary arteries were compared with experimental data found in literature, showing excellent agreement. We found that, unlike radial displacement, longitudinal displacement in stenotic lesions is highly dependent on the stenotic geometry. We also showed that longitudinal displacement in atherosclerotic arteries is smaller than in healthy arteries, which is in line with the recent in vivo measurements that associate plaque burden with reduced total longitudinal wall displacement. This work presents a first step in understanding the role of longitudinal displacement in physiology and pathophysiology of arterial wall mechanics using computer simulations.


Disturbances of taste and smell induced by drugs.
We reviewed the current literature (1980-1990, 1991-1996) concerning drugs associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the impact of these adverse effects. Case reports of patients with sudden and delayed onset of one of these disorders with evidence for implication of a drug were included. Disturbances of taste and smell among the elderly and chronically ill, including those with thermal injury, decreases interest in eating and secondarily impairs healing of wounds. Mechanisms involved with these sensory disturbances include deposition of silver sulfate in nerves after use of topical agents containing silver, altered influx of calcium and other ions, chelation or depletion of tissue-bound zinc, disturbed bradykinin catabolism and second messenger synthesis, catabolism, and altered prostaglandin systems. Other mechanisms, particularly prolonged chemosensory disorders after early drug discontinuation, remain unknown.


Single Cell Transcriptome Sequencing of Zebrafish Testis Revealed Novel Spermatogenesis Marker Genes and Stronger Leydig-Germ Cell Paracrine Interactions.
Spermatogenesis in testis is an important process for sexual reproduction, and worldwide about 10-15 percent of couples suffer from infertility. It is of importance to study spermatogenesis at single cell level in both of human and model organisms. Currently, single-cell RNA sequencing technologies (scRNA-seq) had been extensively applied to the study of cellular components and its gene regulations in the testes of different species, including human, monkey, mouse, and fly, but not in zebrafish. Zebrafish was a widely used model organism in biology and had been extensively used for the study of spermatogenesis in the previous studies. Therefore, it is also important to profile the transcriptome of zebrafish testis at single cell level. In this study, the transcriptomes of 14, 315 single cells from adult male zebrafish testes were profiled by scRNA-seq, and 10 cell populations were revealed, including Leydig cell, Sertoli cell, spermatogonia cell (SPG), spermatocyte, and spermatids. Notably, thousands of cell-type specific novel marker genes were identified, including sumo3b for SPG, krt18a.1 for Sertoli cells, larp1b and edrf1 for spermatids, which were also validated by RNA in situ hybridization experiments. Interestingly, through Ligand-Receptor (LR) analyses, zebrafish Leydig cells demonstrated stronger paracrine influence on germ cells than Sertoli cells. Overall, this study could be an important resource for the study of spermatogenesis in zebrafish and might also facilitate the study of the genes associated with human infertility through using zebrafish as a model organism.


Development of a joint diagnostic model of thyroid papillary carcinoma with artificial neural network and random forest.
Objective: Papillary thyroid carcinoma (PTC) accounts for 80% of thyroid malignancy, and the occurrence of PTC is increasing rapidly. The present study was conducted with the purpose of identifying novel and important gene panels and developing an early diagnostic model for PTC by combining artificial neural network (ANN) and random forest (RF). Methods and results: Samples were searched from the Gene Expression Omnibus (GEO) database, and gene expression datasets (GSE27155, GSE60542, and GSE33630) were collected and processed. GSE27155 and GSE60542 were merged into the training set, and GSE33630 was defined as the validation set. Differentially expressed genes (DEGs) in the training set were obtained by "limma" of R software. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis as well as immune cell infiltration analysis were conducted based on DEGs. Important genes were identified from the DEGs by random forest. Finally, an artificial neural network was used to develop a diagnostic model. Also, the diagnostic model was validated by the validation set, and the area under the receiver operating characteristic curve (AUC) value was satisfactory. Conclusion: A diagnostic model was established by a joint of random forest and artificial neural network based on a novel gene panel. The AUC showed that the diagnostic model had significantly excellent performance.


The complete sequence and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms.
We have isolated and sequenced overlapping cDNA clones covering the entire sequence of human apolipoprotein B-100 (apoB-100). DNA sequence analysis and determination of the mRNA transcription initiation site by S1 nuclease mapping showed that the apoB mRNA consists of 14,112 nucleotides including the 5' and 3' untranslated regions which are 128 and 301 nucleotides respectively. The DNA-derived protein sequence shows that apoB-100 is 513,000 daltons and contains 4560 amino acids including a 24-amino-acid-long signal peptide. The mol. wt of apoB-100 implies that there is one apoB molecule per LDL particle. Computer analysis of the predicted secondary structure of the protein showed that some of the potential alpha helical and beta sheet structures are amphipathic, whereas others have non-amphipathic neutral to apolar character. These latter regions may contribute to the formation of the lipid-binding domains of apoB-100. The protein contains 25 cysteines and 20 potential N-glycosylation sites. The majority of cysteines are distributed in the amino terminal portion of the protein. Four of the potential glycosylation sites are in predicted beta turn structures and may represent true glycosylation positions. ApoB lacks the tandem repeats which are characteristic of other apolipoproteins. The mean hydrophobicity the mean value of H1 and helical hydrophobic moment the mean value of microH profiles of apoB showed the presence of several potential helical regions with strong polar character and high hydrophobic moment. The region with the highest hydrophobic moment, between amino acid residues 3352 and 3369, contains five closely spaced, positively charged residues, and has sequence homology to the LDL receptor binding site of apoE. This region is flanked by three neighbouring regions with positively charged amino acids and high hydrophobic moment that are located between residues 3174 and 3681. One or more of these closely spaced apoB sequences may be involved in the formation of the LDL receptor-binding domain of apoB-100. Blotting analysis of intestinal RNA and hybridization of the blots with carboxy apoB cDNA probes produced a single 15-kb hybridization band whereas hybridization with amino terminal probes produced two hybridization bands of 15 and 8 kb. Our data indicate that both forms of apoB mRNA contain common sequences which extend from the amino terminal of apoB-100 to the vicinity of nucleotide residue 6300. These two messages may have resulted from differential splicing of the same primary apoB mRNA transcript.


Heavy metal contamination in soils and vegetables and health risk assessment of inhabitants in Daye, China.
Objective This study was performed to evaluate the state of heavy metal contamination in soil and vegetables and assess the health risk of inhabitants in the mine-affected area and area far from the mine (reference area) in Daye, China. Methods The heavy metal concentrations in soil and vegetable samples were detected by inductively coupled plasma mass spectrometry. Residents' exposure parameters were obtained through a questionnaire survey. A health risk assessment model recommended by the United States Environmental Protection Agency was used to evaluate the residents' risk of oral exposure. Results The copper, lead, cadmium, and arsenic concentrations in soil and in vegetables were higher in the mine-affected area than in the reference area. The health risk of residents in the reference area was within the acceptable range (hazard index < 1, carcinogen risk < 10-4). In the contaminated area, however, the mean hazard index was 2.25 for children and 3.00 for adults, and the mean carcinogen risk was 4.749 × 10-4 for children and 0.587 × 10-4 for adults. Conclusions Potential health risks exist for inhabitants near the mine area. Cadmium and arsenic should be paid more attention as risk sources.


Influence of water, fat, and glycerol on the mechanism of thermal prion inactivation.
Extending the recent analysis of the safety of industrial bovine fat-derived products for human consumption (Müller, H., Stitz, L., and Riesner, D. (2006) Eur. J. Lip. Sci. Technol. 108, 812-826), we investigated systematically the effects of fat, fatty acids, and glycerol on the heat destruction of prions. Prion destruction was qualitatively and quantitatively evaluated in PrP 27-30, or prion rods, by the inactivation of infectivity as well as by the degradation of the polypeptide backbone. Under all conditions analyzed, inactivation of prion infectivity was achieved more efficiently than backbone degradation by several orders of magnitude. The presence of fat enhanced prion inactivation and offers a mild treatment for prion decontamination. In contrast, the presence of fat, fatty acids, and especially glycerol protected the PrP 27-30 backbone against heat-induced degradation. Glycerol also protected against heat-induced inactivation of prion infectivity. A phase distribution analysis demonstrated that prions migrated to the interphase of a fat/water mixture at room temperature and accumulated in the water phase at higher temperatures. In a systematic study of the mechanism of prion destruction, we found an intermediate structure of PrP that has fewer fibrils in beta-sheet formation, lower resistance to protease digestion, greater aggregation, and reduced solubility compared with PrP 27-30 but retains residual infectivity. These findings suggest that prion infectivity depends on beta-sheet-rich fibrillar structure and that inactivation proceeds in a stepwise manner, which explains the tailing effect frequently observed during inactivation.