Short telomeres drive pessimistic judgement bias in zebrafish.
The role of telomerase reverse transcriptase has been widely investigated in the contexts of ageing and age-related diseases. Interestingly, decreased telomerase activities (and accelerated telomere shortening) have also been reported in patients with emotion-related disorders, opening the possibility for subjective appraisal of stressful stimuli playing a key role in stress-driven telomere shortening. In fact, patients showing a pessimistic judgement bias have shorter telomeres. However, in humans the evidence for this is correlational and the causal directionality between pessimism and telomere shortening has not been established experimentally yet. We have developed and validated a judgement bias experimental paradigm to measure subjective evaluations of ambiguous stimuli in zebrafish. This behavioural assay allows classification of individuals in an optimistic-pessimistic dimension (i.e. from individuals that consistently evaluate ambiguous stimuli as negative to others that perceive them as positive). Using this behavioural paradigm we found that telomerase-deficient zebrafish (tert-/-) were more pessimistic in response to ambiguous stimuli than wild-type zebrafish. The fact that individuals with constitutive shorter telomeres have pessimistic behaviours demonstrates for the first time in a vertebrate model a genetic basis of judgement bias.


Warm skin alters cardiovascular responses to cycling after preheating and precooling.
Exercise in hot conditions increases core (TC) and skin temperature (TSK) and can lead to a progressive rise in HR and decline in stroke volume (SV) during prolonged exercise. Thermoregulatory-driven elevations in skin blood flow (SkBF) adds complexity to cardiovascular regulation during exercise in these conditions. Presently, the dominant, although debated, view is that raising TSK increases SkBF and reduces SV through diminished venous return; however, this scenario has not been rigorously investigated across core and skin temperatures. We tested the hypothesis that high TSK would raise HR and reduce SV during exercise after precooling (cold water bath) and preheating (hot water bath) and that no relationship would exist between SkBF and SV during exercise. Non-endurance-trained individuals cycled for 20 min at 69% ± 1% VO₂peak on four occasions: cool skin-cool core (SkCCC), warm skin-cool core (SkWCC), cool skin-warm core (SkCCW), and warm skin-warm core (SkWCW) on separate days. After precooling of TC, the rise in HR was greater in SkWCC than in SkCCC (P < 0.001), yet SV was similar (P = 0.26), which resulted in higher QC at min 20 in SkWCC (P < 0.01). Throughout exercise after preheating of TC, HR was higher (P < 0.001), SV was reduced (P < 0.01), and QC was similar (P = 0.40) in SkWCW versus SkCCW. When all trials were compared, there was no relationship between SkBF and SV (r = -0.08, P = 0.70); however, there was an inverse relationship between HR and SV (r = -0.75, P < 0.001). These data suggest that when TSK is elevated during exercise, HR and TC will rise but SV will only be reduced when TC is also elevated above 38°C. Furthermore, changes in SV are not related to changes in SkBF.


The Challenge of the Sponge Suberites domuncula (Olivi, 1792) in the Presence of a Symbiotic Bacterium and a Pathogen Bacterium.
Sponges, which are in close contact with numerous bacteria in prey/predator, symbiotic and pathogenic relationships, must provide an appropriate response in such situations. This starts with a discriminating recognition of the partner either by a physical contact or through secreted molecules or both. We investigated the expression of the Toll-like receptor, Caspase 3/7, Tumor Necrosis Factor receptor-associated factor 6, Bcl-2 homology protein-2 and macrophage expressed genes of axenic sponge cells in the presence of a symbiotic bacterium (Endozoicomonas sp. Hex311), a pathogen bacterium (Pseudoalteromonas sp. 1A1), their exoproducts and lipopolysaccharides. The vast majority of answers are in line with what could be observed with the symbiotic bacterium. The pathogenic bacterium seems to profit from the eukaryotic cell: suppression of the production of the antibacterial compound, inhibition of the apoptosis caspase-dependent pathway, deregulation of bacterial recognition. This work contributes new scientific knowledge in the field of immunology and apoptosis in early branching metazoan harboring within its tissue and cells a large number of symbiotic bacteria.


[Fitting hearing aids in early childhood based on auditory evoked potentials in steady states].
The purpose of the Newborn Hearing Screening Program is to achieve early. Identification and appropriate intervention for hearing loss. Hearing aids are the most frequent intervention for deafness. Paediatric specific clinical protocols for fitting hearing aids always recommend accurate characterisation of hearing thresholds in newborns. In this sense, electrophysiological procedures are specially indicated in determined hearing sensibility from the first age of life since it is an objective and reliable procedure. 20 normal hearing subject and 17 hearing loss subjects participated in this study. Auditory Steady State Responses (ASSR) were obtained from all of them. Hearing aid fitting was established from the electrophysiological responses. Dynamic range, gain, compression ratio and maximum output of the hearing aid were obtained from the intensity amplitude function of the ASSR. The procedure discussed in this study is specially indicated in newborns and very young children in which other test are not suitable.


The epidemiology of malignant neoplasms of the large intestine in Canada: 1941-1985.
Morbidity and mortality from malignancies of the large intestine, in Canada, were examined for the periods 1970-1980 and 1941-1985, respectively. Age-standardized morbidity rates for males have increased significantly during the period studied (18.4 to 26.2 new cases per 100,000 population per year; p less than 0.0001), with increases in morbidity being most attributable to significant increases in age-specific rates for males aged 45-54, 55-64, 65-74, and 75-84 years (p less than or equal to 0.015). Standardized rates for females have also increased significantly (21.2 to 23.3 new cases per 100,000 population per year; p = 0.012) as was the case for age-specific rates in women aged 65-74, 75-84, and 85+ years, which have risen sharply (p less than 0.015), whereas rates in women aged 25-34 and 35-44 years have declined significantly (p less than 0.04). Significant reductions in female age-standardized mortality rates (17.0 to 10.2 deaths per 100,000 population per year; p less than 0.0001) are attributable to significant declines in mortality for all of the eight age groups studied (p less than 0.013). The significant reduction in male age-standardized mortality rates (14.2 to 13.3 deaths per 100,000 population per year; p = 0.04) is attributable to significant reductions in mortality for five of the eight age groups studied (0-24, 25-34, 35-44, and 45-54 years)--rates for males aged 85+, however, have increased significantly (p less than 0.0001).


Dynamics and observations of long-term orthodontic tooth movement and subsequent relapse in C57BL/6 mice.
The risk of relapse associated with orthodontic treatment is a major problem. Despite extensive research and discussion regarding the risk of orthodontic relapse, the underlying mechanisms remain to be elucidated. This study aimed to evaluate relapse following orthodontic treatment in mice (C57BL/6) tested via the coil spring method based on tooth movement at 21 days and mechanical retention at 7 days after completion of the procedure. During the experiment, relapse was observed and evaluated over 7 days. At the end of orthodontic tooth movement, the average distance was 259.6 (± 10.9) µm, and tooth movement was observed in all mice. No significant differences in distance were observed at the end of the experimental treatment period or after 7 days of mechanical retention. The distance at the start of observation was 258.6 (± 10.4) µm, whereas that at the end was 155.4 (± 12.4) µm, indicating that the distance had decreased significantly. Relative to the total relapse distance over the 7-day period, 45.7 (± 4.3)% of the relapse was observed on Day 0-1. The mouse model established in the current study provides an effective and reproducible method for the optimal evaluation of relapse. Our findings clarified that most of the relapse occurs within 7 days during the initial observation stage.


"Doctor, will that x-ray harm my unborn child?".
Exposure to ionizing radiation can be a source of anxiety for many pregnant women and their health care providers. An awareness of the radiation doses delivered by different techniques and the acceptable exposure thresholds can help both patients and practitioners. We describe exposure to radiodiagnostic procedures during pregnancy and suggest an approach to assess the potential risk.


Efficacy of humanized high-dose meropenem, cefepime, and levofloxacin against Enterobacteriaceae isolates producing Verona integron-encoded metallo-β-lactamase (VIM) in a murine thigh infection model.
We aimed to describe the in vivo activity of humanized pharmacokinetic exposures of meropenem and comparators against Verona integron-encoded metallo-β-lactamase (MBL) (VIM)-producing Enterobacteriaceae in a murine model. Levofloxacin activity was predicted by its MIC, and cefepime activity displayed variability, whereas meropenem produced a >1 log CFU reduction against all isolates despite high MICs indicative of resistance. Our results suggest that despite in vitro resistance, high-dose meropenem may be a possible option against infections caused by Enterobacteriaceae producing MBL-type carbapenemases.


Improving the ED-to-Home Transition: The Community Paramedic-Delivered Care Transitions Intervention-Preliminary Findings.
To describe a novel model of care that uses community-based paramedics to deliver a modified version of the evidence-based hospital-to-home Care Transitions Intervention (CTI) to a new context: the emergency department (ED)-to-home transition. Single-blind randomized controlled trial. Three EDs in 2 cities. Through June 2017, 422 individuals discharged home from the EDs who provided consent and were randomized to receive the modified CTI. We modified the hospital-to-home CTI, applying it to the ED-to-home transition and delivering services through community paramedics, allowing the program to benefit from the unique attributes of paramedics to deliver care. Through surveys of participants, medical record review, and documentation of activities by CTI coaches, we characterize the participants and program, including feasibility and acceptability. Median age of participants was 70.7, 241 (57.1%) were female, and 385 (91.2%) were white. Coaches successfully completed 354 (83.9%) home visits and 92.7% of planned telephone follow-up for call 1, 90.9% for call 2, and 85.8% for call 3. We found high levels of acceptability among participants, with most participants (76.2%) and their caregivers (83.1%) reporting themselves likely or extremely likely to choose an ED featuring the CTI program in the future. Coaches reported delivering expected services during contact at least 88% of the time. Although final conclusions about program effectiveness must await the results of the randomized controlled trial, the findings reported here are promising and provide preliminary support for an ED-to-home CTI Program's ability to improve outcomes. The coaches' identity as community paramedics is particularly noteworthy, because this is a unique role for this provider type. J Am Geriatr Soc 66:2213-2220, 2018.


Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy.
Lipodystrophy is a rare disorder that is characterized by selective loss of subcutaneous and visceral fat and is associated with hypertriglyceridemia, hepatomegaly, and disordered glucose metabolism. It has recently been shown that chronic leptin treatment ameliorates these abnormalities. Here we show that chronic leptin treatment improves insulin-stimulated hepatic and peripheral glucose metabolism in severely insulin-resistant lipodystrophic patients. This improvement in insulin action was associated with a marked reduction in hepatic and muscle triglyceride content. These data suggest that leptin may represent an important new therapy to reverse the severe hepatic and muscle insulin resistance and associated hepatic steatosis in patients with lipodystrophy.


Submandibular salivary gland tumors: Clinical course and outcome of a 20-year multicenter study.
The purpose of this retrospective chart review study was to review the nature and clinical course of benign and malignant submandibular gland tumors at 2 major university-affiliated tertiary medical centers. All patients who underwent submandibular salivary gland excision between 1990 and 2010 were included. Clinical and disease-related data were collected from the medical charts. One hundred ninety-three patients were identified, of whom 108 (56%) had non-neoplastic disorders (sialolithiasis and sialadenitis). The remaining 85 patients (44%) had a submandibular salivary gland tumor. The most common benign neoplasm was pleomorphic adenoma (53 patients). Twenty tumors (24%) were malignant: adenoid cystic carcinoma in 11 patients, mucoepidermoid carcinoma in 6 patients, and adenocarcinoma in 3 patients. Recurrence was noted in 7 patients with submandibular gland malignancy and in 2 patients with pleomorphic adenoma. The 5-year disease-free survival rate was 63%. Tumors of the submandibular gland are infrequently malignant. Recurrent submandibular salivary gland pleomorphic adenoma is rare compared with recurrences in the parotid gland.


Relationship between endo- and exopeptidases in a processing enzyme system: activation of an endoprotease by the aminopeptidase B-like activity in somatostatin-28 convertase.
The somatostatin-28 convertase activity involved in vitro in the processing of somatostatin-28 into the neuropeptides somatostatin-28-(1-12) and somatostatin-14 is composed of an endoprotease and a basic aminopeptidase. We report herein on the purification to apparent homogeneity of these two constituents and on their functional interrelationship. In particular we observed that after various physicochemical treatments, the 90-kDa endoprotease activity was recovered both at this molecular mass and as a 45-kDa entity. Moreover, the production of [Arg-2,Lys-1]somatostatin-14 from somatostatin-28 by the action of the endoprotease was activated in a cooperative manner by the aminopeptidase B-like enzyme. A 10-fold activation occurred when the exopeptidase was inhibited by 6.5 mM diisopropyl fluorophosphate and allowed the determination of a half-maximal activation constant (K1/2) of approximately equal to 13 nM. These observations strongly suggest that both enzymes act in a concerted manner in vitro and that they may form a complex in vivo.


Early growth, development and allometry of glyphosate-resistant and susceptible Amaranthus palmeri in response to current and elevated temperature and CO2.
This study aimed to evaluate the influence of CO2 and temperature on glyphosate-resistant and susceptible biotypes of Amaranthus palmeri (Palmer amaranth) in terms of morphological development. Height (cm), stem diameter (cm), leaf area (cm2), number of leaves, leaf, stem, and root dry matter, plant volume (m3), as well as shoot-to-root allometry were evaluated. The Palmer amaranth biotypes were grown under four different scenarios: 1-low temperature (23/33 °C) and CO2 (410 ± 25 ppm); 2-low temperature (23/33 °C) and high CO2 (750 ± 25 ppm); 3-high temperature (26/36 °C) and low CO2 (410 ± 25 ppm); and 4-high temperature (26/36 °C) and CO2 (750 ± 25 ppm). Between CO2 and temperature, the majority of differences observed were driven by CO2 levels. Palmer amaranth grown under 750 ppm of CO2 was 15.5% taller, displayed 10% more leaf area (cm2), 18% more stem dry matter, and had a 28.4% increase in volume (m3) compared to 410 ppm of CO2. GA2017 and GA2020 were 18% and 15.5% shorter, respectively. The number of leaves was 27% greater for GA2005. Plant volume decreased in GA2017 (35.6%) and GA2020 (23.8%). The shoot-to-root ratio was isomeric, except at 14 and 21 DAT, where an allometric growth towards shoot development was significant. Palmer amaranth biotypes responded differently to elevated CO2, and the impacts of temperature need further investigation on weed physiology. Thus, environmental and genetic background may affect the response of glyphosate-resistant and susceptible populations to climate change scenarios.


[Methods of measuring hyperinsulinism and insulin resistance].
The author gives an account of methods used for evaluation of hyperinsulinism and insulin resistance such as: hyperinsulinaemic, euglycaemic and hyper- and hypoglycaemic "clamp", minimal model of glucose and insulin kinetics. They evaluate specially indexes used in clinical practice such as: I/G, (insulin/glucose--the so-called insulinogenic index), the G/I index, (the so-called index of insulin resistance) and the index of C-peptide/IRI, basal and during the oral glucose tolerance test. In epidemiological studies of the prevalence of the X syndrome (5H) he recommends to use the G/I index basal and minimal two hours after a glucose load, along with assessment of C-peptide. It is thus possible to estimate not only insulin resistance but also hyperinsulinism and the ratio of distribution-utilization factors in the development of this hyperinsulinism. Hyperinsulinism need not be only hypersecretory but may be also associated with a reduced insulin utilization in the liver and peripheral target tissues. A hyperinsulinaemic response may be observed in four types of glycaemic curves after a glucose load: a in a normal curve, a flat curve, in impaired glucose tolerance and in a diabetic curve. According to the author the limiting value of the I/G index is 0.4 and the limiting value of the G/I index is 6 when the insulinaemia is expressed in mIU/l and the blood sugar level in mg%. The limiting level of insulinaemia after two hours is 63 mIU/l. The ratio of C-peptide: IRI basal is cca 5:1 after a glucose load 2.5:1 when expressed in moles.(ABSTRACT TRUNCATED AT 250 WORDS)


Recovery from release of ureteral obstruction in the rat: relationship to nephrogenesis.
Obstructive nephropathy is a major cause of renal insufficiency in infants and children. Despite release of unilateral ureteral obstruction (UUO) in the first five days of life in the rat, renal growth is impaired, while glomerular filtration rate (GFR) is preserved at one month, but decreases markedly by one year. To test the hypothesis that renal recovery from UUO depends on the stage of nephrogenesis at the time of relief of obstruction, renal recovery from relief of five days UUO following completion of nephrogenesis (days 14 to 19) was compared with UUO during nephrogenesis (days 1 to 5). Rats underwent UUO or sham operation at one day of age, with relief five days later. In additional groups of neonatal rats, the operation was at 14 days, with relief at 19 days. Three months later, blood pressure, GFR, urine flow, sodium and potassium excretion, and kidney weight were measured. In addition, the number of glomeruli, glomerular maturation, glomerular diameter, tubular atrophy, and interstitial fibrosis were determined in each kidney. The effects of five-day UUO on number of glomeruli was determined also in adult rats one month following relief of obstruction. Three months following relief of UUO during days 14 to 19, renal growth was decreased by 50%, compared to a 30% reduction following relief of UUO during days 1 to 5 (P < 0.05). The number of glomeruli was reduced by approximately 50% regardless of the timing of UUO, but glomerular size was reduced only in rats with UUO from days 14 to 19. Blood pressure and tubular atrophy were increased, and GFR, urine flow, sodium and potassium excretion were decreased in the postobstructed kidney of both neonatal groups. In the adult rat, the five-day UUO did not result in a decrease in the number of glomeruli. In the period immediately following nephrogenesis, the kidney is particularly susceptible to long-term injury from temporary UUO. This suggests that a delay in relief of significant ureteral obstruction should be avoided if diagnosed in the perinatal or neonatal period.


Synthesis and biological activities of photoaffinity labeling analogues of substance P.
Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-MetNH2, SP) is an undecapeptide with important properties as a neurotransmitter and with other functions. No specific antagonists and no long-acting analogues of this peptide hormone are known to date. In order to reach these goals, analogues of SP have been prepared which contain potential affinity, as well as photoaffinity labeling functions, suitable for irreversible attachment to SP receptors. We report here the synthesis of SP analogues which have the Phe residues in positions 7 or 8 replaced with (4'-NO2)Phe, (4'-NH2)Phe, (4'-N2+)Phe, and (4'-N3)Phe. Some of these peptides are used for photoaffinity labeling studies using various bioassays. The synthesis of the (NO2)Phe-containing peptide was carried out on solid phase using Nle instead of Met and the Boc strategy up to residue 4; the remaining amino acids were added using an Fmoc strategy. The protected undecapetide was cleaved by ammonolysis, purified by chromatography on silica gel with chloroform/methanol and deprotected afterwards. The amino, diazonium, and azido peptides were obtained in this sequence by chemical modification of the nitro peptides. On guinea pig ileum the modified peptides in position 8 had close to maximal activity, whereas modifications in position 7 produced some reduced activity, especially the nitro modification. No diazonium peptide produced any irreversible effects on guinea pig ileum. Photoinactivation studies were carried out on strips of guniea pig trachea, but no irreversible effects have been observed, neither permanent stimulation nor permanent inactivation. The biological activities and effects are discussed in view of the molecular properties of the synthesized analogues.


FamAnn: an automated variant annotation pipeline to facilitate target discovery for family-based sequencing studies.
FamAnn is an automated variant annotation pipeline designed for facilitating target discovery for family-based sequencing studies. It can apply a different inheritance pattern or a de novo mutations discovery model to each family and select single nucleotide variants and small insertions and deletions segregating in each family or shared by multiple families. It also provides a variety of variant annotations and retains and annotates all transcripts hit by a single variant. Excel-compatible outputs including all annotated variants segregating in each family or shared by multiple families will be provided for users to prioritize variants based on their customized thresholds. A list of genes that harbor the segregating variants will be provided as well for possible pathway/network analyses. FamAnn uses the de facto community standard Variant Call Format as the input format and can be applied to whole exome, genome or targeted resequencing data. https://sites.google.com/site/famannotation/home CONTACT: firstname.lastname@example.com, email@example.com, firstname.lastname@example.com Supplementary information: Supplementary data are available at Bioinformatics online.


Validity of the Narcissistic Personality Inventory (NPI) in a psychiatric sample.
Investigated the validity of the Narcissistic Personality Inventory (NPI) in a psychiatric sample. Fifty psychiatric patients were given the NPI as part of a routine psychological evaluation. Correlations between the NPI and the basic personality style scales of the Millon Clinical Multiaxial Inventory (MCMI) were obtained; the largest correlation was between the NPI and the narcissism scale of the MCMI (r = .66, p less than .001). When classified into the low and high narcissistic groups, there was 74% agreement between the NPI and narcissistic scale of the MCMI. These results provide further support for the construct validity of the NPI.


Aminotransferase elevation in HIV/hepatitis B virus co-infected patients treated with two active hepatitis B virus drugs.
Discerning drug hepatotoxicity from viral hepatitis flares remains an ongoing problem unique to patients coinfected with HIV and hepatitis B (HBV). We present three such coinfected patients who have been on two anti-HBV agents, lamivudine and tenofovir disoproxil fumarate simultaneously, as part of highly active antiretroviral therapy (HAART). All three developed significant aminotransferase elevations 6-12 weeks after initiation of HAART despite being on two active HBV drugs. Two of the three patients were initially thought to have drug-related hepatotoxicity from HIV medications. It seems more likely that all three patients demonstrated hepatitis B reactivation of differing severity as the result of varying degrees of immune recovery. Distinguishing clearly between drug-related hepatotoxicity and hepatitis reactivation may be difficult but is important as their clinical management differs.


Expression of vasa, piwi, and nanos during gametogenesis in Typosyllis antoni (Annelida, Syllidae).
Although model species have proven to be crucial for developmental biology, the evo-devo approach requires a broader picture across phylogeny. Herein, we try to expand the range of studied annelids by presenting a transcriptome of Typosyllis antoni as a tool for the study of developmental and evolutionary processes in Syllidae. Moreover, we provide homologs of the stem-cell markers vasa, piwi, and nanos, and investigate their expression patterns in gamete-producing individuals for the first time in this group. We found no expression in females, while there is a distinct expression pattern in males. Based on this data, we argue that spermatogenesis starts in the gonads and finishes in the coelomic cavity, and it occurs simultaneously in a large number of segments. Surprisingly, no expression of the stem-cell markers was found in the segment addition zone of these reproducing animals (stolonizing). Preliminary explanations like a lack of growth during stolonization, or the absence of a common genetic program between germ and somatic stem cells, are discussed. Finally, no reservoir of primordial cells has been detected, suggesting a possible epigenic origin of the Primordial Germ Cells of this species, though this hypothesis needs to be further investigated.


Assessment of autism in community settings: discrepancies in classification.
Review of 78 evaluations for 29 young children examined practices used in assessment of autism spectrum disorders in three settings: public schools, developmental disabilities eligibility determinations, and our hospital-based early childhood mental health program. While similar rates of classification of autism spectrum disorders were found across sites, the rate of agreement by different evaluators for individual children was only 45%. Further, most community evaluators did not follow best practice guidelines nor use autism diagnostic tools with established psychometric properties. In this sample of primarily Latino, Spanish-speaking children, most community evaluators did not document assessment of the child in their native language, nor address the impact of language in their assessments.


Noralashinol B, a norlignan with cytotoxicity from stem barks of Syringa pinnatifolia.
One new norlignan, noralashinol B (1), and one new natural product, proposed noralashinol C (2), were isolated in a continuous phytochemical investigation on the stem barks of Syringa pinnatifolia. Their structures were elucidated based on the analysis of spectroscopic data, including mass spectrometry and 1D and 2D NMR spectroscopies, and the absolute configuration was determined by experimental and calculated electronic circular dichroism. Compound 1 showed a weak cytotoxicity against HepG2 hepatic cancer cells with its IC50 value of 31.7 μM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-80.0 μM.


Rationalizing inter- and intracrystal heterogeneities in dealuminated acid mordenite zeolites by stimulated Raman scattering microscopy correlated with super-resolution fluorescence microscopy.
Dealuminated zeolites are widely used acid catalysts in research and the chemical industry. Bulk-level studies have revealed that the improved catalytic performance results from an enhanced molecular transport as well as from changes in the active sites. However, fully exploiting this information in rational catalyst design still requires insight in the intricate interplay between both. Here we introduce fluorescence and stimulated Raman scattering microscopy to quantify subcrystal reactivity as well as acid site distribution and to probe site accessibility in the set of individual mordenite zeolites. Dealumination effectively introduces significant heterogeneities between different particles and even within individual crystals. Besides enabling direct rationalization of the nanoscale catalytic performance, these observations reveal valuable information on the industrial dealumination process itself.


Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases.
Persistent or recurrent disease is rare in low risk patients with papillary thyroid cancer, and follow-up of these patients is a matter of debate. Neck ultrasonography (US), serum thyroglobulin (Tg), and whole body scan (WBS) after T(4) withdrawal were performed in 456 patients, followed up to 5 yr. At the end of the first year, 335 patients were Tg negative, and 121 were Tg positive; 65 of 96 patients with Tg levels between 1 and 10 ng/ml became spontaneously Tg negative after 2 yr. During follow-up, WBS discovered node metastases in 13 subjects, and US discovered node metastases in 38 subjects (31 Tg positive and 7 Tg negative). WBS did not add any information, because all WBS-positive patients were also US and Tg positive. Fifty percent of metastases were less than 1 cm and not palpable. Finally, the negative predictive value of both negative Tg and US at first follow-up was 98.8%. We suggest a first follow-up based upon US assessment and stimulated (after T(4) withdrawal or recombinant human TSH) serum Tg determination; subsequently, 1) US should not be mandatory at each examination in initially Tg- and US-negative subjects, but is strongly suggested in all other cases; 2) Tg determination should be repeated 1 yr later, after exogenous or endogenous TSH stimulation only in initially Tg-positive patients without any other evidence of residual disease; and 3) Tg measurement during therapy should be sufficient in all other cases.


Olfactory impairment in the rotenone model of Parkinson's disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation.
Olfactory and rapid eye movement (REM) sleep deficits are commonly found in untreated subjects with a recent diagnosis of Parkinson's disease (PD). Additionally, different studies report declines in olfactory performance during a short period of sleep deprivation. Mechanisms underlying these clinical manifestations are poorly understood, and impairment of dopamine (DA) neurotransmission in the olfactory bulb and the nigrostriatal pathway may have important roles in olfaction and REM sleep disturbances. Therefore, we hypothesized that modulation of the dopaminergic D2 receptors in the olfactory bulb could provide a more comprehensive understanding of the olfactory deficits in PD and REM sleep deprivation (REMSD). We decided to investigate the olfactory, neurochemical, and histological alterations generated through the administration of piribedil (a selective D2 agonist) or raclopride (a selective D2 antagonist) within the glomerular layer of the olfactory bulb, in rats subjected to intranigral rotenone and REMSD. Our findings provide evidence of the occurrence of a negative correlation (r = -0.52, P = 0.04) between the number of periglomerular TH-ir neurons and the bulbar levels of DA in the rotenone, but not sham, groups. A significant positive correlation (r = 0.34, P = 0.03) was observed between nigrostriatal DA levels and olfactory discrimination index (DI) for the sham groups, indicating that increased DA levels in the substantia nigra pars compacta (SNpc) are associated with enhanced olfactory discrimination performance. Also, increased levels in bulbar and striatal DA were induced by piribedil in the rotenone control and rotenone REMSD groups, consistent with reductions in the DI. The present evidence reinforce the idea that DA produced by periglomerular neurons, particularly the bulbar dopaminergic D2 receptors, is an essential participant in olfactory discrimination processes, as the SNpc, and the striatum.


A comprehensive care program for pregnant addicts: obstetrical, neonatal, and child development outcomes.
This study reports the results of a comprehensive care program for pregnant addicts, one that provides medical, counseling, and child development services. Findings include the following. Women who enroll while pregnant generally stay through childbirth, and most deliveries are free of complication. Most newborns are of normal gestational age and birthweight, and these outcomes are directly related to length and amount of prenatal care. Neonatal withdrawal is directly related to prenatal maternal methadone dose. Child development, as measured by the Bayley Scales, is usually in the normal range, although mean scores for cognitive development decrease through age 2. Female babies generally have higher cognitive and motor scores than males, and their cognitive scores decline less sharply than those of the males. Developmental scores are directly related to neonatal maturity, especially birthweight. Prenatal maternal methadone dose tends to be negatively related to developmental scores for boys but not for girls.


Sequence of events leading to apoptosis in long term cultured HeLa cells.
We have maintained HeLa cells in culture in the original medium for increasing times to induce growth arrest. Cell viability was evaluated by trypan blue dye exclusion assay. We observed that when cells are maintained in culture for several days, morphological hallmarks of apoptosis become evident. DNA synthesis rate, followed by (3)H-thymidine incorporation slowed down in long term cultured cells. This evidence was supported by the analysis of cell cycle progression determined by proliferating cell nuclear antigen (PCNA) immunostaining. Apoptotic cells have been characterized with respect to the sequential appearance of high molecular weight and internucleosomal DNA fragmentation. We have provided evidence that in this experimental model the first step in DNA degradation is represented by the formation of high molecular weight fragments, whereas nucleosomal DNA ladder is visible later on. The activation of the enzyme poly(ADP-ribose)polymerase, considered a marker of apoptotic death, has been observed. The results suggest that long term culture conditions activate the apoptotic programme.


Effects of neighbourhood and household sanitation conditions on diarrhea morbidity: Systematic review and meta-analysis.
Sanitation in neighbourhood and household domains can provide primary protection against diarrhea morbidity, yet their distinct health benefits have not been succinctly distinguished and reviewed. We present here the first systematic review and meta-analysis of the distinct effect of neighbourhood and household sanitation conditions on diarrhea morbidity. We identified studies reporting the effect of neighbourhood-level exposure to wastewater or household sanitation facilities on diarrhea, by performing comprehensive search on five databases, namely the Cochrane library, PubMed, Embase, Scopus and Web of Science, from the earliest date available to February 2015. Twenty-one non-randomized studies and one randomized controlled trial met the pre-determined inclusion criteria, consisting of six datasets on neighbourhood sanitation conditions (total 8271 subjects) and 20 datasets on household sanitation (total 20021 subjects). We calculated the pooled effect estimates of neighbourhood and household sanitation conditions on diarrhea morbidity using the inverse variance random-effects model. The pooled effect estimates showed that both neighbourhood sanitation conditions (odds ratio = 0.56, 95%CI: 0.40-0.79) and household sanitation (odds ratio = 0.64, 95%CI: 0.55-0.75) are associated with reduced diarrheal illness, and that the magnitudes of the associations are comparable. Evidence of risk of bias and heterogeneity were found in the included studies. Our findings confirm that both neighbourhood sanitation conditions and household sanitation are associated with considerable reduction in diarrhea morbidity, in spite of a number of methodological shortcomings in the included studies. Furthermore, we find evidence that neighbourhood sanitation conditions is associated with similar magnitude of reduction in diarrhea morbidity as household sanitation. The findings suggest that, in addition to household sanitation provision, dual emphasis on neighbourhood sanitation through public sanitation infrastructure provision and community-wide sanitation adoption is advisable for effective reduction of diarrheal disease burden.


[The presentation of clinical cases: the map is not the territory].
To establish their effectiveness for teaching purposes two different expository methods employed for the presentation of clinical cases are compared: the "traditional or conventional" expository method and the more recently introduced non-conventional expository method. The "traditional" expository method is characterized by its schematization and rigidity, which are features that misrepresent the real clinical situation. The non-conventional expository method is distinguished by its fluidity, by its different cognitive approach (iterative approach) and by its ability to make the cognitive processes underlying all clinical reasoning explicit. This is an element of fundamental importance for teaching. In addition, the authors point out the teaching limits implicit in the presentation of cases whatever their expository method. The authors conclude by maintaining that tutorials at the patient's bedside must form the basis of clinical teaching.


Environmental friendly cold-mechanical/sonic enzymatic assisted extraction of genipin from genipap (Genipa americana).
An efficient cold-mechanical/sonic-assisted extraction technique was developed for extraction of genipin from genipap (Genipa americana) peel. Ultrasound assisted extraction (285 W, 24 kHz) was performed at 5, 10 and 15 °C for 5, 10 and 15 min. After cold-extraction, genipin was separated from pectin and proteins by aid of fungal pectinesterase. The maximum yield of non-cross-linked genipin was 7.85±0.33 mg/g, at 10 °C for 15 min by means of ultrasound extraction. The protein amount in extracts decreased in all samples. If mechanical process is combined with ultrasound assisted extraction the yield is increased by 8 times after the pectinesterase-assisted polyelectrolyte complex formation between pectic polysaccharides and proteins, avoiding the typical cross-linking of genipin. This novel process is viable to obtain non-cross-linked genipin, to be used as a natural colorant and cross-linker in the food and biotechnological industries.


Acquisition of human concentrative nucleoside transporter 2 (hcnt2) activity by gene transfer confers sensitivity to fluoropyrimidine nucleosides in drug-resistant leukemia cells.
CEM-ARAC leukemia cells with resistance to cytarabine were shown to lack equilibrative transporter (hENT1) expression and activity. Stable transfer of hCNT2 cDNA into CEM-ARAC enabled Na(+)-dependent transport of purine and pyrimidine nucleoside analogs and provided a unique in vitro model for studying hCNT2. Analysis of [(3)H]uridine inhibitory activity by test substances in hCNT2 transfectant ARAC/D2 revealed structural requirements for interaction with hCNT2: 1) ribosyl and 2'-deoxyribosyl nucleosides were better inhibitors than 3'-deoxyribosyl, 2',3'-dideoxyribosyl or arabinosyl nucleosides; 2) uridine analogs with halogens at position 5 were better inhibitors than 5-methyluridine or thymidine; 3) 2-chloroadenosine was a better inhibitor than 2-chloro-2'-deoxyadenosine (cladribine); and 4) cytosine-containing nucleosides, 7-deazaadenosine and nucleobases were not inhibitors. Quantification of inhibitory capacity yielded K(i) values of 34-50 microM (5-halogenated uridine analogs, 2'-deoxyuridine), 82 microM (5-fluoro-2'-deoxyuridine), 197-246 microM (5-methyluridine < 5-bromo-2'-deoxyuridine < 5-iodo-2'-deoxyuridine), and 411 microM (5-fluoro-5'-deoxyuridine, capecitabine metabolite). Comparisons of hCNT2-mediated transport rates indicated halogenated uridine analogs were transported more rapidly than halogenated adenosine analogs, even though hCNT2 exhibited preference for physiologic purine nucleosides over uridine. Kinetics of hCNT2-mediated transport of 5-fluorouridine and uridine were similar (K(m) values, 43-46 microM). The impact of hCNT2-mediated transport on chemosensitivity was assessed by comparing antiproliferative activity of nucleoside analogs against hCNT2-containing cells with transport-defective, drug-resistant cells. Chemosensitivity was restored partially for cladribine, completely for 5-fluorouridine and 5-fluoro-2'-deoxyuridine, whereas there was little effect on chemosensitivity for fludarabine, 7-deazaadenosine, or cytarabine. These studies, which demonstrated hCNT2 uptake of halogenated uridine analogs, suggested that hCNT2 is an important determinant of cytotoxicity of this class of compounds in vivo.


Are normative data from the 64-card version of the WCST comparable to the full WCST?
A retrospective study of Wisconsin Card Sorting Test (WCST) protocols was undertaken to determine the equivalence of the full WCST (Heaton, Chelune, Talley, Kay, & Curtiss, 1993) with the single-deck version of the WCST. Census-matched and demographically adjusted standardized scores for the full WCST were compared to the single deck WCST (WCST-64) with 332 clinical protocols using two methods. The comparisons were made using (1) standard scores derived from the new WCST-64 norms (Kongs, Thompson, Iverson, & Heaton, 2000) and from (2) WCST-64 percent scores standardized with the norms intended for the full WCST. The results revealed adequate correlations and accuracy scores for both census-based norms, although WCST-64 scores adjusted for demographic information were not comparable to full WCST scores. Furthermore, the number of cases in which estimated scores performed within an acceptable range of actual full-version WCST scores fell below acceptable ranges. Clinicians are encouraged to use data from the WCST-64 with caution.


Uncovering low-dimensional, miR-based signatures of acute myeloid and lymphoblastic leukemias with a machine-learning-driven network approach.
Complex phenotypic differences among different acute leukemias cannot be fully captured by analyzing the expression levels of one single molecule, such as a miR, at a time, but requires systematic analysis of large sets of miRs. While a popular approach for analysis of such datasets is principal component analysis (PCA), this method is not designed to optimally discriminate different phenotypes. Moreover, PCA and other low-dimensional representation methods yield linear or non-linear combinations of all measured miRs. Global human miR expression was measured in AML, B-ALL, and TALL cell lines and patient RNA samples. By systematically applying support vector machines to all measured miRs taken in dyad and triad groups, we built miR networks using cell line data and validated our findings with primary patient samples. All the coordinately transcribed members of the miR-23a cluster (which includes also miR-24 and miR-27a), known to function as tumor suppressors of acute leukemias, appeared in the AML, B-ALL and T-ALL centric networks. Subsequent qRT-PCR analysis showed that the most connected miR in the B-ALL-centric network, miR-708, is highly and specifically expressed in B-ALLs, suggesting that miR-708 might serve as a biomarker for B-ALL. This approach is systematic, quantitative, scalable, and unbiased. Rather than a single signature, our approach yields a network of signatures reflecting the redundant nature of biological signaling pathways. The network representation allows for visual analysis of all signatures by an expert and for future integration of additional information. Furthermore, each signature involves only small sets of miRs, such as dyads and triads, which are well suited for in depth validation through laboratory experiments. In particular, loss-and gain-of-function assays designed to drive changes in leukemia cell survival, proliferation and differentiation will benefit from the identification of multi-miR signatures that characterize leukemia subtypes and their normal counterpart cells of origin.


Effect of pore-water velocity on chemical nonequilibrium transport of Cd, Zn, and Pb in alluvial gravel columns.
This paper investigates the effects of pore-water velocity on chemical nonequilibrium during transport of Cd, Zn, and Pb through alluvial gravel columns. Three pore-water velocities ranging from 3 to 60 m/day were applied to triplicate columns for each metal. Model results for the symmetric breakthrough curves (BTCs) of tritium (3H2O) data suggest that physical nonequilibrium components were absent in the uniformly packed columns used in these studies. As a result, values of pore-water velocity and dispersion coefficient were estimated from fitting 3H2O BTCs to an equilibrium model. The BTCs of metals display long tailing, indicating presence of chemical nonequilibrium in the system, which was further supported by the decreased metal concentrations during flow interruption. The BTCs of the metals were analysed using a two-site model, and transport parameters were derived using the CXTFIT curve-fitting program. The model results indicate that the partitioning coefficient (beta), forward rate (k1), and backward rate (k2) are positively correlated with pore-water velocity (V); while the retardation factor (R), mass transfer coefficient ((omega), and ratio of k1/k2 are inversely correlated with V. There is no apparent relationship between the fraction of exchange sites at equilibrium (f) and V. The influence of Von k2 is much greater than on R, beta, omega, and k1. A one-order-of-magnitude change in V would cause a two-order-of-magnitude change in k2 while resulting in only a one order-of-magnitude change in R, beta, omega, and k1. The forward rates for the metals are found to be two to three orders-of-magnitude greater than the corresponding backward rate. However, the difference between the two rates reduces with increasing pore-water velocity. Model results also suggest that Cd and Zn behave similarly, while Pb is much more strongly sorbed. At input concentrations of about 4 mg/l and pore-water velocities of 3-60 m/day in the groundwater within alluvial gravel, this study suggests retardation factors of 26-289 for Cd, 24-255 for Zn, and 322-6377 for Pb.


Psychological well-being and workability in child abuse investigators.
Working with victims and offenders of child abuse can impact on the health and well-being of police officers and staff. To identify the effects of tenure, work ability, gender and a personal experience of child abuse on symptoms of anxiety, depression and primary and secondary trauma in child abuse investigators (CAIs). Screening questionnaires were sent to police officers and staff. The officers and staff worked in child protection in seven police forces. The surveillance was undertaken online and the data were encrypted and personal identifiers removed. The four clinical measures were Goldberg Anxiety/Depression Scale, Professional Quality of Life and Impact of Events (extended). Eighty-two per cent of 2798 CAIs returned questionnaires. There was a statistically significant relationship between all four clinical symptoms and workability (P < 0.001), between tenure and primary trauma (P < 0.01) and between anxiety, depression, primary trauma and workability and adverse childhood experience (ACE) scores (P < 0.001). Regression analysis showed that workability, tenure and ACE scores explained between 12 and 23% of the variance. There were gender differences with women having higher levels of symptoms; however, the effect size and clinical significance were negligible for all but the primary trauma scores. Psychological surveillance can provide an important source of evidence for occupational health practitioners working with CAIs in informing them of the factors which could be considered in selecting, training, supporting and retaining officers and staff. Psychological surveillance can also help police management to identify ways to monitor the long-term effectiveness and well-being of CAIs.


RTCB-1 mediates neuroprotection via XBP-1 mRNA splicing in the unfolded protein response pathway.
Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, is characterized by the degeneration of dopamine (DA) neurons and age-dependent formation of protein inclusions that contain the α-synuclein (α-syn) protein. RNA interference (RNAi) screening using Caenorhabditis elegans identified RTCB-1, an uncharacterized gene product, as one of several significant modifiers of α-syn protein misfolding. RTCB-1 is the worm ortholog of the human HSPC117 protein, a component of RNA trafficking granules in mammalian neurons. Here we show that RTCB-1 protects C. elegans DA neurons from age-dependent degeneration induced by human α-syn. Moreover, neuronal-specific RNAi depletion of rtcb-1 enhanced α-syn-induced degeneration. Similar results were obtained when worms were exposed to the DA neurotoxin 6-hydroxydopamine. HSPC117 has been characterized recently as an essential subunit of the human tRNA splicing ligase complex. tRNA ligases have alternative functions in RNA repair and nonconventional mRNA splicing events. For example, in yeast, unconventional splicing of HAC1, a transcription factor that controls the unfolded protein response (UPR), is mediated by a tRNA ligase. In C. elegans, we demonstrate that RTCB-1 is necessary for xbp-1 (worm homolog of HAC1) mRNA splicing. Moreover, using a RNA ligase-dead mutant, we determine that the ligase activity of worm RTCB-1 is required for its neuroprotective role, which, in turn, is mediated through XBP-1 in the UPR pathway. Collectively, these studies highlight the mechanistic intersection of RNA processing and proteostasis in mediating neuroprotection.


Probability of Two-Step Photoexcitation of Electron from Valence Band to Conduction Band through Doping Level in TiO2.
For an Ir-doped TiO2 (Ir:TiO2) photocatalyst, we examined the most dominant electron-transfer path for the visible-light-driven photocatalytic performance. The Ir:TiO2 photocatalyst showed a much higher photocatalytic activity under visible-light irradiation than nondoped TiO2 after grafting with the cocatalyst of Fe3+. For the Ir:TiO2 photocatalyst, the two-step photoexcitation of an electron from the valence band to the conduction band through the Ir doping level occurred upon visible-light irradiation, as observed by electron spin resonance spectroscopy. The two-step photoexcitation through the doping level was found to be a more stable process with a lower recombination rate of hole-electron pairs than the two-step photoexcitation process through an oxygen vacancy. Once electrons are photoexcited to the conduction band by the two-step excitation, the electrons can easily transfer to the surface because the conduction band is a continuous electron path, whereas the electrons photoexcited at only the doping level could not easily transfer to the surface because of the discontinuity of this path. The observed two-step photoexcitation from the valence band to the conduction band through the doping level significantly contributes to the enhancement of the photocatalytic performance.


Adult rats prenatally exposed to ethanol have increased gluconeogenesis and impaired insulin response of hepatic gluconeogenic genes.
Rat offspring exposed to ethanol (EtOH rats) during pregnancy are insulin resistant, but it is unknown whether they have increased gluconeogenesis. To address this issue, we determined blood glucose and liver gluconeogenic genes, proteins, and enzyme activities before and after insulin administration in juvenile and adult EtOH rats and submitted adult EtOH rats to a pyruvate challenge. In juvenile rats, basal glucose; peroxisome proliferator-activated receptor-coactivator-1alpha protein and mRNA; and phosphoenolpyruvate carboxykinase enzyme activity, protein, and mRNA were similar between groups. After insulin injection, these parameters failed to decrease in EtOH rats, but glucose decreased by 30% and gluconeogenic enzymes, proteins, and mRNAs decreased by 50-70% in control rats. In adult offspring, basal peroxisome proliferator-activated receptor-coactivator-1alpha protein and mRNA levels were 40-80% higher in EtOH rats than in controls. Similarly, basal phosphoenolpyruvate carboxykinase activity, protein, and mRNA were approximately 1.8-fold greater in EtOH rats than in controls. These parameters decreased by approximately 50% after insulin injection in control rats, but they remained unchanged in EtOH rats. After insulin injection in the adult rats, glucose decreased by 60% in controls but did not decrease significantly in EtOH rats. A subset of adult EtOH rats had fasting hyperglycemia and an exaggerated glycemic response to pyruvate compared with controls. The data indicate that, after prenatal EtOH exposure, the expression of gluconeogenic genes is exaggerated in adult rat offspring and is insulin resistant in both juvenile and adult rats, explaining increased gluconeogenesis. These alterations persist through adulthood and may contribute to the pathogenesis of Type 2 diabetes after exposure to EtOH in utero.


6,7-Dihydroxy-3-phenylcoumarin inhibits thromboplastin induced disseminated intravascular coagulation.
6,7-Dihydroxy-3-phenylcoumarin (DHPC) was tested to determine whether it had any effect on vitamin K inhibition, by investigating the prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen level and platelet count. The anticoagulant and antithrombotic effects of DHPC were compared with those of warfarin by conducting a 4 h acute trial on thromboplastin-induced disseminated intravascular coagulation (DIC), investigating various haemostatic and antioxidant system parameters and performing a haemogram. Of most significance was that in the 5-d DHPC trial on healthy controls, PT, APTT, fibrinogen, platelet count remained within normal levels. In the 4-h DIC trial, both DHPC (0.025 mg/kg, i.v.) and warfarin (0.25 mg/kg, i.v.) significantly inhibited DIC, by reducing the PT, APTT, and fibrin degradation products and increasing fibrinogen levels and platelet count. In the DIC drug groups, lipid peroxidation significantly increased only in the warfarin group and glutathione significantly increased only in the DHPC group. However leucocyte count was significantly higher in the DHPC than the warfarin group. Further investigation is required for why DHPC is effective on the parameters investigated, at doses one-tenth of those of warfarin.


Assessing the evolutionary history of the fern family Dipteridaceae (Gleicheniales) by incorporating both extant and extinct members in a combined phylogenetic study.
Dipteridaceae is a lineage of ferns that has existed from the early Mesozoic and is known for its extensive fossil record. By integrating information from all described extant and extinct genera into a single phylogenetic study, this paper aims to examine the taxonomy of the group on a whole and explore character evolution within the lineage across time. A morphological matrix of 51 characters was developed for 72 species (43 extinct and 29 extant) based on published information. Morphological characters were combined with nucleotide sequences for four chloroplast genes (rbcL, atpA, atpB, and rps4) for extant taxa, and combined parsimony analyses were conducted to infer evolutionary trends in the group. Dipteridaceae was found to be monophyletic and characterized by highly anastomosing minor veins forming a meshwork of areoles with free-included veinlets. Based on our analyses, we recognize six previously described genera (i.e., Goeppertella, Thaumatopteris, Clathropteris, Digitopteris, Dipteris, and Cheiropleuria) and one new genus (i.e., Sewardalea). Fossils currently described as Dictyophyllum, Kenderlykia, Hausmannia, and Protorhipis are ambiguously placed on the tree and are recognized as possibly unnatural morphogenera. Overall, the evolutionary trend in Dipteridaceae has been toward increasing complexity in the venation pattern and laminal fusion. Only the Hausmannia-type frond with dichotomizing primary veins and relatively fused lamina persisted in the later part of the Mesozoic to the present. Within the crown group, we see evidence of re-radiation of frond forms in Dipteris and Cheiropleuria.


Impact of virtual reality on pain management in transrectal MRI-guided prostate biopsy.
The beneficial effect of virtual reality (VR) on pain management in the context of transrectal MRI-guided prostate biopsy is not well established. However, it remains unclear whether an adjunctive of VR also improves pain management. This study aimed to evaluate the impact of VR as adjunctive in pain management in transrectal MRI-guided prostate biopsy (PB). We retrospectively evaluated the pain intensity incidence in the 153 patients with PB indication (of which 102 were naïve of PB) who were admitted to our hospital since the acquisition of the Healthy Mind virtual reality headset on 19 January 2021. Baseline characteristics of patients who received local anesthesia with 1% lidocaine periprostatic nerve block (PPNB) (Group SOC, N = 78) and patients who received VR associated with PPNB (Group VR, N = 75) were largely similar. One PB with general anesthesia was excluded. The mean pain score at day zero was respectively 3.4 (±2.5) and 2.9 (±2.3) for SOC and VR (p = 0.203). However, the mean pain score at day zero was significantly lower in naïve PB patients with VR [2.7 (±2.0)] than in naïve PB patients with SOC [3.8 (±2.5), p = 0.012] when patients were stratified in PB status. Similar results were found on day 3 for the analysis including naïve-PB patients with SOC vs. with VR [0.4 (±2.5) vs. 0.2 (±2.0); p = 0.023)]. The pain intensity was significantly lower in naïve PB patients with VR than in naïve PB patients with SOC. There were no side effects from VR and tolerability was excellent.


Novel multiprotein complexes identified in the hyperthermophilic archaeon Pyrococcus furiosus by non-denaturing fractionation of the native proteome.
Virtually all cellular processes are carried out by dynamic molecular assemblies or multiprotein complexes, the compositions of which are largely undefined. They cannot be predicted solely from bioinformatics analyses nor are there well defined techniques currently available to unequivocally identify protein complexes (PCs). To address this issue, we attempted to directly determine the identity of PCs from native microbial biomass using Pyrococcus furiosus, a hyperthermophilic archaeon that grows optimally at 100 degrees C, as the model organism. Novel PCs were identified by large scale fractionation of the native proteome using non-denaturing, sequential column chromatography under anaerobic, reducing conditions. A total of 967 distinct P. furiosus proteins were identified by mass spectrometry (nano LC-ESI-MS/MS), representing approximately 80% of the cytoplasmic proteins. Based on the co-fractionation of proteins that are encoded by adjacent genes on the chromosome, 106 potential heteromeric PCs containing 243 proteins were identified, only 20 of which were known or expected. In addition to those of unknown function, novel and uncharacterized PCs were identified that are proposed to be involved in the metabolism of amino acids (10), carbohydrates (four), lipids (two), vitamins and metals (three), and DNA and RNA (nine). A further 30 potential PCs were classified as tentative, and the remaining potential PCs (13) were classified as weakly interacting. Some major advantages of native biomass fractionation for PC identification are that it provides a road map for the (partial) purification of native forms of novel and uncharacterized PCs, and the results can be utilized for the recombinant production of low abundance PCs to provide enough material for detailed structural and biochemical analyses.


Management of biliary stricture in patients with IgG4-related sclerosing cholangitis.
We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.


Ethics of everyday decision making.
Evidence suggests that checklists can prevent episodes of patient harm and they are increasingly being used in patient care to ensure that procedures are being carried out. However, checklists cannot do so alone and in some situations the checklist might indicate that an intervention has been undertaken when it has not. Healthcare providers, particularly nurses, must consider not only the increase in the use of checklists, but also the way in which they present a context for ethical decision making. This article examines the ethical dimensions of using checklists, played out in the context of a scenario, and suggests that failure to take ethics into account when considering checklists might perpetuate rather than prevent unsafe practices or errors. The article is set in a US context, but the issues are relevant to healthcare settings in any part of the world.


Identification of Salmonella abortusovis by PCR amplification of a serovar-specific IS200 element.
Field and collection isolates of Salmonella abortusovis carry one IS200 element in a distinct chromosome location. IS200 is not found in the corresponding region of the chromosome of other Salmonella serovars. Sequencing of the boundaries of the S. abortusovis-specific IS200 insertion permitted the design of primers for the amplification of this IS200 element by PCR. Isolates of S. abortusovis are identified by the amplification of a DNA fragment of about 900 bp or larger. PCR amplification of DNA from salmonellae other than S. abortusovis yields either a fragment of about 200 bp or no product. The high specificity of the assay is confirmed by the absence of cross-reactivity with the following templates: (i) sheep DNA, (ii) DNAs from abortion-causing agents other than S. abortusovis, and (iii) DNAs from microorganisms that do not cause abortion but are common in flocks.


Relationship between semen production and medical comorbidity.
To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility. Cross-sectional study. Fertility clinic. Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011. None. Charlson comorbidity index, medical diagnoses by organ system. At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities. The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man's sperm production, his current condition and health play an important role.


Evaluation of bilaterally implanted adult subjects with the nucleus 24 cochlear implant system.
To evaluate the speech perception benefits of bilateral implantation for subjects who already have one implant. Repeated measures. Thirty adult cochlear implant users who received their second implant from 1 to 7 years with a mean of 3 years after their first device. Ages ranged from 29 to 82 years with a mean of 57 years. Tertiary referral centers across the United Kingdom. Monosyllabic consonant-nucleus-consonant words and City University of New York sentences in quiet with coincident speech and noise and with the noise spatially separated from the speech by +/-90 degrees . At 9 months, results showed the second ear in noise was 13.9 +/- 5.9% worse than the first ear (p < 0.001); a significant binaural advantage of 12.6 +/- 5.4% (p < 0.001) over the first ear alone for speech and noise from the front; a 21 +/- 6% (p < 0.001) binaural advantage over the first ear alone when noise was ipsilateral to the first ear; no binaural advantage when noise was contralateral to the first ear. There is a significant bilateral advantage of adding a second ear for this group. We were unable to predict when the second ear would be the better performing ear, and by implanting both ears, we guarantee implanting the better ear. Sequential implantation with long delays between ears has resulted in poor second ear performance for some subjects and has limited the degree of bilateral benefit that can be obtained by these users. The dual microphone does not provide equivalent benefit to bilateral implants.


The effect of ultraviolet-C technology on viral infection incidence in a pediatric long-term care facility.
Ultraviolet-C (UV-C) technology implementation was associated with a 44% reduction in viral infection incidence among pediatric patients in a long-term care facility (incidence rate ratio, 0.56; 95% confidence interval, 0.37-0.84; P=.003). UV-C was included as an adjunct to standard cleaning protocols over a 12-month period; no other new interventions were introduced during this time. The results suggest that UV-C technology is a potentially important component of eliminating the environment as a source of viral infections.


Catecholamine-containing cells in the nerve plexus of the guinea pig gallbladder.
A population of catecholamine-containing cells, broadly belonging to the class of small intensely fluorescent (SIF) cells, was observed in the ganglionated plexus and around blood vessels of the guinea pig gallbladder. Their morphological features were studied by fluorescence and electron microscopy. Some cells were closely associated with ganglion neurons within the ganglionated plexus. Others were clustered into small groups located along blood vessels. Counts carried out on the whole gallbladder showed that these cells varied greatly in number between individuals and that they were most numerous shortly after birth (on average 230 cells). In the adult, their average number was about 30.


Methylprednisolone for acute spinal cord injury: an increasingly philosophical debate.
Following publication of NASCIS II, methylprednisolone sodium succinate (MPSS) was hailed as a breakthrough for patients with acute spinal cord injury (SCI). MPSS use for SCI has since become very controversial and it is our opinion that additional evidence is unlikely to break the stalemate amongst clinicians. Patient opinion has the potential to break this stalemate and we review our recent findings which reported that spinal cord injured patients informed of the risks and benefits of MPSS reported a preference for MPSS administration. We discuss the implications of the current MPSS debate on translational research and seek to address some misconceptions which have evolved. As science has failed to resolve the MPSS debate we argue that the debate is an increasingly philosophical one. We question whether SCI might be viewed as a serious condition like cancer where serious side effects of therapeutics are tolerated even when benefits may be small. We also draw attention to the similarity between the side effects of MPSS and isotretinoin which is prescribed for the cosmetic disorder acne vulgaris. Ultimately we question how patient autonomy should be weighed in the context of current SCI guidelines and MPSS's status as a historical standard of care.


Development of a multiregional United States Spanish version of the international prostate symptom score and the benign prostatic hyperplasia impact index.
The International Prostate Symptom Score (I-PSS) and Benign Prostatic Hyperplasia Impact Index (BII) have gained widespread use in clinical practice and clinical trials. Although Spanish translations of the I-PSS are available, to our knowledge none was developed for the Spanish speaking population in the United States using a methodology to ensure appropriateness for the diverse United States Spanish speaking population. An existing translation intended for another Spanish speaking country, such as Mexico, or a translation developed without input from each language group may not be understood by those who immigrated from other Latin American regions. Hence, the development of a Spanish translation for the United States should involve input from translators from each region of Latin America. We reviewed and modified an existing United States Spanish translation of I-PSS using a multiregional reconciliation panel comprised of representatives from each of the major Spanish language groups in the United States. For BII full translation methodology was used to develop a translation for the United States, including 2 forward translations using translators from more than 1 region, a multiregional reconciliation panel meeting, a back translation evaluation, cognitive debriefing interviews with representatives from each language group, developer review, a final evaluation for consistency and proofreading. The revised I-PSS better reflects common Spanish wording in the United States, while the BII translation was confirmed to be comprehended by Spanish speakers in the United States originating from multiple regions of Latin America. United States Spanish translations of patient reported outcome measures should consider the diversity of the growing Spanish speaking population in the United States to ensure comprehension across the broad population originating from the multiple regions of Latin America.


[Level of urinary phenol and hippuric acid in control subjects and subjects exposed to benzene and toluene].
Two high-performance liquid chromatographic methods are described, one for assay of phenol in urine, the other for assay of hippuric acid. Steam distillation was used to hydrolyse the sample and separate the phenol from the matrix. A dilution was the only pretreatment of urine for assay of hippuric acid. The upper reference limits obtained from 42 non-exposed subjects were 7.09 mmol/mol creatinine for urinary phenol and 1,174 mmol/mol creatinine for hippuric acid. The mean concentration of urinary phenol was higher in 190 exposed workers (7.21 +/- 5.05 mmol/mol creatinine; mean +/- SD) than in control subjects (3.97 +/- 1.56 mmol/mol creatinine).


Clinical evaluation of HIFU combined with GnRH-a and LNG-IUS for adenomyosis patients who failed to respond to drug therapies: two-year follow-up results.
To investigate the clinical effect of high intensity focused ultrasound (HIFU) ablation combined with gonadotropin-releasing hormone agonist (GnRH-a) and levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of adenomyosis patients who failed to respond to drug therapies. A total of 47 patients with adenomyosis who had failed to respond to drug therapies and had no fertility desires were treated with HIFU combined with GnRH-a and LNG-IUS. The score of dysmenorrhea and menstrual volume were measured at pre and 6-, 12-, 18-, 24-month post-HIFU. All patients completed HIFU ablation without major postoperative complications. Compared with the symptom scores before the HIFU treatment, the score of dysmenorrhea and menstrual volume decreased significantly at 6, 12, 18 and 24 months after HIFU treatment (p < 0.05), but no significant difference was observed between 6, 12, 18 and 24 months after HIFU (p > 0.05). The clinical success rate was 100%, 100%, 95.7% and 93.6% respectively at 6, 12, 18 and 24 months after the combined treatment. The combined therapeutic regimen of HIFU, GnRH-a and LNS-IUS is safe and effective, which can be an alternative treatment option for patients with adenomyosis who failed to respond to drug therapies to avoid adenomyomectomy or hysterectomy.


[Arterialization of the capillary network in the left ventricular subendocardium in young rats subjected to exercise training].
The increase in cardiac activity requires an increase in oxygen supply to the ventricular tissues. Two adaptational changes in the capillary network seem to increase the oxygen supply; one is the increase in capillary density and the other may be the increase in arteriolar capillaries. To test this hypothesis, double staining method, which was validated by microsphere injection, was used for differentiation of arteriolar and venular capillaries in exercise-trained rats in the present study. Male Wistar rats after weaning (3 weeks old) were subjected to treadmill running 1 hour/day in the evening, 6 days/week. The running speed was increased from 10 m/min without gradient to 25 m/min with a 7% gradient for 6 weeks. The total capillary density and capillary to myocyte ratio increased significantly. Capillary domain area decreased, suggesting neoformation of capillaries. In support of the capillary increase two stimulators for angiogenesis, vascular endothelial growth factor and basic fibroblast growth factor were immunohistochemically stained in the ventricular tissues from exercise-trained rats. Capillary of arteriolar type increased with a decrease in the venular capillary. The arteriolar portion of capillaries became significantly longer and the venular portion shorter than in resting control rats. Branching of capillaries increased both in the arteriolar and venular portions. These results suggest that the arterialization of capillary network proceeded with the increase in the capillary density to facilitate the oxygen transport to cardiac tissues.


Parental Educational Attainment and Black-White Adolescents' Achievement Gap: Blacks' Diminished Returns.
Recent research has documented Minorities' Diminished Returns (MDRs), defined as weaker protective effects of parental educational attainment and other socioeconomic status (SES) indicators for racial and ethnic minority groups. To explore racial differences in the associations between parental educational attainment and youth educational outcomes among American high schoolers. This cross-sectional study used baseline data from the Education Longitudinal Study (ELS-2002), a nationally representative survey of 10th grade American youth. This study analyzed 10702 youth who were composed of 2020 (18.9%) non-Hispanic Black and 8682 (81.1%) non-Hispanic White youth. The dependent variables were youth math and reading grades. The independent variable was parental educational attainment. Gender, parental marital status, and school characteristics (% students receiving free lunch, academic risk factors, urban school, public school) were the covariates. Race was the moderating variable. Linear regression was used for data analysis. Overall, higher parental educational attainment was associated with higher math and reading test scores. We found a significant interaction between race (Non-Hispanic Black) and parental education attainment on math and reading test scores, suggesting that the boosting effects of high parental educational attainment on youth educational outcomes might be systemically smaller for Non-Hispanic Black than for Non-Hispanic White youth. While high parental educational attainment promotes educational outcomes for youth, this association is weaker for Non-Hispanic Black youth than non-Hispanic White youth. The diminished returns of parental education are beyond what can be explained by school characteristics that differ between Non-Hispanic Black and non-Hispanic White students. Diminishing returns of parental educational attainment (MDRs) may be an unrecognized source of racial youth disparities. Equalizing SES would not be enough for equalizing outcomes. There is a need for public and economic policies that reduce diminished returns of SES for Black families.


[Classification of malignant tumors of suprarenal glands].
The extent of diagnostic possibilities of medical technique, permitting to reveal the majority of suprarenal tumors, and the most modem information technologies as well demands creation of the suprarenal tumors applicable classification, well-adopted for physician in practice and also for scientist dealing with analysis of the investigation results in these pathology. Taking into account hormonal activity of majority of tumors, influencing the patients management tactic, the authors propose the insight on suprarenal tumor diagnosis of their own.


A Novel SEMA3G Mutation in Two Siblings Affected by Syndromic GnRH Deficiency.
Gonadotropin-releasing hormone (GnRH) deficiency causes hypogonadotropic hypogonadism (HH), a rare genetic disorder that impairs sexual reproduction. HH can be due to defective GnRH-secreting neuron development or function and may be associated with other clinical signs in overlapping genetic syndromes. With most of the cases being idiopathic, genetics underlying HH is still largely unknown. To assess the contribution of mutated Semaphorin 3G (SEMA3G) in the onset of a syndromic form of HH, characterized by intellectual disability and facial dysmorphic features. By combining homozygosity mapping with exome sequencing, we identified a novel variant in the SEMA3G gene. We then applied mouse as a model organism to examine SEMA3Gexpression and its functional requirement in vivo. Further, we applied homology modelling in silico and cell culture assays in vitro to validate the pathogenicity of the identified gene variant. We found that (i) SEMA3G is expressed along the migratory route of GnRH neurons and in the developing pituitary, (ii) SEMA3G affects GnRH neuron development, but is redundant in the adult hypothalamic-pituitary-gonadal axis, and (iii) mutated SEMA3G alters binding properties in silico and in vitro to its PlexinA receptors and attenuates its effect on the migration of immortalized GnRH neurons. In silico, in vitro, and in vivo models revealed that SEMA3G regulates GnRH neuron migration and that its mutation affecting receptor selectivity may be responsible for the HH-related defects.


Quantifying autophagy using novel LC3B and p62 TR-FRET assays.
Autophagy is a cellular mechanism that can generate energy for cells or clear misfolded or aggregated proteins, and upregulating this process has been proposed as a therapeutic approach for neurodegenerative diseases. Here we describe a novel set of LC3B-II and p62 time-resolved fluorescence resonance energy transfer (TR-FRET) assays that can detect changes in autophagy in the absence of exogenous labels. Lipidated LC3 is a marker of autophagosomes, while p62 is a substrate of autophagy. These assays can be employed in high-throughput screens to identify novel autophagy upregulators, and can measure autophagy changes in cultured cells or tissues after genetic or pharmacological interventions. We also demonstrate that different cells exhibit varying autophagic responses to pharmacological interventions. Overall, it is clear that a battery of readouts is required to make conclusions about changes in autophagy.


Multichannel gas-uptake/evolution reactor for monitoring liquid-phase chemical reactions.
The design of a headspace pressure-monitoring reactor for measuring the uptake/evolution of gas in gas-liquid chemical transformations is described. The reactor features a parallel setup with ten-reactor cells, each featuring a low working volume of 0.2-2 ml, a pressure capacity from 0 to 150 PSIa, and a high sensitivity pressure transducer. The reactor cells are composed of commercially available disposable thick-walled glassware and compact monolithic weld assemblies. The software interface controls the reactor temperature while monitoring pressure in each of the parallel reactor cells. Reactions are easy to set up and yield high-density gas uptake/evolution data. This instrument is especially well suited to acquire quantitative time-course data for reactions with small quantities of gas consumed or produced.


A Prospective Biopsychosocial Repeated Measures Study of Stress and Dropout from Substance Addiction Treatment.
This prospective, repeated-measures observational study tested biopsychosocial variables as risk factors for dropping out of inpatient substance addiction treatment. Substance use disorder (SUD) is viewed as a chronic relapsing disease caused by an interaction between biological, psychological, and social factors. However, there is a lack of prospective studies that combine biopsychosocial variables when assessing dropout. The aims of this study were to investigate whether there was 1) An association between biopsychosocial factors and dropping out of inpatient substance addiction treatment, 2) An interaction with SUD diagnosis and cortisol, and 3) Different dropout rates between short-term and long-term institutions. Patients (n = 173) were recruited from two inpatient treatment centers in Norway between 2018 and 2021. The following biopsychosocial variables were measured at four timepoints: ward atmosphere (Ward Atmosphere Scale, WAS), psychological distress (Hopkins Symptom Checklist 10, HSCL-10), motivation (M-scale of the Circumstances, Motivation, Readiness, and Suitability questionnaire), and concentration of salivary cortisol (CORT- nmol/L). Cortisol levels were measured for two consecutive days at each timepoint and calculated by two cortisol indices, daytime cortisol slope (DCS) and area under the curve with respect to the ground (AUCG). A multivariate logistic regression analysis was performed to find an association between dropout rates and the biopsychosocial variables. The results suggest a lower dropout odds for patients with high motivation (OR = 0.76, p = 0.022) and patients admitted to short-term treatment (OR = 0.06, p = 0.005). An interaction with stimulant SUD and DCS (OR = 13.74, p = 0.024) also revealed higher dropout odds. No statistical significance was found for psychological distress, WAS, and cortisol AUCG. The results support monitoring motivation during treatment and further investigating biopsychosocial variables when assessing dropout risk together with SUD diagnosis.


Association and interaction between model for end-stage liver disease score and minimally invasive treatment with regard to mortality of patients with hepatitis B virus-associated hepatocellular carcinoma and portal vein tumor thrombi.
The development of minimally invasive treatment over the last two decades has had a great impact on hepatitis B virus (HBV)-associated primary liver cancer. The model for end-stage liver disease (MELD) score is the optimal evaluated parameter for mortality in patients with end-stage liver disease. However, the association between MELD score and minimally invasive treatment with regard to the mortality of patients with HBV-associated hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT) remains unclear. In the present study, a total of 173 patients who had been diagnosed with HBV-associated HCC and PVTT in the Beijing Ditan Hospital (Beijing, China), between January 2012 and January 2015, were screened. Follow-up was performed to observe the survival time and collect information on the demographic characteristics and associated clinical indicators present in the cohort. The patient's age, sex, laboratory parameters and the use of minimally invasive treatment were analyzed with SPSS 20.0 software. Independent risk factors for mortality were screened by Cox regression analysis. Logistic regression indicated that there was an interaction between the MELD score and minimally invasive treatment. In addition, a MELD score ≤17.85 was associated with a lower mortality rate subsequent to minimally invasive treatment.


Trait Rumination Influences Neural Correlates of the Anticipation but Not the Consumption Phase of Reward Processing.
Cumulative evidence suggests that trait rumination can be defined as an abstract information processing mode, which leads people to constantly anticipate the likely impact of present events on future events and experiences. A previous study with remitted depressed patients suggested that enhanced rumination tendencies distort brain mechanisms of anticipatory processes associated with reward and loss cues. In the present study, we explored the impact of trait rumination on neural activity during reward and loss anticipation among never-depressed people. We analyzed the data of 37 healthy controls, who performed the monetary incentive delay (MID) task which was designed for the simultaneous measurement of the anticipation (motivational) and consumption (hedonic) phase of reward processing, during functional magnetic resonance imaging (fMRI). Our results show that rumination-after controlling for age, gender, and current mood-significantly influenced neural responses to reward (win) cues compared to loss cues. Blood-oxygenation-level-dependent (BOLD) activity in the left inferior frontal gyrus (IFG) triangularis, left anterior insula, and left rolandic operculum was positively related to Ruminative Response Scale (RRS) scores. We did not detect any significant rumination-related activations associated with win-neutral or loss-neutral cues and with reward or loss consumption. Our results highlight the influence of trait rumination on reward anticipation in a non-depressed sample. They also suggest that for never-depressed ruminators rewarding cues are more salient than loss cues. BOLD response during reward consumption did not relate to rumination, suggesting that rumination mainly relates to processing of the motivational (wanting) aspect of reward rather than the hedonic (liking) aspect, at least in the absence of pathological mood.


Ethnic disparities in type 2 diabetes: pathophysiology and implications for prevention and management.
Based on 2000 census data, ethnic minorities constitute approximately 25% of the overall population of the United States, and the population of minority groups has been increasing at a faster rate than the general U.S. population. Compared with caucasians, persons from minority ethnic groups suffer disproportionately from type 2 diabetes and its long-term complications. Acute complications of diabetes occur with varying frequencies in the different demographic groups, but there are indications that the rate of hospitalization for diabetic ketoacidosis and nonketotic coma may be higher among certain minority populations. Genetic and lifestyle factors likely account for the increased prevalence of type 2 diabetes among ethnic minorities. However, the increase in morbidity and mortality from diabetes may be the result, in part, of socioeconomic factors. Pathophysiologically, several studies have documented a higher prevalence of insulin resistance in minority groups, even after correction for obesity and lifestyle factors. These findings underscore the need for a more aggressive approach to diabetes management in high-risk populations. Behavioral and pharmacologic interventions that reduce insulin resistance have profound beneficial effects in African-American patients and subjects with diabetes from other ethnic groups. Indeed, much of the ethnic difference in morbidity from diabetic complications disappears when caucasians and non-caucasians are treated to identical degrees of glycemic control.


Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in patients with elevated triglycerides (200-499 mg/dL) on statin therapy: Rationale and design of the EVAPORATE study.
Despite reducing progression and promoting regression of coronary atherosclerosis, statin therapy does not fully address residual cardiovascular (CV) risk. High-purity eicosapentaenoic acid (EPA) added to a statin has been shown to reduce CV events and induce regression of coronary atherosclerosis in imaging studies; however, data are from Japanese populations without high triglyceride (TG) levels and baseline EPA serum levels greater than those in North American populations. Icosapent ethyl is a high-purity prescription EPA ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults with TG levels >499 mg/dL. The objective of the randomized, double-blind, placebo-controlled EVAPORATE study is to evaluate the effects of icosapent ethyl 4 g/d on atherosclerotic plaque in a North American population of statin-treated patients with coronary atherosclerosis, TG levels of 200 to 499 mg/dL, and low-density lipoprotein cholesterol levels of 40 to 115 mg/dL. The primary endpoint is change in low-attenuation plaque volume measured by multidetector computed tomography angiography. Secondary endpoints include incident plaque rates; quantitative changes in different plaque types and morphology; changes in markers of inflammation, lipids, and lipoproteins; and the relationship between these changes and plaque burden and/or plaque vulnerability. Approximately 80 patients will be followed for 9 to 18 months. The clinical implications of icosapent ethyl 4 g/d treatment added to statin therapy on CV endpoints are being evaluated in the large CV outcomes study REDUCE-IT. EVAPORATE will provide important imaging-derived data that may add relevance to the clinically derived outcomes from REDUCE-IT.


High Endogenous Testosterone Levels Are Associated With Diminished Neural Emotional Control in Aggressive Police Recruits.
Although police officers are carefully selected for their high emotion-regulation abilities, excessive aggression in police officers has been reported, particularly in socially challenging situations known to elicit high state testosterone levels. Adequate regulation of emotional actions depends on the prefrontal cortex's control over the amygdala. We investigated the effects of trait aggression and endogenous testosterone on this emotional-control neurocircuitry in 275 healthy, high-functioning police recruits using a functional MRI social-emotional task eliciting impulsive and controlled approach-and-avoidance actions. Higher levels of aggression were counteracted by increased anterior prefrontal cortex (aPFC) control over the amygdala when control over automatic emotional actions was required. Crucially, testosterone had a detrimental effect on this aggression-dependent aPFC recruitment: Police recruits with relatively high trait aggression and high state testosterone showed reduced aPFC control over the amygdala during emotion regulation. This provides a mechanistic explanation for inadequate behavioral control during socially challenging situations in otherwise well-functioning individuals.


Characterization of water sorption, solubility, and roughness of silorane- and methacrylate-based composite resins.
The objective of this study was to evaluate the surface roughness (SR), water sorption (WS), and solubility (SO) of four composite resins after finishing/polishing and after one year of water storage. Two low-shrinkage composites (Filtek Silorane [3M ESPE] and Aelite LS [Bisco Inc]) and two composites of conventional formulations (Heliomolar and Tetric N-Ceram [Ivoclar Vivadent]) were tested. Their respective finishing and polishing systems (Sof-Lex Discs, 3M ESPE; Finishing Discs Kit, Bisco Inc; and Astropol F, P, HP, Ivoclar Vivadent) were used according to the manufacturers' instructions. Ten disc-shaped specimens of each composite resin were made for each evaluation. Polished surfaces were analyzed using a profilometer after 24 hours and one year. For the WS and SO, the discs were stored in desiccators until constant mass was achieved. Specimens were then stored in water for seven days or one year, at which time the mass of each specimen was measured. The specimens were dried again and dried specimen mass determined. The WS and SO were calculated from these measurements. Data were analyzed by two-way analysis of variance and Tukey post hoc test (α=0.05). Filtek Silorane showed the lowest SR, WS, and SO means. Water storage for one year increased the WS means for all composite resins tested. The silorane-based composite resin results were better than those obtained for methacrylate-based resins. One-year water storage did not change the SR and SO properties in any of the composite resins.


Evaluation of pathological diagnosis using ultrasonography-guided lymph node core-needle biopsy.
Image-guided core-needle biopsy as a minimally invasive procedure has partially replaced excisional biopsy of the lymph node. However, it is still a great challenge to pathologists. The aim of this study was to survey and evaluate the accuracy of pathological diagnosis using the ultrasonography (US)-guided core-needle biopsy (CNB) of the lymph node. Lymph node CNBs of 1119 consecutive patients from the Chinese People's Liberation Army (PLA) General Hospital were reviewed retrospectively. Biopsies were performed following outpatient procedures with direct US guiding by using 18-gauge cutting needle. The tissues of CNB were prepared according to the routine paraffin embedding and hematoxylin-eosin staining. Ancillary studies, including acid-fast staining and immunohistochemical staining, were performed when necessary. The age range was 1 year old to 85 years old. Locations of the lymph node were as follows: cervical area (n = 482), clavicular region (n = 227), retroperitoneum (n = 150), axilla (n = 93), groin (n = 79), abdomen/mesentery (n = 44), submaxillary region (n = 33), postauricular region (n = 4), iliac fosa (n = 3), parotid (n = 2), hepatic hilar region (n = 1), and elbow (n = 1). The histological diagnoses were conclusive in 815 cases (73%) and inconclusive in 304 cases (27%). The conclusive cases mainly included metastatic carcinoma (n = 449), tuberculosis (n = 111), lymphoma/leukemia (n = 124), reactive hyperplasia (n = 87), and other rare diseases (n = 44). The reasons for inconclusive cases were insufficient material for diagnosis, noncompliance of outpatients, or crushing artifacts of tissues caused by operation. US-guided CNB can obtain lymphoid tissues from nearly all parts of the body for diagnostic purposes. Conclusive pathological diagnosis can be made in most of cases when adequate material was provided. Besides metastatic carcinoma, lymphomas with special immunophenotype can be accurately diagnosed and subclassified by US-guided CNB.


Super-reaction: The collective enhancement of a reaction rate by molecular polaritons in the presence of energy fluctuations.
Recent experiments have demonstrated that molecular polaritons, hybrid states of light and matter formed by the strong coupling between molecular electronic or vibrational excitations and an optical cavity, can substantially modify the physical and chemical properties of molecular systems. Here, we show that by exploiting the collective character of molecular polaritons in conjunction with the effect of polaron decoupling, i.e., the suppression of environmental influence on the polariton, a super-reaction can be realized, involving a collective enhancement of charge or excitation-energy transfer reaction rate in a system of donors all coupled to a common acceptor. This effect is analogous to the phenomenon of super-radiation. Since the polariton is a superposition state of excitations of all the molecules coupled to the cavity, it is vulnerable to the effect of decoherence caused by energy fluctuations in molecular systems. Consequently, in the absence of a strong light-matter interaction, the reaction rate decreases significantly as the number of molecules increases, even if the system starts from the polariton state. By turning on the light-matter interaction, the dynamic behavior of the system changes dramatically, and the reaction rate increases with the number of molecules, as expected for a super-reaction. The underlying mechanism is shown to be the protection of quantum coherence between different donors as the light-matter interaction becomes stronger.