Hearing loss among military personnel in relation to occupational and leisure noise exposure and usage of personal protective equipment.
Hearing loss (HL) is a major health concern among military personnel due to noise from shooting, blasts, military vehicles, and noisy training environments. Nevertheless, one's exposure can be partially reduced by using personal protective equipment (PPE). The aim of this study is to estimate the prevalence of HL among military personnel, to analyse associations between HL and self-reported occupational and leisure noise exposure, and use of PPEs. A cross-sectional study was conducted among 150 military personnel during their routine medical examinations. First, all participants filled in a questionnaire about their exposure to noise and later the respondents went through an audiometric test. The diagnostic criteria for slight, moderate, and severe HL was HL of 25-40, 41-60, and >60 dB at 4 and 6 kHz, respectively. The associations between noise exposure and HL were studied with multinomial logistic regression analysis. The prevalence of slight to severe HL in high frequencies (4 and 6 kHz) among study participants was 62.7%. Nevertheless, the majority of it was slight, as the prevalence of severe HL was 9.3%. The prevalence of any kind of HL was highest in the Navy and the prevalence of severe HL was highest in the Central Command Units. The relative risk ratios (RRRs) for HL were higher among those who had been working for a long time in a noisy environment, working with noise-producing equipment, driving in a PASI or a Bandvagn or had been shooting with blanks at least once per week. It also appeared that military personnel who had HL, reported tinnitus more often. Respondents' previous health problems, music-listening habits, and amount of exposure to loud noise in non-military environments were not independently associated with HL, but in several cases it increased the RRRs together with military exposure. We also found significantly more frequent HL among those never using PPEs. HL loss was more prevalent among personnel who are more often exposed to military noise, especially among those who never use PPEs. The effect was enhanced by leisure time noise, but it was not independently associated to HL.


Temporal expression of the Candida albicans genes CHK1 and CSSK1, adherence, and morphogenesis in a model of reconstituted human esophageal epithelial candidiasis.
We previously demonstrated that genes encoding a putative two-component histidine kinase (CHK1) or a response regulator (CSSK1) are each required for virulence in a murine model of hematogenously disseminated candidiasis and that strains with each gene deleted are also defective in morphogenesis under certain growth conditions. In the present study, the role of these two genes in the adherence to and colonization of reconstituted human esophageal tissue (RHE) is described. We compared strains of Candida albicans with deletions of chk1 (strain CHK21) and cssk1 (strain CSSK21) to wild-type cells (CAF2), as well as strains with CHK1 and CSSK1 reconstituted (strains CHK23 and CSSK23, respectively). Adherence and colonization of RHE were evaluated in periodic acid-Schiff-stained sections, as well as by SEM. We observed that both deletion-containing strains colonized the RHE to a lesser extent than did CAF2 and that the percent germination by both strains was reduced in comparison to that of control strains at 1 h postinfection. Expression of CHK1 or CSSK1 was quantitated by reverse transcription (RT)-PCR from RHE tissues infected with wild-type C. albicans yeast cells. Expression of both CHK1 and CSSK1 increased over the 48-h period following infection of the tissue, although expression of CHK1 was greater than that of CSSK1. By RT-PCR, we have also shown that expression of CHK1 and CSSK1 in the strains with cssk1 and chk1 deleted, respectively, was similar to that of CAF2, indicating that CHK1 and CSSK1 do not regulate each other but probably encode signal proteins of different pathways. Our observations indicate that CHK1 and CSSK1 are each partially required for colonization and conversion to filamentous growth on RHE tissue.


Intergenic complementation truncation mutants of cyclin-dependent kinase.
The Saccharomyces cerevisiae genes PHO80 and PHO85 encode, respectively, a cyclin and cyclin-dependent kinase, which negatively regulate PHO5 gene transcription by phosphorylating the transcription activator Pho4p. Cyclin-dependent kinases (CDKs) are highly conserved proteins, both within and between species. It was previously demonstrated, using reporter genes activated in yeast by Pho4p, that hybrid proteins in which over two-thirds of Pho85p were replaced with the homologous region from human Cdk2 retained the function of native Pho85p with respect to promoter repression. In the present study, various truncated forms of the hybrid human-yeast CDKs were tested for function. Surprisingly, truncations in which significant portions of the C-terminal region of the 291-residue hybrid CDK were deleted retained activity. Genes encoding human Cdk2 proteins which terminated after amino acids 151, 140, 130, 120 and 90 each complement a chromosomal pho85 gene disruption in which the HIS3 gene is inserted at codon 49. Truncated Cdk2 proteins containing less than 60 amino acids failed to complement the pho85::HIS3 gene disruption. Although the functional C-terminal truncations disrupt the ATP-binding and active sites of Cdk2, reporter gene repression mediated by these truncated proteins is apparently due to phosphorylation of Pho4p, since a gene in which the essential lysine codon at position 33 was converted to an arginine codon does not complement the chromosomal gene disruption. The human Cdk2 truncations were demonstrated to function through intergenic complementation. The intact Cdk2-Pho85 hybrid CDK complemented the pho85 mutation in yeast strains in which the entire PHO85 coding region was deleted from chromosome XVI. The C-terminal Cdk2 truncations, however, were non-functional in these strains and thus dependent for activity on the pho85 coding region which remained in the mutant pho85::HIS3 chromosomal locus. These genetic results are consistent with a model involving protein fragment complementation in which the active site of the CDK is bisected.


Short-term results of catheter-directed intrathrombus thrombolysis versus anticoagulation in acute proximal deep vein thrombosis.
Deep vein thrombosis (DVT) is a potentially progressive disease with complex clinical sequelae. The clinical practice guidelines of the American College of Chest Physicians (ACCP) recommend various treatments for all patients with objectively proven DVT. This study retrospectively compares enoxaparin with CDT on treatment efficacy and safety and the evolution of acute proximal DVT in the lower limbs. This study comprised 53 patients with acute proximal DVT, who received either CDT followed by intravenous unfractionated heparin (UFH) or adjusted subcutaneous low-molecular-weight heparin (LMWH) (enoxaparin) for 7-14 days. Warfarin was administered to all patients for at least 6 months. The study endpoints included the evolution of DVT and treatment efficacy and safety, which were assessed with frequent duplex ultrasounds, plethysmography, and venography. The mean duration of the follow-up was 15.2 months. In the CDT group, patency of the iliofemoral vein segment was observed in 42.3% of the patients after 1 week (p < 0.001) and in 69.2% after 6 months. In the control group, patency was present in 15.4% of the patients after 3 months and in 38.5% after 6 months (p = 0.05). Femoral venous obstruction was found in 30.8% of CDT patients and in 61.5% of the control group (p = 0.05). Furthermore, femoral venous insufficiency was present in 46.2% of the CDT group and 53.9% of the control group after 6 months (p = 0.587). After 12 months, post-thrombotic syndrome (PTS) was found in 19.2% of the CDT patients compared to 50% of the LMWH group (p = 0.04). Duplex ultrasound analysis of thrombus progression is useful for assessing the treatment of a patient with acute proximal DVT. In this study, patients undergoing CDT experienced higher thrombus resolution and early recanalization of their veins, which may preserve venous function and further prevent development of post-thrombotic syndrome.


GENE SILENCING. Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells.
Forward genetic screens in Drosophila melanogaster for modifiers of position-effect variegation have revealed the basis of much of our understanding of heterochromatin. We took an analogous approach to identify genes required for epigenetic repression in human cells. A nonlethal forward genetic screen in near-haploid KBM7 cells identified the HUSH (human silencing hub) complex, comprising three poorly characterized proteins, TASOR, MPP8, and periphilin; this complex is absent from Drosophila but is conserved from fish to humans. Loss of HUSH components resulted in decreased H3K9me3 both at endogenous genomic loci and at retroviruses integrated into heterochromatin. Our results suggest that the HUSH complex is recruited to genomic loci rich in H3K9me3, where subsequent recruitment of the methyltransferase SETDB1 is required for further H3K9me3 deposition to maintain transcriptional silencing.


Cassette recruitment in the chromosomal Integron of Vibrio cholerae.
Integrons confer a rapid adaptation capability to bacteria. Integron integrases are able to capture and shuffle novel functions embedded in cassettes. Here, we investigated cassette recruitment in the Vibrio cholerae chromosomal integron during horizontal transfer. We demonstrated that the endogenous integrase expression is sufficiently triggered, after SOS response induction mediated by the entry of cassettes during conjugation and natural transformation, to mediate significant cassette insertions. These insertions preferentially occur at the attIA site, despite the presence of about 180 attC sites in the integron array. Thanks to the presence of a promoter in the attIA site vicinity, all these newly inserted cassettes are expressed and prone to selection. We also showed that the RecA protein is critical for cassette recruitment in the V. cholerae chromosomal integron but not in mobile integrons. Moreover, unlike the mobile integron integrases, that of V. cholerae is not active in other bacteria. Mobile integrons might have evolved from the chromosomal ones by overcoming host factors, explaining their large dissemination in bacteria and their role in antibioresistance expansion.


Variable biological activity of thyroid-stimulating hormone.
Thyroid-stimulating hormone (TSH), like the other pituitary glycoprotein hormones, is produced and secreted as a mixture of isoforms, the majority of which represent differences in oligosaccharide structure and possess different bioactivity. When samples are quantified simultaneously by immunometric assay and bioassay, the ratio between bioactivity (B) and immunoreactivity (I) may serve as an index of the overall potency of TSH. Variations of the TSH B/I ratio have been documented in both physiological and pathological conditions associated with alteration of the two most important mechanisms controlling TSH synthesis and secretion, i.e. TRH release and the thyroid hormone feedback system. Major examples of this assumption are the low TSH bioactivity found in samples from patients lacking TRH and thus bearing a hypothalamic hypothyroidism, and the enhanced bioactivity that is invariably found in TSH from patients with thyroid hormone resistance. Moreover, variations of TSH bioactivity have been recorded in normal subjects during the nocturnal TSH surge, in normal fetuses during the last trimester of pregnancy, in patients with primary hypothyroidism and in patients with TSH-secreting pituitary adenoma and non-thyroidal illness. In conclusion, the secretion of TSH molecules with altered bioactivity plays an important pathogenetic role in various thyroid disorders, while in some particular physiological conditions the bioactivity of TSH may vary in order to adjust thyroid hormone secretion to temporary needs.


Ethylene glycol poisoning following ingestion of brake fluid.
A 32-year old male, with a history of depression and previous suicide attempts, was brought to hospital comatose after ingestion of brake fluid. He developed severe metabolic acidosis with an increased anion gap, hypotension, seizures and mild renal impairment. He required intensive care treatment for ventilatory and inotropic support. The clinical features, diagnosis and treatment of this unusual poison are discussed.


Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAAC) phase three.
Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.


Racial and ethnic differences in diffuse large B-cell lymphoma survival among an underserved, urban population.
Racial/ethnic differences in diffuse large B-cell lymphoma (DLBCL) survival have focused on non-Hispanic Whites (NHW) and non-Hispanic Blacks (NHB), often excluding Hispanics/Latinos. To further assess these racial/ethnic survival differences, we identified incident DLBCL cases diagnosed between 2005 and 2016 (n = 404; NHW = 136, NHB = 106, Hispanic/Latino = 162) at Montefiore Medical Center (Bronx, NY). All-cause mortality survival curves were assessed by the Kaplan-Meier method and log-rank test. Cox proportional hazards regression assessed the association between demographic/clinical factors and all-cause mortality. Hispanic/Latino patients experienced 52% lower risk of mortality compared to NHWs (HR = 0.48, 95%CI = 0.28-0.83), after adjusting for clinical prognostic factors. This reduced risk experienced by Hispanics/Latinos was similarly observed by age at diagnosis (≤60 years, >60 years), stage (I/II, III/IV), and receipt of chemotherapy. NHBs and NHWs experienced similar risk of mortality (HR = 0.85, 95%CI = 0.52-1.40). Overall, among DLBCL patients, Hispanics/Latinos had improved survival compared to NHWs. Additional research should seek to identify the drivers of this survival benefit.


Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen.
The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets. A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir.


Acetaldehyde production from ethanol and glucose by non-Candida albicans yeasts in vitro.
Major environmental risk factors for upper digestive tract cancers are tobacco smoking, alcohol intake and poor oral hygiene. They all result in increased acetaldehyde (ACH) levels in saliva which has been shown to be carcinogenic. During alcohol challenge the oral microbiota is the main determinant of the local ACH concentration. Many bacteria and Candida albicans have been shown to be capable of ACH production. Moreover, chronic candidal mucositis can be carcinogenic. The ability of non-C. albicans Candida to produce ACH has not been studied. The aim of this study was to explore the ability of non-C. albicans Candida species to produce ACH in vitro during ethanol and glucose incubation. A total of 30 non-C. albicans Candida isolates and one C. albicans reference strain were used. The cells were exposed to 11 mM of ethanol and to 100mM glucose in vitro. ACH was measured by gas chromatography. All Candida isolates produced significant amounts of ACH in ethanol incubation. C. tropicalis isolates were the highest (252.3 microM) and C. krusei isolates were the lowest (54.6 microM) producers of ACH from ethanol. Only C.glabrata produced significant amounts of ACH by fermentation from glucose. Colonization of oral mucosa with a non-C.albicans species such as C. glabrata, capable of producing carcinogenic amounts of ACH from both ethanol and glucose, may contribute to the development of oral cancer.


Further Reductions in Road-Related Deaths and Injuries in Irish Children.
The aim was to study road-related injuries and fatalities in under 15-year-olds in three time periods (1996-2000, 2004-2008 and 2009 -2013 respectively) to assess whether progress has been made via cross-sectoral efforts (legislation, public awareness campaigns and police enforcement) to reduce this injury toll in Ireland. For road traffic collisions where an injury has occurred, police assistance is required and at the time a detailed CT 68 form is completed by the attending police officer and sent to the Road Safety Authority for analysis. Details regarding the severity of injury, light and road conditions and safety measures such as seat belt or car restraint use, seat position and helmet use if a cyclist is involved are recorded. Injuries were sub-classified as fatalities, serious (detained in hospital, fractures, severe head injury, severe internal injuries or shock requiring treatment) or minor. All data for the three time periods was entered onto an SPSS database. A concerted national campaign re road safety media campaign allied to random breath testing, penalty points for driving offences, on the spot fines for speeding and greater police enforcement took place over the 17-year timeframe and continues to this day. When results were compared between the three cohorts, total injuries dropped from 5928 (1996-2000) to 3903 (2009-2013).Fatal injuries dropped from 163 to 43 with car occupant fatalities fell from 69 to 17 between 1996-2000 and 2009-2013. Serious injuries dropped from 347 in the first cohort to 201 in the third cohort. Minor injuries fell from 5,063 to 3,659 between first and last cohort. Pedestrian injuries dropped from 1719 to 1258 with pedestrian fatalities decreased from 61 (1996-2000) to 21 (2009-2013) and serious pedestrian injuries decreased from 261 down to 129. Cyclist fatalities saw the most significant fall (76%) with a dramatic reduction in fatalities from 25 down to 6. A national road safety campaign, greater police enforcement and a cultural change has seen road-related deaths and injuries in children drop very significantly (by over 70%) over the three time periods (spanning 1996 to 2013) and this campaign should continue.


Real-Time Polymerase Chain Reaction for One-Hour On-Site Diagnosis of Pierce's Disease of Grape in Early Season Asymptomatic Vines.
ABSTRACT Molecular-based techniques, such as polymerase chain reaction (PCR), can reduce the time needed for diagnosis of plant diseases when compared with classical isolation and pathogenicity tests. However, molecular techniques still require 2 to 3 days to complete. To the best of our knowledge, we describe for the first time a real-time PCR technique using a portable Smart Cycler for one-hour on-site diagnosis of an asymptomatic plant disease. Pierce's disease (PD) of grape, caused by the fastidious bacterium Xylella fastidiosa, causes serious losses in grapes in California and the southeastern United States. The disease has been difficult to diagnose because typical leaf scorching symptoms do not appear until late (June and after) in the season and the organism is very difficult to isolate early in the season. Sap and samples of macerated chips of secondary xylem from trunks of vines were used in a direct real-time PCR without extraction of DNA. Using two different sets of primers and probe, we diagnosed PD in 7 of 27 vines (26%) from four of six vineyards sampled 10 to 12 days after bud break in Kern, Tulare, and Napa counties of California. The diagnosis was confirmed by isolation of Xylella fastidiosa from two of the original PCR positive samples and later from symptomatic leaf petioles of four out of four vines from one vineyard that were originally PCR positive.


Nanomedicines Lost in Translation.
Nanomedicines have historically struggled to find clinical relevance and to achieve translation successfully. In this Perspective, we discuss possible reasons for this difficulty and highlight several key features of nanomedicines that are often overlooked by biomedical engineers. We present the notion of clinical multifunctionality as distinct from multifunctionality as it is traditionally described at the nanoscale and emphasize its importance through examples of nanomedicines that have demonstrated emergent clinical multifunctionality once translated. We also describe a phenomenon in which clinical multifunctionality results in diagonal translation after a nanomedicine is adopted by clinicians to serve as a solution for a clinical problem that it was not designed to solve. Biomedical engineers can take advantage of these phenomena to assist in achieving clinical translation of new nanomedicines.


Sac ligation in inguinal hernia repair: A meta-analysis of randomized controlled trials.
Traditionally, hernia sac ligation during inguinal hernia repair is considered mandatory to prevent postoperative development of hernia. However, ligation may induce postoperative pain. The aim of this study was to evaluate the outcomes of hernia sac ligation after inguinal hernia repair. We conducted a systematic review and meta-analysis of randomized controlled trials to investigate the outcomes of hernia sac ligation for open or laparoscopic inguinal hernia repair. Incidence of hernia recurrence was assessed following the surgery. The secondary outcomes included pain scores and postoperative complications. Five trials were selected and their results were summarized. These 5 trials were published between 1984 and 2014, and the sample sizes ranged from 50 to 467 patients. Four trials had recruited patients with inguinal hernia who underwent open repair, and one study enrolled patients who underwent laparoscopic procedures. We observed no difference in the incidence of hernia recurrence and postoperative complications between the sac ligation and nonligation groups. Postoperatively, the intensity of pain was significantly higher in the ligation group than in the nonligation group at Day 7 (Weight mean difference 1.46; 95% confident interval: 0.98-1.95). Hernia sac ligation was associated with higher postoperative pain, and did not show any benefit over sac nonligation regarding the incidence of recurrence and postoperative complications in patients undergoing open tension-free mesh repair or laparoscopic procedures.


[Prevention and treatment of viral hepatitis in renal insufficiency conditions].
Viral hepatotropic infections may lead to diagnostic and therapeutic problems in hemodialysis patients and kidney recipients. The parenteral and community-acquired routes of contamination of hepatitis B and C viruses explain their high frequency in this population. Their impact, because the immunosuppressive treatments, is harmful with a decrease in patients and allografts survival; cirrhosis is a contra-indication for renal transplantation since associated with a bad short-term prognosis and may require a combined kidney-liver transplantation. Thus, a liver biopsy is recommended in order to evaluate the histopathological severity of the liver disease (stage and grade) and to precise if an antiviral treatment appears necessary, especially because interferon-alpha, the main treatment of hepatitis B and C infections, is contra-indicated in kidney recipients because of the risk of graft rejection. In summary, the diagnosis of viral hepatotropic infections has to be early undergone and its pathological impact has to be evaluated by a liver biopsy. The best treatment has to be prophylactic (vaccination against hepatitis B virus and the respect of universal hygiene rules for hepatitis C virus).


Time to wake up: reactive countermeasures to sleep inertia.
Sleep inertia is the period of impaired performance and grogginess experienced after waking. This period of impairment is of concern to workers who are on-call, or nap during work hours, and need to perform safety-critical tasks soon after waking. While several studies have investigated the best sleep timing and length to minimise sleep inertia effects, few have focused on countermeasures -especially those that can be implemented after waking (i.e. reactive countermeasures). This structured review summarises current literature on reactive countermeasures to sleep inertia such as caffeine, light, and temperature and discusses evidence for the effectiveness and operational viability of each approach. Current literature does not provide a convincing evidence-base for a reactive countermeasure. Caffeine is perhaps the best option, although it is most effective when administered prior to sleep and is therefore not strictly reactive. Investigations into light and temperature have found promising results for improving subjective alertness; further research is needed to determine whether these countermeasures can also attenuate performance impairment. Future research in this area would benefit from study design features highlighted in this review. In the meantime, it is recommended that proactive sleep inertia countermeasures are used, and that safety-critical tasks are avoided immediately after waking.


Maternal and perinatal risk factors for Wilms' tumor: a nationwide nested case-control study in Sweden.
This report describes maternal and perinatal risk factors for Wilms' tumor analyzed in a case-control study nested in a nationwide cohort in Sweden. The Swedish National Cancer Registry ascertained 110 cases from among successive birth cohorts from 1973 through 1984, identified by the Swedish Medical Birth Registry, the latter based on medical records. From the Birth Registry, we matched 5 controls without cancer to each case by sex and date of birth. Wilms'-tumor children were more likely to have mothers who had been exposed to penthrane (methoxyflurane) anesthesia during delivery than mothers of controls (odds ratio (OR) = 2.4; 95% confidence interval (CI) 1.1 to 5.1); this excess risk was higher in females than males and increased with age at diagnosis. Wilms'-tumor cases were also more likely to have had physiologic jaundice (OR = 2.3; 95% CI 1.1 to 5.0). Higher parity of the mother decreased the risk of Wilms' tumor among females (OR = 0.7; 95% CI 0.5 to 1.0). We were unable to confirm the reported increased risks of Wilms' tumor for those with high birth weights or with a maternal history of hypertension or fluid retention during pregnancy, nor did we find any association with mother's age at delivery, previous stillbirth, previous live birth, gestational length or height of the child.


Sex differences in the perception of affective facial expressions: do men really lack emotional sensitivity?
There is evidence that men and women display differences in both cognitive and affective functions. Recent studies have examined the processing of emotions in males and females. However, the findings are inconclusive, possibly the result of methodological differences. The aim of this study was to investigate the perception of emotional facial expressions in men and women. Video clips of neutral faces, gradually morphing into full-blown expressions were used. By doing this, we were able to examine both the accuracy and the sensitivity in labelling emotional facial expressions. Furthermore, all participants completed an anxiety and a depression rating scale. Research participants were 40 female students and 28 male students. Results revealed that men were less accurate, as well as less sensitive in labelling facial expressions. Thus, men show an overall worse performance compared to women on a task measuring the processing of emotional faces. This result is discussed in relation to recent findings.


Microlunatus parietis sp. nov., isolated from an indoor wall.
A Gram-positive, coccoid, non-endospore-forming actinobacterium (strain 12-Be-011(T)) was isolated from indoor wall material. Based on 16S rRNA gene sequence comparisons, strain 12-Be-011(T) was clearly shown to belong to the genus Microlunatus and was most closely related to Microlunatus panaciterrae Gsoil 954(T) (95.7 %), Microlunatus soli CC-12602(T) (94.9 %), Microlunatus ginsengisoli Gsoil 633(T) (94.8 %), Microlunatus aurantiacus YIM 45721(T) (95.5 %) and Microlunatus phosphovorus DSM 10555(T) (94.7 %). The cell-wall peptidoglycan contained LL-diaminopimelic acid as the diagnostic diamino acid. Mycolic acids were absent. The major menaquinone was MK-9(H₄). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two unknown phospholipids and one unknown glycolipid. The major fatty acids of iso-C₁₅:₀, anteiso-C₁₅:₀ and iso-C₁₆:₀ supported the affiliation of strain 12-Be-011(T) to the genus Microlunatus. Physiological and biochemical test results allowed a clear phenotypic differentiation of strain 12-Be-011(T) from all other species of the genus Microlunatus. Hence, strain 12-Be-011(T) can be regarded as a representative of a novel species, for which the name Microlunatus parietis sp. nov. is proposed, with the type strain 12-Be-011(T) (=DSM 22083(T)=CCM 7636(T)).


Randomized trials of directional coronary atherectomy: implications for clinical practice and future investigation.
This study compared and contrasted the randomized trials of directional atherectomy and coronary angioplasty for de novo native coronary artery lesions. The results of two randomized trials, the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT) and the Canadian Coronary Atherectomy Trial (CCAT), comparing initial and intermediate-term outcome of directional coronary atherectomy and conventional coronary angioplasty in de novo native vessels, have been reported. In CAVEAT any coronary artery segment that could be treated by either technique was included; in CCAT only nonostial proximal left anterior descending coronary artery stenoses were studied. The primary end point was 6-month angiographic restenosis. Clinical outcome end points at 6 months included death, myocardial infarction, emergency bypass surgery and abrupt closure. Initial angiographic success rates were significantly improved with directional coronary atherectomy compared with conventional angioplasty (89% vs. 80% for CAVEAT; 98% vs. 91% for CCAT). Also, the initial improvement in minimal lumen diameter and final immediate postprocedural residual diameter stenosis were better with atherectomy. In CCAT, there was no difference in initial complications; in CAVEAT, non-Q wave myocardial infarction rates and abrupt closure were increased with atherectomy. Despite improved success rates and better lumen achieved with atherectomy, in CCAT there was no difference in angiographic restenosis (46% for directional atherectomy vs. 43% for angioplasty). In CAVEAT, in a prespecified subset analysis involving the proximal left anterior descending coronary artery, restenosis was both significantly and clinically less for directional atherectomy (51% vs. 63%). For non-left anterior descending coronary artery segments, there was no difference. These studies document the difference between achievement of an excellent initial angiographic result and the longer term issue of clinical restenosis. Widespread use of directional coronary atherectomy to treat lesions that would be well treated by angioplasty in an attempt to decrease restenosis rates substantially does not appear indicated by the data. In individual lesions, directional atherectomy should be selected with the view toward optimizing initial results. Further trials are needed to determine whether more aggressive or better targeted directional coronary atherectomy may improve not only the initial gain but the long-term outcome as well.


Using Genome Query Language to uncover genetic variation.
With high-throughput DNA sequencing costs dropping <$1000 for human genomes, data storage, retrieval and analysis are the major bottlenecks in biological studies. To address the large-data challenges, we advocate a clean separation between the evidence collection and the inference in variant calling. We define and implement a Genome Query Language (GQL) that allows for the rapid collection of evidence needed for calling variants. We provide a number of cases to showcase the use of GQL for complex evidence collection, such as the evidence for large structural variations. Specifically, typical GQL queries can be written in 5-10 lines of high-level code and search large datasets (100 GB) in minutes. We also demonstrate its complementarity with other variant calling tools. Popular variant calling tools can achieve one order of magnitude speed-up by using GQL to retrieve evidence. Finally, we show how GQL can be used to query and compare multiple datasets. By separating the evidence and inference for variant calling, it frees all variant detection tools from the data intensive evidence collection and focuses on statistical inference. GQL can be downloaded from http://cseweb.ucsd.edu/~ckozanit/gql.


Spemann's influence on Japanese developmental biology.
The discovery of the organizer by H. Spemann and Hilde Mangold, prompted a number of studies of embryonic induction in Japan. C.O. Whitman, N. Yatsu, T. Sato, H. Oka, T. Yamada, and Y.K. Okada were the pioneers in the field of embryonic induction. T. Yamada postulated the double potential theory for embryonic induction. O. Nakamura has modified the fate map of Vogt using newt and Xenopusblastulae. T.S. Okada and G. Eguchi proposed the new concept of "transdifferentiation" based on in vitro experiments in the retina and lens. T.S. Okada is not only an excellent scientist, but he has also nurtured many active developmental biologists. M. Takeichi, from his school, discovered the cell adhesion molecle, cadherin. Nakamura and colleagues tried to determine the origin and formation of the organizer. They performed recombination experiments using the ectoderm, endoderm and mesoderm, and concluded that the phenomenon in which various mesoderm tissues are formed by the recombination of the presumptive ectoderm with endoderm was "regulation of the vegetal-animal gradient". Some groups have also tried to purify specific inducing factors. T. Yamada and colleagues isolated two different types of ribonucleoproteins. I. Kawakami and colleagues showed that the ribosome fraction has neural inducing capacity, and that the extracellular matrix contains mesodermal inducing factors. Finally Asashima and colleagues isolated and identified activin A as a MIF factor. This finding had a great influence not only in the field of developmental biology, but also in molecular biology. Using activin, Asashima's group has successfully generated various organs, tissues, trunk-tail and head structures in vitro using animal caps (undifferentiated cells). Some other important molecules such as BMP, chordin and bFGF are also being studied by young Japanese scientists.


Interactive virtual probing of 4D MRI blood-flow.
Better understanding of hemodynamics conceivably leads to improved diagnosis and prognosis of cardiovascular diseases. Therefore, an elaborate analysis of the blood-flow in heart and thoracic arteries is essential. Contemporary MRI techniques enable acquisition of quantitative time-resolved flow information, resulting in 4D velocity fields that capture the blood-flow behavior. Visual exploration of these fields provides comprehensive insight into the unsteady blood-flow behavior, and precedes a quantitative analysis of additional blood-flow parameters. The complete inspection requires accurate segmentation of anatomical structures, encompassing a time-consuming and hard-to-automate process, especially for malformed morphologies. We present a way to avoid the laborious segmentation process in case of qualitative inspection, by introducing an interactive virtual probe. This probe is positioned semi-automatically within the blood-flow field, and serves as a navigational object for visual exploration. The difficult task of determining position and orientation along the view-direction is automated by a fitting approach, aligning the probe with the orientations of the velocity field. The aligned probe provides an interactive seeding basis for various flow visualization approaches. We demonstrate illustration-inspired particles, integral lines and integral surfaces, conveying distinct characteristics of the unsteady blood-flow. Lastly, we present the results of an evaluation with domain experts, valuing the practical use of our probe and flow visualization techniques.


Comparative Proteomic and Transcriptomic Analysis of Follistatin-Induced Skeletal Muscle Hypertrophy.
Skeletal muscle, the most abundant body tissue, plays vital roles in locomotion and metabolism. Myostatin is a negative regulator of skeletal muscle mass. In addition to increasing muscle mass, Myostatin inhibition impacts muscle contractility and energy metabolism. To decipher the mechanisms of action of the Myostatin inhibitors, we used proteomic and transcriptomic approaches to investigate the changes induced in skeletal muscles of transgenic mice overexpressing Follistatin, a physiological Myostatin inhibitor. Our proteomic workflow included a fractionation step to identify weakly expressed proteins and a comparison of fast versus slow muscles. Functional annotation of altered proteins supports the phenotypic changes induced by Myostatin inhibition, including modifications in energy metabolism, fiber type, insulin and calcium signaling, as well as membrane repair and regeneration. Less than 10% of the differentially expressed proteins were found to be also regulated at the mRNA level but the Biological Process annotation, and the KEGG pathways analysis of transcriptomic results shows a great concordance with the proteomic data. Thus this study describes the most extensive omics analysis of muscle overexpressing Follistatin, providing molecular-level insights to explain the observed muscle phenotypic changes.


Tocotrienol and cancer metastasis.
Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs.


The endonasal patient reference tracker: a novel solution for accurate noninvasive electromagnetic neuronavigation.
Electromagnetic (EM) navigation provides the advantages of continuous guidance and tip-tracking of instruments. The current solutions for patient reference trackers are suboptimal, as they are either invasively screwed to the bone or less accurate if attached to the skin. The authors present a novel EM reference method with the tracker rigidly but not invasively positioned inside the nasal cavity. The nasal tracker (NT) consists of the EM coil array of the AxiEM tracker plugged into a nasal tamponade, which is then inserted into the inferior nasal meatus. Initially, a proof-of-concept study was performed on two cadaveric skull bases. The stability of the NT was assessed in simulated surgical situations, for example, prone, supine, and lateral patient positioning and skin traction. A deviation ≤ 2 mm was judged sufficiently accurate for clinical trial. Thus, a feasibility study was performed in the clinical setting. Positional changes of the NT and a standard skin-adhesive tracker (ST) relative to a ground-truth reference tracker were recorded throughout routine surgical procedures. The accuracy of the NT and ST was compared at different stages of surgery. Ex vivo, the NT proved to be highly stable in all simulated surgical situations (median deviation 0.4 mm, range 0.0-2.0 mm). In 13 routine clinical cases, the NT was significantly more stable than the ST (median deviation at procedure end 1.3 mm, range 0.5-3.0 mm vs 4.0 mm, range 1.2-11.2 mm, p = 0.002). The loss of accuracy of the ST was highest during draping and flap fixation. Application of the EM endonasal patient tracker was found to be feasible with high procedural stability ex vivo as well as in the clinical setting. This innovation combines the advantages of high precision and noninvasiveness and may, in the future, enhance EM navigation for neurosurgery.


Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant.
PIK3R1 encodes three regulatory subunits of class IA phosphoinositide 3-kinase (PI3K), each associating with any of three catalytic subunits, namely p110α, p110β or p110δ. Constitutional PIK3R1 mutations cause diseases with a genotype-phenotype relationship not yet fully explained: heterozygous loss-of-function mutations cause SHORT syndrome, featuring insulin resistance and short stature attributed to reduced p110α function, while heterozygous activating mutations cause immunodeficiency, attributed to p110δ activation and known as APDS2. Surprisingly, APDS2 patients do not show features of p110α hyperactivation, but do commonly have short stature or SHORT syndrome, suggesting p110α hypofunction. We sought to investigate this. In dermal fibroblasts from an APDS2 patient, we found no increased PI3K signalling, with p110δ expression markedly reduced. In preadipocytes, the APDS2 variant was potently dominant negative, associating with Irs1 and Irs2 but failing to heterodimerise with p110α. This attenuation of p110α signalling by a p110δ-activating PIK3R1 variant potentially explains co-incidence of gain-of-function and loss-of-function PIK3R1 phenotypes.


Disparities in Female Breast Cancer Stage at Diagnosis in New Jersey: A Spatial-Temporal Analysis.
Despite improvements in early detection of breast cancer, disparities persist in stage at diagnosis, which is an important prognostic factor. We used the space-time scan statistic in SaTScan to identify geographic areas and time periods with significantly elevated proportions of female breast cancer diagnosed at the in situ or distant stage in New Jersey. The analyses were conducted with census tracts as the geographic unit of analysis, elliptical spatial windows, 3-year temporal windows, and Poisson models. Statistical significance was determined by 999 Monte Carlo simulations (P < .05); significant clusters were mapped in ArcMap. Breast cancer cases within the clusters were compared with breast cancer cases outside the clusters on demographic, socioeconomic, and clinical factors using the Pearson chi-square test (P < .05). In addition, populations within the clusters were compared with the population outside the clusters on demographic and socioeconomic factors. After exclusions, 126 756 cases of primary female breast cancer diagnosed in 1997 to 2011 from the New Jersey State Cancer Registry were included in the analysis. One distant stage breast cancer cluster was identified in northeastern New Jersey from 1997 through 2011 (n = 26 244, relative risk [RR] = 1.42, P < .001). Two in situ breast cancer clusters were found in northeastern New Jersey from 2004 through 2011 (n = 12 496, RR = 1.35, P < .001) and in central New Jersey from 2006 through 2011 (n = 29 319, RR = 1.24, P < .001). The distant stage cluster contained relatively high percentages of minority and lower socioeconomic status (SES) breast cancer cases and populations, whereas the in situ clusters had relatively low percentages of minority and lower SES breast cancer cases and populations. Although there have been improvements since an earlier study of distant stage breast cancer diagnosed in 1995 to 1997, disparities in stage at diagnosis continue. These findings can be used by our local cancer control partners to target specific populations for interventions such as breast cancer education and mammography screening, as well as by state legislative and public health authorities for resource allocation.


Odor source localization in complex visual environments by fruit flies.
Flying insects routinely forage in complex and cluttered sensory environments. Their search for a food or a pheromone source typically begins with a whiff of odor, which triggers a flight response, eventually bringing the insect near the odor source. However, pinpointing the precise location of an odor source requires use of both visual and olfactory modalities, aided by odor plumes. Here, we investigated odor-tracking behavior in fruit flies (Drosophila melanogaster) presented with low- or high-contrast visual landmarks, either paired with or separate from an attractive odor cue. These experiments were conducted either in a gentle air stream which generated laminar odor plumes or in still air in which odor dissipates uniformly in all directions. Trajectories of flies revealed several novel features of their odor-tracking behavior in addition to those previously documented. First, in both moving and still air, odor-seeking flies rely on the co-occurrence of visual landmarks with olfactory cues to guide them to odorant objects. Second, flies abruptly decelerate upon encountering an odor plume, thereafter steering towards the nearest visual objects that had no inherent salience in the absence of odor. Thus, interception of an attractive odor increases their salience to nearby high-contrast visual landmarks. Third, flies adopt distinct odor-tracking strategies during flight in moving versus still air. Whereas they weave in and out of plumes towards an odor source in airflow, their approach is more incremental in still air. Both strategies are robust and flexible, and enable flies to reliably find odor sources under diverse visual and airflow environments.


Effects of nitrogen deposition on soil microbial communities in temperate and subtropical forests in China.
Increasing nitrogen (N) deposition has aroused large concerns because of its potential negative effects on forest ecosystems. Although microorganisms play a vital role in ecosystem carbon (C) and nutrient cycling, the effect of N deposition on soil microbiota still remains unclear. In this study, we investigated the responses of microbial biomass C (MBC) and N (MBN) and microbial community composition to 4-5years of experimentally simulated N deposition in temperate needle-leaf forests and subtropical evergreen broadleaf forests in eastern China, using chloroform fumigation extraction and phospholipid fatty acid (PLFA) methods. We found idiosyncratic effects of N addition on microbial biomass in these two types of forest ecosystems. In the subtropical forests, N addition showed a significant negative effect on microbial biomass and community composition, while the effect of N addition was not significant in the temperate forests. The N addition decreased MBC, MBN, arbuscular mycorrhizal fungi, and the F/B ratio (ratio of fungi to bacteria biomass) in the subtropical forests, likely due to a decreased soil pH and changes in the plant community composition. These results showed that microbial biomass and community composition in subtropical forests, compared with the temperate forests, were sensitive to N deposition. Our findings suggest that N deposition may have negative influence on soil microorganisms and potentially alter carbon and nutrient cycling in subtropical forests, rather than in temperate forests.


Diagnosis of traumatic cardiac contusion.
Cardiac contusion following blunt chest trauma remains a diagnostic problem because of a lack of sensitive diagnostic tests. This study evaluated thallous chloride Tl 201 single-photon-emission computed tomography in a series of 48 patients following blunt chest trauma. Of the 48 patients, 23 had normal scans. None of these patients proved to have serious arrhythmias during three days of continuous monitoring. Of 25 patients with abnormal or ambiguous studies, five (20%) developed serious arrhythmias requiring therapy. Single-photon-emission computed tomography scanning thus was sensitive in indicating that group of patients at risk of serious arrhythmias, and may therefore prove to be a useful screening test to determine the need for hospitalization and arrhythmia monitoring following blunt chest trauma.


Proximal femoral canal shape is more accurately assessed on AP hip radiographs than AP pelvis radiographs in primary hip osteoarthritis.
The objectives of the present study were to determine whether differences in the radiographic appearance of the of the proximal femoral canal exist on corresponding AP pelvis and AP hip radiographs, and whether radiographic assessment of canal shape is accurate with reference to computed tomography (CT). In a retrospective study, corresponding radiographs and CT scans of 100 consecutive patients with primary hip OA were evaluated. Active shape modelling (ASM) was performed to assess the variation in proximal femoral canal shape and to identify differences between AP hip and AP pelvis views. Differences in the medial cortical flare between radiographs and CT were quantified using least squares curve fitting. ASM identified significant differences in the assessment of canal shape on corresponding AP hip and AP pelvis views. Curve fitting demonstrated a good agreement between AP hip radiographs and CT. Agreement between AP pelvis radiographs and CT was less good. In contrast to AP pelvis radiographs, AP hip radiographs allow a more accurate and reliable assessment of proximal femoral canal shape in the frontal plane in primary hip OA. Our findings may improve stem fit in total hip arthroplasty without the routine use of CT.


Revision of a single type of large metal head metal-on-metal hip prosthesis.
Large-head metal-on-metal (MoM) total hip arthroplasties were introduced because of their purported advantages. Inflammatory pseudotumours occasionally occur after MoM hip arthroplasty and often lead to revision. The purpose of this study was to assess the outcome of revision of large-head MoM total hip arthroplasties after an extensive screening protocol for all MoM articulations with a minimum 2 year follow-up. We identified 50 hips that had undergone large-head MoM total hip arthoplasty and required revision at a mean of 44 months after index operation. Of these, 38 were revised for pseudotumours, 7 for loosening, 2 for infection and 3 for instability. There was bone loss in 44 hips. The majority were revised to a 28 mm metal or ceramic head on a polyethylene-cemented cup. In 12 patients there was a complication. There was a decrease of whole blood cobalt from 20.8 µg/L preoperatively to 1.8 µg/L 1 year after revision. We found 6 residual masses on routine postoperative CT scans. The indication for revision of this cohort is inevitable but the clinical outcome 2 years after revision for pseudotumour is disappointing. Revising a MoM hip arthroplasty to a conventional cemented polyethylene or dual-mobility cup with bone impaction grafting and a 28 mm head can adequately treat the high ion levels and probably the disease of ARMD.


Histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis) in an HIV-positive patient.
Histiocytic necrotizing lymphadenitis, or Kikuchi's lymphadenitis (KL), is an unusual form of lymphadenitis, generally with self-limited clinical course. KL has been reported in rare patients infected with the human immunodeficiency virus (HIV). Pathogenesis of the lesion is probably related to an impaired immune function. The purpose of the present article is to report on one case in which KL was diagnosed in an HIV-infected patient. Histomorphology and immunophenotype were similar to previous reports, but a focus of activated CD30+ macrophages was seen, what might be due to the immunological status of the patient. EBV was not detected on the sections using the in situ hybridization technique. Although rare, the occurrence of KL in HIV-infected subjects must be emphasized, because of the potential misdiagnosis of malignancy, especially in the presence of CD30+ cells.


Prediction of kidney-related outcomes in patients with type 2 diabetes.
Tools are needed to predict which individuals with diabetes will develop kidney disease and its complications. An observational analysis of a randomized controlled trial. The ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) Study followed up 11,140 participants with type 2 diabetes for 5 years. Readily available baseline demographic and clinical variables. (1) Major kidney-related events (doubling of serum creatinine to ≥2.26 mg/dL [≥200 μmol/L], renal replacement therapy, or renal death) in all participants, and (2) new-onset albuminuria in participants with baseline normoalbuminuria. Cox proportional hazard regression models predicting the outcomes were used to generate risk scores. Discrimination of the risk prediction models was compared with that of models based on estimated glomerular filtration rate (eGFR) alone, urinary albumin-creatinine ratio (ACR) alone, and their combination. Risk scores for major kidney-related events and new-onset albuminuria were derived from 7- and 8-variable models, respectively. Baseline eGFR and ACR were dominant although models based on the 2 factors, alone or combined, had less discrimination (P<0.05) than the risk prediction models containing additional variables (risk prediction model C statistics of 0.847 [95% CI, 0.815-0.880] for major kidney-related events, and 0.647 [95% CI, 0.637-0.658] for new-onset albuminuria). Novel risk factors for new-onset albuminuria included Asian ethnicity and greater waist circumference, and for major kidney-related events, less education. The risk prediction models had acceptable calibration for both outcomes (modified Hosmer-Lemeshow test, P=0.9 and P=0.06, respectively). The follow-up period was limited to 5 years. Results are applicable to people with type 2 diabetes at risk of vascular disease. Risk scores have been developed for early and late events in diabetic nephropathy. Although eGFR and urinary ACR are important components of the prediction models, the extra variables considered add significantly to discrimination and, in the case of new-onset albuminuria, are required to achieve satisfactory calibration.


Dose-response relationship of topically applied mitomycin C for the prevention of laser myringotomy closure.
We sought to determine a dose-response curve for topical mitomycin C when used to prolong the patency of laser-assisted myringotomies. Bilateral myringotomies were performed using the argon laser in 40 guinea pigs with normal ears. Pledgets with (0.05, 0.2, 0.4, or 2.0 mg/mL) mitomycin C were applied topically. Monitoring consisted of weekly or biweekly otomicroscopy. As in previous studies, all saline-treated myringotomies closed by day 7. By day 14, all myringotomies (100%) in the 0.05 mg/mL group were closed. By contrast, all myringotomies (100%) remained patent in the 0.2 and 0.4 mg/mL treatment groups, and 56% of the myringotomies remained patent in the 2.0 mg/mL group at day 14. By day 56, all myringotomies were closed in the 2.0 mg/mL group, 5 (50%) myringotomies were patent in the 0.4 mg/mL group, and 1 (11%) myringotomy was patent in the 0.2 mg/mL group. The study was terminated on day 84 (12 weeks). At that time, only the 0.4 mg/mL group had patent myringotomies (n = 3; 30%). The highest dose (2.0 mg/mL) of mitomycin was significantly associated with otorrhea. Otorrhea also appeared to be associated with earlier myringotomy closure. There is a dose-response curve for topical mitomycin C when used for prolonging myringotomy patency in doses up to 0.4 mg/mL. Higher doses do not appear to prolong patency and are associated with greater otorrhea, suggesting middle ear toxicity.


Plasma-volume contraction and exercise-induced hypoxaemia modulate erythropoietin production in healthy humans.
This study examined exercise-induced hypoxaemia (EIH) and plasma volume contraction as modulators of serum erythropoietin (Epo) production. Five athletes cycled for 3 min at supra-maximal power outputs, at each of two different elevations (1,000 m and 2,100 m). Five subjects were exposed to normobaric hypoxia (F(I)O(2)=0.159), seven subjects underwent plasmapheresis to reduce plasma volume and eight subjects were time controls for Epo levels. Oxyhaemoglobin saturation was significantly reduced during exercise and during normobaric hypoxia. The time period of haemoglobin oxygen saturation <91% was 24+/-29 s (mean+/-S.D., n=5) for exercise at 1000 m, 136+/-77 s (mean+/-S.D., n=5) for exercise at 2100 m and 178+/-255 s (mean+/-S.D., n=5) with resting hypoxic exposure. However, significantly increased serum Epo levels were observed only following exercise (24+/-3%; mean+/-S.D., n=5 at 1,000 m and 36+/-5%; mean+/-S.D., n=5 at 2,100 m). Volume contraction also resulted in increased serum Epo (35+/-6%; mean+/-S.D., n=7) in spite of a significant rise in haematocrit of 2.2%. Despite similar degrees of arterial desaturation, only the hypoxaemia induced by exercise was associated with an increase in serum Epo. This finding indicates that other factors, in addition to hypoxaemia, are important in modulating the production of Epo in response to exercise. Volume depletion in the absence of exercise resulted in increases in Epo levels that were comparable with those observed in response to exercise. The paradoxical responses of the increased haematocrit and the increase in Epo in subjects undergoing plasmapheresis suggests that plasma volume may also modulate the production of Epo.


Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis.
Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons (n = 4) by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected during the midsecretory phase (Days 9-11 postovulation) at 1, 3, 6-7, 10-12, and 15-16 mo after disease induction and compared with tissue from disease-free baboons. RNA was hybridized to Human Genome U133 Plus 2.0 Arrays, and data were extracted using Gene-Chip Operating Software. Subsequently, both Gene Set Enrichment Analysis and Ingenuity Pathways Analysis were used to find biological states that have a statistically significant enrichment concomitant with pairwise comparison of human endometriosis arrays. Within 1 mo of induction of the disease, 4331 genes were differentially expressed (P < 0.05). Hierarchical clustering revealed self-segregation into two groups-a) 1, 3, and 10-12 mo and b) 6-7 and 15-16 mo-together with controls. Clustering analysis at each stage of disease validated dysregulation of several signaling pathways, including Nodal-like receptor, EGF, ERK/MAPK, and PI3/AKT. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype; however, as the disease progressed, a progesterone-resistant phenotype became evident. Furthermore, we demonstrate a 38.6% differential gene expression overlap with endometrial samples in the midsecretory phase from women with endometriosis, concomitant with similar dysregulation in human disease candidate genes Fos, Nodal, Suclg2, and Kras, among others. Molecular changes in the eutopic endometrium, associated with endometriosis, are directly impacted by endometriotic lesions, providing strong evidence that it is the disease rather than inherent defective endometrium that results in aberrant gene expression in the eutopic endometrium. Furthermore, this baboon model provides a powerful means whereby the early events associated with the pathology of disease and the resulting infertility may be elucidated.


Dietary supplementation with lactic acid bacteria attenuates the development of atopic-dermatitis-like skin lesions in NC/Nga mice in a strain-dependent manner.
Dietary supplementation with lactic acid bacteria (LAB) is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis (AD). However, the influence of different bacterial strains and their immunomodulating capacities is still largely unknown. AD-like skin lesions were induced by sensitization to and repeated challenges with picrylchloride in the Th2-skewed NC/Nga mouse strain. The effects of LAB supplementation were assessed over time by monitoring clinical scores and plasma IgE levels. In some cases, mast cell infiltration, cutaneous hypersensitivity responses and cytokine mRNA expression in auricles were also examined. Additionally, cytokine production in vitro and cytokine mRNA accumulation in major lymphoid tissues were measured, comparing Lactobacillus paracasei KW3110 with L. rhamnosus GG (LGG). Supplementation with KW3110 significantly reduced the development of AD-like skin lesions, accompanied by less mast cell infiltration and lower plasma IgE levels. KW3110 also suppressed immediate hypersensitivity reactions and IL-4 mRNA expression in the auricles. These preventive effects sustained when supplementation was terminated; moreover, inhibitory effects were also observed even when supplementation was initiated after the onset of symptoms. In accordance with its effects on IL-12 and IL-4 production in vitro, KW3110 prevented the emergence of clinical symptoms more effectively than LGG in vivo. Supplementation with KW3110 significantly attenuated the onset and exacerbation of AD-like symptoms in NC/Nga mice. The effects were more prominent than those obtained with LGG, suggesting the importance of differences between LAB strains and their immunomodulating capacity.


Convection-enhanced delivery of sulfasalazine prolongs survival in a glioma stem cell brain tumor model.
Expression of CD44 in glioma cells was previously correlated with tumor grade and is considered a stem cell marker. CD44 stabilizes the cystine-glutamate transporter (xCT) and inhibits apoptosis in cancer stem cells (CSCs). Recently it was found that Sulfasalazine (SSZ), an anti-inflammatory drug, acts as an inhibitor of xCT and therefore has potential as a targeted therapy for CSCs. In this study, we tested an efficacy of SSZ against glioma stem cell model developed in rats. As poor penetration of blood-brain barrier resulted in insufficient efficacy of systemic SSZ treatment, SSZ was delivered locally with convection-enhanced delivery (CED). In vitro, expression of CD44 in glioma cells and efficacy of SSZ against glioma cells and glioma stem cells were confirmed. SSZ demonstrated anti-proliferative activity in a dose dependent manner against these cells. This activity was partially reversible with the addition of antioxidant, N-acetyl-L-cysteine, to the medium. In vivo, CED successfully delivered SSZ into the rat brain parenchyma. When delivered at 5 mM concentration, which was the highest possible concentration when SSZ was dissolved in water, CED of SSZ resulted in almost no tissue damage. Against highly malignant bRiTs-G3 brain tumor xenografted rat model; the glioma stem cell model, CED of SSZ at 5 mM concentration induced apoptosis and prolonged survival. Consequently, CED of SSZ induced glioma stem cell death without evidence of tissue damage to normal brain parenchyma. This strategy may be a promising targeted treatment against glioma stem cells.


[Mechanisms of electron transfer to insoluble terminal acceptors in chemoorganotrophic bacteria].
The mechanisms of electron transfer of association of chemoorganotrophic bacteria to the anode in microbial fuel cells are summarized in the survey. These mechanisms are not mutually exclusive and are divided into the mechanisms of mediator electron transfer, mechanisms of electron transfer with intermediate products of bacterial metabolism and mechanism of direct transfer of electrons from the cell surface. Thus, electron transfer mediators are artificial or synthesized by bacteria riboflavins and phenazine derivatives, which also determine the ability of bacteria to antagonism. The microorganisms with hydrolytic and exoelectrogenic activity are involved in electron transfer mechanisms that are mediated by intermediate metabolic products, which are low molecular carboxylic acids, alcohols, hydrogen etc. The direct transfer of electrons to insoluble anode is possible due to membrane structures (cytochromes, pili, etc.). Association of microorganisms, and thus the biochemical mechanisms of electron transfer depend on the origin of the inoculum, substrate composition, mass transfer, conditions of aeration, potentials and location of electrodes and others, that are defined by technological and design parameters.


Coevolution of the ATPase ClpV, the sheath proteins TssB and TssC, and the accessory protein TagJ/HsiE1 distinguishes type VI secretion classes.
The type VI secretion system (T6SS) is a bacterial nanomachine for the transport of effector molecules into prokaryotic and eukaryotic cells. It involves the assembly of a tubular structure composed of TssB and TssC that is similar to the tail sheath of bacteriophages. The sheath contracts to provide the energy needed for effector delivery. The AAA(+) ATPase ClpV disassembles the contracted sheath, which resets the systems for reassembly of an extended sheath that is ready to fire again. This mechanism is crucial for T6SS function. In Vibrio cholerae, ClpV binds the N terminus of TssC within a hydrophobic groove. In this study, we resolved the crystal structure of the N-terminal domain of Pseudomonas aeruginosa ClpV1 and observed structural alterations in the hydrophobic groove. The modification in the ClpV1 groove is matched by a change in the N terminus of TssC, suggesting the existence of distinct T6SS classes. An accessory T6SS component, TagJ/HsiE, exists predominantly in one of the classes. Using bacterial two-hybrid approaches, we showed that the P. aeruginosa homolog HsiE1 interacts strongly with ClpV1. We then resolved the crystal structure of HsiE1 in complex with the N terminus of HsiB1, a TssB homolog and component of the contractile sheath. Phylogenetic analysis confirmed that these differences distinguish T6SS classes that resulted from a functional co-evolution between TssB, TssC, TagJ/HsiE, and ClpV. The interaction of TagJ/HsiE with the sheath as well as with ClpV suggests an alternative mode of disassembly in which HsiE recruits the ATPase to the sheath.


Resistance to Bacterial Spot in Bell Pepper Induced by Acibenzolar-S-Methyl.
Bell pepper plants sprayed with the chemical acibenzolar-S-methyl (ABM, Actigard 50 WG) showed resistance to subsequent infections with the bacterial spot agent Xanthomonas axonopodis pv. vesicatoria. Induction of resistance was independent of the cultivar used, and was expressed as early as 3 days after treatment and continued for at least 2 weeks. In the field, applications of ABM every 2 weeks, alone or in combination with copper, resulted in disease control similar to the standard treatment of copper plus maneb. Yield response was variable, with certain combinations of chemical treatments and cultivars producing yields as large as the copper plus maneb treatment. In contrast, weekly applications during the entire crop season had a negative impact on yield. In plots maintained free of bacterial spot, applications of ABM every 2 weeks caused a reduction in yield for one cultivar of six tested. The use of chemical inducers for the control of bacterial spot on bell pepper, while generally promising, may result in an unpredictable loss in fruit yield.


A musculoskeletal profile of elite female soccer players.
The purpose of this study is to identify lower-extremity (LE) musculoskeletal characteristics of elite female soccer players and to determine whether differences between dominant and nondominant extremities exist with respect to strength, flexibility, and range of motion. Physical data were collected from 26 female professional soccer players. Core control, hip and knee passive range of motion (PROM), LE flexibility, hip abductor strength, and dynamic functional alignment were assessed for each LE. Of 26 subjects, 21 scored 2/5 or less on core control. Mean hip internal rotation and external rotation were 33 degrees (+/-8 degrees) and 25 degrees (+/-6.7 degrees), respectively. All subjects had shortened two-joint hip flexors with an average knee flexion angle of 50 degrees (+/-11 degrees) and increased femoral anteversion. Forty one of 48 dominant limbs and 42 of 48 nondominant limbs demonstrated deviations from neutral alignment during step down or single-leg squat. Of 25 subjects, 15 demonstrated a stiff-knee landing and/or takeoff. All subjects demonstrated limitations in hip external rotation PROM and hip flexor length. There was no difference between dominant and nondominant LEs in all variables including hip abductor strength. Additional research is needed to determine if there is a correlation between the musculoskeletal characteristics, LE biomechanics, and potential risk for injury. IV.


Mariner transposition and transformation of the yellow fever mosquito, Aedes aegypti.
The mariner transposable element is capable of interplasmid transposition in the embryonic soma of the yellow fever mosquito, Aedes aegypti. To determine if this demonstrated mobility could be utilized to genetically transform the mosquito, a modified mariner element marked with a wild-type allele of the Drosophila melanogaster cinnabar gene was microinjected into embryos of a kynurenine hydroxylase-deficient, white-eyed recipient strain. Three of 69 fertile male founders resulting from the microinjected embryos produced families with colored-eyed progeny individuals, a transformation rate of 4%. The transgene-mediated complementation of eye color was observed to segregate in a Mendelian manner, although one insertion segregates with the recessive allele (female-determining) of the sex-determining locus, and a separate insertion is homozygous lethal. Molecular analysis of selected transformed families demonstrated that a single complete copy of the construct had integrated independently in each case and that it had done so in a transposase-mediated manner. The availability of a mariner transformation system greatly enhances our ability to study and manipulate this important vector species.


Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence.
Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it is well established that virus decay is more rapid. In studies of incidence that employ meteorological data, outdoor AH may be serving as a proxy for indoor RH in temperate regions during the wintertime heating season. Finally, we present a mechanistic explanation based on droplet evaporation and its impact on droplet physics and chemistry for why RH is more likely than AH to modulate virus survival and transmission.


Anthropomorphism and 'mental welfare' of fishes.
Anthropomorphism, the use of human characteristics as a foundation for interpreting behavior and mental capacities of animals, is a bias undermining our understanding of other species, especially species as evolutionarily distant from humans as fishes. Anthropomorphism is not justified by allusions to evolutionary continuity among vertebrates, because no living vertebrate was ever a descendant of humans, so none could have inherited human traits. Nonetheless, it has recently been claimed that fishes are capable of conscious experiences of pain and emotional feelings and that mental welfare is an important issue for fishes. This paper shows that the evidence supporting claims for experiences of pain or conscious emotions by fishes is conceptually and methodologically flawed. In addition, the paper shows that the natural history and behavior of diverse fish species is inconsistent with a presumption of human-like awareness. This behavioral evidence is in accord with neurobiological observations showing that fishes are very different from us and are unlikely to have a capacity for awareness of pain or emotional feelings that meaningfully resemble our own. The factors that are detrimental to fish welfare have been well delineated by valid, objective indicators of physiological and behavioral well-being. This knowledge should guide welfare decisions. An empirical and non-anthropomorphic examination of diverse fishes and their adaptations should be the foundation for welfare decisions that would be truly beneficial to fishes and humans alike.


Pre-intervention triage incorporating perfusion imaging improves outcomes in patients undergoing endovascular stroke therapy: a comparison with the device trials.
Endovascular therapy of acute ischemic stroke is evolving towards thrombectomy devices for vessel recanalization. High rates of revascularization have been reported in stroke device trials. However, the discrepancy between recanalization and outcomes raises the question whether patients with irreversible ischemic injury are being exposed to these interventions. This study evaluated a triage methodology that incorporates perfusion imaging against previous device trials that treated all patients within a certain time frame. 99 consecutive patients were identified with anterior circulation strokes who had undergone endovascular therapy. All patients had a baseline NIHSS score ≥8 and had undergone pre-intervention CT perfusion. Rates of recanalization and functional outcomes were compared with the MERCI, Multi-MERCI and Penumbra trials. This study's recanalization rate of 55.6% is not significantly different from the 46% for MERCI (p=0.15) and 68% for Multi-MERCI (p=0.08) but was significantly lower than the 82% for the Penumbra trial (p<0.0001). Successfully recanalized patients had a significantly higher good outcome of 67% in this cohort versus 46% in MERCI, 49% in Multi-MERCI and 29% in Penumbra. The rate of futile recanalization was 33% compared with 54% for MERCI, 51% for Multi-MERCI and 71% for Penumbra. A small cerebral blood volume (CBV) abnormality (p<0.0001) and large mean transit time-CBV mismatch (p<0.0001) were strong predictors of a good outcome. Despite similar or lower recanalization rates, there was a significantly higher rate of good outcomes in the recanalized population and thus a significantly lower rate of futile recanalization in this study versus the device trials, suggesting a role for pre-intervention perfusion imaging for patient selection.


Socioeconomic Inequalities in the Prescription of Oral Anticoagulants in Stroke Patients With Atrial Fibrillation.
Oral anticoagulants (OACs) are effective against ischemic stroke in patients with atrial fibrillation. Our aim was to investigate differences in the prescribing of OACs after ischemic stroke in patients with atrial fibrillation based on age, sex, country of birth, and socioeconomic status. Patients with first-ever ischemic stroke and atrial fibrillation without OAC treatment were included from the Swedish stroke register from 2009 to 2012. The outcome was OAC prescribed at discharge. Income, education, country of birth, and risk factors were obtained from official registers. Risk factors and health status were controlled for in multivariable logistic regression. Of 12 088 stroke patients, 36.3% were prescribed an OAC. Prescribing was less common with older age and, in patients born in other Nordic countries (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.68-0.98) or countries outside of Europe (OR, 0.65; 95% CI, 0.42-0.99) compared with those born in Sweden. University education (OR, 1.20; 95% CI, 1.05-1.36) and highest income (OR, 1.19; 95% CI, 1.06-1.33) were associated with higher levels of OAC prescribing compared with those with primary school education or lowest income level. Differences by age, income, education, and country of birth were found in the prescribing of OACs after stroke. Differences were not explained by common risk factors. This indicates socioeconomic inequalities in the prescribing of preventive treatment after stroke.


Multiple session early psychological interventions for the prevention of post-traumatic stress disorder.
The prevention of long-term psychological distress following traumatic events is a major concern. Systematic reviews have suggested that individual Psychological Debriefing is not an effective intervention at preventing post traumatic stress disorder (PTSD). Recently other forms of intervention have been developed with the aim of preventing PTSD. To examine the efficacy of multiple session early psychological interventions commenced within three months of a traumatic event aimed at preventing PTSD. Single session individual/group psychological interventions were excluded. Computerised databases were searched systematically, the most recent search was conducted in August 2008. The Journal of Traumatic Stress and the Journal of Consulting and Clinical Psychology were handsearched for the last two years. Personal communication was undertaken with key experts in the field. Randomised controlled trials of any multiple session early psychological intervention or treatment (two or more sessions) designed to prevent symptoms of PTSD. Data were entered using Review Manager software. The methodological quality of included studies was assessed individually by two review authors. Data were analysed for summary effects using Review Manager 4.2. Mean difference was used for meta-analysis of continuous outcomes and relative risk for dichotomous outcomes. Eleven studies with a total of 941 participants were found to have evaluated brief psychological interventions aimed at preventing PTSD in individuals exposed to a specific traumatic event, examining a heterogeneous range of interventions. Eight studies were entered into meta-analysis. There was no observable difference between treatment and control conditions on primary outcome measures for these interventions at initial outcome (k=5, n=479; RR 0.84; 95% CI 0.60 to 1.17). There was a trend for increased self-report of PTSD symptoms at 3 to 6 month follow-up in those who received an intervention (k=4, n=292; SMD 0.23; 95% CI 0.00 to 0.46). Two studies compared a memory structuring intervention against supportive listening. There was no evidence supporting the efficacy of this intervention. The results suggest that no psychological intervention can be recommended for routine use following traumatic events and that multiple session interventions, like single session interventions, may have an adverse effect on some individuals. The clear practice implication of this is that, at present, multiple session interventions aimed at all individuals exposed to traumatic events should not be used. Further, better designed studies that explore new approaches to early intervention are now required.


Serum and dietary potassium and risk of incident type 2 diabetes mellitus: The Atherosclerosis Risk in Communities (ARIC) study.
Serum potassium levels affect insulin secretion by pancreatic β-cells, and hypokalemia associated with diuretic use has been associated with dysglycemia. We hypothesized that adults with lower serum potassium levels and lower dietary potassium intake are at higher risk for incident diabetes mellitus (DM), independent of diuretic use. We analyzed data from 12 209 participants from the Atherosclerosis Risk in Communities (ARIC) Study, an ongoing prospective cohort study, beginning in 1986, with 9 years of in-person follow-up and 17 years of telephone follow-up. Using multivariate Cox proportional hazard models, we estimated the hazard ratio (HR) of incident DM associated with baseline serum potassium levels. During 9 years of in-person follow-up, 1475 participants developed incident DM. In multivariate analyses, we found an inverse association between serum potassium and risk of incident DM. Compared with those with a high-normal serum potassium level (5.0-5.5 mEq/L), adults with serum potassium levels lower than 4.0 mEq/L, 4.0 to lower than 4.5 mEq/L, and 4.5 to lower than 5.0 mEq/L had an adjusted HR (95% confidence interval [CI]) of incident DM of 1.64 (95% CI, 1.29-2.08), 1.64 (95% CI, 1.34-2.01), and 1.39 (95% CI, 1.14-1.71), respectively. An increased risk persisted during an additional 8 years of telephone follow-up based on self-report with HRs of 1.2 to 1.3 for those with a serum potassium level lower than 5.0 mEq/L. Dietary potassium intake was significantly associated with risk of incident DM in unadjusted models but not in multivariate models. Serum potassium level is an independent predictor of incident DM in this cohort. Further study is needed to determine if modification of serum potassium could reduce the subsequent risk of DM.


Inhibition of adrenergic vasoconstriction by endothelial cell shear stress.
Isolated perfused rabbit carotid arteries were used to determine the effects of endothelial cell shear stress on the response to adrenergic nerve stimulation. Arterial segments with and without endothelium were cannulated and perfused with physiological salt solution. Adrenergic nerves were activated by transmural electrical field stimulation. Neurogenic vasoconstriction was significantly greater in segments without endothelium when compared with that of segments with endothelium. In segments with endothelium only, vasoconstriction was depressed when shear stress was increased by increasing the viscosity of the perfusate with dextran. Perfusion with methylene blue (2 X 10(-6) M), a guanylate cyclase inhibitor, increased vasoconstriction in segments with endothelium only. In the presence of methylene blue, vasoconstriction was no longer different between segments with and without endothelium, and perfusion with dextran had no effect. In a perfusion-cascade system, perfusion with dextran of donor segments with but not without endothelium caused further relaxation of a contracted bioassay ring. These results suggest that shear stress on endothelial cells modulates adrenergic vasoconstriction by augmenting release of endothelial cell-derived vasodilators.


Pseudoduganella danionis sp. nov., isolated from zebrafish (Danio rerio).
One beige-pigmented, Gram-staining-negative, rod-shaped bacterium, strain E3/2T, was isolated from a zebrafish, Daniorerio. Phylogenetic analysis based on nearly full-length 16S rRNA gene sequences showed that the isolate shared 97.7 % 16S rRNA gene sequence similarity to the species Pseudoduganella violaceinigra and between 97.4 to 97.0 % to some species of the genera Duganella and Massilia, including Duganella radicis, Duganella phyllosphaerae, Massilia dura, Massilia lutea, Duganella sacchari, Duganella zoogloeoides, Massiliaalbidiflava and Massilia umbonata. Sequence similarities to all other species were below 97 %. The main cellular fatty acids of the strain were summed feature 3 fatty acids (C16 : 1ω7c/iso-C15 : 0 2-OH), C10 : 0 3-OH, C16 : 0 and C12 : 0. The polyamine pattern of strain E3/2T contained predominantly putrescine and 2-hydroxyputrescine. The major quinone was ubiquinone Q-8. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based on phylogenetic, chemotaxonomic, genomic and phenotypic analyses we propose a novel species of the genus Pseudoduganella named Pseudoduganella danionis sp. nov., with strain E3/2T (=LMG 29678T=CCM 8698T) as the type strain.


Cortisol reduces recall of explicit contextual pain memory in healthy young men.
Remembering painful incidents has important adaptive value but may also contribute to clinical symptoms of posttraumatic stress disorder and chronic pain states. Because glucocorticoids are known to impair memory retrieval processes, we investigated whether cortisol affects recall of previously experienced pain in healthy young men. In a double-blind, placebo-controlled crossover study, 20 male participants were presented pictures, half of them combined with a heat-pain stimulus. The next day, the same pictures were shown in the absence of pain. Cortisol (20 mg) administered 1h before retention testing reduced recall of explicit contextual pain memory, whereas it did not affect pain threshold or pain tolerance.


A polymorphism of the ability to smell urinary metabolites of asparagus.
The urinary excretion of (an) odorous substance(s) after eating asparagus is not an inborn error of metabolism as has been supposed. The detection of the odour constitutes a specific smell hypersensitivity. Those who could smell the odour in their own urine could all smell it in the urine of anyone who had eaten asparagus, whether or not that person was able to smell it himself. Thresholds for detecting the odour appeared to be bimodal in distribution, with 10% of 307 subjects tested able to smell it at high dilutions, suggesting a genetically determined specific hypersensitivity.


Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes.
Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10(-) (4). Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10(-) (8)). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10(-) (5) to P = 9.40 × 10(-) (8). The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10(-) (17)) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10(-) (11)) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network.


Vascular Disease in Young Indians (20-40 years): Role of Hypertension.
Hypertension (HTN) being one of the important risk factors for cardiovascular disease (CVD) is a significant health concern, especially in India. With age, prevalence of HTN, especially systolic HTN increases. Special attention needs to be directed to HTN in young ages (20-40 years) due to lower awareness, need for early treatment and better control of HTN. HTN in the age group of 20-40 years needs critical reappraisal. Given the high prevalence of HTN in the general population in India, in this review we attempt to provide current evidence and expert opinion on epidemiology, aetiopathogenesis and treatment of HTN in young (20-40 years) Indians.


Parathyroid nuclear scan. A focused review on the technical and biological factors affecting its outcome.
Technetium Parathyroid Scintigraphy (TS) is the most popular noninvasive localization procedure in patients with primary hyperparathyroidism (PHPT). Awareness of various factors involved in technetium uptake helps understand the outcome of TS. We utilize a case of changing TS scans in a patient to review the literature on the various biological and technical factors involved in technetium uptake by the abnormal parathyroid tissue. A 56 year female was diagnosed with PHPT and osteopenia. An initial scan using (99m)Tc-Tetrofosmin showed no definite areas of abnormal parathyroid tissue. Patient refused surgical exploration, was started on Bisphosponates and subsequently monitored. Five years later she suffered fracture of her right wrist. A repeat TS using (99m)Tc-Sestamibi revealed hypervascular parathyroid lesion in the right lower neck. She underwent successful removal of a right lower parathyroid adenoma. Technical factors like the type of Tc isotope used, imaging techniques and biological factors like biochemical parameters (calcium, vitamin D levels), adenoma size, content of oxyphilic cells, vascularity can affect the outcome of the scan. Clinicians should be aware of technical and biological factors that could result in negative scan in parathyroid nuclear scintigraphy.


Age biases in a large HIV and sexual behaviour-related internet survey among MSM.
Behavioural data from MSM are usually collected in non-representative convenience samples, increasingly on the internet. Epidemiological data from such samples might be useful for comparisons between countries, but are subject to unknown participation biases. Self-reported HIV diagnoses from participants of the European MSM Internet Survey (EMIS) living in the Czech Republic, Germany, The Netherlands, Portugal, Sweden and the United Kingdom were compared with surveillance data, for both the overall diagnosed prevalence and for new diagnoses made in 2009. Country level prevalence and new diagnoses rates per 100 MSM were calculated based on an assumed MSM population size of 3% of the adult male population. Survey-surveillance discrepancies (SSD) for survey participation, diagnosed HIV prevalence and new HIV diagnoses were determined as ratios of proportions. Results are calculated and presented by 5-year age groups for MSM aged 15-64. Surveillance derived estimates of diagnosed HIV prevalence among MSM aged 15-64 ranged from 0.63% in the Czech Republic to 4.93% in The Netherlands. New HIV diagnoses rates ranged between 0.10 per 100 MSM in the Czech Republic and 0.48 per 100 in The Netherlands. Self-reported rates from EMIS were consistently higher, with prevalence ranging from 2.68% in the Czech Republic to 12.72% in The Netherlands, and new HIV diagnoses rates from 0.36 per 100 in Sweden to 1.44 per 100 in The Netherlands. Across age groups, the survey surveillance discrepancies (SSD) for new HIV diagnoses were between 1.93 in UK and 5.95 in the Czech Republic, and for diagnosed prevalence between 1.80 in Germany and 4.26 in the Czech Republic.Internet samples of MSM were skewed towards younger age groups when compared to an age distribution of the general adult male population. Survey-surveillance discrepancies (SSD) for EMIS participation were inverse u-shaped across the age range. The two HIV-related SSD were u- or j-shaped with higher values for the very young and for older MSM. The highest discrepancies between survey and surveillance data regarding HIV-prevalence were observed in the oldest age group in Sweden and the youngest age group in Portugal. Internet samples are biased towards a lower median age because younger men are over-represented on MSM dating websites and therefore may be more likely to be recruited into surveys. Men diagnosed with HIV were over-represented in the internet survey, and increasingly so in the older age groups. A similar effect was observed in the age groups younger than 25 years. Self-reported peak prevalence and peak HIV diagnoses rates are often shifted to higher age groups in internet samples compared to surveillance data. Adjustment for age-effects on online accessibility should be considered when linking data from internet surveys with surveillance data.


Hydrogen Gas Ameliorates Hepatic Reperfusion Injury After Prolonged Cold Preservation in Isolated Perfused Rat Liver.
Hydrogen gas reduces ischemia and reperfusion injury (IRI) in the liver and other organs. However, the precise mechanism remains elusive. We investigated whether hydrogen gas ameliorated hepatic I/R injury after cold preservation. Rat liver was subjected to 48-h cold storage in University of Wisconsin solution. The graft was reperfused with oxygenated buffer with or without hydrogen at 37° for 90 min on an isolated perfusion apparatus, comprising the H2 (+) and H2 (-) groups, respectively. In the control group (CT), grafts were reperfused immediately without preservation. Graft function, injury, and circulatory status were assessed throughout the perfusion. Tissue samples at the end of perfusion were collected to determine histopathology, oxidative stress, and apoptosis. In the H2 (-) group, IRI was indicated by a higher aspartate aminotransferase (AST), alanine aminotransferase (ALT) leakage, portal resistance, 8-hydroxy-2-deoxyguanosine-positive cell rate, apoptotic index, and endothelial endothelin-1 expression, together with reduced bile production, oxygen consumption, and GSH/GSSG ratio (vs. CT). In the H2 (+) group, these harmful changes were significantly suppressed [vs. H2 (-)]. Hydrogen gas reduced hepatic reperfusion injury after prolonged cold preservation via the maintenance of portal flow, by protecting mitochondrial function during the early phase of reperfusion, and via the suppression of oxidative stress and inflammatory cascades thereafter.