Comparison of arthrodesis, resurfacing hemiarthroplasty, and total joint replacement in the treatment of advanced hallux rigidus.
The purpose of the present study was to compare the functional results of arthrodesis, resurfacing hemiarthroplasty, and total joint replacement in hallux rigidus. The data from patients treated from 2006 to 2010 for advanced stage hallux rigidus were retrospectively reviewed. A total of 38 patients who had at least 2 years (range 24 to 66 months, mean 31.1) of follow-up were included in the present study. Of the 38 patients, 12 were included in the total joint replacement group (group A), 14 in the resurfacing hemiarthroplasty group (group B), and 12 in the arthrodesis group (group C). At the last follow-up visit, the functional outcomes were evaluated using the American Orthopaedic Foot and Ankle Society-Hallux Metatarsophalangeal Interphalangeal (AOFAS-HMI) scale, visual analog scale (VAS), and metatarsophalangeal range of motion. Significant improvements were seen in the AOFAS-HMI score, with a decrease in the VAS score in all 3 groups. According to the AOFAS-HMI score, no significant difference was found between groups A and B. However, in group C, the AOFAS-HMI scores were significantly lower than in the other groups owing to the lack of motion. According to the final VAS scores, no significant difference was found between groups A and B; however, the VAS score had decreased significantly more in group C than in the other groups. No major complications occurred in any of the 3 groups. After 2 years of follow-up, all the groups had good functional outcomes. Although arthrodesis is still the most reliable procedure, implant arthroplasty is also a good alternative for advanced stage hallux rigidus.


Abdominal Wall Reconstruction Utilizing the Combination of Absorbable and Permanent Mesh in a Retromuscular Position: A Multicenter Prospective Study.
Optimal mesh reinforcement for abdominal wall reconstruction (AWR) in complex hernias remains questionable. Use of biologic, absorbable and synthetic meshes has been described. The idea of using an absorbable mesh (AM) under a permanent mesh (PM) in a retromuscular position may help in these challenging situations. Between 2011 and 2016, consecutive patients undergoing open AWR utilizing an AM as posterior layer reinforcement and configuration of a large PM were identified in a multicenter prospectively maintained database in four hospitals. Main outcomes included demographics, ventral hernia classifications, perioperative data, complications and recurrences. A total of 169 complex incisional hernias were analyzed. Mean age was 60.9, with mean body mass index 30.7 (range: 20-46). Location of incisional hernias (IH) was: 80 midline, 59 lateral and 30 midline and lateral. 78% were grade I and II in Ventral Hernia Working Group classification. 52% of patients were discharged with no complication. There were 19% seromas, 13% hematomas, 12% surgical-site infection and 10% skin dehiscence. Only partial mesh removal was necessary in one patient. After a mean follow-up of 26 months (range 15-59), there were five (3.2%) recurrences. Reoperations on patients showed a band of fibrosis separating the peritoneum from the PM. The combination of AM with very large PM in the same retromuscular position in AWR seems to be safe. The efficacy with recurrence rates below 4% in complex midline and lateral IH may be explained by the use of larger PMs that are extended and configured with the support of AMs. Reoperations on patients have confirmed the previous experimental reports on the use of the AM.


Generation of antigen-specific CD8+ CTLs from naive precursors.
Class I MHC-restricted CTLs are an important component of the host immune response against viral infections, and CTL effectors can often be isolated from infected individuals. However, the mechanism responsible for the induction of CTLs is incompletely understood because, in part, of the difficulty in generating such cells in vitro from naive precursors. In the present study we have used human peripheral blood dendritic cells (DCs), devoid of CD4+ T cells, to sensitize naive CD8+ T cells to exogenous Ags, resulting in the generation of Ag specific CTL effectors. With this system, Ag-specific CTL lines were generated to a complex glycoprotein, keyhole limpet hemocyanin, and to multiple small (9-15 amino acids) synthetic peptides derived from conserved regions of the HIV-1 gag and envelope proteins. The HIV-1-specific CTLs demonstrated potent HLA class I restricted killing of both Ag pulsed and virally infected target cells. In contrast to Ag-pulsed DCs, Ag-pulsed monocytes failed to sensitize CTL precursors although they could be used as feeders for purposes of CTL expansion and as target cells in cytolytic assays. With the use of the system described herein, a detailed analysis of the primary human T cell response to foreign Ags is now feasible, and CTL of desired specificity can be generated for potential clinical use in adoptive immunotherapy protocols.


Molecular mechanism for alkyl sulfide-modulated carbon tetrachloride-induced hepatotoxicity: the role of cytochrome P450 2E1, P450 2B and glutathione S-transferase expression.
The modulation of CCl4-induced hepatotoxicity in response to alkyl sulfides and alkyl ethers including allyl disulfide (ADS), allyl sulfide (AS), allyl ether (AE), propyl disulfide (PDS), propyl sulfide (PS), propyl ether (PE) and butyl sulfide (BS) was studied. Whereas pretreatment of rats with either ADS or AS (50 mg/kg, 7 days) blocked a CCl4-induced increase in plasma alanine aminotransferase (ALT) activity by 91 and 56%, respectively, AE, PDS, PS, PE or BS treatment enhanced CCl4-induced ALT activity by 52, 55, 238, 25 or 86%, respectively. Histochemical examinations supported the results of plasma ALT activity. Injection of GdCl3 to PS-pretreated rats failed to block the potentiated ALT increase, whereas GdCl3 completely prevented vitamin A-enhanced elevation of ALT activity. AS treatment completely blocked PS-potentiated CCl4 intoxication. Concomitant treatment of animals with both PS and vitamin A followed by a CCl4 insult resulted in super-potentiation of CCl4-induced hepatotoxicity, suggesting that the mechanism of PS-enhanced hepatotoxicity differs from that caused by vitamin A. Pyridine or phenobarbital potentiation of CCl4-induced increases in ALT activity implys that cytochrome P450 2E1 (P450 2E1) and P450 2B expression may be associated with the increased toxicity. P450 2E1 expression appeared to be associated with the alkyl sulfide-modulated hepatotoxicity, as evidenced by both immunoblot analyses and metabolic activity. P450 2B immunoblot analysis revealed that either AS or PS substantially induced hepatic P450 2B1/2 levels. Thus, PS-enhanced CCL4 hepatotoxicity may be related in part with P450 2B induction. ADS, AS or PS treatment caused increases in the glutathione S-transferase (GST) conjugating activity toward 1-chloro-2,4-dinitro-benzene. ADS, AS or PS induced Ya and Yb1 subunits by 2- to 3-fold. ADS or AS treatment also significantly elevated the levels of Yc subunits. PS failed to induce Yc expression, although this agent effectively increased Yb2 expression. Northern blot analyses revealed that ADS and AS concomitantly stimulated GST Ya, Yb1 and Yc2 gene expression, whereas PS increased the levels of Ya, Yb1, and Yb2 mRNA, but not Yc2 mRNA levels. The expression of GST subunit Yc2 in response to these compounds might be associated with hepatoprotective effects. These results demonstrate that ADS and AS have distinct capability of blocking CCl4-induced hepatotoxicity, whereas certain saturated alkyl sulfides rather potentiate CCl4-induced hepatotoxicity and that the underlying mechanism is associated with P450 2E1 and P450 2B expression, and possibly with certain GST expression.


Interactions between 2,4-bis-pteridine-1,5-benzodiazepine and group 12 dihalides: synthesis, spectral and XRD structural studies and theoretical calculations.
2,4-Bis(1,3,7-trimethyl-pteridine-2,4(1H,3H)-dione-6-yl)-2,3-dihydro-2-methyl-1H-1,5-benzodiazepine (DLMBZD) has been prepared and its molecular and crystal structures have been determined from spectral and XRD data. The benzodiazepine ligand was reacted with zinc(ii), cadmium(ii) and mercury(ii) chloride, bromide and iodide to give complexes with general formula [M(DLMBZD)X2]. The complexes have been synthesized and characterized by IR, NMR and elemental analysis. The structure of seven complexes has been obtained by single crystal X-ray diffraction. In all the cases, the metal is (2 + 2 + 1)-five-coordinated by two halide ligands, two nitrogen atoms from pyrazine and diazepine rings and a carbonyl oxygen from a pteridine ring. The coordinated-metal environment is a square-based pyramid, with increasing trigonality from Hg(ii) to Zn(ii) complexes. To coordinate the metals, the ligand folds itself, establishing four intramolecular σ-π interactions with the pyrimidine and pyrazine rings. A topological analysis of the electron density using the Quantum Theory of Atoms in Molecules and the complexes stability has been performed.


Dynamin-related protein 1 is implicated in endoplasmic reticulum stress-induced pancreatic β-cell apoptosis.
Pancreatic β-cell dysfunction is a critical component in the pathogenesis of diabetes. Endoplasmic reticulum (ER) stress is one of the factors that induces pancreatic β-cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we report that a mitochondrial fission modulator, dynamin-related protein 1 (DRP-1), plays an important role in ER stress-induced β-cell apoptosis. Induction of DRP-1 expression significantly promoted ER stress-induced apoptosis in the DRP-1 WT (DRP-1 wild- type) inducible β-cell line, but not in the DRP-1 K38A (a dominant negative mutant of DRP-1) inducible β-cell line. We further demonstrated that the mitochondrial membrane potential decreased, and that cytochrome c release, caspase-3 activation and generation of reactive oxygen species (ROS) were enhanced by induction of DRP-1 WT, but prevented by DRP-1 K38A in pancreatic β-cells under ER stress conditions. These results indicate that DRP-1 mediates ER stress-induced pancreatic β-cell apoptosis.


There should be more help out here! A qualitative study of the needs of Aboriginal adolescents in rural Australia.
Aboriginal adolescents living in or near rural towns have different social and cultural needs than Aboriginal adolescents living in large cities or remote areas. Identification of health needs by the community is an established principle of health promotion for improving community health. The objective of this study was to identify the views of rural Aboriginal adolescents regarding health promotion topics, the most important health problems they faced, their support networks and their beliefs about who should help them meet their health needs. Ninety-nine adolescents aged between 12 and 18 years were involved in in-depth interviews or focus group discussions using a tested and trialled questionnaire. Data collection took place at three sites in rural Australia from 2006 to 2008: two Aboriginal-controlled communities and one rural town. All locations were de-identified at the request of participants because confidentiality and anonymity were concerns of the adolescents, who felt that identifying their own community would result in stereotyping. After preliminary interviews with parents, teachers, youth and health workers, snowball sampling was used to identify 'vulnerable' adolescents with low school attendance. The mean age of respondents was 13 years. There were 40 male participants and 59 female participants, representing 6 language groups. Informed consent was obtained from both participants and their guardians. Data were analysed using thematic matrices and cross-checked in subsequent interactions with participants. Alcohol, drugs and violence were identified as the biggest problems facing Aboriginal adolescents in rural areas and the topic they would most like to know about. The youth from a smaller Aboriginal community near a town with a population of 1500 stated that boredom was an equally important problem. Racism and bullying were noted as reasons for poor school attendance. Family members were the most important supports, and the people they felt would help solve their health problems. They strongly identified with sports and were proud to be Aboriginal although there were many adolescents who had no future plans or ambitions. Most participants wanted a 'safe and fun' place to go to in the evenings. The importance of engaging the community and being sensitive to social and cultural contexts in research and programming was confirmed. Policy-makers, health providers and agencies working with youth need to focus on inclusion of families in youth health promotion and drug and alcohol prevention for Aboriginal adolescents in rural areas. Mentorship and peer-support programs are more effective than health professionals and agencies in working with youth. The expertise of those traditionally working with youth could be channelled into coordinating a mentorship program. Personal wellbeing and safety is an important issue and multipurpose youth centres may provide a secure place for adolescents to learn, interact and develop a vision for their futures.


Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter.
The role of members of the nuclear receptor superfamily of transcription factors in regulating hepatitis B virus (HBV) transcription was investigated. Hepatocyte nuclear factor 4 (HNF4), the retinoid X receptor (RXR), and the peroxisome proliferator-activated receptor (PPAR) were examined for their capacity to modulate the level of transcriptional activity from the four HBV promoters by transient-transfection analysis in the dedifferentiated hepatoma cell line, HepG2.1. It was found that the nucleocapsid and large surface antigen promoters were transactivated in the presence of HNF4 whereas the enhancer I/X gene, nucleocapsid, and large surface antigen promoters were transactivated in the presence of RXR and PPAR. Characterization of the nuclear receptors interacting with the nucleocapsid promoter region demonstrated that HNF4 is the primary transcription factor binding to the regulatory region spanning nucleotides -127 to -102 whereas HNF4, RXR-PPAR heterodimers, COUPTF1, and ARP1 bind the regulatory region spanning nucleotides -34 to -7. Transcriptional transactivation from the nucleocapsid promoter by HNF4 appears to be mediated through the two HNF4 binding sites in the promoter, whereas modulation of the level of transcription from the nucleocapsid promoter by RXR-PPAR appears to be regulated by the regulatory sequence element spanning nucleotides -34 to -7 and the HBV enhancer 1 region. These observations indicate that HBV transcription, and pregenomic RNA synthesis in particular, is regulated by ligand-dependent nuclear receptors. Agonists and antagonists capable of regulating the activity of these nuclear receptors may permit the modulation of HBV transcription and consequently replication during viral infection.


New taxa and taxonomic revisions to the Poraniidae (Valvatacea; Asteroidea) with comments on feeding biology.
New molecular phylogenetic data and new specimens provide the basis for a revision of the family Poraniidae. We present molecular phylogenetic data for five out of 11 genera in the Poraniidae including a newly discovered taxon from the North Pacific. Bathyporania ascendens nov. gen., nov. sp., is described from Davidson Seamount (35º43'N, 122º43'W). Another newly discovered poraniid taxon, Clavaporania fitchorum nov. gen., nov. sp. is described from south of Macquarie Island (56º21'S, 158º 28'E) but was not included in the analysis. Revision of the Poraniidae has been undertaken. We present two new genera and reinstate the previously synonymized genus Glabraster and return Culcitopsis to genus level. The genus Porania sensu Clark (1993) and Clark and Downey (1992) is not monophyletic. Porania, Poraniomorpha and Poraniopsis are revised. In situ feeding observations of Bathyporania are described and compared with other poraniid feeding accounts.


Reversible and formaldehyde-mediated covalent binding of a bis-amino mitoxantrone analogue to DNA.
The ability of a bis-amino mitoxantrone anticancer drug (named WEHI-150) to form covalent adducts with DNA, after activation by formaldehyde, has been studied by electrospray ionisation mass spectrometry and HPLC. Mass spectrometry results showed that WEHI-150 could form covalent adducts with d(ACGCGCGT)2 that contained one, two or three covalent links to the octanucleotide, whereas the control drugs (daunorubicin and the anthracenediones mitoxantrone and pixantrone) only formed adducts with one covalent link to the octanucleotide. HPLC was used to examine the extent of covalent bond formation of WEHI-150 with d(CGCGCG)2 and d(CG(5Me)CGCG)2. Incubation of WEHI-150 with d(CG(5Me)CGCG)2 in the presence of formaldehyde resulted in the formation of significantly greater amounts of covalent adducts than was observed with d(CGCGCG)2. In order to understand the observed increase of covalent adducts with d(CG(5Me)CGCG)2, an NMR study of the reversible interaction of WEHI-150 at both CpG and (5Me)CpG sites was undertaken. Intermolecular NOEs were observed in the NOESY spectra of d(ACGGCCGT)2 with added WEHI-150 that indicated that the drug selectively intercalated at the CpG sites and from the major groove. In particular, NOEs were observed from the WEHI-150 H2,3 protons to the H1' protons of G3 and G7 and from the H6,7 protons to the H5 protons of C2 and C6. By contrast, intermolecular NOEs were observed between the WEHI-150 H2,3 protons to the H2'' proton of the (5Me)C3 in d(CG(5Me)CGCG)2, and between the drug aliphatic protons and the H1' proton of G4. This demonstrated that WEHI-150 preferentially intercalates at (5Me)CpG sites, compared to CpG sequences, and predominantly via the minor groove at the (5Me)CpG site. The results of this study demonstrate that WEHI-150 is likely to form interstrand DNA cross-links, upon activation by formaldehyde, and consequently exhibit greater cytotoxicity than other current anthracenedione drugs.


Osteopathia striata with cranial sclerosis owing to WTX gene defect.
Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition marked by linear striations mainly affecting the metaphyseal region of the long bones and pelvis in combination with cranial sclerosis. Recently, the disease-causing gene was identified as the WTX gene (FAM123B), an inhibitor of WNT signaling. A correlation was suggested between the position of the mutation and male lethality. We performed genotype and phenotype studies using 18 patients from eight families with possible WTX gene defects and expanded the clinical spectrum of the affected females. All investigated families diagnosed with OSCS had WTX gene defects. One family had a WTX gene deletion; three of four point mutations were novel. The earlier reported WTX c.1072C>T was detected in four sporadic patients and appears to be a hotspot for mutations. Based on the nature of the mutation present in a surviving male patient, our data do not support the hypothesis raised by Jenkins et al. (2009) regarding a genotype-phenotype correlation for male lethality. The finding of a gene involved in WNT signaling as the cause of this sclerosing bone phenotype is not unexpected, but further functional studies are needed to explain the specific features. The WTX gene is mutated in different types of cancer, and it remains to be explained why osteopathia striata patients appear not to have an increased risk of cancer.


Dietary fiber for the treatment of type 2 diabetes mellitus: a meta-analysis.
The evidence of the relationship between fiber intake and control of diabetes is mixed. The purpose of this study was to determine if an increase in dietary fiber affects glycosylated hemoglobin (HbA1c) and fasting blood glucose in patients with type 2 diabetes mellitus. Randomized studies published from January 1, 1980, to December 31, 2010, that involved an increase in dietary fiber intake as an intervention, evaluated HbA1c and/or fasting blood glucose as an outcome, and used human participants with known type 2 diabetes mellitus were selected for review. Fifteen studies met inclusion and exclusion criteria. The overall mean difference of fiber versus placebo was a reduction of fasting blood glucose of 0.85 mmol/L (95% CI, 0.46-1.25). Dietary fiber as an intervention also had an effect on HbA1c over placebo, with an overall mean difference of a decrease in HbA1c of 0.26% (95% CI, 0.02-0.51). Overall, an intervention involving fiber supplementation for type 2 diabetes mellitus can reduce fasting blood glucose and HbA1c. This suggests that increasing dietary fiber in the diet of patients with type 2 diabetes is beneficial and should be encouraged as a disease management strategy.


Changes over time in the use of aspirin in patients hospitalized with acute myocardial infarction (1975 to 1997): a population-based perspective.
The purpose of this study was to examine 2 decade-long trends in the use of aspirin and associated outcomes in patients hospitalized with acute myocardial infarction. Aspirin has been shown to be beneficial in the secondary prevention of AMI. However, little is known about changes over time in the use of aspirin in patients hospitalized with AMI and associated outcomes, particularly from a more generalizable population-based perspective. We examined trends in aspirin use and hospital and long-term outcomes in 9336 metropolitan Worcester, Mass, residents hospitalized with validated AMI in all area hospitals between 1975 and 1997. Between 1975 and 1986, the hospital use of aspirin remained stable at approximately 20%. Use of aspirin increased markedly after this time from 49% in 1988 to 91% in 1997. Younger age, male sex, and a history of hypertension or stroke were associated with an increased likelihood of receiving aspirin. Patients with diabetes were less likely to receive aspirin than were patients without diabetes. Patients who received aspirin during hospitalization were more likely to receive beta-blockers and coronary interventions. Patients treated with aspirin were significantly less likely to have heart failure or cardiogenic shock develop or to die during hospitalization as compared with patients not treated with aspirin. Patients treated with aspirin had significantly higher survival rates over a 10-year follow-up period. The results of this community-wide study show that aspirin use in patients hospitalized with AMI has dramatically increased over time. Despite the beneficial effects associated with the use of aspirin, this therapy remains underused in several high-risk groups.


THRIVE score predicts outcomes with a third-generation endovascular stroke treatment device in the TREVO-2 trial.
Several outcome prediction scores have been tested in patients receiving acute stroke treatment with previous generations of endovascular stroke treatment devices. The TREVO-2 trial was a randomized controlled trial comparing a novel endovascular stroke treatment device (the Trevo device) to a previous-generation endovascular stroke treatment device (the Merci device). We used data from the TREVO-2 trial to validate the Totaled Health Risks in Vascular Events (THRIVE) score in patients receiving treatment with a third-generation endovascular stroke treatment device and to compare THRIVE to other predictive scores. We used logistic regression to model outcomes and compared score performance with receiver operating characteristic curve analysis. In the TREVO-2 trial, the THRIVE score strongly predicts clinical outcome and mortality. The relationship between THRIVE score and outcome is not influenced by either success of recanalization or the type of device used (Trevo versus Merci). The superiority of the Trevo device to the Merci device is evident particularly among patients with a low-to-moderate THRIVE score (0-5; 53.8% good outcome with Trevo versus 27.5% good outcome with Merci). In receiver operating characteristic curve analysis, the THRIVE score was comparable or superior to several other outcome prediction scores (HIAT, HIAT-2, SPAN-100, and iScore). The THRIVE score strongly predicts clinical outcome and mortality in the TREVO-2 trial. Taken together with THRIVE validation data from patients receiving intravenous tissue-type plasminogen activator or no acute treatment, the THRIVE score has broad predictive power in patients with acute ischemic stroke, which is likely because THRIVE reflects a set of strong nonmodifiable predictors of stroke outcome. A free Web calculator for the THRIVE score is available at http://www.thrivescore.org.


Crohn's disease mimicking as bowel endometriosis. Are the symptoms reduced by nafarelin acetate?
We report a 27-year-old female with Crohn's disease clinically misdiagnosed with intestinal endometriosis. Her complaints were abdominal pain and fullness, which occurred monthly during her menstrual period. Although we had no histopathological evidence, we diagnosed her as bowel endometriosis on the basis of her clinical course. Since nafarelin acetate therapy started, the symptoms due to mechanical subileus have improved. The transverse colon, a 70 cm segment of the ileum, including the terminal ileum, were resected because of repeated symptoms of bowel obstruction despite prolonged nafarelin therapy. Histopathological findings of the resected specimen revealed Crohn's disease without endometrial tissue. In our patient, an increased cortisol and ACTH secretion, a side effect of nafarelin, was noted during the therapy. This case showed that nafarelin therapy could increase serum concentration of ACTH and cortisol, which was considered to suppress the pathology of Crohn's disease by its anti-inflammatory action. We emphasize that intestinal examination must be performed with Crohn's disease in mind, even if nafarelin acetate is effective.


Autoimmune pancreatitis/IgG4-associated cholangitis and primary sclerosing cholangitis--overlapping or separate diseases?
Autoimmune pancreatitis is a recently described fibroinflammatory disease which is characterised by raised serum levels of IgG4 (in >70% of cases), and an IgG4-positive lymphoplasmacytic tissue infiltrate. A favourable and rapid clinical response to oral steroid therapy is often seen. Biliary involvement is common, and the term IgG4-associated cholangitis has recently been coined. The cholangiographic appearances of IgG4-associated cholangitis and primary sclerosing cholangitis can be difficult to differentiate. Moreover, raised levels of serum IgG4 have been recently found in 9% of patients with primary sclerosing cholangitis (a much higher frequency than for other gastrointestinal diseases), and those with raised levels appear to progress more rapidly to liver failure. Here we review the similarities and differences between the biliary disease in autoimmune pancreatitis and primary sclerosing cholangitis, and address the issue of disease overlap. Improvements in understanding the relationship between these conditions might lead to an enhanced understanding of the aetiopathogenesis, and improved treatment of both conditions.


Molecular mechanism of endothelial growth arrest by laminar shear stress.
This study was designed to elucidate the mechanism underlying the inhibition of endothelial cell growth by laminar shear stress. Tumor suppressor gene p53 was increased in bovine aortic endothelial cells subjected to 24 h of laminar shear stress at 3 dynes (1 dyne = 10 microN)/cm(2) or higher, but not at 1.5 dynes/cm(2). One of the mechanisms of the shear-induced increase in p53 is its stabilization after phosphorylation by c-Jun N-terminal kinase. To investigate the consequence of the shear-induced p53 response, we found that prolonged laminar shear stress caused increases of the growth arrest proteins GADD45 (growth arrest and DNA damage inducible protein 45) and p21(cip1), as well as a decrease in phosphorylation of the retinoblastoma gene product. Our results suggest that prolonged laminar shear stress causes a sustained p53 activation, which induces the up-regulation of GADD45 and p21(cip1). The resulting inhibition of cyclin-dependent kinase and hypophosphorylation of retinoblastoma protein lead to endothelial cell cycle arrest. This inhibition of endothelial cell proliferation by laminar shear stress may serve an important homeostatic function by preventing atherogenesis in the straight part of the arterial tree that is constantly subjected to high levels of laminar shearing.


Use of night vision goggles and low-level light source in obtaining intravenous access in tactical conditions of darkness.
The tactical environment of the nighttime battlefield precludes the use of white light to perform medical procedures. This study sought differences between two alternatives to white light used to facilitate intravenous access. A comparison was made between night vision goggles (NVG) and a low level light source (Fingerlite). Fifty-eight volunteers were paired. Each member of the pair attempted intravenous access on his or her partner in darkness using both techniques. One attempt per method was allowed. Success was confirmed by the free flow of blood from the catheter. Of the 58 attempts using NVG, 32 were successful and 26 failed. In the Fingerlite group, there were 46 successful attempts and 12 failures. These differences reached statistical significance (p < 0.02). This study suggests that in conditions requiring darkness, a Fingerlite offers a clinical advantage over NVG in obtaining intravenous access.


Drug therapy in the elderly.
Age-related biologic and physiologic changes in the elderly may lead to altered pharmacokinetics. Volume of distribution, half-life, systemic clearance, and receptor sensitivity have been shown to change with increasing age. Unique features of illness in the elderly may interfere with effective drug therapy more than changed pharmacokinetics in some patients. Physical, psychologic, and socioeconomic considerations often interfere with ability to obtain and comply with health care. Disease is often difficult to recognize in elderly patients. Multiple chronic conditions, many of which may be undetected, may be exacerbated by or alter drug therapy for other illnesses. Cognitive impairment and diminished vision and hearing may make patient education difficult, and compliance poor. The elderly are also more susceptible to adverse drug reactions. The recommendations for clinical practice and directions for future research that are presented should help make drug therapy in the elderly safer and more effective.


Life transitions and health insurance coverage of the near elderly.
This study addresses three issues. (1) What are demographic wealth, employment, and health characteristics of near-elderly persons losing or acquiring health insurance coverage? Specifically, (2) what are the effects of life transitions, including changes in employment status, health, and marital status? (3) To what extent do public policies protect such persons against coverage loss, including various state policies recently implemented to increase access to insurance? The authors used the 1992 and 1994 waves of the Health and Retirement Study to analyze coverage among adults aged 51 to 64 years. One in five near-elderly persons experienced a change in insurance coverage from 1992 to 1994. Yet, there was no significant change in the mix of coverage as those losing one form of coverage were replaced by others acquiring similar coverage. Individuals whose health deteriorated significantly were not more likely than others to suffer a subsequent loss of coverage, due to substitution of retiree or individual coverage for those losing private coverage and acquisition of Medicaid and Medicare coverage for one in five uninsured. State policies to increase access to private health insurance generally did not prevent individuals from losing coverage or allow the uninsured to gain coverage. Major determinants of the probability of being insured were education, employment status of person and spouse, and work disability status. Other measures of health and functional status did not affect the probability of being insured, but had important impacts on the probability of having public coverage, conditional on being insured.


Myopia Development Among Young Schoolchildren: The Myopia Investigation Study in Taipei.
To investigate the annual incidence of myopia and associated factors among young schoolchildren in Taipei City. The Myopia Investigation Study in Taipei was a citywide, population-based cohort study. During the fall 2013 semester (baseline), a total of 11,590 grade 2 schoolchildren completed ocular examination and were included for further analysis. A parent-completed questionnaire was administered to collect data on risk factors for myopia development. Follow-up visits were arranged biannually over 3 years. The first-year results are reported here. Schoolchildren who were emmetropic/hyperopic at baseline and had myopia (spherical equivalent ≤ -0.5 diopters) in either eye at follow-up were identified as having incident myopia. Among 7376 baseline nonmyopic participants, 6794 (92.1%) were examined during the first-year follow-up, and 1856 (25.2%) with incident myopia were identified. The incidence density of myopia was 31.7 (95% confidence interval [CI]: 30.6-32.8) per 100 person-years. Cox hazard proportional regression analysis revealed that participants who were emmetropic at baseline (hazards ratio [HR]: 19.37; 95% CI: 4.84-77.57), who had two myopic parents (HR: 1.21; 95% CI: 1.04-1.42), and who spent ≥5 hours every week on after-school tutoring programs (HR: 1.12; 95% CI: 1.02-1.22) had greater risk for incident myopia. By contrast, protective factors included suburban area of residence (HR: 0.91; 95% CI: 0.83-1.00) and spending ≥30 minutes outdoors after school every weekday (HR: 0.90; 95% CI: 0.82-0.99). This study provides population-based data on the annual incidence of myopia among Taiwanese schoolchildren, and found that baseline refractive status, parental myopia, area of residence, time outdoors after school on weekdays, and time spent on after-school tutoring programs are associated with risk of new-onset myopia.


Analysis of carboxy terminal domain of metalloprotease of elastolytic Aeromonas hydrophila.
We examined the ability of Aeromonas hydrophila to lyse elastin. Eight of 13 strains showed elastolytic activity on agar medium containing elastin and 5 strains did not. In order to examine the involvement of the metalloprotease of A. hydrophila (AMP) in elastolytic activity, we made the amp-deletion mutant strain from an elastolytic strain. The elastolytic activity of the strain decreased with this deletion. The analysis of AMP released into the culture supernatant showed that AMP appeared outside of the cell as the intermediate consisting of a mature domain and carboxy terminal (C-terminal) propeptide domain. Further analysis showed that the intermediate has the ability to lyse elastin and that loss of the C-terminal domain causes loss of the elastolytic activity of the intermediate. We then determined the nucleotide sequence of the amps of all strains used in this study. Phylogenetic analysis revealed that these AMPs were divided into three groups. The AMPs from elastolytic strains belong to group I or group II, and AMPs from non-elastolytic strains belong to group III. The distance between group I and group II is small, but group III is located separately from groups I and II. Comparison of the amino acid residues of the C-terminal domain revealed that there are 13 amino acid residues specific to the C-terminal domain of group III. This indicates that the conformation of the C-terminal propeptide domain formed by these specific amino acid residues is important for AMP to express elastolytic activity.


Suicide and deliberate self-harm in Pakistan: a scoping review.
Suicide is a major global public health problem with more than 800,000 incidents worldwide annually. Seventy-five percent of the global suicides occur in low and middle-income countries (LMICs). Pakistan is a LMIC where information on suicidal behavior is limited. The aim of the review is to map available literature on determinants, risk factors and other variables of suicidal behavior in Pakistan. This study was based on Arksey and O'Malley's methodological framework of scoping review, combining peer reviewed publications with grey literature. Ten databases including Applied Social Sciences Index and Abstracts (ASSIA), Cochrane Trials Register (CRG), Cumulative Index to Nursing and Allied Health (CINAHL), National Library of Medicine Gateway (NLMG), ExcerptaMedica (EMBASE), National Library of Medicine's MEDLINE (PUBMED), PSYCHINFO, Social Science Citation Index and Science Citation Index (SCI) and Pakmedinet.com were searched from the beginning of their time frames until December 2016 using a combination of key terms. The inclusion criteria included studies of various study designs covering different aspects of suicidal behavior in English language. Six hundred and twenty three articles were initially retrieved from all ten databases. Two independent reviewers screened the titles and abstracts for relevance. One hundred and eighteen articles were read in full, out of which 11 were excluded because they did not fit the eligibility criteria. One hundred and ten articles, including two student theses and one report, were included in the final review. Most studies were descriptive in nature, with only three that used a case-control design. Majority of the studies were from urban areas, and addressed determinants rather than risk factors. Gender differences and age were predominantly reported, with more males committing suicide. Suicidal behavior was more common among individuals younger than 30 years of age. The three most common methods for suicides were hanging, poisoning and use of firearms. Mental illness as a risk factor for suicides was mentioned in only three studies. This review is the first attempt to synthesize available literature on suicidal behavior in Pakistan. The evidence is limited, and calls for more robust analytical research designs, along with a focus on risk factors.


Harnessing the web information ecosystem with wiki-based visualization dashboards.
We describe the design and deployment of Dashiki, a public website where users may collaboratively build visualization dashboards through a combination of a wiki-like syntax and interactive editors. Our goals are to extend existing research on social data analysis into presentation and organization of data from multiple sources, explore new metaphors for these activities, and participate more fully in the web!s information ecology by providing tighter integration with real-time data. To support these goals, our design includes novel and low-barrier mechanisms for editing and layout of dashboard pages and visualizations, connection to data sources, and coordinating interaction between visualizations. In addition to describing these technologies, we provide a preliminary report on the public launch of a prototype based on this design, including a description of the activities of our users derived from observation and interviews.


A chalcogen-bonded complex H3N⋯S=C=S formed by ammonia and carbon disulfide characterised by chirped-pulse, broadband microwave spectroscopy.
Ground-state rotational spectra were observed for ten symmetric-top isotopologues H3N⋯S=C=S, H3N⋯34S=C=S, H3N⋯S=C=34S, H3N⋯S=13C=S, H3 15N⋯S=C=S, H3 15N⋯34S=C=S, H3 15N⋯S=C=34S, H3 15N⋯S=13C=S, H3 15N⋯33S=C=S, and H3 15N⋯S=C=33S, the first five in their natural abundance in a mixture of ammonia and carbon disulphide in argon and the second group with enriched 15NH3. The four asymmetric-rotor isotopomers H2DN⋯S=C=S, H2DN⋯34S=C=S, H2DN⋯S=C=34S, and HD2N⋯S=C=S were investigated by using a sample composed of ND3 mixed with CS2. Rotational constants, centrifugal distortion constants, and 33S nuclear quadrupole coupling constants were determined from spectral analyses and were interpreted with the aid of models of the complex to determine its symmetry, geometry, one measure of the strength of the intermolecular binding, and information about the subunit dynamics. The complex has C3v symmetry, with nuclei in the order H3N⋯S=C=S, thereby establishing that the non-covalent interaction is a chalcogen bond involving the non-bonding electron pair of ammonia as the nucleophile and the axial region near one of the S atoms as the electrophile. The small intermolecular stretching force constant kσ = 3.95(5) N m-1 indicates a weak interaction and suggests the assumption of unperturbed component geometries on complex formation. A simple model used to account for the contribution of the subunit angular oscillations to the zero-point motion leads to the intermolecular bond length r(N⋯S) = 3.338(10) Å.


Deep-LUMEN assay - human lung epithelial spheroid classification from brightfield images using deep learning.
Three-dimensional (3D) tissue models such as epithelial spheroids or organoids have become popular for pre-clinical drug studies. In contrast to 2D monolayer culture, the characterization of 3D tissue models from non-invasive brightfield images is a significant challenge. To address this issue, here we report a deep-learning uncovered measurement of epithelial networks (Deep-LUMEN) assay. Deep-LUMEN is an object detection algorithm that has been fine-tuned to automatically uncover subtle differences in epithelial spheroid morphology from brightfield images. This algorithm can track changes in the luminal structure of tissue spheroids and distinguish between polarized and non-polarized lung epithelial spheroids. The Deep-LUMEN assay was validated by screening for changes in spheroid epithelial architecture in response to different extracellular matrices and drug treatments. Specifically, we found the dose-dependent toxicity of cyclosporin can be underestimated if the effect of the drug on tissue morphology is not considered. Hence, Deep-LUMEN could be used to assess drug effects and capture morphological changes in 3D spheroid models in a non-invasive manner.


A Brief Historic Overview of Clinical Disorders Associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM).
Last century there was a short burst of interest in the tryptophan related disorders of pellagra and related abnormalities that are usually presented in infancy.1,2 Nutritional physiologists recognized that a severe human dietary deficiency of either tryptophan or the B group vitamins could result in central nervous system (CNS) sequelae such as ataxia, cognitive dysfunction and dysphoria, accompanied by skin hyperpigmentation.3,4 The current paper will focus on the emerging role of tryptophan in chronic fatigue syndrome (CFS) and fibromyalgia (FM).


Color structured light imaging of skin.
We illustrate wide-field imaging of skin using a structured light (SL) approach that highlights the contrast from superficial tissue scattering. Setting the spatial frequency of the SL in a regime that limits the penetration depth effectively gates the image for photons that originate from the skin surface. Further, rendering the SL images in a color format provides an intuitive format for viewing skin pathologies. We demonstrate this approach in skin pathologies using a custom-built handheld SL imaging system.


Mass Cytometry Reveals the Immaturity of Circulating Neutrophils during SIV Infection.
The infected host fails to eradicate HIV-1, despite significant control of viral replication by combinational antiretroviral therapy. Here, we assessed the impact of HIV infection on immune-cell compartments in a SIVmac251 nonhuman primate infection model, which allowed the choice of contamination route, time of infection, and treatment follow-up. We performed high-throughput multiparameter single-cell phenotyping by mass cytometry to obtain a global vision of the immune system in blood and bone marrow. Circulating polymorphonuclear neutrophils (PMNs) with impaired phagocytosis had altered surface expression of CD62L and CD11b during early chronic infection. The initiation of combinational antiretroviral treatment during primary infection did not restore PMN function. The maturation state of PMNs was highly altered during late chronic SIV infection, showing a primarily immature phenotype. Our results provide new insights into PMN involvement in the pathogenesis of HIV infection and may play a role in the establishment and maintenance of chronic immune activation.


Ketamine modulates theta and gamma oscillations.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor glutamatergic antagonist, has been studied as a model of schizophrenia when applied in subanesthetic doses. In EEG studies, ketamine affects sensory gating and alters the oscillatory characteristics of neuronal signals in a complex manner. We investigated the effects of ketamine on in vivo recordings from the CA3 region of mouse hippocampus referenced to the ipsilateral frontal sinus using a paired-click auditory gating paradigm. One issue of particular interest was elucidating the effect of ketamine on background network activity, poststimulus evoked and induced activity. We find that ketamine attenuates the theta frequency band in both background activity and in poststimulus evoked activity. Ketamine also disrupts a late, poststimulus theta power reduction seen in control recordings. In the gamma frequency range, ketamine enhances both background and evoked power, but decreases relative induced power. These findings support a role for NMDA receptors in mediating the balance between theta and gamma responses to sensory stimuli, with possible implications for dysfunction in schizophrenia.


IceBreaker: Software for high-resolution single-particle cryo-EM with non-uniform ice.
Despite the abundance of available software tools, optimal particle selection is still a vital issue in single-particle cryoelectron microscopy (cryo-EM). Regardless of the method used, most pickers struggle when ice thickness varies on a micrograph. IceBreaker allows users to estimate the relative ice gradient and flatten it by equalizing the local contrast. It allows the differentiation of particles from the background and improves overall particle picking performance. Furthermore, we introduce an additional parameter corresponding to local ice thickness for each particle. Particles with a defined ice thickness can be grouped and filtered based on this parameter during processing. These functionalities are especially valuable for on-the-fly processing to automatically pick as many particles as possible from each micrograph and to select optimal regions for data collection. Finally, estimated ice gradient distributions can be stored separately and used to inspect the quality of prepared samples.


The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases.
Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green leafy vegetables, orange and yellow fruits that form the macular pigment of the human eyes. It was hypothesized that they protect against visual disorders and cognition diseases, such as age-related macular degeneration (AMD), age-related cataract (ARC), cognition diseases, ischemic/hypoxia induced retinopathy, light damage of the retina, retinitis pigmentosa, retinal detachment, uveitis and diabetic retinopathy. The mechanism by which they are involved in the prevention of eye diseases may be due their physical blue light filtration properties and local antioxidant activity. In addition to their protective roles against light-induced oxidative damage, there are increasing evidences that L and Z may also improve normal ocular function by enhancing contrast sensitivity and by reducing glare disability. Surveys about L and Z supplementation have indicated that moderate intakes of L and Z are associated with decreased AMD risk and less visual impairment. Furthermore, this review discusses the appropriate consumption quantities, the consumption safety of L, side effects and future research directions.


Improved flexible refinement of protein docking in CAPRI rounds 22-27.
Since the fourth evaluation for critical assessment of prediction of interactions (CAPRI), we have made improvements in three major areas in our refinement approach, namely the treatment of conformational flexibility, the binding free energy model, and the search algorithm. First, we incorporated backbone flexibility into our previous approach, which only optimized rigid backbone poses with limited side-chain flexibility. Here, we formulated and solved the conformational search as a hierarchical optimization problem (involving rigid-body poses, backbone flexibility, and side-chain flexibility). Second, we used continuum electrostatic calculations to include solvation effects in the binding free energy model. Finally, we eliminated sloppy modes (directions in which the free energy is essentially constant) to improve the efficiency of the search. With these improvements, we produced correct predictions for 6 of the 10 latest CAPRI targets, including one high, three medium, and two acceptable accuracy predictions. Compared to our previous performance in CAPRI, substantial improvements have been made for targets requiring homology modeling.


The role of temperament in the relationship between early onset of tobacco and cannabis use: the TRAILS study.
While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1) temperamental characteristics predispose to EOT that on its turn predisposes to EOC, and (2) temperament moderates the importance of EOT on the progression to EOC. Data from 1848 (83%) participants in the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective population study of Dutch adolescents, were analyzed. We used parent-reports on the Early Adolescent Temperament Questionnaire to assess the dimensions of high-intensity pleasure, frustration, effortful control, shyness and fearfulness at age 10-12. EOT and EOC were defined as use at least once before the ages of 12 and 13 years, respectively, assessed by means of self-reports. We performed mediation and moderation analyses in Mplus. High levels of high-intensity pleasure predisposed to entrance in the trajectory from EOT to EOC. Once tobacco use had been initiated at early age, low levels of shyness and high levels of high-intensity pleasure increased the risk of progression to EOC. Besides a common liability for EOT and EOC based on temperament, the risk of transition from tobacco to cannabis use is modified by temperamental characteristics. Differences in interplay with other risk factors may explain the impact of temperament on distinct points along the substance use trajectory.


Early activation of CD4+ and CD8+ T lymphocytes by myelin basic protein in subjects with MS.
Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. In this study, whole blood samples were analyzed for activation capacity and the activatability of CD4+ and CD8+ T-lymphocytes by human total myelin basic protein (MBP), human MBP 104-118 fragment, and guinea pig MBP 68-82 fragment. Whole blood samples from healthy human subjects were compared with samples from patients with multiple sclerosis (MS). In particular, the expression of CD69, a surface marker of T-lymphocyte activity, was measured via flow cytometry before and after 14 h of incubation with human total MBP, MBP 104-118 fragment and/or guinea pig MBP 68-82 fragment. The results were compared between 15 patients with MS and 15 healthy subjects. In response to all three MBP forms, CD4+ and CD8+ T-lymphocytes from patients with MS demonstrated greater activatability than those from healthy subjects. These results indicate that in patients with MS, latent pre-activation to MBP epitopes results in an increased activation capacity of T-lymphocytes. This effect may occur because immunization against MBP (at least in a subset of patients) plays a pathophysiological role in MS pathogenesis. Alternatively, this result may represent a non-specific, bystander autoimmune phenomenon.


In vitro neurotoxic hazard characterization of different tricresyl phosphate (TCP) isomers and mixtures.
Exposure to tricresyl phosphates (TCPs), via for example contaminated cabin air, has been associated with health effects including the so-called aerotoxic syndrome. While TCP neurotoxicity is mainly attributed to ortho-isomers like tri-ortho-cresyl phosphate (ToCP), recent exposure and risk assessments indicate that ToCP levels in cabin air are very low. However, the neurotoxic potential of non-ortho TCP isomers and TCP mixtures is largely unknown. We therefore measured effects of exposure (up to 48h) to different TCP isomers, mixtures and the metabolite of ToCP (CBDP: cresyl saligenin phosphate) on cell viability and mitochondrial activity, spontaneous neuronal electrical activity, and neurite outgrowth in primary rat cortical neurons. The results demonstrate that exposure to TCPs (24-48h, up to 10μM) increases mitochondrial activity, without affecting cell viability. Effects of acute TCP exposure (30min) on neuronal electrical activity are limited. However, electrical activity is markedly decreased for the majority of TCPs (10μM) following 48h exposure. Additional preliminary data indicate that exposure to TCPs (48h, 10μM) did not affect the number of neurites per cell or average neurite length, except for TmCP and the analytical TCP mixture (Sigma) that induced a reduction of average neurite length. The combined neurotoxicity data demonstrate that the different TCPs, including ToCP, are roughly equipotent and a clear structure-activity relation is not apparent for the studied endpoints. The no-observed-effect-concentrations (1μM) are well above current exposure levels indicating limited neurotoxic health risk, although exposures may have been higher in the past. Moreover, prolonged and/or repeated exposure to TCPs may exacerbate the observed neurotoxic effects, which argues for additional research.


Sound production and hearing in the blue cracker butterfly Hamadryas feronia (Lepidoptera, nymphalidae) from Venezuela.
Certain species of Hamadryas butterflies are known to use sounds during interactions with conspecifics. We have observed the behaviour associated with sound production and report on the acoustic characteristics of these sounds and on the anatomy and physiology of the hearing organ in one species, Hamadryas feronia, from Venezuela. Our observations confirm previous reports that males of this species will take flight from their tree perch when they detect a passing conspecific (male or female) and, during the chase, produce clicking sounds. Our analyses of both hand-held males and those flying in the field show that the sounds are short (approximately 0.5 s) trains of intense (approximately 80-100 dB SPL at 10 cm) and brief (2-3 ms) double-component clicks, exhibiting a broad frequency spectrum with a peak energy around 13-15 kHz. Our preliminary results on the mechanism of sound production showed that males can produce clicks using only one wing, thus contradicting a previous hypothesis that it is a percussive mechanism. The organ of hearing is believed to be Vogel's organ, which is located at the base of the forewing subcostal and cubital veins. Vogel's organ consists of a thinned region of exoskeleton (the tympanum) bordered by a rigid chitinous ring; associated with its inner surface are three chordotonal sensory organs and enlarged tracheae. The largest chordotonal organ attaches to a sclerite positioned near the center of the eardrum and possesses more than 110 scolopidial units. The two smaller organs attach to the perimeter of the membrane. Extracellular recordings from the nerve branch innervating the largest chordotonal organ confirm auditory sensitivity with a threshold of 68 dB SPL at the best frequency of 1.75 kHz. Hence, the clicks with peak energy around 14 kHz are acoustically mismatched to the best frequencies of the ear. However, the clicks are broad-banded and even at 1-2 kHz, far from the peak frequency, the energy is sufficient such that the butterflies can easily hear each other at the close distances at which they interact (less than 30 cm). In H. feronia, Vogel's organ meets the anatomical and functional criteria for being recognized as a typical insect tympanal ear.


Audit of oxygen use in emergency ambulances and in a hospital emergency department.
Oxygen is widely used but poorly studied in emergency medicine, with a limited evidence base for its use in specific conditions. There are safety concerns about the underuse of oxygen in patients with critical illness and its overuse in conditions such as chronic obstructive pulmonary disease (COPD). A baseline audit was required to assess current practice prior to the introduction of new national emergency oxygen guidelines in late 2008. The use of pulse oximetry and oxygen therapy was audited in patients brought by ambulance to the "majors" section of the emergency department (ED) in a university hospital. Oxygen therapy in the ambulance and the ED was subsequently documented. Oxygen use in ambulances was compared with Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidance and with subsequent patient management. The ambulance and ED records of 1022 patients were audited manually. Oxygen saturation (SpO(2)) was recorded for 90% of patients, 17% of whom had SpO(2) <94% at some time and 7% had SpO(2) <90%, including 33% of patients with COPD and 5.5% of patients without COPD. 34% of patients received oxygen in the ambulance and almost half of these had oxygen discontinued in the ED. Only 62% of ambulance oxygen use was in accordance with JRCALC guidance, but most "undertreated" patients were stable normoxaemic patients for whom guidance recommends high-flow oxygen. Only 58% of patients with COPD were correctly identified in the ambulance and 73% of these patients were treated with flow rates >4 l/min (equivalent to >35% oxygen). Oxygen use in ambulances is very common, equivalent to 2.2 million episodes annually in the UK. The quality of oxygen use is suboptimal, especially for patients with COPD. Emergency oxygen therapy will become simpler when new evidence-based UK emergency oxygen guidelines are published, and it is hoped that future audits will show better protocol adherence.


Recapitulating the human tumor microenvironment: Colon tumor-derived extracellular matrix promotes angiogenesis and tumor cell growth.
Extracellular matrix (ECM) is an essential and dynamic component of all tissues and directly affects cellular behavior by providing both mechanical and biochemical signaling cues. Changes in ECM can alter tissue homeostasis, potentially leading to promotion of cellular transformation and the generation of tumors. Therefore, understanding ECM compositional changes during cancer progression is vital to the development of targeted treatments. Previous efforts to reproduce the native 3D cellular microenvironment have utilized protein gels and scaffolds that incompletely recapitulate the complexity of native tissues. Here, we address this problem by extracting and comparing ECM from normal human colon and colon tumor that had metastasized to liver. We found differences in protein composition and stiffness, and observed significant differences in vascular network formation and tumor growth in each of the reconstituted matrices, both in vitro and in vivo. We studied free/bound ratios of NADH in the tumor and endothelial cells using Fluorescence Lifetime Imaging Microscopy as a surrogate for the metabolic state of the cells. We observed that cells seeded in tumor ECM had higher relative levels of free NADH, consistent with a higher glycolytic rate, than those seeded in normal ECM. These results demonstrate that the ECM plays an important role in the growth of cancer cells and their associated vasculature.


Photobiomodulation therapy (PBMT) and/or cryotherapy in skeletal muscle restitution, what is better? A randomized, double-blinded, placebo-controlled clinical trial.
Cryotherapy for post-exercise recovery remains widely used despite the lack of quality evidence. Photobiomodulation therapy (PBMT) studies (with both low-level laser therapy and light-emitting diode therapy) have demonstrated positive scientific evidence to suggest its use. The study aims to evaluate PBMT and cryotherapy as a single or combined treatment on skeletal muscle recovery after eccentric contractions of knee extensors. Fifty healthy male volunteers were recruited and randomized into five groups (PBMT, cryotherapy, cryotherapy + PBMT, PMBT + cryotherapy, or placebo) for a randomized, double-blinded, placebo-controlled trial that evaluated exercise performance (maximum voluntary contraction (MVC)), delayed onset muscle soreness (DOMS), and muscle damage (creatine kinase (CK)). Assessments were performed at baseline; immediately after; and at 1, 24, 48, 72, and 96 h. Comparator treatments was performed 3 min after exercise and repeated at 24, 48, and 72 h. PBMT was applied employing a cordless, portable GameDay™ device (combination of 905 nm super-pulsed laser and 875- and 640-nm light-emitting diodes (LEDs); manufactured by Multi Radiance Medical™, Solon - OH, USA), and cryotherapy by flexible rubber ice packs. PBMT alone was optimal for post-exercise recovery with improved MVC, decreased DOMS, and CK activity (p < 0.05) from 24 to 96 h compared to placebo, cryotherapy, and cryotherapy + PBMT. In the PBMT + cryotherapy group, the effect of PBMT was decreased (p > 0.05) but demonstrated significant improvement in MVC, decreased DOMS, and CK activity (p < 0.05). Cryotherapy as single treatment and cryotherapy + PBMT were similar to placebo (p > 0.05). We conclude that PBMT used as single treatment is the best modality for enhancement of post-exercise restitution, leading to complete recovery to baseline levels from 24 h after high-intensity eccentric contractions.


A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis.
Osteoporosis, especially in postmenopausal women, delineates a major health and economic problem in the world. Regarding the pathogenesis of osteoporosis and the interaction between various cells and mediators, many studies have been conducted to evaluate the benefit of different therapeutic options. Over the past several years evidence has been growing on the effects of dietary fatty acids on bone health. The objective of this paper was to provide a review of the current knowledge of dietary fatty acids and osteoporosis. Medline/Index Medicus and EMBASE/Excerpta Medica were searched for relevant papers regarding the effects of n-3 fatty acids on osteoporosis between 1963 and 2007 using the key words: osteoporosis, bone health, n-3 fatty acids, and PUFA. Bone mineral density and bone markers have been used in several animal studies to evaluate the beneficial effect of n-3 fatty acids on bone health and the prevention of osteoporosis. Generally, animal studies support the beneficial effects of n-3 fatty acids on bone health and osteoporosis; however, the dissimilar lipid metabolism in human and animals, the various study designs, and controversies over the human study outcomes make it difficult to draw a definite conclusion. The authors believe that conclusive findings in humans are still lacking in this area and it needs to be further investigated.


Methicillin Resistant Staphylococcus aureus Transmission in a Ghanaian Burn Unit: The Importance of Active Surveillance in Resource-Limited Settings.
Objectives:Staphylococcus aureus infections in burn patients can lead to serious complications and death. The frequency of S. aureus infection is high in low- and middle-income countries presumably due to limited resources, misuse of antibiotics and poor infection control. The objective of the present study was to apply population genomics to precisely define, for the first time, the transmission of antibiotic resistant S. aureus in a resource-limited setting in sub-Saharan Africa. Methods:Staphylococcus aureus surveillance was performed amongst burn patients and healthcare workers during a 7-months survey within the burn unit of the Korle Bu Teaching Hospital in Ghana. Results: Sixty-six S. aureus isolates (59 colonizing and 7 clinical) were obtained from 31 patients and 10 healthcare workers. Twenty-one of these isolates were ST250-IV methicillin-resistant S. aureus (MRSA). Notably, 25 (81%) of the 31 patients carried or were infected with S. aureus within 24 h of admission. Genome comparisons revealed six distinct S. aureus clones circulating in the burn unit, and demonstrated multiple transmission events between patients and healthcare workers. Further, the collected S. aureus isolates exhibited a wide range of genotypic resistances to antibiotics, including trimethoprim (21%), aminoglycosides (33%), oxacillin (33%), chloramphenicol (50%), tetracycline (59%) and fluoroquinolones (100%). Conclusion: Population genomics uncovered multiple transmission events of S. aureus, especially MRSA, within the investigated burn unit. Our findings highlight lapses in infection control and prevention, and underscore the great importance of active surveillance to protect burn victims against multi-drug resistant pathogens in resource-limited settings.


Dietary supplementation practices in Canadian high-performance athletes.
Dietary supplementation is a common practice in athletes with a desire to enhance performance, training, exercise recovery, and health. Supplementation habits of elite athletes in western Canada have been documented, but research is lacking on supplement use by athletes across Canada. The purpose of this descriptive study was to evaluate the dietary supplementation practices and perspectives of high-performance Canadian athletes affiliated with each of the country's eight Canadian Sport Centres. Dietitians administered a validated survey to 440 athletes (63% women, 37% men; M=19.99±5.20 yr) representing 34 sports who predominantly trained≥16 hr/wk, most competing in "power" based sports. Within the previous 6 months, 87% declared having taken≥3 dietary supplements, with sports drinks, multivitamin and mineral preparations, carbohydrate sports bars, protein powder, and meal-replacement products the most prevalent supplements reported. Primary sources of information on supplementation, supplementation justification, and preferred means of supplementation education were identified. Fifty-nine percent reported awareness of current World Anti-Doping Agency legislation, and 83% subjectively believed they were in compliance with such anti-doping regulations. It was concluded that supplementation rates are not declining in Canada, current advisors on supplementation for this athletic population are not credible, and sports medicine physicians and dietitians need to consider proactive strategies to improve their influence on supplementation practices in these elite athletes.


Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas.
Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.


Impaired control of renal hemodynamics and renin release during hyperkalemia in rabbits.
We analyzed the changes in control of renal hemodynamics and renin release resulting from hyperkalemia in the rabbit. Plasma potassium activity was maintained at a controlled elevated level by intravenous infusion of KCl. The potassium activity of the control group (n = 23) averaged 3.20 +/- 0.06 meq/l and that of the hyperkalemic group (n = 13) averaged 5.80 +/- 0.13 meq/l. Renal blood flow (RBF), glomerular filtration rate (GFR), and renin release were measured over a range of renal perfusion pressures achieved by constriction of the suprarenal aorta. The control group's RBF and GFR exhibited excellent autoregulatory capability from 100 to 80 mmHg. However, significant impairment of autoregulation was apparent in the hyperkalemic group. At 100 mmHg, RBF and GFR in the hyperkalemic group averaged 33 and 34% greater, respectively, than those of the control group (P less than 0.005); both variables in the hyperkalemic group were greater than the values of the control group over the autoregulatory range (100-80 mmHg). The renin release values for the two groups were not different at the 100-mmHg pressure level, although renin release of the hyperkalemic group increased to higher levels than those of the control group as perfusion pressure was reduced. At the 70- and 60-mmHg levels renin release from the hyperkalemic group averaged approximately 300% greater than that of the control group (P less than 0.05). However, when expressed as percentage change, the stimulatory effect of hyperkalemia was not apparent.(ABSTRACT TRUNCATED AT 250 WORDS)


Immune responses following cocktails of inactivated measles vaccine and Arachis hypogaea L. (groundnut) or Cocos nucifera L. (coconut) oils adjuvant.
Haemagglutination inhibition (HAI), geometric mean titre (GMT) and lymphocyte transformation test (LTT) were measured following inoculation of Erythrocebus patas with inactivated measles vaccine (IMV) and oils of Arachis hypogaea L (GO), Cocos nucifera L (CO), Freund's complete and incomplete adjuvants (FCA, FIA). The GMT of HAI were: GO + IMV = 8.50 +/- 4.15: CO + IMV = 8.08 +/- 4.03; FCA + IMV = 7.67 +/- 4.08. FIA + IMV = 7.08 +/- 4.08 compared with controls of live measles vaccine (LMV) = 7.33 +/- 4.33 and IMV = 4.33 +/- 4.56. The mean stimulation ratio (SR) of lymphocyte transformation data were: GO + IMV = 109 69; CO + IMV = 58.47; FCA + IMV = 55.81. FIA + IMV = 55.48; LMV = 94.73; IMV = 55.64. The results when compared by a two-way multiple pairwise comparison of Tuskey's procedure at alpha = 0.05 showed that HAI antibody titres were not significantly different in all the groups under investigation. The lymphocyte transformation data for GO + IMV and LMV were identical but significantly different from the other groups. The study suggests that the oils under investigation, particularly the GO oil should be considered as an adjuvant with IMV after extensive study in humans; since it stimulated cellular immune response comparable to that of LMV. This is a promising alternative to the use of LMV in the tropical developing countries with poor storage facilities.


Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF.
The aim of this study was to investigate the effect of treatment with dehydroepiandrosterone (DHEA) on fertility outcomes among women with diminished ovarian reserve. This is a case-control study in an academically affiliated private infertility centre. Twenty-five women with significantly diminished ovarian reserve had one IVF cycle before and after DHEA treatment, with otherwise identical hormonal stimulation. Women received 75 mg of DHEA daily (25 mg three times daily) for an average of 17.6 +/- 2.13 weeks. We performed a comparison of IVF outcome parameters, before and after DHEA treatment, including peak estradiol (E(2)) levels, oocyte and embryo numbers, oocyte and embryo quality and embryo transfer statistics. Paired analysis of IVF cycle outcomes in 25 patients, who underwent cycles both before and after DHEA supplementation, demonstrated significant increases in fertilized oocytes (P < 0.001), normal day 3 embryos (P = 0.001), embryos transferred (P = 0.005) and average embryo scores per oocyte (P < 0.001) after DHEA treatment. This study confirms the previously reported beneficial effects of DHEA supplementation on ovarian function in women with diminished ovarian reserve.


dSPRINT: predicting DNA, RNA, ion, peptide and small molecule interaction sites within protein domains.
Domains are instrumental in facilitating protein interactions with DNA, RNA, small molecules, ions and peptides. Identifying ligand-binding domains within sequences is a critical step in protein function annotation, and the ligand-binding properties of proteins are frequently analyzed based upon whether they contain one of these domains. To date, however, knowledge of whether and how protein domains interact with ligands has been limited to domains that have been observed in co-crystal structures; this leaves approximately two-thirds of human protein domain families uncharacterized with respect to whether and how they bind DNA, RNA, small molecules, ions and peptides. To fill this gap, we introduce dSPRINT, a novel ensemble machine learning method for predicting whether a domain binds DNA, RNA, small molecules, ions or peptides, along with the positions within it that participate in these types of interactions. In stringent cross-validation testing, we demonstrate that dSPRINT has an excellent performance in uncovering ligand-binding positions and domains. We also apply dSPRINT to newly characterize the molecular functions of domains of unknown function. dSPRINT's predictions can be transferred from domains to sequences, enabling predictions about the ligand-binding properties of 95% of human genes. The dSPRINT framework and its predictions for 6503 human protein domains are freely available at http://protdomain.princeton.edu/dsprint.


The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions.
Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920-1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program (http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_home.html).


Observational Evidence of the Association Between Handgrip Strength, Hand Dexterity, and Cognitive Performance in Community-Dwelling Older Adults: A Systematic Review.
Deterioration of hand motor function is a possible risk factor of cognitive impairment in older adults. Despite a growing body of research, a lack of clarity exists regarding the relationships. This review offers a synthesis of existing observational studies evaluating the associations of handgrip strength and hand dexterity with cognitive performance in community-dwelling older adults. PubMed, PsycINFO, and ScienceDirect were systematically searched (search dates: 1990-2016), and relevant articles were cross-checked for related and relevant publications. Twenty-two observational studies assessed the association of handgrip strength or hand dexterity with cognitive performance; none evaluated handgrip strength and hand dexterity together. Handgrip strength was associated with global cognition, mostly assessed using the Mini-Mental State Examination, cross-sectionally and longitudinally. Also, one cross-sectional and three longitudinal studies found an association with cognitive domains, such as language, memory, visuospatial ability, working memory, and processing speed. Hand dexterity was only assessed cross-sectionally in four studies. These studies found an association with cognitive domains, such as executive function. Although handgrip strength was associated with cognitive performance, it is unclear which variable at baseline affects the other in the long-term. Cross-sectional studies indicate an association between hand dexterity and cognitive performance, yet longitudinal studies are needed to elucidate this association. The interaction effects of both decreased grip strength and hand dexterity on cognitive performance is still unclear; therefore, future studies will need to consider the interaction of the three variables cross-sectionally and longitudinally.


Extracellular signal-regulated kinases phosphorylate 5-lipoxygenase and stimulate 5-lipoxygenase product formation in leukocytes.
5-lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. Here, we demonstrate that extracellular signal-regulated kinases (ERKs) can phosphorylate 5-LO in vitro. Efficient phosphorylation required the presence of unsaturated fatty acids and was abolished when Ser-663 was mutated to alanine. In intact HeLa cells stimulated with arachidonic acid (AA), impaired 5-LO product formation was evident in cells expressing the S663A-5-LO mutant compared with cells expressing wild-type 5-LO. For Mono Mac 6 cells, priming with phorbol myristate acetate (PMA) before stimulation with ionophore was required for ERK1/2 activation and efficient 5-LO phosphorylation, in parallel with substantial AA release and 5-LO product formation. Inhibition of PKC by GF109203x or MEK1/2 by U0126 (or PD98059) abolished the 5-LO up-regulation effects of PMA. In contrast, these inhibitors failed to suppress 5-LO product formation induced by stimuli such as AA plus ionophore, which apparently do not involve the ERK1/2 pathway. Based on inhibitor studies, ERKs are also involved in AA-stimulated 5-LO product formation in PMNL, whereas a role for ERKs is not apparent in 5-LO activation induced by ionophore or cell stress. Finally, the data suggest that ERKs and p38 MAPK-regulated MAPKAPKs can act in conjunction to stimulate 5-LO by phosphorylation.


Biological motion perception is cue-invariant.
Previous work investigating whether biological motion is supported by local second-order motion has been contradictory, with different groups finding either a difference or no difference in performance compared to that obtained with first-order stimuli. Here we show psychophysically, using randomized-polarity and contrast-modulated stimuli, that detection of second-order biological motion walkers is worse for stimuli defined by second-order cues, but this difference is explained by a difference in visibility of the local motion in the stimuli. By mixing first-order and second-order dots within the same stimulus, we show that, when the two types of dot are equally visible, first-order noise dots can mask a second-order walker, and vice-versa. We also show that direction-discrimination of normal, inverted and scrambled walkers follow the same pattern for second-order as that obtained with first-order stimuli. These results are consistent with biological motion being processed by a mechanism that is cue-invariant.


Evidence for a fundamental and pervasive shift away from nature-based recreation.
After 50 years of steady increase, per capita visits to U.S. National Parks have declined since 1987. To evaluate whether we are seeing a fundamental shift away from people's interest in nature, we tested for similar longitudinal declines in 16 time series representing four classes of nature participation variables: (i) visitation to various types of public lands in the U.S. and National Parks in Japan and Spain, (ii) number of various types of U.S. game licenses issued, (iii) indicators of time spent camping, and (iv) indicators of time spent backpacking or hiking. The four variables with the greatest per capita participation were visits to Japanese National Parks, U.S. State Parks, U.S. National Parks, and U.S. National Forests, with an average individual participating 0.74-2.75 times per year. All four time series are in downtrends, with linear regressions showing ongoing losses of -1.0% to -3.1% per year. The longest and most complete time series tested suggest that typical declines in per capita nature recreation began between 1981 and 1991, are proceeding at rates of -1.0% to -1.3% per year, and total to date -18% to -25%. Spearman correlation analyses were performed on untransformed time series and on transformed percentage year-to-year changes. Results showed very highly significant correlations between many of the highest per capita participation variables in both untransformed and in difference models, further corroborating the general downtrend in nature recreation. In conclusion, all major lines of evidence point to an ongoing and fundamental shift away from nature-based recreation.


Spatial Distribution and Burden of Emerging Arboviruses in French Guiana.
Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6-75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7-23.1), 23.3% (20.9-25.9) and 3.3% (2.7-4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns.


The Kynurenine Pathway and Polycystic Ovary Syndrome: Inflammation as a Common Denominator.
Polycystic ovary syndrome (PCOS) is a complex metabolic disorder commonly seen in females of reproductive age. The pathophysiology of PCOS is multifactorial and includes dysfunction in ovarian steroidogenesis and folliculogenesis, impaired gonadotropin levels, insulin resistance, gut microbiota imbalance, genetic predisposition, and lifestyle preferences. Low-grade inflammatory conditions such as obesity and impaired glucose tolerance are common metabolic disturbances in women with PCOS. A growing body of literature suggests strong evidence rendering PCOS in close proximity with chronic inflammation as documented by high levels of serum white blood cells, C-reactive protein, and various proinflammatory cytokines seen in this condition. Inflammation seems to be the most common metabolic denominator between the kynurenine pathway and PCOS. The association of tryptophan and kynurenine pathway has already been well documented in mood disorders, neurodegenerative diseases, chronic pain conditions, and different inflammatory states. In this manuscript, we describe the influence of sex steroid hormones on different enzymes of the KP; inflammatory nature of PCOS and CRP as a marker of IDO/TDO activity; and the effects of altered gut flora in women with PCOS. This review provides a novel view of the available evidence of tryptophan and downstream metabolites in PCOS in the context of underlying inflammation.


Conservative and individualized surgery for early squamous carcinoma of the vulva: the treatment of choice for stage I and II (T1-2N0-1M0) disease.
We studied the outcome of patients undergoing radical local excision (modified radical vulvectomy) with inguinal-femoral lymphadenectomy through separate groin incisions for stage I and II invasive squamous carcinoma of the vulva. The purpose was to determine whether less radical and more individualized surgery is consistent with local control and cure. We have reported previously our experience using radical local excision and modified radical vulvectomy in stage I disease (Obstet. Gynecol. 63, 155 (1984)) and with separate groin incisions (Obstet. Gynecol. 58, 574 (1981)). This current report expands our experience with stage I and adds stage II patients treated over the past decade. Seventy-four patients were studied retrospectively over the 5-year period ending in January 1990. Reviews of both patient charts and histopathology reports were correlated with recurrence and survival. Factors analyzed included FIGO stage and grade, histology, lesion size and depth of invasion, surgical procedure, radiotherapy, lymph node status, interval to and site of recurrence, and survival. Thirty-nine patients had stage I disease and 35 had stage II. The primary operation was a radical local excision (modified radical vulvectomy) in 56 patients and radical vulvectomy in 18 patients; 13 underwent ipsilateral inguinal-femoral lymphadenectomy and 58 bilateral lymphadenectomy, each through separate groin incisions. The survival of those treated conservatively (97 and 90% for stages I and II, respectively) is the same as those undergoing a radical vulvectomy (100 and 75% for stages I and II, respectively) with only the presence of inguinal-femoral lymph node metastases impacting negatively on survival. In the entire group, the survival for negative and positive nodes was 98 and 45%, respectively. In conclusion, conservative, modified, and individualized vulvectomy in both stage I and II disease is associated with the same outcome and survival as radical vulvectomy, and lymph node status is the most important prognostic factor.


Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study.
The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (κ) was utilized to measure the degree of agreement between MS definitions. The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (κ= 0.89), in particular between JIS and IDF (κ = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels.


CNE article: safety culture in Australian intensive care units: establishing a baseline for quality improvement.
Workplace safety culture is a crucial ingredient in patients' outcomes and is increasingly being explored as a guide for quality improvement efforts. To establish a baseline understanding of the safety culture in Australian intensive care units. In a nationwide study of physicians and nurses in 10 Australian intensive care units, the Safety Attitudes Questionnaire intensive care unit version was used to measure safety culture. Descriptive statistics were used to summarize the mean scores for the 6 subscales of the questionnaire, and generalized-estimation-equations models were used to test the hypotheses that safety culture differed between physicians and nurses and between nurse leaders and bedside nurses. A total of 672 responses (50.6% response rate) were received: 513 (76.3%) from nurses, 89 (13.2%) from physicians, and 70 (10.4%) from respondents who did not specify their professional group. Ratings were highest for teamwork climate and lowest for perceptions of hospital management and working conditions. Four subscales, job satisfaction, teamwork climate, safety climate, and working conditions, were rated significantly higher by physicians than by nurses. Two subscales, working conditions and perceptions of hospital management, were rated significantly lower by nurse leaders than by bedside nurses. Measuring the baseline safety culture of an intensive care unit allows leaders to implement targeted strategies to improve specific dimensions of safety culture. These strategies ultimately may improve the working conditions of staff and the care that patients receive.


Measuring the condensate fraction of rapidly rotating trapped boson systems: off-diagonal order from the density profile.
We demonstrate a direct connection between the density profile of a system of ultracold trapped bosonic particles in the rapid-rotation limit and its condensate fraction. This connection can be used to probe the crossover from condensed vortex-lattice states to uncondensed quantum-fluid states that occurs in rapidly rotating boson systems as the particle density decreases or the rotation frequency increases. We illustrate our proposal with a series of examples, including ones based on models of realistic finite trap systems, and comment on its application to freely expanding boson density profile measurements.


Health care inequities in north India: role of public sector in universalizing health care.
Income inequality is associated with poor health. Inequities exist in service utilization and financing for health care. Health care costs push high number of households into poverty in India. We undertook this study to ascertain inequities in health status, service utilization and out-of-pocket (OOP) health expenditures in two States in north India namely, Haryana and Punjab, and Union Territory of Chandigarh. Data from National Sample Survey 60 th Round on Morbidity and Health Care were analyzed by mean consumption expenditure quintiles. Indicators were devised to document inequities in the dimensions of horizontal and vertical inequity; and redistribution of public subsidy. Concentration index (CI), and equity ratio in conjunction with concentration curve were computed to measure inequity. Reporting of morbidity and hospitalization rate had a pro-rich distribution in all three States indicating poor utilization of health services by low income households. Nearly 57 and 60 per cent households from poorest income quintile in Haryana and Punjab, respectively faced catastrophic OOP hospitalization expenditure at 10 per cent threshold. Lower prevalence of catastrophic expenditure was recorded in higher income groups. Public sector also incurred high costs for hospitalization in selected three States. Medicines constituted 19 to 47 per cent of hospitalization expenditure and 59 to 86 per cent OPD expenditure borne OOP by households in public sector. Public sector hospitalizations had a pro-poor distribution in Haryana, Punjab and Chandigarh. Our analysis indicates that public sector health service utilization needs to be improved. OOP health care expenditures at public sector institutions should to be curtailed to improve utilization of poorer segments of population. Greater availability of medicines in public sector and regulation of their prices provide a unique opportunity to reduce public sector OOP expenditure.


Vomeronasal and olfactory system modulation of maternal behavior in the rat.
The onset of maternal responsiveness by virgin female rats to foster pups was observed after (i) complete vomeronasal nerve cuts, (ii) partial olfactory bulb cuts, or (iii) the combined procedures. Although both vomeronasal nerve cuts and olfactory bulb cuts resulted in a more rapid onset of maternal care, relative to control animals with sham operations, animals sustaining the loss of both sources of olfactory input exhibited the shortest response latency. These findings are discussed in terms of the probable distinct functions of the two olfactory systems in the control of maternal behavior in the rat.


Isotopic Labeling Studies Reveal the Patulin Detoxification Pathway by the Biocontrol Yeast Rhodotorula kratochvilovae LS11.
Patulin (1) is a mycotoxin contaminant in fruit and vegetable products worldwide. Biocontrol agents, such as the yeast Rhodotorula kratochvilovae strain LS11, can reduce patulin (1) contamination in food. R. kratochvilovae LS11 converts patulin (1) into desoxypatulinic acid (DPA) (5), which is less cytotoxic than the mycotoxin (1) to in vitro human lymphocytes. In the present study, we report our investigations into the pathway of degradation of patulin (1) to DPA (5) by R. kratochvilovae. Isotopic labeling experiments revealed that 5 derives from patulin (1) through the hydrolysis of the γ-lactone ring and subsequent enzymatic modifications. The ability of patulin (1) and DPA (5) to cause genetic damage was also investigated by the cytokinesis-block micronucleus cytome assay on in vitro human lymphocytes. Patulin (1) was demonstrated to cause much higher chromosomal damage than DPA (5).


Design, synthesis, evaluation and optimization of novel azole analogues as potent antifungal agents.
In order to develop antifungal drugs, a series of novel azole analogues were designed and synthesized based on our previous work. Most of the target compounds had broad-spectrum antifungal activity, which showed excellent to moderate inhibitory activity against the tested strains, except A. fum 0504656. Among these, compounds B3, B7, B8, B11, B12 and E9 showed excellent activity against C. alb Y0109 and C. alb SC5314 (with the MIC80: 0.0156 ug/mL). In addition, compound B3 showed the best inhibitory activity against fluconazole-resistant strains C. alb 901 and C. alb 904, and had low toxicity against NIH/3T3 cells at the effective MIC range against fungi. Structure-activity relationship and docking studies of the derivatives suggest that the presence of the 2-fluoro-4-hydroxyphenyl and 1,2,3-triazole group enhance the antifungal activity of the compounds, which may be related to the interaction of the key groups with the amino acids surrounding the target enzyme.