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23259923

Stigma, an important source of dissatisfaction of health workers in HIV response in Vietnam: a qualitative study.

Like in many other low- and middle-income countries, the recent development of an HIV epidemic in Vietnam has led to a growing need for prevention, treatment, care, and support services for people living with HIV (PLHIV). This puts greater demands on the national HIV services, primarily on health workers, which increases the importance of their job satisfaction and working conditions. This study describes health worker perceptions and explores the factors that influence job satisfaction and dissatisfaction of health personnel working on the HIV response in Vietnam. Spector's job satisfaction model was used as the theoretical framework for the study design and analysis. The study employed a qualitative design with 7 focus group discussions and 15 semi-structured interviews with health workers, purposively selected from national and provincial organizations responsible for HIV services in 5 cities and provinces in Vietnam. Data were analyzed using a hybrid approach of theory-driven and data-driven coding and theme development using qualitative analysis software. HIV services are perceived by Vietnamese health workers as having both positive and negative aspects. Factors related to job satisfaction included training opportunities, social recognition, and meaningful tasks. Factors related to job dissatisfaction included unsatisfactory compensation, lack of positive feedback and support from supervisors, work-related stress from a heavy workload, fear of infection, and HIV-related stigma because of association with PLHIV. An adjusted Spector's model of job satisfaction for HIV service health workers was developed from these results. This study confirmed the relationship between stigmatization of PLHIV and stigma experienced by staff because of association with PLHIV from families, colleagues, and society. The experiencing stigma results in additional work-related stress, low self-esteem, poor views of their profession, and lower income. The study shows the importance of actions to improve staff job satisfaction such as pay raises, supportive supervision, stress management, stigma reduction and workplace safety. Immediate actions could be the provision of more information; education and communication in mass media to improve the public image of HIV services, as well as improvement of workplace safety, therefore making health workers feel that their work is valued and safe.

23259922

Selective fluorescent detection of RNA in living cells by using imidazolium-based cyclophane.

A water-soluble imidazolium-based fluorescent chemosensor senses RNA selectively through fluorescence enhancement over other biologically relevant biomolecules in aqueous solution at physiological pH 7.4. Fluorescence image detection of RNA in living cells such as onion cells, HeLa cells, and animal model cells was successfully demonstrated which displays a chelation-enhanced fluorescence effect. These affinities can be attributed to the strong electrostatic (C-H)(+)···A(-) ionic H-bonding and the aromatic moiety driven π-stacking of imidazolium-based cyclophane with the size-complementary major groove of RNA.

23259920

Formation of stable nanocarriers by in situ ion pairing during block-copolymer-directed rapid precipitation.

We present an in situ hydrophobic salt forming technique for the encapsulation of weakly hydrophobic, ionizable active pharmaceutical ingredients (API) into stable nanocarriers (NCs) formed via a rapid precipitation process. Traditionally, NC formation via rapid precipitation has been difficult with APIs in this class because their intermediate solubility makes achieving high supersaturation difficult during the precipitation process and the intermediate solubility causes rapid Ostwald ripening or recrystallization after precipitation. By forming a hydrophobic salt in situ, the API solubility and crystallinity can be tuned to allow for NC formation. Unlike covalent API modification, the hydrophobic salt formation modifies properties via ionic interactions, thus circumventing the need for full FDA reapproval. This technique greatly expands the types of APIs that can be successfully encapsulated in NC form. Three model APIs were investigated and successfully incorporated into NCs by forming salts with hydrophobic counterions: cinnarizine, an antihistamine, clozapine, an antipsychotic, and α-lipoic acid, a common food supplement. We focus on cinnarizine to develop the rules for the in situ nanoprecipitation of salt NCs. These rules include the pK(a)s and solubilities of the API and counterion, the effect of the salt former-to-API ratio on particle stability and encapsulation efficiency, and the control of NC size. Finally, we present results on the release rates of these ion pair APIs from the NCs.

23259921

Prevalence of Schistosoma japonicum in wild rodents in five islands of the West Dongting Lake, China.

To estimate the prevalence of Schistosoma japonicum in field rodents, we conducted surveys of S. japonicum infection on 5 islands in the west Dongting Lake, China: Julinyuan, Jiangjiazui, Longwangmiao, Goutouzhou, and Niujiaojian. Thirty-five Rattus flavipectus, 43 Rattus norvegicus, 42 Rattus rattus , and 48 Microtus fortis were captured and examined from July to August 2011. Schistosoma japonicum was found in the 3 rat species but not in the vole M. fortis . No statistically significant differences in infection rates were found among the 5 locations or the 3 species of Rattus (P > 0.05). The average prevalence in the Rattus species was 14.2% (17/120), revealing that S. japonicum infection within field rodents was widespread in the Dongting Lake region. Wild rodents can be an important reservoir for S. japonicum transmission in the region and are of public health concern.

23259919

Black currant anthocyanins normalized abnormal levels of serum concentrations of endothelin-1 in patients with glaucoma.

Our recent study, which involved a randomized, placebo-controlled, double-masked 24-month trial (Ophthalmologica 2012;228:26-35), revealed that oral administration of black currant anthocyanins (BCACs) slowed down the visual field deterioration and elevation of ocular blood flow of open-angle glaucoma (OAG). To elucidate the underlying mechanisms of these BCAC-induced effects, as possible factors affecting glaucomatous optic neuropathy, changes of serum endothelin-1 (ET-1), nitric oxide (NO), and antioxidative activities were examined in the present study. From among patients with OAG who participated in the randomized, placebo-controlled, double-masked trial, serum specimens were obtained from BCAC-treated (n=19) or placebo-treated (n=19) patients at baseline and every 6 months. Healthy volunteers (n=20) with age and gender matching the patients were used as a control. Serum ET-1 concentration, [NO2(-)] and [NO2(-) + NO3(-)] levels, advanced oxidation protein products (AOPP), and antioxidant activities were measured by using commercially available kits. At the trial baseline, serum ET-1 concentrations were significantly lower in patients with OAG (BCACs, 3.18±1.06 pg/mL; placebo, 3.44±0.84 pg/mL) than those in healthy volunteers (4.38±1.03 pg/mL) (one-way analysis of variance and a Tukey's multiple comparison post hoc test, P<0.05). Upon administration of BCACs, serum ET-1 concentrations increased to the levels of those in healthy volunteers during the 24-month period. In contrast, those of placebo-treated patients remained at lower levels (3.82±1.14 pg/mL). While [NO2(-)] and [NO2(-)+NO3(-)] levels, AOPP, and antioxidative activities of patients from both the BCACs and placebo groups showed comparable levels to those of healthy subjects at baseline, no significant changes were observed during the observational period in either the BCAC or placebo groups. Among the possible beneficial effects of BCACs toward visual field progression in patients with OAG, our present results suggest that BCACs caused normalization of serum ET-1 levels, and this may modulate ET-1-dependent regulation of the ocular blood hemodynamics.

23259918

Primary myelofibrosis and the "bad seeds in bad soil" concept.

Primary Myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by a clonal myeloproliferation and a myelofibrosis. The concomitant presence of neoangiogenesis and osteosclerosis suggests a deregulation of medullar stem cell niches in which hematopoietic stem cells are engaged in a constant crosstalk with their stromal environment. Despite the recently discovered mutations including the JAK2(Val617F) mutation, the primitive molecular event responsible for the clonal hematopoietic proliferation is still unknown. We propose that the "specificity" of the pathological process that caracterizes PMF results from alterations in the cross talk between hematopoietic and stromal cells. These alterations contribute in creating a abnormal microenvironment that participates in the maintenance of the neoplasic clone leading to a misbalance disfavouring normal hematopoiesis; in return or simultaneously, stromal cells constituting the niches are modulated by hematopoietic cells resulting in stroma dysfunctions. Therefore, PMF is a remarkable "model" in which deregulation of the stem cell niche is of utmost importance for the disease development. A better understanding of the crosstalk between stem cells and their niches should imply new therapeutic strategies targeting not only intrinsic defects in stem cells but also regulatory niche-derived signals and, consequently, hematopoietic cell proliferation.

23259917

Relationships among sense of coherence, resources, and mental health in urban and rural residents in Japan.

The salutogenic model states that coping resources are defined within sociocultural and historical contexts and that various social and historical factors influence the availability of such resources. Though previous studies have suggested the need for an interregional comparison of psychological and social resources, few studies have undertaken such an investigation. The aim of this study is to investigate the associations among coping resources, sense of coherence (SOC), and health status in a comparison of urban and rural residents. General residents (aged 30-69 years) in two areas were targeted for the current study. Through a random sampling selection, 1,000 residents from each area were picked, and an anonymous questionnaire was mailed to each resident. Ultimately, 269 and 363 valid responses from the urban and rural areas, respectively, were analyzed. SOC, both social and psychological resources, and mental health were assessed. To examine relationships between SOC and resources associated with mental health, mental health was defined as a dependent variable. Hierarchical multiple regression was conducted with variables entered from sociodemographic characteristics, social and psychological resources, and SOC. Regarding regional characteristics, social capital and participation in community activities were significantly greater in the rural area than in the urban area. Urban residents reported significantly higher self-esteem and optimism than rural residents. SOC showed the most significant association with mental health in both areas. Mental health was significantly associated with physical activity limitations and life stressors in both areas. However, the associations were weakened when social and psychological resources and SOC were added, which demonstrated their buffering effect on the negative influence of life stressors on health. When SOC was added, the association of self-esteem with mental health disappeared in both areas, but optimism in the urban area and humor in the rural area were directly and independently associated with mental health. Our findings indicate that resources available to urban and rural residents are characteristic of the area where they live, and that social and psychological resources as well as SOC are associated with better mental health. Possible directions for health support strategies, reflecting regional characteristics, are suggested.

23259916

Microwave-assisted synthesis, microstructure, and physical properties of rare-earth chromites.

The full rare-earth (RE) chromites series (RE)CrO(3) with an orthorhombic distorted (Pnma) perovskite structure and the isostructural compound YCrO(3) can be synthesized through a simple microwave-assisted technique, yielding high-quality materials. Magnetization measurements evidence that the Néel temperature for antiferromagnetic Cr(3+)-Cr(3+) ordering strongly depends on the RE(3+) ionic radius (IOR), and a rich variety of different magnetic spin interactions exists. Dielectric spectroscopy on sintered pellets indicates electronic inhomogeneity in all samples as manifested by the presence of at least two dielectric relaxation processes associated with grain boundary and grain interior bulk contributions. X-ray diffraction, Raman spectroscopy, and temperature-dependent dielectric permittivity data do not indicate potential noncentrosymmetry in the crystal or concomitant ferroelectricity. Strong correlations between the magnetic and dielectric properties were not encountered, and microwave-synthesized (RE)CrO(3) may not be classified as magnetoelectric or multiferroic materials.

23259914

A chromosome-centric human proteome project (C-HPP) to characterize the sets of proteins encoded in chromosome 17.

We report progress assembling the parts list for chromosome 17 and illustrate the various processes that we have developed to integrate available data from diverse genomic and proteomic knowledge bases. As primary resources, we have used GPMDB, neXtProt, PeptideAtlas, Human Protein Atlas (HPA), and GeneCards. All sites share the common resource of Ensembl for the genome modeling information. We have defined the chromosome 17 parts list with the following information: 1169 protein-coding genes, the numbers of proteins confidently identified by various experimental approaches as documented in GPMDB, neXtProt, PeptideAtlas, and HPA, examples of typical data sets obtained by RNASeq and proteomic studies of epithelial derived tumor cell lines (disease proteome) and a normal proteome (peripheral mononuclear cells), reported evidence of post-translational modifications, and examples of alternative splice variants (ASVs). We have constructed a list of the 59 "missing" proteins as well as 201 proteins that have inconclusive mass spectrometric (MS) identifications. In this report we have defined a process to establish a baseline for the incorporation of new evidence on protein identification and characterization as well as related information from transcriptome analyses. This initial list of "missing" proteins that will guide the selection of appropriate samples for discovery studies as well as antibody reagents. Also we have illustrated the significant diversity of protein variants (including post-translational modifications, PTMs) using regions on chromosome 17 that contain important oncogenes. We emphasize the need for mandated deposition of proteomics data in public databases, the further development of improved PTM, ASV, and single nucleotide variant (SNV) databases, and the construction of Web sites that can integrate and regularly update such information. In addition, we describe the distribution of both clustered and scattered sets of protein families on the chromosome. Since chromosome 17 is rich in cancer-associated genes, we have focused the clustering of cancer-associated genes in such genomic regions and have used the ERBB2 amplicon as an example of the value of a proteogenomic approach in which one integrates transcriptomic with proteomic information and captures evidence of coexpression through coordinated regulation.

23259915

Ureteroscopy in pediatric patients with spinal abnormalities.

Ureteroscopy (URS) is considered a safe and effective treatment modality for ureteral stones in the pediatric population. Patients with scoliosis or spinal hardware, however, may have anatomic variability that makes URS challenging because of ureteral deviation or tortuosity. We reviewed 130 ureteroscopic procedures at our institution to determine if presence of spinal hardware or severe spinal deformities was associated with increased complications or worsened treatment efficacy. A retrospective chart review was performed on 130 ureteroscopic procedures in 102 patients. Patients were divided into two groups: Those with normal spinal anatomy and those with spinal abnormalities including spinal hardware or moderate to severe scoliosis. Parameters evaluated included patient demographics, stone burden, intraoperative complications (including urinary extravasation, bleeding, or need to abort procedure), and stone-free status. Of 130 ureteroscopic procedures between 2002 and 2010, 25 URS were performed for purposes other than stone disease (gross hematuria, filling defects, or encrusted ureteral stents). The remainder of URS (105) were performed for stone disease. Nine patients had spinal hardware or significant spinal deformities including moderate to severe scoliosis. When comparing both the intraoperative complications as well as stone-free status, there was a difference between those patients with spinal abnormalities and those without. Of 90 URS performed for stones in normal anatomy patients, the stone-free rate was 61%, compared with 35.7% in patients with spinal deformities. There were 13 total complications (Satava grade I or II): 40% in spinal deformity patients compared with 6.1% in normal anatomy patients. Spinal hardware and spinal deformities contribute to increased complications and worsened stone-free rates during pediatric URS compared with pediatric patients with normal anatomy. Our experience with URS in patients with spinal deformities suggests it may not be as safe or efficacious as in the general pediatric population but it can still be used as a primary modality.

23259913

Auricular acupuncture for chemically dependent pregnant women: a randomized controlled trial of the NADA protocol.

The prevalence of maternal drug use during pregnancy in North America has been estimated to be as high as 6-10%. The consequences for the newborn include increased risk for perinatal mortality and ongoing physical, neurobehavioral, and psychosocial problems. Methadone is frequently used to wean women off street drugs but is implicated as a cause of adverse fetal/neonatal outcomes itself. The purpose of our study was to test the ability of maternal acupuncture treatment among mothers who use illicit drugs to reduce the frequency and severity of withdrawal symptoms among their newborns. We randomly assigned chemically dependent pregnant women at BC Women's Hospital in Vancouver, British Columbia to daily acupuncture treatments versus usual care. By necessity, neither our participants nor acupuncturists were blinded as to treatment allocation. Our primary outcome was days of neonatal morphine treatment for symptoms of neonatal withdrawal. Secondary neonatal outcomes included admission to a neonatal ICU and transfer to foster care. We randomized 50 women to acupuncture and 39 to standard care. When analyzed by randomized groups, we did not find benefit of acupuncture; the average length of treatment with morphine for newborns in the acupuncture group was 2.7 (6.3) compared to 2.8 (7.0) in the control group. Among newborns of women who were compliant with the acupuncture regime, we observed a reduction of 2.1 and 1.5 days in length of treatment for neonatal abstinence syndrome compared to the non-compliant and control groups, respectively. These differences were not statistically significant. Acupuncture may be a safe and feasible treatment to assist mothers to reduce their dosage of methadone. Our results should encourage ongoing studies to test the ability of acupuncture to mitigate the severity of neonatal abstinence syndrome among their newborns.

23259912

Cognitive function in ecstasy naive abstinent drug dependants and MDMA users.

'Hidden' symptoms, or subtle cognitive deficits and long-term changes in mood, have been linked to the recreational use of 3, 4-methylenedioxymethamphetamine/MDMA, and are notionally present in non-heavy polydrug users. This study assessed the cognitive functioning and mood profiles of clinically diagnosed drug dependents who had never consumed MDMA, recreational drug users that had previously consumed MDMA, with both groups having not consumed illicit drugs for 6-months, and a control group with limited illicit drug use and no MDMA usage in their past. Cognitive functioning was assessed using the Cognitive Drug Research computerised cognitive assessment system and participants completed the Profile of Mood States and Beck Depression Inventory to assess their current mood and depression. Participants in the clinically diagnosed drug dependent group scored significantly worse on the 'Quality of Working Memory' cognitive factor score than both the MDMA and control group (F (2, 33) = 5.75, p = 0.007). The control and clinical groups also differed on depression scores (U [16] = 13.00, p = 0.016) and Tension/Anxiety scores (U [16] = 16.00, p = 0.034), with the clinical group scoring significantly higher in both cases. The MDMA group did not differ from the control group on the measures of cognition or mood. These results suggest that despite a 6-month prolonged abstinence the cognitive deficits ostensibly caused by 'heavy' usage or the dependence on or abuse of illicit drugs are not reversed by abstinence.

23259911

A case of cola dependency in a woman with recurrent depression.

Cola is an extremely popular caffeinated soft drink. The media have recently cited a poll in which 16% of the respondents considered themselves to be addicted to cola soft drinks. We find the contrast between the apparent prevalence of cola addiction and the lack of scientific literature on the subject remarkable. To our knowledge, this is the first case of cola dependency described in the scientific literature. The patient is a 40-year-old woman, who when feeling down used cola to give her an energy boost and feel better about herself. During the past seven years her symptoms increased, and she was prescribed antidepressant medication by her family doctor. Due to worsening of symptoms she was hospitalised and later referred to a specialised outpatient clinic for affective disorders. At entry to the clinic she suffered from constant tiredness, lack of energy, failing concentration, problems falling asleep as well as interrupted sleep. She drank about three litres of cola daily, and she had developed a metabolic syndrome.The patient fulfilled the ICD-10 criteria for dependency, and on the Yale Food Addiction Scale (YFAS) she scored 40 points. Her clinical mental status was at baseline assessed by the Major Depression Inventory (MDI) = 41, Hamilton Depression - 17 item Scale (HAMD-17) = 14, Young Mania Rating Scale (YMRS) = 2 and the Global Assessment of Functioning (GAF) Scale = 45.During cognitive therapy sessions she was guided to stop drinking cola and was able to moderate her use to an average daily consumption of 200 ml of cola. Her concentration improved and she felt mentally and physically better. At discharge one year after entry her YFAS was zero. She was mentally stable (MDI =1, HAMD-17 = 0, YMRS = 0 and GAF = 85) and without antidepressant medication. She had lost 7.2 kg, her waistline was reduced by 13 cm and the metabolic syndrome disappeared. This case serves as an example of how the overconsumption of a caffeinated soft drink likely was causing or accentuating the patient's symptoms of mental disorder. When diagnosing and treating depression, health professionals should pay attention to potential overuse of cola or other caffeinated beverages.

23259910

Epidemic of Klebsiella pneumoniae ST11 clone coproducing KPC-2 and 16S rRNA methylase RmtB in a Chinese University Hospital.

Emergence of rmtB-positive Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) poses a great threat to antimicrobial treatment options. From January 2010 to December 2010, non-duplicate KPC-KP isolates from our hospital were screened for rmtB and multiple other resistance determinants with PCR. Subsequent studies included MIC determination, PFGE, and multilocus sequence typing. Records from patients with KPC-KP isolated were retrospectively reviewed. Comparisons of molecular and clinical characteristics between rmtB-positive and rmtB-negative isolates were systematically performed, as well as the environmental colonization study in ICU wards. A total of 84 KPC-KP strains were collected, including 48 rmtB-positive KPC-KP (RPKP) and 36 rmtB-negative KPC-KP (RNKP) isolates. All KPC-KP isolates were multidrug resistant, with colistin and tigecycline being the most active agents. Compared with RNKP, RPKP displayed a much severer resistance phenotype. Susceptibility rates for amikacin (0% for RPKP versus 88.9% for RNKP, p < 0.01), fosfomycin (8.5% for RPKP versus 88.9% for RNKP, p < 0.01), and minocycline (6.7% for RPKP versus 52.8% for RNKP, p < 0.01), were all significantly lower in RPKP strains. Isolates belonging to PFGE pulsetype A and sequence type 11 were predominant in both groups, including 39 (81.3%) RPKP and 22 (61.1%) RNKP isolates. Nevertheless, RNKP showed more complex genetic backgrounds compared with RPKP. Diverse clinical characteristics were found in both cohorts, however, no significant differences were observed between RPKP and RNKP patients. RPKP strains have spread widely and gradually replaced RNKP in our hospital. They seemed to show much severer resistance phenotypes compared with RNKP and had a bigger dissemination potential. Prudent use of available active agents combined with good control practices is therefore mandatory.

23259908

Whole mitochondrial genome scan for population structure and selection in the Atlantic herring.

Marine fish, such as the Atlantic herring (Clupea harengus), often show a low degree of differentiation over large geographical regions. Despite strong environmental gradients (salinity and temperature) in the Baltic Sea, population genetic studies have shown little genetic differentiation among herring in this area, but some evidence for environmentally-induced selection has been uncovered. The mitochondrial genome is a likely target for selection in this system due to its functional role in metabolism. We sequenced whole mitochondrial genomes for herring from throughout the Baltic region (n=98) in order to investigate evidence for geographical structuring, selection, and associations between genetic and environmental variation. Three well-supported clades that predate the formation of the Baltic Sea were identified, but geographic structuring of this variation was weak (ΦST = 0.036). There was evidence for significant positive selection, particularly in the ND2, ND4 and ND5 genes, and amino acids under significant selection in these genes explained some of the clade formation. Despite uncovering evidence for selection, correlations between genetic diversity or differentiation with environmental factors (temperature, salinity, latitude) were weak. The results indicate that most of the current mtDNA diversity in herring predates the formation of the Baltic Sea, and that little structuring has evolved since. Thus, fisheries management units in this region cannot be determined on the basis of mtDNA variability. Preliminary evidence for selection underlying clade formation indicates that the NADH complex may be useful for examining adaptation and population structuring at a broader geographical scale.

23259909

Stepwise differentiation of human adipose-derived mesenchymal stem cells toward definitive endoderm and pancreatic progenitor cells by mimicking pancreatic development in vivo.

Pancreatic progenitor (PP) cells are tissue-committed cells, which can differentiate into all kinds of pancreatic cells. They are potential candidates for regeneration of pancreatic tissue. However, it is unfeasible to acquire PP cells from pancreatic tissues and expand them in vitro. Generation of PP cells from adipose tissue-derived mesenchymal stem cells (AD-MSCs) would provide an unlimited source of PP cells. Here we developed a 2-step stepwise protocol, which induced AD-MSCs to generate FOXA2- or SOX17-positive definitive endoderm (DE) (5 days) and pancreatic and duodenal homeobox gene 1 (PDX1)-positive PP cells (4-6 days). By mimicking the developmental progress in embryonic development, we optimized the timing and combination of cytokines to activate the key signaling pathways during pancreatic development. We found that activating the Nodal/Activin signal with Activin A could induce differentiation of AD-MSCs toward DE, which could be further promoted by the Wnt signaling pathway activator Wnt3a. Besides, transient T (BRACHYURY)(+) mesendodermal cells were observed during formation of DE from AD-MSCs. Subsequently, the Wnt signaling pathway inhibitor Dkk1 along with retinoic acid/FGF2 (60 ng/mL) further induced AD-MSC-derived DE cells to differentiate into PDX1-positive PP cells. The derived PP cells were capable to form pancreatic endocrine or exocrine cells. In conclusion, we established a stepwise protocol that could derive DE and PP cells from AD-MSCs. It might provide an unlimited source of autologous PP cells for pancreatic diseases.

23259907

Abdominal obesity and prolonged prone positioning increase risk of developing sclerosing cholangitis in critically ill patients with influenza A-associated ARDS.

Secondary sclerosing cholangitis is a severe disease of the biliary tract. Over the last decade, several cases of sclerosing cholangitis in critically ill patients (SC-CIP) were reported. Reports in the literature so far are characterized by a wide variety of underlying causes of critical illness, thereby hindering a risk-factor analysis. We report on a homogenous cohort of critically ill patients with influenza A (H1N1) pneumonia and severe acute respiratory distress syndrome (ARDS), of whom a subgroup developed sclerosing cholangitis, allowing for probing of risk factors associated with SC-CIP. Twenty-one patients (5 female, 16 male, 46.3 ± 10.8 years) with severe ARDS due to H1N1 pneumonia were retrospectively divided into two groups, characterized by the presence (n = 5) and absence of SC-CIP (n = 16). A large array of clinical data, laboratory parameters, and multi-detector computed tomography-derived measures were compared. Both patient groups showed severe pulmonary impairment. Severity of disease on admission day and during the first 14 days of treatment showed no difference. The patients developing SC-CIP had a higher body mass index (BMI) (37.4 ± 6.0 kg/m(2) vs. 29.3 ± 6.8 kg/m(2); P = 0.029) and a higher volume of intraperitoneal fat (8273 ± 3659 cm(3) vs. 5131 ± 2268 cm(3); P = 0.033) and spent a longer cumulative period in the prone position during the first 14 days (165 ± 117 h vs. 78 ± 61 h; P = 0.038). Our results suggest that obesity, intraperitoneal fat volume, and a longer cumulative duration spent in the prone position may put patients with ARDS at risk of developing SC-CIP. These results lead us to propose that the prone position should be carefully deployed, particularly in abdominally obese patients, and that frequent checks be made for early hepatic dysfunction.

23259906

Personal characteristics related to the risk of adolescent internet addiction: a survey in Shanghai, China.

Paralleling the rapid growth in computers and internet connections, adolescent internet addiction (AIA) is becoming an increasingly serious problem, especially in developing countries. This study aims to explore the prevalence of AIA and associated symptoms in a large population-based sample in Shanghai and identify potential predictors related to personal characteristics. In 2007, 5,122 adolescents were randomly chosen from 16 high schools of different school types (junior, senior key, senior ordinary and senior vocational) in Shanghai with stratified-random sampling. Each student completed a self-administered and anonymous questionnaire that included DRM 52 Scale of Internet-use. The DRM 52 Scale was adapted for use in Shanghai from Young's Internet Addiction Scale and contained 7 subscales related to psychological symptoms of AIA. Multiple linear regression and logistic regression were both used to analyze the data. Of the 5,122 students, 449 (8.8%) were identified as internet addicts. Although adolescents who had bad (vs. good) academic achievement had lower levels of internet-use (p < 0.0001), they were more likely to develop AIA (odds ratio 4.79, 95% CI: 2.51-9.73, p < 0.0001) and have psychological symptoms in 6 of the 7 subscales (not in Time-consuming subscale). The likelihood of AIA was higher among those adolescents who were male, senior high school students, or had monthly spending >100 RMB (all p-values <0.05). Adolescents tended to develop AIA and show symptoms in all subscales when they spent more hours online weekly (however, more internet addicts overused internet on weekends than on weekdays, p < 0.0001) or when they used the internet mainly for playing games or real-time chatting. This study provides evidence that adolescent personal factors play key roles in inducing AIA. Adolescents having aforementioned personal characteristics and online behaviors are at high-risk of developing AIA that may compound different psychological symptoms associated with AIA. Spending excessive time online is not in itself a defining symptom of AIA. More attention is needed on adolescent excessive weekend internet-use in prevention of potential internet addicts.

23259905

Y3MnAu5: three distinctive d-metal functions in an intergrown cluster phase.

The new Y(3)MnAu(5) intermetallic phase is obtained from the arc-melted elements in virtually quantitative yields after annealing at 1000 °C for ~3 d. Its remarkable structure [rhombohedral, R3, Z = 6; a = 8.489(1) Å, c = 18.144(2) Å] consists of a 2:1 cubic-close-packed intergrowth between edge-shared Mn-centered Au rhombohedra (Mn@Au(8)) with gold-centered antiprismatic (Au@Y(6)) clusters via a common gold network. Magnetic susceptibility (χ) data for Y(3)MnAu(5) were fitted by a Curie-Weiss law. The Curie constant indicates a large effective moment corresponding to nearly localized Mn spins S = 5/2, and the Weiss temperature demonstrates the dominance of ferromagnetic (FM) interactions. An antiferromagnetic (AFM) transition at T(N) = 75 K and a possible spin reorientation transition at 65 K were observed. Analysis of the χ data for T < T(N) suggests a planar noncollinear helical AFM structure that arises from competing AFM interactions between FM-aligned layers of spins in the ab-plane with a turn angle of 69° between the spins along the helix c-axis. A magnetic field-induced spin flop transition is observed below T(N). Spin-polarized LMTO-LSDA calculations indicate an ~2 eV splitting of the Mn 3d states and a metallic ground state, and their COHP analyses demonstrate that ~81% of the total Hamilton populations originate from heteroatomic polar Y-Au and Mn-Au bonding. The Mn 3d, Y 4d, and Au 5d characteristics are remarkably diverse: localized and magnetically polarized for Mn; reducing and cationic for Y; and relativistically strongly bonded and oxidizing for Au, bonding of the latter two being broadly delocalized.

23259904

Short-term antiretroviral therapy fails to reduce the expanded activated CCR5-expressing CD4+ T lymphocyte population or to restore the depleted naive population in chronically HIV-infected individuals with active pulmonary tuberculosis.

The effective role of antiretroviral (ARV) therapy in the regulation of CD4 T cell subset distribution, coreceptor expression, and activation status in individuals with chronic HIV also presenting with active pulmonary TB is not clearly understood. A cross-sectional analysis was performed on a total of 137 South African individuals. CCR5, CXCR4, and CD38 expression of CD4 T cell subsets in HIV-infected individuals with and without active pulmonary tuberculosis (TB) disease, pre- and post-ARV therapy, were determined by flow cytometry. In treatment-naive patients, CD4 T cells showed elevated surface expression of CCR5 and CD38 in TB/HIV coinfection as compared to HIV infection alone despite the overall percentage of CD4 T cells expressing CCR5 being reduced. Total CD38+ CD4 T cells were not significantly increased in either group; however, mean CD38 fluorescence was significantly higher in the context of TB infection. HIV/TB-coinfected individuals also displayed an increased percentage of activated (CD38+) CCR5+ CD4 T cells as compared to HIV patients alone. The naive CD4 T cell subset was depleted similarly in both HIV and HIV/TB groups. Only the HIV treatment group and not the TB-coinfected treatment group showed significantly decreased activated CCR5+ CD4 T cells, an increased percentage of naive T cells, and a decreased percentage of antigen-experienced T cells. This study highlighted an association of TB disease with immune activation, particularly of the CCR5+ CD4 T cell subset in HIV infection and the differential impact of ARV treatment. Further studies are needed to understand how TB coinfection confounds normal responses to ARV.

23259903

Nanoscale optical and electrical characterization of horizontally aligned single-walled carbon nanotubes.

During the recent years, a significant amount of research has been performed on single-walled carbon nanotubes (SWCNTs) as a channel material in thin-film transistors (Pham et al. IEEE Trans Nanotechnol 11:44-50, 2012). This has prompted the application of advanced characterization techniques based on combined atomic force microscopy (AFM) and Raman spectroscopy studies (Mureau et al. Electrophoresis 29:2266-2271, 2008). In this context, we use confocal Raman microscopy and current sensing atomic force microscopy (CS-AFM) to study phonons and the electronic transport in semiconducting SWCNTs, which were aligned between palladium electrodes using dielectrophoresis (Kuzyk Electrophoresis 32:2307-2313, 2011). Raman imaging was performed in the region around the electrodes on the suspended CNTs using several laser excitation wavelengths. Analysis of the G+/G- splitting in the Raman spectra (Sgobba and Guldi Chem Soc Rev 38:165-184, 2009) shows CNT diameters of 2.5 ± 0.3 nm. Neither surface modification nor increase in defect density or stress at the CNT-electrode contact could be detected, but rather a shift in G+ and G- peak positions in regions with high CNT density between the electrodes. Simultaneous topographical and electrical characterization of the CNT transistor by CS-AFM confirms the presence of CNT bundles having a stable electrical contact with the transistor electrodes. For a similar load force, reproducible current-voltage (I/V) curves for the same CNT regions verify the stability of the electrical contact between the nanotube and the electrodes as well as the nanotube and the AFM tip over different experimental sessions using different AFM tips. Strong variations observed in the I/V response at different regions of the CNT transistor are discussed.

23259902

Prevalence of Toxoplasma gondii from free-range chickens (Gallus domesticus) from Addis Ababa, Ethiopia.

Prevalence of Toxoplasma gondii in free-range chickens (Gallus domesticus) is a good indicator of the environmental contamination with oocysts because chickens become infected mainly by feeding from ground, feed, or soil contaminated with oocysts. The seroprevalence of T. gondii antibodies in 125 free-range chickens from the Addis Ababa, Ethiopia, was determined. Antibodies to T. gondii were assayed by the modified agglutination test; 48 of 125 (38.4%) chickens were seropositive, with titers of 1:5 in 14, 1:10 in 12, 1:20 in 14, 1: 40 in 3, 1: 80 in 1, 1:160 in 1, 1:320 in 1, and ≥1:640 in 2 chickens. The hearts of 115 chickens were bioassayed for T. gondii infection. Hearts of 72 seronegative (modified agglutination test [MAT] < 1:5) chickens were pooled in 4 groups (20 + 18 + 19 + 15) and fed to 4 T. gondii -free cats; none of these 4 cats shed oocysts in their feces examined 3-21 days after feeding chicken tissues. Hearts of 43 seropositive chickens (MAT ≥ 1:5) were bioassayed individually in mice. Toxoplasma gondii was isolated from only 1 chicken, with a MAT titer of 1:80. This isolate was designated TgCKEt1 and was not pathogenic for outbred mice. Restricted fragment length polymorphism (RFLP) genotyping using 10 loci indicated the TgCKEt1 was ToxoDB polymerase chain reaction-RFLP genotype #1 (Type II clonal). Results of this study indicate very low environmental contamination with T. gondii oocysts around Addis Ababa.

23259888

Abnormal cervical cytology in pregnant adolescents.

A retrospective, cohort study of pregnant adolescents with abnormal cervical cytology including: atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) was done to determine the regression, persistence and progression of abnormal cervical cytology in adolescent pregnancies. Follow-up cervical cytology within 1 year was assessed. Results suggest that pregnant adolescents have a high regression rate of abnormal cervical cytology. The likelihood of regression, persistence, or progression, is independent of the initial cytological diagnosis.

23259887

Minimally invasive vaginal hysterectomy using bipolar vessel sealing: preliminary experience with 500 cases.

The objective of our study was to evaluate surgical outcome of minimally invasive vaginal hysterectomy (MIVH), using the bipolar vessel sealing system (BVSS; BiClamp®). The design was a retrospective analysis (Canadian Task-force Classification II-3). The setting was a secondary care hospital. Records of patients who underwent vaginal hysterectomy for benign indications in our centre between November 2005 and March 2011 were reviewed. The demographic patients' data, indications for surgery, patient history with regard to previous surgery, duration of surgery, blood loss (postoperative hemoglobin drop '∆Hb'), perioperative complications, and length of inpatient stay were collected from the medical records. The intervention was vaginal hysterectomy using BVSS (BiClamp®). Results showed that the mean duration of surgery was 48.9 ± 15.3 min (95% CI, 49.2-52.5). The mean duration of hospital stay was 3.2 ± 1.2 days (95% CI, 2.8-3.2). The mean ∆Hb was 1.4 ± 1.8 g/dl. Overall, conversion to laparotomy was required in three cases (0.6%). Only one haemoperitoneum occurred (0.2%) and this is the only case who required blood transfusion. The main indication for VH was uterine prolapse in 52.0% (n = 260) of cases; uterine fibroids in 37.4% (n = 187); adenomyosis uteri in 4.2% (n = 21); cervical dysplasia in 22 patients (4.4%) and in 2% (n = 10) of patients, endometrial hyperplasia and other pathologies were the indications for VH. It was concluded that electrosurgical bipolar vessel sealing by (BiClamp®) can provide a safe and feasible alternative to sutures in vaginal hysterectomy, resulting in reduced operative time and blood loss, with acceptable surgical outcomes.

23259886

Analysis of uterine and ovarian arterial blood flow and ovarian hormone levels prior to and after hysteroscopic endometrial resection.

The objective of this study was to evaluate the effect of hysteroscopic endometrial ablation on the ovarian and uterine artery blood flow and on follicle stimulating hormone (FSH) and oestradiol (E2) levels. A total of 26 consecutive women with abnormal uterine bleeding refractory to medical treatment had undergone hysteroscopic electrosurgical transcervical resection of the endometrium (TCRE). Ultrasonographic measurement of ovarian volumes and colour Doppler flow assessment of the uterine and ovarian arteries were performed on all patients before surgery (group 1) and 1 week (group 2) and 6 months (group 3) after surgery. Blood samples were also collected for determination of FSH and E2 levels, 4 weeks before and 1 month after surgery. No statistically significant change was observed between preoperative and postoperative (1st week and 3rd month) volumes of the ovaries. The mean pulsatility index (PI) of the uterine and ovarian artery did not show statistically significant differences between postoperative 1st week and 3rd month measurements of uterine and ovarian artery PI. The increase in serum levels of FSH and E2 after endometrial resection did not reach statistical significance. Although, women may present with climacteric complaints of hot flushes and nocturnal sweating after endometrial resection, this is probably a psychological response to hypomenorrhoea and amenorrhoea, as no statistically significant changes in FSH and E2 levels and uterine/ovarian blood flow were demonstrated in the early postoperative period.

23259885

The need for repeat evacuation of retained products of conception: how common is it?

Evacuation of retained products of conception with suction curettage is a widely used method for the management of missed miscarriage, incomplete miscarriage and termination of pregnancy. This procedure carries a risk of incomplete evacuation, which may lead to a further repeat evacuation. There are limited data on the incidence of repeat evacuation for suspected retained products. We undertook a retrospective audit on patients who underwent suction curettage for retained products of conception between January 2006 and February 2008, in order to evaluate the rate of repeat evacuation. Our study showed 3.1% (17 of 541) of patients underwent a repeat evacuation for suspected retained products. Suction curettage remains a safe and common procedure, however, it is important to minimise the recurrence of repeat evacuations through the use of medical management, improved training and local guidelines. This in turn should lower the risk of further complications associated with a surgical procedure.

23259884

The understanding and acceptability of assisted reproductive technology (ART) among infertile women in urban Lagos, Nigeria.

This descriptive study was carried out to assess the awareness and acceptability of Assisted Reproductive Technology (ART) among infertile women in Lagos, Nigeria. Self-administered questionnaires on the knowledge of ART in the women were used. After a brief exposé on ART, questions relating to their attitude were answered. A total of 166 women were studied. Only 51.8% had any knowledge of ART and most of these had poor knowledge. A total of 137 women would embrace ART if offered but 29 would not, for reasons such as religion, fear of side-effects, failure and unaffordable costs. There is a paucity of good knowledge of ART. A significant number of the women would consider ART if offered. There is thus a need to create more awareness about the possibilities offered by ART, as well as instituting low cost ART strategies in developing world countries.

23259883

Conventional vs unconventional assisted reproductive technologies: opinions of young physicians.

In the last three and a half decades, an increasing number of assisted reproductive technologies (ARTs) have been developed, some of them already being used in clinical practice, while others will probably remain purely theoretical due to their associated ethical issues. The purpose of this study was to analyse the opinions of medical residents regarding various ARTs, both classical and unconventional. We conducted a multi-institutional survey among 142 medical residents in order to assess the views of young physicians of regarding ARTs. Most responders were in favour of medical procedures like gamete donation and surrogacy. When asked about more controversial procedures such as posthumous sperm procurement or reproductive cloning, most were against. Progress in reproductive medicine is made at a fast pace, as more and more couples are found infertile and as the birth rate in developed countries becomes smaller and smaller. If not carefully followed and regulated, this can easily lead to the development of highly controversial procedures, which can significantly alter the way we see human reproduction. As the law has a very traditional approach, it is often left behind by progress in this field, leaving potentially controversial procedures unregulated for long periods of time. During these periods, physicians have the very important role of analysing what is good and what is not and when to recognise procedures that go against general ethical and medical principles.

23259882

Clinical complications after transvaginal oocyte retrieval: a retrospective analysis.

There are little systematic data reported in the literature on complications observed after transvaginal oocyte retrieval (OR) guided by ultrasound. We report our experience in 542 in vitro fertilisation cycles. The frequency of severe complications in our patients was 0.72%; of these, two cases were bronchospasm during anaesthesia (0.36%) and two were cases of intraperitoneal bleeding (0.36%); minor vaginal bleeding was the most frequent complication (18.08%), which was treated easily. Through this retrospective analysis, it is evident that clinical suspicion is of particular importance in detecting post-OR complications on one hand, but on the other these complications are rare and most are treated conservatively.

23259881

Evaluation of urogynaecology care of an elderly population in a specialist urogynaecology centre.

The ageing population of the UK means that demand for urogynaecology services is expected to increase substantially, particularly in patients aged over 65 years. To assess service provision and predict future needs, we reviewed the demographic profile and service requirements of elderly patients referred to our urogynaecology service. We performed a retrospective review of case notes of 125 patients over 65 years of age who attended our urogynaecology clinic within a 6 month period, including comorbidity scoring using a validated instrument. A substantial proportion (56%) of patients did not require hospital-based management, and none of the patients had an adult comorbidity evaluation (ACE-27) score >2. Hence, we recommend assessing patients using the ACE-27 score and not on chronological age alone. A restructuring of urogynaecology services towards better access to community-based clinics is required to reflect the treatment needs of the patient population. This would be in line with national continence care guidance.

23259880

Pre-incisional, post-incisional and combined pre- and post-incisional local wound infiltrations with lidocaine in elective caesarean section delivery: a randomised clinical trial.

The objective of this study was to compare maternal and fetal outcomes in caesarean deliveries received pre-incisional, post-incisional or combined pre- and post-incisional local wound infiltrations with lidocaine. In a randomised, double-blind clinical trial, candidates of elective caesarean section received local wound infiltration with an anaesthetic mixture including 1% lidocaine pre-incisionally (n = 94), post-incisionally (n = 92) or both (n = 95). Postoperative pain, duration of analgesia, number of postoperative rescue analgesic demands, time to ambulation, time of first breast-feeding and neonatal Apgar score were compared. Main outcome variables were comparable between the pre- and post-incisional groups. Pain scores and duration of analgesia were significantly lower in the mixed group. Time of breast-feeding and number of analgesic demand were significantly lower in 'mixed' group than those in pre- and post-incisional groups, respectively. The other variables were comparable. Combined pre- and post-incisional local wound infiltration in post-caesarean pain relief is superior to each one alone.

23259879

Full-term pregnant women have higher lumbar epidural pressure than non-pregnant women: a preliminary report.

The objective of this study was to compare the lumbar epidural pressure of full-term pregnant women with that of non-pregnant women. The epidural pressure of 20 full-term pregnant women and 15 non-pregnant women was measured during epidural needle insertion in the lateral position (T0), and at 30-s intervals following insertion (T1-T3), after the patient was turned supine (T4-T6), and after local anaesthetic injection (T7-T9). Results showed that the average epidural pressures following epidural insertion in the lateral position (average of T1-T3), in the supine position (average of T4-T6), and after local anaesthetic injection (average of T7-T9) were all significantly higher in the pregnant women compared with those who were not pregnant (p= 0.0293, 0.0109 and 0.0309, respectively). Epidural pressures increased significantly after women were turned supine (p < 0.001). Average epidural pressures were positive for all time points, T0-T9. It was concluded that the epidural pressure in the pregnant women was higher than in those who were not pregnant, both in the lateral and the supine position.

23259878

Low 3rd trimester haemoglobin level and the risk of post-term pregnancy.

The aim of this study was to examine the association between haemoglobin (Hb) concentration during pregnancy and the risk of post-term pregnancy (PTP). Based on data from a population-based prenatal care programme in South China, a total of 102,484 women who delivered during 1995-2000 were identified. Haemoglobin concentration was determined by using standard methods. Risk of PTP was analysed according to severity of anaemia and multiple Hb categories. Multivariable logistic regression models were used to control potential confounding factors. Results showed that the overall prevalence rate of PTP in the population was 4.8% (4,947/102,484). The rate was 5.0%, 4.7% and 4.8% for women who were anaemic, while it was 4.5%, 4.4% and 4.2% for women who were non-anaemic in the 1st, 2nd and 3rd trimester, respectively. Although anaemia in either of the trimesters was not significantly associated with an increased risk of PTP, the risk was two-fold higher (odds ratio, 2.06; 95% CI, 1.18-3.59) for women whose last trimester haemoglobin concentration was lower than 80 g/l, when compared with women whose last trimester haemoglobin concentration was 140 g/l or higher. Our findings suggest that a very low 3rd trimester haemoglobin level is associated with an increased risk of PTP.

23259877

Atosiban and nifedipine in the suppression of pre-term labour: a comparative study.

This is a retrospective study comparing the efficacy and safety of atosiban and nifedipine in the suppression of pre-term labour. A total of 75 patients were included in this study; 34 received atosiban and 41 received nifedipine. There were no statistically significant differences in the baseline characteristics for both groups. A total of 68.3% of women in the atosiban group remained undelivered at 7 days or more, compared with 64.7% in the nifedipine group, which was not statistically significant. Average birth weight, admission to the neonatal intensive care unit and mode of delivery were similar in both groups. However, the gestational age at delivery was significantly higher in the nifedipine group. We concluded that atosiban and nifedipine are effective in delaying delivery for 7 days or more in women presenting with pre-term labour. They have the same efficacy and associated minor side-effects. However, flushing, palpitation and hypotension were significantly higher in the nifedipine group.

23259876

Neonatal morbidity mortality outcomes in pre-term premature rupture of membranes.

We present a retrospective review of 228 pre-term premature rupture of membranes (PPROM) singleton pregnancies followed-up in our clinic between 1996 and 2005. The most common neonatal morbidities in PPROM cases are respiratory distress syndrome (RDS), sepsis and intraventricular haemorrhage (IVH). The route of delivery does not affect newborn intensive care unit (NICU) requirements, perinatal asphyxia, sepsis and IVH rates in PPROM cases. NICU and PPV requirements, RDS, sepsis and IVH rates increase if the Apgar score is < 5. Neonatal morbidity and mortality rates increase as the latent period lengthens. C reactive protein (CRP) on admission, last CRP, birth weight and the 5 min Apgar score was found to be associated with NICU requirements; only the 5 min Apgar score was found to be associated with RDS; and last leukocyte count and maternal haemotocrit was found to be associated with sepsis and pneumonia, independently. In PPROM cases, CRP on admission, last CRP, birth weight, the 5 min Apgar score, last leukocyte count and maternal haemotocrit, should be considered to predict neonatal outcomes.

23259875

The effect of chronic pelvic pain scoring on pre-term delivery rate.

A total of 57 pregnant women, who were admitted to the outpatient clinic having high visual analogue scale (VAS) and a history of chronic pelvic pain before pregnancy, were evaluated with the international pelvic pain assessment form (IPPAF). Gynaecological disorders, pain at ovulation, dysmenorrhoea, level of cramps with period and suspicion of endometriosis were determined to be higher in the pre-term group (p < 0.05). Regarding urological disorders, pain when the bladder was full, pain with urination, a positive answer to the question, 'Does your urgency bother you?' and suspicion of interstitial cystitis were also determined to be higher in the pre-term group (p < 0.05). Thus, the total IPPAF scores were significantly higher in the pre-term group (p < 0.05). The pregnant women with a higher total IPPAF score before pregnancy may thus have a higher probability of pre-term labour.

23259874

Maternal age as a predictive factor of pre-term birth. An epidemiological study from 1999 to 2008 in Greece.

The aim of the study was to estimate the risk of pre-term birth in women giving birth in Greece in different age groups. Data about women giving birth in Greece were retrieved from the Hellenic Vital Statistics covering the years from 1999 to 2008. Relative risk using χ(2) contingency tables was estimated among maternal age groups formed. These groups included mothers < 15 years of age, 15-19, 20-34 (used as a control group) and women > 34 (35-39, 40-44, 45-49 and ≥ 50) years of age. Relative risk of each age group was compared with mothers 20-34 years of age. A total of 1,069,413 valid births were included in the study and 72,156 of them were pre-term (6.75% of total count). Results exhibit a 'U'-shaped distribution of risk. Higher risk of pre-term birth is noted in the groups of < 15 years (Pearson χ(2) = 14.964, p < 0.001, risk = 1.569, CI = 1.249-1.970) and above 34 years of age (Pearson χ(2) = 2991.26, p < 0.001, risk = 1.572, CI = 1.546-1.597). For older women, a steep rise in the relative risk for pre-term birth was noted beyond the 40-44 years of age group. Finally, of interest is the fact that 'late' pre-terms (34-36 gestational weeks) account for most of the pre-term birth in mothers beyond 34 years of age.

23259873

Spot urinary protein analysis for excluding significant proteinuria in pregnancy.

The aim of this research was to compare the accuracy of urinary protein/creatinine ratio (PCR) and albumin/creatinine ratio (ACR) in defining optimal cut-off points to rule-out significant proteinuria (>300 mg/24 h) in pregnancy. The secondary outcome measure was to determine the investigation of choice to evaluate proteinuria used by maternity units in the UK. PCR and ACR were calculated on first (PCR1, ACR1) void urine samples of the 24-hour urinary protein collection (24UP). Sensitivity and specificity was calculated for different cut-off points for PCR1 and ACR1 to rule-out significant proteinuria. An online survey was sent to RCOG members questioning them on their investigation of choice to evaluate proteinuria. We concluded from our results that both PCR and ACR are good rule-out tests for significant proteinuria in pregnancy using cut-off points of <20 mg/mmol and <2.5 mg/mmol. PCR is the investigation of choice in 56% of UK units studied.

23259871

Multicystic ovaries and pituitary pseudo-adenoma associated with primary hypothyroidism.

Ovarian hyperstimulation syndrome (OHSS) is a well known but poorly understood iatrogenic complication of superovulation. Spontaneous OHSS has been reported with pregnancy, polycystic ovary syndrome, primary hypothyroidism and pituitary adenoma. Only a few cases of massive ovarian enlargement in non-pregnant women with primary hypothyroidism have been reported in the English literature. A definitive pathophysiology remains uncertain, although several postulations were proposed. A 23-year-old nulliparous woman presented with transient bloating of her abdomen associated with menstruation for the last four cycles. She had nausea, headache, faintness, galactorrhoea and clinical signs and symptoms of hypothyroidism (swelling in the hands and feet, cold intolerance, decreased activity, excessive sleepiness, loss of hair and dry skin) for 6 months. Thyroid stimulating hormone and serum prolactin levels were highly elevated (> 100 μg/l and 4,095 μg/l, respectively) and free thyroxine level was low. Abdominal ultrasound showed bilateral multiple thin-walled ovarian cysts. Contrast enhanced CT of brain showed a pituitary macroadenoma. Treatment with levothyroxine was started and showed marked clinical improvement with return to normal menstruation within 4 months. Serial ultrasound showed gradual regression of the ovarian cysts within 6 months. Serum prolactin level was gradually diminished. Awareness that ovarian and pituitary enlargement may be associated with severe hypothyroidism which can be managed successfully, will spare patients dangerous and unnecessary operative intervention for ovarian cysts or pituitary adenoma.

23259870

Recurrent short rib polydactyly syndrome.

We present three consecutive cases of skeletal dysplasias of a non-consanguineous couple with five pregnancies. The diagnosis of short-rib polydactyly syndrome (SRPS) was feasible by ultrasound during the 1st trimester of pregnancy. SRPS represents a heterogeneous group of lethal skeletal dysplasias. It is characterised by short limb dwarfism complicated by thoracic hypoplasia, polydactyly and different anomalies of major organs such as congenital heart defects and renal dysplasia. Four major types of the SRPS have been described: type I (Saldino-Noonan); type II (Majewski); type III (Verma-Naumoff) and type IV (Beemar-Langer). However, there is phenotypic overlapping between four types and with those of non-lethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). Our cases show the importance of the nuchal translucency (NT) scan that offers the opportunity to examine fetal anatomy in the 1st trimester and diagnose rare skeletal abnormalities early in pregnancy.

23259869

Pregnancy with known syndrome of inappropriate antidiuretic hormone.

Syndrome of inappropriate antidiuretic hormone (SIADH) is rarely encountered in pregnancy. We report a case of severe hyponatraemia with idiopathic SIADH. A total of 18 cases of hyponatraemia in pregnancy have been reported; seven fit the criteria of SIADH. Unlike our case, none were diagnosed before pregnancy. Of the cases, 13 were associated with pre-eclampsia. Our patient developed intrauterine growth restriction (IUGR) but did not develop pre-eclampsia.

23259868

The fetal safety of thiopurines for the treatment of inflammatory bowel disease in pregnancy.

Maintaining remission of inflammatory bowel disease (IBD) during pregnancy is critical for positive pregnancy outcomes. Conflicting data exist regarding the association between thiopurine use for IBD treatment in pregnancy and adverse pregnancy outcomes and this meta-analysis aims to clarify this association. A meta-analysis was performed of all original human studies reporting outcomes in pregnancy in patients receiving thiopurines. Nine studies satisfied the inclusion criteria and a total of 494 patients with IBD and 2,782 IBD controls were reported. When compared with healthy women, those receiving thiopurines had an increased risk for congenital malformations (RR 1.45; 95% CI 1.07-1.96; p = 0.02); however, when compared with IBD controls, there was no increased risk (RR 1.37; 95% CI 0.92-2.05; p = 0.1). These data provide support for thiopurines having a minimal risk, if any, to the fetus.

23259867

Dissolved nitrous oxide concentrations and fluxes from the eutrophic San Joaquin River, California.

Agriculturally impacted ecosystems can be a source of the greenhouse gas, nitrous oxide (N(2)O); yet in situ measurements of N(2)O fluxes are sparse, particularly in streams and rivers. Dissolved N(2)O was measured from 9 sites over a 13-month period and a gas exchange model was used to predict N(2)O fluxes. N(2)O fluxes were measured at 4 sites on 7 sampling dates using floating chambers. In addition, dissolved N(2)O in porewaters was measured at 4 sites at various depths from 2 to 30 cm. Dissolved N(2)O-N concentrations in surface waters (0.31-1.60 μg L(-1)) varied seasonally with highest concentrations in late fall and early summer and lowest in winter. Estimated N(2)O-N fluxes (26.2-207 μg m(-2) hr(-1)) were in relative agreement with measured N(2)O fluxes using floating chambers (9.5-372 μg m(-2) hr(-1)) and correlated strongly with temperature and nitrate concentrations (R(2) = 0.86). Maximum dissolved N(2)O-N:NO(3)(-)-N ratios were higher in sediment-porewaters at 0.16, compared to surface waters (0.010). The calculated EF5-r value (mean = 0.0028; range = 0.0012-0.0069) was up to 3 times greater than the current IPCC EF5-r emissions factor (0.0025 kg N(2)O-N emitted per kg of NO(3)(-)-N leached). The highest EF5-r values were found in the high-flow sampling events when dissolved N(2)O and NO(3)(-) concentrations were low, highlighting potential constraints in the IPCC methodology for large rivers.

23259865

Synthesis and biological evaluation of indenoisoquinolines that inhibit both tyrosyl-DNA phosphodiesterase I (Tdp1) and topoisomerase I (Top1).

Tyrosyl-DNA phosphodiesterase I (Tdp1) plays a key role in the repair of damaged DNA resulting from the topoisomerase I (Top1) inhibitor camptothecin and a variety of other DNA-damaging anticancer agents. This report documents the design, synthesis, and evaluation of new indenoisoquinolines that are dual inhibitors of both Tdp1 and Top1. Enzyme inhibitory data and cytotoxicity data from human cancer cell cultures were used to establish structure-activity relationships. The potencies of the indenoisoquinolines against Tdp1 ranged from 5 μM to 111 μM, which places the more active compounds among the most potent known inhibitors of this target. The cytotoxicity mean graph midpoints ranged from 0.02 to 2.34 μM. Dual Tdp1-Top1 inhibitors are of interest because the Top1 and Tdp1 inhibitory activities could theoretically work synergistically to create more effective anticancer agents.

23259866

Morphologies of ABC triblock terpolymer melts containing poly(cyclohexadiene): effects of conformational asymmetry.

We have synthesized linear ABC triblock terpolymers containing poly(1,3-cyclohexadiene), PCHD, as an end block and characterized their morphologies in the melt. Specifically, we have studied terpolymers containing polystyrene (PS), polybutadiene (PB), and polyisoprene (PI) as the other blocks. Systematically varying the ratio of 1,2- /1,4-microstructures of poly(1,3-cyclohexadiene), we have studied the effects of conformational asymmetry among the three blocks on the morphologies using transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS), and self-consistent field theory (SCFT) performed with PolySwift++. Our work reveals that the triblock terpolymer melts containing a high percentage of 1,2-microstructures in the PCHD block are disordered at 110 °C for all the samples, independent of sequence and volume fraction of the blocks. In contrast, the triblock terpolymer melts containing a high percentage of 1,4-microstructure form regular morphologies known from the literature. The accuracy of the SCFT calculations depends on calculating the χ parameters that quantify the repulsive interactions between different monomers. Simulations using χ values obtained from solubility parameters and group contribution methods are unable to reproduce the morphologies as seen in the experiments. However, SCFT calculations accounting for the enhancement of the χ parameter with an increase in the conformational asymmetry lead to an excellent agreement between theory and experiments. These results highlight the importance of conformational asymmetry in tuning the χ parameter and, in turn, morphologies in block copolymers.

23259864

On the effects of temperature, pressure, and dissolved salts on the hydrogen-bond network of water.

We study the structure of water through molecular dynamics, specifically the compression/expansion of the hydrogen-bond (H-bond) network, with temperature and pressure, and in salt solutions of alkali chlorides and sodium halides, and relate the observed local spatial perturbations with the tetrahedrality and the average number and lifetime of water H-bonds. The effect of transient H-bonds and transient broken H-bonds on H-bond lifetimes is further investigated, and results are compared with depolarized Rayleigh scattering lifetimes for neat water. A significant electrostriction is observed in the first hydration shell of Li(+) and F(-), while larger ions cause a small expansion of the H-bond network of water instead. However, both alkali cations and halide anions induce a minor contraction of the H-bond network in the second hydration shell. Further, water in the second hydration shell of Li(+), Na(+), and K(+) is less tetrahedral than neat water, resembling water at high pressures, while the H-bond network in the respective hydration shell of halide anions resembles water at low temperatures. Nevertheless, neither ion induced H-bond contraction nor expansion can be exactly mapped onto P or T effects on the local structure of water. Even though the average number and lifetime of H-bonds in the ionic hydration shells of most ions are not very different from those found in neat water, Li(+) and F(-) significantly increase the lifetime of water donor and acceptor H-bonds, respectively, in the first hydration shell. The non-monotonic increase of cation and anion mobility, with ionic size, observed experimentally, is interpreted in terms of the water local tetrahedrality around cations and anions.

23259863

Developmental responses to lung injury: repair or fibrosis.

Lung development is a complex and finely balanced process. Yet the lung has a relatively limited repertoire of responses to injury, which, depending on severity of the injury and developmental stage and susceptibility of the lung, culminate in stopping development, followed by more or less successful repair or alternatively in fibrosis. Unlike fetal skin, which heals scarlessly early in gestation, but scars later in gestation and increasingly so postnatally, the damaged fetal lung does heal, but not very well. Thus lung injury appears to entrain a default developmental/repair mechanism involving increased amounts of activated TGF beta ligand signaling. When this occurs prior to or very early in the process of alveolarization, excessive TGF beta ligand inhibits further alveolarization, a disease process phenotype that has been termed Bronchopulmonary Dysplasia in extreme human prematurity. However, once alveolarization is sufficiently advanced as in mid to late gestation fetal monkey, late gestation human or adult mouse, rat or human lung, excessive TGF beta signaling results in pulmonary fibrosis. Recently we have further shown that FGF10 signaling, a process that is necessary for distal lung morphogenesis, can also antagonize bleomycin-induced lung fibrosis in adult mice by a mechanism involving inhibition of active TGF beta ligand bioavailability. We therefore suggest that lung development, repair and fibrosis have many fundamental mechanisms in common, that potentially can be manipulated using cells or soluble factors that optimize the alveolar milieu to prevent and possibly even to reverse lung fibrosis.

23259861

Genetic diversity of Mycobacterium tuberculosis isolates from Beijing, China assessed by Spoligotyping, LSPs and VNTR profiles.

Tuberculosis is one of the most infectious diseases in the world. Molecular typing methods such as spoligotyping, and VNTR (variable number tandem repeats), IS6110 in the NTF region and LSP (large sequence polymorphisms) analysis are generally useful tools for the resolution of various issues related to the classical epidemiology of Mycobacterium tuberculosis (M. tuberculosis). To determine the transmission characteristics of M. tuberculosis strains isolated in Beijing, China, and their genetic relationships, especially those among Beijing family strains, 260 M. tuberculosis strains isolated from patients presenting pulmonary tuberculosis were analyzed by spoligotyping, and by examining 22 VNTR loci and the presence/absence of IS6110 in the NTF region, RD105 and RD181. 81% (211 strains) of the isolates studied were Beijing family strains, 174 (82.5%) of which were identified as modern Beijing strains based on the presence of IS6110 upstream of the NTF region. RD181 was intact in 9 of the other 37 (17.5%) ancestral Beijing strains. The percentage of Beijing family strains in this study was consistent with previous reports. There are many differences, however, in allele diversity among VNTR loci between reports on strains from different areas. The Beijing family is the most prevalent genotype in Beijing city and the predominance of Beijing family strains has not altered in almost twenty years. Differences in the alleles and discrimination ability of VNTR loci between different regions is likely due to population differences in the regions where these M. tuberculosis strains were isolated or to differences in sampling times.

23259862

A user-friendly tool to transform large scale administrative data into wide table format using a MapReduce program with a Pig Latin based script.

Secondary use of large scale administrative data is increasingly popular in health services and clinical research, where a user-friendly tool for data management is in great demand. MapReduce technology such as Hadoop is a promising tool for this purpose, though its use has been limited by the lack of user-friendly functions for transforming large scale data into wide table format, where each subject is represented by one row, for use in health services and clinical research. Since the original specification of Pig provides very few functions for column field management, we have developed a novel system called GroupFilterFormat to handle the definition of field and data content based on a Pig Latin script. We have also developed, as an open-source project, several user-defined functions to transform the table format using GroupFilterFormat and to deal with processing that considers date conditions. Having prepared dummy discharge summary data for 2.3 million inpatients and medical activity log data for 950 million events, we used the Elastic Compute Cloud environment provided by Amazon Inc. to execute processing speed and scaling benchmarks. In the speed benchmark test, the response time was significantly reduced and a linear relationship was observed between the quantity of data and processing time in both a small and a very large dataset. The scaling benchmark test showed clear scalability. In our system, doubling the number of nodes resulted in a 47% decrease in processing time. Our newly developed system is widely accessible as an open resource. This system is very simple and easy to use for researchers who are accustomed to using declarative command syntax for commercial statistical software and Structured Query Language. Although our system needs further sophistication to allow more flexibility in scripts and to improve efficiency in data processing, it shows promise in facilitating the application of MapReduce technology to efficient data processing with large scale administrative data in health services and clinical research.

23259860

Actual exclusive breastfeeding rates and determinants among a cohort of children living in Gampaha district Sri Lanka: A prospective observational study.

Exclusive breastfeeding (EBF) during the early months of life reduce infant morbidity and mortality. Current recommendation in Sri Lanka is to continue exclusive breastfeeding up to six months of age. Exclusive breastfeeding rates are generally assessed by the 24 recall method which overestimates the actual rates. The objective of this study was to determine actual exclusive breast feeding rates in a cohort of Sri Lankan children and to determine the reasons that lead to cessation of breastfeeding before six months of age. From a cohort of 2215 babies born in Gampaha district, 500 were randomly selected and invited for the study. They were followed up at two (n = 404), four (n = 395) and six (n = 286) months. An interviewer administered questionnaire asked about feeding history and socio-demographic characteristics. Child health development record was used to assess the growth. Exclusive breastfeeding rates at two, four and six months were 98.0%, 75.4% and 71.3% respectively. The main reasons to stop exclusive breastfeeding between two to four months was concerns regarding weight gain and between four to six months were mothers starting to work. Majority of the babies that were not exclusively breastfed still continued to have breast milk. Mothers above 30 years had lower exclusive breastfeeding rates compared to younger mothers. Second born babies had higher rates than first borns. There was no significant association between maternal education and exclusive breastfeeding rates. Exclusive breastfeeding rates were high among this cohort of children. A decrease in EBF was noted between two and four months. EBF up to six months does not cause growth failure. Mothers starting to work and concerns regarding adequacy of breast milk were the major reasons to cease EBF. The actual exclusive breastfeeding rates up to six months was 65.9%.

23259859

Sporadic incidence of Fascioliasis detected during hepatobiliary procedures: a study of 18 patients from Sulaimaniyah governorate.

Fascioliasis is an often-neglected zoonotic disease and currently is an emerging infection in Iraq. Fascioliasis has two distinct phases, an acute phase, exhibiting the hepatic migratory stage of the fluke's life cycle, and a chronic biliary phase manifested with the presence of the parasite in the bile ducts through hepatic tissue. The incidence of Fascioliasis in Sulaimaniyah governorate was unexpected observation. We believe that shedding light on this disease in our locality will increase our physician awareness and experience in early detection, treatment in order to avoid unnecessary surgeries. We retrospectively evaluated this disease in terms of the demographic features, clinical presentations, and managements by reviewing the medical records of 18 patients, who were admitted to the Sulaimani Teaching Hospital and Kurdistan Centre for Gastroenterology and Hepatology. Patients were complained from hepatobiliary and/or upper gastrointestinal symptoms and diagnosed accidentally with Fascioliasis during hepatobiliary surgeries and ERCP by direct visualization of the flukes and stone analysis. Elevated liver enzymes, white blood cells count and eosinophilia were notable laboratory indices. The dilated CBD, gallstones, liver cysts and abscess were found common in radiological images. Fascioliasis diagnosed during conventional surgical CBD exploration and choledochodoudenostomy, open cholecystectomy, surgical drainage of liver abscess, ERCP and during gallstone analysis. Fascioliasis is indeed an emerging disease in our locality, but it is often underestimated and ignored. We recommend the differential diagnosis of patients suffering from Rt. Hypochondrial pain, fever and eosinophilia. The watercress ingestion was a common factor in patient's history.

23259858

A structural diagnostics diagram for metallofullerenes encapsulating metal carbides and nitrides.

Systematic structural studies of 24 different kinds of endohedral metallofullerenes, M(x)C(2n) (M = La, Y, Sc, Lu, Ti, Eu, Er, Hf, Sc(3)N; 34 ≤ n ≤ 43), as 1:1 cocrystals with solvent toluene molecules have been carried out using synchrotron radiation powder diffraction. Thirteen of the 24 molecular structures, including five metal carbides, one metal nitride endohedral fullerene, and one hollow fullerene, have been determined by a combination of the maximum entropy method and Rietveld refinement of the X-ray diffraction data obtained. We have found that the volume for one fullerene and one toluene molecule depends linearly on the number of carbon atoms in the fullerene cage. Fifteen different kinds of metal carbide endohedral fullerenes have been identified, which can be structurally characterized from the obtained lattice constants using only this linear dependence. The linear dependence found in the present study provides a metallofullerene diagnostics diagram that may have universal importance for structural characterization of the so-called cluster endohedral fullerenes.

23259856

Release of matrix metalloproteinase-8 during physiological trafficking and induced mobilization of human hematopoietic stem cells.

Previous studies indicate that the release of proteases, including the gelatinase matrix metalloproteinase (MMP)-9, from mature granulocytes plays a crucial role in cytokine-induced hematopoietic stem and progenitor cell (HSPC) mobilization. However, studies with MMP-9-deficient mice revealed that HSPC mobilization was normal in these animals, suggesting that additional proteases must be active at clinically relevant cytokine concentrations. In the present study, we provide evidence that the collagenase MMP-8 is involved in stem cell mobilization. A rapid release of MMP-8 from isolated neutrophil granulocytes can be observed during an in vitro culture. During granulocyte colony-stimulating factor-induced HSPC mobilization, highly elevated serum concentrations of MMP-8 were observed on days 4 to 6 of the mobilization regimen, concomitantly with elevated MMP-9 serum levels and higher numbers of circulating CD34(+) cells. Elevated serum concentrations of both proteases were also found in umbilical cord blood serum. In functional assays, adhesion of HSPC to osteoblasts as an essential component of the endosteal stem cell niche is negatively influenced by MMP-8. The chemokine CXCL12, which is critically involved in stem cell trafficking, can be proteolytically processed by MMP-8 treatment. This degradation has a strong inhibitory influence on HSPC migration. Taken together, our data strongly suggest that MMP-8 can be directly involved in hematopoietic stem cell mobilization and trafficking.

23259857

Dual inhibition of PI3-kinase and mTOR in renal cell carcinoma.

Although PI3-kinase mutations are uncommon in renal cell carcinoma (RCC), the PI3-kinase/Akt signalingpathway is active in most RCC. The activation of PI3-kinase would be expected to drive protein and lipid synthesisthrough its effects on mTORC1 and SREBP1, respectively. PI3-kinase also activates numerous transcription factors (e.g.the FOXO family, c-myc, NF-κB) that regulate cell proliferation and viability. The consequences of blocking PI3-kinasein RCC are just now beginning to be elucidated and are expected to include effects on tumor cell proliferation,metabolism, and angiogenesis. Several PI3-kinase inhibitors currently undergoing clinical testing are active site inhibitorsof mTOR as well and it is likely that these agents will prove particularly useful in the treatment of RCC.

23259855

Exercise therapy for chronic low back pain: protocol for an individual participant data meta-analysis.

Low back pain (LBP) is one of the leading causes of disability and has a major socioeconomic impact. Despite a large amount of research in the field, there remains uncertainty about the best treatment approach for chronic LBP, and identification of relevant patient subgroups is an important goal. Exercise therapy is a commonly used strategy to treat chronic low back pain and is one of several interventions that evidence suggests is moderately effective.In parallel with an update of the 2005 Cochrane review, we will undertake an individual participant data (IPD) meta-analysis, which will allow us to standardize analyses across studies and directly derive results, and to examine differential treatment effects across individuals to estimate how patients' characteristics modify treatment benefit. We will use standard systematic review methods advocated by the Cochrane Collaboration to identify relevant trials. We will include trials evaluating exercise therapy compared to any or no other interventions in adult non-specific chronic LBP. Our primary outcomes of interest include pain, functional status, and return-to-work/absenteeism. We will assess potential risk of bias for each study meeting selection criteria, using criteria and methods recommended by the Cochrane BRG.The original individual participant data will be requested from the authors of selected trials having moderate to low risk of bias. We will test original data and compile a master dataset with information about each trial mapped on a pre-specified framework, including reported characteristics of the study sample, exercise therapy characteristics, individual patient characteristics at baseline and all follow-up periods, subgroup and treatment effect modifiers investigated. Our analyses will include descriptive, study-level meta-analysis and meta-regression analyses of the overall treatment effect, and individual-level IPD meta-analyses of treatment effect modification. IPD meta-analyses will be conducted using a one-step approach where the IPD from all studies are modeled simultaneously while accounting for the clustering of participants with studies. We will analyze IPD across a large number of LBP trials. The resulting larger sample size and consistent presentation of data will allow additional analyses to explore patient-level heterogeneity in treatment outcomes and prognosis of chronic LBP.

23259854

Active trachoma and associated risk factors among children in Baso Liben District of East Gojjam, Ethiopia.

Trachoma is the leading cause of preventable blindness worldwide. It is common in areas where the people are socio-economically deprived. The aim of this study was to assess active trachoma and associated risk factors among children 1-9 years in East Gojjam. Community-based cross-sectional study was conducted in Baso Liben District from February to April 2012. A two-stage random cluster-sampling technique was employed and all children 1-9 years old from each household were clinically assessed for trachoma based on simplified WHO 1983 classification. Data were collected by using semi-structured interview, pre-tested questionnaire and observation. The data were entered and analyzed using SPSS version 16 statistical package. From a total of 792 children screened for trachoma (of which 50.6% were girls), the overall prevalence of active trachoma was 24.1% consisting of only 17.2% [95% CI: 14.8, 20.1] TF and 6.8% TI. There were variations among children living in low land (29.3%) and in medium land (21.4%). In multivariate analysis, low monthly income (AOR = adjusted odds ratio) 2.98; 95% CI (confidence interval): 1.85-7.85), illiterate family (AOR = 5.18; 95% CI: 2.92-9.17); unclean face (AOR = 18.68; 95% CI: 1.98-175.55); access to water source (AOR = 2.01; 95% CI: 1.27-3.15); less than 20 liters of water use (AOR = 4.88; 95% CI: 1.51-15.78); not using soap for face washing (AOR = 5.84; 95% CI: 1.98-17.19); not using latrine frequently (AOR = 1.75; 95% CI: 0.01-0.42); density of flies (AOR = 3.77; 95% CI: 2.26-6.29); less knowledgeable family (AOR = 3.91; 95% CI: 2.40-6.38) and average monthly income (AOR = 2.98; 95% CI: 1.85-7.85) were found independently associated with trachoma. Active trachoma is a major public problem among 1-9 years children and significantly associated with a number of risky factors. Improvement in awareness of facial hygiene, environmental conditions, mass antibiotic distribution and health education on trachoma transmission and prevention should be strengthened in the District.

23259853

Effects of creatine supplementation on oxidative stress profile of athletes.

Creatine (Cr) supplementation has been widely used among athletes and physically active individuals. Secondary to its performance-enhancing ability, an increase in oxidative stress may occur, thus prompting concern about its use. The purpose of this study is to investigate the effects of Cr monohydrate supplementation and resistance training on muscle strength and oxidative stress profile in healthy athletes. A randomized, double-blind, placebo-controlled method was used to assess twenty-six male elite Brazilian handball players divided into 3 groups: Cr monohydrate supplemented group (GC, N = 9), placebo group (GP, N = 9), no treatment group (COT, N = 8) for 32 days. All subjects underwent a resistance training program. Blood samples were drawn on 0 and 32 days post Cr supplementation to analyze the oxidative stress markers, thiobarbituric acid reactive species (TBARS), total antioxidant status (TAS), and uric acid. Creatine phosphokinase, urea, and creatinine were also analyzed, as well. Fitness tests (1 repetition maximum - 1RM and muscle endurance) were performed on the bench press. Body weight and height, body fat percentage (by measuring skin folds) and upper muscular area were also evaluated. Statistical analysis was performed using ANOVA. Only GC group showed increase in 1RM (54 ± 9 vs. 63 ± 10 kg; p = 0.0356) and uric acid (4.6 ± 1.0 vs. 7.4 ± 1.6 mg/dl; p = 0.025), with a decrease in TAS (1.11 ± 0.34 vs. 0.60 ± 0.19 mmol/l; p = 0.001). No differences (pre- vs. post-training) in TBARS, creatine phosphokinase, urea, creatinine, body weight and height, body fat percentage, or upper muscular area were observed in any group. When compared to COT, GC group showed greater decrease in TAS (-0.51 ± 0.36 vs. -0.02 ± 0.50 mmol/l; p = 0.0268), higher increase in 1RM (8.30 ± 2.26 vs. 5.29 ± 2.36 kg; p = 0.0209) and uric acid (2.77 ± 1.70 vs. 1.00 ± 1.03 mg/dl; p = 0.0276). We conclude that Cr monohydrate supplementation associated with a specific resistance program promoted a meaningful increase in muscle strength without inducing changes in body composition. The observed significant increase in uric acid and the decrease in TAS suggest that creatine supplementation, despite promoting acute effects on muscle strength improvement, might induce oxidative stress and decreases total antioxidant status of subjects.

23259852

Lungurra Ngoora--a pilot model of care for aged and disabled in a remote Aboriginal community--can it work?

The literature on the health of and services for older Aboriginal and Torres Strait Islander populations is relatively sparse. This study explored the development and implementation of a locally designed community service model of care for older people, and people with disability and/or mental health problems in remote Aboriginal Australia. Based on extensive community consultation with older people, families, carers, community members and stakeholders, a model of care was developed to address unmet needs for the target population and their carers in the remote community of Looma, in the Kimberley region of Australia. The model was implemented and evaluated over 12 months. The main outcome measures included the number of services (including home services, meals, transport, respite, personal care and advocacy) provided. Outcomes of community participation, capacity building, resources, partnerships, workforce, service delivery and cultural protection were assessed qualitatively by an external evaluator. The number of people receiving community care services in Looma increased from eight to 22, and services increased in all domains from 140 total services delivered for 1 month at baseline to 2356 by the final month of the program. The Lungurra Ngoora community care service model pilot project demonstrated a successful collaborative service model that addressed the care needs of older persons, those with disability and mental illness, and their carers in this remote community. The developmental approach, and model structure, could serve as a template for future delivery of services in remote Aboriginal communities.

23259851

Unlocking the potential of publicly available microarray data using inSilicoDb and inSilicoMerging R/Bioconductor packages.

With an abundant amount of microarray gene expression data sets available through public repositories, new possibilities lie in combining multiple existing data sets. In this new context, analysis itself is no longer the problem, but retrieving and consistently integrating all this data before delivering it to the wide variety of existing analysis tools becomes the new bottleneck. We present the newly released inSilicoMerging R/Bioconductor package which, together with the earlier released inSilicoDb R/Bioconductor package, allows consistent retrieval, integration and analysis of publicly available microarray gene expression data sets. Inside the inSilicoMerging package a set of five visual and six quantitative validation measures are available as well. By providing (i) access to uniformly curated and preprocessed data, (ii) a collection of techniques to remove the batch effects between data sets from different sources, and (iii) several validation tools enabling the inspection of the integration process, these packages enable researchers to fully explore the potential of combining gene expression data for downstream analysis. The power of using both packages is demonstrated by programmatically retrieving and integrating gene expression studies from the InSilico DB repository [https://insilicodb.org/app/].

23259850

Executive performance in older Portuguese adults with low education.

Evaluation of executive functions is essential in clinical diagnosis, yet there are limited data regarding the performance of participants with low education. We present results on several measures of executive functions obtained in community-dwelling adults with an overall low education and study the effect of this variable in each test. A sample of 479 adults (64% female, mean age 66.4 years) was assessed by a battery comprising 13 measures of executive function (Trail Making Test; Symbol Search; Matrix reasoning; Semantic and phonemic verbal fluencies; Stroop test; and digit spans). Tests' psychometric properties and the effects of age, gender, and education were studied across education levels within each age group. Tests showed good psychometric properties. Education explained more variance than age in the majority of measures, with lower educational levels being significantly associated to worse scores. Tables are presented with mean scores, standard deviation, and the value of extreme percentiles for younger (50-65, N = 232) and older (>65 years, N = 247) × education (0-3, 4, 5-9, and >9 years) subgroups. Education-adjusted norms are necessary for an adequate interpretation of test results. The present data may be useful for clinicians caring for populations with low literacy.

23259849

Methylations of tryptophan-modified naphthoquinone affect its inhibitory potential toward Aβ aggregation.

Aggregation of amyloid beta (Aβ) is the hallmark of Alzheimer's disease (AD). Small molecules inhibiting Aβ can be valuable therapeutics for AD. We have previously reported that 1,4-naphthoquinon-2-yl-l-tryptophan (NQTrp), reduces aggregation and oligomerization of Aβ in vitro and in vivo. In silico analysis further showed that certain functional groups of NQTrp, not in the aromatic rings, are also involved in binding and inhibiting Aβ. To better understand the exact mode of action and identify the groups crucial for NQTrp inhibitory activity, we conducted structure-activity analysis. Four derivatives of NQTrp were studied in silico: a D-isomer, two single-methylated and one double-methylated derivative. In silico results showed that the NQTrp groups involved in hydrogen bonds are the anilinic NH (i.e., the NH linker between the quinone and tryptophan moieties), the quinonic carbonyls, and the carboxylic acid. These predictions were supported by in vitro results. Our results should aid in designing improved small-molecule inhibitors of Aβ aggregation for treating AD.

23259848

Simple strategy to functionalize polymeric substrates via surface-initiated ATRP for biomedical applications.

The functionalization of polymer surfaces via surface-initiated atom transfer radical polymerization (ATRP) is of crucial importance to prepare various functional materials. It is generally complicated to conduct ATRP on different organic material surfaces. In this work, a facile photoinduced one-step method was first developed for the covalent immobilization of ATRP initiators on the C-H group-containing substrates such as biaxially oriented polypropylene (BOPP). The C-H bonds of precise location of inert polymer surfaces were readily transferred to bromoalkyl initiator, followed by ATRP of 2-(dimethylamino)ethyl methacrylate (DMAEMA) and glycidyl methacrylate (GMA), respectively, to produce the resultant patterned BOPP-g-P(DMAEMA) and BOPP-g-P(GMA) films. The epoxy groups of the P(GMA) microdomains can be aminated for covalently coupling IgG, while the P(DMAEMA) microdomains were used for immobilizing IgG via electronic interactions. The resultant IgG-coupled microdomains could interact with the corresponding target proteins, anti-IgG.

23259847

Dietary intake of radiocesium in adult residents in Fukushima prefecture and neighboring regions after the Fukushima nuclear power plant accident: 24-h food-duplicate survey in December 2011.

Since the nuclear power plant accident in Fukushima in March 2011, the Japanese government has conducted screening and removal of contaminated foods from the market that exceed provisional regulation limits for radionuclides. This study aimed to provide an urgent estimate of the dietary exposure of adult residents recruited from three areas in Japan to cesium 134 ((134)Cs), cesium 137 ((137)Cs), and, for comparison, natural potassium 40 ((40)K) on December 4, 2011. Fifty-three sets of 24-h food-duplicate samples were collected in Fukushima Prefecture and neighboring regions. The (134)Cs, (137)Cs, and (40)K levels in the samples were measured using a germanium detector. Items in the food-duplicate samples were recorded and analyzed for radiocesium intake. Radiocesium was detected in 25 of 26 samples from Fukushima. The median dietary intake of radiocesium was 4.0 Bq/day (range <0.26-17 Bq/day). The estimated annual dose from radiocesium was calculated assuming that the daily intake of radiocesium was constant throughout the year. The median estimated dose level was 23 μSv/year (range <2.6-99 μSv/year). The estimated dose level of radiocesium was significantly higher in Fukushima than in the Kanto region and western Japan. Stepwise multiple linear regression analyses demonstrated that the intake of fruits and mushrooms produced in Fukushima were significant factors for the dietary intake of (137)Cs in the 26 participants from Fukushima. The average radioactivity (±SD) of locally produced persimmons and apples (n = 16) were 23 ± 28 and 30 ± 35 Bq/kg for (134)Cs and (137)Cs, respectively. The preliminary estimated dietary dose levels among Fukushima residents were much lower than the maximum permissible dose 1 mSv/year, based on new Japanese standard limits for radiocesium in foods (100 Bq/kg for general foods). In future studies, the exposure estimates should be refined by probability sampling to eliminate biases.

23259846

Evaluation of the clinical process in a critical care information system using the Lean method: a case study.

There are numerous applications for Health Information Systems (HIS) that support specific tasks in the clinical workflow. The Lean method has been used increasingly to optimize clinical workflows, by removing waste and shortening the delivery cycle time. There are a limited number of studies on Lean applications related to HIS. Therefore, we applied the Lean method to evaluate the clinical processes related to HIS, in order to evaluate its efficiency in removing waste and optimizing the process flow. This paper presents the evaluation findings of these clinical processes, with regards to a critical care information system (CCIS), known as IntelliVue Clinical Information Portfolio (ICIP), and recommends solutions to the problems that were identified during the study. We conducted a case study under actual clinical settings, to investigate how the Lean method can be used to improve the clinical process. We used observations, interviews, and document analysis, to achieve our stated goal. We also applied two tools from the Lean methodology, namely the Value Stream Mapping and the A3 problem-solving tools. We used eVSM software to plot the Value Stream Map and A3 reports. We identified a number of problems related to inefficiency and waste in the clinical process, and proposed an improved process model. The case study findings show that the Value Stream Mapping and the A3 reports can be used as tools to identify waste and integrate the process steps more efficiently. We also proposed a standardized and improved clinical process model and suggested an integrated information system that combines database and software applications to reduce waste and data redundancy.

23259845

Molecular targets for therapy in systemic sclerosis.

Despite significant advances have been made in the recent years regarding organ-specific therapies, there is no approved 'disease-modifying' antifibrotic drug for systemic sclerosis (SSc) available to date. Although non-selective immunosuppressive agents are routinely used to treat patients with SSc, large well-controlled studies are lacking for almost all immunosuppressive agents and further evidence is required for long-term beneficial effects of these drugs. Considering these facts about immunosuppressive agents in SSc and also considering the high mortality of SSc, other therapeutic strategies are urgently needed. Recently an important role of the 5-hydroxytryptamine (5-HT: serotonin) pathway in fibrosis was reported. In this review, we discuss the role of 5-HT in fibrosis and therapeutic potential of this molecule. Besides 5-HT, there are a number of promising targets that have been extensively characterized in recent years. For many of these molecular targets, modifiers are readily available for clinical studies, and often these modifiers are used already in clinical use for other diseases. Results from these studies will show, in how far the promising preclinical results for novel antifibrotic strategies can be translated to clinical practice.

23259844

Ciprofloxacin-resistant Escherichia coli in Central Greece: mechanisms of resistance and molecular identification.

Fluoroquinolone resistant E. coli isolates, that are also resistant to other classes of antibiotics, is a significant challenge to antibiotic treatment and infection control policies. In Central Greece a significant increase of ciprofloxacin-resistant Escherichia coli has occurred during 2011, indicating the need for further analysis. A total of 106 ciprofloxacin-resistant out of 505 E. coli isolates consecutively collected during an eight months period in a tertiary Greek hospital of Central Greece were studied. Antimicrobial susceptibility patterns and mechanisms of resistance to quinolones were assessed, whereas selected isolates were further characterized by multilocus sequence typing and β-lactamase content. Sequence analysis of the quinolone-resistance determining region of the gyrA and parC genes has revealed that 63% of the ciprofloxacin-resistant E. coli harbored a distinct amino acid substitution pattern (GyrA:S83L + D87N; ParC:S80I + E84V), while 34% and 3% carried the patterns GyrA:S83L + D87N; ParC:S80I and GyrA:S83L + D87N; ParC:S80I + E84G respectively. The aac (6')-1b-cr plasmid-mediated quinolone resistance determinant was also detected; none of the isolates was found to carry the qnrA, qnrB and qnrS.Genotyping of a subset of 35 selected ciprofloxacin-resistant E. coli by multilocus sequence typing has revealed the presence of nine sequence types; ST131 and ST410 were the most prevalent and were exclusively correlated with hospital and health care associated infections, while strains belonging to STs 393, 361 and 162 were associated with community acquired infections. The GyrA:S83L + D87N; ParC:S80I + E84V substitution pattern was found exclusively among ST131 ciprofloxacin-resistant E. coli. Extended-spectrum β-lactamase-positive ST131 ciprofloxacin-resistant isolates produced CTX-M-type enzymes; eight the CTX-M-15 and one the CTX-M-3 variant. CTX-M-1 like and KPC-2 enzymes were detected in five and four ST410 ciprofloxacin-resistant E. coli isolates, respectively. Our findings suggest that, ST131 and ST410 predominate in the ciprofloxacin resistant E. coli population.

23259843

Breastfeeding and its impact on daily life in women with type 1 diabetes during the first six months after childbirth: a prospective cohort study.

For mothers with diabetes, breastfeeding is a great challenge due to their struggle with potentially unstable blood glucose levels. This paper explores breastfeeding attitudes and impact of breastfeeding on the daily life of mothers with type 1 diabetes compared with non-diabetic mothers. We performed a prospective cohort study of 108 mothers with type 1 diabetes and a reference group of 104 mothers in the west of Sweden. Data were collected through medical records and structured telephone interviews at 2 and 6 months after childbirth. Women in both the diabetes group and the reference group had high levels of confidence (84% and 93% respectively) in their breastfeeding capacity before childbirth, and 90% assessed breastfeeding as a positive and an important experience during the six months of follow-up. About 80% assessed breastfeeding as influencing daily life 'very much' or 'quite a lot' at 2 months as did 60% at 6 months, with no difference between the groups. In mothers with diabetes, the impact of breastfeeding on the priority of other duties decreased over time, as did feelings of time pressure and negative effects on patterns of sleep. Compared to the reference group, mothers with diabetes at 6 months remained more affected by disruptions in daily life and they felt more worried about their health both at 2 and 6 months after childbirth. For the reference group mothers' sensitivity to unexpected disruptions in daily routines decreased between 2 and 6 months after childbirth, and they expressed a greater need to organize their time than mothers with diabetes. Mothers with diabetes type 1 express more worry for own health and are more sensitive to distruptions. To balance their everyday life and to reduce the risk of stress and illhealth they are therefor, compared to other mothers, likely to need additional professional and peer support.

23259842

Structural and mechanistic studies of HpxO, a novel flavin adenine dinucleotide-dependent urate oxidase from Klebsiella pneumoniae.

HpxO is a flavin-dependent urate oxidase that catalyzes the hydroxylation of uric acid to 5-hydroxyisourate and functions in a novel pathway for purine catabolism found in Klebsiella pneumoniae. We have determined the structures of HpxO with and without uric acid at 2.0 and 2.2 Å, respectively. We have also determined the structure of the R204Q variant at 2.0 Å resolution in the absence of uric acid. The variant structure is very similar to that of wild-type HpxO except for the conformation of Arg103, which interacts with FAD in the variant but not in the wild-type structure. Interestingly, the R204Q variant results in the uncoupling of nicotinamide adenine dinucleotide oxidation from uric acid hydroxylation. This suggests that Arg204 facilitates the deprotonation of uric acid, activating it for the oxygen transfer. On the basis of these data, a mechanism for this reaction consisting of a nucleophilic attack of the urate anion on the flavin hydroperoxide resulting in the formation of 5-hydroxyisourate is proposed.

23259841

Visualization and virtual screening of the chemical universe database GDB-17.

The chemical universe database GDB-17 contains 166.4 billion molecules of up to 17 atoms of C, N, O, S, and halogens obeying rules for chemical stability, synthetic feasibility, and medicinal chemistry. GDB-17 was analyzed using 42 integer value descriptors of molecular structure which we term "Molecular Quantum Numbers" (MQN). Principal component analysis and representation of the (PC1, PC2)-plane provided a graphical overview of the GDB-17 chemical space. Rapid ligand-based virtual screening (LBVS) of GDB-17 using the city-block distance CBD(MQN) as a similarity search measure was enabled by a hashed MQN-fingerprint. LBVS of the entire GDB-17 and of selected subsets identified shape similar, scaffold hopping analogs (ROCS > 1.6 and T(SF) < 0.5) of 15 drugs. Over 97% of these analogs occurred within CBD(MQN) ≤ 12 from each drug, a constraint which might help focus advanced virtual screening. An MQN-searchable 50 million subset of GDB-17 is publicly available at www.gdb.unibe.ch .

23259840

pH tuning of DNA translocation time through organically functionalized nanopores.

Controlling DNA translocation speed is critically important for nanopore sequencing as free electrophoretic threading is far too rapid to resolve individual bases. A number of promising strategies have been explored in recent years, largely driven by the demands of next-generation sequencing. Engineering DNA-nanopore interactions (known to dominate translocation dynamics) with organic coatings is an attractive method as it does not require sample modification, processive enzymes, or complicated and expensive fabrication steps. In this work, we show for the first time 4-fold tuning of unfolded, single-file translocation time through small, amine-functionalized solid-state nanopores by varying the solution pH in situ. Additionally, we develop a simple analytical model based on electrostatic interactions to explain this effect which will be a useful tool in designing future devices and experiments.

23259839

Thermodynamics of anion-π interactions in aqueous solution.

Thermodynamic parameters (ΔG°, ΔH°, TΔS°), obtained by means of potentiometric and isothermal titration calorimetry (ITC) methods, for the binding equilibria involving anions of high negative charge, like SO(4)(2-), SeO(4)(2-), S(2)O(3)(2-) and Co(CN)(6)(3-), and nitroso-amino-pyrimidine receptors in water suggested that anion-π interactions furnish a stabilization of about -10 kJ/mol to the free energy of association. These anion-π interactions are almost athermic and favored by large entropic contributions which are likely due to the reduced hydrophobic pyrimidine surface exposed to water after anion aggregation, and the consequent reduced disruptive effect on the dynamic water structure. The crystal structure of the {H(4)L[Co(CN)(6)]}·2H(2)O complex showed strong anion-π interactions between Co(CN)(6)(3-) and the protonated H(4)L(3+) receptor. The CN···centroid distance (2.786(3) Å), occurring with a cyanide N atom located almost above the centroid of the pyrimidine ring, is the shortest distance till now reported for the interaction between CN(-) ions and heteroaromatic rings.

23259838

Deleted in azoospermia-like enhances in vitro derived porcine germ cell formation and meiosis.

Evidence supporting that deleted in azoospermia-like (DAZL) plays a key role during gametogenesis and meiosis continues to emerge. Our study aimed to determine whether overexpression of DAZL using a lentiviral approach in a somatic stem cell to germ cell in vitro differentiation culture could enhance the formation of primordial germ cell-like cells (PLCs) and oocyte-like cells (OLCs). Introduction of DAZL at the beginning of induced differentiation significantly increased the formation of Fragilis-positive PLCs, which was independent of mitotic proliferation. In addition, mRNA levels of the germ cell markers Oct4, Stella, and Vasa were also higher in the DAZL-transduced group and suppressed when DAZL was knocked down using small interference RNA. At later stages of differentiation, the expression of several genes associated with meiosis, including Scp3, Dmc1, Rec8, and Stra8, was determined to be significantly higher when DAZL was overexpressed, which was abrogated by its knockdown. Exogenous introduction of DAZL also increased the protein levels of SCP3 and VASA, which again was reversed by its knockdown. Although not a common phenomenon in the in vitro differentiation system, the percentage of SCP3-positive cells displaying meiotic chromosome patterns in the DAZL-transduced group was higher than in the control, as was the overall percentage of OLCs that were generated. The introduction of factors such as DAZL into a stem cell-to-germ cell differentiation culture may provide an opportunity to better understand the key genes and their interactions during gametogenesis, also providing a means to enhance the generation of germ cells in vitro.

23259837

Extracellular purines promote the differentiation of human bone marrow-derived mesenchymal stem cells to the osteogenic and adipogenic lineages.

Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions, mostly within the processes of tissue damage and repair and flogosis. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation of human bone marrow-derived mesenchymal stem cells (BM-hMSCs), while stimulating, in vitro and in vivo, their migration. Here, we investigated the effects of ATP on BM-hMSC differentiation capacity. Molecular analysis showed that ATP treatment modulated the expression of several genes governing adipogenic and osteoblastic (i.e., WNT-pathway-related genes) differentiation of MSCs. Functional studies demonstrated that ATP, under specific culture conditions, stimulated adipogenesis by significantly increasing the lipid accumulation and the expression levels of the adipogenic master gene PPARγ (peroxisome proliferator-activated receptor-gamma). In addition, ATP stimulated osteogenic differentiation by promoting mineralization and expression of the osteoblast-related gene RUNX2 (runt-related transcription factor 2). Furthermore, we demonstrated that ATP stimulated adipogenesis via its triphosphate form, while osteogenic differentiation was induced by the nucleoside adenosine, resulting from ATP degradation induced by CD39 and CD73 ectonucleotidases expressed on the MSC membrane. The pharmacological profile of P2 purinergic receptors (P2Rs) suggests that adipogenic differentiation is mainly mediated by the engagement of P2Y1 and P2Y4 receptors, while stimulation of the P1R adenosine-specific subtype A2B is involved in adenosine-induced osteogenic differentiation. Thus, we provide new insights into molecular regulation of MSC differentiation.

23259835

Reproducibility of in-vivo diffusion tensor cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

Myocardial disarray is an important histological feature of hypertrophic cardiomyopathy (HCM) which has been studied post-mortem, but its in-vivo prevalence and extent is unknown. Cardiac Diffusion Tensor Imaging (cDTI) provides information on mean intravoxel myocyte orientation and potentially myocardial disarray. Recent technical advances have improved in-vivo cDTI, and the aim of this study was to assess the interstudy reproducibility of quantitative in-vivo cDTI in patients with HCM. A stimulated-echo single-shot-EPI sequence with zonal excitation and parallel imaging was implemented. Ten patients with HCM were each scanned on 2 different days. For each scan 3 short axis mid-ventricular slices were acquired with cDTI at end systole. Fractional anisotropy (FA), mean diffusivity (MD), and helix angle (HA) maps were created using a cDTI post-processing platform developed in-house. The mean ± SD global FA was 0.613 ± 0.044, MD was 0.750 ± 0.154 × 10-3 mm2/s and HA was epicardium -34.3 ± 7.6°, mesocardium 3.5 ± 6.9° and endocardium 38.9 ± 8.1°. Comparison of initial and repeat studies showed global interstudy reproducibility for FA (SD = ± 0.045, Coefficient of Variation (CoV) = 7.2%), MD (SD = ± 0.135 × 10-3 mm2/s, CoV = 18.6%) and HA (epicardium SD = ± 4.8°; mesocardium SD = ± 3.4°; endocardium SD = ± 2.9°). Reproducibility of FA was superior to MD (p = 0.003). MD was significantly higher in the septum than the reference lateral wall (0.784 ±0.188 vs 0.714 ±0.155 ×10-3 mm2/s, p <0.001) [corrected]. Septal HA was significantly lower than the reference lateral wall in all 3 transmural layers (from -8.3° to -10.4°, all p < 0.001). To the best of our knowledge, this is the first study to assess the interstudy reproducibility of DTI in the human HCM heart in-vivo and the largest cDTI study in HCM to date. Our results show good reproducibility of FA, MD and HA which indicates that current technology yields robust in-vivo measurements that have potential clinical value. The interpretation of regional differences in the septum requires further investigation.

23259836

Anthelmintic-resistant nematodes in Irish commercial sheep flocks- the state of play.

Anthelmintic resistance has been reported in most sheep producing countries. Prior to the mid 1990s, reports of anthelmintic resistance in Ireland were sparse and focused on benzimidazole, one of the three classes of anthelmintic available during this period. This evidence for efficacy issues on Irish farms combined with awareness that anthelmintic resistance was increasingly being reported in other countries prompted the need for more comprehensive investigations on Irish farms. Faecal egg count reduction and micro-agar larval development tests were employed to investigate resistance to benzimidazole, levamisole and macrocyclic lactone. There is compelling evidence for resistance to both benzimidazole (>88% of flocks) and levamisole (>39% of flocks). Resistance of nematode populations to macrocyclic lactone was suspected on a small number of farms (11%) but needs to be confirmed. The recent introduction of two new classes of anthelmintics, after over a 25 year interval, together with the evidence that anthelmintic resistance is reported within a relatively short time following the introduction of a new anthelmintic compound means that the challenge to the industry is immediate. Actions are urgently required to manage anthelmintic resistance so as to prolong the lifespan of anthelmintics.

23259834

Detection of hantavirus in bats from remaining rain forest in São Paulo, Brazil.

The significant biodiversity found in Brazil is a potential for the emergence of new zoonoses. Study in some places of the world suggest of the presence to hantavirus in tissues of bats. Researches of hantavirus in wildlife, out rodents, are very scarce in Brazil. Therefore we decided to investigate in tissues of different species of wild animals captured in the same region where rodents were detected positive for this virus. The present work analyzed ninety-one animals (64 rodents, 19 opossums, and 8 bats) from a region of the Atlantic forest in Biritiba Mirin City, São Paulo State, Brazil. Lungs and kidneys were used for RNA extraction. The samples were screened for evidence of hantavirus infection by SYBR-Green-based real-time RT-PCR. Sixteen samples positive were encountered among the wild rodents, bats, and opossums. The detection of hantavirus in the lungs and kidneys of three marsupial species (Micoureus paraguayanus, Monodelphis ihering, and Didelphis aurita) as well in two species of bats (Diphylla ecaudata and Anoura caudifer) is of significance because these new hosts could represent an important virus reservoirs. The analysis of nucleotide sequences of the partial S segment revealed that these genes were more related to the Araraquara virus strains. This work reinforces the importance of studying hantavirus in different animal species and performing a continued surveillance before this virus spreads in new hosts and generated serious problems in public health.

23259833

Protein interface classification by evolutionary analysis.

Distinguishing biologically relevant interfaces from lattice contacts in protein crystals is a fundamental problem in structural biology. Despite efforts towards the computational prediction of interface character, many issues are still unresolved. We present here a protein-protein interface classifier that relies on evolutionary data to detect the biological character of interfaces. The classifier uses a simple geometric measure, number of core residues, and two evolutionary indicators based on the sequence entropy of homolog sequences. Both aim at detecting differential selection pressure between interface core and rim or rest of surface. The core residues, defined as fully buried residues (>95% burial), appear to be fundamental determinants of biological interfaces: their number is in itself a powerful discriminator of interface character and together with the evolutionary measures it is able to clearly distinguish evolved biological contacts from crystal ones. We demonstrate that this definition of core residues leads to distinctively better results than earlier definitions from the literature. The stringent selection and quality filtering of structural and sequence data was key to the success of the method. Most importantly we demonstrate that a more conservative selection of homolog sequences - with relatively high sequence identities to the query - is able to produce a clearer signal than previous attempts. An evolutionary approach like the one presented here is key to the advancement of the field, which so far was missing an effective method exploiting the evolutionary character of protein interfaces. Its coverage and performance will only improve over time thanks to the incessant growth of sequence databases. Currently our method reaches an accuracy of 89% in classifying interfaces of the Ponstingl 2003 datasets and it lends itself to a variety of useful applications in structural biology and bioinformatics. We made the corresponding software implementation available to the community as an easy-to-use graphical web interface at http://www.eppic-web.org.

23259832

Assessing community health center (CHC) assets and capabilities for recruiting physicians: the CHC Community Apgar Questionnaire.

Recent trends suggest that community health centers (CHCs) may experience a shortage of qualified physicians required to meet current and future demand. The purpose of this study was to develop an evaluation instrument, the CHC Community Apgar Questionnaire (CHC CAQ) for Idaho CHCs to use in physician recruitment. The instrument was developed based on the Critical Access Hospital Community Apgar Questionnaire (CAH CAQ). The CHC CAQ was customized for CHC use and 12 new factors were identified for substitution in the CHC instrument. All 13 CHCs in Idaho participated in this study. One site was chosen per CHC if the CHC had multiple service locations. In each community, the administrator of the CHC and the physician with recruiting responsibilities participated individually in a structured interview. A total of 11 physicians and 11 administrators participated in the study. Differences were found across and within classes of factors associated with success in physician recruitment. Alpha communities, those historically having more success in physician recruitment, scored higher on CAQ metrics than less successful beta communities. No material differences were noted across physician and administrator ratings. Cumulative mean Community Apgar scores (CHC CAQ) were mostly higher in alpha communities. The CHC CAQ, like the CAH CAQ, seems to discriminate between communities with differing assets and capabilities based on historical community-specific workforce trends. This assessment may suggest which factors are most important for a community to address with limited available resources and which factors are useful in marketing their CHC to prospective physicians.

23259831

Current and potential treatments for cervical cancer.

Cervical cancer is the third most common carcinoma in women worldwide. Despite increasing efforts to improve therapy in this disease, a significant proportion of women still die, mostly from recurrent or chemoresistant disease. This review discusses current treatments for early cervical cancer, advanced disease, and recurrent cervical cancer, and covers concurrent chemoradiation, neoadjuvant chemotherapy before surgery and radiation, single agent treatment, combination treatment, platinum-based and non-platinum based therapy. We also discuss promising therapeutics trategies for cervical cancer including targeted therapy, cell-based therapy, combined siRNA and chemotherapy, and immunotherapy.

23259830

Normative data for healthy older adults and an abbreviated version of the Stroop test.

Normative data for the Kaplan version of the Stroop Test are presented for 153 healthy, cognitively intact older adults aged 50-89 years. Increasing age was associated with decreased performance on all three subtests (Stroop A, Stroop B, and Stroop C), while years of education was only associated with Stroop B performance. Hence the normative data were stratified by age into three groups (50-64, 65-74, 75-89). Completion times for the first half of each trial (half-time scores) were found to have good split-half reliability and correlated highly with the original full administration scores. Means and standard deviations for the half-time administration are also presented for this sample. The current study provides more comprehensive normative data for older adults than previously available, as well as normative information for half-time scores that may have future clinical utility as an alternative, abbreviated version of the Kaplan Stroop Test.

23259829

Healthy migrants but unhealthy offspring? A retrospective cohort study among Italians in Switzerland.

In many countries, migrants from Italy form a substantial, well-defined group with distinct lifestyle and dietary habits. There is, however, hardly any information about all-cause mortality patterns among Italian migrants and their offspring. In this paper, we compare Italian migrants, their offspring and Swiss nationals. We compared age-specific and age-standardized mortality rates and hazard ratios (adjusted for education, marital status, language region and period) for Swiss and Italian nationals registered in the Swiss National Cohort (SNC), living in the German- or French-speaking part of Switzerland and falling into the age range 40-89 during the observation period 1990-2008. Overall, 3,175,288 native Swiss (48% male) and 224,372 individuals with an Italian migration background (57% male) accumulated 698,779 deaths and 44,836,189 person-years. Individuals with Italian background were categorized by nationality, country of birth and language. First-generation Italians had lower mortality risks than native Swiss (reference group), but second-generation Italians demonstrated higher mortality risks. Among first-generation Italians, predominantly Italian-speaking men and women had hazard ratios (HRs) of 0.89 (95% CI: 0.88-0.91) and 0.90 (0.87-0.92), respectively, while men and women having adopted the regional language had HRs of 0.93 (0.88-0.98) and 0.96 (0.88-1.04), respectively. Among second-generation Italians, the respective HRs were 1.16 (1.03-1.31), 1.06 (0.89-1.26), 1.10 (1.05-1.16) and 0.97 (0.89-1.05). The mortality advantage of first-generation Italians decreased with age. The mortality risks of first- and second-generation Italians vary substantially. The healthy migrant effect and health disadvantage among second-generation Italians show characteristic age/sex patterns. Future investigation of health behavior and cause-specific mortality is needed to better understand different mortality risks. Such insights will facilitate adequate prevention and health promotion efforts.

23259828

A supramolecular cross-linked conjugated polymer network for multiple fluorescent sensing.

A supramolecular cross-linked network was fabricated and demonstrated to act as a multiple fluorescent sensor. It was constructed from a fluorescent conjugated polymer and a bisammonium salt cross-linker driven by dibenzo[24]crown-8/secondary ammonium salt host-guest interactions. Compared with the conjugated polymer, the network has weak fluorescence due to the aggregation of polymer chains. Thanks to the multiple stimuli-responsiveness of host-guest interactions, the fluorescence intensity of the system can be enhanced by four types of signals, including potassium cation, chloride anion, pH increase, and heating. Hence, the network can serve as a cation sensor, an anion sensor, a pH sensor, and a temperature sensor. It can be used in both solution and thin film. Interestingly, exposure of a film made from this supramolecular cross-linked network to ammonia leads to an increase of fluorescence, making it a good candidate for gas detection.

23259827

Effects of platelet and plasma transfusion on outcome in traumatic brain injury patients with moderate bleeding diatheses.

Object Coagulopathy and thrombocytopenia are common after traumatic brain injury (TBI), yet transfusion thresholds for mildly to moderately abnormal ranges of international normalized ratio and platelet count remain controversial. This study evaluates associations between fresh frozen plasma (FFP) and platelet transfusions with long-term functional outcome and survival in TBI patients with moderate hemostatic laboratory abnormalities. Methods This study is a retrospective review of prospectively collected data of patients with mild to severe TBI. Data include patient demographics, several initial injury severity metrics, daily laboratory values, Glasgow Outcome Score- Extended (GOSE) scores, Functional Status Examination (FSE) scores, and survival to 6 months. Correlations were evaluated between these variables and transfusion of FFP, platelets, packed red blood cells (RBCs), cryoprecipitate, recombinant factor VIIa, and albumin. Ordinal regression was performed to account for potential confounding variables to further define relationships between transfusion status and long-term outcome. By analyzing collected data, mild to moderate coagulopathy was defined as an international normalized ratio 1.4-2.0, moderate thrombocytopenia as platelet count 50 × 10(9)/L to 107 × 10(9)/L, and moderate anemia as 21%-30% hematocrit. Results In patients with mild to moderate laboratory hematological abnormalities, univariate analysis shows significant correlations between poor outcome scores and FFP, platelet, or packed RBC transfusion; the volume of FFP or packed RBCs transfused also correlated with poor outcome. Several measures of initial injury and laboratory abnormalities also correlated with poor outcome. Patient age, initial Glasgow Coma Scale score, and highest recorded serum sodium were included in the ordinal regression model using backward variable selection. In the moderate coagulopathy subgroup, patients transfused with FFP were more likely to have a lower GOSE score relative to those who did not receive a transfusion (OR 5.20 [95% CI 1.72-15.73]). Patients with moderate coagulopathy who received FFP and packed RBCs were even more likely to be have a lower GOSE score (OR 7.17 [95% CI 2.12-24.12]). Moderately anemic patients who received packed RBCs alone were more likely to have a worse long-term functional outcome as determined by GOSE and FSE scores (GOSE: OR 2.41 [95% CI 1.51-3.85]; and FSE: OR 3.27 [95% CI 2.00-5.35]). No transfusion types or combinations were noted to significantly correlate with the 6-month mortality in ordinal regression. Conclusions In TBI patients with moderate coagulopathy, FFP transfusions alone or a combination of FFP and packed RBCs were associated with poorer long-term functional outcomes as measured by the GOSE. Red blood cell transfusions were associated with poor long-term functional outcome in TBI patients with moderate anemia. Platelet transfusion in patients with moderate thrombocytopenia was not significantly associated with outcome. Although transfusion is beneficial to many patients with severe hematological abnormalities, it is not without risk, and the indications for transfusion should be carefully considered in patients with moderate hematological abnormalities.

23259823

Adjustment of the endoscopic third ventriculostomy entry point based on the anatomical relationship between coronal and sagittal sutures.

The coronal suture is often used as an empirical landmark for the entry point for endoscopic third ventriculostomy. The trajectory for the approach is often drawn based on midsagittal MRI findings. However, because the coronal suture is not perpendicular to the midline, this method may be inaccurate. The junction of the coronal and sagittal sutures was exposed at the outer table of the cranium of 15 cadavers. An ideal coronal line was established perpendicular to the sagittal suture at the junction of the sagittal and coronal sutures. The distance from this ideal coronal line at the level of the coronal-sagittal junction to the actual coronal suture was measured at 1-cm intervals. The measured distance between the 2 planes was termed the distance to the coronal suture. The coronal suture bows forward as it moves from medial to lateral. From 1-6 cm lateral to the sagittal suture, the distance to the coronal suture was 0.1, 0.3, 0.5, 0.8, 1.0, and 1.4 cm, respectively. There was no significant difference between the right and left sides. The position of a bur hole for endoscopic third ventriculostomy should be moved posteriorly with respect to the coronal suture the more laterally it is placed. Although the adjustment is small, it may be crucial. Failure to make this adjustment may result in suboptimal bur hole placement and increase the risk of morbidity.

23259822

A single center's experience with the bedside subdural evacuating port system: a useful alternative to traditional methods for chronic subdural hematoma evacuation.

Object The traditional methods for managing symptomatic chronic subdural hematoma (SDH) include evacuation via a bur hole or craniotomy, both with or without drain placement. Because chronic SDH frequently occurs in elderly patients with multiple comorbidities, the bedside approach afforded by the subdural evacuating port system (SEPS) is an attractive alternative method that is performed under local anesthesia and conscious sedation. The goal of this study was to evaluate the radiographic and clinical outcomes of SEPS as compared with traditional methods. Methods A prospectively maintained database of 23 chronic SDHs treated by bur hole or craniotomy and of 23 chronic SDHs treated by SEPS drainage at Tufts Medical Center was compiled, and a retrospective chart review was performed. Information regarding demographics, comorbidities, presenting symptoms, and outcome was collected. The volume of SDH before and after treatment was semiautomatically measured using imaging software. Results There was no significant difference in initial SDH volume (94.5 cm(3) vs 112.6 cm(3), respectively; p = 0.25) or final SDH volume (31.9 cm(3) vs 28.2 cm(3), respectively; p = 0.65) between SEPS drainage and traditional methods. In addition, there was no difference in mortality (4.3% vs 9.1%, respectively; p = 0.61), length of stay (11 days vs 9.1 days, respectively; p = 0.48), or stability of subdural evacuation (94.1% vs 83.3%, respectively; p = 0.60) for the SEPS and traditional groups at an average follow-up of 12 and 15 weeks, respectively. Only 2 of 23 SDHs treated by SEPS required further treatment by bur hole or craniotomy due to inadequate evacuation of subdural blood. Conclusions The SEPS is a safe and effective alternative to traditional methods of evacuation of chronic SDHs and should be considered in patients presenting with a symptomatic chronic SDH.

23259821

Characteristics and long-term outcome of 251 patients with dural arteriovenous fistulas in a defined population.

Management of dural arteriovenous fistulas (DAVFs) has changed during the last decades due to increased knowledge of their pathophysiology and natural history as well as advances in treatment modalities. The authors describe the characteristics and long-term outcome of a large consecutive series of patients with DAVFs. Altogether 251 patients with 261 DAVFs were treated in 2 of the 5 neurosurgery departments at Helsinki and Kuopio University Hospitals between 1944 and 2006. Clinical data and radiological examinations were reviewed to assess patients' overall long-term clinical outcome. The detection rate of DAVFs increased markedly in the 1970s and again in the 1990s when digital subtraction angiography was introduced. The incidence of DAVFs in a defined southern Finnish population was 0.51 per 100,000 individuals per year, which represents 32% of all the brain arteriovenous malformations. In the early part of the series, DAVFs were treated by proximal ligation of the feeding arteries. Later, most of the patients underwent preoperative embolization and subsequent craniotomy, and since 2000 stereotactic radiosurgery has been increasingly used in the treatment of DAVFs. Fifty-nine percent of the 261 fistulas were totally occluded. Treatment-related major complications were seen in 21 patients. The advances in diagnostic methods (digital subtraction angiography, CT, and MRI) increased the detection rate of DAVFs, and as treatment modalities developed, the results of treatment and outcome of patients markedly improved with the introduction of endovascular techniques and stereotactic radiosurgery. Microsurgery is of limited use in DAVFs resistant to other treatment modalities.

23259820

Decreasing ventricular infections through the use of a ventriculostomy placement bundle: experience at a single institution.

Ventricular infection after ventriculostomy placement carries a high mortality rate. Responding to ventriculostomy infection rates, a multidisciplinary performance improvement team was formed, a comprehensive protocol for ventriculostomy placement was developed, and the efficacy was evaluated. A best-practice protocol was developed, including hand hygiene before the procedure; prophylactic antibiotics; sterile gloves changed between preparation, draping, and procedure; hair removal by clipping for dressing adherence; skin preparation using iodine povacrylex (0.7% available iodine) and isopropyl alcohol (74%); full body and head drape; full surgical attire for the surgeon and other bedside providers; and an antimicrobial-impregnated catheter. A checklist of critical components was used to confirm proper insertion and to monitor practice. Procedure-specific infection rates were calculated using the number of infections divided by the number of patients in whom an external ventricular drainage (EVD) device was inserted × 100 (%). Data were reported back to providers and to the committee. Bundle compliance was monitored over a 4-year period. At the authors' institution, 2928 ventriculostomies were performed between the beginning of the fourth quarter of 2006 and the end of the first quarter of 2012. Although the best-evidence bundle was applied to all patients, only 588 (20.1%) were checklist monitored (increasing from 7% to 23% over the study period). The infection rate for the 2 quarters before bundle implementation was 9.2%. During the study period, the rate decreased quarterly to 2.6% and then to 0%. Over a 4-year period, the rate was 1.06% (2007), 0.66% (2008), 0.15% (2009), and 0.34% (2010); it was 0% in 2011 and the first quarter of 2012. The overall EVD infection rate was 0.46% after bundle implementation. Bundle implementation including an antimicrobial-impregnated catheter dramatically decreased EVD-related infections. Training and situational awareness of appropriate practice, assisted by the checklist, plus use of the antibiotic-impregnated catheter resulted in sustained reduction in ventriculitis.

23259818

Hair as a biomarker of environmental manganese exposure.

The absence of well-validated biomarkers of manganese (Mn) exposure in children remains a major obstacle for studies of Mn toxicity. We developed a hair cleaning methodology to establish the utility of hair as an exposure biomarker for Mn and other metals (Pb, Cr, Cu), using ICPMS, scanning electron microscopy, and laser ablation ICPMS to evaluate cleaning efficacy. Exogenous metal contamination on hair that was untreated or intentionally contaminated with dust or Mn-contaminated water was effectively removed using a cleaning method of 0.5%Triton X-100 sonication plus 1 N nitric acid sonication. This cleaning method was then used on hair samples from children (n = 121) in an ongoing study of environmental Mn exposure and related health effects. Mean hair Mn levels were 0.121 μg/g (median = 0.073 μg/g, range = 0.011-0.736 μg/g), which are ∼4 to 70-fold lower than levels reported in other pediatric Mn studies. Hair Mn levels were also significantly higher in children living in the vicinity of active, but not historic, ferroalloy plant emissions compared to controls (P < 0.001). These data show that hair can be effectively cleaned of exogenous metal contamination, and they substantiate the use of hair Mn levels as a biomarker of environmental Mn exposure in children.

23259819

Novel strategy for preparation of graphene-Pd, Pt composite, and its enhanced electrocatalytic activity for alcohol oxidation.

As advanced electrodes for direct alcohol fuel cells, graphene-Pd and graphene-Pt composites with a trace of SnO(2) have been successfully synthesized by a modified electroless plating technique. The surface of graphene oxide is first sensitized by Sn(2+) ions, and subsequently, Pd or Pt nanoparticles are deposited on the surface of graphene oxide. Finally, graphene oxide was reduced to graphene by further adding NaBH(4). Compared to other carbon-(e.g., Vulcan XC-72R) supported Pd and Pt, the resultant graphene-Pd and Pt composites exhibit better electrocatalytic activity and long-term stability toward alcohol electrooxidation. Additionally, a trace amount of SnO(2) formed around active catalysts may also be beneficial to the enhancement of electrochemical activity.

23259817

Students' view upon graduation: a survey of medical education in Taiwan.

Improving the quality of medical education is a key goal of government policy in Taiwan. The aim of this study was to reflect the responses of medical education from the perspective of graduating medical students in Taiwan. This is the first survey study of medical education in Taiwan. Using the Medical School Graduation Questionnaire from the Association of American Medical Colleges (AAMC), we distributed 406 questionnaires to medical students of four medical schools in their last semester, and received 270 back (response rate, 66.5%). There were 11 medical schools in Taiwan. Most questions were assessed on a 5-point Likert scale. Students identified genetics, biochemistry, and ethics as the three most important premedical subjects preparing them for medical education and gross anatomy, physiology, and pharmacology as the three most helpful basic science subjects preparing them for clinical clerkships and electives. Most Taiwanese students were satisfied with their learning experience in internal medicine. Only 55.9% of students were confident that they had acquired the clinical skills required to become a resident, and 70.7% were satisfied with the quality of their medical education. The study offers preliminary results on the views of graduating students on the medical education system in Taiwan. In particular, our government and medical educators need to continuously put more effort into building students' confidence in their clinical skills.

23259815

Fibrosis in systemic sclerosis: common and unique pathobiology.

Fibrosis in systemic sclerosis (SSc), a complex polygenic disease associated with autoimmunity and proliferative/obliterative vasculopathy, shares pathobiologic features in common with other fibrosing illnesses, but also has distinguishing characteristics. Fibroblast activation induced by transforming growth factor-β (TGF-β), Wnts and innate immune receptors, along with oxidative stress and reactive oxygen species (ROS) are implicated in pathogenesis. On the other hand, the roles of endothelial-mesenchymal differentiation and bone marrow-derived fibrocytes remain to be established. Fibrotic responses are modulated by transcriptional activators and cofactors, epigenetic factors, and microRNAs that can amplify or inhibit ligand-induced signaling. The nuclear orphan receptor PPAR-γ appears to be important in governing the duration and intensity of fibroblast activation and mesenchymal progenitor cell differentiation, and defects in PPAR-γ expression or function in SSc may underlie the uncontrolled progression of fibrosis. Identifying the perturbations in signaling pathways and cellular differentiation programs responsible for tissue damage and fibrosis in SSc allows their selective targeting using novel compounds, or by innovative uses of already-approved drugs (drug repurposing).

23259816

Electronic charge density analysis of Li-doped polyacetylene: molecular vs periodic descriptions and nature of Li-to-chain bonding.

A detailed analysis of the electronic structure and charge distribution around the trigonal site of Li-doped polyacetylene is reported using finite chain and periodic descriptions of the polymer. Atoms-in-molecules (AIM) analysis is done to characterize the nature of the bond between Li and the polymer backbone through the location of the bond critical points and computation of the total charge on the atomic basins around the doping site. We find that the Li atom donates practically one electron to the π-system, in accordance with the classical Su-Schriffer-Heeger model. However, despite that the Li atom is equidistant from the three closest C atoms in the geometric soliton, a single Li-C bond critical point is found. The AIM quantitative analysis of the electronic density reveals that the Li(+) ion is immersed into the polymer π-cloud in a way that resembles a metallic bonding interaction.

23259814

Clostridium difficile 027 infection in Central Italy.

Clostridium difficile (CD) has increasingly become recognised as a significant international health burden, often associated with the healthcare environment. The upsurge in incidence of CD coincided with the emergence of a hypervirulent strain of CD characterized as 027. In 2010, 8 cases of CD 027 infections were identified in Italy. Since then, no further reports have been published. We describe 10 new cases of CD 027 infection occurring in Italy. Since December 2010, stool samples of patients with severe diarrhea and clinical suspicion of the presence of a hypervirulent strain, were tested for CD 027 by the Xpert C. difficile PCR assay (Cepheid, Sunnyvale, CA). Clinical, epidemiological and laboratory data were collected. From December 2010 to April 2012, 24 faecal samples from 19 patients who fit the above criteria were submitted to our laboratory. Samples were collected from 7 different hospitals.Of these, 17 had a positive PCR for CD and 10 were the epidemic 027 strain (59%). All PCR positive samples had a positive EIA toxin A/B test. Nine of 10 patients were recently exposed to antimicrobials and were healthcare-associated, including 4 with a history of long term care facility (LTCF) admission; the remaining case was community-associated, namely the wife of a patient with hospital-acquired CD 027 infection. Five patients experienced at least one recurrence of CD associated diarrhea (CDAD) with a total of 12 relapsing episodes. Of these, two patients had 5 and 6 relapses respectively.We compared the 10 patients with 027 CDAD versus the 7 patients with non-027 CDAD. None of the 7 patients with non-027 CDAD had a recent history of LTCF admission and no subsequent relapses were observed (p = 0.04). Our study shows that CD 027 is emerging in healthcare facilities in Italy. Whilst nosocomial acquisition accounted for the majority of such cases, 4 patients had history of a recent stay in a LTCF. We highlight the substantial risks of this highly transmissible organism in such environments. Moreover, 50% of our patients with CDAD from the 027 strain had high relapse rates which may serve to further establish this strain within the Italian health and social care systems.

23259813

Speech recognition index of workers with tinnitus exposed to environmental or occupational noise: a comparative study.

Tinnitus is considered the third worst symptom affecting humans. The aim of this article is to assess complaints by workers with tinnitus exposed to environmental and occupational noise. 495 workers went through an epidemiological survey at the Audiology Department of the Center for Studies on Workers' Health and Human Ecology, from 2003 to 2007. The workers underwent tonal and vocal audiometry, preceded by a clinical and occupational history questionnaire. Two-factor ANOVA and Tukey were the statistical tests used. All the analysis set statistical significance at α=5%. There was a higher prevalence of occupational tinnitus (73.7%), a predominance of female domestic workers (65.4%) in cases of environmental exposure, and predominance of male construction workers (71.5%) for occupational exposure. There was a significant difference in workers with hearing loss, who showed a mean speech recognition index (SRI) of 85%, as compared to healthy workers with a mean SRI greater than 93.5%. Signs and symptoms, speech perception, and interference in sound localization with the type of noise exposure (environmental versus occupational) comparisons found no significant differences. Studied group's high prevalence of tinnitus, major difficulties in speech recognition with hearing loss and the presence of individuals with normal hearing with both types of exposure justify the importance of measures in health promotion, prevention, and hearing surveillance. The findings highlight the importance of valuing the patients' own perception as the first indication of tinnitus and hearing loss in order to help develop appropriate public policies within the Unified National Health System (SUS).

23259809

Matrix-assisted laser desorption ionization imaging mass spectrometry: in situ molecular mapping.

Matrix-assisted laser desorption ionization imaging mass spectrometry (IMS) is a relatively new imaging modality that allows mapping of a wide range of biomolecules within a thin tissue section. The technology uses a laser beam to directly desorb and ionize molecules from discrete locations on the tissue that are subsequently recorded in a mass spectrometer. IMS is distinguished by the ability to directly measure molecules in situ ranging from small metabolites to proteins, reporting hundreds to thousands of expression patterns from a single imaging experiment. This article reviews recent advances in IMS technology, applications, and experimental strategies that allow it to significantly aid in the discovery and understanding of molecular processes in biological and clinical samples.

23259811

Direct atomic-scale imaging of hydrogen and oxygen interstitials in pure niobium using atom-probe tomography and aberration-corrected scanning transmission electron microscopy.

Imaging the three-dimensional atomic-scale structure of complex interfaces has been the goal of many recent studies, due to its importance to technologically relevant areas. Combining atom-probe tomography and aberration-corrected scanning transmission electron microscopy (STEM), we present an atomic-scale study of ultrathin (~5 nm) native oxide layers on niobium (Nb) and the formation of ordered niobium hydride phases near the oxide/Nb interface. Nb, an elemental type-II superconductor with the highest critical temperature (T(c) = 9.2 K), is the preferred material for superconducting radio frequency (SRF) cavities in next-generation particle accelerators. Nb exhibits high solubilities for oxygen and hydrogen, especially within the RF-field penetration depth, which is believed to result in SRF quality factor losses. STEM imaging and electron energy-loss spectroscopy followed by ultraviolet laser-assisted local-electrode atom-probe tomography on the same needle-like sample reveals the NbO(2), Nb(2)O(5), NbO, Nb stacking sequence; annular bright-field imaging is used to visualize directly hydrogen atoms in bulk β-NbH.

23259810

Kinome-wide activity modeling from diverse public high-quality data sets.

Large corpora of kinase small molecule inhibitor data are accessible to public sector research from thousands of journal article and patent publications. These data have been generated employing a wide variety of assay methodologies and experimental procedures by numerous laboratories. Here we ask the question how applicable these heterogeneous data sets are to predict kinase activities and which characteristics of the data sets contribute to their utility. We accessed almost 500,000 molecules from the Kinase Knowledge Base (KKB) and after rigorous aggregation and standardization generated over 180 distinct data sets covering all major groups of the human kinome. To assess the value of the data sets, we generated hundreds of classification and regression models. Their rigorous cross-validation and characterization demonstrated highly predictive classification and quantitative models for the majority of kinase targets if a minimum required number of active compounds or structure-activity data points were available. We then applied the best classifiers to compounds most recently profiled in the NIH Library of Integrated Network-based Cellular Signatures (LINCS) program and found good agreement of profiling results with predicted activities. Our results indicate that, although heterogeneous in nature, the publically accessible data sets are exceedingly valuable and well suited to develop highly accurate predictors for practical Kinome-wide virtual screening applications and to complement experimental kinase profiling.

23259807

Understanding the native nucleus pulposus cell phenotype has important implications for intervertebral disc regeneration strategies.

Low back pain is a leading cause of morbidity in developed societies and is strongly linked to degeneration of the intervertebral disc. The central nucleus pulposus (NP) region is most severely affected during disc degeneration and, consequently, is a focus for novel cell-based regenerative strategies. However, in order to develop such techniques, it is essential to first understand the biology and phenotype of the NP cells intended for repair. Microarray studies have highlighted novel NP markers that will allow a more accurate identification of cells for implantation, and along with other studies, have also revealed the potential importance of a developmental or immature NP cell phenotype in disseminating the optimal cell type for use. Additionally, the degenerative intervertebral disc is a harsh native environment and the effects of this on cells intended for implantation have yet to be fully elucidated; this is crucial for clinical translation of tissue engineered cell-based therapies.

23259806

Regenerative medicine interventions for orthopedic disorders: ethical issues in the translation into patients.

Regenerative medicine (RM) technologies, such as cell therapy, gene transfer and tissue engineering, are expected to move the field of orthopedics into a new era. Now that more and more attempts are underway to translate preclinical research into clinical studies, it is time to proactively discuss the ethical issues associated with first-in-human applications of RM interventions for musculoskeletal disorders. The design and launch of early clinical trials will be ethically challenging due to the specific features of RM in general, and the application for musculoskeletal disorders specifically. In this paper, we identify three sets of ethical issues that need to be addressed when considering initiating early clinical trials: assessment of risks and benefits; designing a study in terms of outcome measures and comparators; and participant selection. These issues are particularly emphasized in RM research that aims to apply these approaches in an early stage of degenerative musculoskeletal disorders.

23259805

Tissue engineering strategies in spinal arthrodesis: the clinical imperative and challenges to clinical translation.

Skeletal disorders requiring the regeneration or de novo production of bone present considerable reconstructive challenges and are one of the main driving forces for the development of skeletal tissue engineering strategies. The skeletal or mesenchymal stem cell is a fundamental requirement for osteogenesis and plays a pivotal role in the design and application of these strategies. Research activity has focused on incorporating the biological role of the mesenchymal stem cell with the developing fields of material science and gene therapy in order to create a construct that is not only capable of inducing host osteoblasts to produce bone, but is also osteogenic in its own right. This review explores the clinical need for reparative approaches in spinal arthrodesis, identifying recent tissue engineering strategies employed to promote spinal fusion, and considers the ongoing challenges to successful clinical translation.