Partner violence and postnatal mental health: cross-sectional analysis of factors associated with depression and anxiety in new mothers.
Intimate-partner violence and poor mental health are common, harmful issues for women of childbearing age. Although the prevalence and correlates of postpartum depression are well established, far less is known about postpartum anxiety. We aimed to investigate the association between postnatal depression and anxiety, and intimate-partner violence among women attending Victorian Maternal and Child Health services, using data from a randomised control trial: Improving Maternal and Child Health care for Vulnerable Mothers (MOVE). These data included postnatal women who had given birth between May and December 2010. Multiple logistic regression was used to estimate the association between intimate partner violence (using the Composite Abuse Scale) and postnatal depression and anxiety (Depression, Anxiety and Stress Scale), controlling for participant socio-demographic characteristics. Findings showed that abused women were more likely to report postnatal depressive and anxiety symptoms. There was an almost two-fold (odds ratio (OR) 1.76, 95% CI 1.03-3.01) and three-fold (OR 2.6, 95% CI 1.58-4.28) increase in the odds of reporting depressive and anxiety symptoms respectively, among abused compared with non-abused women. Abused women are at a higher risk of mental health problems. This study validated findings that intimate-partner violence is strongly associated with an increased risk of postnatal depression and highlighted the previously under-reported relationship with postnatal anxiety.


Fine needle aspiration cytology of oral and oropharyngeal lesions with an emphasis on the diagnostic utility and pitfalls.
This study was undertaken to evaluate the diagnostic utility and pitfalls of fine needle aspiration cytology (FNAC) in oral and oropharyngeal lesions. This was a retrospective audit of oral and oropharyngeal lesions diagnosed with FNAC over a period of six years (2005-2010). Oral/oropharyngeal lesions [n=157] comprised 0.35% of the total FNAC load. The age ranged 1-80 years with the male: female ratio being 1.4:1. Aspirates were inadequate in 7% cases. Histopathology was available in 73/157 (46.5%) cases. Palate was the most common site of involvement [n=66] followed by tongue [n=35], buccal mucosa [n=18], floor of the mouth [n=17], tonsil [n=10], alveolus [n=5], retromolar trigone [n=3], and posterior pharyngeal wall [n=3]. Cytodiagnoses were categorized into infective/inflammatory lesions and benign cysts, and benign and malignant tumours. Uncommon lesions included ectopic lingual thyroid and adult rhabdomyoma of tongue, and solitary fibrous tumor (SFT), and leiomyosarcoma in buccal mucosa. A single false-positive case was dense inflammation with squamous cells misinterpreted as squamous cell carcinoma (SCC) on cytology. There were eight false-negative cases mainly due to sampling error. One false-negative case due to interpretation error was in a salivary gland tumor. The sensitivity of FNAC in diagnosing oral/oropharyngeal lesions was 71.4%; specificity was 97.8% with diagnostic accuracy of 87.7%. Salivary gland tumors and squamous cell carcinoma (SCC) are the most common lesions seen in the oral cavity. FNAC proves to be highly effective in diagnosing the spectrum of different lesions in this region. Sampling error is the main cause of false-negative cases in this region.


[Antimicrobial susceptibility and serotypes of Streptococcus pneumoniae isolated from the patients with respiratory tract infections in Hokusetsu Area of Osaka].
One hundred and thirteen strains of Streptococcus pneumoniae (S. pneumoniae) were isolated from the clinical specimens of patients with respiratory tract infections between January and December 1998 in three hospitals in Hokusetsu area of Osaka. We investigated susceptibility of 113 strains of S. pneumoniae to benzylpenicillin (PCG) and other antimicrobial agents and their serotypes. 1) Of the 113 strains of S. pneumoniae isolated, 25.7% were susceptible (PSSP), 51.3% were intermediate (PISP) and 23% were resistant to benzylpenicillin (PRSP). 2) The MICs of cefaclor, cefditoren, cefpodoxime, cefdinir, erythromycin, clindamycin and minocycline were elevated, but the MIC values of cefditoren ranged from < or = 0.03 to 1.0 microgram/ml. The susceptibility of 113 strains to cefditoren was comparatively high. 3) The MIC values of imipenem, meropenem and vancomycin for 81 strains of PISP and PRSP ranged from < or = 0.015 to 1.0 microgram/ml, from < or = 0.015 to 2.0 micrograms/ml and from 0.13 to 0.5 microgram/ml, respectively. The susceptibility of these strains to three antimicrobial agents was superior to that to the other antimicrobial agents examined. 4) Of the 60 strains examined, 19, 6, and 23 serotypes were 30, 25 and 18.3%, respectively. The three serotypes were observed in PISP and PRSP with a high frequency. 5) Isolates of S. pneumoniae were 37.2% for children under 2 years of age and 30.9% for children from 2 to 6 years of age. Most of the strains isolated from these children were resistant.


System Pharmacology-Based Strategy to Decode the Synergistic Mechanism of Zhi-zhu Wan for Functional Dyspepsia.
Functional dyspepsia (FD) is a widely prevalent gastrointestinal disorder throughout the world, whereas the efficacy of current treatment in the Western countries is limited. As the symptom is equivalent to the traditional Chinese medicine (TCM) term "stuffiness and fullness," FD can be treated with Zhi-zhu Wan (ZZW) which is a kind of Chinese patent medicine. However, the "multi-component" and "multi-target" feature of Chinese patent medicine makes it challenge to elucidate the potential therapeutic mechanisms of ZZW on FD. Presently, a novel system pharmacology model including pharmacokinetic parameters, pharmacological data, and component contribution score (CS) is constructed to decipher the potential therapeutic mechanism of ZZW on FD. Finally, 61 components with favorable pharmacokinetic profiles and biological activities were obtained through ADME (absorption, distribution, metabolism, and excretion) screening in silico. The related targets of these components are identified by component targeting process followed by GO analysis and pathway enrichment analysis. And systematic analysis found that through acting on the target related to inflammation, gastrointestinal peristalsis, and mental disorder, ZZW plays a synergistic and complementary effect on FD at the pathway level. Furthermore, the component CS showed that 29 components contributed 90.18% of the total CS values of ZZW for the FD treatment, which suggested that the effective therapeutic effects of ZZW for FD are derived from all active components, not a few components. This study proposes the system pharmacology method and discovers the potent combination therapeutic mechanisms of ZZW for FD. This strategy will provide a reference method for other TCM mechanism research.


Effect of muscarinic receptor agonists xanomeline and sabcomeline on acetylcholine and dopamine efflux in the rat brain; comparison with effects of 4-[3-(4-butylpiperidin-1-yl)-propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one (AC260584) and N-desmethylclozapine.
We have demonstrated that the main metabolite of clozapine, N-desmethylclozapine, has a significant role in the ability of clozapine to improve some aspects of cognition in schizophrenia. Furthermore, there is also evidence to suggest that it is the muscarinic M(1) receptor agonist effect of N-desmethylclozapine that underlies its cognitive effects. In the present study we examined the efficacy of two muscarinic receptor agonists xanomeline and sabcomeline to increase the efflux of acetylcholine and dopamine in rat medial prefrontal cortex and nucleus accumbens. Microdialysis in awake, freely moving rats was used to demonstrate that xanomeline at 10, but not 1 or 3 mg/kg (s.c.), significantly increased acetylcholine efflux in both the medial prefrontal cortex and nucleus accumbens. Sabcomeline, at 1 but not 0.1 or 0.5 mg/kg (s.c.), significantly increased acetylcholine efflux in the medial prefrontal cortex but not the nucleus accumbens. Both xanomeline and sabcomeline dose-dependently increased dopamine efflux in the medial prefrontal cortex but only high dose of xanomeline (10 mg/kg, s.c.) and sabcomeline (1 mg/kg, s.c.) increased that in the nucleus accumbens. The acetylcholine and dopamine efflux induced by xamomeline (10 mg/kg, s.c.) and sabcomeline (1 mg/kg, s.c.) were significantly blocked by the preferential muscarinic M(1) receptor antagonist telenzepine (3 mg/kg, s.c.), but significantly potentiated by the atypical antipsychotic drug risperidone (0.1 mg/kg, s.c.), which does not have much affinity for muscarinic receptor(s). According to the analysis of net-AUC (area under the curve) values of acetylcholine and dopamine levels, the rank order of ability of these drugs to increase acetylcholine or dopamine levels is sabcomeline>xanomeline approximately AC260584>N-desmethylclozapine. The present study suggests that the binding potency of muscarinic M(1) receptors is greatly related to their ability to increase cortical acetylcholine and dopamine efflux, and that this may have some relevance for treatment of the cognitive deficit of schizophrenia.


Seroprevalence of Toxoplasma gondii among Nunavik Inuit (Canada).
As a result of their intimate contact with the land and their nutritional habits, the Inuit of Nunavik are considered to be at risk from zoonotic infections. To better understand the risk factors for Toxoplasma gondii infection, a serosurvey was conducted in Nunavik, Québec, in September 2004. A representative sample of the Inuit adult population of Nunavik participated in this cross-sectional study (n = 917). Antibodies (IgG) against T. gondii were detected by immunoassay. Information on sociodemographic characteristics, traditional activities, domestic environment and nutrition was gathered by questionnaire and explored as variables explanatory of seropositive results. Associations found to be statistically significant in univariate analyses were assessed by multivariable logistic regression to control for confounding factors. Almost two thirds (59.8%) of the Inuit of Nunavik were found to be seropositive for T. gondii. In multivariate analyses, risk factors for seropositivity were: increasing age, gender (women > men), lower level of education, consumption of potentially contaminated water (determined by an index of risk from waterborne infections), frequent cleaning of water reservoirs, and consumption of seal meat and feathered game. There was some variation in seroprevalence between the Ungava Bay coast (52.3%) and the Hudson Bay coast (65.6%), the two main regions of Nunavik, but this variation was not significant in the multivariable logistic regression model. This cross-sectional study demonstrated high T. gondii seroprevalence in the Inuit population and revealed that age, gender, schooling and community of residence all influence serostatus in this population. Variables related to drinking water and food choices may also influence the risk of infection. These results raise important questions about T. gondii transmission in Nunavik including possible links between terrestrial and marine cycles.


Metabolic and Microbial Profiling of Soil Microbial Community under Per- and Polyfluoroalkyl Substance (PFAS) Stress.
Per- and polyfluoroalkyl substances (PFAS) represent significant stress to organisms and are known to disrupt microbial community structure and function. Nevertheless, a detailed knowledge of the soil microbial community responding to PFAS stress at the metabolism level is required. Here we integrated UPLC-HRMS-based metabolomics data with 16S rRNA and ITS amplicon data across soil samples collected adjacent to a fluoropolymer production facility to directly identify the biochemical intermediates in microbial metabolic pathways and the interactions with microbial community structure under PFAS stress. A strong correlation between metabolite and microbial diversity was observed, which demonstrated significant variations in soil metabolite profiles and microbial community structures along with the sampling locations relative to the facility. Certain key metabolites were identified in the metabolite-PFAS co-occurrence network, functioning on microbial metabolisms including lipid metabolism, amino acid metabolism, and secondary metabolite biosynthesis. These results provide novel insights into the impacts of PFAS contamination on soil metabolomes and microbiomes. We suggest that soil metabolomics is an informative and useful tool that could be applied to reinforce the chemical evidence on the disruption of microbial ecological traits.


Cytoreductive nephrectomy for metastatic RCC in the era of targeted therapy.
Metastatic renal cell carcinoma (RCC) has traditionally been associated with a poor prognosis with few effective treatments. In the multimodal treatment of metastatic RCC, cytoreductive nephrectomy (CN) became the standard of care after two randomized trials demonstrated a benefit in overall survival in patients who received CN prior to treatment with interferon. More recently, several agents (sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab) have been developed that target angiogenesis and the cellular growth pathways involved in metastatic RCC. These targeted agents have demonstrated improved outcomes compared to cytokine therapy, and have transformed metastatic RCC treatment. Targeted agents are being used as a first-line systemic treatment in patients with metastatic RCC with unprecedented success, and many studies are now focusing on the role of CN in combination with these agents for patients with metastatic RCC.


Arf6 recruits the Rac GEF Kalirin to the plasma membrane facilitating Rac activation.
Many studies implicate Arf6 activity in Rac-mediated membrane ruffling and cytoskeletal reorganization. Although Arf6 facilitates the trafficking of Rac1 to the plasma membrane and in many cases Arf6 activation leads to the activation of Rac1, the details of how Arf6 influences Rac function remain to be elucidated. We demonstrate in binding assays and by co-immunoprecipitation that GDP-bound Arf6 binds to Kalirin5, a Rho family guanine nucleotide exchange factor, through interaction with the spectrin repeat region. In cells, expression of wild type Arf6 recruits spectrin repeat 5 and Kalirin to the plasma membrane and leads to enhanced Kalirin5-induced ruffling. By contrast, expression of an Arf6 mutant that cannot become activated, Arf6 T27N, still recruits spectrin repeat 5 and Kalirin to membranes but inhibits Kalirin5-induced ruffling in HeLa cells. Kalirin5-induced Rac1 activation is increased by the expression of wild type Arf6 and decreased by Arf6T27N. Furthermore, expression of a catalytically-inactive mutant of Kalirin5 inhibits cytoskeletal changes observed in cells expressing EFA6, an Arf6 guanine nucleotide exchange factor that leads to activation of Rac. We show here with over-expressed proteins that the GDP-bound form of Arf6 can bind to the spectrin repeat regions in Kalirin Rho family GEFs thereby recruiting Kalirin to membranes. Although Kalirin is recruited onto membranes by Arf6-GDP, subsequent Rac activation and membrane ruffling requires Arf6 activation. From these results, we suggest that Arf6 can regulate through its GTPase cycle the activation of Rac.


Clinical features and therapeutic implications of 104 episodes of monomicrobial Aeromonas bacteraemia.
Aeromonas bacteraemia is not a common infectious disease, but can cause a grave outcome in infected cases. In this study, clinical presentations and prognostic factors of cases of monomicrobial Aeromonas bacteraemia were analysed. Also, the impact of beta-lactam and aminoglycoside in combination and of emerging cephalosporin-resistance during therapy was discussed. From 1989 to 1998 in a medical centre in southern Taiwan, those cases with monomicrobial Aeromonas bacteraemia were included for study. A total of 104 episodes of monomicrobial Aeromonas bacteraemia, accounting for 74% of all Aeromonas bacteraemia, were encountered. The infections usually occurred in the patients with hepatic cirrhosis (54%) or malignancy (21%) and were community-acquired (74%). Cases of community-acquired bacteraemia were more likely to have cirrhosis, a high severity score at onset, and a worse prognosis than those of nosocomial bacteraemia did and nosocomial isolates were less susceptible to cefoxitin and cefotaxime. Forty-three percent of cases had a concomitant infection focus, such as primary peritonitis, invasive cellulitis or necrotizing fasciitis, biliary tract or burn wound infections. Crude fatality rate within 2 weeks after the onset was 30%. Secondary bacteraemia and a higher severity score ( > or = 4) for illness at the first presentation were independently associated with a fatal outcome. The therapeutic superiority of beta-lactam and aminoglycoside in combination cannot be demonstrated in patients with Aeromonas bacteraemia. Cefotaxime resistance emerged in 3.4% of 58 patients treated with a cephalosporin for at least 72 h. None of the community-acquired isolates, but one-quarter of the nosocomial isolates, were resistant to cefotaxime. Aeromonas bacteraemia usually occurred in patients with liver cirrhosis or malignancy, and heralded a poor prognosis, especially while associated with a relevant infectious source or with a higher severity score at presentation. The superiority of aminoglycoside and beta-lactam in combination cannot be demonstrated while treating those patients, and the emergence of antimicrobial resistance to cephalosporin was a rare event during cephalosporin therapy. Thus, a broad-spectrum cephalosporin remains one of the antimicrobial alternatives for invasive community-acquired Aeromonas infections.


How mobility restrictions policy and atmospheric conditions impacted air quality in the State of São Paulo during the COVID-19 outbreak.
Mobility restrictions are among actions to prevent the spread of the COVID-19 pandemic and have been pointed as reasons for improving air quality, especially in large cities. However, it is crucial to assess the impact of atmospheric conditions on air quality and air pollutant dispersion in the face of the potential variability of all sources. In this study, the impact of mobility restrictions on the air quality was analyzed for the most populous Brazilian State, São Paulo, severely impacted by COVID-19. Ground-based air quality data (PM10, PM2.5, CO, SO2, NOx, NO2, NO, and O3) were used from 50 automatic air quality monitoring stations to evaluate the changes in concentrations before (January 01 - March 25) and during the partial quarantine (March 16 - June 30). Rainfall, fires, and daily cell phone mobility data were also used as supplementary information to the analyses. The Mann-Whitney U test was used to assess the heterogeneity of the air quality data during and before mobility restrictions. In general, the results demonstrated no substantial improvements in air quality for most of the pollutants when comparing before and during restrictions periods. Besides, when the analyzed period of 2020 is compared with the year 2019, there is no significant air quality improvement in the São Paulo State. However, special attention should be given to the Metropolitan Area of São Paulo (MASP), due to the vast population residing in this area and exposed to air pollution. The region reached an average decrease of 29% in CO, 28% in NOx, 40% in NO, 19% in SO2, 15% in PM2.5, and 8% in PM10 concentrations during the mobility restrictions period compared to the same period in 2019. The only pollutant that showed an increase in concentration was ozone, with a 20% increase compared to 2019 during the mobility restrictions period. Before the mobility restrictions period, the region reached an average decrease of 30% in CO, 39% in NOx, 63% in NO, 12% in SO2, 23% in PM2.5, 18% in PM10, and 16% in O3 concentrations when compared to the same period in 2019. On the other hand, Cubatão, a highly industrialized area, showed statistically significant increases above 20% for most monitored pollutants in both periods of 2020 compared to 2019. This study reinforces that the main driving force of pollutant concentration variability is the dynamics of the atmosphere at its various time scales. An abnormal rainy season, with above average rainfall before the restrictions and below average after it, generated a scenario in which the probable significant reductions in emissions did not substantially affect the concentration of pollutants.


Click communication in wild harbour porpoises (Phocoena phocoena).
Social delphinids employ a vocal repertoire of clicks for echolocation and whistles for communication. Conversely, the less social and acoustically cryptic harbour porpoises (Phocoena phocoena) only produce narrow-band high-frequency (NBHF) clicks with properties that appear poorly suited for communication. Nevertheless, these small odontocetes likely mediate social interactions, such as mate choice and mother-calf contact, with sound. Here, we deployed six tags (DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate if the patterns and use of stereotyped NBHF click trains are consistent with a communication function. We show that wild porpoises produce frequent (up to 27 • min-1), high-repetition rate click series with repetition rates and output levels different from those of foraging buzzes. These sounds are produced in bouts and frequently co-occur with emission of similar sounds by nearby conspecifics, audible on the tags for >10% of the time. These results suggest that social interactions are more important to this species than their limited social encounters at the surface may indicate and that these interactions are mediated by at least two broad categories of calls composed of short, high-repetition rate click trains that may encode information via the repetition rate of their stereotyped NBHF clicks.


Regulation of expression of N-methylpurine DNA glycosylase in human mammary epithelial cells: role of transcription factor AP-2.
The DNA repair enzyme, N-methylpurine DNA glyclosylase (MPG), is overexpressed in breast cancer as compared with its expression in normal breast epithelial cells. In an effort to determine the mechanism responsible for this difference in expression, we studied rates and regulation of transcription of the MPG gene in normal (HMEC), spontaneously immortalized (MCF10A), and malignant (T47D) mammary epithelial cells. Steady state levels of MPG mRNA are 3-4-fold greater in T47D cells than in MCF10A cells. Nuclear "run-off" transcription measurements revealed MPG transcription rates to be approximately 3-fold greater in the tumor cells than in normal cells. Characterization of the MPG promoter by deletion analysis and transient transfection experiments revealed that all basal promoter activity resided between nucleotides -227 and -81 upstream from the ATG translation start site. Constructs containing this region were expressed at 4-fold greater levels when transfected into malignant T47D cells (56 x baseline) than in MCF10A cells (14 x baseline). Computer database analysis of the region of nucleotides -227 to -81 revealed multiple overlapping Sp1 consensus binding sites and two overlapping consensus AP-2 binding sites located between bases -181 and -169. Electrophoretic mobility shift assays indicated that while Sp1 bound this region of the promoter, nuclear extracts from both cell types contained equal Sp1 binding activity. In contrast, AP-2 binding activity was significantly greater in T47D cells, and Western blots confirmed increased AP-2 protein levels in these cells. Cotransfection into MCF10A cells of the MPG promoter construct and an AP-2 expression plasmid increased MPG promoter activity 2.1-fold. Cotransfection of a dominant negative mutant of AP-2 into T47D cells reduced the extent of MPG promoter-driven transcription by 50%. To investigate the functional significance of the two overlapping AP-2 consensus binding sites, each site was mutated separately. Mutation of the upstream site decreased promoter activity by 15%, but mutation of the downstream site decreased promoter activity by 45% and abolished AP-2 binding to the promoter sequence. These data suggest that AP-2 is important in regulating MPG expression in breast cancer cells, and that the increased amount of AP-2 in these cells plays a major role in directing the increased expression of MPG.


Meningitis, pneumonitis, and arthritis caused by Neisseria meningitidis group Y.
Neisseria meningitidis subgroup Y, although commonly isolated from the nasopharynx, rarely has caused meningitis in nonmilitary individuals. Meningococcus (serogroup Y) caused pneumonitis, meningitis, and arthritis in a previously healthy woman. Findings from examination of spinal fluid were minimal, but the clinical aspects of the illness were similar to those seen with other meningococcal serotypes.


Effects of Repeated Jump Testing and Diurnal Changes on Subsequent Countermovement Jump and Squat Jump Output and Force-Time Characteristics.
Harrison, PW, James, LP, Jenkins, DG, Holmberg, PM, and Kelly, VG. Effects of repeated jump testing and diurnal changes on subsequent countermovement jump and squat jump output and force-time characteristics. J Strength Cond Res 38(1): 174-179, 2024-The aim of this brief study was to investigate the effects of repeated jump testing on performance over 2 consecutive days while considering the possibility of diurnal changes. Fourteen male subjects and 14 recreationally active female subjects completed countermovement jump (CMJ) and squat jump (SJ) testing on 5 occasions (baseline [0,800], 5 minutes [0,820], 8 hours [1,600], 24 hours [0,800], and 32 hours [1,600]) over 32 hours. An additional rested baseline test was conducted on a separate day in the afternoon (1,600) to compare jump performance between morning and afternoon baseline values. Excluding small decreases in CMJ height at 24 hours (p = 0.292, Cliff's delta = -0.225) in male subjects and similar decreases in CMJ height at 5 minutes (p = 0.034, Cliff's delta = -0.245) in addition to SJ height:contraction time at 32 hours (p = 0.126, Cliff's delta = 0.153) in female subjects, findings generally showed no changes in jump performance over multiple assessments. Squat jump metrics may have showed small improvements between morning and afternoon baseline values in male subjects (SJ height:contraction time [p = 0.030, Cliff's delta = 0.225]) and female subjects (SJ height [p = 0.013, Cliff's delta = 0.173] and SJ height:contraction time [p = 0.091, Cliff's delta = 0.163)]. As jump performance was largely unaffected by repeated jump testing, the present findings support the use of monitoring practices and research designs that require multiple jump assessments within acute periods (∼32 hours).


Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.
Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production.


A convenient 'one-pot' synthesis and in vitro microbiological evaluation of novel 2,7-diaryl-[1,4] -diazepan-5-ones.
A convenient method for the 'one-pot' synthesis of novel target molecule 2,7-diaryl-[1,4]-diazepan-5-ones from the respective 2,6-diaryl-piperidin-4-ones was catalyzed by NaHSO4.Al2O3 heterogeneous catalyst in dry media under microwave irradiation in solvent-free conditions. Moreover, the catalyst could be recovered and re-used up to 4 times after washing with ethyl acetate. They were evaluated for potential antibacterial activity against Staphylococcus aureus, beta-Haemolytic streptococcus, Vibreo cholerae, Salmonella typhii, Escherichia coli, Klebsiella pneumonia, Pseudomonas and antifungal activity against Aspergillus flavus, Aspergillus fumigatus, Mucor, Candida albicans and Rhizopus. Structure-Activity Relationship (SAR) led to the conclusion that, of all the compounds 25-32 tested, compound 30 exerted strong in vitro antibacterial activity against S. aureus, S. typhii, and Pseudomonas and all the compounds 25-32 were less active against E. coli, whereas all the compounds 25-32 displayed potent in vitro antifungal activity against all the fungal strains used, except compound 30, which was more effectual against Mucor.


Fruit, Vegetable and Dietary Carotenoid Intakes Explain Variation in Skin-Color in Young Caucasian Women: A Cross-Sectional Study.
Fruit and vegetables contain carotenoid pigments, which accumulate in human skin, contributing to its yellowness. This effect has a beneficial impact on appearance. The aim was to evaluate associations between diet (fruit, vegetable and dietary carotenoid intakes) and skin color in young women. Ninety-one Caucasian women (Median and Interquartile Range (IQR) age 22.1 (18.1-29.1) years, BMI 22.9 (18.5-31.9) kg/m2) were recruited from the Hunter region (Australia). Fruit, vegetable and dietary carotenoid intakes were estimated by a validated food frequency questionnaire. Skin color was measured at nine body locations (sun exposed and unexposed sites) using spectrophotometry. Multiple linear regression was used to assess the relationship between fruit and vegetable intakes and skin yellowness adjusting for known confounders. Higher combined fruit and vegetable intakes (β = 0.8, p = 0.017) were associated with higher overall skin yellowness values. Higher fruit combined fruit and vegetable intakes (β = 1.0, p = 0.004) were associated with increased unexposed skin yellowness. Combined fruit and vegetables plus dietary carotenoid intakes contribute to skin yellowness in young Caucasian women. Evaluation of interventions using improvements in appearance as an incentive for increasing fruit and vegetable consumption in young women is warranted.


LuxR-type quorum-sensing regulators that are detached from common scents.
The ability of LuxR-type proteins to regulate transcription is controlled by bacterial pheromones, N-acylhomoserine lactones (AHLs). Most LuxR-family proteins require their cognate AHLs for activity, and at least some of them require AHLs for folding and protease resistance. However, a few members of this family are able to fold, dimerize, bind DNA, and regulate transcription in the absence of AHLs; moreover, these proteins are antagonized by their cognate AHLs. Complexes between some of these proteins and their DNA binding sites are disrupted by AHLs in vitro. All such proteins are fairly closely related within the larger LuxR family, indicating that they share a relatively recent common ancestor. The 3' ends of the genes encoding these receptors invariably overlap with the 3' ends of the cognate AHL synthase genes, suggesting additional antagonism at the level of mRNA synthesis, stability or translation.


Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice.
The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection.


Phytoremediation of polycyclic hydrocarbon contaminated soil: part II. Impact on ecotoxicity.
Several biological assays were used to evaluate the toxic effects of contaminants in soil after phytoremediation. During the treatment process, significant decreases in overall toxicity were observed. Specifically, earthworm survivability and lettuce germination increased over the study period. Microbial respiration improved, but only in planted treatments. Toxicity and total polycyclic aromatic hydrocarbon concentrations showed some correlation, but the relationships generally were not significant. Soil moisture was less of a predictor for biological responses. The presence of plants did not provide a clear advantage for improving toxicity compared to unplanted treatments.


Development of real-time polymerase chain reaction for detection of Borrelia burgdorferi sensu lato in China.
Universal primers and probes were selected on the basis of the 16S rRNA gene sequence of Borrelia burgdorferi in GenBank®, and a real-time polymerase chain reaction (PCR) method for detection of B. burgdorferi was established. The results showed that this method could specifically detect the B31 strain (Borrelia burgdorferi sensu stricto), the BO23 strain (Borrelia afzelii), and the SZ strain (Borrelia garinii), without cross-reaction with genome DNA of Theileria (T. luwenshuni, T. uilenbergi, T. sinensis, T. annulata, T. sergenti, T. annulata), Babesia (B. bigemina, B. ovate, B. sp. (Xinjiang)), Anaplasma (A. marginale, A. ovis), Mycoplasma mycoides subsp. capri, and Chlamydia psittaci, which are the infective pathogens to yak and/or sheep. The sensitivity of this real-time PCR is 10⁴ times greater than that of a conventional PCR. The real-time PCR was able to amplify 16S rRNA gene from as few as 22.88 fg genomic DNA of B. burgdorferi sensu lato. Tick DNAs from 369 field samples collected from Shangzhi City of Heilongjiang Province were tested, resulting in an infection rate of 42.80%, and a total of 332 genomic DNAs from the blood of 186 yaks and 146 sheep in the Gannan Tibetan Autonomous Prefecture of Gansu Province were tested, resulting in 24.19% positive rate for the yaks and 39.04% positive rate for the sheep.


Homologue destabilization by a putative transposable element in Drosophila melanogaster.
We postulate the presence of a transposable element, designated the L factor, to explain the properties of an unstable X chromosome and its derivatives. These chromosomes generate recessive lethal mutations at high rates, as does a stable X chromosome that has been associated with them for only one generation. The stable X chromosome does not become highly mutable in the absence of the unstable X chromosome, even when autosomes from the unstable stock are present. These facts suggest that the L factor is confined to the X chromosome and that it transposes to other X chromosomes paired with it. We propose the term "homologue destabilization" to denote the change in the stable chromosome brought about by this transposition. The lethal mutations caused by the L factor occur preferentially in the region around the cut wing locus (ct) and are sometimes associated with recognizable chromosome aberrations. The breakpoints of these aberrations are most often in the vicinity of ct, implying that the L factor is located near ct on the unstable chromosome, but it may reside at other sites as well. Alternately, the ct region may simply be a preferred target for the insertion of this transposable element.


Laparoscopic surgery for large hydatide liver cyst after two previous laparotomies.
Laparoscopic surgery for hepatic echinococcosis is a technically difficult and demanding surgical procedure even for the most experienced abdominal surgeon. Surgery is performed after the conservative treatment with albendazole for 28 days. We report a case of laparoscopic partial pericystectomy with biliostasis and omentoplasty in a patient with two previously open surgeries (laparotomies)--right subcostal laparotomy for acute inflammation of the gallbladder and right pararectal laparotomy for perforated gangrenous appendix. The patient underwent extensive laparoscopic adhesiolysis due to pronounced intra-abdominal adhesions to gain access to a large hydatid cyst with the diameter of 11 cm. Laparoscopic surgery is much less traumatic to the patient with a better cosmetic effect.


Representing the forest before the trees: a global advantage effect in monkey inferotemporal cortex.
Hierarchical stimuli (large shapes composed of small shapes) have long been used to study how humans perceive the global and the local content of a scene--the forest and the trees. Studies using these stimuli have revealed a global advantage effect: humans consistently report global shape faster than local shape. The neuronal underpinnings of this effect remain unclear. Here we demonstrate a correlate and possible mechanism in monkey inferotemporal cortex (IT). Inferotemporal neurons signal the global content of a hierarchical display approximately 30 ms before they signal its local content. This is a specific expression of a general principle, related to spatial scale or spatial frequency rather than to hierarchical level, whereby the representation of a large shape develops in IT before that of a small shape. These findings provide support for a coarse-to-fine model of visual scene representation.


Climate change mitigation in food systems: the environmental and health impacts of shifting towards sustainable diets, a systematic review protocol.
Food systems contribute greatly to global climate change due to their substantial contributions to greenhouse gas emissions, water use, and resource allocation. In addition, current food systems fail to deliver healthy and sustainable foods for all, with obesity as well as undernourishment remaining a pertinent global issue. Mounting pressures such as population growth and urbanisation urge rapid and transformational adaptations in food systems to sustainably feed a growing population. Sustainable diets have been promoted as a potential climate change mitigation strategy, and are characterized by high plant based foods and reduced animal-sourced and processed foods. While the evidence base on the potential health and environmental impacts of shifts towards sustainable diets has been growing rapidly over the past decade, there has been no recent synthesis of the evidence surrounding the health and climate mitigation benefits of sustainable consumption patterns. This systematic review will synthesize the evidence of both empirical and modelling studies assessing the direct health outcomes (such as all-cause mortality and body mass index) as well as environmental impacts (greenhouse gas emissions, land use, water use etc.) of shifts towards sustainable diets. Eight literature databases will be searched to identify studies published between 1999-2019 that report both health and environmental outcomes of sustainable diets. Evidence will be mapped and subsequently analysed based on the comparability of results and reported outcomes.


Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants.
Corticosteroids have been used late in the neonatal period to treat chronic lung disease (CLD) in preterm babies and early to try to prevent it. CLD is likely to be the result of persisting inflammation in the lung and the use of powerful anti-inflammatory drugs like dexamethasone has some rationale. Early use tends to be associated with increased adverse effects so that studies of moderately early treatment (7-14 days postnatal) might have the dual benefits of fewer side effects and onset of action before chronic inflammation is established. To determine if moderately early (7-14 days) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the prevention and/or treatment of early chronic lung disease in the preterm infant. Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, Cochrane Database of Controlled Trials, Medline, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. Randomised controlled trials of postnatal corticosteroid treatment from 7-14 days of birth in high risk preterm infants were selected for this review. Data regarding clinical outcomes including mortality up to 28 days and before discharge, failure to extubate, mortality and / or chronic lung disease at 28 days and 36 weeks, CLD at 28 days and 36 weeks, infection, hyperglycaemia, hypertension, severe retinopathy of prematurity (ROP), pneumothorax, necrotizing enterocolitis (NEC), gastrointestinal bleeding, severe intraventricular hemorrhage (IVH), hypertrophic cardiomyopathy, late rescue with dexamethasone and abnormal neurological examination at follow-up were abstracted and analysed using Revman 4.0.4. Moderately early steroid treatment (vs placebo or nothing) reduced mortality by 28 days, chronic lung disease at 28 days and 36 weeks, and death or chronic lung disease at 28 days or 36 weeks. Earlier extubation was facilitated. There was no significant effect on the rates of pneumothorax, severe ROP, and NEC. Adverse effects included hypertension, hyperglycaemia, gastrointestinal bleeding, hypertrophic cardiomyopathy and infection. Steroid-treated infants were less likely to need late rescue with dexamethasone. There was only one small study of longterm follow-up and it did not show any increase in adverse neurological outcome. Moderately early corticosteroid therapy (started at 7-14 days) reduces neonatal mortality and CLD, but at the cost of important short term adverse effects. No reliable evidence concerning long term effects is provided by the trials included in this review. In view of the evidence of an important increase in cerebral palsy and other adverse neurodevelopmental outcomes from trials in which postnatal steroid was begun either earlier or later than 7-14 days, there are reasonable grounds for extending this concern to moderately early initiation of steroid therapy. More research is urgently needed, including long term follow-up of survivors included in previous and any future trials, before the benefits and risks of postnatal steroid treatment, including initiation at 7-14 days, can be reliably assessed.


[Current trends in surgical treatment of radial nerve injuries associated with injuries of the humerus].
Radial nerve is the most common injured peripheral nerve after bone and wrist injuries in human body. Radial nerve can be injured by force causing fracture of the humeral shaft, due to compound fracture of the bone or by direct injury with small fragments of the bone. This happen in of cases and in remaining caseswas caused by manipulation during the treatment of the fracture of the humeral shaft. Because of the possibility of spontaneous recovery, indication and timing of surgical treatment of the radial nerve still remain controversial. There is contradictory approach in the treatment of the injured radial nerve. In a period betwen 1979 and 2005 year we have operated 193 patients with injury of radial nerve. Among them, 97 (50.2%) have had combined injury of the humeral shaft or proximal part of radius. Rest of injuries of the radial nerve were associated with manipulation during treatment. Surgical treatment has been performed in a period between three and four months after neurological deficit. Analysing our result regarding recovery of the motor function we have used combination of gradation including British Medical Council Score and modified Highet Scale to obtain satisfactory analysis of useful functional recovery of motor function after surgical procedure. We have classified results as bad M O-2 for all muscles innervated by the radial nerve; satisfactory M3, for extensors of the wrist and fingers and M O-2 for abductor of the thumb, good M 4-5 extensors of the wrist and fingers and M3 for abductor of the thumb, and excellent M 4-5 for all muscles.


High content of long-chain n-3 polyunsaturated fatty acids in red blood cells of Kenyan Maasai despite low dietary intake.
Increasing land restrictions and a reduced livestock-to-human ratio during the 20th century led the Maasai to lead a more sedentary, market-orientated lifestyle. Although plant-derived food nowadays contributes substantially to their diet, dairy products being high in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA) still are an important energy source. Since reliable data regarding the Maasai diet date back to the 1980s, the study objective was to document current diet practices in a Kenyan Maasai community and to investigate the fatty acid distribution in diet and red blood cells. A cross-sectional study was conducted among 26 Maasai (20 women, 6 men) from Loodokilani, Kajiado District, Kenya. Food intake was described by the subjects via 24-h recall, and both food and blood samples were analysed. Two main foods--milk and ugali--constituted the Maasai diet in this region. A total of 0.9 L of milk and 0.6 kg of ugali were consumed per person and day to yield an energy intake of 7.6 MJ/d per person. A major proportion of ingested food contributing 58.3% to the total dietary energy (en%) was plant-derived, followed by dairy products representing 41.1 en%. Fat consumed (30.5 en%) was high in SFA (63.8%) and low in PUFA (9.2%). Long-chain n-3 PUFA (EPA, DPA and DHA) made up only 0.15% of the ingested fatty acids, but 5.9% of red blood cell fatty acids. The study indicates the Maasai diet is rich in SFA and low in PUFA. Nevertheless, red blood cells are composed of comparable proportions of long-chain n-3 PUFA to populations consuming higher amounts of this fatty acid group.


A practical approach to compartmental syndrome. Part III. Management.
Early diagnosis and appropriate treatment of an established compartment syndrome usually results in a functional extremity for the patient. In my experience, the commonest causes for failure of a fasciotomy are (1) delay in initiation of the operative procedure and (2) an incomplete fasciotomy. Thorough knowledge of the anatomy of the upper and lower extremity should allow the surgeon to confidently decompress any compartment with relative ease and safety for the patient. Most of these extremities have already suffered closed blunt trauma, and many are associated with an underlying fracture. It is mandatory that the surgeon minimize the operative trauma by careful handling of soft tissue and expeditious fixation of a coexistent fracture.


Tumorous Conditions of the Hand: A Retrospective Review of 402 Cases.
Knowledge concerning treatment and care of hand lesions is often based on small case series, case reports and a few large general case series. The aim of this study is to present our experience with hand tumors' and tumor-like lesions' incidence, age range and localizations. Between 2006-2016, 402 patients operated and histopathologically diagnosed with bone and soft tissue tumorous conditions of the hand were evaluated retrospectively. Three hundred sixty one out of 402 cases (89.8%) were soft tissue tumors and 41 cases (10.2%) were osseous tumors of the hand. A total of 10 malignant tumors (2.5%) were encountered in the hand. The average age of the patients was 41.9 years (ranged from 1 to 83 years). Among 361 soft tissue tumors, only 6 cases (1.6%) were malignant and they were squamous cell tumors (n=5) and synovial sarcoma (n=1). The most common soft tissue pathology was ganglion cyst (n=125). The most common bone tumor was enchondroma, diagnosed in 26 patients (6.4% of all patients). Primary malignant bone tumors were extremely rare in the hand; one osteosarcoma and one chondrosarcoma were reported. Metastatic tumors to the hand were seen in two patients; and they were lung carcinoma and chondrosarcoma metastasis. Up-date knowledge and a thorough understanding of the nature and demographic characteristics of the tumorous conditions of the hand are crucial for accurate diagnosis and appropriate treatment.


Nationwide content analysis of undergraduate obstetrics and gynaecology clinical curricula in Turkish medical schools.
The aim was to perform a document content analysis of the subject titles in the undergraduate obstetrics and gynaecology (OG) curricula in Turkish medical schools regarding the National Core Curriculum revised in 2014 (NCC-2014). Two mini-focus group discussions with four voluntary OG faculty members in each session and one of the authors as the moderator were employed within a 1-week time frame to identify the primary (n = 36) and secondary (n = 15) NCC-2014 OG titles that were then compared for the alignment with the curricula of the various medical schools published on their website. The internet search and data analyses were each completed within 3 months. Overall, about 80% and 23% of primary and secondary OG topics were present in 54 medical schools, respectively. Teaching sessions on high-risk pregnancy and ovarian cancer were present in all of the curricula. Chromosomal disorders (11 schools), candidiasis/vaginal discharge (13 schools) and female sexual dysfunction (15 schools) were the least represented primary topics. None of the curricula had a title on neural tube defects or oncological emergencies. Obesity (one school), iron deficiency anaemia (four schools), genitourinary trauma (four schools) and domestic violence (four schools) were among the underrepresented secondary subject titles. This nationwide analysis revealed deficiencies in undergraduate OG core curricular content of the medical schools.


Alcohol consumption in relation to aortic stiffness and aortic wave reflections: a cross-sectional study in healthy postmenopausal women.
Moderate alcohol consumption has been postulated to be cardioprotective. Such an effect might be reflected in large-artery properties, such as arterial stiffness and wave reflections. Three hundred seventy-one healthy postmenopausal women aged 50 to 74 years were sampled from a population-based study. Alcohol intake was calculated from a standardized questionnaire. Applanation tonometry was applied to assess the augmentation index and aortic pulse-wave velocity. Those drinking 1 to 3, 4 to 9, 10 to 14, and 15 to 35 glasses of alcoholic beverages per week had a 0.044 (95% CI -0.47 to 0.56), -0.085 (95% CI -0.59 to 0.43), -0.869 (95% CI -1.44 to -0.29), and -0.225 (95% CI -0.98 to 0.53) m/s difference in mean pulse-wave velocity compared with nondrinkers, respectively, which indicates a J-shaped relationship. Adjustment for potential confounders of pulse-wave velocity or alcohol intake did not materially change the strength of the association. Adjustment for HDL further attenuated the relationship. The augmentation index was not related to alcohol consumption when adjustments were made for physiological determinants such as age, height, and ejection duration. Among postmenopausal women, alcohol consumption is inversely associated with pulse-wave velocity. This supports the presence of a decreased risk of cardiovascular disease with moderate alcohol consumption, which may be mediated in part by HDL cholesterol.


Ticagrelor-Associated Conduction Disorder: A Case Report and Review of the Literature.
A 47-year-old female presented to emergency clinic due to non-ST-elevation myocardial infarction (NSTEMI). After receiving acetylsalicylic acid, a loading dose of ticagrelor 180 mg and intravenous unfractionated heparin, she underwent successful placement of drug eluting stent on the distal part of non-dominant left circumflex artery. The patient had no pre-existing atrioventricular (AV) block and did not use AV blocking agent. Approximately 10 h after taking a loading dose of ticagrelor, baseline normal rhythm degenerated to the first and then complete AV block, with mild dizziness. Following cessation of ticagrelor, cardiac rhythm returned to normal level within 2 days. The close monitoring of patients after starting ticagrelor is imperative, so ticagrelor may result in advanced conduction disorders. Here, we report a patient who developed various types of AV block associated with the ticagrelor taken during successful percutaneous coronary intervention for NSTEMI. We also reviewed the literature on the association between ticagrelor use and conduction abnormalities.


Increased synthesis of low-molecular-weight nuclear ribonucleic acids of rat liver after gamma irradiation and hepatectomy.
Incorporation of [3H]orotic acid into low-molecular-weight nRNA of rat liver, fractionated on polyacrylamide gels, increased 6-12h after partial hepatectomy and 6h after gamma-irridation at 2000 R. The incorporation of orotic acid was particularly increased into the 4.5S, 5S and approx. 10S nRNA fractions. If the irradiation was given after 6h of regeneration and RNA was isolated from the nucleus 12h after hepatectomy then the incorporation of orotic acid into these low-molecular-weight nRNA components was greater than after hepatectomy or irradiation alone.


Gain of the EGFR gene located on 7p12 is a frequent and early event in squamous cell carcinoma of the lung.
Identification of molecular alterations in biological fluids has been proposed as a powerful tool for cancer diagnosis. The purpose of this study was to identify cells that carry chromosomal alterations indicative of malignancy-specifically, gains in the loci 5p15.2 (D5S23, D5S721), 6p11 approximately q11, 7p12 (EGFR), and 8q24.12 approximately q24.13 (MYC)-for the detection of lung cancer using induced sputum. The overall sensitivity of the multicolor fluorescence in situ hybridization (FISH) assay from 52 lung cancer patients was 71% and the specificity was 100% (15 of 15). The most frequently detected gains were at 7p12 (EGFR) in 17 of 24 completely resectable early-stage (II+IIIA) non-small cell lung cancers (NSCLC) (71%). There was a statistically significant increase in the proportion of cases with gains of EGFR in squamous cell carcinomas (SCC), compared with adenocarcinomas (AC) (82 vs. 43%, respectively; P = 0.017), and a higher average EGFR gene copy number in the SCCs than in the ACs (5.04 vs. 3.78, respectively; P = 0.013) in 41 NSCLCs. Conversely, a gain at the 6p11 approximately q11 and 8q24.12 approximately q24.13 (MYC) regions appears to have a higher frequency of gain in the ACs (71 and 86%, respectively) than in the SCCs (48 and 56%, respectively). The results of this study showed the potential utility of the LAVysion FISH assay for the detection of lung cancer by a noninvasive technique based on the analysis of genetic alterations of induced sputum. Defining abnormalities in sputum specimens as FISH aneusomy may be a possible diagnostic method for the early detection of lung cancer in screening of high-risk populations and monitoring for recurrence.


Dietary omega-3 fatty acids and ganglion cell function.
Diet-induced deficiencies in Omega-3 (omega-3) fatty acids are well known to alter photoreceptor function. In this study, the broader functional changes in a diversity of retinal neurons were considered. Sprague-Dawley dams were fed either omega-3-sufficient (omega-3(+), n = 21) or -deficient (omega-3(-), n = 19) diets 5 weeks before conception, with the pups continued on the mothers' diet. After 20 weeks of age, electroretinograms (ERGs) were recorded by using protocols that isolate separate cellular generators, including; photoreceptors (PIII), ON-bipolar cells (PII), and ganglion/amacrine cells (STR). At the brightest energies, rod and cone responses were isolated with a paired-flash paradigm. Retinal tissue (omega-3(+), n = 5; omega-3(-), n = 5) was harvested at 23 weeks of age for fatty acid assays with thin layer and gas liquid chromatography. Omega-3 deficiency caused a 48.6% decrease in total retinal docosahexaenoic acid (DHA). This change induced significant amplitude decreases only in the rod PII (-8.2%) and positive (p)STR components (-27.4%), with widespread delays in all signals (PIII 5.7%, PII 13.6%, pSTR 7.6%, and negative [n]STR 8.3%). Omega-3 deficiency exerted its greatest effects on signals originating in the inner retina (pSTR). Increasing dietary omega-3 has beneficial effects across the retina, with the greatest improvement occurring in ganglion cell function.


Spectral sensitivity transition in the compound eyes of a twilight-swarming mayfly and its visual ecological implications.
Aquatic insect species that leave the water after larval development, such as mayflies, have to deal with extremely different visual environments in their different life stages. Measuring the spectral sensitivity of the compound eyes of the virgin mayfly (Ephoron virgo) resulted in differences between the sensitivity of adults and larvae. Larvae were primarily green-, while adults were mostly UV-sensitive. The sensitivity of adults and larvae was the same in the UV, but in the green spectral range, adults were 3.3 times less sensitive than larvae. Transmittance spectrum measurements of larval skins covering the eye showed that the removal of exuvium during emergence cannot explain the spectral sensitivity change of the eyes. Taking numerous sky spectra from the literature, the ratio of UV and green photons in the skylight was shown to be maximal for θ ≈ -13° solar elevation, which is in the θmin = -14.7° and θmax = -7.1° typical range of swarming that was established from webcam images of real swarmings. We suggest that the spectral sensitivity of both the larval and adult eyes are adapted to the optical environment of the corresponding life stages.


Respiratory and cardiovascular responses of the exercising chicken to spinal cord cooling at different ambient temperatures. II. Respiratory responses.
We measured oxygen consumption (VO2), carbon dioxide production (VCO2), minute volume (VE), respiratory frequency (f) and tidal volume (VT) of chickens during 15 min treadmill exercise at 0.5 ms-1 and 0.8 ms-1 at thermoneutral (23 degrees C), low (9 degrees C) and high (34 degrees C) ambient temperature (Ta); the vertebral canal was cooled to 34 degrees C during the middle 5 min of each exercise period. Temperatures of the vertebral canal (TVC) and rectum (Tre) were also measured. Exercise at 0.5 ms-1 caused increases in O2 consumption, CO2 production, minute volume and tidal volume compared to resting controls at each Ta. Minute volume and respiratory frequency were higher and tidal volume was lower in birds exercising at 34 degrees C than at 23 or 9 degrees C. Spinal cord cooling during exercise (0.5 ms-1) at 9 degrees C caused further increases in O2 consumption, tidal volume and respiratory frequency almost equivalent to those produced by an increase in the running speed to 0.8 ms-1. Spinal cord cooling during exercise (0.5 ms-1) at 23 degrees C did not significantly affect O2 consumption, CO2 production, minute volume, tidal volume or respiratory frequency. Spinal cord cooling during exercise (0.5 ms-1) at 34 degrees C did not affect O2 consumption or CO2 production, but caused decreases in minute volume and respiratory frequency and an increase in tidal volume. We conclude that the domestic fowl exhibits spinal thermosensitivity during exercise, although these responses appear to be smaller than those previously reported for the resting bird. Decreased external temperature potentiates the effects of spinal cord cooling during exercise.


[Medication errors: who is responsible?].
New diagnostic and therapeutic technologies are used with growing frequency, improving the quality of medical assistance and increasing life expectancy. Health care, however, is becoming progressively more expensive and complex. Adverse events related to medical assistance, particularly errors, are becoming public, being debated and judged in courts. Given their training, health workers are not prepared to deal with errors, which are associated with shame, fear and punishment. The approach to errors in the health system is usually individualistic, considering such events as acts of insecurity performed by careless, non-motivated and ill-trained persons. The tendency is to hide errors when they occur, with the result that an important learning opportunity is lost. There is another way to deal with errors, a systemic view that has obtained positive results in sectors such as aviation, anesthesiology and unit-dose drug distribution systems. These systems have varied degrees of safety and should take into account human limitations when designed and applied. A change in paradigm is needed when dealing with drugs, as it is not enough for a drug to have quality assurance, but the complete process of drug use should be safe. Medication errors, avoidable by definition, are at present a serious public health issue, leading to loss of lives and significant financial losses. A systemic approach to medication errors may disclose failures in the process as a whole, and improvements can be implemented to reduce their occurrence.


Stimulation of inducible nitric oxide synthase by monosodium urate crystals in macrophages and expression of iNOS in gouty arthritis.
From the studies on the involvement of iNOS in arthritis, it is clear that attention has focused primarily on rheumatoid arthritis (RA) and osteoarthritis (OA). To date, little is known about the role of iNOS in the pathophysiology of gouty arthritis (GA). Here, we investigated the significance of iNOS expression in cell culture system as well as in GA patients. Gouty crystals monosodium urate (MSU) appeared to up-regulate inducible nitric oxide synthase (iNOS) mRNA and protein expression in a concentration- and time-dependent manner in RAW264.7 macrophages. This increase of iNOS expression is attributable to the activation of multiple signaling pathways. Evidence for this was initially established by inhibitor treatment of cells in the presence of MSU. While the JAK inhibitor AG490, the PI3K inhibitor LY294002, and the NFkappaB inhibitor PDTC abrogated almost completely the expression of iNOS induced by MSU, the ERK1/2 inhibitor PD98059 was only partially effective. Furthermore, the effect of MSU on the activation of PI3K/Akt, JAK/STAT, ERK1/2, and NFkappaB signaling molecules was carefully examined. Moreover, it was shown that GAS and NFkappaB motifs are required for iNOS expression mediated by MSU. In addition, synovial tissues obtained from GA patients displayed enhanced expression of iNOS when compared with normal synovium. Taken together, these findings provide the first evidence for the potential importance of iNOS in the pathogenesis of GA as well as RA and OA, and in turn raise the possibility that iNOS may be an ideal target for preventive therapy in human arthritis.


Fishing in urban New Jersey: ethnicity affects information sources, perception, and compliance.
Recreational and subsistence angling are important aspects of urban culture for much of North America where people are concentrated near the coasts or major rivers. Yet there are fish and shellfish advisories for many estuaries, rivers, and lakes, and these are not always heeded. This paper examines fishing behavior, sources of information, perceptions, and compliance with fishing advisories as a function of ethnicity for people fishing in the Newark Bay Complex of the New York-New Jersey Harbor. We test the null hypothesis that there were no ethnic differences in sources of information, perceptions of the safety of fish consumption, and compliance with advisories. There were ethnic differences in consumption rates, sources of information about fishing, knowledge about the safety of the fish, awareness of fishing advisories or of the correct advisories, and knowledge about risks for increased cancer and to unborn and young children. In general, the knowledge base was much lower for Hispanics, was intermediate for blacks, and was greatest for whites. When presented with a statement about the potential risks from eating fish, there were no differences in their willingness to stop eating fish or to encourage pregnant women to stop. These results indicate a willingness to comply with advisories regardless of ethnicity, but a vast difference in the base knowledge necessary to make informed risk decisions about the safety of fish and shellfish. Although the overall median income level of the population was in the $25,000-34,999 income category, for Hispanics it was on the border between $15,000-24,999 and $25,000-34,999.


Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein-coupled receptors: a co-culture system for identifying intermediates upstream and downstream of heparin-binding EGF shedding.
"Transactivation" of epidermal growth factor receptors (EGFRs) in response to activation of many G protein-coupled receptors (GPCRs) involves autocrine/paracrine shedding of heparin-binding EGF (HB-EGF). HB-EGF shedding involves proteolytic cleavage of a membrane-anchored precursor by incompletely characterized matrix metalloproteases. In COS-7 cells, alpha(2A)-adrenergic receptors (ARs) stimulate ERK phosphorylation via two distinct pathways, a transactivation pathway that involves the release of HB-EGF and the EGFR and an alternate pathway that is independent of both HB-EGF and the EGFR. We have developed a mixed culture system to study the mechanism of GPCR-mediated HB-EGF shedding in COS-7 cells. In this system, alpha(2A)AR expressing "donor" cells are co-cultured with "acceptor" cells lacking the alpha(2A)AR. Each population expresses a uniquely epitope-tagged ERK2 protein, allowing the selective measurement of ERK activation in the donor and acceptor cells. Stimulation with the alpha(2)AR selective agonist UK14304 rapidly increases ERK2 phosphorylation in both the donor and the acceptor cells. The acceptor cell response is sensitive to inhibitors of both the EGFR and HB-EGF, indicating that it results from the release of HB-EGF from the alpha(2A)AR-expressing donor cells. Experiments with various chemical inhibitors and dominant inhibitory mutants demonstrate that EGFR-dependent activation of the ERK cascade after alpha(2A)AR stimulation requires Gbetagamma subunits upstream and dynamin-dependent endocytosis downstream of HB-EGF shedding and EGFR activation, whereas Src kinase activity is required both for the release of HB-EGF and for HB-EGF-mediated ERK2 phosphorylation.


Physical stress testing of bovine jugular veins using magnetic resonance imaging, echocardiography and electrical velocimetry.
Bovine jugular veins (BJVs) (Contegra) are valve-bearing pulmonary artery substitutes. Their valves have higher profiles than human pulmonary valves; this might result in less optimal performance. Therefore, we investigated the impact of stress and undersizing on conduit performance with ergometry, echocardiography and magnetic resonance imaging (MRI). Between April 2007 and June 2008, 20 BJV recipients (age 7.9-19.6 years) underwent spiroergometry and subsequent echocardiography; after due rest, ergometry was repeated and followed by MRI during recovery. A year later, exams were repeated. Data was evaluated as follows: comparison of stress related maximal individual valve performance changes (magnetic resonance: exercise induced average stroke volume changes by 61+/-49%; mean insufficiency increased by 2% in patients with <1% rest insufficiency and by 8% after rest insufficiency of >10%; the average rest gradient of 24+/-11 mmHg rose to 40+/-20 mmHg), and stratification of pooled observations by regurgitation fraction, insufficiency grades and z-values (insufficiency rose with increasing heart rate and decreasing stroke volume; undersizing increased gradients during recovery by 7+/-0.7 mmHg/z-value). Contegras high-profile valves tolerate stress without performance drop. Stress induced changes of insufficiency and gradient were clinically not significant, but sufficient to distort examination results; therefore, constant examination conditions are indispensable for a correct follow-up.


Endonasal access to the upper cervical spine, part one: radiographic morphometric analysis.
Objectives To determine the anatomical relationships that may influence endonasal access to the upper cervical spine. Setting We retrospectively analyzed computed tomography of 100 patients at a single institution. Participants Participants included adults with imaging of the hard palate, clivus, and cervical spine without evidence of fracture, severe spondylosis, or previous instrumentation. Main Outcome Measures Morphometric analyses of hard palate length and both distance and angle between the hard palate and odontoid process were based on radiographic measurements. Descriptive zones were assigned to cervical spine levels, and endoscopic visualization was simulated with projected lines at 0, 30, and 45 degrees from the hard palate to the cervical spine. Results We found an inverse relationship between hard palate length and the lowest zone of the cervical spine potentially visualized by nasal endoscopy. The distance between the posterior tip of the hard palate and the odontoid tip, and the angle formed between the two, directly influenced the lowest possible cervical exposure. Conclusions Radiographic relationships between hard palate length, distance to the odontoid, and the angle formed between the two predict the limits of endonasal access to the cervical spine. These results are supported by cadaveric data in Part Two of this study.


Diffusion-weighted imaging in the abdomen and pelvis: concepts and applications.
Diffusion-weighted magnetic resonance (MR) imaging allows the detection of focal solid and cystic lesions in the abdomen and pelvis and, if pitfalls are to be avoided, is most effectively used in conjunction with other imaging sequences. It is important to recognize that the strength of the diffusion sensitizing gradient (b value) can and should be adjusted to ensure optimal evaluation of the body region or organ being imaged, and that more than one b value is necessary for tissue characterization. The success of lesion detection and characterization largely depends on the extent of tissue cellularity because increased cellularity is associated with impeded diffusion, as indicated by a reduction in the apparent diffusion coefficient. It is also important to recognize that certain normal tissues such as the endometrium are highly cellular and as such demonstrate restricted diffusion, which should not be misinterpreted as disease. Impeded diffusion can also be seen in highly viscous cystic lesions such as abscesses. Diffusion-weighted imaging is an evolving technology with the potential to improve tissue characterization when findings are interpreted in conjunction with findings obtained with other conventional MR imaging sequences.


Comparison of a radioimmunoassay and a microbiological assay for measurement of serum vancomycin concentrations.
A newly developed radioimmunoassay was used to measure the concentration of vancomycin in 137 specimens of serum from patients being treated with this antibiotic. Of these sera, 84 were also analyzed with a microbiological assay technique for vancomycin. Duplicate determinations were done with each of the techniques. Individual values and averaged values for both methods were used for statistical analyses. The correlation coefficients between all possible combinations of radioimmunoassay and microbiological assay results for the 84 sera were greater than or equal to 0.99 (P less than 0.01). Values for the regression coefficients of radioimmunoassay results on microbiological assay results ranged from 0.98 +/- 0.01 to 1.03 +/- 0.01. The mean percent deviation of radioimmunoassay versus microbiological assay results was -1.56 +/- 0.60. A one-way analysis of variance demonstrated that the use of different standard curves for each batch of specimens assayed by microbiological assay did not significantly influence the results (P = 0.07). The microbiological assay and the radioimmunoassay for measurement of serum vancomycin levels yielded essentially identical results.


Whole blood PT/aPTT assay based on non-contact drop-of-sample acoustic tweezing spectroscopy.
Most coagulation tests are photo-optical turbidimetric assays that require the removal of cellular components from whole blood for optical clearing. If the resulting blood plasma samples are hemolyzed, they may become unsuitable for turbidimetric analysis. To resolve this issue, whole-blood analogs to plasma turbidimetric assays need to be developed. Using samples collected from non-smokers (normal group), smokers (thrombotic group), and hemophilia A (bleeding group) patients, we demonstrate that the reaction time assessed from whole blood viscosity data of the drop-of-blood acoustic tweezing spectroscopy (ATS) technique strongly correlates (Rp ≥ 0.95) with PT/aPTT values obtained from plasma turbidimetric data. Linear correlation (Rp ≥ 0.88) was also obtained between the viscous and elastic outputs of the ATS technique and the fibrinogen concentration. The integration of ATS data enabled the assessment of the functional level of fibrin cross-linkers such as factor XIII. Overall, ATS allows comprehensive sample-sparing analysis of whole blood coagulation for reliable and safe diagnosis of bleeding/thrombosis risks.


Development of a decision-support framework to support professionals and promote comfort among older hospital inpatients living with dementia.
Acute hospital wards can be difficult places for many people living with dementia. Promoting comfort and wellbeing can be challenging in this environment. There is little evidence-based support for professionals working on acute care wards on how to respond to distress and maximise comfort and wellbeing among patients living with dementia. Our overall aim was to codesign an evidence-based easy-to-use heuristic decision-support framework, which was acceptable and practical but acknowledges the complex and acute nature of caring for patients with dementia in the hospital. This paper presents the development process and resulting framework. A codesign study was informed by data from (1) a literature review of the care and management of people living with dementia in acute hospitals; (2) a cohort study of comfort and discomfort in people with dementia in acute hospitals; and (3) interviews with family carers and health care professionals. We synthesised evidence from these data sources and presented to key stakeholders through codesign meetings and workshops to produce our decision-support framework. The framework consists of a series of flowcharts and operates using a three-stage process of: (1) assess comfort/discomfort; (2) consider causes of discomfort; and (3) address patient needs to manage the discomfort. Working with key stakeholders, synthesising diverse quantitative and qualitative evidence to build a clinical framework is a feasible approach to help address the needs of patients living with dementia in an acute hospital setting. The result is a framework which is now ready for evaluation and implementation. We worked closely with people living with dementia and family carers throughout this study, including the development of the study protocol with input on study development and design, through to inclusion in stakeholder workshops and codesign of the decision support framework.


Object-image-based method to construct an unweighted quality map for phase extraction and phase unwrapping.
A method to construct an unweighted quality map for phase extraction and phase unwrapping is proposed, based on an object image pattern. The object image pattern must be recorded under the same conditions as that of the corresponding interference patterns, except that the lights coming from the reference arm of the interferometer are hidden. An unweighted quality map that can represent the valid and invalid regions in the interference patterns is completed successfully, based on two factors: the fact that the object region in the object image pattern is homologous with the valid region (i.e., the interference region) in the interference patterns, and on distinguishing between the object and background regions in the object image pattern using neighbor window threshold filtering and fitting the boundary of the object image. The application of the proposed method to the real measurement shows its feasibility and correctness. This paper might provide an alternative method for constructing an unweighted quality map for phase extraction and phase unwrapping.


Breast Cancer Incidence and Behavior in Younger Patients: A Study From the Surveillance, Epidemiology and End Results Database.
Breast cancer screening for women less than 40 years old is practically non-existent. Since screening can detect cancer at an early stage, not having a surveillance guideline for breast cancer in younger women can result in detection of the cancer at advanced stages. The purpose of this study was to investigate the incidence and behavior of breast cancer in younger women. The Surveillance, Epidemiology and End Results (SEER) registry data from 2004 to 2014 were accessed for the study. All women diagnosed with breast cancer and with complete information were included in the study. The data were further divided into two groups based on the age of the patient at the time of diagnosis. The younger group consisted of women < 40 years old (group 1) and the older group consisted of women ≥ 40 years old (group 2). Both groups were compared on demography and characteristics of the cancer. The continuous variables were tested using Student's t-tests and categorical variables were compared using Chi-squared or Fisher's exact tests. Multivariate analysis was done to find the association of high-grade cancer using a logistic regression model. All P-values are two-sided and values < 0.05 were considered statistically significant. Of 599,782 patients who satisfied the inclusion criteria, 28,243 (4.71%) diagnosed with breast cancer were younger women aged < 40 years old. A higher proportion of these younger women presented with larger tumor sizes (between 5.1 and 10.0 cm) (11.61% vs. 5.70%, P < 0.001), poorly differentiated cancer cells (55.88% vs. 32.85%, P < 0.001) and triple negative receptors (6.83% vs. 3.81%, P < 0.001) than older women respectively. Younger age was significantly associated with high-grade tumor at presentation when controlling for race and marital status. There was roughly 3% increased risk of a high-grade tumor with each decrease of 1 year (odds ratio 0.97, 95% confidence interval 0.96 - 0.99, P = 0.001). This study found that the proportion of breast cancer cases in younger women was just below 5%; however, when the cancer was diagnosed, these women presented in advanced stages and more aggressive cancer types.


Alpha-actinin binding kinetics modulate cellular dynamics and force generation.
The actin cytoskeleton is a key element of cell structure and movement whose properties are determined by a host of accessory proteins. Actin cross-linking proteins create a connected network from individual actin filaments, and though the mechanical effects of cross-linker binding affinity on actin networks have been investigated in reconstituted systems, their impact on cellular forces is unknown. Here we show that the binding affinity of the actin cross-linker α-actinin 4 (ACTN4) in cells modulates cytoplasmic mobility, cellular movement, and traction forces. Using fluorescence recovery after photobleaching, we show that an ACTN4 mutation that causes human kidney disease roughly triples the wild-type binding affinity of ACTN4 to F-actin in cells, increasing the dissociation time from 29 ± 13 to 86 ± 29 s. This increased affinity creates a less dynamic cytoplasm, as demonstrated by reduced intracellular microsphere movement, and an approximate halving of cell speed. Surprisingly, these less motile cells generate larger forces. Using traction force microscopy, we show that increased binding affinity of ACTN4 increases the average contractile stress (from 1.8 ± 0.7 to 4.7 ± 0.5 kPa), and the average strain energy (0.4 ± 0.2 to 2.1 ± 0.4 pJ). We speculate that these changes may be explained by an increased solid-like nature of the cytoskeleton, where myosin activity is more partitioned into tension and less is dissipated through filament sliding. These findings demonstrate the impact of cross-linker point mutations on cell dynamics and forces, and suggest mechanisms by which such physical defects lead to human disease.


Regulation of NHE3 by lysophosphatidic acid is mediated by phosphorylation of NHE3 by RSK2.
Na(+)/H(+) exchange by Na(+)/H(+) exchanger 3 (NHE3) is a major route of sodium absorption in the intestine and kidney. We have shown previously that lysophosphatidic acid (LPA), a small phospholipid produced ubiquitously by all types of cells, stimulates NHE3 via LPA5 receptor. Stimulation of NHE3 activity by LPA involves LPA5 transactivating EGF receptor (EGFR) in the apical membrane. EGFR activates proline-rich tyrosine kinase 2 (Pyk2) and ERK, both of which are necessary for NHE3 regulation. However, Pyk2 and ERK are regulated by EGFR via independent pathways and appear to converge on an unidentified intermediate that ultimately targets NHE3. The p90 ribosomal S6 kinase (RSK) family of Ser/Thr protein kinases is a known effector of EGFR and ERK. Hence, we hypothesized that RSK may be the convergent effector of Pyk2 and ERK although it is not known whether Pyk2 regulates RSK. In this study, we show that Pyk2 is necessary for the maintenance of phosphoinositide-dependent kinase 1 (PDK1) autophosphorylation, and knockdown of Pyk2 or PDK1 mitigated LPA-induced phosphorylation of RSK and stimulation of NHE3 activity. Additionally, we show that RSK2, but not RSK1, is responsible for NHE3 regulation. RSK2 interacts with NHE3 at the apical membrane domain, where it phosphorylates NHE3. Alteration of S663 of NHE3 ablated LPA-induced phosphorylation of NHE3 and stimulation of the transport activity. Our study identifies RSK2 as a new kinase that regulates NHE3 activity by direct phosphorylation.


Omeprazole does not interfere with the antiplatelet effect of low-dose aspirin in man.
Experimental studies have shown that omeprazole and other anti-inflammatory agents compromise the therapeutic activity of nonsteroidal anti-inflammatory drugs and aspirin in rats. It is not known whether this effect will occur in humans. Our aim was to determine whether omeprazole affects the antiplatelet effects of low-dose aspirin in humans. Platelet lumiaggregation, skin bleeding time, plasma levels of aspirin and salicylic acid, and serum gastrin levels were determined in 14 healthy men before and after the ingestion of 125 mg aspirin with or without previous treatment with 20 mg/day of omeprazole for 4 days before testing. Omeprazole increased serum gastrin levels from 64 (median; range, 52-91) pg/ml to 80.5 (median; range, 56-455) pg/ml (P < 0.05) but did not significantly affect the plasma concentration of aspirin or salicylic acid. Aspirin increased skin bleeding time in all subjects, and the increase was similar with and without previous omeprazole treatment. Aspirin inhibited platelet aggregation in response to both collagen and arachidonic acid regardless of omeprazole treatment. A single dose of 20 mg omeprazole daily does not interfere with the biologic activity of 125 mg aspirin on platelets in humans.


Spaceborne imaging radar: geologic and oceanographic applications.
Synoptic, large-area radar images of the earth's land and ocean surface, obtained from the Seasat orbiting spacecraft, show the potential for geologic mapping and for monitoring of ocean surface patterns. Structural and topographic features such as lineaments, anticlines, folds and domes, drainage patterns, stratification, and roughness units can be mapped. Ocean surface waves, internal waves, current boundaries, and large-scale eddies have been observed in numerous images taken by the Seasat imaging radar. This article gives an illustrated overview of these applications.


Validation of dHPLC for molecular diagnosis of beta-thalassemia in Southern Italy.
Beta-thalassemia, the most common hereditary anemia in the Mediterranean area, results from over 200 causative mutations in the beta-globin locus. The aim of this study was to validate a denaturing high-performance liquid chromatography (dHPLC)-based assay for postnatal and prenatal molecular diagnosis of beta-thalassemia in Southern Italy. Sixty beta-thalassemic patients, affected either by thalassemia intermedia or thalassemia major, were analyzed in a blind study. We also carried out prenatal molecular diagnosis in 12 couples at-risk for having affected offspring. Chorionic villi samples were subjected to dHPLC analysis upon molecular characterization of the parental beta-globin alleles. Direct sequence analysis was used to validate each result, showing an accuracy rate of 100% for dHPLC. Overall, our protocol was able to identify the responsible mutations in all 96 analyzed subjects (including 12 prenatals in at-risk pregnancies), detecting the eight most common mutations in Southern Italy. Three rare mutations (one of which, reported here for the first time) that standard mutation detection methods failed to reveal, were also identified. dHPLC assay proved to be a reliable, rapid, and sensitive method for detecting both common and rare mutations within the beta-globin gene. Because of this property our protocol has the potential to be implemented for mutational screening in different areas of high prevalence for beta-thalassemia.


Evaluating the 0-10 Point Pain Scale on Adolescent Opioid Use in US Emergency Departments.
To evaluate trends in national emergency department (ED) adolescent opioid use in relation to reported pain scores. A retrospective, cross-sectional analysis on National Hospital Ambulatory Medical Care Survey (NHAMCS) data was conducted on ED visits involving patients aged 11-21 from 2008-2017. Crude observational counts were extrapolated to weighted estimates matching total population counts. Multivariate models were used to evaluate the role of a pain score in the reported use of opioids. Anchors for pain scores were 0 (no pain) and 10 (worst pain imaginable). 31,355 observations were captured, which were extrapolated by the NHAMCS to represent 162,515,943 visits nationwide. Overall, patients with a score of 10 were 1.35 times more likely to receive an opioid than patients scoring a 9, 41.7% (CI95 39.7-43.8%) and 31.0% (CI95 28.8-33.3%), respectively. Opioid use was significantly different between traditional pain score cutoffs of mild (1-3) and moderate pain (4-6), where scores of 4 were 1.76 times more likely to receive an opioid than scores of 3, 15.5% (CI95 13.7-17.3%) and 8.8% (CI95 7.1-10.6%), respectively. Scores of 7 were 1.33 times more likely to receive opioids than scores of 6, 24.7% (CI95 23.0-26.3%) and 18.5% (CI95 16.9-20.0%), respectively. Fractures had the highest likelihood of receiving an opioid, as 49.2% of adolescents with a fracture received an opioid (CI95 46.4-51.9%). Within this subgroup, only adolescents reporting a fracture pain score of 10 had significantly higher opioid use than adjacent pain scores, where fracture patients scoring a 10 were 1.4 times more likely to use opioids than those scoring 9, 82.2% (CI95 76.1-88.4%) and 59.8% (CI95 49.0-70.5%), respectively. While some guidelines in the adult population have revised cut-offs and groupings of the traditional tiers on a 0-10 point pain scale, the adolescent population may also require further examination to potentially warrant a similar adjustment.


Trans-tibial amputee gait: time-distance parameters and EMG activity.
Gait analysis of trans-tibial (TT) amputees discloses asymmetries in gait parameters between the amputated and sound legs. The present study aimed at outlining differences between both legs with regard to kinematic parameters and activity of the muscles controlling the knees. The gait of 14 traumatic TT amputees, walking at a mean speed of 74.96 m/min, was analysed by means of an electronic walkway, video camera, and portable electromyography system. Results showed differences in kinematic parameters. Step length, step time and swing time were significantly longer, while stance time and single support time were significantly shorter on the amputated side. A significant difference was also found between knee angle in both legs at heel strike. The biceps femoris/vastus medialis ratio in the amputated leg, during the first half of stance phase, was significantly higher when compared to the same muscle ratio in the sound leg. This difference was due to the higher activity of the biceps femoris, almost four times higher than the vastus medialis in the amputated leg. The observed differences in time-distance parameters are due to stiffness of the prosthesis ankle (the SACH foot) that impedes the normal forward advance of the amputated leg during the first half of stance. The higher knee flexion at heel strike is due to the necessary socket alignment. Unlike in the sound leg, the biceps femoris in the amputated leg reaches maximal activity during the first half of stance, cocontracting with the vastus medialis, to support body weight on the amputated leg. The obtained data can serve as a future reference for evaluating the influence of new prosthetic components on the quality of TT amputee's gait.


ESU safety and the clinical engineer: purchasing, preventive maintenance, incident investigation.
The clinical engineer and his or her staff, by virtue of their responsibility for the equipment control program, can make a significant contribution in assuring that electrosurgical units and their accessories are effective and cause minimal harm to patients and staff. This is accomplished not only through the preventive maintenance/periodic inspection/repair functions that they are so well known for providing, but also through their active participation in the process of equipment selection and in the investigation of incidents suspected of arising from the use of these devices. This article outlines specific responsibilities in each of these three areas, including a detailed periodic inspection program for electrosurgical units.


Cardiovascular biomarkers: increasing impact of laboratory medicine in cardiology practice.
The practice of cardiology is in continual evolution, in parallel with the progress achieved by medical research in understanding the pathophysiology of cardiovascular disease and in developing new therapeutic procedures. Consequently, manufacturers of cardiac biomarkers are pressed with new demands to improve the performance of the existing and the development of novel ones. Several highly sensitive and/or specific assays for myocardial ischemic damage and myocardial function detection have already become commercially available. Moreover, an increasing number of novel risk factors have been added to the classical risk factors of cardiovascular disease. Finally, the recent surge of genetic analysis procedures will likely soon provide the clinical cardiologist with a number of laboratory tests for defining the molecular diagnosis, assessing new risk factors, and better targeting the pharmaceutical approaches in patients with cardiovascular disease. In this review, we first present the general characteristics of a biomarker followed by the analytical and clinical performance of assay methods.


[Variants in the formation and topography of the cervical cardiac nerves in man].
Studies performed on complexes of organs of neck and mediastinum obtained from 50 human corpses have demonstrated that cardiac nerves of neck have multiple variants of formation and topography and constantly form connections with each other and with vagal nerves branches without reaching the heart in unchanged fashion.


[Standards, guidelines and principles for clinical trials: medical products].
In addition to existing legislation there have been valid european and international Good Clinical Practice (GCP) guidelines and standards for the planning management and evaluation of clinical research projects and of clinical investigation of medical products since the 1990's. GCP regulates patient protection, the responsibilities of the sponsors, information management, data processing and quality assurance. The Draft International Standard (ISO/DIS 14155) and the European Standard (CEN/EN 540) stipulate the prerequisites and conditions for the clinical testing of medical products and devices. The essential documents for any research or investigative project include the trial protocol and the investigator's brochure. Observation of the guidelines and standards must be emphasized chiefly for reasons of publication suitability and the international recognition of the research and development findings.


MicroRNAs in development and disease.
Since the discovery of microRNAs (miRNAs) in Caenorhabditis elegans, mounting evidence illustrates the important regulatory roles for miRNAs in various developmental, differentiation, cell proliferation, and apoptosis pathways of diverse organisms. We are just beginning to elucidate novel aspects of RNA mediated gene regulation and to understand how heavily various molecular pathways rely on miRNAs for their normal function. miRNAs are small non-protein-coding transcripts that regulate gene expression post-transcriptionally by targeting messenger RNAs (mRNAs). While individual miRNAs have been specifically linked to critical developmental pathways, the deregulated expression of many miRNAs also has been shown to have functional significance for multiple human diseases, such as cancer. We continue to discover novel functional roles for miRNAs at a rapid pace. Here, we summarize some of the key recent findings on miRNAs, their mode of action, and their roles in both normal development and in human pathology. A better understanding of how miRNAs operate during the normal life of a cell as well as in the pathogenesis of disease when deregulated will provide new avenues for diagnostic, prognostic, and therapeutic applications.


The role of self-reported stress in the development of breast cancer and prostate cancer: a prospective cohort study of employed males and females with 30 years of follow-up.
We investigate the association between psychological stress and breast cancer and, as oestrogen may provide a common mechanism, the association between stress and prostate cancer. A prospective study of 991 women and 5743 men employed in Scotland in the 1970s provided data. Risk exposure was measured by questionnaire and physical examination, routine data collection provided cancer outcomes over the subsequent 30 years. There was weak evidence of elevated incidences in those reporting moderate (breast cancer: hazard ratio [HR] 2.16, 95% CI 1.00-4.71; prostate cancer: HR 1.65, 95% CI 1.20-2.27) and high stress (breast cancer: HR 1.92, 95% CI 0.81-4.55; prostate cancer: HR 1.35, 95% CI 0.87-2.10) compared to those reporting low stress. These estimates are adjusted for socioeconomic circumstances and health-related behaviours. With no dose-response relationship and no established mechanism linking stress with breast and prostate cancer, confounding is the parsimonious explanation of these findings.


Putative histiocytic sarcoma in redfin needlefish Strongylura notata (Beloniformes: Belonidae) in Florida, USA.
Redfin needlefish Strongylura notata from Florida coastal waters were observed with unusual neoplastic lesions. Affected specimens were collected from 1 Atlantic estuary (Indian River Lagoon, prevalence = 0.32%, n = 5314) and 2 Gulf of Mexico estuaries (Tampa Bay, prevalence = 0.02%, n = 10762; Charlotte Harbor, prevalence = 0.02%, n = 5112) during routine fisheries-independent monitoring surveys conducted from 1999-2009. Grossly, each lesion manifested as a large (18-30 mm × 20-50 mm), raised (approximately 10 mm), white, creamy, or pinkish nodule on the flank, dorsal trunk, base of the pectoral fin, or head. Multiple small (<5 mm) nodules possessing poorly demarcated borders with neighboring tissues on the external jaw surface and at the base of the teeth were also observed. Histopathologically, neoplastic cells were found in the dermis, beneath the skeletal muscle, and in the soft tissue at the base of teeth of the premaxilla and the dentary jaw processes. Neoplastic cells usually had prominently invaded among the myosepta of the skeletal muscle. Neoplastic parenchymal cells had the basic characteristics of atypical, mononuclear, round, histiocytic cells with an eccentric, reniform nucleus and abundant cytoplasmic vacuolation, while some exhibited bizarre nuclear pleomorphism. Transmission electron microscopy revealed that neoplastic cells had a grooved nucleus and cytoplasmic organelles with rough endoplasmic reticulum, mitochondria, Golgi apparatus, and lysosomes. Neoplastic cells had possibly metastasized to liver, spleen, and kidney. Positive immunohistochemical staining with Ki67, p53, S-100, and CD163 support neoplastic features and a putative diagnosis of histiocytic sarcoma.