Influence of retinal vessel printings on metamorphopsia and retinal architectural abnormalities in eyes with idiopathic macular epiretinal membrane.
To investigate whether the presence of retinal vessel printings (RVPs) in eyes having idiopathic epiretinal membrane (ERM) is associated with a higher degree of metamorphopsia or with more prominent abnormalities in the retinal architecture compared with eyes not having RVPs. A cross-sectional study of 36 eyes in 36 patients was conducted. The patients were divided into two groups (18 eyes per group) on the basis of the presence or absence of RVPs on fundus autofluorescence (FAF) imaging. Metamorphopsia was assessed using M-CHARTS. The optical coherence tomography (OCT) and FAF images were recorded using the Spectralis HRA+OCT. The macula was divided into 15 squares, and the areas between the displaced retinal vessels and the corresponding RVPs were calculated. Vertical, horizontal, and average metamorphopsia scores did not differ between the two groups. However, only two patients in the group with RVPs had an average metamorphopsia score of 0.6 or less versus nine patients in the group without RVPs (P = 0.029). There was no correlation between the area of displacement and vertical (P = 0.44), horizontal (P = 0.8), or average (P = 0.38) metamorphopsia scores. The eyes with RVPs manifested a higher degree of irregularity of the external limiting membrane (ELM) and the photoreceptor inner segment/outer segment (IS/OS) lines (P = 0.042 and P = 0.014, respectively). The presence of RVPs was the only independent variable associated with an average metamorphopsia score of 0.6 or higher. The presence of RVPs in eyes with idiopathic macular ERM is usually associated with an average metamorphopsia score of 0.6 or higher using M-CHARTS and with a higher degree of irregularity of the ELM and IS/OS lines at the fovea.


On the trail of Dr. Fifer.
A gift from a patient drew Hope, BC, family physician Gerd Asche irrevocably into the local medical history of the 1858 Fraser River Gold Rush. Because of his interest in Dr. Max William Fifer, Asche undertook research missions in British Columbia, England and the US, converted his computer room to a research and writing centre, and wrote a biography of his predecessor and colleague. He recounts his experience and the growing satisfaction provided by his interest in medical history.


The role of oxidant status on the etiopathogenesis of unexplained infertility and intracytoplasmic sperm injection - embryo transfer success: a case-control study.
The present study aims to evaluate the role of follicular fluid (FF) and serum (s) total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) on the etiopathogenesis of unexplained infertility (UI) and intracytoplasmic sperm injection-embryo transfer (ICSI-ET) success. Twenty UI patients and 20 controls with male factor undergoing an ICSI-ET cycle were recruited. FF samples aspirated from mature follicles and blood samples collected just before the oocyte retrieval were stored until analysis. Embriyo quality and implantation, clinical pregnancy and living birth rates were evaluated.FF-TOS and FF-OSI of the UI patients were higher than the control group. s-TOS and s-OSI were significantly increased in the UI group compared to the control group. However, only s-TOS was positively associated with UI diagnosis after age-adjustment. FF-OSI was negatively associated with embryo quality in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI on implantation, clinical pregnancy and live birth rate was observed. In conclusion, especially s-TOS can have a partial role in the etiopathogenesis of UI. High FF-OSI can decrease the quality of embryo in patients with UI.Impact statementWhat is already known? Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), which is the ratio of TOS to TAS, provide a broad overview of redox status.What do the results of this study add? An elevated serum TOS (s-TOS) was associated with UI after age-adjustment. Follicular fluid OSI (FF-OSI) was negatively associated with embryo quality and embryo score in the UI group (but not in the whole group) after age-adjustment. No significant effect of TAS, TOS, and OSI was observed on implantation, clinical pregnancy, and live birth rate.What are the implications of these findings for clinical practice and/or further research? Evaluation of FF-OSI in women with unexplained infertility can be considered to predict embryo quality. Further studies that evaluate antioxidant agents to decrease oxidative stress in UI and its' clinical implications are warranted.


Generation and diagnostic application of monoclonal antibodies against Seneca Valley virus.
Seneca Valley virus (SVV), a member of the Picornaviridae family, was implicated in a suspicious vesicular disease discovered in pigs from Canada in 2007. Because any outbreak of vesicular disease in pigs is assumed to be foot-and-mouth disease (FMD) until confirmed otherwise, a test for diagnosing the presence of SVV would be a very useful tool. To develop the diagnostic tests for SVV infection, 5 monoclonal antibodies (mAbs) were produced from mice immunized with binary ethylenimine (BEI)-inactivated SVV. Using a dot blot assay, the reactivity of the mAbs was confirmed to be specific for SVV, not reacting with any of the other vesicular disease viruses tested. The mAbs demonstrated reactivity with SVV antigen in infected cells by an immunohistochemistry assay. An SVV-specific competitive enzyme-linked immunosorbent assay (cELISA) was developed using BEI-inactivated SVV antigen and a mAb for serodiagnosis. The cELISA results were compared to the indirect isotype (immunoglobulin [Ig]M and IgG) ELISA and the virus neutralization test. All SVV experimentally inoculated pigs exhibited a positive SVV-specific antibody response at 6 days postinoculation, and the sera remained positive until the end of the experiment on day 57 (>40% inhibition) using the cELISA. The cELISA reflected the profile of the indirect ELISA for both IgM and IgG. This panel of SVV-specific mAbs is valuable for the identification of SVV antigen and the serological detection of SVV-specific antibodies.


User attitudes toward a physical activity promotion website.
The goal of the present study was to examine participants' perceptions of a theory-driven, physical activity promotion website. Participants in the present study were individuals in the website condition of a randomized trial designed to test the efficacy of the website. At 1 month, participants were surveyed regarding their self-report of barriers, frequency of use, and helpfulness of the website. Overall, 30 worksite participants were randomized to the website condition and 24 (80%) completed the survey at 1 month. The main barrier to using the website was a "lack of time" (63%). No participants endorsed trouble using the website, a lack of interest in using the internet, or a lack of interest in changing their activity level as barriers to using the website. Furthermore, most sections of the website were found to be "helpful." Patterns of use and perceived utility differed by readiness to become active. For example, more respondents in the "preparation" stage at baseline reported using the overall website, in addition to the "becoming active" and "physical activity and health" sections, than those in the "contemplation" stage at baseline. Perceived utility and frequency of use of specific sections were often divergent, where some sections were rated more helpful and used less frequently (the "Overcoming Barriers" section, for example), while the reverse was true for other sections (the "Walking Fitness Test" section, for example). In conclusion, the website was well accepted and few barriers were noted. Areas of the website that were used less frequently or found to be less helpful will become areas of focus for future iterations of the site.


Myosin light-chain phosphatase.
1. A method for the isolation of a new enzyme, myosin light-chain phosphatase, from rabbit white skeletal muscle by using a Sepharose-phosphorylated myosin light-chain affinity column is described. 2. The enzyme migrated as a single component on electrophoresis in sodium dodecyl sulphate/polyacrylamide gel at pH7.0, with apparent mol.wt. 70000. 3. The enzyme was highly specific for the phosphorylated P-light chain of myosin, had pH optima at 6.5 and 8.0 and was not inhibited by NaF. 4. A Ca2+-sensitive 'ATPase' (adenosine triphosphatase) system consisting of myosin light-chain kinase, myosin light-chain phosphatase and the P-light chain is described. 5. Evidence is presented for a phosphoryl exchange between Pi, phosphorylated P-light chain and myosin light-chain phosphatase. 6. Heavy meromyosin prepared by chymotryptic digestion can be phosphorylated by myosin light-chain kinase. 7. The ATPase activities of myosin and heavy meromyosin, in the presence and absence of F-actin, were not significantly changed (+/- 10%) by phosphorylation of the P-light chain.


Antihypertensive effect of diet compared with drug treatment in obese men with mild hypertension.
To determine whether dietary treatment has a similar antihypertensive effect to conventional drug treatment while being superior to drugs in improving serum lipid concentrations in obese men with mild hypertension. Six week run in period followed by randomisation to either diet or drug treatment groups for one year. Outpatient clinic in city hospital. 61 Men aged 40-69 years, body mass index greater than or equal to 26, diastolic blood pressure 90-104 mm Hg when untreated. Exclusion criteria were signs of organ damage secondary to hypertension and diseases that might have interfered with compliance or with interpretation of results. Dietary treatment was based on weight reduction, restriction of sodium, and decrease of excess alcohol intake (defined as greater than or equal to 250 g alcohol per week). Drug treatment used a stepped care approach with atenolol as drug of first choice. Diastolic blood pressure less than 90 mm Hg; absolute reductions in blood pressure and serum lipid concentrations. Mean body weight decreased 7.6 kg in the diet group and increased 0.9 kg in the drug treatment group (p less than 0.0001), and mean sodium excretion decreased 42 and 10 mmol/24 h respectively (p = 0.019). There was no difference in reported alcohol intake. Mean systolic blood pressure decreased 4 mm Hg in the diet group and 16 mm Hg in the drug group (p = 0.003) and diastolic blood pressure 3 and 11 mm Hg respectively (p = 0.002). Diastolic blood pressure of 90 mm Hg was attained by 29% of the diet group (nine men) and 73% (22) of those receiving drug treatment (mean difference 44%, 95% confidence interval 21 to 67%, p = 0.001). Dietary treatment produced decreases in mean serum concentrations of total and low density lipoprotein cholesterol as well as triglycerides and an increase in high density lipoprotein cholesterol concentration. In the drug treatment group the changes were in the opposite direction, and the groups differed significantly in all but total cholesterol. Dietary treatment was inferior to conventional drug treatment in controlling mild hypertension but superior in lowering serum concentrations of lipids.


Sexual relationships of patients with kleptomania.
Kleptomania, a disorder of impulse control in which the patients feel a compelling urge to steal objects of no value to them, has long been considered a disorder related in some fashion to sexual impulses. Recent advances in the clinical understanding of human sexual functioning have not been accompanied by an effort to refine our thinking about its relationship to kleptomania. Research is hampered by the relative rarity of the disorder and the propensity of patients to avoid seeking professional help. Consequently, the available literature is restricted to case studies or small series that fail to differentiate between kleptomania and other forms of shoplifting. This paper describes the six patients I have seen with the primary diagnosis of kleptomania; all had dysfunctional sexual relationships. The sole male patient was a homosexual, and compulsively promiscuous. Sexual counseling and/or therapy may provide an additional method for treating this difficult disorder.


Effects of Expressive Arts-Based Interventions on Adults With Intellectual Disabilities: A Stratified Randomized Controlled Trial.
People with intellectual disabilities have difficulties expressing their views and can manifest psychological and behavioral symptoms. The present study aimed to examine the effects of expressive arts-based intervention (EABI) on the behavioral and emotional well-being of adults with intellectual disabilities. This study assigned 109 Chinese adults with intellectual disabilities into EABI (N = 55) or control groups (N = 54) using stratified randomization. Pre- and post-intervention quantitative assessments were conducted of aberrant behaviors, personal well-being, mood and color usage in drawings. Focus group interviews were conducted with the EABI participants and their caseworkers at the post-intervention stage. Repeated-measures analysis of covariance evaluated the EABI effects with age, gender and degree of intellectual disability as covariates, and latent profile analysis examined the patterns of color usage in drawings. Qualitative thematic analysis was performed on the interview data. The interview findings suggest that the EABI group was more emotionally expressive and stable after the intervention. Compared to the control group, the EABI group tended to use more diverse colors and leave less empty space in their drawings. No significant overall improvements were found in the EABI group with respect to aberrant behaviors, mood or personal well-being. Among males, the EABI participants showed significantly more anger and less energetic moods than those in the control group. Among females, the EABI participants showed significantly lower levels of aberrant behavior than those in the control group. The results of this study suggest that expressive arts-based interventions have different effects on the emotional and behavioral well-being of male and female participants. Moreover, increased color usage may imply a more positive state of emotional well-being.


A hybrid proton and hyperpolarized gas tagging MRI technique for lung respiratory motion imaging: a feasibility study.
The aim of this work was to develop a novel hybrid 3D hyperpolarized (HP) gas tagging MRI (t-MRI) technique and to evaluate it for lung respiratory motion measurement with comparison to deformable image registrations (DIR) methods. Three healthy subjects underwent a hybrid MRI which combines 3D HP gas t-MRI with a low resolution (Low-R, 4.5 mm isotropic voxels) 3D proton MRI (p-MRI), plus a high resolution (High-R, 2.5 mm isotropic voxels) 3D p-MRI, during breath-holds at the end-of-inhalation (EOI) and the end-of-exhalation (EOE). Displacement vector field (DVF) of the lung motion was determined from the t-MRI images by tracking tagging grids and from the High-R p-MRI using three DIR methods (B-spline based method implemented by Velocity, Free Form Deformation by MIM, and B-spline by an open source software Elastix: denoted as A, B, and C, respectively), labeled as tDVF and dDVF, respectively. The tDVF from the HP gas t-MRI was used as ground-truth reference to evaluate performance of the three DIR methods. Differences in both magnitude and angle between the tDVF and dDVFs were analyzed. The mean lung motion of the three subjects was 37.3 mm, 8.9 mm and 12.9 mm, respectively. Relatively large discrepancies were observed between the tDVF and the dDVFs as compared to previously reported DIR errors. The mean ± standard deviation (SD) DVF magnitude difference was 8.3 ± 5.6 mm, 9.2 ± 4.5 mm, and 9.3 ± 6.1 mm, and the mean ± SD DVF angular difference was 29.1 ± 12.1°, 50.1 ± 28.6°, and 39.0 ± 6.3°, for the DIR Methods A, B, and C, respectively. These preliminary results showed that the hybrid HP gas t-MRI technique revealed different lung motion patterns as compared to the DIR methods. It may provide unique perspectives in developing and evaluating DIR of the lungs. Novelty and Significance We designed a MRI protocol that includes a novel hybrid MRI technique (3D HP gas t-MRI with a low resolution 3D p-MRI) plus a high resolution 3D p-MRI. We tested the novel hybrid MRI technique on three healthy subjects for measuring regional lung respiratory motion with comparison to deformable image registrations (DIR) methods, and observed relatively large discrepancies in lung motion between HP gas t-MRI and DIR methods.


The effect of beta-adrenergic blockade on patterns of urinary sodium excretion, blood pressure and plasma renin activity in patients with essential and renovascular hypertension.
The effects of beta-adrenergic blockade, using oxprenolol, were studied in plasma renin activity, urinary sodium excretion and blood pressure in ten normal subjects and in 120 patients with essential and renovascular hypertension. Blood pressure was reduced by oxprenolol administration. The hypotensive action of the drug was independent of either the basal plasma renin activity or of the plasma renin activity response. Oxprenolol decreased plasma renin activity in normal subjects and in patients with essential hypertension with normal or high basal plasma renin activity. Patients with low plasma renin activity may show a lack of response to the beta-blockade. In patients with renovascular disease the response of plasma renin activity to oxprenolol was not a discriminant factor between patients cured or not cured by surgery. Some renovascular patients were unresponsive to beta-blockade with oxprenolol.


Contribution of Iron-Transport Systems and β-Lactamases to Cefiderocol Resistance in Clinical Isolates of Acinetobacter baumannii Endemic to New York City.
The development of resistance to cefiderocol among multidrug resistant Acinetobacter baumannii has been attributed to downregulation in iron transport systems and a variety of β-lactamases. However, the precise contribution of each in clinical isolates remains to be determined. Sixteen clinical isolates with varying degrees of cefiderocol resistance were investigated. Susceptibility testing was performed with and without the presence of iron and avibactam. Expression of 10 iron transport systems and blaADC and blaOXA-51-type were analyzed by real time RT-PCR. The acquisition of a variety of β-lactamases was also determined. In 2 isolates the impact of silencing the blaADC gene was achieved using a target specific group II intron. For most resistant isolates, MICS for cefiderocol were similar with or without the presence of iron, and there was an overall decrease in expression of receptors (including pirA and piuA) involved in ferric uptake. However, expression of the ferrous uptake system (faoA) persisted. The addition of avibactam (4 μg/mL) lowered most cefiderocol MICs to 2 to 4 μg/mL. Most isolates possessed ADC-25 or ADC-33. Cefiderocol resistance correlated with over-expression of blaADC; silencing of this β-lactamase resulted in a ≥ 8-fold decrease in cefiderocol MICs. Over-expression of specific blaADC subtypes, in a background of generalized repression of ferric uptake systems, were consistent features in clinical isolates of cefiderocol-resistant A. baumannii.


[The experience of biliary self-expendable nitinol stents for malignant jaundice].
to analyze the effectiveness and possible complications of endoscopic biliary drainage (BD) using self-expanding metal stent (SEMS) in patients with malignant jaundice (MJ). From January 2010 to January 2014 in endoscopy department of Pirogov National medical and surgical Center were operated 64 patients with MJ, 38 of them with SEMS. The average patient's age was 65.4 ± 14.5 years. The mean duration of jaundice was 13 ± 5.4 days before drainage. The remaining 6 patients (15.8%) were operated with preliminary PTBD. In all 38 patients were diagnosed unresectable tumors. successful endoscopic BD were achieved in all 38 patients. 35 patients were drained with transpapillary SEMS and 3 patients with EUS-guided choledochoduodenoanastomoses (EUS-CDA). Early postoperative complications were observed in 3 (7.8%) patients with no lethality. endoscopic BD with SEMS is an effective method of internal drainage for inoperable pancreatobiliary tumors, providing adequate BD for the entire duration of life expectancy. In case of failed transpapillary drainage EUS-guided biliodigestive anastomoses were performed. The complication rate of endoscopic BD in patients with malignant pancreatobiliary tumors in our study was 7.8% and comparable with complication level due to ERCP/EST for benign pathology.


Air Force Medical Personnel: Perspectives Across Deployment.
Contingency operations during the past 18 years have exposed millions of U.S. military service members to numerous combat and operational stressors. Despite this, a relative dearth of literature has focused on the experiences of deployed military medical personnel. As such, the present study aimed to address this gap in the literature by conducting individual and small group interviews with Air Force medical personnel who had recently returned from a deployment to Iraq. Interviews targeted self-reported factors related to psychological risk and resiliency across the deployment cycle, while also seeking recommendations for future military medical personnel preparing for medical deployments. Inductive thematic analyses were conducted on transcripts from 12 individual and structured group interviews conducted with recently deployed U.S. Air Force medical personnel (N = 28). An interview script consisting of 18 prompts was carefully developed based on the experiences of study personnel. Two team members (n = 1 research psychologist; n = 1 military medical provider) coded exemplars from interview transcripts. A third team member (research psychologist) reviewed coded exemplars for consistency and retained themes when saturation was reached. In total we report on 6 primary themes. Participants reported feeling prepared to conduct their mission while deployed but often felt unprepared for the positions they assumed and the traumas they commonly experienced. Most participants reported deployment to be a rewarding experience, citing leader engagement, and social support as key protective factors against deployment-related stressors. Finally, following deployment, participants largely reported positive experiences reintegrating with their families but struggled to reintegrate into their workplace. Findings from the present study indicate that the military is largely doing a good job preparing Air Force medical providers to deploy. Results of the present study indicate that military medical personnel would benefit from: (1) increased predictability surrounding deployment timelines, (2) improved cross-cultural training, (3) advanced training for atypical injuries in unconventional patient populations, and (4) improvements in postdeployment workplace reintegration. The present research has the potential to positively impact the overall quality of life for deploying military service members and their families; while simultaneously highlighting the successes and shortfalls in the deployment process for U.S. military medical personnel.


Noncoding RNAs in molecular characterization of cancer preneoplasia.
Molecular biomarkers are widely recognized as having tremendous utility in cancer early detection, prediction, and prevention. Huge efforts have been put into searching of various molecular biomarkers for these purposes, yet there are few molecular biomarkers that have been approved by the Food and Drug Administration for clinical use. Discovery of novel molecular biomarkers is still urgently needed to create biological insights into early events of carcinogenesis and to predict the aggressiveness of early cancer. Noncoding RNAs (ncRNAs) are relatively unexplored molecules identified only one decade ago. With research on the basic biology and mechanisms of ncRNAs, they have rapidly been linked to etiology of diseases, particularly cancer. In this chapter, we will summarize ncRNAs, particularly microRNAs (miRNAs), a type of ncRNAs, as a new frontier for the discovery of cancer biomarkers in preneoplastic lesions and their usefulness as markers for the risk assessment, early detection, and diagnosis of cancer.


Community-based physical activity and/or nutrition interventions to promote mobility in older adults: An umbrella review.
Background: Physical activity and a healthy diet are important in helping to maintain mobility and quality of life with aging. Delivery of physical activity and nutrition interventions in a group setting adds the benefits of social participation. Several published systematic reviews have explored a broad range of PA and/or nutrition interventions for older adults, making it challenging to bring together the best scientific evidence to inform program design and to inform multicomponent intervention development. This umbrella review aims to identify group-based physical activity and nutrition interventions for community-dwelling older adults that improve mobility. Methods: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Sociological Abstracts) were searched from inception to April 28, 2020. Eligibility criteria included systematic reviews exploring the effectiveness of physical activity and/or nutrition interventions, delivered in a group setting for community-dwelling older adults. Two reviewers independently performed eligibility screening, critical appraisal (using AMSTAR 2) and data extraction. The GRADE approach was used to assess the overall certainty of the evidence. Older adult/provider research partners informed data synthesis and results presentation. Results: In total, 54 systematic reviews (1 high, 21 moderate, 32 low/critically low quality) were identified; 46 included physical activity only, and eight included both physical activity and nutritional supplements. No reviews included nutrition interventions alone. Combined aerobic/resistance, general physical activity, and mind-body exercise all improved physical function and balance (moderate-high certainty). Aerobic/resistance training improved aerobic capacity (high certainty). Resistance training and general physical activity improved muscle strength (moderate certainty). Aerobic/resistance training and general physical activity are likely to reduce falls among older adults (moderate certainty). There was no evidence of benefit for nutritional supplementation with physical activity. Conclusions: Multicomponent group-based physical activity interventions can improve measures of mobility in community-dwelling older adults. We found no reviews focused on nutrition only, highlighting a gap in the literature.


Blood flow distributions by microsphere deposition methods.
The art and science of the use of deposition markers for the estimation of blood flow distributions throughout the body and within organs is reviewed. Development of diffusible tracer techniques started 50 years ago. Twenty years later, radioactive 15 micron microspheres became the standard marker. Early studies on small animals, fetal sheep in 1967 and rats in 1976, provoked much of the technical development. Needs for avoiding the use of radioactivity, for having long lasting labels, and for providing higher spatial resolution, are driving the continuing exploration of newer techniques using colored and fluorescent microspheres and molecular deposition markers. Strengths and weaknesses of the various methods are compared.


A Drosophila toolkit for HA-tagged proteins unveils a block in autophagy flux in the last instar larval fat body.
For in vivo functional analysis of a protein of interest (POI), multiple transgenic strains with a POI that harbors different tags are needed but generation of these strains is still labor-intensive work. To overcome this, we have developed a versatile Drosophila toolkit with a genetically encoded single-chain variable fragment for the HA epitope tag: 'HA Frankenbody'. This system allows various analyses of HA-tagged POI in live tissues by simply crossing an HA Frankenbody fly with an HA-tagged POI fly. Strikingly, the GFP-mCherry tandem fluorescent-tagged HA Frankenbody revealed a block in autophagic flux and an accumulation of enlarged autolysosomes in the last instar larval and prepupal fat body. Mechanistically, lysosomal activity was downregulated at this stage, and endocytosis, but not autophagy, was indispensable for the swelling of lysosomes. Furthermore, forced activation of lysosomes by fat body-targeted overexpression of Mitf, the single MiTF/TFE family gene in Drosophila, suppressed the lysosomal swelling and resulted in pupal lethality. Collectively, we propose that downregulated lysosomal function in the fat body plays a role in the metamorphosis of Drosophila.


Musculoskeletal Injuries in Elite Collegiate Tenpin Bowling Athletes.
Collegiate tenpin bowling participation is increasing. Accordingly, the experience level of athletes participating, factors related to performance, as well as training workload and sport specialization are likely evolving. However, literature regarding injury rates remains extremely limited. The purpose of this study was to characterize injuries in collegiate tenpin bowlers. Retrospective cohort survey study. Tenpin bowling athletes of top-ranked collegiate programs in the United States were invited to participate. Each participant completed an online survey to report on their injury history and additional factors of interest. Descriptive statistics were generated for participant characteristics, injury counts, and overall injury prevalence and recurrence. Chi-square tests were used to determine if overall injury prevalence and recurrence occurred by chance, and to evaluate the influence of gender and conditioning program participation on injury frequencies. The response rate was 40.6% (101/249; N = 101). The sample was 20.02 (1.43) years old and 54.5% female. There were a total of 235 singular and recurrent injuries reported across all body parts. Upper-extremity injuries were the most common (n = 112). Injury prevalence (87%) and recurrence (75%) were more likely than chance (χ2 > 21.3, both P < .001) and not different based on gender (χ2 ≤ 1.1, both P ≥ .33). Injuries were more frequent in the absence of a conditioning program (χ2 = 50.6, P < .001). Injuries and injury recurrence in elite tenpin bowlers were frequent, most common in the upper-extremity, not different based on gender, and more frequent in those without conditioning programs. Findings may serve as foundational knowledge for developing sport-specific rehabilitation and conditioning programs.


The Prognostic and Predictive Role of Chromogranin A in Gastroenteropancreatic Neuroendocrine Tumors - A Single-Center Experience.
Chromogranin A (CgA) is a non-specific biomarker excreted by neuroendocrine tumor (NET) cells. Elevation of circulating CgA level can be detected in gastroenteropancreatic (GEP)-NET patients and has been shown to correlate with tumor burden. The prognostic and predictive roles of CgA level and the change of CgA level are controversial. In this study, we retrospectively analyzed 102 grade 1/2 GEP-NET patients with available baseline or serial follow-up CgA levels from the National Cheng Kung University Hospital to evaluate the association between circulating CgA level and the tumor extent, overall survival (OS), and tumor response prediction. The baseline characteristics, baseline CgA level, and change of CgA level during follow-up and their association was analyzed. Sixty cases had baseline CgA levels available prior to any treatment and ninety-four cases had serial follow-up CgA levels available during treatment or surveillance. Baseline CgA levels were associated with stage and sex. Higher baseline CgA levels were associated with worse OS after adjusting for sex, stage, grade, primary site, and functionality (hazard ratio=13.52, 95% confidence interval (CI), 1.06-172.47, P=0.045). The cross-sectional analysis for the change of CgA level during follow-up showed that a ≥ 40% increase of CgA meant a higher probability of developing tumor progression or recurrence than those with a < 40% increase of CgA level (odds ratio=5.04, 95% CI, 1.31-19.4, P=0.019) after adjusting for sex, age, grade, stage, and functionality. Our study results suggest that CgA may be a predictive marker for tumor burden, OS, and tumor progression in GEP-NET patients.


Expertise in ill-defined problem-solving domains as effective strategy use.
Expertise consists of many different cognitive structures. Lemaire and Siegler (1995) have proposed a four-layered account of expertise from a strategies perspective: Experts have better strategies, tend to use strategies that are better overall more often, are better able to select the circumstances to which a strategy best applies, and are better able to execute a given strategy. Originally, this account came from work in simple, well-defined domains. We explored this account in the complex, ill-defined domain of platoon leadership. In Experiment 1A, we elicited free-text responses to leadership scenarios from novices, intermediates, and experts, finding expertise effects for strategy base rates and choice, but not for strategy existence or the number of strategies used. In Experiment 1B, we used a new group of experts to gather ratings of the execution accuracy of the responses in Experiment 1A and found expertise differences in the ability to execute the same strategies. We propose several elaborations to the original four-layered strategies account of expertise on the basis of these results.


Correcting the literature following fraudulent publication.
To gain a better understanding of the problem of dealing with publications whose integrity is subsequently challenged, experience in a well-documented case of research fraud was reviewed. At the University of California San Diego, a faculty committee evaluated 135 publications of Robert Slutsky, MD, and reported to each of the corresponding 30 journals whether each article was valid, questionable, or fraudulent, requesting publication of the criteria and the conclusions. Journals responded slowly to this request; half required additional letters over a 2-year period to elicit a reply. Of the 13 journals that had only valid articles, 5 printed a statement to that effect. Statements concerning 46 of 60 nonvalid articles were eventually published. Journals' inconsistent identification of published statements made it difficult to retrieve them by electronic searching. Only 7 notices covering 15 articles were found by searching under the Medical Subject Heading "Retraction of Publication"; scanning the entire bibliography retrieved 18 articles with retraction notations. A poll showed that journals rarely have written procedures for responding to allegations of research misconduct; in our experience, journals were reluctant to accept authorized retractions or corrections when coauthors failed to act.


Freeze-fracture and electrophysiological studies of newly developed acetylcholine receptors in Xenopus embryonic muscle cells.
The development of acetylcholine receptors on Xenopus embryonic muscle cells both in culture and in situ was studied using electrophysiology and freeze-fracture electron microscopy. Acetylcholine sensitivity first appeared at developmental stage 20 and gradually increased up to about stage 31. Freeze-fracture of muscle cells that were nonsensitive to acetylcholine revealed diffusely distributed small P-face intramembraneous particles. When cells acquired sensitivity to acetylcholine, a different group of diffusely distributed large P-face particles began to appear. This group of particles was analyzed by subtracting the size distribution found on nonsensitive cells from that found on sensitive cells. We call this group of particles difference particles. The sizes of difference particles were large (peak diameter 11 nm). The density of difference particles gradually increased with development. The density of small particles (less than 9 nm) did not change with development. At later stages (32-36) aggregates of large particles appeared, which probably represent acetylcholine receptor clusters. The size distribution of difference particles was close to that of the aggregated particles, suggesting that at least part of difference particles represent diffusely distributed acetylcholine receptors. Difference particles exist mostly in solitary form (occasionally double), indicating that an acetylcholine receptor can be functional in solitary form. This result also shows that diffuse acetylcholine receptors that have previously been observed with 125I-alpha-bungarotoxin autoradiography do indeed exist in solitary forms not as microaggregates.


Chemotherapy for hormone-refractory prostate cancer: now it's a question of "when?".
Recently, data from two randomized phase III studies that compared docetaxel-based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with docetaxel can prolong life in a significant way for patients with hormone-refractory prostate cancer. For many patients who experience disease progression after androgen-deprivation therapy, however, chemotherapy may not be immediately indicated. Such cases include those individuals with hormone-refractory disease in the absence of clinical metastases, and those with asymptomatic metastatic disease, for example. As a result, clinicians treating patients with hormone-refractory disease must weigh the benefits of earlier chemotherapy against its risks, and may consider other therapies such as secondary hormonal approaches before initiating chemotherapy. This decision is further complicated by the fact that a phase III study designed to compare secondary hormonal therapy with chemotherapy has failed due to lack of accrual. Furthermore, the limitations of chemotherapy for prostate cancer are being clarified and include a lack of standard second-line therapy as well as uncertain benefits for those with nonmetastatic disease. In this review, we will highlight some of the issues that impact on the decision of when to start chemotherapy and in whom as well as the potential benefits of secondary hormonal approaches.


Health complaints and satisfied with the job? A cross-sectional study on work environment, job satisfaction, and subjective health complaints.
The aim of this study was to examine the prevalence of subjective health complaints (SHCs) among satisfied and dissatisfied workers. The second aim was to evaluate whether any SHC differences were attributable directly to the work environment or mediated by the individual perception of the environment (satisfactory or not). In a cross-sectional study of 458 employees (56% women) in 5 different organizations, work environment, job satisfaction, and SHC were measured. Satisfied workers reported an average of five to six subjective health complaints that correspond to the prevalence found in a Norwegian general population. Work environment explained 43% of the variance for job satisfaction and 9% of the variance in SHCs. SHCs are common among satisfied workers. Work environment has only a limited influence on this validated health indicator.


Nuclear Export as a Novel Therapeutic Target: The CRM1 Connection.
The integrity of eukaryotic cellular function depends on molecular and biochemical compartmentalization. The transport of macromolecules between compartments requires specific and energydriven mechanisms. It occurs through a class of transport proteins known as karyopherins, which are divided in three different groups (exportins, importins, and transportins). The ubiquitous exportin Chromosome Region Maintenance 1 (CRM1) is involved in the transport of many proteins and RNA molecules from nucleus to cytoplasm. We have reviewed the available evidence supporting the relevance of CRM1 in the biology of several human neoplasms, its potential role in drug resistance, and its promise as a therapeutic target. Here we discuss different cancer related proteins (tumor suppressor genes, oncogenes, and enzymatic therapeutic targets), their function, and their association with CRM1, as well as agents that specifically inhibit CRM1, their mechanism of action, and their clinical relevance in certain human neoplasms. The directionality of nuclear transport and the specific molecular cargo in question are of paramount importance when examining the effects that CRM1 inhibition may have on cellular pathophysiology. The available data point out the potential role of CRM1-dependent nuclear export of regulatory proteins in the biology of certain human malignancies. Further studies should expand and clarify the importance of this mechanism in the pathobiology of human neoplasia.


Healthy weight services in England before, during and after pregnancy: a mixed methods approach.
Maternal overweight and obesity are associated with numerous adverse outcomes including higher rates of maternal and infant mortality and morbidity. Overweight and obesity before, during and after pregnancy are therefore a significant public health priority in England. This project explored and mapped healthy weight service availability at different stages of the childbearing cycle. A mixed methods approach included a questionnaire-based survey disseminated through Local Maternity Systems and semi-structured interviews or focus groups with providers and commissioners. Current maternal weight service provision was explored along with some of the barriers and facilitators for providing, delivering and accessing healthy weight services. Descriptive statistics were reported for quantitative data and content analysis was used for thematic reporting of qualitative data. A total of 88 participants responded to the survey. All services were offered most frequently during pregnancy; with healthy eating and/or weight management services offered more often than physical activity services. Few services were targeted specifically at women with a raised body mass index. There was a high degree of inconsistency of service provision in different geographical areas. Several themes were identified from qualitative data including "equity and variation in service provision", "need for rigorous evaluation", "facilitators" to encourage better access or more effective service provision, including prioritisation, a change in focus and co-design of services, "barriers" encountered including financial and time obstacles, poor communication and insufficiently clear strategic national guidance and "the need for additional support". There is a need to reduce geographical variation in services and the potential health inequalities that this may cause. Improving services for women with a raised body mass index as well as services which encourage physical activity require additional emphasis. There is a need for more robust evaluation of services to ensure they are fit for purpose. An urgent need for clear national guidance so that healthcare providers can more effectively assist mothers achieve a healthy weight gain was identified. Commissioners should consider implementing strategies to reduce the barriers of access identified such as childcare, transport, location and making services free at the point of use.


Social cognition in social anxiety: first evidence for increased empathic abilities.
Individuals with social phobia (SP) show sensitivity and attentiveness to other peoples states of mind. Although cognitive processes in SP have been extensively studied, these individuals social cognition characteristics have never been examined before. We hypothesized that high socially anxious individuals (HSA) may exhibit elevated mentalizing and empathic abilities. Empathy was assessed using self-rating scales in HSA individuals (n=21) and low socially anxious (LSA) individuals (n=22), based on their score on the Liebowitz social anxiety scale. A computerized task was used to assess the ability to judge first and second order affective vs. cognitive mental state attributions. HSA individuals exhibited elevated affective empathy tendencies. However, controlling for the general anxiety variable revealed that social anxiety was related to cognitive empathy measures, rather than affective empathy. In addition, compared with LSA participants, HSA participants exhibited higher accuracy levels on the affective mental state attribution conditions, but were less accurate than LSA individuals on the parallel cognitive mental state attribution conditions. Additional research with larger samples and clinically diagnosed individuals is required. Results support the hypothesis that high socially anxious individuals may demonstrate a unique social-cognitive abilities profile with elevated cognitive empathy tendencies and high accuracy in affective mental state attributions.


A solid-phase immunosorbent technique for the rapid detection of rubella IgM by haemagglutination inhibition.
The rubella haemagglutination inhibition (HAI) test has been modified for the detection of rubella-specific IgM. The rubella HAI test is performed in microtitre plate wells in which IgM from patients' sera has been selectively retained by anti-human IgM bound to the polystyrene surface. The test requires only anti-human IgM-coated microtitre plates, in addition to the standard rubella HAI reagents. The results obtained in this test, a solid-phase immunosorbent technique (SPIT), are in good agreement with results obtained by the sucrose density gradient centrifugation technique (DGCT). Advantages include the essentially unrestricted number of sera which can be tested daily, the availability of results within 24 h and the lack of interference by rheumatoid factor and by rubella-specific IgG.


Modifications of residual viraemia in human immunodeficiency virus-1-infected subjects undergoing repeated highly active antiretroviral therapy interruptions.
Residual viraemia is detectable in the majority of human immunodeficiency virus (HIV)-infected subjects with plasma HIV-1 RNA <50 copies ml(-1). In the present study, the impact of repeated treatment interruptions on residual HIV-1 viraemia was investigated in 58 subjects enrolled in the ISS-PART, a multicentre, randomized clinical trial comparing 24 months of continuous (arm A) and intermittent (arm B) highly active antiretroviral therapy (HAART). Residual viraemia was measured by a modified Roche Amplicor HIV-1 RNA assay (limit of detection 2.5 copies ml(-1)). At baseline, the median value of residual viraemia was 2.5 copies ml(-1) in both arms; after 24 months, the median value was 2.5 in arm A and 8.3 in arm B. The median change from baseline to month 24 was significantly different between patients under continuous or intermittent HAART: 0 copies ml(-1) (range -125.2 to +82.7) of HIV-1 RNA in arm A versus 2.1 copies ml(-1) (range -80 to +46.8) in arm B (P=0.024). These results suggest that intermittent HAART tends to modify HIV-1 viraemia set point even if a virological response is achieved after HAART reinstitution.


Expression of SPARC in normal and fibrotic livers.
SPARC (secreted protein, acidic and rich in cysteine)--also known as osteonectin, BM-40, and 43K glycoprotein--is secreted by endothelial cells and fibroblasts in response to culture shock. SPARC has been found in association with tissues undergoing cell proliferation, migration, and extracellular matrix remodeling. We demonstrate that normal livers from humans, rats, and mice express substantial levels of SPARC messenger RNA (mRNA). Moreover, when compared with control specimens, significantly increased levels of SPARC mRNA were found in fibrotic livers from two animal models of liver disease: murine schistosomiasis and carbon tetrachloride-induced fibrosis in rats. Fibrotic human livers also had markedly increased levels of SPARC mRNA in comparison with normal livers. We also detected an increased production of SPARC protein in the liver of animals treated with carbon tetrachloride. By immunocytochemical analysis, SPARC protein was apparent in freshly isolated Ito cells. Hybridization studies showed Ito cells to be the main source of SPARC mRNA. Extracts from a Kupffer-endothelial cell fraction exhibited traces of SPARC transcript, but expression of SPARC mRNA was absent in extracts from freshly isolated hepatocytes. These studies demonstrate the increased expression of SPARC--a protein that modulates cell shape and disrupts cell-matrix interactions--during the initial stages of hepatic fibrosis.


[Stenting for the occlusive carotid and subclavian arteries in Takayasu arteritis].
The authors report the initial results of stenting in four patients of Takayasu arteritis for 11 occlusive carotid and subclavian arteries between January 1999 and December 2000. The lesions included stenoses of two right subclavian, three right common carotid, two left common carotid, and two left subclavian arteries, and total occlusion of two subclavian arteries. A total of 14 stents were implanted in 10 arterial lesions, resulting in a 91% procedural success rate. One failure was due to inability to cross the total occlusion of the subclavian artery. Procedural complications and problems were pain during balloon angioplasty in three patients, vaso-vagal reflex in two, carotid artery perforation associated with transient horseness in one, and stent migration in one. There was no permanent morbidity. Follow-up over a mean duration of 12 months revealed one symptomatic recurrence of left subclavian stenosis, followed by a successful re-dilatation. The results of the current study indicated that primary stenting is an excellent therapeutic option for the occlusive carotid and subclavian arteries in Takayasu arteritis. A long-term follow-up is required to determine the response or behavior of stented segments of the affected arteries.


Deceleration capacity as a risk predictor in patients presenting to the emergency department with syncope: A prospective exploratory pilot study.
Syncope is a common cause for admission to the emergency department (ED). Due to limited clinical resources there is great interest in developing risk stratification tools that allow identifying patients with syncope who are at low risk and can be safely discharged. Deceleration capacity (DC) is a strong risk predictor in postinfarction and heart failure patients. The aim of this study was to evaluate whether DC provides prognostic information in patients presenting to ED with syncope.We prospectively enrolled 395 patients presenting to the ED due to syncope. Patient's electrocardiogram (ECG) for the calculation of DC was recorded by monitoring devices which were started after admission. Both the modified early warning score (MEWS) and the San Francisco syncope score (SFSS) were determined in every patient. Primary endpoint was mortality after 180 days.Eight patients (2%) died after 180 days. DC was significantly lower in the group of nonsurvivors as compared with survivors (3.1 ± 2.5 ms vs 6.7 ± 2.4 ms; P < .001), whereas the MEWS was comparable in both was comparable in both groups. (2.1 ± 0.8 vs 2.1 ± 1.0; P = .84). The SFSS failed at identifying 4 of 8 nonsurvivors (50%) as high risk patients. No patient with a favorable DC (≥7 ms) died (0.0% vs 3.7%; P = .01, OR 0.55 (95% CI 0.40-0.76), P < .001). In the receiver operating characteristic (ROC) analysis DC yielded an area under the curve of 0.85 (95% CI 0.71-0.98).Our study demonstrates that DC is a predictor of 180-days-mortality in patients admitted to the ED due to syncope. Syncope patients at low risk can be identified by DC and may be discharged safely.


Conference scene: Nanoneuroprotection and nanoneurotoxicity: recent progress and future perspectives.
Recent developments in research related to nanoparticles in neuroscience necessitated the establishment of a new discipline known as 'nanoneuroscience'. In order to understand the possible role of nanoparticles in the development of neurotoxicity or their potential use in neuroprotection, nine top experts across the world in this newly developing discipline were invited to present their cutting edge research in the 7th annual meeting of the Global College of Neuroprotection & Neuroregeneration in Stockholm, Sweden. The new developments suggest that more research is needed to understand the potential use of nanoparticles in nanomedicine. Highlights of these presentations are summarized in this article.


Predictors of Perceived Stress among Medical and Nonmedical College Students, Minia, Egypt.
Nowadays, stress has been tagged a global phenomenon. Many undergraduate students undergo considerable stress, and a variety of sources of stress have been identified among university students. The aim of this study is to identify the level of perceived stress and its predictors among medical and nonmedical Minia University students. This was a cross-sectional study comparing between medical and nonmedical students in Minia University, conducted during the period from March to April 2017. The sample consisted of 314 medical and 291 nonmedical students chosen through cluster random sampling as a section was chosen randomly from each academic year and collectively form the final sample. Data were collected through interview by a questionnaire inquiring about sociodemographic data, common stressors as academic, financial, family, and transportation stressors and Cohen Perceived Stress Scale 10. The prevalence of perceived stress was slightly higher (88.9%) among medical students than among nonmedical students (83.5%). Severe stress was found among (18.8%) of medical students compared to (12.4%) among nonmedical students (P < 0.05). The significant predictors of perceived stress were academic stressors, no exercise and being female among medical students, and were academic and financial stressors among nonmedical students. Medical students perceived more stress than nonmedical students. The academic stressors were significant predictors among all students; hence, there is a need for the establishment of students counseling unit, to facilitate coping with the stress of study and examination.


Mass spectrometry and tandem mass spectrometry analysis of rat mitochondrial ATP synthase: up-regulation in pancreatic acinar cells treated with cerulein.
Mitochondrion is a vulnerable intracellular target to reactive oxygen species (ROS). ROS have been considered to be important regulators of the pathogenesis of pancreatitis. This study aims to determine whether ROS induces mitochondrial damage by monitoring the expression level of mitochondrial ATP synthase as the key molecular component in mitochondria associated with cellular damage. Pancreatic acinar AR42J cells were treated with cerulein which induces symptoms similar to that associated with human acute pancreatitis. Proteins were separated by two-dimensional electrophoresis using pH gradients of 5-8 and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MS), quadrupole time-of-flight MS and MS/MS with nano-electrospray. Following cerulein treatment, mitochondrial ATP synthase beta chain was highly expressed compared to nontreated cell. The protein was identified by its pI of 5.2 and molecular weight (56 354 Da) with 27 matched peptides. Among the MS spectrum, precursor ions m/z 488.28, 544.81, 631.82, 693.34, 718.38, 729.41, 801.40, 809.39, 825.94, and 994.52 were further identified using MS/MS and confirmed the isolated protein to be mitochondrial ATP synthase beta chain. In conclusion, cerulein-induced oxidative injury may result in the induction of mitochondrial ATP synthase, which may act as an adaptive pathophysiological process in the pancreas.


Laryngoscopic and spectral analysis of laryngeal and pharyngeal configuration in non-classical singing styles.
The present study aimed to assess three different singing styles (pop, rock, and jazz) with laryngoscopic, acoustic, and perceptual analysis in healthy singers at different loudness levels. Special emphasis was given to the degree of anterior-posterior (A-P) laryngeal compression, medial laryngeal compression, vertical laryngeal position (VLP), and pharyngeal compression. Prospective study. Twelve female trained singers with at least 5 years of voice training and absence of any voice pathology were included. Flexible and rigid laryngeal endoscopic examinations were performed. Voice recording was also carried out. Four blinded judges were asked to assess laryngoscopic and auditory perceptual variables using a visual analog scale. All laryngoscopic parameters showed significant differences for all singing styles. Rock showed the greatest degree for all of them. Overall A-P laryngeal compression scores demonstrated significantly higher values than overall medial compression and VLP. High loudness level produced the highest degree of A-P compression, medial compression, pharyngeal compression, and the lowest VLP for all singing styles. Additionally, rock demonstrated the highest values for alpha ratio (less steep spectral slope), L1-L0 ratio (more glottal adduction), and Leq (more vocal intensity). Statistically significant differences between the three loudness levels were also found for these acoustic parameters. Rock singing seems to be the style with the highest degree of both laryngeal and pharyngeal activity in healthy singers. Although, supraglottic activity during singing could be labeled as hyperfunctional vocal behavior, it may not necessarily be harmful, but a strategy to avoid vocal fold damage.


Selective detection of sub-atto-molar Streptavidin in 10(13)-fold impure sample using photonic crystal nanolaser sensors.
Biosensors selectively detecting a very small amount of biomarker protein in human blood are desired for early and reliable diagnoses of severe diseases. This paper reports the detection of protein (streptavidin: SA) in ultra-low concentration, with an ultra-high selectivity against contaminants, using photonic crystal nanolasers. For biotin-modified nanolasers in pure water with SA, an extremely-low detection limit of 16 zM is evaluated. Even in a mixture with 1 μM bovine serum albumin as the contaminant, 100 zM SA is detected, meaning a selectivity of 10(13). These are remarkable capabilities that are promising for practical biosensing in the medical applications mentioned above.


The novel CD4+CD25+ regulatory T cell effector molecule fibrinogen-like protein 2 contributes to the outcome of murine fulminant viral hepatitis.
Fulminant viral hepatitis (FH) remains an important clinical problem in which the underlying pathogenesis is not well understood. Here, we present insight into the immunological mechanisms involved in FH caused by murine hepatitis virus strain 3 (MHV-3), indicating a critical role for CD4(+)CD25(+) regulatory T cells (Tregs) and production of the novel Treg effector molecule FGL2. Before infection with MHV-3, susceptible BALB/cJ mice had increased numbers of Tregs and expression of fgl2 messenger RNA (mRNA) and FGL2 protein compared with resistant A/J mice. After MHV-3 infection, plasma levels of FGL2 in BALB/cJ mice were significantly increased, correlating with increased percentage of Tregs. Treatment with anti-FGL2 antibody completely inhibited Treg activity and protected susceptible BALB/cJ mice against MHV-3-liver injury and mortality. Adoptive transfer of wild-type Tregs into resistant fgl2(-/-) mice increased their mortality caused by MHV-3 infection, whereas transfer of peritoneal exudate macrophages had no adverse effect. This study demonstrates that FGL2 is an important effector cytokine of Tregs that contributes to susceptibility to MHV-3-induced FH. The results further suggest that targeting FGL2 may lead to the development of novel treatment approaches for acute viral hepatitis infection.


Integration of World-to-Chip Interfaces with Digital Microfluidics for Bacterial Transformation and Enzymatic Assays.
Digital microfluidics (DMF) represents an alternative to the conventional microfluidic paradigm of transporting fluids in enclosed channels. One of the major benefits of DMF is that fluid motion and control is achieved without external pumps. The automation component of DMF have pushed the barriers of this "lab-on-chip" technology. However, integration with external components (i.e., "world-to-chip") interfaces have been a challenge. Two common "world-to-chip" challenges are (1) delivering biological samples to DMF devices and (2) accurately controlling temperatures on device. To address these challenges, this work describes two "world-to-chip" interface features that have been integrated on a DMF platform: a reagent delivery system and a thermal control apparatus. This platform enables a variety of biological or chemical experiments to be conducted on-chip while reducing manual intervention. Specifically, our platform increases reagent volumes available to device reservoirs volume by at least 50-fold eliminating the need to manually refill reservoirs while improving droplet dispensing reproducibility. In addition, we have integrated a closed-loop temperature control system that offers precise temperature control on-chip. To validate our "world-to-chip" interface, we have automated bacterial transformation and enzymatic assay protocols, showing that such a system enhances DMF performance. Overall, we propose that this system will improve biological experimentation which requires fluidic and temperature control integrated on DMF platforms.


Complementary and alternative medicine use by glioma patients in Switzerland.
During the course of disease, most glioma patients learn that there is no cure for their tumor. It is therefore not uncommon for patients or caregivers to seek complementary and alternative medicine (CAM) treatments. Patterns of CAM use vary across the globe, but little is known about the type of, and motivation for, CAM use in most countries. Here we conducted a cross-sectional survey of CAM use in patients harboring gliomas of World Health Organization (WHO) grades II to IV at 3 specialized neuro-oncology centers in Switzerland. Of 208 patients who returned the survey, approximately half reported having used or using CAM. CAM use was associated with younger age. Patients suffering from WHO grade II gliomas were less likely to indicate CAM use. The leading motivation for CAM use was to contribute actively to the treatment of the disease. CAM use was commonly not counseled or supervised by a health care professional. Cost and issues of reimbursement were not an important factor in the decision against or for CAM use. Physicians caring for glioma patients should be aware of and explore CAM use to better understand patients' attitudes toward their disease, to provide counseling, and to identify potential interactions of CAM with standard treatments for gliomas.


Method of unconfounding orientation and direction tunings in neuronal response to moving bars and gratings.
When an oriented bar or grating is drifted across the receptive field of a cortical neuron at various orientations, the tuning function reflects both, and thus confounds the orientation (ORI) and the direction-of-motion (DIR) selectivity of the cell. Since ORI (or DIR), by definition, has a period of 180(or 360) deg/cycle, a popular method for separating these two components, due to Wörgötter and Eysel [Biol. Cybern. 57, 349 (1987)], is to Fourier decompose the neuron's response along the angular direction and then identify the first and the second harmonic with DIR and ORI, respectively (the SDO method). Zhang [Biol. Cybern. 63, 135 (1990)] pointed out that this interpretation is misconceived--all odd harmonics (not just the first harmonic) reflect the DIR component, whereas all even harmonics (including the second harmonic) contain contributions from both DIR and ORI. Here, a simplified procedure is proposed to accomplish the goal of unconfounding ORI and DIR. We first construct the sum of all odd harmonics of the overall tuning curve, denoted ODDSUM, by calculating the difference in the neuronal response to opposite drifting directions. Then we construct ODDSUM+/ODDSUM/ and identify it with DIR (here . denotes the absolute value). Subtracting DIR, that is ODDSUM+ /ODDSUM/, from the overall tuning curve gives ORI. Our method ensures that (i) the reconstructed DIR contains only one, positive peak at the preferred direction and can have power in all harmonics, and (ii) the reconstructed ORI has two peaks separated by 180 degrees and has zero power for all odd harmonics. Using this procedure, we have unconfounded orientation and direction components for a considerable sample of macaque striate cortical cells, and compared the results with those obtained using Wörgötter and Eysel's SDO method. We found that whereas the estimate of the peak angle of ORI remains largely unaffected, Wörgötter and Eysel's method considerably overestimated the relative strength of ORI. To conclude, a simple method is provided for appropriately separating the orientation and directional tuning in a neuron's response that is confounded as a result of the use of drifting oriented stimuli.


When silence is not golden: an integrated approach to selective mutism.
Selective mutism (SM) is a rare disorder that is associated with both anxiety and communication impairments. Preliminary evidence suggests that educational attainment and development of social skills and self-esteem may be affected by SM in a significant proportion of cases. There is a critical need for cross-disciplinary research from the fields of speech-language pathology, psychiatry, and clinical psychology to develop protocols for assessing language and cognitive functioning in children with SM and developing interventions that address psychiatric, communicative, and social aspects of this disorder.


Backgrounds and challenges of food education policy in Taiwan: risk or chance in the reflexive food modernity?
In 2022, Taiwan enacted the Food and Agricultural Education Act, thus officially launching its food education policy. The objective of this article is to elucidate the social background to this Act and current challenges to promoting food education. The data were obtained from the relevant literature and interviews with 11 key actors, who represented academia, the government, public education and civil society. Although having much in common with the Japanese equivalent policy, Taiwan's food education contains some notable features. Food education began as a reaction to recent food safety scandals, growing food anxiety, the prevalence of eating out, the globalisation of food systems and increasing instability, all of which characterise reflexive food modernity. The Taiwanese policy aims to avoid the nutrition-centered, gendered and nationalistic tendencies of food education in countries such as Japan by stressing the interconnection of food system actors, social responsibility for family meals and an openness to diverse food cultures. However, achieving such objectives requires consciousness of the reflexive food modernity facing Taiwan and addressing operational issues, notably the strengthening of inter-ministerial collaboration and the integration of dialogue with diverse food education actors in defining educational content and professional qualifications.


Insulin receptor binding and tyrosine kinase activity in skeletal muscle from normal pregnant women and women with gestational diabetes.
To ascertain whether the decreased glucose tolerance and insulin resistance found in normal and gestational diabetic pregnancy might be associated with changes in insulin receptor function. Eight nonpregnant healthy women (nonpregnant controls), eight healthy pregnant women (pregnant controls), and eight women with gestational diabetes were investigated. All were non-obese. Muscle biopsies were obtained from the vastus lateralis muscle, and insulin binding and tyrosine kinase activities in partially purified skeletal muscle insulin receptors were studied. The pregnant controls were investigated in late pregnancy, and the women with gestational diabetes were investigated at the time of diagnosis of gestational diabetes. A further examination was carried out 2 months after delivery. Insulin binding at tracer insulin concentration (60 pmol/L) was diminished in women with gestational diabetes compared to nonpregnant controls (P < .05), whereas normal pregnant women did not differ from the other two groups. Postpartum, no differences in insulin binding were found between the groups. Basal and maximal tyrosine kinase activities toward the exogenous substrate poly(Glu4Tyr1) were the same in nonpregnant controls, pregnant controls, and women with gestational diabetes. Postpartum, no differences in tyrosine kinase activity were found among the groups. Moreover, no significant differences in insulin binding or tyrosine kinase activity were found comparing pregnancy and postpartum values within the groups. The insulin resistance found in normal and gestational diabetic pregnancy is not likely to be caused by a defective insulin receptor tyrosine kinase, whereas decreased insulin receptor binding might have some pathogenic importance in gestational diabetes.


First effective mHealth nutrition and lifestyle coaching program for subfertile couples undergoing in vitro fertilization treatment: a single-blinded multicenter randomized controlled trial.
To study compliance and effectiveness of the mHealth nutrition and lifestyle coaching program Smarter Pregnancy in couples undergoing in vitro fertilization (IVF) treatment with or without intracytoplasmic sperm injection (ICSI). Multicenter, single-blinded, randomized controlled trial, conducted from July 2014 to March 2017. IVF clinics. A total of 626 women undergoing IVF treatment with or without ICSI and 222 male partners. Couples were randomly assigned to the light (control group) or regular (intervention group) Smarter Pregnancy program. Both groups filled out a baseline screening questionnaire on nutrition and lifestyle behaviors, and the intervention group received coaching tailored to inadequate behaviors during the 24-week period. Difference in improvement of a composite dietary and lifestyle risk score for the intake of vegetables, fruits, folic acid supplements, smoking, and alcohol use after 24 weeks of the program. Compared with control subjects, women and men in the intervention group showed a significantly larger improvement of inadequate nutrition behaviors after 24 weeks of coaching. At the same time, the women also showed a significantly larger improvement of inadequate lifestyle behaviors. The mHealth coaching program Smarter Pregnancy is effective and improves the most important nutritional and lifestyle behaviors among couples undergoing IVF/ICSI treatment. International multicenter randomized trials are recommended to study the effect of using Smarter Pregnancy on pregnancy, live birth, and neonatal outcome. NTR4150.


Cathodal transcranial direct current stimulation over the right dorsolateral prefrontal cortex cancels out the cost of selective retrieval on subsequent analogical reasoning.
Analogical reasoning involves mapping the relation between two concepts within a specific field into a new domain to selectively retrieve a possible solution. Neuroimaging studies have shown that both selective retrieval and reasoning by analogy are related to activity in prefrontal regions such as the dorsolateral prefrontal cortex (DLPFC). In the present study, we investigate the role of the right DLPFC in modulating memory accessibility and its impact on analogical reasoning by using transcranial direct current stimulation (tDCS). Participants performed a four-term reasoning task after performing repeated selective retrieval of previously presented items, some of which could be used as solutions in the analogical test. During selective retrieval, half of the participants received cathodal tDCS over the right DLPFC and the other half received sham stimulation. The results reveal that whereas the sham group showed the expected cost in performance that is associated with selective retrieval, the cathodal group did not exhibit such an impairment in reasoning. No general effects of tDCS on analogical performance were observed. Altogether, our results support the involvement of the right DLPFC as a core component of a control network that selectively contributes to the retrieval component of analogical reasoning, but with little role in mapping relations between different domains.


Molecular Cloning and Expression Analysis of hyp-1 Type PR-10 Family Genes in Hypericum perforatum.
Hypericum perforatum L. is an important medicinal plant for the treatment of depression. The plant contains bioactive hypericins that accumulate in dark glands present especially in reproductive parts of the plant. In this study, pathogenesis-related class 10 (PR-10) family genes were identified in H. perforatum, including three previously unidentified members with sequence homology to hyp-1, a phenolic coupling protein that has earlier been suggested to participate in biosynthesis and binding/transportation of hypericin. The PR-10 genes showed constitutive but variable expression patterns in different H. perforatum tissues. They were all expressed at relatively high levels in leaves, variably in roots and low levels in stem and reproductive parts of the plant with no specific association with dark glands. The gene expression was up-regulated in leaves after salicylic acid, abscisic acid and wounding treatments but with variable levels. To study exact location of the gene expression, in situ hybridization of hyp-1 transcripts was performed and the accumulation of the Hyp-1 protein was examined in various tissues. The presence of Hyp-1 protein in H. perforatum tissues mostly paralleled with the mRNA levels. In situ RNA hybridization localized the hyp-1 transcripts predominantly in vascular tissues in root and stem, while in leaf the mRNA levels were high also in mesophyll cells in addition to vasculature. Our results indicate that the studied PR-10 genes are likely to contribute to the defense responses in H. perforatum. Furthermore, despite the location of the hyp-1 transcripts in vasculature, no support for the transportation of the Hyp-1 protein to dark glands was found in the current study. The present results together with earlier data question the role of the hyp-1 as a key gene responsible for the hypericin biosynthesis in dark glands of H. perforatum.


Double-blind comparison of 2.5 and 5.0 mg of prostaglandin E2 gel for preinduction cervical ripening.
To compare the effectiveness and safety of 2.5 vs. 5.0 mg of prostaglandin E2 (PGE2) gel for preinduction cervical ripening. Patients presenting for induction of labor with an unfavorable Bishop score (< or 4) were assigned randomly, in a double-blind manner, to receive either 2.5 or 5.0 mg of PGE2 gel intravaginally. A repeat Bishop score was determined in four to six hours, and if the score was still unfavorable, the same dose of gel was administered a second time. All patients returned within 12 hours for induction of labor. A total of 119 patients received PGE2 gel, 55 in the 2.5-mg group and 64 in the 5.0-mg group. Both groups were similar with respect to age, parity, race, indication for induction and preinduction Bishop score. Both doses of PGE2 gel were safe and effective. The need for additional doses of gel, the need for and duration of oxytocin use, and the duration of labor were similar in both groups. More infants whose mothers received the 5.0-mg dose had one-minute Apgar scores < 7 (P = .027). No significant difference in five-minute Apgar scores was noted. Cesarean delivery for failed induction was uncommon, occurring in 3.6% of patients who received 2.5 mg and in 4.7% of patients who received 5.0 mg of PGE2 gel (P = NS). Finally, the incidence of hyperstimulation was 3.6% in the 2.5-mg group and 1.6% in the 5.0-mg group (P = NS). A 5-mg dose of PGE2 gel was neither more effective nor associated with more side effects than the more commonly used 2.5-mg dose.


The impact of the Women's Health Initiative study on incident clonidine use in Ontario, Canada.
Following publication of the Women's Health Initiative (WHI) study, many women discontinued use of estrogen replacement therapy. There is some evidence that the antihypertensive agent clonidine can reduce the frequency of hot flashes associated with menopause. To determine the impact of the WHI study on incident use of clonidine in elderly women in Ontario, Canada. Retrospective, population-based administrative database design. Data on all residents of Ontario over the age of 65 years were included. Time series methods were used to analyze change in incident clonidine use following publication of the WHI study. Following publication of the WHI study, incident use of clonidine increased substantially among elderly women in Ontario, Canada. Similar trends were not observed for incident use of other antihypertensive medications. During a period of time in which a large proportion of women discontinued estrogen replacement therapy, incident use of clonidine increased. There is some evidence that a small number of women may have sought alternative relief from menopausal symptoms using other pharmacological therapies.


Review: automatic particle detection in electron microscopy.
Advances in cryoEM and single-particle reconstruction have led to results at increasingly high resolutions. However, to sustain continuing improvements in resolution it will be necessary to increase the number of particles included in performing the reconstructions. Manual selection of particles, even when assisted by computer preselection, is a bottleneck that will become significant as single-particle reconstructions are scaled up to achieve near-atomic resolutions. This review describes various approaches that have been developed to address the problem of automatic particle selection. The principal conclusions that have been drawn from the results so far are: (1) cross-correlation with a reference image ("matched filtering") is an effective way to identify candidate particles, but it is inherently unable to avoid also selecting false particles; (2) false positives can be eliminated efficiently on the basis of estimates of particle size, density, and texture; (3) successful application of edge detection (or contouring) to particle identification may require improvements over currently available methods; and (4) neural network techniques, while computationally expensive, must also be investigated as a technology for eliminating false particles.


Expression of AMPA-selective glutamate receptor subunits in morphologically defined neurons of the mammalian cochlear nucleus.
Glutamate and related amino acids mediate fast excitatory neurotransmission in the vertebrate CNS via ligand-gated cationic channels in the neuronal membrane. These channels are composed of different subunits that assemble into a functional receptor/channel complex. Although studies have shown that these subunits are differentially expressed in neurons, few studies have quantitatively addressed the cell-specific expression of glutamate subunits in relation to known glutamatergic pathways. In the vertebrate auditory system, glutamate is the proposed neurotransmitter of the auditory nerve and parallel fiber pathways. In situ hybridization histochemistry was used to localize AMPA-selective glutamate receptor subunit mRNAs in seven cell types of the rat cochlear nucleus. GluR1-GluR4 AMPA-selective subunits were all expressed in cochlear nucleus neurons; however, the subunits expressed in identified cells varied with the cell type. Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits. Cartwheel and stellate interneurons in the dorsal cochlear nucleus, which receive parallel fiber input, expressed all four subunits. Neurons receiving synaptic input from the auditory nerve, including globular, round, spherical, and fusiform cells, expressed GluR2, GluR3, and GluR4 subunits. Furthermore, a subpopulation of round cells in the ventral cochlear nucleus, and fusiform cells in the dorsal cochlear nucleus, expressed the GluR3 subunit at greatly reduced levels compared to neighboring cells. The results confirm the auditory nerve and parallel fiber pathways as glutamatergic and identify a third synaptic population, projecting to granule cells, which is likely glutamatergic. The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present.


Tamoxifen prevents bone loss in ovariectomized mice.
Bone density and mineral content of the femora were significantly decreased in ovariectomized mice compared with intact control animals. Tamoxifen treated ovariectomized mice did not develop any decrease either in the bone density or in calcium and phosphate content of the femora which were observed in ovariectomized mice. In addition, the weight of uterus in tamoxifen treated ovariectomized mice was the same as in intact controls. It was concluded that tamoxifen administered in vivo prevented the loss of bone mineral and uterus weight in ovariectomized mice and thus it showed a true estrogen like action in this respect.


Decreased metal accumulation in passerines as a result of reduced emissions.
Technological advances in industrial processes have resulted in reduced atmospheric emissions from metal industries all over the globe, but the response of the environment is not well known. The authors studied metal (As, Cd, Cu, Ni, Pb, and Se) accumulation in passerine birds (pied flycatcher, Ficedula hypoleuca, and great tit, Parus major) following almost 20 years of reduced metal emissions from the largest nonferrous smelter in Finland. Close to the industry, emission reductions resulted in reduced exposure to several of the elements and, more importantly, reduced accumulation by 58 to 95% in liver tissue. Albeit showing significant tissue reductions, nestlings had elevated concentrations of arsenic, cadmium, lead, and selenium close to the industry. Single-element concentrations were below critical levels associated with subclinical effects, but the mixture of toxic elements indirectly affected health and reproduction. Our study indicates that in environments with moderate duration of industrial activity, impact, and soil pollution, metal accumulation in organisms can decrease relatively rapidly when atmospheric emissions are reduced.


Is allergy increasing?--early life influences.
Data from epidemiological studies conducted in several countries worldwide have revealed that the prevalences of allergic conditions, including allergic rhinitis, asthma and eczema, have increased from the 1940s/50s to the 1990s. These allergic conditions involve specific IgE-mediated responses, and a few studies have demonstrated that IgE levels have increased in some communities over time in a manner similar to the incidences of allergic conditions. The predisposition for atopy appears to be determined in early life, and evidence indicates that events occurring in utero and in infancy can influence the future development of atopy. The intrauterine environment favours TH2 cell development and IgE production and could predispose to atopy. It can be hypothesized that dietary or other factors favouring TH2 proliferation might contribute to the development of atopic disease. Conversely, early infection has been found to have a negative association with the development of atopy, perhaps through promotion of a TH response; the reduction in infection in the very young as a consequence of modern healthcare may have contributed to the increase in atopic disease. Thus, it is a plausible hypothesis that changes in the conditions of the intrauterine environment and/or in infancy (for example, in nutrition and in rates of infection) may explain the observed increases in atopy and allergic conditions.


Intestinal parasite screening in internationally adopted children: importance of multiple stool specimens.
Our goal was to determine the prevalence of intestinal parasites in internationally adopted children, to examine factors associated with infection, and to determine if evaluating multiple stool specimens increases the yield of parasite identification. We evaluated internationally adopted children with at least 1 stool specimen submitted for ova and parasite testing within 120 days after arrival to the United States. In children submitting 3 stool specimens, in which at least 1 specimen was positive for the pathogen studied, we examined whether multiple stool specimens increased the likelihood of pathogen identification. Of the 1042 children studied, 27% had at least 1 pathogen identified; with pathogen-specific prevalence of Giardia intestinalis (19%), Blastocystis hominis (10%), Dientamoeba fragilis (5%), Entamoeba histolytica (1%), Ascaris lumbricoides (1%), and Hymenolepsis species (1%). The lowest prevalence occurred in South Korean (0%), Guatemalan (9%), and Chinese (13%) children, and the highest prevalence occurred in Ethiopian (55%) and Ukrainian (74%) children. Increasing age was significantly associated with parasite identification, whereas malnutrition and gastrointestinal symptoms were not. Overall, the yield of 1 stool specimen was 79% with pathogen recovery significantly increasing for 2 (92%) and 3 (100%) specimens, respectively (P < .0001). Pathogen identification also significantly increased with evaluation of additional stool specimens for children with and without gastrointestinal symptoms. We provide data for evidence-based guidelines for intestinal parasite screening in internationally adopted children. Gastrointestinal symptoms were not predictive of pathogen recovery, and multiple stool specimens increased pathogen identification in this high-risk group of children.


Effect of endovascular hypothermia on acute ischemic edema: morphometric analysis of the ICTuS trial.
Pilot studies of hypothermia for stroke suggest a potential benefit in humans. We sought to test whether hypothermia decreases post-ischemic edema using CT scans from a pilot trial of endovascular hypothermia for stroke. Eighteen patients with acute ischemic stroke underwent therapeutic hypothermia (target = 33 degrees C) for 12 or 24 h followed by a 12-h controlled re-warm using an endovascular system. CT scans obtained at baseline, 36-48 h (right after cooling and re-warming) and 30 days were digitized, intracranial compartment volumes measured using a validated stereological technique, and the calculated change in CSF volume between the three time-points were used as an estimate of edema formation in each patient. Patients were grouped retrospectively for analysis based on whether they cooled effectively (i.e., to a temperature nadir of less than 34.5 degrees C within 8 h) or not. Eleven patients were cooled partially or not at all, and seven were effectively cooled. Baseline demographics and compartment volumes and densities were similar in both groups. At 36-48 h, the total CSF volume had significantly decreased in the not-cooled group compared to the cooled group (P < 0.05), with no significant difference in mean volume of ischemia between them (73 +/- 73 ml vs. 54 +/- 59 ml, respectively), suggesting an ameliorative effect of hypothermia on acute edema formation. At 30 days, the difference in CSF volumes had resolved, and infarct volumes (73 +/- 71 ml vs. 84 +/- 102 ml, respectively) and functional outcomes were comparable. Endovascular hypothermia decreases acute post-ischemic cerebral edema. A larger trial is warranted to determine if it affects final infarct volume and outcome in stroke.


ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia.
Studies of patients with severe acute respiratory syndrome (SARS) demonstrate that the respiratory tract is a major site of SARS-coronavirus (CoV) infection and disease morbidity. We studied host-pathogen interactions using native lung tissue and a model of well-differentiated cultures of primary human airway epithelia. Angiotensin converting enzyme 2 (ACE2), the receptor for both the SARS-CoV and the related human respiratory coronavirus NL63, was expressed in human airway epithelia as well as lung parenchyma. As assessed by immunofluorescence staining and membrane biotinylation, ACE2 protein was more abundantly expressed on the apical than the basolateral surface of polarized airway epithelia. Interestingly, ACE2 expression positively correlated with the differentiation state of epithelia. Undifferentiated cells expressing little ACE2 were poorly infected with SARS-CoV, while well-differentiated cells expressing more ACE2 were readily infected. Expression of ACE2 in poorly differentiated epithelia facilitated SARS spike (S) protein-pseudotyped virus entry. Consistent with the expression pattern of ACE2, the entry of SARS-CoV or a lentivirus pseudotyped with SARS-CoV S protein in differentiated epithelia was more efficient when applied to the apical surface. Furthermore, SARS-CoV replicated in polarized epithelia and preferentially exited via the apical surface. The results indicate that infection of human airway epithelia by SARS coronavirus correlates with the state of cell differentiation and ACE2 expression and localization. These findings have implications for understanding disease pathogenesis associated with SARS-CoV and NL63 infections.


Type V secretion: mechanism(s) of autotransport through the bacterial outer membrane.
Autotransport in Gram-negative bacteria denotes the ability of surface-localized proteins to cross the outer membrane (OM) autonomously. Autotransporters perform this task with the help of a β-barrel transmembrane domain localized in the OM. Different classes of autotransporters have been investigated in detail in recent years; classical monomeric but also trimeric autotransporters comprise many important bacterial virulence factors. So do the two-partner secretion systems, which are a special case as the transported protein resides on a different polypeptide chain than the transporter. Despite the great interest in these proteins, the exact mechanism of the transport process remains elusive. Moreover, different periplasmic and OM factors have been identified that play a role in the translocation, making the term 'autotransport' debatable. In this review, we compile the wealth of details known on the mechanism of single autotransporters from different classes and organisms, and put them into a bigger perspective. We also discuss recently discovered or rediscovered classes of autotransporters.


Fetal behaviour and the cardiovascular system.
With increasing gestation both in the human and in animals clear fetal behavioural state cycles develop. Fetal heart rate patterns are closely related to the phenomenon of behavioural state. In this review article fetal heart rate patterns will be analysed in relation to particular behavioural states, individual movement patterns and diurnal variations. Attention will also be paid to maturational changes. Differences between human and animal states are emphasized. It is concluded, that understanding of the basic mechanisms underlying the normal heart rate patterns throughout gestation, improves the reliability of fetal surveillance.


Systematic and experimental investigations of the anti-colorectal cancer mediated by genistein.
Recent evidences have suggested that genistein, a beneficial isoflavonoid, exerts marked anti-proliferative action on colorectal cancer (CRC) cells. However, the exact molecular mechanisms behind anti-CRC effect of genistein have not been elucidated. In current report, a systemic pharmacology analysis was used to disclose the anti-CRC mechanism of genistein prior to performing experimentative certification. As shown in network pharmacology findings, a total of 189 common targets and 9 hard-core targets of genistein-anti-CRC were collected and identified. And the detailed anti-CRC functions and pathways mediated by genistein were uncovered. In further certification, human CRC samples resulted in elevated protein and mRNA expressions of myeloid leukemia cell differentiation protein (MCL1), beta amyloid A4 protein (APP), and vascular endothelial growth factor receptor 2 (KDR). In animal experiment, genistein-treated tumor-transplanted nude mice exhibited reduced tumor growth, accompanied with dose-dependent down-regulations of MCL1, APP, and KDR proteins and mRNAs. Taken together, the integrated bioinformatic and experimental findings uncover the anti-CRC mechanisms and targets mediated by genistein. Significantly, parts of hard-core biotargets were experimentally verified before clinical application, including MCL1, APP, and KDR.


Engineering the Chloroplast Genome of Oleaginous Marine Microalga Nannochloropsis oceanica.
Plastid engineering offers an important tool to fill the gap between the technical and the enormous potential of microalgal photosynthetic cell factory. However, to date, few reports on plastid engineering in industrial microalgae have been documented. This is largely due to the small cell sizes and complex cell-wall structures which make these species intractable to current plastid transformation methods (i.e., biolistic transformation and polyethylene glycol-mediated transformation). Here, employing the industrial oleaginous microalga Nannochloropsis oceanica as a model, an electroporation-mediated chloroplast transformation approach was established. Fluorescent microscopy and laser confocal scanning microscopy confirmed the expression of the green fluorescence protein, driven by the endogenous plastid promoter and terminator. Zeocin-resistance selection led to an acquisition of homoplasmic strains of which a stable and site-specific recombination within the chloroplast genome was revealed by sequencing and DNA gel blotting. This demonstration of electroporation-mediated chloroplast transformation opens many doors for plastid genome editing in industrial microalgae, particularly species of which the chloroplasts are recalcitrant to chemical and microparticle bombardment transformation.


[Sexual activity after surgery for benign prostatic hypertrophy].
A retrospective study was conducted in 57 patients who had undergone surgery at our center for benign prostatic hyperplasia over a period of one year. Postoperative sexual activity and the presence or absence of antegrade ejaculation were determined. Of these patients, 19 had no sexual activity before or after the operation and were therefore excluded from the study. The surgical techniques utilized were transvesical adenomectomy in 27 cases and TUR in 11 cases. Three patients (8%) were impotent after surgery, the difference between the two surgical techniques not being statistically significant. Retrograde ejaculation was observed in 58% (70% of the patients who underwent open surgery and 27.2% of those who underwent TUR). We analyze the results reported elsewhere and underscore the need to conduct prospective studies on one or several techniques using the same terminology in order to draw more reliable conclusions.


Artificial Intelligence in Healthcare.
Modern technology development created significant innovations in delivery of healthcare. Artificial intelligence as "a branch of computer science dealing with the simulation of intelligent behaviour in computers" when applied in health care resulted in intelligent support to decision-making, optimised business processes, increased quality, monitoring and delivering of personalised treatment plans and many other applications. Even though the benefits are clear and numerous, there are still open issues in creating automation of healthcare processes, ensuring data protection and integrity, reduction of medical waste etc. However, due to rapid development of AI techniques, more advances and improvements are still expected.


Effect of auriculotherapy on menstrual irregularities in single girls with polycystic ovarian syndrome and aged 18-35 years in Isfahan in 2012.
Polycystic ovarian syndrome is one of the most common endocrine disorders with a prevalence of 5-10% in women. This syndrome is one of the major causes for menstrual disorders and is treated by medicational and non-medicational methods. This study aimed to define the effect of auriculotherapy on menstruation disorders in girls with polycystic ovarian syndrome. This is a clinical trial conducted on 60 single girls aged 18-35 years with clinical, laboratory, and sonography signs. The subjects were randomly assigned to two groups of auriculotherapy and medication, which underwent treatment for 2 and 3 months, respectively. Clinical signs were investigated in three steps in both groups. Data were collected through observation, laboratory tests, and sonography, and were analyzed by SPSS version 15. In 60 subjects, Chi-square test showed a significant difference in menstruation disorders in both groups 1 month after the start of intervention (P = 0.001); but 2 months after the start of intervention (P = 0.11) and immediately after the end of the intervention (P = 0.16), the difference was not significant. Three months after the end of the intervention, this variable showed a significant difference (P = 0.02). Medicational treatment and auriculotherapy are both effective on menstruation disorders, but auriculotherapy is more effective on reduction of menstruation disorders, compared to medicational therapy.


[Malignant melanoma of the meninges--MR and CT diagnosis].
Malignant melanoma of the meninges is a rare neoplasm derived from melanocytes of the cranial or spinal meninges. Histologically classified as grade IV tumours, malignant melanoma may present either as a diffuse meningeal neoplasm, first described by Virchow in 1859, or as a circumscribed tumour attached to the meninges. Although diagnosis is rarely established prior to surgery or autopsy, MR and CT may provide indispensable information probably leading to earlier diagnosis. In 4 patients, diagnosis of a primary meningeal melanoma was based on MR and CT findings and histology. Histology was obtained in 3 cases by surgery, in one patient by autopsy and showed a melanotic and an amelanotic malignant melanoma in 2 patients each. Autopsy was carried out in 3 cases after survival of 4, 5, and 18 months; in a single case, the follow-up period is almost 3 years.