Furosemide inhibits glucose transport in isolated rat adipocytes via direct inactivation of carrier proteins.
Furosemide inhibits 3-O-methyl-D-glucose equilibrium flux in isolated adipocytes. The inhibition is saturable with an increasing concentration of furosemide and shows a noncompetitive type of kinetics. Both basal and insulin-stimulated fluxes are equally affected by the inhibition. Hydrochlorothiazide and piretanide also inhibit the flux with a similar potency, whereas bumetanide, a more potent diuretic, is much less potent. To understand the molecular basis of this inhibition, effects of furosemide on the glucose-sensitive cytochaslasin B binding activities of adipocytes were studied. Furosemide inhibits the glucose-sensitive cytochalasin B binding of both microsomal and plasma membrane preparations. For both preparations, the inhibition is time dependent and only slowly reversible, is saturable with an increasing concentration of furosemide, shows a noncompetitive type of kinetics with apparent Ki (the inhibitor concentration that gives the half-maximum effect) of 3.5 and 0.7 mM after 2 and 18 h incubation, respectively, and is essentially identical between the basal and insulin-stimulated adipocytes. The inhibition develops with a first-order rate constant of approximately 0.12/h at 4 degrees C. These results indicate that furosemide inhibits glucose transport in adipocytes by directly inactivating transport carriers of both plasma membranes and microsomal reserve pool. This inactivation of glucose carrier may play a part in the diuretic-induced glucose intolerance frequently observed during diuretic therapy.


A Comparative Evaluation on Antimicrobial Effect of Honey, Neem Leaf Extract and Sodium Hypochlorite as Intracanal Irrigant: An Ex-Vivo Study.
The major determinant of the success of root canal treatment depends on meticulous disinfection of the root canal using intracanal irrigants. The most commonly used root canal irrigant is sodium hypochlorite which has disadvantages of cytotoxicity and unpleasant taste. So there is a need to identify a more biocompatible root canal irrigant. The aim of this ex-vivo study was to evaluate the efficacy of 40% honey, 100% neem leaf extract and 5.25% sodium hypochlorite as an intracanal irrigant against the isolated microorganisms from infected root canal. The samples were collected from infected root canals of 60 primary molar teeth indicated for pulpectomy. Alpha hemolytic Streptococci, gram negative bacilli, Candida, Staphylococci, Lactobacilli, Enterococci, Spore bearing gram positive bacilli and Micrococci were the microorganisms isolated from the samples. The zone of inhibition against the microbial growth was measured by agar well diffusion method. Statistical analysis was done by Repeated Analysis of Variance (ANOVA) and Bonferroni method. Statistical analysis showed that the means of the zones of inhibition measured in this study were 18.56mm, 2.09mm and 1.62mm for sodium hypochlorite, 100% neem leaf extract and 40% honey respectively. The significance was greater between sodium hypochlorite and the other two agents as p-value was <0.001. The results indicated that 5.25% sodium hypochlorite is more effective as root canal irrigant when compared with 100% neem leaf extract and 40% honey. It was also observed that 100% neem leaf extract has greater antimicrobial effect than 40% honey.


Palovarotene Inhibits Heterotopic Ossification and Maintains Limb Mobility and Growth in Mice With the Human ACVR1(R206H) Fibrodysplasia Ossificans Progressiva (FOP) Mutation.
Fibrodysplasia ossificans progressiva (FOP), a rare and as yet untreatable genetic disorder of progressive extraskeletal ossification, is the most disabling form of heterotopic ossification (HO) in humans and causes skeletal deformities, movement impairment, and premature death. Most FOP patients carry an activating mutation in a bone morphogenetic protein (BMP) type I receptor gene, ACVR1(R206H) , that promotes ectopic chondrogenesis and osteogenesis and, in turn, HO. We showed previously that the retinoic acid receptor γ (RARγ) agonist palovarotene effectively inhibited HO in injury-induced and genetic mouse models of the disease. Here we report that the drug additionally prevents spontaneous HO, using a novel conditional-on knock-in mouse line carrying the human ACVR1(R206H) mutation for classic FOP. In addition, palovarotene restored long bone growth, maintained growth plate function, and protected growing mutant neonates when given to lactating mothers. Importantly, palovarotene maintained joint, limb, and body motion, providing clear evidence for its encompassing therapeutic potential as a treatment for FOP. © 2016 American Society for Bone and Mineral Research.


[MRI evaluation of residual breast carcinoma after neoadjuvant chemotherapy].
This study aims to evaluate the sensibility and specificity of MRI in the detection and size measuring of residual breast cancer in patients treated with neoadjuvant chemotherapy before surgery. This is a retrospective study of 32 women, who underwent breast MRI before and after neoadjuvant treatment. MRI has been confronted to surgical pathology results. The sensibility of MRI to assess pathologic Complete Response (no invasive residual tumor) was excellent (100%) but the specificity was low (55,5%). There was no false negative case and four false positive cases (Two ductal carcinomas in situ and two scars-like fibrosis). When MRI outcomes were compared with the presence or absence of invasive or in situ residual carcinoma, only one false negative case was noticed (one "in situ" residual tumor). The correlation between tumor size measured by MRI and histopathology was low (r=0,32). Underestimations of tumor size were due to non-continuous tumor regression or invasive lobular carcinoma or association of invasive carcinoma and intra ductal breast cancer. Over estimations of tumor size were due to chemotherapy-induced changes. MRI is a sensitive but poorly specific method to assess the pathological complete response after neoadjuvant chemotherapy. Estimation of tumor size and detection of isolated residual in situ carcinoma are fare. Therefore, surgical intervention remains necessary whatever the MRI outcomes.


Notch and Delta are required for survival of the germline stem cell lineage in testes of Drosophila melanogaster.
In all metazoan species, sperm is produced from germline stem cells. These self-renew and produce daughter cells that amplify and differentiate dependent on interactions with somatic support cells. In the male gonad of Drosophila melanogaster, the germline and somatic cyst cells co-differentiate as cysts, an arrangement in which the germline is completely enclosed by cytoplasmic extensions from the cyst cells. Notch is a developmentally relevant receptor in a pathway requiring immediate proximity with the signal sending cell. Here, we show that Notch is expressed in the cyst cells of wild-type testes. Notch becomes activated in the transition zone, an apical area of the testes in which the cyst cells express stage-specific transcription factors and the enclosed germline finalizes transit-amplifying divisions. Reducing the ligand Delta from the germline cells via RNA-Interference or reducing the receptor Notch from the cyst cells via CRISPR resulted in cell death concomitant with loss of germline cells from the transition zone. This shows that Notch signaling is essential for the survival of the germline stem cell lineage.


Anti-apoptotic and antioxidant effect of leptin on CCl₄-induced acute liver injury in rats.
The aim of this study is to investigate the effect of leptin in rats on carbon tetrachloride (CCl(4)) induced acute liver damage using immunohistochemical methods for apoptosis and biochemical parameters. In this experimental study, 18 Spraque-Dawley rats were divided into three groups viz; control, CCl(4) and CCl(4)+leptin treatment. 0.8 ml/kg olive oil was administered intraperitoneally (i.p.) to the control group and 0.8 ml/kg CCl(4) (1:1 dissolved in olive oil) was administered i.p. to the CCl(4) and CCl(4)+leptin treatment groups, respectively. After 6 h of administrating CCl(4), CCl(4)+leptin treatment group was given i.p. leptin (10 μg/kg). Twenty-four hours after administrating CCl(4) all of the groups were euthanized. Biochemical assessments were performed using serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), plasma tumor necrosis factor alpha (TNF-α) levels and tissue malondialdehyde (MDA), and TNF-α levels. Histological assessments were then performed using Hematoxylin&Eosin (H&E) staining in light microscope and apoptosis assessment using Terminal Transferase dUTP Nick End Labeling (TUNEL)-staining. Serum AST, ALT, ALP and plasma TNF-α levels, tissue MDA and TNF-α levels had all increased in CCl(4) group, but were found to be significantly decreased in CCl(4)+leptin treatment group. Moreover, TUNEL-positive cell counts in liver had significantly increased in CCl(4) group, but decreased in CCl(4)+leptin treatment group (P < 0.05). The results of our study the biochemical, histological and TUNEL-staining showed that leptin has treatment effects on liver CCl(4) induced injury. It plays a role as a potent free radical scavenger, a powerful antioxidant and it also has anti-apoptotic effects.


Effect of ω-3 supplementation on placental lipid metabolism in overweight and obese women.
The placentas of obese women accumulate lipids that may alter fetal lipid exposure. The long-chain omega-3 fatty acids (n–3 FAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) alter FA metabolism in hepatocytes, although their effect on the placenta is poorly understood. We aimed to investigate whether n–3 supplementation during pregnancy affects lipid metabolism in the placentas of overweight and obese women at term. A secondary analysis of a double-blind randomized controlled trial was conducted in healthy overweight and obese pregnant women who were randomly assigned to DHA plus EPA (2 g/d) or placebo twice a day from early pregnancy to term. Placental FA uptake, esterification, and oxidation pathways were studied by measuring the expression of key genes in the placental tissue of women supplemented with placebo and n–3 and in vitro in isolated trophoblast cells in response to DHA and EPA treatment. Total lipid content was significantly lower in the placentas of overweight and obese women supplemented with n–3 FAs than in those supplemented with placebo (14.14 ± 1.03 compared with 19.63 ± 1.45 mg lipid/g tissue; P < 0.05). The messenger RNA expression of placental FA synthase (FAS) and diacylglycerol O-acyltransferase 1 (DGAT1) was negatively correlated with maternal plasma enrichment in DHA and EPA (P < 0.05). The expression of placental peroxisome proliferator–activated receptor γ (r = −0.39, P = 0.04) and its target genes DGAT1 (r = −0.37, P = 0.02) and PLIN2 (r = −0.38, P = 0.04) significantly decreased, with an increasing maternal n–3:n–6 ratio (representing the n–3 status) near the end of pregnancy. The expression of genes that regulate FA oxidation or uptake was not changed. Birth weight and length were significantly higher in the offspring of n–3-supplemented women than in those in the placebo group (P < 0.05), but no differences in the ponderal index were observed. Supplementation of n–3 significantly decreased FA esterification in isolated trophoblasts without affecting FA oxidation. Supplementing overweight and obese women with n–3 FAs during pregnancy inhibited the ability of the placenta to esterify and store lipids. This trial was registered at clinicaltrials.gov as NCT00957476.


Community Pediatric Hospitalist Workload: Results from a National Survey.
As a newly recognized subspecialty, understanding programmatic models for pediatric hospital medicine (PHM) programs is vital to lay the groundwork for a sustainable field. Although variability has been described within university-based PHM programs, there remains no national benchmark for community-based PHM programs. In this report, we describe the workload, clinical services, employment, and perception of sustainability of 70 community-based PHM programs in 29 states through a survey of community site leaders. The median hours for a full-time hospitalist was 1,882 hours/year with those employed by community hospitals working 8% more hours/year and viewing appropriate morning pediatric census as 20% higher than those employed by university institutions. Forty-three out of 70 (63%) site leaders perceived their programs as sustainable, with no significant difference by employer structure. Future studies should further explore root causes for workload discrepancies between community and academic employed programs along with establishing potential standards for PHM program development.


Atomic resolution (1.0 A) crystal structure of Fusarium solani cutinase: stereochemical analysis.
X-ray data have been recorded to 1.0 A resolution from a crystal of Fusarium solani cutinase using synchrotron radiation and an imaging-plate scanner. The anisotropic treatment of thermal motion led to a fivefold increase in accuracy and to a considerable quality improvement in the electron density maps with respect to an intermediate isotropic model. The final model has an R-factor of 9.4%, with a mean coordinate error of 0.021 A, as estimated from inversion of the least-squares matrix. The availability of an accurate structure at atomic resolution and of meaningful estimates of the errors in its atomic parameters, allowed an extensive analysis of several stereochemical parameters, such as peptide planarity, main-chain and some side-chain bond distances. The hydrogen atoms could be clearly identified in the electron density, thus providing unambiguous evidence on the protonation state of the catalytic histidine residue. The atomic resolution revealed an appreciable extent of flexibility in the cutinase active site, which might be correlated with a possible adaptation to different substrates. The anisotropic treatment of thermal factors provided insights into the anisotropic nature of motions. The analysis of these motions in the two loops delimiting the catalytic crevice pointed out a "breath-like" movement in the substrate binding region of cutinase.


Ultrasonographic and endocrine characterization of follicular waves in llamas with a special reference to the overlapping phenomenon during successive waves.
Ovarian follicular growth in non-mated llamas occurs in successive waves that generally superimpose their origin on the regression of the preceding wave (overlapping), originating prolonged sexual receptivity in the species. The aim of this study was to perform an ultrasonographic and endocrine characterization of individual and successive waves in non-mated llamas with a special interest on the overlapping phenomenon. Twelve llamas were examined daily by transrectal ultrasonography for at least two consecutive waves. In six females, blood samples were collected daily at the end of each examination. The development of the largest follicle (F) showed a wavelike pattern with a mean duration of 25 days. All waves evaluated were partially overlapped on the preceding wave and emerged at a mean interval of 15.8 ± 0.5 days. This interwave interval determines a mean overlapping degree of 32% of the wave length. Similarly, mean plasma oestradiol-17β (E2 ) concentrations followed a wavelike pattern. However, E2 concentrations started to decline before the structural regression of the F was observed. Mean basal E2 concentrations remain higher than 10.9 ± 0.6 pmol/l. In conclusion, follicular activity in non-mated llamas is characterized by continuous emergence of successive waves that always overlap the preceding wave with variable degrees. E2 production during the follicular wave is shorter in duration than the morphological development of the F. Finally, the overlapping phenomenon maintains increased plasma E2 concentrations persistently and this could explain the prolonged periods of sexual receptivity registered in llamas.


An exploration of gender-based violence in eastern Myanmar in the context of political transition: findings from a qualitative sexual and reproductive health assessment.
In March 2011, the Myanmar Government transitioned to a nominally civilian parliamentary government, resulting in dramatic increases in international investments and tenuous peace in some regions. In March 2015, Community Partners International, the Women's Refugee Commission, and four community-based organisations (CBOs) assessed community-based sexual and reproductive health (SRH) services in eastern Myanmar amidst the changing political contexts in Myanmar and Thailand. The team conducted 12 focus group discussions among women of reproductive age (18-49 years) with children under five and interviewed 12 health workers in Kayin State, Myanmar. In Mae Sot and Chiang Mai, Thailand, the team interviewed 20 representatives of CBOs serving the border regions. Findings are presented through the socioecological lens to explore gender-based violence (GBV) specifically, to examine continued and emerging issues in the context of the political transition. Cited GBV includes ongoing sexual violence/rape by the military and in the community, trafficking, intimate partner violence, and early marriage. Despite the political transition, women continue to be at risk for military sexual violence, are caught in the burgeoning economic push-pull drivers, and experience ongoing restrictive gender norms, with limited access to SRH services. There is much fluidity, along with many connections and interactions among the contributing variables at all levels of the socioecological model; based on a multisectoral response, continued support for innovative, community-based SRH services that include medical and psychosocial care are imperative for ethnic minority women to gain more agency to freely exercise their SR rights.


Protons and glucose metabolism in shock.
When oxygen is limiting, animals can ferment glucose via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, succinate, or propionate). Because the pH dependence of H+ production by fermentation is opposite to that by hydrolysis of adenosine triphosphate formed in the fermentation, the total number of moles of protons generated is always two per mole of fermentable substrate. However, two and three times more adenosine triphosphate can be turned over per mole of protons produced in succinate and propionate fermentations, respectively, than in lactate fermentation. At its limit, this advantage would achieve the same balance between H+ production and H+ consumption during ATP cycling that is observed in aerobic metabolism, a situation observed in certain alcohol fermentations. Since proton balance during anaerobiosis is clearly adaptable, we consider possible impact and functions of net H+ accumulation during carbohydrate metabolism in endotoxin shock.


Qualitative study of motivators and outcomes of Sri Lankan doctors achieving MRCGPInternational.
The UK's Royal College of General Practitioners accredits overseas examinations in family medicine through MRCGP[INT] rather than exporting MRCGP UK. There is limited research on the motivating factors and outcomes of this practice on candidates. To explore factors motivating Sri Lankan doctors to pursue the South Asian MRCGP[INT] and their perceived benefits and barriers to sitting the examination. Qualitative semi-structured 1:1 interviews with 14 successful past MRCGP[INT]SA candidates were undertaken in Sri Lanka. Findings were analysed with N-Vivo software. A phenomenological approach was used. Interpretive dimensions were applied drawing on information from interviews, informal conversations and observations. Motivators to sit the examination included a desire to improve patient care and seeking recognition as a family doctor. Younger doctors had hopes of increased future income and there was some expectation that the examination may improve overseas employment prospects. The examination conferred greater confidence, new patient-centred communication skills, introduced the use of evidence-based guidelines and increased awareness of the UK health system to most participants. There were examples of diffusion of knowledge through different teaching channels. Relative to Sri Lankan examinations, formal training opportunities were limited and value for money of annual membership fees were questioned. Financial and geographical barriers to the examination were noted. Currently MRCGP[INT]SA offers additional value for successful candidates in Sri Lanka who perceive accreditation by a UK college favourably. Improvement of pre- and post-exam support linked to MRCGP[INT]SA in Sri Lanka is needed. Further research into the long-term impact is necessary, in particular regarding equity of access, migration and local training development.


Oxytocin modulates dopamine-mediated reward in the rat subthalamic nucleus.
The subthalamic nucleus (STh) is increasingly recognized as an important region involved in the motivation for drug reward. It is not yet known if dopamine, the neurotransmitter primarily responsible for reward signaling, is also involved in mediating reward-related activity in the STh. The neuropeptide oxytocin acts within the STh to reduce the rewarding effects of the psychostimulant methamphetamine, through a proposed interaction with dopamine. However, the mechanisms of this interaction are unclear. The current study aimed to determine whether (i) dopamine microinjected into the STh would result in a significant place preference following a single-trial conditioning session, (ii) co-administered dopamine receptor antagonist would block the formation of a conditioned place preference (CPP) for dopamine, (iii) co-administered oxytocin would prevent CPP for dopamine and (iv) whether the selective oxytocin antagonist desGly-NH(2),d(CH(2))(5)[D-Tyr(2),Thr(4)]OVT, when co-administered with oxytocin and dopamine, would reverse the effects of oxytocin and result in a CPP for dopamine. Results showed that male Sprague Dawley rats i) formed a preference for the context paired with dopamine (100 nmol/side) administration into the STh, which was prevented by co-administration of ii) the mixed dopamine receptor antagonist fluphenazine (10 nmol/side) or iii) oxytocin (0.6 pmol/side), [corrected] with the oxytocin effect on dopamine CPP reversed by the co-administration of the oxytocin receptor antagonist (3 nmol/side). These data suggest that dopamine neurotransmission in the STh produces rewarding effects that can be reduced by activation of local oxytocin receptors.


Functional dyspepsia: New insights into the pathophysiology.
The pathogenesis of functional dyspepsia remains poorly understood. There is increasing evidence pointing to a predominant role of gastroduodenal visceral hypersensitivity in the pathogenesis, where patients have abnormally reduced gastric and small intestinal sensory thresholds. Motor abnormalities observed in subgroups of patients include delayed gastric emptying, antral hypomotility, gastric dysrhythmias, abnormal gastrointestinal reflexes and small intestinal dysmotility, but these may be secondary pheno nena. The central nervous system modifies peripheral visceral afferent pathways and, hente, psychological factors may possibly alter symptom status. Other putative mechanisms include Helicobacter pylori gastritis and gastric acid hypersecretion or sensitivity, but the role of these remain controversial.


Methane efflux from lake sediments through water lilies.
During winter, when water lilies have no surface leaves, the gases in the rhizome lacunae approach equilibrium with the gases of the sediment water. The resulting increase of internal pressure is manifested by the sustained streams of bubbles (up to 37 percent methane and 6 percent carbon dioxide) that escape when emerging leaves are torn in the spring. Methane continues to enter the roots and rhizome during summer, rapidly moves up the petioles, and passes out through the emergent leaves into the atmosphere.


Transport of superparamagnetic beads through a two-dimensional potential energy landscape.
The nonlinear dynamic behavior of superparamagnetic beads transported through a two-dimensional potential energy landscape is explored empirically and through numerical simulation. The beads are driven through a periodic array of micromagnets by an external rotating field oriented at an angle θ relative to the magnetization direction of the substrate. The bead's motion was highly sensitive to the angle of the driving field near critical angles and to various system parameters, including bead size, rotation frequency, and substrate pole density. Our results suggest the possibility of using this behavior in a highly discriminative colloidal separation system, in which two different bead types can be tuned to move in orthogonal directions.


Effects of non-nutritive (artificial vs natural) sweeteners on 24-h glucose profiles.
Replacing nutritive sweetener with non-nutritive sweeteners (NNS) has the potential to improve glycaemic control. The objective of this study was to investigate the effects of consuming artificial NNS (that is, aspartame), natural NNS (that is, monk fruit and stevia), and sucrose-sweetened beverages on 24-h glucose profiles. Ten healthy males took part in this randomised, crossover study with the following four treatments: aspartame-, monk fruit-, stevia-, and sucrose- (65 g) sweetened beverages. Participants were asked to consume the test beverage as a preload mid-morning. Medtronic iPro2 continuous glucose monitoring system was used to measure mean 24-h glucose, incremental area under the curve (iAUC) and total area under the curve (AUC) for glucose, and 24-h glycaemic variability. Overall no significant differences were found in mean 24-h glucose, iAUC and total AUC for glucose, and 24-h glycaemic variability between the four test beverages. Twenty-four-hour glucose profiles did not differ between beverages sweetened with non-nutritive (artificial vs natural) and nutritive sweeteners. The simple exchange of a single serving of sucrose-sweetened beverage with NNS over a day appears to have minimal effect on 24-h glucose profiles in healthy males.


Hepatitis medical care coordinators: Comprehensive and seamless support for patients with hepatitis.
Chronic liver disease, especially viral hepatitis, is an urgent issue in Japan. Human resource management is important to promote appropriate care for patients with chronic liver disease in medical institutions and in the community. In 2011 the Ministry of Health, Labour and Welfare in Japan started training hepatitis medical care coordinators (HMCCs). Various medical professionals (such as public health nurses, general nurses, and clinical technicians), patients, and ordinary citizens are certified as HMCCs by the prefectural government after learning about liver diseases in a training program. The training program can be optimized in accordance with the regional circumstances and basic knowledge and skills of the applicants. HMCCs encourage residents and patients to undergo a hepatitis screening test, after which positive patients undergo detailed examination, treatment, and follow-up. HMCCs contribute to the expansion of knowledge about hepatitis in their workplace and community. By 2018, there were HMCCs in all 47 prefectures of Japan. There were 20,049 HMCCs in 2019. The most common professions of HMCCs were public health nurses, followed by general nurses, hospital pharmacists, laboratory technicians, and medical social workers. After certification, the activities of HMCCs vary; to ensure that HMCCs are adequately used in medical institutions, the supervisor and physicians must recognize the importance of HMCCs and generate opportunities for HMCC activity. The training and effective utilization of HMCCs is a promising way to decrease the prevalence and mortality of chronic liver diseases in Japan.


Molecular and expression analysis of the Allograft inflammatory factor 1 (AIF-1) in the coelomocytes of the common sea urchin Paracentrotus lividus.
Allograft inflammatory factor 1 (AIF-1) is a highly conserved gene involved in inflammation, cloned and characterized in several evolutionary distant animal species. Here, we report the molecular identification, characterization and expression of AIF-1 from the common sea urchin Paracentrotus lividus. In this species, AIF-1 encodes a predicted 151 amino acid protein with high similarity to vertebrate AIF-1 proteins. Immunocytochemical analyses on coelomocytes reveal localization of the AIF-1 protein in amoebocytes (perinuclear cytoplasmic zone) and red sphaerulocytes (inside granules), but not in vibratile cells and colorless sphaerula cells. The significant increase of AIF-1 expression (mRNA and protein) found in the coelomocytes of the sea urchin after Gram + bacterial challenge suggests the involvement of AIF-1 in the inflammatory response. Our analysis on P. lividus AIF-1 contributes to elucidate AIF-1 function along the evolutionary scale and consolidate the key evolutionary position of echinoderms throughout metazoans with respect to the common immune paths.


[Chemotherapy strategy for colorectal cancer under the outbreak of novel coronavirus pneumonia].
The outbreak of novel coronavirus pneumonia (NCP) makes the medical treatment of colorectal cancers difficult. Cancer patients are more susceptible to infection and tumor history is defined as an important factor of poor prognosis, which challenges both doctors and patients. For metastatic colorectal cancer (CRC) patients, maintenance therapy is the optimal choice. The patients with tumor progression or poor biological behaviorshould receive or or continue combination chemotherapy. Adjuvant chemotherapy should reduce the intensity of treatment and shorten the therapy time. Fever patients during chemotherapy need to receive differential diagnosis and screening according to national standards. Patients with stable diseases and good general conditions may delay imaging examination.. Clinicians should make individual clinical decisions based on the specifics of each patient durding epidemic situation.


Mass data massage: an automated data processing system used for NHEXAS, Arizona. National Human Exposure Assessment Survey.
Data entry and management are critical components of all large survey projects; data quality objectives must be met and data must be quickly and readily accessible. We developed a comprehensive system for data entry and management utilizing scannable forms with bubble fields and handwriting recognition. This 'Mass Data Massage' (MDM) system had three components: (1) form creation and database definition; (2) programming of data dictionaries for documentation and preliminary logic and range checks; and (3) data entry, management and documentation using the 'Mass Data Cleaning Program' (MDCP). Scannable forms were written in Teleform, where the data field definition, variable names and ranges were defined as the form was created. Completed forms were returned from the field, subjected to final field quality control (QC) checks, and transferred to the data management section. They were batched and coded as necessary. Once a batch of data was scanned and visually verified, the operator called up the menu for the MDCP. The MDCP had 31 program modules with 500-1200 lines of code each. The operator could select and run the appropriate dictionary on each data batch 'correcting' apparent errors in responses. This process was iterative until the data batch passed all dictionary checks. Proposed 'changes' were forwarded to the data coordinator (DC) for acceptance or rejection. After all errors had been resolved, each data batch was subjected to a 10% quality assurance (QA) check. The original data batch and associated file of applied changes were archived. Time expenditure using the scanning approach varied with the number of questions and the types of responses (handwritten or bubble fields). One-page forms took 42-60% of the time needed for hand entry; forms longer than 10 pages took 35-38% of the time. Use of faster machines will further speed the process. The main advantage of the system was the reduction of systematic errors. Scanning alone reduced errors found on 995 NHEXAS Baseline Questionnaires. Overall, the dictionary identified 0.55% errors on the scanned forms. Ten percent QC checks, performed on corrected batches ready for appendage to the master database, revealed an overall error rate of 0.02%. Similar checks on a laboratory form scanned from numeric handwriting detected 0.3% errors following dictionary application and 0.2% errors during the 10% QA check. This system was faster, more accurate, and more cost-effective than hand entry of data. A batch of data that took >1 week to process using the hand entry method was processed within 1 day using MDM. Human coding of specific answers and the final verification were the most time-consuming processes.


Things I wish I had done as a graduate student.
Making the most of opportunities available during graduate school can pay dividends later on.


Smoking is Associated with Higher Disease-related Costs and Lower Health-related Quality of Life in Inflammatory Bowel Disease.
Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.


If you feel you can't, you won't: the role of subjective and objective cognitive competence on psychosocial functioning in depression.
The purpose of this exploratory study is to examine the role of sociodemographic, clinical, and cognitive - both objective and subjective - factors in overall and in specific domains of psychosocial functioning, in patients with depression at different clinical states of the disease (remitted and non-remitted). A sample of 325 patients with major depressive disorder, 117 in remission and 208 in non-remission, were assessed with a semi-structured interview collecting sociodemographic, clinical, cognitive (with neuropsychological tests and the Perceived Deficit Questionnaire), and functional (Functioning Assessment Short Test) characteristics. Backward regression models were conducted to determine associations of global and specific areas of functioning with independent factors, for both clinical states. Residual depressive symptomatology and self-appraisal of executive competence were significantly associated with psychosocial functioning in remitted patients, in overall and some subdomains of functioning, particularly cognitive and interpersonal areas. While depressive symptoms, executive deficits and self-appraisal of executive function were significantly related to functional outcomes in non-remitted patients, both in overall functioning and in most of subdomains. This study evidences the strong association of one's appraisal of executive competence with psychosocial functioning, together with depressive symptoms, both in remitted and non-remitted patients with depression. Therefore, to achieve full recovery, clinical management of patients should tackle not only the relief of core depressive symptoms, but also the cognitive ones, both those that are objectified with neuropsychological tests and those that are reported by the patients themselves.


C-di-AMP levels modulate Staphylococcus aureus cell wall thickness, response to oxidative stress, and antibiotic resistance and tolerance.
Beta-lactam antibiotics are widely used to treat infections caused by the important human pathogen Staphylococcus aureus. Resistance to beta-lactams, as found in methicillin-resistant S. aureus, renders effective treatment difficult. The second messenger cyclic di-3',5'-adenosine monophosphate (c-di-AMP) promotes beta-lactam resistance in clinical S. aureus isolates. C-di-AMP plays a crucial role in the regulation of cellular processes such as virulence, cell wall homeostasis, and resistance to beta-lactams in many bacterial species. In S. aureus, c-di-AMP synthesis is mediated by the diadenylate cyclase DacA, while its degradation is carried out by the phosphodiesterases GdpP and Pde2. In this work, we assessed the effect of altered c-di-AMP levels due to mutations in dacA, gdpP, or gdpP/pde2 on virulence determinants. We report that a previously described growth defect in bacteria producing high c-di-AMP levels is mainly attributable to smaller cell size. High c-di-AMP levels also led to decreased survival upon oxidative stress, reduced production of the antioxidant staphyloxanthin, increased oxacillin and fosfomycin resistance, and increased cell wall thickness. While resistance to ceftaroline was not affected, high c-di-AMP levels promoted tolerance to this antibiotic. In response to cell wall stress induced by antibiotics, the three-component regulatory system VraTSR mediates an increase in cell wall synthesis via the cell wall stress stimulon (CWSS). Increased c-di-AMP levels led to an activation of the CWSS. Upon deletion of vraR, resistance to oxacillin and fosfomycin as well as cell wall thickness diminished in the ΔgdpP mutant, indicating a contribution of the VraTSR system to the cell wall related phenotypes.IMPORTANCEAntibiotic resistance and tolerance are substantial healthcare-related problems, hampering effective treatment of bacterial infections. Mutations in the phosphodiesterase GdpP, which degrades cyclic di-3', 5'-adenosine monophosphate (c-di-AMP), have recently been associated with resistance to beta-lactam antibiotics in clinical Staphylococcus aureus isolates. In this study, we show that high c-di-AMP levels decreased the cell size and increased the cell wall thickness in S. aureus mutant strains. As a consequence, an increase in resistance to cell wall targeting antibiotics, such as oxacillin and fosfomycin as well as in tolerance to ceftaroline, a cephalosporine used to treat methicillin-resistant S. aureus infections, was observed. These findings underline the importance of investigating the role of c-di-AMP in the development of tolerance and resistance to antibiotics in order to optimize treatment in the clinical setting.


Return to sports after surgery to correct adolescent idiopathic scoliosis: a survey of the Spinal Deformity Study Group.
There are no guidelines for when surgeons should allow patients to return to sports and athletic activities after spinal fusion for adolescent idiopathic scoliosis (AIS). Current recommendations are based on anecdotal reports and a survey performed more than a decade ago in the era of first/second-generation posterior implants. To identify current recommendations for return to sports and athletic activities after surgery for AIS. Questionnaire-based survey. Adolescent idiopathic scoliosis after corrective surgery. Type and time to return to sports. A survey was administered to members of the Spinal Deformity Study Group. The survey consisted of surgeon demographic information, six clinical case scenarios, three different construct types (hooks, pedicle screws, hybrid), and questions regarding the influence of lowest instrumented vertebra (LIV) and postoperative physical therapy. Twenty-three surgeons completed the survey, and respondents were all experienced expert deformity surgeons. Pedicle screw instrumentation allows earlier return to noncontact and contact sports, with most patients allowed to return to running by 3 months, both noncontact and contact sports by 6 months, and collision sports by 12 months postoperatively. For all construct types, approximately 20% never allow return to collision sports, whereas all surgeons allow eventual return to contact and noncontact sports regardless of construct type. In addition to construct type, we found progressively distal LIV resulted in more surgeons never allowing return to collision sports, with 12% for selective thoracic fusion to T12/L1 versus 33% for posterior spinal fusion to L4. Most respondents also did not recommend formal postoperative physical therapy (78%). Of all surgeons surveyed, there was only one reported instrumentation failure/pullout without neurologic deficit after a patient went snowboarding 2 weeks postoperatively. Modern posterior instrumentation allows surgeons to recommend earlier return to sports after fusion for AIS, with the majority allowing running by 3 months, noncontact and contact sports by 6 months, and collision sports by 12 months.


Effects of lead exposure on sperm concentrations and testes weight in male rats: a meta-regression analysis.
The correlation between exposure to lead (PB) and sperm concentrations and testes weight are important in risk assessment of metal toxicity to male reproductive functions. The authors carried out two systematic reviews and meta-analyses of rats. In addition, a meta-regression analysis was taken to explore a dose-response relationship between the mean difference of testes weight (MD(testes)) and available confounding factors. Data were obtained from computerized literature searches of several databases from their inception through December 2005. The reference lists of identified articles were examined further for relevant articles. The authors identified 6 and 12 studies, separated into 16 and 28 subgroups, in the two meta-analyses. The authors conducted random- or fixed-effect models toward the effect size. Heterogeneity between study results was explored through chi-square tests and meta-regression. Results showed that a decrease in sperm concentrations was found as low as mean difference of sperm concentrations (MD(sperm)) = 30.9 and 95%CI = (25.43-36.37) in a fixed-effect model or MD(sperm) = 35.47 and 95%CI = (15.27-55.68) in a random-effect model after Pb exposure. Similarly, a significantly lower testes weight was also evident: MD(testes) = 0.033 and 95%CI = (0.021-0.046) in a fixed-effect model or MD(testes) = 0.047 and 95%CI = (0.0044-0.089) in a random-effect model. In the meta-regression analysis, two confounders, age and body weight, explained part of the observed heterogeneity. The body weight after Pb exposure was inversely associated with MD(testes). These findings support the notion that Pb exposure produced decreased sperm concentrations and testes weight in rats.


Real-Time UV Measurement With a Sun Protection System for Warning Young Adults About Sunburn: Prospective Cohort Study.
Melanoma is attributable to predisposing phenotypical factors, such as skin that easily sunburns and unprotected exposure to carcinogenic UV radiation. Reducing the proportion of young adults who get sunburned may reduce the incidence of melanoma, a deadly form of skin cancer. Advances in technology have enabled the delivery of real-time UV light exposure and content-relevant health interventions. This study aims to examine the feasibility of young adults performing the following tasks daily: wearing a UV dosimeter, receiving text messages and real-time UV-B doses on their smartphone, and responding to daily web-based surveys about sunburn and sun protection. Young adults aged 18-39 years (n=42) were recruited in the United States in June 2020 via social media. Participants received the UV Guard sun protection system, which consisted of a UV dosimeter and a smartphone app. During 3 consecutive periods, intervention intensity increased as follows: real-time UV-B dose; UV-B dose and daily behavioral facilitation text messages; and UV-B dose, goal setting, and daily text messages to support self-efficacy and self-regulation. Data were self-reported through daily web-based surveys for 28 days, and UV-B doses were transmitted to cloud-based storage. Patients' median age was 22 years (IQR 20, 29), and all patients had sun-sensitive skin. Sunburns were experienced during the study by fewer subjects (n=18) than those in the preceding 28 days (n=30). In July and August, the face was the most commonly sunburned area among 13 body locations; 52% (22/42) of sunburns occurred before the study and 45% (19/42) occurred during the study. The mean daily UV-B dose decreased during the 3 periods; however, this was not statistically significant. Young adults were most often exercising outdoors from 2 to 6 PM, walking from 10 AM to 6 PM, and relaxing from noon to 2 PM. Sunburn was most often experienced during exercise (odds ratio [OR] 5.65, 95% CI 1.60-6.10) and relaxation (OR 3.69, 95% CI 1.03-4.67) relative to those that did not exercise or relax in each category. The self-reported exit survey indicated that participants felt that they spent less time outdoors this summer compared to the last summer because of the COVID-19 pandemic and work. In addition, 38% (16/42) of the participants changed their use of sun protection based on their app-reported UV exposure, and 48% (20/42) shifted the time they went outside to periods with less-intense UV exposure. A total of 79% (33/42) of the participants were willing to continue using the UV Guard system outside of a research setting. In this proof-of-concept research, young adults demonstrated that they used the UV Guard system; however, optimization was needed. Although some sun protection behaviors changed, sunburn was not prevented in all participants, especially during outdoor exercise. ClinicalTrials.gov NCT03344796; http://clinicaltrials.gov/ct2/show/NCT03344796.


[Mutation process and malignant transformation induced by adenoviruses in mammalian cells].
Both oncogenic adenovirus (BAV-3) and nononcogenic adenovirus (Ad-1) are able to induce gene mutations in cultured mammalian cells. In the case of equal multiplicity of the infection the frequency of induced mutations is higher in variants with Ad-1. Unlike Ad-1 both mutagenic and transforming effects of BAV-3 are intensified by means of TPA promoters. TPA modifies analogously mutagenic and transforming effect of much less than oncogenic fragment much greater than of DNA BAV-3. Oncogene and, probably, other viral genes reveal mutagenic activity.


Blocking yersiniabactin import attenuates extraintestinal pathogenic Escherichia coli in cystitis and pyelonephritis and represents a novel target to prevent urinary tract infection.
The emergence and spread of extended-spectrum beta-lactamases and carbapenemases among common bacterial pathogens are threatening our ability to treat routine hospital- and community-acquired infections. With the pipeline for new antibiotics virtually empty, there is an urgent need to develop novel therapeutics. Bacteria require iron to establish infection, and specialized pathogen-associated iron acquisition systems like yersiniabactin, common among pathogenic species in the family Enterobacteriaceae, including multidrug-resistant Klebsiella pneumoniae and pathogenic Escherichia coli, represent potentially novel therapeutic targets. Although the yersiniabactin system was recently identified as a vaccine target for uropathogenic E. coli (UPEC)-mediated urinary tract infection (UTI), its contribution to UPEC pathogenesis is unknown. Using an E. coli mutant (strain 536ΔfyuA) unable to acquire yersiniabactin during infection, we established the yersiniabactin receptor as a UPEC virulence factor during cystitis and pyelonephritis, a fitness factor during bacteremia, and a surface-accessible target of the experimental FyuA vaccine. In addition, we determined through transcriptome sequencing (RNA-seq) analyses of RNA from E. coli causing cystitis in women that iron acquisition systems, including the yersiniabactin system, are highly expressed by bacteria during natural uncomplicated UTI. Given that yersiniabactin contributes to the virulence of several pathogenic species in the family Enterobacteriaceae, including UPEC, and is frequently associated with multidrug-resistant strains, it represents a promising novel target to combat antibiotic-resistant infections.


Hybrid Petri net representation of gene regulatory network.
It is important to provide a representation method of gene regulatory networks which realizes the intuitions of biologists while keeping the universality in its computational ability. In this paper, we propose a method to exploit hybrid Petri net (HPN) for representing gene regulatory networks. The HPN is an extension of Petri nets which have been used to represent many kinds of systems including stochastic ones in the field of computer sciences and engineerings. Since the HPN has continuous and discrete elements, it can easily handle biological factors such as protein and mRNA concentrations. We demonstrate that, by using HPNs, it is possible to translate biological facts into HPNs in a natural manner. It should be also emphasized that a hierarchical approach is taken for our construction of the genetic switch mechanism of lambda phage which is realized by using HPNs. This hierarchical approach with HPNs makes easier the arrangement of the components in the gene regulatory network based on the biological facts and provides us a prospective view of the network. We also show some computational results of the protein dynamics of the lambda phage mechanism that is simulated and observed by implementing the HPN on a currently available tool.


The Use of a Modified Script Concordance Test in Clinical Rounds to Foster and Assess Clinical Reasoning Skills.
The development of clinical reasoning skills is a high priority during clinical service, but an unpredictable case load and limited time for formal instruction makes it challenging for faculty to foster and assess students' individual clinical reasoning skills. We developed an assessment for learning activity that helps students build their clinical reasoning skills based on a modified version of the script concordance test (SCT). To modify the standard SCT, we simplified it by limiting students to a 3-point Likert scale instead of a 5-point scale and added a free-text box for students to provide justification for their answer. Students completed the modified SCT during clinical rounds to prompt a group discussion with the instructor. Student feedback was positive, and the instructor gained valuable insight into the students' thought process. A modified SCT can be adopted as part of a multimodal approach to teaching on the clinic floor. The purpose of this article is to describe our modifications to the standard SCT and findings from implementation in a clinical rounds setting as a method of formative assessment for learning and developing clinical reasoning skills.


Improvement in dynamic balance and core endurance after a 6-week core-stability-training program in high school track and field athletes.
Core training specifically for track and field athletes is vague, and it is not clear how it affects dynamic balance and core-endurance measures. To determine the effects of a 6-week core-stabilization-training program for high school track and field athletes on dynamic balance and core endurance. Test-retest. High school in north central West Virginia. Thirteen healthy high school student athletes from 1 track and field team volunteered for the study. Subjects completed pretesting 1 wk before data collection. They completed a 6-wk core-stabilization program designed specifically for track and field athletes. The program consisted of 3 levels with 6 exercises per level and lasted for 30 min each session 3 times per week. Subjects progressed to the next level at 2-wk intervals. After 6 wk, posttesting was conducted The subjects were evaluated using the Star Excursion Balance Test (SEBT) for posteromedial (PM), medial (M), and anteromedial (AM) directions; abdominal-fatigue test (AFT); back-extensor test (BET); and side-bridge test (SBT) for the right and left sides. Posttest results significantly improved for all 3 directions of the SEBT (PM, M, and AM), AFT, BET, right SBT, and left SBT. Effect size was large for all variables except for PM and AM, where a moderate effect was noted. Minimal-detectable-change scores exceeded the error of the measurements for all dependent variables. After the 6-wk core-stabilization-training program, measures of the SEBT, AFT, BET, and SBT improved, thus advocating the use of this core-stabilization-training program for track and field athletes.


Depression in African American men: a review of what we know and where we need to go from here.
Depression is one of the most common mental disorders in the United States and affects an estimated 17 million people each year. Projections about depression have generated concern on both the domestic and global levels because of its impact on health outcomes and quality of life. We examined and summarized published research focusing on depression among African American men with the goal of identifying prevalence of depression, risk factors, treatment-seeking behaviors, and treatment-seeking barriers. In the use of a systematic review, inclusion criteria were studies focused on depression among African American or Black men, separated analysis by race and gender, and conducted in the United States. Each study was critically reviewed to identify depression prevalence, risk factors, treatment-seeking behaviors, and barriers. Only 19 empirical studies focusing on depression among African American men were identified in a 25-year time span. Findings suggest the prevalence of depression among African American men ranges from 5% to 10%, they face a number of risk factors, yet evidence low use of mental health services. Consequently, depression among African American men needs to be at the forefront of our research, practice, and outreach agendas. A focus on this group has the potential to reduce mental health disparities experienced by African American men.


Research-based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2-positive breast cancer in the NOAH study.
We report a retrospective exploratory analysis of the association of the research-based prediction analysis of microarray 50 (PAM50) subtype predictor with pathologic complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial. Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded core biopsies from 114 pretreated patients with HER2-positive (HER2(+)) tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in combination with trastuzumab for one year. A control cohort of 42 patients with HER2-negative tumors treated with AT-CMF was also included. The PAM50 subtypes, the PAM50 proliferation score, and the PAM50 risk of relapse score based on subtype (RORS) and subtype and proliferation (RORP) were evaluated. HER2-enriched (HER2-E) tumors predominated within HER2(+) disease, although all PAM50 intrinsic subtypes were identified across the three cohorts. The OR for achieving pCR with trastuzumab-based chemotherapy for HER2(+)/HER2-E and HER2(+)/RORP-high were 5.117 (P = 0.009) and 8.469 (P = 0.025), respectively, compared with chemotherapy only. The pCR rates of HER2(+)/HER2-E and HER2(+)/RORP-high after trastuzumab-based chemotherapy were 52.9% and 75.0%, respectively. A statistically nonsignificant trend was observed for more pronounced survival benefit with trastuzumab in patients with HER2(+)/HER2-E and HER2(+)/RORP-high tumors compared with patients with HER2(+)/non-HER2-E and HER2(+)/non-RORP-high tumors, respectively. As determined by EFS and pCR, patients with HER2(+)/HER2-E tumors, or HER2(+)/RORP-high tumors, benefit substantially from trastuzumab-based chemotherapy. The clinical value of this genomic test within HER2(+) disease warrants further investigation.


Postoperative Outcomes Following Tension-Free Vaginal Mesh Surgery for Pelvic Organ Prolapse: A Retrospective Study.
We retrospectively reviewed the postoperative outcomes of patients who underwent tension-free vaginal mesh (TVM) surgery in our institution. In total, 195 TVM surgeries were performed at the Shimane University School of Medicine from January 2010 to May 2016 in patients with Pelvic Organ Prolapse-Quantification (POP-Q) stage II or higher. Perioperative complications and problems arising following surgery were assessed from medical charts. Among the 195 patients, only 1 patient required blood transfusion due to massive intraoperative blood loss. None of the patients experienced intraoperative complications, such as injury to the bladder or rectum during surgery. Mesh exposure was observed in 10 patients (5.1%). Overall, 6 of these 10 patients were asymptomatic, and surgical treatment was required in only 1 patient. Mesh exposure occurred at significantly higher frequencies in patients aged less than 60 years. Postoperative recurrence of POP, which was defined as recurrence over POP-Q stage 2, was noted in 13 of the 195 patients (6.6%). Re-operation was performed in 1 patient in whom recurrence was observed within 3 months postoperatively. Recurrence of POP was likely to occur in patients with higher POP-Q stages. Overall, 31 of the 195 patients (15.9%) required medication for postoperative stress urinary incontinence (SUI) after surgery. Among these, 2 patients underwent surgical treatment for SUI. Outcomes following the TVM procedure were satisfactory. However, caution should be exercisedagainst mesh exposure in younger patients and recurrence of POP in patients with advanced POP-Q stage.


Complex cytokine profiles induced by BCG vaccination in UK infants.
IFNgamma plays an important part in immunity to tuberculosis (TB), but although it is necessary, it is not on its own sufficient for protection against TB. To identify other cytokines that play a role in the protection against TB induced by BCG vaccination, immune responses were compared between vaccinated and unvaccinated infants from the UK where BCG is known to provide protection. Twenty-one cytokines and chemokines were tested in supernatants from diluted whole blood cultures that had been stimulated for 6 days with Mycobacterium tuberculosis PPD. For 15 out of 21 of the cytokines tested responses were much higher in BCG vaccinated infants than in unvaccinated infants. These included: pro-inflammatory cytokines; IFNgamma (median 1705 pg/ml vs. 1.6 pg/ml in vaccinated and unvaccinated infants, respectively), TNFalpha (median 226 pg/ml vs. 18 pg/ml), as well as IL-2, IL-1alpha and IL-6; TH2 cytokines: IL-4, IL-5 and IL-13 (median 104 pg/ml vs. 1.6 pg/ml); the regulatory cytokine IL-10 (median response 96 pg/ml vs. 8 pg/ml); the TH17 cytokine IL-17, chemokines (IP-10, MIP-1alpha and IL-8) and growth factors (GM-CSF and G-CSF). The greatest increase in cytokine production in BCG vaccinees compared to unvaccinated infants was seen with IFNgamma. While responses for many cytokines were correlated with the IFNgamma response, others including IL-17 and IL-10 were not. The pattern of cytokine induction following BCG vaccination is complex and measurement of one of two cytokines does not reveal the whole picture of vaccine-induced protection.


Feasibility of atlantoaxial pedicle screws' placement in children 6-8 years of age: a cadaveric and tomographic study.
The aims of this study were to evaluate the linear and angular dimensions of children's atlantoaxial pedicle using cadavers combined with axial computed tomography (CT) and to examine the feasibility of placing atlantoaxial pedicle screws (3.5 mm diameter) on the vertebrae of children 6-8 years of age. Fourteen cadaveric specimens, ranging in age from 6 to 8 years, were dissected to obtain their atlantoaxial vertebrae. We manually measured 12 linear anatomic parameters related to the atlantoaxial pedicle, its lateral mass, and the posterior arch under the vertebral artery groove. CT axial scanning of the atlantoaxial region was performed on 32 healthy children ranging in age from 6 to 8 years. The length of the atlantoaxial pedicles and the angle between the pedicle axis and the midline of the vertebral body were measured on the atlantoaxial transverse CT imaging. It is feasible to place a 3.5 mm screw in the atlantoaxial pedicle of children ranging in age from 6 to 8 years when the appropriate entry point and trajectory of the screw are chosen.


Differential progression of coronary atherosclerosis according to plaque composition: a cluster analysis of PARADIGM registry data.
Patient-specific phenotyping of coronary atherosclerosis would facilitate personalized risk assessment and preventive treatment. We explored whether unsupervised cluster analysis can categorize patients with coronary atherosclerosis according to their plaque composition, and determined how these differing plaque composition profiles impact plaque progression. Patients with coronary atherosclerotic plaque (n = 947; median age, 62 years; 59% male) were enrolled from a prospective multi-national registry of consecutive patients who underwent serial coronary computed tomography angiography (median inter-scan duration, 3.3 years). K-means clustering applied to the percent volume of each plaque component and identified 4 clusters of patients with distinct plaque composition. Cluster 1 (n = 52), which comprised mainly fibro-fatty plaque with a significant necrotic core (median, 55.7% and 16.0% of the total plaque volume, respectively), showed the least total plaque volume (PV) progression (+ 23.3 mm3), with necrotic core and fibro-fatty PV regression (- 5.7 mm3 and - 5.6 mm3, respectively). Cluster 2 (n = 219), which contained largely fibro-fatty (39.2%) and fibrous plaque (46.8%), showed fibro-fatty PV regression (- 2.4 mm3). Cluster 3 (n = 376), which comprised mostly fibrous (62.7%) and calcified plaque (23.6%), showed increasingly prominent calcified PV progression (+ 21.4 mm3). Cluster 4 (n = 300), which comprised mostly calcified plaque (58.7%), demonstrated the greatest total PV increase (+ 50.7mm3), predominantly increasing in calcified PV (+ 35.9 mm3). Multivariable analysis showed higher risk for plaque progression in Clusters 3 and 4, and higher risk for adverse cardiac events in Clusters 2, 3, and 4 compared to that in Cluster 1. Unsupervised clustering algorithms may uniquely characterize patient phenotypes with varied atherosclerotic plaque profiles, yielding distinct patterns of progressive disease and outcome.


miRNA-301 As a molecule promoting necrotizing enterocolitis by inducing inflammation.
Necrotizing enterocolitis (NEC) is a devastating inflammatory disease with high morbidity and mortality, mainly affecting premature infants. This study aimed to explore the role of miRNA-301a in the pathogenesis of NEC. The differentially expressed miRNAs and mRNAs were screened by collating RNA-Seq data from the GEO database of intestinal tissue samples. The differential miRNA-mRNAs regulatory network was constructed based on functional enrichment analysis. Newborn BALB/c mice were used to establish the NEC model. Haematoxylin and eosin staining was used to assess intestinal damage. The levels of IL-8 and TNF-α in mouse serum were evaluated by ELISA. qRT-PCR was used to detect the expression of miRNA-301a in intestinal tissues. Bioinformatics analysis showed that miRNA-301a was involved in intestinal lesions. Intestinal tissue damage was reduced and serum levels of the inflammatory cytokines IL-8 and TNF-α were lower in NEC model mice treated with miRNA-301a antagonists. The level of miRNA-301a in intestinal tissues of NEC model mice was significantly higher than in the control group and miRNA-301a antagonists treated group. miRNA-301a plays an important role in the pathogenesis of NEC by promoting inflammation, and is a potential therapeutic target of NEC.


Punicalagin improves hepatic lipid metabolism via modulation of oxidative stress and mitochondrial biogenesis in hyperlipidemic mice.
Hyperlipidemia is closely associated with various liver diseases, and effective intervention for prevention and treatment is in great need. Here, we aim to explore the protective effects of punicalagin (PU), a major ellagitannin in pomegranate, on acute hyperlipidemia-induced hepatic lipid metabolic disorders. Male C57bl/6J mice were pretreated with 50 or 200 mg kg-1 day-1 PU for 9 days before the injection of poloxamer 407 to induce acute hyperlipidemia. PU significantly lowered lipids and liver damage markers in serum, reduced excessive lipid accumulation in the liver, attenuated hepatic oxidative stress by activating the NF-E2 related factor 2 (Nrf2)-mediated antioxidant pathway, and enhanced hepatic mitochondrial complex activities and mitochondrial DNA copy number by promoting the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathway. Moreover, the decreased mitochondrial fusion-related proteins were also restored by PU treatment. In vitro, PU effectively decreased triglycerides and total cholesterol levels, up-regulated Nrf2 and mitochondrial biogenesis pathways and partially restored the mitochondrial morphology in palmitic acid-treated HepG2 cells. These results suggest that PU could improve acute hyperlipidemia-induced hepatic lipid metabolic abnormalities via decreasing oxidative stress and improving mitochondrial function both in vivo and in vitro, indicating that PU might be a potential intervention for hyperlipidemia-related liver diseases.


Novel brugada SCN5A mutation leading to ST segment elevation in the inferior or the right precordial leads.
Mutations in the SCN5A gene can lead to the Brugada syndrome, a genetically inherited form of idiopathic ventricular fibrillation that has a characteristic ECG phenotype usually restricted to precordial leads V1-V3. We identified a novel G752R SCN5A missense mutation leading to various degrees of the Brugada ECG phenotype in members of a French family. In the proband, the G752R mutation produced ST segment elevation and prominent J wave in leads II, III, and aVF. In four other relatives, ST segment elevation in the right precordial but not in the inferior leads was observed either spontaneously or under flecainide challenge. Recombinant G752R mutant exhibited a markedly reduced Na+ current amplitude and a voltage shift in both activation and inactivation curves. The mutant was found in all affected but not in nonaffected family members. One additional gene-carrier had an almost normal ECG (silent gene-carrier). We provide genetic demonstration that Brugada ECG anomalies related to a unique SCN5A mutation can be observed either in the inferior or the right precordial leads.


Physicochemical Drivers of Microbial Community Structure in Sediments of Lake Hazen, Nunavut, Canada.
The Arctic is undergoing rapid environmental change, potentially affecting the physicochemical constraints of microbial communities that play a large role in both carbon and nutrient cycling in lacustrine environments. However, the microbial communities in such Arctic environments have seldom been studied, and the drivers of their composition are poorly characterized. To address these gaps, we surveyed the biologically active surface sediments in Lake Hazen, the largest lake by volume north of the Arctic Circle, and a small lake and shoreline pond in its watershed. High-throughput amplicon sequencing of the 16S rRNA gene uncovered a community dominated by Proteobacteria, Bacteroidetes, and Chloroflexi, similar to those found in other cold and oligotrophic lake sediments. We also show that the microbial community structure in this Arctic polar desert is shaped by pH and redox gradients. This study lays the groundwork for predicting how sediment microbial communities in the Arctic could respond as climate change proceeds to alter their physicochemical constraints.


Dealing with conflict in caring for the seriously ill: "it was just out of the question".
Physicians often assume that conflict is undesirable and destructive, yet conflict handled well can be productive, and the clarity that results can lead to clearer decision making and greater family, patient, and clinician satisfaction. We review the course of Mrs B, an 84-year-old woman with advanced dementia and an advance directive stating no artificial hydration or nutrition. Over the course of her illness, her family and physicians had conflicting opinions about the use of short-term tube feeding and intravenous hydration in her care. We describe the conflicts that arose between her physicians and family and a typology of conflicts common in care of patients who are seriously ill (family vs team, team member vs team member). Drawing from the business, psychology, and mediation literature, we describe useful communication tools and common pitfalls. We outline a step-wise approach that physicians can use to deal with conflicts and the use of treatment trials as a strategy to address conflicts about the use of life-sustaining medical interventions.


Reliability assessment and validation of the Melasma Area and Severity Index (MASI) and a new modified MASI scoring method.
The Melasma Area and Severity Index (MASI), the most commonly used outcome measure for melasma, has not been validated. We sought to determine the reliability and validity of the MASI. After standardized training, 6 raters independently rated 21 patients with mild to severe melasma once daily over a period of 2 days to determine intrarater and interrater reliability. Validation was performed by comparing the MASI with the melasma severity scale. The darkness component of the MASI was validated by comparing it with the difference between mexameter scores for affected versus adjacent normal-appearing skin. The area component of the MASI was validated by comparing it with the area of each section of the face determined by computer-based measurement software. The MASI score showed good reliability within and between raters and was found to be valid when compared with the melasma severity scale, mexameter scores, and area measurements. Homogeneity assessment by raters showed the least agreement and can be removed from the MASI score without any loss of reliability. Patients were limited to Hispanic, African, and Asian backgrounds. The MASI is a reliable measure of melasma severity. Area of involvement and darkness are sufficient for accurate measurement of the severity of melasma and homogeneity can be eliminated.


Rapid differentiation of isomeric lipids by photodissociation mass spectrometry of fatty acid derivatives.
Both traditional electron ionization and electrospray ionization tandem mass spectrometry have demonstrated limitations in the unambiguous identification of fatty acids. In the former case, high electron energies lead to extensive dissociation of the radical cations from which little specific structural information can be obtained. In the latter, conventional collision-induced dissociation (CID) of even-electron ions provides little intra-chain fragmentation and thus few structural diagnostics. New approaches that harness the desirable features of both methods, namely radical-driven dissociation with discrete energy deposition, are thus required. Herein we describe the derivatization of a structurally diverse suite of fatty acids as 4-iodobenzyl esters (FAIBE). Electrospray ionization of these derivatives in the presence of sodium acetate yields abundant [M + Na](+) ions that can be mass-selected and subjected to laser irradiation (λ = 266 nm) on a modified linear ion-trap mass spectrometer. Photodissociation (PD) of the FAIBE derivatives yields abundant radical cations by loss of atomic iodine and in several cases selective dissociation of activated carbon-carbon bonds (e.g., at allylic positions) are also observed. Subsequent CID of the [M + Na - I](•+) radical cations yields radical-directed dissociation (RDD) mass spectra that reveal extensive carbon-carbon bond dissociation without scrambling of molecular information. Both PD and RDD spectra obtained from derivatized fatty acids provide a wealth of structural information including the position(s) of unsaturation, chain-branching and hydroxylation. The structural information obtained by this approach, in particular the ability to rapidly differentiate isomeric lipids, represents a useful addition to the lipidomics tool box.


[Anatomic illustration and its authors at the Medical School in Prague].
This article is a longer version of the introductory address opening the exhibition of anatomical illustration in the Academic Club of First Medical Faculty of Charles University in May 1999. The history of anatomical illustration, its significance and its two main forms, scientific drawing and didactical illustration, are shortly introduced. The development of this form of art at the Medical Faculty in Prague is shown and is demonstrated by examples of illustrations. Two old authors of illustrations are mentioned: an unknown author of illustrations of the first illustrated textbook of anatomy in Prague that was written by Ch. S. a Zeidlern, and F. Bĕlopotocký who illustrated the Atlas of Anatomy by W. Stanĕk written in Czech in 1840. In more detail are discussed the following artists and anatomical illustrators of 20th century connected with the Institute of Anatomy of Charles University: J. Rejsek, E. Illing, S. Machácek, M. Med, V. Seichert, I. Helekal a J. Kacvinský.


Cluster analysis of radionuclide concentrations in beach sand.
This paper presents a method in which natural radionuclide concentrations of beach sand minerals are traced along a stretch of coast by cluster analysis. This analysis yields two groups of mineral deposit with different origins. The method deviates from standard methods of following dispersal of radionuclides in the environment, which are usually based on the construction of lines of equal concentrations. The paper focuses on the methodology of quantitatively correlating activity concentrations of natural radionuclides in two groups of minerals. The methodology is widely applicable, but is demonstrated for natural radioactivity in beach sands along the coast of South West Australia.


Isolation.
This article is a messy account not of the COVID-19 pandemic but one written during the pandemic. Although written over several successive evenings it is not a linear narrative that builds on a chain of passing moments teleologically to an end. It is not a diary, just a collection of scattered thoughts about living during COVID-19, the (lack of) care that many elderly people receive and how we, or perhaps only I, struggle to cope in these exceptional times. This is not a typical autoethnography, it is not reflexive writing and there is no conclusion albeit that the article ends.


Computational Equilibrium Thermodynamic and Kinetic Analysis of K-Ras Dimerization through an Effector Binding Surface Suggests Limited Functional Role.
Dimer formation is believed to have a substantial impact on regulating K-Ras function. However, the evidence for dimerization and the molecular details of the process are scant. In this study, we characterize a K-Ras pseudo-C2-symmetric dimerization interface involving the effector interacting β2-strand. We used structure matching and all-atom molecular dynamics (MD) simulations to predict, refine, and investigate the stability of this interface. Our MD simulation suggested that the β2-dimer is potentially stable and remains relatively close to its initial conformation due to the presence of a number of hydrogen bonds, ionic salt bridges, and other favorable interactions. We carried out potential of mean force calculations to determine the relative binding strength of the interface. The results of these calculations indicated that the β2 dimerization interface provides a weak binding free energy in solution and a dissociation constant that is close to 1 mM. Analyses of Brownian dynamics simulations suggested an association rate kon ≈ 10(5)-10(6) M(-1) s(-1). Combining these observations with available literature data, we propose that formation of auto-inhibited β2 K-Ras dimers is possible but its fraction in cells is likely very small under normal physiologic conditions.


Excessive Worrying as a Central Feature of Anxiety during the First COVID-19 Lockdown-Phase in Belgium: Insights from a Network Approach.
Since the WHO declared the COVID-19 pandemic on March 11, 2020, the novel coronavirus, SARS-CoV-2, has profoundly impacted public health and the economy worldwide. But there are not the only ones to be hit. The COVID-19 pandemic has also substantially altered mental health, with anxiety symptoms being one of the most frequently reported problems. Especially, the number of people reporting anxiety symptoms increased significantly during the first lockdown-phase compared to similar data collected before the pandemic. Yet, most of these studies relied on a unitary approach to anxiety, wherein its different constitutive features (i.e., symptoms) were tallied into one sum-score, thus ignoring any possibility of interactions between them. Therefore, in this study, we seek to map the associations between the core features of anxiety during the first weeks of the first Belgian COVID-19 lockdown-phase (n = 2,829). To do so, we implemented, in a preregistered fashion, two distinct computational network approaches: a Gaussian graphical model and a Bayesian network modelling approach to estimate a directed acyclic graph. Despite their varying assumptions, constraints, and computational methods to determine nodes (i.e., the variables) and edges (i.e., the relations between them), both approaches pointed to excessive worrying as a node playing an especially influential role in the network system of the anxiety features. Altogether, our findings offer novel data-driven clues for the ongoing field's larger quest to examine, and eventually alleviate, the mental health consequences of the COVID-19 pandemic.


Structure of the Hybrid-2 type intramolecular human telomeric G-quadruplex in K+ solution: insights into structure polymorphism of the human telomeric sequence.
Formation of the G-quadruplex in the human telomeric sequence can inhibit the activity of telomerase, thus the intramolecular telomeric G-quadruplexes have been considered as an attractive anticancer target. Information of intramolecular telomeric G-quadruplex structures formed under physiological conditions is important for structure-based drug design. Here, we report the first structure of the major intramolecular G-quadruplex formed in a native, non-modified human telomeric sequence in K(+) solution. This is a hybrid-type mixed parallel/antiparallel-G-stranded G-quadruplex, one end of which is covered by a novel T:A:T triple capping structure. This structure (Hybrid-2) and the previously reported Hybrid-1 structure differ in their loop arrangements, strand orientations and capping structures. The distinct capping structures appear to be crucial for the favored formation of the specific hybrid-type intramolecular telomeric G-quadruplexes, and may provide specific binding sites for drug targeting. Our study also shows that while the hybrid-type G-quadruplexes appear to be the major conformations in K(+) solution, human telomeric sequences are always in equilibrium between Hybrid-1 and Hybrid-2 structures, which is largely determined by the 3'-flanking sequence. Furthermore, both hybrid-type G-quadruplexes suggest a straightforward means for multimer formation with effective packing in the human telomeric sequence and provide important implications for drug targeting of G-quadruplexes in human telomeres.


Synthesis of human adenovirus early RNA species is similar in productive and abortive infections of monkey and human cells.
Northern (RNA) blot analysis has been used to show that synthesis of early mRNA species is similar in monkey cells productively or abortively infected with human adenovirus. mRNA species from all five major early regions (1A, 1B, 2, 3, 4) are identical in size and comparable in abundance whether isolated from monkey cells infected with adenovirus type 2 or with the host range mutant Ad2hr400 or coinfected with adenovirus type 2 plus simian virus 40. The mRNA species isolated from monkey cells are identical in size to those isolated from human cells. Production of virus-associated RNA is also identical in productive and abortive infections of monkey cells. Synthesis of virus-associated RNA is, however, significantly greater in HeLa cells than in CV1 cells at late times after infection regardless of which virus is used in the infection.


Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.
Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.


Learning management systems and lecture capture in the medical academic environment.
As residents work disparate schedules at multiple locations and because of workweek hour limits mandated by the ACGME, residents may be unable to attend lectures, seminars, or other activities that would enhance their skills. Further, the ACGME requires that residency programs document resident learning in six stated core competencies and provide proof of completion for various other requirements. LMS/LC is a promising technology to provide a means by which residency programs may overcome these obstacles. More studies are needed to show under what conditions an LMS/LC program actually enhances learning, and which elements are most useful to the new generation of learners comfortable with Web 2.0 technologies.


Group virtue: the importance of morality (vs. competence and sociability) in the positive evaluation of in-groups.
Although previous research has focused on competence and sociability as the characteristics most important to positive group evaluation, the authors suggest that morality is more important. Studies with preexisting and experimentally created in-groups showed that a set of positive traits constituted distinct factors of morality, competence, and sociability. When asked directly, Study 1 participants reported that their in-group's morality was more important than its competence or sociability. An unobtrusive factor analytic method also showed morality to be a more important explanation of positive in-group evaluation than competence or sociability. Experimental manipulations of morality and competence (Study 4) and morality and sociability (Study 5) showed that only in-group morality affected aspects of the group-level self-concept related to positive evaluation (i.e., pride in, or distancing from, the in-group). Consistent with this finding, identification with experimentally created (Study 2b) and preexisting (Studies 4 and 5) in-groups predicted the ascription of morality, but not competence or sociability, to the in-group.


Personalized orthoses as a good treatment option for Charcot neuro-osteoarthropathy of the foot.
We sought to assess the biomechanical characteristics of the feet of patients with Charcot neuro-osteoarthropathy and to determine reulceration rates before and after personalized conservative orthotic treatment. A longitudinal prospective study was performed in 35 patients with Charcot's foot. Although some patients had a history of ulcers, at the study outset no patient had ulcers. All of the patients underwent biomechanical testing and a radiographic study. A radiophotopodogram was prepared by superimposing an imprint of the sole on a plantar radiograph. Based on the results of these tests, an orthopedic insole was prepared and therapeutic footwear prescribed for each foot. The following variables were compared between the Charcot and unaffected feet: previous ulcers and ulcer sites, reulcerations produced after treatment, type of foot (neuropathic/neuroischemic), ankle mobility, first-ray mobility, and relaxed calcaneal stance position. Treatment efficacy was determined by comparing ulcers presenting in patients in the year leading up to the study period and the year in which treatment was received. In a 1-year period, 70 feet received orthotic treatment, of which 41 were Charcot's feet. Ulceration rates before the study were 73.2% in feet with Charcot's and 31.0% in those without. After 1 year of wearing the customized orthoses, rates fell significantly to 9.8% in the Charcot feet and 0% in the feet without this condition. Conservative customized orthotic treatment was effective at preventing ulcers and the complications that often lead these patients to surgery.


CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation.
CHIP (C terminus of Hsc-70 interacting protein) is an E3 ligase that links the protein folding machinery with the ubiquitin-proteasome system and has been implicated in disorders characterized by protein misfolding and aggregation. Here we investigate the role of CHIP in protecting from ataxin-1-induced neurodegeneration. Ataxin-1 is a polyglutamine protein whose expansion causes spinocerebellar ataxia type-1 (SCA1) and triggers the formation of nuclear inclusions (NIs). We find that CHIP and ataxin-1 proteins directly interact and co-localize in NIs both in cell culture and SCA1 postmortem neurons. CHIP promotes ubiquitination of expanded ataxin-1 both in vitro and in cell culture. The Hsp70 chaperone increases CHIP-mediated ubiquitination of ataxin-1 in vitro, and the tetratricopeptide repeat domain, which mediates CHIP interactions with chaperones, is required for ataxin-1 ubitiquination in cell culture. Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1. Overexpression of CHIP in a Drosophila model of SCA1 decreases the protein steady-state levels of both expanded and unexpanded ataxin-1 and suppresses their toxicity. Finally we investigate the ability of CHIP to protect against toxicity caused by expanded polyglutamine tracts in different protein contexts. We find that CHIP is not effective in suppressing the toxicity caused by a bare 127Q tract with only a short hemagglutinin tag, but it is very efficient in suppressing toxicity caused by a 128Q tract in the context of an N-terminal huntingtin backbone. These data underscore the importance of the protein framework for modulating the effects of polyglutamine-induced neurodegeneration.


Negatively supercoiled DNA from plants infected with a single-stranded DNA virus.
A method for isolating covalently closed circular double-stranded DNA from plants infected with the geminivirus, tomato golden mosaic virus, is described. Ethidium bromide titration showed this DNA to be negatively supercoiled with a superhelical density of -0.062. The presence of S1 nuclease-sensitive secondary structure in the supercoiled DNA was demonstrated by its conversion to the open circular and linear DNA forms on treatment with this enzyme.


Prevalence of Femoroacetabular Impingement Morphology in Asymptomatic Adolescents.
Femoroacetabular impingement (FAI) can lead to acetabular chondrolabral damage and has been theorized as a causative factor in the development of osteoarthritis. The pathogenesis of FAI is unknown. The purpose of this study was to determine the prevalence of FAI morphology in asymptomatic adolescents. We identified children 10 to 18 years of age who had undergone a pelvic CT between 2007 and 2012. Exclusion criteria included hip pain, any hip pathology, bone tumor, long-term steroid use, history of chemotherapy or radiation therapy, nonambulatory status, neuromuscular disorder, chromosomal abnormality, and metabolic bone disease. Multiplanar reformatted images were created from axial images to calculate α angles and lateral center-edge angles (LCEA). Cam morphology was defined as an α-angle ≥55 degrees and pincer morphology as a LCEA≥40 degrees. We analyzed 558 patients (1116 hips). There were 276 males and 282 females. The average age was 14.4 years (range, 10.0 to 18.2 y). The mean α-angle was 47.9 degrees (range, 25.7 to 78 degrees) and the mean LCEA was 34.4 degrees (range, 3.9 to 58.6 degrees). Males had a significantly higher mean α-angle (49.7 vs. 46.0 degrees) (P<0.0005) and females had a significantly higher mean LCEA (35.7 vs. 33.0 degrees) (P<0.0005). Ninety-four adolescents (16.8%) had an α-angle ≥55 degrees. Cam morphology was significantly more common in males (23.9% vs. 9.9%) (P<0.001). A total of 181 adolescents (32.4%) had a LCEA≥40 degrees. Pincer morphology was equally common in males and females (29.7% vs. 35.1%) (P=0.17). Thirty-four adolescents (6.1%) had mixed morphologies. Mixed morphologies were found in 21 males (7.6%) and 13 females (4.6%) (P=0.19). The prevalence of pincer morphology increased significantly with increased age in males (P<0.001). The prevalence of cam-type FAI morphology in asymptomatic adolescents is similar to the reported prevalence in asymptomatic adults. Pincer morphology may be more common than cam morphology in adolescents. Cam morphology is more prevalent in males, whereas pincer and mixed morphologies are equally prevalent in both sexes. Level III-diagnostic.


A facile method of forming nanoscale patterns on poly(ethylene glycol)-based surfaces by self-assembly of randomly grafted block copolymer brushes.
Poly(oligo(ethylene glycol) methacrylate) (POEGMA) block poly(methyl methacrylate) (PMMA) brushes were synthesized on the silicon wafer surfaces by the surface-initiated atom transfer radical polymerization (ATRP) method. Atomic force microscopy, ellipsometry, and water contact angle methods were employed to study the surface morphology and stimulus-response behavior. It was found that simple solvent treatments could induce phase segregation of the POEGMA and PMMA segments thus introducing nanoscale patterns. The feature size could be less than 10 nm and was tunable on the nanoscale. Various patterns including spherical aggregates, wormlike aggregates, stripe patterns, perforated layers, and complete overlayers were obtained through adjusting the upper block layer thickness. These patterns could switch between the different morphologies reversibly after the treatment with selective solvents.


Study about the effects of dental noises on the emotional experiences of children aged 6 to 10 years. A pilot study.
The aim of our study is to verify if some of the noises produced in a dental surgery, especially those of high- speed drill and Erbium laser, might cause anxiety to children. In order to confirm our hypothesis, we recorded these noises and then reproduced them to a group of children in a neutral setting, in this case at school. The children were aged 6 to 10 years, 55.9% were Italian, while the remaining 44.1% were of other nationalities. Some of them already had a previous experience at the dentist's. The range of images recalled by the children is very small, and they all refer to a realistic, imaginary and sometimes daily context (domestic, family and game related). Such representations have rarely been associated to negative sensations. The noise environment of the dentist's surgery, for what concerns the two stimuli we analysed (high-speed Drill and Erbium laser), does not cause an anxious reaction to the majority of children; as a matter of fact the percentage of positive sensations and emotions turns out to be predominant. The results obtained suggest it would be useful to protect this natural tendency, finding out the best method to prevent adult models, such as parents or clinical staff, from affecting it in a negative way.


Aspects of Point-of-Care Diagnostics for Personalized Health Wellness.
Advancements in analytical diagnostic systems for point-of-care (POC) application have gained considerable attention because of their rapid operation at the site required to manage severe diseases, even in a personalized manner. The POC diagnostic devices offer easy operation, fast analytical outcome, and affordable cost, which promote their advanced research and versatile adoptability. Keeping advantages in view, considerable efforts are being made to design and develop smart sensing components such as miniaturized transduction, interdigitated electrodes-based sensing chips, selective detection at low level, portable packaging, and sustainable durability to promote POC diagnostics according to the needs of patient care. Such effective diagnostics systems are in demand, which creates the challenge to make them more efficient in every aspect to generate a desired bio-informatic needed for better health access and management. Keeping advantages and scope in view, this mini review focuses on practical scenarios associated with miniaturized analytical diagnostic devices at POC application for targeted disease diagnostics smartly and efficiently. Moreover, advancements in technologies, such as smartphone-based operation, paper-based sensing assays, and lab-on-a-chip (LOC) which made POC more sensitive, informative, and suitable for major infectious disease diagnosis, are the main focus here. Besides, POC diagnostics based on automated patient sample integration with a sensing platform is continuously improving therapeutics interventions against specific infectious disease. This review also discussed challenges associated with state-of-the-art technology along with future research opportunities to design and develop next generation POC diagnostic systems needed to manage infectious diseases in a personalized manner.


Memory for temporally dynamic scenes.
Recognition memory was investigated for individual frames extracted from temporally continuous, visually rich film segments of 5-15 min. Participants viewed a short clip from a film in either a coherent or a jumbled order, followed by a recognition test of studied frames. Foils came either from an earlier or a later part of the film (Experiment 1) or from deleted segments selected from random cuts of varying duration (0.5 to 30 s) within the film itself (Experiment 2). When the foils came from an earlier or later part of the film (Experiment 1), recognition was excellent, with the hit rate far exceeding the false-alarm rate (.78 vs. 18). In Experiment 2, recognition was far worse, with the hit rate (.76) exceeding the false-alarm rate only for foils drawn from the longest cuts (15 and 30 s) and matching the false-alarm rate for the 5 s segments. When the foils were drawn from the briefest cuts (0.5 and 1.0 s), the false-alarm rate exceeded the hit rate. Unexpectedly, jumbling had no effect on recognition in either experiment. These results are consistent with the view that memory for complex visually temporal events is excellent, with the integrity unperturbed by disruption of the global structure of the visual stream. Disruption of memory was observed only when foils were drawn from embedded segments of duration less than 5 s, an outcome consistent with the view that memory at these shortest durations are consolidated with expectations drawn from the previous stream.