Appendectomy in pediatric patients with synchronous oncologic diagnosis is safe: an analysis using the national surgical quality improvement project, pediatric.
Optimal treatment of children who develop appendicitis while undergoing treatment for an oncologic diagnosis has not been defined, in part due to theoretical concerns for an increased risk of postoperative wound complications. We hypothesized that synchronous oncologic diagnosis conferred no increased odds of developing a wound complication in pediatric patients undergoing appendectomy. Retrospective cohort study using the National Surgical Quality Improvement Program, Pediatric (2012-2017) of patients < 18 years of age undergoing appendectomy. The main exposure variable was active treatment for an oncologic diagnosis. The primary outcomes of interest were 30-day wound complications (superficial or deep infections or dehiscence, and abscess). For univariate analysis comparison of baseline differences between patients with/without a cancer diagnosis we employed Pearson's χ2 and two sample t tests. Multivariate logistic regression was used to evaluate which covariates were independently associated with our outcome. We identified 28,219 patients who had undergone appendectomy; 95 (0.3%) were undergoing oncologic treatment at the time of surgery. Patients in the cancer group were more likely to be receiving steroids, have lower white blood cell counts and have higher American Society of Anesthesiology classes as compared to the noncancer patients. Age, gender, rates of perforation, and laparoscopy were similar between the two groups. Patients with an active cancer diagnosis suffered wound complications (measured individually and as an aggregate) at no higher odds than those without a cancer diagnosis. Pediatric patients undergoing treatment for cancer do not have increased odds of suffering postoperative wound complications following appendectomy as compared to the general population.


Optimization of hydrogen bonds for combined DNA/collagen complex.
Many natural and biological systems including collagen and DNA polymers are formed by a process of molecular self-assembly. In this paper, we developed two novel structural models and built heterogeneous DNA/collagen complexes through a preferable arrangement of multiple hydrogen bonds (H-bonds) between DNA and collagen molecules. The simulation results based on three sets of criteria indicate that one of the models with five collagen molecules, which are positioned around each strand of DNA molecules emerged to form a suitable polymer complex with the maximum number of H-bonds. Our predictions quantitatively validated and agreed with the molecular structure reported by Mrevlishvili and Svintradze [2005. Int. J. Biol. Macromol. 36, 324-326].


The assessment of psychometric properties for the subjective wellbeing-5 dimensions (SWB-5D) questionnaire in the general Dutch population.
Financial resources for health care are limited, so assessment of intervention effectiveness in terms of health in relation to its costs is important. Measuring health outcomes in cost-effectiveness analyses is usually done by health-related quality of life measures, like the EQ-5D. However, over the past decade, innovations on the conceptual level of health have evolved and novel approaches are rising such as the capability approach, subjective wellbeing, and Positive Health. This study assesses the psychometric properties of the subjective wellbeing-5 dimension (SWB-5D) outcome measure. A quantitative, cross-sectional study design was used to determine the concurrent and construct (convergent and known group) validity for the SWB-5D. Concurrent and convergent validity were estimated as correlations between the SWB-5D and the Dutch version of the EQ-5D, ICECAP-A, and PH-17. Assessment of known-groups validity was based on the variables illness, education, and the overall happiness (Cantril Ladder) and overall health scale (EQ-5D VAS). A representative sample of 1016 respondents of the Dutch population completed an online questionnaire. The SWB-5D showed reasonable concurrent validity and showed good convergent and known-group validity. The SWB-5D had a lower ceiling effect compared to the EQ-5D and ICECAP-A. Compared to traditional health measurement approaches, novel approaches are more focused on the mental and social pillars of health. The SWB-5D shows psychometric feasibility of comprehensive measurement of health, as indicated by a range of validity measures in a large representative sample of the Dutch population.


Spatially multiplexed single-molecule translocations through a nanopore at controlled speeds.
In current nanopore-based label-free single-molecule sensing technologies, stochastic processes influence the selection of translocating molecule, translocation rate and translocation velocity. As a result, single-molecule translocations are challenging to control both spatially and temporally. Here we present a method using a glass nanopore mounted on a three-dimensional nanopositioner to spatially select molecules, deterministically tethered on a glass surface, for controlled translocations. By controlling the distance between the nanopore and glass surface, we can actively select the region of interest on the molecule and scan it a controlled number of times and at a controlled velocity. Decreasing the velocity and averaging thousands of consecutive readings of the same molecule increases the signal-to-noise ratio by two orders of magnitude compared with free translocations. We demonstrate the method's versatility by assessing DNA-protein complexes, DNA rulers and DNA gaps, achieving down to single-nucleotide gap detection.


Dendritic cells produce TSLP that limits the differentiation of Th17 cells, fosters Treg development, and protects against colitis.
Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and keratinocytes, and is involved in immune homeostasis or inflammation. The mechanism through which TSLP regulates intestinal inflammation is unclear. Here, we report that mouse dendritic cells (DCs) express TSLP both in vitro and in vivo in response to Toll-like receptor ligation in a MyD88-dependent fashion. TSLP is produced by the CD103(+) subset of tolerogenic gut DCs and is downregulated during experimental colitis. TSLP produced by DCs acts directly on T cells by reducing their capacity to produce interleukin (IL)-17 and fostering the development of Foxp3(+) T cells. Consistently, TSLP protects against colitis development through a direct action on T cells, as adoptive transfer of naïve T cells from TSLPR(-/-) to SCID mice results in a more severe colitis, with increased frequency of IL-17-producing T cells and inflammatory cytokines. Hence, we describe a new anti-inflammatory role of TSLP in the gut.


Simultaneous determination of four alkaloids in Lindera aggregata by ultra-high-pressure liquid chromatography-tandem mass spectrometry.
A new separation and quantification method using liquid chromatography under ultra-high-pressure in combination with tandem mass spectrometry (MS/MS) was developed for simultaneous determination of four alkaloids in Lindera aggregata. The analysis was performed on an Acquity UPLC BEH C(18) column (50mmx2.1mm, 1.7microm particle size; Waters, Milford, MA, USA) utilizing a gradient elution profile and a mobile phase consisting of (A) water containing 10mM ammonium acetate adjusted to pH 3 with acetic acid and (B) acetonitrile. An electrospray ionization (ESI)-tandem interface in the positive mode was employed prior to mass spectrometric detection. The calibration curve was linear over the range of 17.1-856ng for boldine, 42.4-2652ng for norboldine, 6.1-304ng for reticuline and 0.5-50ng for linderegatine, respectively. The average recoveries ranged from 99.2 to 101.4% with RSDs< or =2.7%. Then, four L. aggregata samples from different batches were analyzed using the established method. The results indicated that ultra-high-pressure liquid chromatography-tandem mass spectrometry provided improved chromatographic parameters resulting in significantly increased sample throughput including lower solvent consumption and lower limits of quantitation (LOQs) for most of target analytes compared to previous method employing conventional high-performance liquid chromatography (HPLC) separation. So, the established method was validated, sensitive and reliable for the determination of four alkaloids in L. aggregata.


Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response.
Data on the effects of sustained virologic response (SVR) to hepatitis C virus (HCV) therapy on the outcome of extrahepatic complications are scarce. We conducted this study to assess the impact of SVR on the occurrence of chronic kidney disease (CKD), diabetes mellitus (DM), and cardiovascular disease (CVD) in a cohort of human immunodeficiency virus (HIV)-infected patients. We analyzed coinfected HIV/HCV patients in the Management of Standardized Evaluation of Retroviral HIV Infection (MASTER) cohort. Only event-free patients with a serum HCV-RNA determination at baseline were included. Patients were divided into four groups: INF-exposed with SVR; INF-exposed without SVR; spontaneous HCV clearance; untreated viremic patients. We estimated the incidence of extrahepatic complications and employed Kaplan-Meier curves and Cox regression to assess the association of SVR/INF strata adjusted for a series of confounders. Data from 1676 patients were analyzed (20.29 % started an INF-based regimen). Overall, the incidence of CKD, DM, CVD, and death was 5.32 [95 % confidence interval (CI) 3.99-6.98], 10.13 (95 % CI 8.20-12.37), 6.79 (95 % CI 5.26-8.65), and 13.49 (95 % CI 11.29-16.0) per 1000 person-years of follow-up, respectively. In the Cox model for treated patients, SVR was not associated with a lower risk of CKD, DM, CVD, and death compared to non-SVR. Cirrhosis was significantly associated with a higher risk of CKD [hazard ratio (HR) 2.13; 95 % CI 1.06-4.31], DM (HR 3.48; 95 % CI 2.18-5.57), and death (HR 6.18; 95 % CI 4.1-9.31), but not of CVD (HR 1.14; 95 % CI 0.57-2.3). There are still many unknowns regarding the impact of SVR on the occurrence of extrahepatic complications in coinfected HIV/HCV patients. Further investigations are needed in order to elucidate the role of SVR as an independent prognostic factor for extrahepatic events.


Efficacy of color Doppler ultrasonography for the diagnosis of duodenal varices successfully treated with percutaneous transhepatic obliteration.
We treated a 74-year-old woman who complained of tarry stool. Neither endoscopic examination of the upper gastrointestinal tract nor colonoscopy revealed any finding indicative of bleeding, and (99m)Tc-HSA-D pool scintigraphic imaging showed no accumulation of blood in the digestive tract. Small tortuous collateral veins were observed on computed tomography (CT) in the distal third portion of the duodenum. Color Doppler ultrasonography obtained color flow images of varices in the distal third portion of the duodenum indicating turbulent flow, and color flow imaging showed the outflow vessel from duodenal varices. Duodenoscopy revealed tortuous varices, with erosions and blue in appearance, in the same area. Percutaneous transhepatic portography was carried out 18 days after the treatment of ascites, and hepatofugal blood flow was confirmed in the pancreatic duodenal vein originating near the junction between the splenic and inferior mesenteric veins with the passage of contrast medium into the duodenal varices, which drained into the left ovarian vein. We performed selective catheterization into the afferent vein of the varices, and injected 8 ml of a 5% solution of ethanolamine oleate containing iopamidol. Microcoil embolization using steel coils was added because the therapeutic effect resulting after the relatively rapid washout of sclerosant was insufficient. CT and color Doppler ultrasonography showed absence of blood flow in the varices 1 week after the therapy. This patient has had no episodes of rebleeding in the 24 months after therapy. Color Doppler ultrasonography was useful in diagnosing this case of duodenal varices and in evaluating therapeutic effect.


Obstetric implications of minor müllerian anomalies in oligomenorrheic women.
The obstetric performance of 50 consecutive women with minor müllerian anomalies was compared with that of 141 subjects having a normal uterine cavity on hysterosalpingography. All 191 patients had a history of some years' infertility. Spontaneous abortion was the outcome of the first pregnancy in 27.8% of women with müllerian anomalies (not statistically different from the outcome of the control group). However, the evidence of a greater risk of variously complicated first pregnancies and labors (30.3% versus 12.9%, p less than 0.05) and of emergency cesarean sections (21.2% versus 7.1%, p less than 0.05) in the group of minor müllerian anomalies than in the group with normal uteri confirmed the innate pathologic condition and clinical significance of these mild to moderate malformations present in about 40% to 50% of oligomenorrheic women. The most frequent complications were threatened abortion and abnormal fetal lie. Even the very mildest müllerian anomalies seemed to have gynecologic and obstetric implications, but the clinical impact in this group still remains uncertain. It is concluded that a genital tract anomaly of a certain obstetric significance (ratio between distance from nadir of fundal indentation to line connecting summits of uterine horns and length of this line or H/L ratio greater than 0.15) must be suspected in about one third of women with oligomenorrhea. Consequently a high risk in the event of a future pregnancy is evident, and about half the pregnancies (42.1%) in this group will be complicated in one or more ways.


Elements Influencing Recruitment and Retention of Millennial Hospitalists Born in or after 1982: a Survey-Based Study.
Hospitalist turnover is exceedingly high, placing financial burdens on hospital medicine groups (HMGs). Following training, many begin their employment in medicine as early-career hospitalists, the majority being millennials. To understand what elements influence millennial hospitalists' recruitment and retention. We developed a survey that asked participants to rate the level of importance of 18 elements (4-point Likert scale) in their decision to choose or remain at an HMG. The survey was electronically distributed to hospitalists born in or after 1982 across 7 HMGs in the USA. Elements were grouped into four major categories: culture of practice, work-life balance, financial considerations, and career advancement. We calculated the means for all 18 elements reported as important across the sample. We then calculated means by averaging elements within each category. We used unpaired t-tests to compare differences in means for categories for choosing vs. remaining at an HMG. One hundred forty-four of 235 hospitalists (61%) responded to the survey. 49.6% were females. Culture of practice category was the most frequently rated as important for choosing (mean 96%, SD 12%) and remaining (mean 96%, SD 13%) at an HMG. The category least frequently rated as important for both choosing (mean 69%, SD 35%) and remaining (mean 76%, SD 32%) at an HMG was career advancement. There were no significant differences between respondent gender, race, or parental status and ratings of elements for choosing or remaining with HMGs. Culture of practice at an HMG may be highly important in influencing millennial hospitalists' decision to choose and stay at an HMG. HMGs can implement strategies to create a millennial-friendly culture which may help improve recruitment and retention.


Chlorpropamide alters AVP-receptor binding of rat renal tubular membranes.
The effects of chlorpropamide on AVP-receptor binding in rat renal tubular basolateral membranes were investigated utilizing [3H][Arg8]vasopressin (AVP). Our data indicate that chlorpropamide alters AVP-receptor binding in a competitive manner.


Effect of glutamine on intestinal mucosal integrity and bacterial translocation after abdominal radiation.
This study evaluates the effect of oral glutamine on intestinal mucosal integrity and bacterial translocation in rats. 80 animals were randomised into four groups: group 1 (chow diet and water), group 2 (chow diet and glutamine 3%), group 3 (radiation, chow diet and water), group 4 (radiation, chow diet and glutamine 3%). Groups 1 and 2 were fed for 5 days, then sacrificed. Groups 3 and 4 were fed for 12 days, irradiated on the 5th day and sacrificed on 1st, 3rd and 7th post-radiation days. Cultures from the mesenteric lymph nodes (MLN), portal vein (PV) and aorta (A) were taken and two tissue samples were also taken from the terminal ileum for light and electron microscopic examination. In non-radiated rats glutamine did not alter the histologic parameters of villous height (VH), mitoses per crypt (M/C) and muscle thickness (MT). Group 3 rats had severe mucosal damage associated with a significant decrease of VH (p < 0.0001) and M/C (p < 0.01) on 1st and 3rd post-radiation days respectively. In contrast, group 4 rats maintained their mucosal structure and had a significant increase of VH and M/C (p < 0.0001) on post-radiation days 1 and 3. Bacterial translocation in MLN was 87.5% (p < 0.002) and 75% (p < 0.04) on 1st and 3rd post-radiation days respectively in group 3, and fell significantly to 12.5% (p < 0.002) in group 4. The data demonstrate that glutamine helps maintain the integrity of the intestinal mucosa and thereby reduces the incidence of bacterial translocation following abdominal irradiation.


Adsorption-induced stability reversal of photochromic diarylethene on metal surfaces.
A scanning tunneling microscopy study of a photochromic diarylethene adsorbed on Au and Cu reveals the reversal of thermodynamic stability between its two isomers compared to the gas phase, in solution, and its single crystal, which could result from the molecule-substrate interaction such as charge transfer and hybridization.


(1)H NMR Metabolomic Footprinting Analysis for the In Vitro Screening of Potential Chemopreventive Agents.
Metabolomics is the quantification and analysis of the concentration profiles of low-molecular-weight compounds present in biological samples. In particular metabolic footprinting analysis, based on the monitoring of metabolites consumed from and secreted into the growth medium, is a valuable tool for the study of pharmacological and toxicological effects of drugs. Mass spectrometry and nuclear magnetic resonance (NMR) are the two main complementary techniques used in this field. Although less sensitive, NMR gives a direct fingerprint of the system, and the spectra obtained contain metabolic information that can be distilled by chemometric techniques. In this chapter, we present how metabolomic footprinting can be used to assess in vitro a potential chemopreventive molecule as metformin.


Comparison of a calixarene-based ion-selective electrode with two automated analyzers for the clinical determination of sodium in blood plasma.
Neutral-carrier ion-selective electrodes based on methyl p-t-butylcalix[4]aryl acetate have been prepared that are responsive to sodium ions. The miniaturized catheter-type electrodes were obtained by dip-coating their porcelain tips in a PVC membrane cocktail. Examination of the general performance of the electrodes revealed excellent characteristics in terms of Nernstian response, selectivity, stability, reproducibility and response time. The results from the indirect potentiometric assessment of a large number of plasma samples with the electrodes showed a good correlation with the results from two automated analyzers (Technicon Smac 3, Hitachi 704) and with flame photometric data. Although inconsistencies were observed in the measurement of some plasma samples, the variance seemed to be method-dependent, and the overall performance of the electrodes showed promise as an alternative to the sodium glass electrode. Some factors influencing the standard potential of the measuring cell are discussed as a source of error.


Structures of the yeast dynamin-like GTPase Sey1p provide insight into homotypic ER fusion.
Homotypic membrane fusion of the endoplasmic reticulum is mediated by dynamin-like guanosine triphosphatases (GTPases), which include atlastin (ATL) in metazoans and Sey1p in yeast. In this paper, we determined the crystal structures of the cytosolic domain of Sey1p derived from Candida albicans. The structures reveal a stalk-like, helical bundle domain following the GTPase, which represents a previously unidentified configuration of the dynamin superfamily. This domain is significantly longer than that of ATL and critical for fusion. Sey1p forms a side-by-side dimer in complex with GMP-PNP or GDP/AlF4(-) but is monomeric with GDP. Surprisingly, Sey1p could mediate fusion without GTP hydrolysis, even though fusion was much more efficient with GTP. Sey1p was able to replace ATL in mammalian cells, and the punctate localization of Sey1p was dependent on its GTPase activity. Despite the common function of fusogenic GTPases, our results reveal unique features of Sey1p.


Understanding implementation costs of a pediatric weight management intervention: an economic evaluation protocol.
Understanding the cost and/or cost-effectiveness of implementation strategies is crucial for organizations to make informed decisions about the resources needed to implement and sustain evidence-based interventions (EBIs). This economic evaluation protocol describes the methods and processes that will be used to assess costs and cost-effectiveness across implementation strategies used to improve the reach, adoption, implementation, and organizational maintenance of an evidence-based pediatric weight management intervention- Building Health Families (BHF). A within-trial cost and cost-effectiveness analysis (CEA) will be completed as part of a hybrid type III effectiveness-implementation trial (HEI) designed to examine the impact of an action Learning Collaborative (LC) strategy consisting of network weaving, consultee-centered training, goal-setting and feedback, and sustainability action planning to improve the adoption, implementation, organizational maintenance, and program reach of BHF in micropolitan and surrounding rural communities in the USA, over a 12-month period. We discuss key features of implementation strategy components and the associated cost collection and outcome measures and present brief examples on what will be included in the CEA for each discrete implementation strategy and how the results will be interpreted. The cost data will be collected by identifying implementation activities associated with each strategy and using a digital-based time tracking tool to capture the time associated with each activity. Costs will be assessed relative to the BHF program implementation and the multicomponent implementation strategy, included within and external to a LC designed to improve reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of BHF. The CEA results will be reported by RE-AIM outcomes, using the average cost-effectiveness ratio or incremental cost-effectiveness ratio. All the CEAs will be performed from the community perspective. The proposed costing approach and economic evaluation framework for dissemination and implementation strategies and EBI implementation will contribute to the evolving but still scant literature on economic evaluation of implementation and strategies used and facilitate the comparative economic analysis. ClinicalTrials.gov NCT04719442 . Registered on January 22, 2021.


How has the efficiency of China's green development evolved? An improved non-radial directional distance function measurement.
As a key choice for human sustainable development, green development is also one of China's five major vision points. To explore the level of green development in China since it was first written into national documents in 2011, this paper applies an improved non-radial distance function based on Data Envelopment Analysis method to analyze the progress against the development targets set in related national documents. The results show that: (1) China's green development efficiency has kept increasing in 2011-2017. (2) The growth in green development efficiency was significantly higher in the 13th Five-Year Plan period compared to the 12th Five-Year Plan period. (3) The green development efficiency shows a decreasing trend from south to north, east of the Hu line. This study provides a more practical idea for evaluating the quality of green development in mainland China.


Activation of CFTR by genistein in human airway epithelial cell lines.
Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel expressed in epithelial cells. The effects of genistein and 4-phenylbutyrate (PBA) on CFTR were studied in three human airway epithelial cell lines expressing wild-type or DeltaF508 CFTR: Calu-3, CFSMEo-, and CFBE41o- cells. The cells were loaded with the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) and chloride efflux was studied. Forskolin and 3-isobutyl-1-methylxanthine (IBMX) induced chloride efflux in Calu-3 cells but not in CF lines. Genistein (2.5-50 microM) alone was able to induce chloride efflux in all cell lines. Genistein did not enhance the effect of forskolin and IBMX. PBA had little or no effect on genistein-induced chloride efflux. The effect of genistein seen at low concentrations makes genistein interesting for possible pharmacological treatment of CF, since it is known that similar concentrations can be obtained in plasma by a soy-rich diet.


In situ proteo-metabolomics reveals metabolite secretion by the acid mine drainage bio-indicator, Euglena mutabilis.
Euglena mutabilis is a photosynthetic protist found in acidic aquatic environments such as peat bogs, volcanic lakes and acid mine drainages (AMDs). Through its photosynthetic metabolism, this protist is supposed to have an important role in primary production in such oligotrophic ecosystems. Nevertheless, the exact contribution of E. mutabilis in organic matter synthesis remains unclear and no evidence of metabolite secretion by this protist has been established so far. Here we combined in situ proteo-metabolomic approaches to determine the nature of the metabolites accumulated by this protist or potentially secreted into an AMD. Our results revealed that the secreted metabolites are represented by a large number of amino acids, polyamine compounds, urea and some sugars but no fatty acids, suggesting a selective organic matter contribution in this ecosystem. Such a production may have a crucial impact on the bacterial community present on the study site, as it has been suggested previously that prokaryotes transport and recycle in situ most of the metabolites secreted by E. mutabilis. Consequently, this protist may have an indirect but important role in AMD ecosystems but also in other ecological niches often described as nitrogen-limited.


Are fur farms a potential source of persistent organic pollutants or mercury to nearby freshwater ecosystems?
Farming of carnivorous animals for pelts potentially contaminates nearby ecosystems because animal feed and waste may contain persistent organic pollutants (POPs) and metals. Mink farms in Nova Scotia (NS), Canada, provide mink with feed partially composed of marine fish meal. To test whether mink farms potentially contribute contaminants to nearby lakes, we quantified organochlorine pesticides (OCP), polychlorinated biphenyls (PCB), and total mercury (THg) in mink/aquaculture feed, waste, and sediment collected from 14 lakes within rural southwest NS where mink farms are abundant and have operated for decades. Mercury, PCBs, dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), and dieldrin were present in mink/aquaculture feed and mink waste, indicating they are potential contaminant sources. Lakes with mink farms in their catchment exhibited significantly higher THgflux than lakes downstream of mink farming activity and reference lakes (p < 0.0001) after the intensification of mink farming in 1980, indicating mink farming activity is likely associated with increased lacustrine THgflux. Sedimentary ƩPCBflux was elevated in lakes with mink farms in their catchments, suggesting possible PCB contributions from mink farming, local agriculture, and atmospheric deposition. Elevated ƩDDT in lakes near mink farms relative to reference lakes suggests a possible enrichment related to mink farming, although mixed land use and historical DDT usage related to forestry in the region complicates DDT source attribution. Maximum dieldrinflux and HCHflux in lake sediment occurred coeval with peak worldwide usage in the 1970s and are unlikely to be associated with local mink farming. Lakes with mink farming activities in their catchments were associated with increased THgflux, ƩPCBflux, and possibly ƩDDTflux, suggesting a possible connection between marine fish meal, fur farms, and aquatic ecosystems in NS.


Readiness for Parkinson's disease genetic testing and counseling in patients and their relatives in urban settings in the Dominican Republic.
Genetic testing for Parkinson's disease (PD) is increasing globally, and genetic counseling is an important service that provides information and promotes understanding about PD genetics and genetic testing. PD research studies have initiated outreach to underrepresented regions in North America, including regions in Latin America, such as the Dominican Republic (DR); some studies may include return of genetic test results. Thus, understanding what individuals know about PD, genetic testing for PD, and their interest in speaking with a genetic counselor, is crucial when assessing readiness. In this cross-sectional study, a survey was distributed to people with Parkinson's disease (PwP) and their unaffected biological relatives in the DR. Questions assessed genetics knowledge, attitude toward genetic testing, and interest in genetic testing and counseling. Of 45 participants, 69% scored the maximum on the attitude scale, indicating an overall positive attitude toward genetic testing; 95% indicated interest in genetic testing for PD, and 98% were at least somewhat interested in meeting with a genetic counselor. The mean PD genetics knowledge score was similar to previously published data. Through free text responses, participants expressed a desire to know more about PD treatment and management, prevention, cause, and their personal risk for PD. These results provide further evidence of readiness for genetic testing in this country but also underscore some gaps in knowledge that should be addressed with targeted educational efforts, as part of building genetic testing and counseling capacities.


Barbiturate poisoning and gastrointestinal propulsion.
Anaesthetic doses of pentobarbitone (50 mg/kg) were found to inhibit gastric emptying and gastrointestinal transit in the rat. Gastric emptying was more profoundly suppressed than gastrointestinal transit. Phenobarbitone (150 mg/kg) had a similar effect. Since pentobarbitone and phenobarbitone also blocked the peristaltic reflex in the isolated small intestine of the guinea-pig, it would appear that the inhibitory effect of anaesthetic doses of barbiturates on gastrointestinal motility is mainly due to a direct action on the digestive tract. Together with the observation that considerable amounts of phenobarbitone were found in the stomach of an intoxicated patient 3 days after drug intake, these results might indicate that gastric lavage should also be considered in the treatment of protracted barbiturate poisoning.


Decomposing noise in biochemical signaling systems highlights the role of protein degradation.
Stochasticity is an essential aspect of biochemical processes at the cellular level. We now know that living cells take advantage of stochasticity in some cases and counteract stochastic effects in others. Here we propose a method that allows us to calculate contributions of individual reactions to the total variability of a system's output. We demonstrate that reactions differ significantly in their relative impact on the total noise and we illustrate the importance of protein degradation on the overall variability for a range of molecular processes and signaling systems. With our flexible and generally applicable noise decomposition method, we are able to shed new, to our knowledge, light on the sources and propagation of noise in biochemical reaction networks; in particular, we are able to show how regulated protein degradation can be employed to reduce the noise in biochemical systems.


Cost-effectiveness analysis of a chronic back pain multidisciplinary biopsychosocial rehabilitation (MBR) compared to standard care for privately insured in Germany.
Multidisciplinary biopsychosocial rehabilitation (MBR) is highly recommended for chronic lower back pain (CLBP) treatment, but its economic benefit remains to be clearly demonstrated. The purpose of this study is to analyse the effect of a 12-month MBR programme of behavioural change coaching and device-supported exercise on direct medical costs, sick leave and health-related quality of life (HRQOL) at 24 months. An incremental cost-effectiveness analysis was conducted in Germany from a private health insurance perspective using data from a multi-centre, two-arm randomised controlled trial with parallel-group Zelen's randomisation and 24-month follow-up. After removing dissimilarities in characteristics between MBR and usual care (control) via propensity score matching, treatment effects were calculated using a difference-in-difference approach. Base-case analysis of the MBR (n=112) and usual care group (n=111) showed an incremental cost-effectiveness ratio (ICER) of €8,296 per quality-adjusted life year (QALY) gained, indicating that the intervention was cost-effective. Compared to the controls, MBR reduced economically unaccounted sick leave due to back pain in the last six months by 17.5 days (p = 0.001) and had a positive effect on health-related quality of life (HRQOL) (0.046, p=0.026). Subgroup analysis of participants with major impairment demonstrated that a dominant intervention was possible, as reflected by an ICER of - €7,302 per QALY. Savings were driven by a - €1,824 reduction in back pain-specific costs. Moreover, sick leave was 27 days (p = 0.006) less in the MBR group. This first cost-effectiveness study with combined data from a private health insurer and a controlled trial in Germany demonstrated that long term MBR for the treatment of CLBP is cost-effective. Subgroups with major impairment from back pain benefitted more from the intervention than those with minor impairment. MBR significantly reduced sick leave in all participants. Hence, it is a profitable intervention from a societal point of view. The trial of the evaluation study was retrospectively registered in the German Clinical Trials Register under trial number DRKS00015463 retrospectively (dated 4 Sept 2018).


Differential expression analysis throughout the weaning period in the mouse cerebral cortex.
At weaning, mammals switch from drinking mother's milk to eating foods of environmental origin. These foods contain natural compounds with novel tastes and textures, which are provided to the young for the first time following the termination of breastfeeding. This novel eating experience may alter the cognitive brain function of mammalian babies, increasing their reactions to their food environments. Because the cerebral cortex is a central organ for cognition and learning, we investigated differences in whole-gene expression profiles in the mouse cerebral cortex using microarray analysis before and after weaning. Of 45,037 murine genes, 35 genes were upregulated and 31 genes were downregulated, in response to weaning. In particular, immediate early genes, molecular chaperones, and myelin-related genes were upregulated. In situ hybridization analysis revealed that the mRNA for an immediate early gene, Egr-2/KROX-20, was transported from the nucleus to the cell body at layer 5/6 of the somatosensory cortex during weaning. In contrast, in animals without any food supply other than mother's milk, Egr-2/KROX-20 mRNA was retained within the nucleus at the somatosensory cortex. These data suggest that the novel experience of food intake modulates gene expression profiles in the murine cerebral cortex at the weaning stage.


Right lobe living related liver transplantation in adults without venous drainage of the paramedian sector.
There is some controversy on the necessity of venous reconstruction of the right paramedian sector (segments V and VIII) during right lobe living related liver transplantation. In this report we describe the evolution of posttransplant graft function in five consecutive right lobe recipients without specific drainage of the right paramedian sector. The technique of common right hepatectomy for right lobe graft harvesting and transplantation did not include the middle hepatic vein in the graft. The mean total ischemic time was 51 minutes (ranges: 35 to 64 minutes). The mean graft to recipient weight ratio was 1.35% +/- 0.15%. No patient developed small-for-size syndrome. All patients showed a rise in transaminases with a maximum at postoperative day 2 (mean aspartate aminotransferase: 1067 +/- 432 IU/mL). Liver function improved rapidly, with coagulation normalized at postoperative day 5. Bilirubin decreased progressively to normalize in three patients at postoperative day 14. Ultrasonography and computed tomography demonstrated that the paramedian sector of the right liver was congested, a state that was temporary with normalization of the liver tests and congestion disappeared at follow-up. No complication was linked to congestion. This series showed that in right lobe liver transplantation with a relatively large-size graft, reconstruction of the hepatic veins of the paramedian sector may not be necessary despite the induction of some degree of venous congestion. In smaller grafts, this congestion might be avoided by reconstruction of the large veins draining segments V and VIII.


Behavioural phenotypic characterization of CD-1 mice lacking the neuropeptide S receptor.
Neuropeptide S (NPS) is the endogenous ligand of a previously orphan receptor now named NPSR. In the brain NPS regulates several biological functions including anxiety, arousal, locomotion, food intake, learning and memory, pain and drug abuse. Mice lacking the NPSR gene (NPSR(-/-)) represent an useful tool to investigate the neurobiology of the NPS/NPSR system. NPSR(-/-) mice have been generated in a 129S6/SvEv genetic background. In the present study we generated CD-1 congenic NPSR(+/+) and NPSR(-/-) mice and investigated their phenotype and sensitivity to NPS in various behavioural assays. The phenotype analysis revealed no locomotor differences between NPSR(+/+) and NPSR(-/-) mice. The behaviour of NPSR(+/+) and NPSR(-/-) mice in the righting reflex test was superimposable. No differences were recorded between the two genotypes in the elevated plus maze, open field and stress-induced hyperthermia tests, with the exception of rearing behaviour that was reduced in knockout animals. Moreover the behaviour of NPSR(+/+) and NPSR(-/-) mice in the forced swimming, novel object recognition and formalin assays was similar. The stimulatory effects of NPS in the locomotor activity test and its anxiolytic-like actions in the elevated plus maze and open field assays were evident in NPSR(+/+) but not NPSR(-/-) animals. In conclusion, the present study indicates that the NPS/NPSR system does not tonically control locomotion, sensitivity to diazepam, anxiety, depressive-like behaviours, memory and pain transmission in mice. Furthermore our results clearly show that the product of the NPSR gene represents the mandatory protein for all the NPS biological effects so far described.


Relationship of sulfation to ongoing chondroitin polymerization during biosynthesis of chondroitin 4-sulfate by microsomal preparations from cultured mouse mastocytoma cells.
A microsomal preparation from chondroitin 4-sulfate-synthesizing cultured mouse mastocytoma cells was incubated with UDP-[3H]GalNAc, UDP-GlcA, and 3'-phosphoadenylylphosphosulfate (PAPS) for 30 s at 10 degrees C and with UDP-[14C]GlcA, UDP-GalNAc, and PAPS for 4 h at 37 degrees C for synthesis of 3H- and 14C-labeled chondroitin/chondroitin sulfate. The latter incubation provided more than 100 times as much product as did the short incubation at 10 degrees C. Upon chromatography of the isolated labeled glycosaminoglycans on a Sepharose CL-6B column, most of the [14C]glycosaminoglycan from the 4 h, 37 degrees C incubation was excluded from the column, indicating that this nascent glycosaminoglycan had been polymerized fully. In contrast, most of the [3H]glycosaminoglycan from the 30 s, 10 degrees C incubation was mostly retarded upon cochromatography on this same column, indicating that the nascent glycosaminoglycan was still growing in size. The labeled fractions representing chondroitin/chondroitin sulfate of varying sizes were analyzed for degree of sulfation by degradation with chondroitin ABC lyase followed by paper electrophoresis of the products. Results indicated that the [14C]chondroitin/chondroitin sulfate formed in the 4-h incubation was 60-70% sulfated. Incomplete chains of [3H]chondroitin/chondroitin sulfate formed in the 30-s incubation were also sulfated as much as 20-25%. As the size of the [3H]chondroitin/chondroitin sulfate increased, there was a concomitant increase in sulfation. These results demonstrate that in this microsomal system sulfation takes place while the nascent chondroitin glycosaminoglycan chains are still actively growing in length, although the sulfation lags somewhat behind the polymerization. This not only indicates a common membrane location for both polymerization and sulfation of chondroitin but also demonstrates that the sulfation of chondroitin by these mastocytoma cells may occur during the process of glycosaminoglycan polymerization rather than subsequent to completion of the glycosaminoglycan chains.


Synthesis of SF5-containing benzisoxazoles, quinolines, and quinazolines by the Davis reaction of nitro-(pentafluorosulfanyl)benzenes.
Meta- or para-nitro-(pentafluorosulfonyl)benzenes underwent the Davis reaction with arylacetonitriles to provide the SF5-containing benzisoxazoles. Good yields were obtained with arylacetonitriles containing the electron-neutral or electron-donor group, while those with the electron-acceptor group were found to be unreactive. Reductions of the benzisoxazoles gave ortho-aminobenzophenones in high yields. Their synthetic utility was demonstrated by condensation reactions with carbonyl compounds or amines to provide SF5-containing quinolines and quinazolines, respectively.


Classification of the deviated nose and its treatment.
To present a simplified classification of the deviated nose and the associated treatment outcome. Retrospective analysis. Tertiary care rhinology clinic. Seventy-five individuals (49 males and 26 females) who underwent rhinoplasty for a deviated nose with minimum follow-up of 36 months. Depending on the orientation of 2 horizontal subunits (the bony pyramid and the cartilaginous vault) with respect to the facial midline, the nasal deviations are classified into 5 types: I, a straight tilted bony pyramid with a straight tilted cartilaginous vault in the opposite direction; II, a straight tilted bony pyramid with a concavely or convexly bent cartilaginous vault; III, a straight bony pyramid with a tilted cartilaginous vault; IV, a straight bony pyramid with a bent cartilaginous vault, and V, a straight tilted bony pyramid and a tilted cartilaginous dorsum in the same direction. Deformities of types I through V occurred in 24 (32%), 19 (25%), 19 (25%), 7 (9%), and 6 (8%) patients, respectively, in whom 1, 3, 2, 1, and 1 unsuccessful outcomes were found. Four of the 8 failed cases had been approached endonasally. The proposed classification for the deviated nose could serve as a valuable adjunct in the treatment of these patients.


Review for the Korean Health Professionals and International Cooperation Doctors Dispatched to Peru by the Korea International Cooperation Agency (KOICA).
South Korea dispatches Korean nationals to partner developing countries as an Official Development Assistance (ODA) project through the Korea International Cooperation Agency (KOICA). In the health sector, KOICA dispatches international cooperation doctors (ICDs), nurses, physical therapists, radiologic technologists, nutritionists, medical laboratory technologists, occupational therapists, and dental hygienists. A total of 216 ICDs were dispatched over 19 times from 1995 until 2013. There were 19 areas of specialties among the ICDs. The most common specialty was internal medicine (61/216, 28.2%), the second most common specialty was general surgery (43/216, 19.9%), followed by oriental medicine (27/216, 12.5%), pediatrics (17/216, 7.9%), orthopedics (16/216, 7.4%), family medicine (16/216, 7.4%), and odontology (14/216, 6.5%). The ICDs have worked in 21 countries. KOICA dispatched the highest number of ICDs to Asia (97/216, 44.9%), followed by Africa (50/216, 23.1%), Latin America (34/216, 15.7%), the commonwealth of independent states (31/216, 14.4%), and Oceania (4/216, 1.9%). Nobody was dispatched to the Middle East. A total of 134 KOICA health professionals were dispatched to Peru from 1996 until October 1, 2014. Of these, 19.4% (26/134) were ICDs, 44.8% (60/216) were nurses, 20.1% (27/134) were physical therapists, 6.7% (9/134) were radiologic technologists, 2.2% (3/134) were nutritionists, and 6.7% (9/134) were medical laboratory. ICDs' specialties comprised internal medicine (13/26, 50%), family medicine (8/26, 30.8%), pediatrics (2/26, 7.7%), otorhinolaryngology (1/26, 3.8%), orthopedics (1/26, 3.8%), and oriental medicine (1/26, 3.8%). Most of the dispatched health professionals worked at institutions that were supported by KOICA. For this reason, the proportion of health professionals who worked at public health centers (PHCs) was the highest (58.2%, 78/134) when classified by workplace type. Other KOICA health professionals worked at hospitals, governmental organizations (GOs), or schools.


Oscillatory interactions between sensorimotor cortex and the periphery.
Field potential recordings from motor cortex show oscillations in the beta-band (approximately 20 Hz), which are coherent with similar oscillations in the activity of contralateral contracting muscles. Recent findings have revised concepts of how this activity might be generated in the cortex, suggesting it could achieve useful computation. Other evidence shows that these oscillations engage not just motor structures, but also return from muscle to the central nervous system via feedback afferent pathways. Somatosensory cortex has strong beta-band oscillations, which are synchronised with those in motor cortex, allowing oscillatory sensory reafference to be interpreted in the context of the oscillatory motor command which produced it.


New strategies for enhancing the speed and rate of coronary reperfusion.
Large, controlled clinical trials have conclusively demonstrated that intravenous thrombolytic therapy reduces mortality in patients with acute myocardial infarction. The recently published Global Utilization of Streptokinase and t-PA for Occluded Arteries (GUSTO) study demonstrated that patency within 90 minutes is predictive of survival. As a consequence, the interest in new strategies for enhancing the speed and rate of coronary reperfusion has been renewed. Further improvements in coronary patency can be anticipated by adopting a variety of approaches. Some of these approaches are simple and require only the application of proven principles, whereas others are more complex and require further research. The first approaches include earlier treatment after the onset of clinical symptoms, because of the strong relation between early treatment and improved clinical efficacy. Other approaches include development of more effective dosage regimens for the available thrombolytic agents, development of more fibrin-specific agents in an attempt to speed up lysis, and development of safer, more effective adjunctive antithrombotic agents to accelerate thrombolysis and prevent rethrombosis. The potential benefits from these latter approaches must not be offset by unacceptable increases in major bleeding or in the costs of treatment. The application of proven principles to improve coronary reperfusion should not be obscured by the research of more effective pharmacologic approaches. Actually, earlier and wider use of the currently available thrombolytic agents could potentially save more lives than the development of technically more exciting new approaches.


Specific cognitive abilities are associated with diabetes self-management behavior among patients with type 2 diabetes.
Patients with diabetes differ in compliance to diabetes self-management which influences their long-term health. Psychological factors, namely depression and cognitive abilities, are associated with diabetes self-management behavior. The aim of the study was to identify independent association of particular cognitive functions with diabetes self-management. In a cross sectional study 98 adults with type 2 diabetes attending Diabetes Outpatient Clinic were examined using the measures of diabetes self-management (Summary of Diabetes Self-Care Activities (SDSCA) measure), depression (Hamilton Depression Inventory (HDI)), diabetes distress (Problem Areas In Diabetes scale (PAID)), and the neuropsychological battery of tests for assessment of cognitive functions. Sociodemographic and diabetes-related data were collected. Univariate and multivariate regression analyses were used to identify and evaluate the predictors of diabetes self-management. Specific cognitive functions, namely immediate memory, visuospatial/constructional abilities, attention, and specific executive functions (planning and problem solving) were significantly associated with diabetes self-management. Among cognitive factors, planning and problem solving abilities were strongest predictors; furthermore, in a multivariate regression their association was independent from depression. Specific cognitive abilities, particularly planning and problem solving, play an independent role in diabetes self-management behaviors. Assessing patients' cognitive abilities may be of value for adjusting self-management education and treatment regimen.


Preparation of visually cued arm movements in monkey. Involvement of inferior parietal cortex.
Single-unit activity was recorded in monkey inferior parietal lobule (IPL) during performance of a visually cued limb motor task. Many neurons in the IPL modulated their activity just after the visual cue was presented, similar to the neuronal activity observed in the premotor cortex in a previous experiment. It is suggested that IPL neurons are involved in preparation of visually cued limb movement. The present results are discussed in view of a possible role for IPL and premotor cortex in processing visual information for use by the primary motor area.


No pervasive relationship between species size and local abundance trends.
Although there is some evidence that larger species could be more prone to population declines, the potential role of size traits in determining changes in community composition has been underexplored in global-scale analyses. Here, we combine a large cross-taxon assemblage time series database (BioTIME) with multiple trait databases to show that there is no clear correlation within communities between size traits and changes in abundance over time, suggesting that there is no consistent tendency for larger species to be doing proportionally better or worse than smaller species at local scales.


Comparison of different immunoassay methods to detect human anti-drug antibody using the WHO erythropoietin antibody reference panel for analytes.
Development of an appropriate assay to detect anti-drug antibody (ADA) is important for assessing immunogenicity to therapeutic protein products. However, characterizing ADA assay methods is difficult because human ADA as a reference standard is not available in most cases. We compared the analytical performance of three ligand-binding assay methods for ADA, namely, surface plasmon resonance (SPR), electrochemiluminescence (ECL), and biolayer interferometry (BLI) methods, by using the anti-erythropoietin (EPO) monoclonal antibody reference panel developed by the World Health Organization (WHO) in 2015. Dose-dependent binding responses were observed for all nine anti-EPO antibodies in the anti-EPO panel by the SPR and BLI methods. In contrast, the ECL method did not clearly detect binding of low-affinity anti-EPO antibodies. Regarding IgG2 and IgM antibodies derived from the same clone, IgG2 exhibited a higher binding response in the SPR assay, whereas the IgM binding response was higher than that of IgG2 in the ECL assay. In the case of the BLI method, there was no consistent pattern observed in the binding responses of IgG2 or IgM. Results of the anti-EPO antibody reference panel, which contains a variety of monoclonal antibodies, indicated that the ability to detect ADAs differed among these assay methods. Therefore, with ligand-binding assays, differences in assay platforms can affect the sensitivity and other characteristics of assays to detect ADAs. These results show that understanding the analytical performance of ADA assays is important for an appropriate assessment of immunogenicity. Our study also indicated the benefits of using the established human ADA reference panel to assess the assay methods for ADA detection.


Generation of hepatitis E virus-like particles of two new genotypes G5 and G6 and comparison of antigenic properties with those of known genotypes.
In addition to the four major genotypes (G1 through G4) known for human hepatitis E virus (HEV), two new genotypes (G5 and G6) were suggested, based on unique viral nucleotide sequences derived from wild boars in Japan. It has been unknown whether the virus of these new genotypes can cause hepatitis in humans; neither G5 nor G6 HEV has been found in patients to date. To study the antigenic properties of G5 and G6 HEV, we expressed N-terminus-truncated HEV ORF2 protein by a recombinant baculovirus system, and we obtained virus-like particles (VLPs) for both G5 and G6. The VLPs showed antigenic cross-reactivity against G1, G3 and G4 HEV more strongly than against ferret or rat HEV. Moreover, both anti-G5 and anti-G6 VLPs antibodies could neutralize G3 HEV's ability to infect PLC/PRF/5 cells, suggesting that G5 and G6 HEV have the same serotype as human HEV.


Localization of a multi-catalytic, high-molecular mass proteinase in the nuclei of muscle cells.
A multi-catalytic protease in muscle cells was uniquely localized to the nucleus of muscle cells, both in cell culture and in sections of muscle tissue. Although no specific substructure of the nucleus could be identified as the site of the enzyme by immunocytochemical techniques, the enzyme was nevertheless present in all muscle cell nuclei. It appears that MCP is a useful marker for nuclei found specifically in muscle tissue.


After praise and encouragement: emotional support strategies used by birth doulas in the USA and Canada.
to describe in detail the emotional support techniques employed by birth doulas during labour. grounded theory methodology was utilised in collecting and analysing interviews given by doulas and mothers who had doula care. By using both informants, a clearer picture of what constitutes emotional support by doulas emerged. 10 mothers from three different states in the Midwestern USA and 30 doulas from 10 different states and two Canadian provinces were interviewed. Two doulas worked in hospital-based programmes whereas the others had independent practices. Doulas usually attended births in hospitals where medical attendants spent little focused time with the mother. nine different strategies were distinguished. Four strategies (reassurance, encouragement, praise, explaining) were similar to those attributed to nurses in published research. Five were original and described as only being used by doulas (mirroring, acceptance, reinforcing, reframing, debriefing). emotional support by professional birth doulas is more complex and sophisticated than previously surmised. Mothers experienced these strategies as extremely meaningful and significant with their ability to cope and influencing the course of their labour. the doula's role in providing emotional support is distinct from the obstetric nurse and midwife. Professional doulas utilise intricate and complex emotional support skills when providing continuous support for women in labour. Application of these skills may provide an explanation for the positive 'doula effect' on obstetric and neonatal outcomes in certain settings.


Functional topography of the thalamo-cortical system during development and its relation to cognition.
The thalamus has complex connections with the cortex and is involved in various cognitive processes. However, little is known about the age-related changes of thalamo-cortical connections and their relation to cognitive abilities. The present study analyzed resting-state functional connectivity between the thalamus and nine cortical functional networks (default mode network (DMN), posterior DMN, left/right executive, dorsal attention, salience, motor, visual and auditory network) in a healthy human sample (N = 95, aged 5-25 years). Cognitive abilities, including processing speed, selective attention, and cognitive flexibility were assessed using neuropsychological tests. All nine cortical resting-state networks showed functional connections to the thalamus at rest, with no effect for sex (p > 0.05). For the motor, visual, auditory, DMN, posterior DMN, salience and dorsal attention network, we found mainly bilateral thalamic projections in the mediodorsal nucleus, pulvinar and in nuclei of the lateral group. For the right and left lateralized executive network, corresponding lateralized thalamic projections were found. Thalamo-cortical connectivity strength showed significant age-related changes from distinct sub-nuclei of the thalamus to different cortical networks including the visual, DMN, salience and dorsal attention network. Further, connectivity strength of thalamo-cortical networks was associated with cognitive abilities, including processing speed, selective attention and cognitive flexibility. Better cognitive abilities were associated with increased thalamo-cortical connectivity in the pulvinar, mediodorsal nucleus, intralaminar nucleus, and nuclei from the lateral group. Alterations in the integrity of the thalamo-cortical system seem to be crucial for the development of cognitive abilities during brain maturation.


Long-term treatment with beclomethasone dipropionate aerosol in asthmatic children with special reference to growth.
Thirty-one children, 19 boys and 12 girls, aged 3.4--10.8 years, with severe perennial bronchial asthma were treated with beclomethasone dipropionate aerosol (BDA) for 16-40 months. The dose was initially 400 micrograms a day and was gradually reduced to the lowest level giving control of symptoms. Earlier steroid or ACTH-treatment in six children was stopped during the BDA-treatment. At the start of the treatment the mean deviation of height compared with normal values for Swedish children was -0.10 s.d. for the boys and -0.51 s.d. for the girls. At the end of the observation period the deviation was -0.22 s.d. and -0.58 s.d., respectively. The increase in deviation was not significant. Bone age was also slightly retarded before beclomethasone treatment but this deviation was not accentuated during the observation period. It is concluded that treatment with BDA does not retard growth or skeletal maturation in children. The number of acute admissions to hospital was reduced by more than 50% during the first year of treatment.


[Studies on the kinetics of methaqualone during the late stage of pregnancy (author's transl)].
After oral administration of 0.4 g of methaqualone to pregnant and non-pregnant women, the authors stated that the half-life of this drug was significantly reduced during the last trimester of pregnancy. The two experimental groups showed no significant differences in the volume of distribution and the fictitious initial concentration. The commonly used therapeutical dosages are not likely to produce increased blood levels during normal pregnancy.


miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes.
IL-6 is an inflammatory cytokine and its overexpression plays an important role in osteoarthritis (OA) pathogenesis. Expression of IL-6 is regulated post-transcriptionally by MCPIP1. The 3' untranslated region (UTR) of MCPIP1 mRNA harbors a miR-139 'seed sequence', therefore we examined the post-transcriptional regulation of MCPIP1 by miR-139 and its impact on IL-6 expression in OA chondrocytes. Expression of miR-139 was found to be high in the damaged portion of the OA cartilage compared with unaffected cartilage from the same patient and was also induced by IL-1β in OA chondrocytes. Inhibition of miR-139 decreased the expression of IL-6 mRNA by 38% and of secreted IL-6 protein by 40%. However, overexpression of miR-139 increased the expression of IL-6 mRNA by 36% and of secreted IL-6 protein by 56%. These data correlated with altered expression profile of MCPIP1 in transfected chondrocytes. Studies with a luciferase reporter construct confirmed the interactions of miR-139 with the 'seed sequence' located in the 3' UTR of MCPIP mRNA. Furthermore, miR-139 overexpression increased the catabolic gene expression but expression of anabolic markers remained unchanged. Overexpression of miR-139 also induced apoptosis in OA chondrocytes. Importantly, we also discovered that IL-6 is a potent inducer of miR-139 expression in OA chondrocytes. These findings indicate that miR-139 functions as a post-transcriptional regulator of MCPIP1 expression and enhances IL-6 expression, which further upregulates miR-139 expression in OA chondrocytes. These results support our hypothesis that miR-139-mediated downregulation of MCPIP1 promotes IL-6 expression in OA. Therefore, targeting miR-139 could be therapeutically beneficial in the management of OA.


Protein kinases and their protein substrates associated with chromatin and ribosomes in SV40-transformed rat cells.
The level of endogenous protein phosphorylation in non-histone chromosomal and ribosomal wash proteins is 7--10 times greater in SV40-transformed rat cells than in untransformed parental cells. Protein kinase activity in these proteins was fractionated by either phosphocellulose or DEAE-cellulose chromatography. One major and one minor component were detected in non-histone proteins and only one component in ribosomal wash proteins when the activity in each fraction was measured with an exogenous substrate, casein. These enzymes prefer casein to whole histone as substrate and are cyclic AMP-independent. The enzyme activity in a major peak of non-histone proteins and in ribosomal wash proteins measured with casein as substrate is 3 times greater in transformed cells than in untransformed cells, whereas pH optimum, cation requirements and apparent Km values for casein and ATP are identical or very similar in the two cell types. No significant phosphatase was detected in non-histone and ribosomal wash proteins from the two types of cell. The patterns of endogenous protein phosphorylation in these protein fractions analysed by gel electrophoresis are significantly different between these cells. These results suggest that the high level of endogenous protein phosphorylation in non-histone and ribosomal wash proteins from SV40-transformed cells is caused mainly by the increased activity of protein kinase and the nature of protein substrates.


Dual activation profile of monocytes is associated with protection in Mexican patients during SARS-CoV-2 disease.
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been one of the most catastrophic diseases observed in recent years. It has reported nearly 550 million cases worldwide, with more than 6.35 million deaths. In Mexico, an increased incidence and mortality of this disease were observed, where the immune response has been involved in the magnitude and severity. A critical version of the disease is accompanied by hyperinflammatory responses, with cytokine and defective cellular responses. A detailed understanding of the role of molecules and cells in the immune response during COVID-19 disease may help to generate effective protection mechanisms, improving those we already have. Here we analyzed blood samples obtained from patients at the Hospital Regional de Alta Especialidad de Ixtapaluca (HRAEI), Mexico, which were classified according to living guidance for clinical management of COVID-19 by the World Health Organization: asymptomatic, mild, severe, and critical disease. We observed increased interleukin (IL)-6 levels and a T-CD8+ and T-CD4+ cell reduction correlated with the critical disease version. Importantly, here, we described a significant reduction of CD11b+CD45highCD14low monocytes during severe disease, which displayed a non-classical profile, expressing IL-10, transforming growth factor (TGF)-β, and indoleamine 2,3-dioxygenase (IDO)1 molecule. Moreover, CD11b+CD45highCD14low monocytes obtained from infected one-dose vaccinated patients (Pfizer® vaccine) who suffered minimal symptoms showed simultaneously a dual classical and no-classical profile expressing pro- and anti-inflammatory cytokines. These results suggest that blood monocytes expressing a dual pro- and anti-inflammatory profile might be a predictive marker for protection in the Mexican population during COVID-19 disease. KEY POINTS : • Exacerbated immune response is associated with COVID-19 severe disease. • Dual monocyte activation profile is crucial for predicting protection during COVID-19. • Vaccination is crucial to induce the dual activation profile in monocytes.


Inactivation of p15INK4b in chronic arsenic poisoning cases.
Arsenic exposure from burning high arsenic-containing coal has been associated with human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation or genetic modification might contribute to arsenic-induced carcinogenicity. This study aims to clarify the correlation between arsenic pollution and functional defect of p15INK4b gene in arsenic exposure residents from a region of Guizhou Province, China. To this end, 103 arsenic exposure residents and 105 control subjects were recruited in this study. The results showed that the exposure group exhibited higher levels of urinary and hair arsenic compared with the control group (55.28 vs 28.87 μg/L, 5.16 vs 1.36 μg/g). Subjects with higher arsenic concentrations are more likely to have p15INK4b methylation and gene deletion (χ2 = 4.28, P = 0.04 and χ2 = 4.31, P = 0.04). We also found that the degree of p15INK4b hypermethylation and gene deletion occurred at higher incidence in the poisoning cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin cancer group), and were significantly associated with the stage of skin lesions (χ2 = 12.82, P < 0.01 and χ2 = 7.835, P = 0.005). These observations indicate that inactivation of p15INK4b through genetic alteration or epigenetic modification is a common event that is associated with arsenic exposure and the development of arsenicosis.


Randomised clinical trial: arbaclofen placarbil in gastro-oesophageal reflux disease--insights into study design for transient lower sphincter relaxation inhibitors.
Arbaclofen placarbil is a pro-drug of the gamma-aminobutyric acid-B agonist R-baclofen that has been shown to reduce reflux episodes in patients with gastro-oesophageal reflux disease (GERD). To evaluate the efficacy and safety of arbaclofen placarbil vs. placebo as adjunctive therapy in subjects with troublesome GERD symptoms despite therapy with once-daily doses of a proton pump inhibitor (PPI) and to identify the characteristics of patients who were responders. Patients (n = 460) with symptomatic GERD experiencing troublesome symptoms on once-daily PPI therapy were enrolled in this phase II, randomised, multicentre, double-blind, placebo-controlled, dose-ranging study. Patients were randomised to receive placebo or arbaclofen placarbil (20 or 40 mg once daily, 20 or 30 mg twice daily) with their current PPI for 6 weeks. Patients recorded heartburn and other GERD symptoms in a daily diary and rated severity of each event. The primary endpoint was percent change from baseline in heartburn events per week. In the primary analysis, there was no significant difference between arbaclofen placarbil and placebo. Post hoc analyses removing mild and very mild heartburn events resulted in greater percent reductions for all arbaclofen placarbil doses with nominal P values <0.05 for each dose compared with placebo. There was a dose-related increase for the most common adverse events. Arbaclofen placarbil was not superior to placebo in the primary analysis. Post hoc analyses suggest that subjects with more clinically relevant moderate or severe symptoms are more likely to respond to arbaclofen placarbil (clinicaltrials.gov NCT00978016).


Early warning for SpO2 decrease by the oxygen reserve index in neonates and small infants.
Continuously assessing the oxygenation levels of patients to detect and prevent hypoxemia can be advantageous for safe anesthesia, especially in neonates and small infants. The oxygen reserve index (ORI) is a new parameter that can assess oxygenation through a relationship with arterial oxygen partial pressure (PaO2 ). The aim of this study was to examine whether the ORI provides a clinically relevant warning time for an impending SpO2 (pulse oximetry hemoglobin saturation) reduction in neonates and small infants. ORI and SpO2 were measured continuously in infants aged <2 years during general anesthesia. The warning time and sensitivity of different ORI alarms for detecting impending SpO2 decrease were calculated. Subsequently, the agreement of the ORI and PaO2 with blood gas analyses was assessed. The ORI of 100 small infants and neonates with a median age of 9 months (min-max, 0-21 months) and weight of 8.35 kg (min-max, 2-13 kg) were measured. For the ORI/PaO2 correlation, 54 blood gas analyses were performed. The warning time and sensitivity of the preset ORI alarm during the entire duration of anesthesia were 84 s (25th-75th percentile, 56-102 s) and 55% (95% CI 52%-58%), and those during anesthesia induction were 63 s (40-82 s) and 56% (44%-68%), respectively. The positive predictive value of the preset ORI alarm were 18% (95% CI 17%-20%; entire duration of anesthesia) and 27% (95% CI 21%-35%; during anesthesia induction). The agreement of PaO2 intervals with the ORI intervals was poor, with a kappa of 0.00 (95% CI = [-0.18; 0.18]). The weight (p = .0129) and height (p = .0376) of the infants and neonates were correlated to the correct classification of the PaO2 interval with the ORI interval. The ORI provided an early warning time for detecting an impending SpO2 decrease in small infants and neonates in the defined interval in this study. However, the sensitivity of ORI to forewarn a SpO2 decrease and the agreement of the ORI with PaO2 intervals in this real-life scenario were too poor to recommend the ORI as a useful early warning indicator for this age group.


Central adiposity and other anthropometric factors in relation to risk of macrosomia in an African American population.
Previous studies have consistently identified maternal obesity and gestational weight gain (GWG) as risk factors for macrosomia, but little is known about the effects of central adiposity and body fat distribution. Using self-reported data from the Black Women's Health Study (BWHS), a large follow-up study of US black women, we examined the risk of macrosomia in relation to prepregnancy waist circumference, prepregnancy waist-to-hip ratio (WHR), prepregnancy BMI, and GWG. During 1995-2003, BWHS participants ages 21-44 years delivered 6,687 full-term singleton births (gestational age >37 weeks). We compared mothers of 691 infants weighing ≥ 4,000 g with mothers of 5,996 infants weighing <4,000 g. Generalized estimating equation models (GEE) that accounted for more than one birth per mother were used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI). Independent of prepregnancy BMI, prepregnancy waist circumference was positively associated with risk of macrosomia (OR = 1.58, 95% CI: 1.07-2.32, for ≥ 35.0 vs. <27.0 inches (≥ 88.9 vs. <68.6 cm); P trend = 0.04). As expected, prepregnancy BMI was also positively associated with macrosomia (OR = 1.74, 95% CI: 1.25-2.41 for BMI ≥ 35.0 vs. 18.5-24.9 kg m(-2)). GWG above the amount recommended by the 2009 Institute of Medicine report was associated with an increased risk of macrosomia and the association was present in each category of prepregnancy BMI (18.5-24.9, 25.0-29.9, and ≥ 30.0 kg m(-2); P trend <0.001). Our data suggest that overall obesity, high GWG, and high waist circumference are independent risk factors for macrosomia among US black women.


Designing a sustainable reverse supply chain network for COVID-19 vaccine waste under uncertainty.
The vast nationwide COVID-19 vaccination programs are implemented in many countries worldwide. Mass vaccination is causing a rapid increase in infectious and non-infectious vaccine wastes, potentially posing a severe threat if there is no well-organized management plan. This paper develops a mixed-integer mathematical programming model to design a COVID-19 vaccine waste reverse supply chain (CVWRSC) for the first time. The presented problem is based on minimizing the system's total cost and carbon emission. The uncertainty in the tendency rate of vaccination is considered, and a robust optimization approach is used to deal with it, where an interactive fuzzy approach converts the model into a single objective problem. Additionally, a Lagrangian relaxation (LR) algorithm is utilized to deal with the computational difficulty of the large-scale CVWRSC network. The model's practicality is investigated by solving a real-life case study. The results show the gain of the developed integrated network, where the presented framework performs better than the disintegrated vaccine and waste supply chain models. According to the results, vaccination operations and transportation of non-infectious wastes are responsible for a large portion of total cost and emission, respectively. Autoclaving technology plays a vital role in treating infectious wastes. Moreover, the sensitivity analyses demonstrate that the vaccination tendency rate significantly impacts both objective functions. The case study results prove the model's robustness under different realization scenarios, where the average objective function of the robust model is less than the deterministic model ones' in all scenarios. Finally, some insights are given based on the obtained results.


The prevalence of borderline personality disorder among individuals with obesity: a critical review of the literature.
Through a MEDLINE and PsycLIT database search, all US studies relating to the prevalence of borderline personality disorder (BPD) among obese individuals were reviewed. The highest rates of BPD among these individuals were found in samples recruited from psychologically oriented settings (i.e., eating disorders program, mental health setting). Lowest rates were found among those seeking weight loss in non-psychological programs or those in primary care settings. Among those studies examining individuals with binge-eating disorder (BED), all indicated a higher-than-community prevalence of BPD. These data suggest that the prevalence of BPD appears increased among those obese individuals seeking psychological care or who have BED.


Binding of inositol hexakisphosphate to the oxygenated derivative of dromedary (Camelus dromedarius) and human hemoglobin: 31P-NMR study.
Binding of inositol hexakisphosphate (IHP) to the oxygenated derivative of dromedary (Camelus dromedarius) and human hemoglobin (Hb) was investigated by 31P-NMR. The results obtained show that dromedary Hb binds, with different affinity, two IHP molecules per tetramer at distinct sites, while human Hb binds only one IHP molecule per tetramer.


Ischemia-induced seizures and cortical monoamine levels.
Seizure activity as a component of the ischemic process possibly responsible for monoamine changes described in the gerbil stroke model was the subject of this study. Abnormal motor activity suggestive of seizures developed one to three hours after unilateral ligation of the common carotid artery in approximately 50% of gerbils that exhibited signs of stroke. Reduction of cortical levels of dopamine and norepinephrine was observed only when seizures occurred in association with stroke. The levels of 5-hydroxytryptamine were reduced bilaterally in animals with and without signs of stroke and were reduced further in animals with stroke plus seizures. Further study is needed to establish whether the catecholamine changes associated with ischemia-induced seizures are primary and causative or secondary to seizure activity itself. In the ischemic brain, 5-hydroxytryptamine metabolism appears disordered independent of seizure activity. Seizure activity must be taken into account when the mechanisms of disordered monoamine metabolism are being examined in the gerbil stroke model.


Behavioural function and development of body-to-limb proportions and active movement ranges in three stick insect species.
Overall body proportions and relative limb length are highly characteristic for most insect taxa. In case of the legs, limb length has mostly been discussed with regard to parameters of locomotor performance and, in particular cases, as an adaptation to environmental factors or to the mating system. Here, we compare three species of stick and leaf insects (Phasmatodea) that differ strongly in the length ratio between antennae and walking legs, with the antennae of Medauroidea extradentata being much shorter than its legs, nearly equal length of antennae and legs in Carausius morosus, and considerably longer antennae than front legs in Aretaon asperrimus. We show that that relative limb length is directly related to the near-range exploration effort, with complementary function of the antennae and front legs irrespective of their length ratio. Assuming that these inter-species differences hold for both sexes and all developmental stages, we further explore how relative limb length differs between sexes and how it changes throughout postembryonic development. We show that the pattern of limb-to-body proportions is species-characteristic despite sexual dimorphism, and find that the change in sexual dimorphism is strongest during the last two moults. Finally, we show that antennal growth rate is consistently higher than that of front legs, but differs categorically between the species investigated. Whereas antennal growth rate is constant in Carausius, the antennae grow exponentially in Medauroidea and with a sudden boost during the last moult in Aretaon.


Bacterial signalling mechanism: An innovative microbial intervention with multifaceted applications in microbial electrochemical technologies: A review.
Microbial electrochemical technologies (METs) are a set of inventive tools that generate value-added by-products with concomitant wastewater remediation. However, due to the bottlenecks, like higher fabrication cost and inferior yield of resources, these inventive METs are still devoid of successful field-scale implementation. In this regard, application of quorum sensing (QS) mechanism to improve the power generation of the METs has gained adequate attention. The QS is an intercellular signalling mechanism that controls the bacterial social network in its vicinity via the synthesis of diffusible signal molecules labelled as auto inducers, thus ameliorating yield of valuables produced through METs. This state-of-the-art review elucidates different types of QS molecules and their working mechanism with the special focus on the widespread application of QS in the field of METs for their performance enhancement. Thus, this review intends to guide the researchers in rendering scalability to METs by integrating innovative QS mechanisms into them.


Photocrosslinkable gelatin-treated dentin matrix hydrogel as a novel pulp capping agent for dentin regeneration: I. synthesis, characterizations and grafting optimization.
In recent years, treated dentin matrix (TDM) has been introduced as a bioactive hydrogel for dentin regeneration in DPC. However, no study has introduced TDM as a photocrosslinkable hydrogel with a natural photoinitiating system. Therefore, the present study aimed to explore the synthesis, characterizations and grafting optimization of injectable gelatin- glycidyl methacrylate (GMA)/TDM hydrogels as a novel photocrosslinkable pulp capping agent for dentin regeneration. G-GMA/TDM hydrogel was photocrosslinked using a new two-component photoinitiating system composed of riboflavin as a photoinitiator under visible light and glycine as a first time coinitiator with riboflavin. The grafting reaction conditions of G-GMA/TDM e.g. GMA concentration and reaction time were optimized. The kinetic parameters e.g. grafting efficiency (GE) and grafting percentage (GP%) were calculated to optimize the grafting reaction, while yield (%) was determined to monitor the formation of the hydrogel. Moreover, G-GMA/TDM hydrogels were characterized by swelling ratio, degradation degree, and cytotoxicity. The instrumental characterizations e.g. FTIR, 1H-NMR, SEM and TGA, were investigated for verifying the grafting reaction. Statistical analysis was performed using F test (ANOVA) and Post Hoc Test (P = 0.05). The grafting reaction dramatically increased with an increase of both GMA concentration and reaction time. It was realized that the swelling degree and degradation rate of G-GMA/TDM hydrogels were significantly reduced by increasing the GMA concentration and prolonging the reaction time. When compared to the safe low and moderate GMA content hydrogels (0.048, 0.097 M) and shorter reaction times (6, 12, 24 h), G-GMA/TDM with high GMA contents (0.195, 0.391 M) and a prolonged reaction time (48 h) demonstrated cytotoxic effects against cells using the MTT assay. Also, the morphological surface of G-GMA/TDM freeze-dried gels was found more compacted, smooth and uniform due to the grafting process. Significant thermal stability was noticed due to the grafting reaction of G-GMA/TDM throughout the TGA results. G-GMA/TDM composite hydrogel formed by the riboflavin/glycine photoinitiating system is a potential bioactive and biocompatible system for in-situ crosslinking the activated-light pulp capping agent for dentin regeneration.


The Impact of Gallbladder Status on Biliary Complications After the Endoscopic Removal of Choledocholithiasis.
Endoscopic sphincterotomy (EST) with stone extraction is the standard management for choledocholithiasis. However, the necessity for subsequent management of gallstone to prevent the biliary complications remained controversial and few data were evaluated for the impact of status of gallbladder on recurrent biliary complications. We retrospectively investigated the relationship between the status of gallbladder and the occurrence of biliary complications after endoscopic removal of choledocholithiasis. Between January 1998 and December 2008, we enrolled 453 patients with intact gallbladder who underwent EST for choledocholithiasis and allocated into two groups: calculous gallbladder (n = 256) and acalculous gallbladder (n = 197). By reviewing patients' medical records, we compared the occurrence of biliary complications according to the presence or absence of gallstone in GB in situ. In total, biliary complications occurred in 83 patients (18.3 %) during the follow-up period. Calculous GB group had higher rate of overall complications (22.7 vs. 12.7 %; p = 0.007) and GB-associated complications (11.3 vs. 2.5 %; p = 0.001) than acalculous GB group. On the multivariate analysis, only the presence of gallstone was shown to be significant risk factor for overall biliary complication (OR 2.029; 95 % CI 1.209-3.405; p = 0.007) and GB-associated complications (OR 5.077; 95 % CI 1.917-13.446; p = 0.001). Mean event-free period was shorter in calculous GB group than acalculous GB group for overall complications (1774 vs. 2159 days; p = 0.012) and GB-associated complication (2153 vs. 2591 days; p = 0.001). Prophylactic cholecystectomy may not be necessary to prevent biliary complication in patients with acalculous gallbladder after endoscopic removal of pigment stones from bile duct.


Opioids and TRPV1 in the peripheral control of neuropathic pain--Defining a target site in the injured nerve.
Targeting peripheral neuropathic pain at its origin may prevent the development of hypersensitivity. Recently we showed this can be mediated by opioid receptors at the injured nerve trunk. Here, we searched for the most relevant peripheral site to block transient receptor potential vanilloid 1 (TRPV1), and investigated analgesic interactions between TRPV1 and opioids in neuropathy. In a chronic constriction injury (CCI) of the sciatic nerve in mice, we assessed the effects of μ-, δ- and κ-opioid receptor agonists and TRPV1 antagonist (SB366791) injected at the CCI site or into the injured nerve-innervated paw on spontaneous paw lifting, heat and mechanical sensitivity. We also examined TRPV1 expression in total membrane and plasma membrane fractions from nerves and paws. We found that opioids and SB366791 co-injected in per se nonanalgesic doses at the CCI site or into the paw diminished heat and mechanical sensitivity. SB366791 alone dose-dependently alleviated heat and mechanical sensitivity. TRPV1 blockade in the paw was more effective than at the CCI site. None of the treatments diminished spontaneous paw lifting. TRPV1 expression analysis suggests that the levels of functional TRPV1 do not critically determine the TRPV1 antagonist-mediated analgesia. Together, the identification of the primary action site in damaged nerves is crucial for effective pain control. Contrary to opioids, the TRPV1 blockade in the injured nerve peripheral terminals, rather than at the nerve trunk, appears promising against heat pain. Opioid/TRPV1 antagonist combinations at both locations partially reduced neuropathy-triggered heat and mechanical pain.


Tetraploidy and 5q deletion in myelodysplastic syndrome: a case report.
Tetraploidy is a very rare cytogenetic abnormality in myelocytic malignancies, and its significance is unclear to date. We report here on a 68-year-old male diagnosed with myelodysplastic syndrome/refractory anemia with excess blasts (MDS/RAEB). Cytogenetic analysis of his bone marrow biopsy at initial clinical presentation and in subsequent studies revealed the presence of two abnormal clones, 92,XXYY and 92,XXYY,del(5)(q13q33). Interphase fluorescence in situ hybridization analysis of abnormal cells confirmed interstitial deletion in 5q, demonstrated predominance of the tetraploid clone and persistent presence of the tetraploid clone with 5q deletion. The patient was not responsive to Revlimid (lenalidomide) treatment, which is routinely used in patients with 5q- syndrome. However, a subsequent course of therapy with the methyl-transferase inhibitor decitabine resulted in clinical and cytogenetic remission. Our data suggest that the unique complex abnormality of tetraploidy and 5q deletion described here for the first time in MDS is characterized by distinct disease etiology, the mechanism of which could involve epigenetic inactivation of gene expression via methylation.


Dual effects of single-walled carbon nanotubes coupled with near-infrared radiation on Bacillus anthracis spores: inactivates spores and stimulates the germination of surviving spores.
Bacillus anthracis is a pathogen that causes life-threatening disease--anthrax. B. anthracis spores are highly resistant to extreme temperatures and harsh chemicals. Inactivation of B. anthracis spores is important to ensure the environmental safety and public health. The 2001 bioterrorism attack involving anthrax spores has brought acute public attention and triggered extensive research on inactivation of B. anthracis spores. Single-walled carbon nanotubes (SWCNTs) as a class of emerging nanomaterial have been reported as a strong antimicrobial agent. In addition, continuous near infrared (NIR) radiation on SWCNTs induces excessive local heating which can enhance SWCNTs' antimicrobial effect. In this study, we investigated the effects of SWCNTs coupled with NIR treatment on Bacillus anthracis spores. The results showed that the treatment of 10 μg/mL SWCNTs coupled with 20 min NIR significantly improved the antimicrobial effect by doubling the percentage of viable spore number reduction compared with SWCNTs alone treatment (88% vs. 42%). At the same time, SWCNTs-NIR treatment activated the germination of surviving spores and their dipicolinic acid (DPA) release during germination. The results suggested the dual effect of SWCNTs-NIR treatment on B. anthracis spores: enhanced the sporicidal effect and stimulated the germination of surviving spores. Molecular level examination showed that SWCNTs-NIR increased the expression levels (>2-fold) in 3 out of 6 germination related genes tested in this study, which was correlated to the activated germination and DPA release. SWCNTs-NIR treatment either induced or inhibited the expression of 3 regulatory genes detected in this study. When the NIR treatment time was 5 or 25 min, there were 3 out of 7 virulence related genes that showed significant decrease on expression levels (>2 fold decrease). The results of this study demonstrated the dual effect of SWCNTs-NIR treatment on B. anthracis spores, which enhanced the sporicidal effect and stimulated the germination of surviving spores. SWCNTs-NIR treatment also altered the expression of germination, regulatory, and virulence-related genes in B. anthracis.


Assessment of the visual field by anyone, anywhere and at any time.
A visual field test for use in situations where conventional perimetry is impossible is presented. The test is entitled 'Oculo-Kinetic Perimetry' because it is the subject's eye that moves and not the test stimulus.


Collagen glycopeptides from the sea cucumber Stichopus japonicus.
Structures of several hydroxylysine-containing glycopeptides derived from the body wall of the sea cucumber have been determined. The glycosylated hydroxylysines were all the Y positions of Gly-X-Y triplets. They are thought to be distributed throughout the peptide chain, in contrast to vertebrate skin collagens. One glycopeptide demonstrated the existence of the sequence Gly-Gly-Hyp in invertebrates for the first time.


MeCP2 expression and function during brain development: implications for Rett syndrome's pathogenesis and clinical evolution.
Most cases of Rett syndrome (RTT) are associated with mutations of the transcriptional regulator MeCP2. On the basis of molecular structure, ontogeny, and subcellular and regional distribution, MeCP2 appears to be a link between synaptic activity and neuronal transcription. Integrating data on MeCP2 neurobiology, RTT neurobiology, MeCP2 mutational patterns in RTT and other disorders, histone profiles of relevance to RTT, and genotype-phenotype correlations in RTT, we update here our synaptic hypothesis of RTT. We postulate that MeCP2 dysfunction leads to abnormal brain development through maladjustment of neuronal gene expression to synaptic and other extra-cellular signals, mainly during the critical period of synaptic maturation. RTT phenotype will develop, only if severe MeCP2 dysfunction is present during early neuronal differentiation. Two models are proposed for explaining general and regional neuronal abnormalities in RTT and the phenotypical outcome of MeCP2 dysfunction, respectively.


Quality and Characteristics of 4241 Case Reports of Lactic Acidosis in Metformin Users Reported to a Large Pharmacovigilance Database.
Metformin-associated lactic acidosis (MaLA) occurs rarely and is thus difficult to study. We analysed 4241 individual case safety reports of lactic acidosis (LA) that implicated metformin as a suspected drug reported to the pharmacovigilance database of Merck KGaA, Darmstadt, Germany. The primary objective was to review reports for quality and completeness of data to support diagnoses of MaLA. We also explored the correlations between reported biomarkers, and associations between biomarkers and outcomes. Records were analysed for completeness in supporting diagnoses of LA or metformin-associated LA (MaLA), against commonly used diagnostic criteria. Correlations between indices of exposure to metformin and biomarkers of LA and mortality were investigated. Missing data was common, especially for plasma metformin. Clinical/biomarker evidence supported a diagnosis of LA in only 33% of cases (LA subpopulation) and of MaLA in only 9% (MaLA subpopulation). The metformin plasma level correlated weakly with plasma lactate (positive) and pH (negative). About one-fifth (21.9%) of cases reported a fatal outcome. Metformin exposure (plasma level or dose) was not associated with increased mortality risk (there was a suggestion of decreased risk at higher levels of exposure to metformin). Plasma lactate was the only variable associated with increased risk of mortality. Examination of concomitant risk factors for MaLA identified renal dysfunction (including of iatrogenic origin) as a potential driver of mortality in this population. Despite the high frequency of missing data, this is the largest analysis of cases of MaLA supported by measurements of circulating metformin, and lactate, and pH, to date. Plasma lactate, and not metformin dose or plasma level, appeared to be the main driver of mortality in the setting of LA or MaLA. Further research with more complete case reports is required.


Maximizing Electroactive Sites in a Three-Dimensional Covalent Organic Framework for Significantly Improved Carbon Dioxide Reduction Electrocatalysis.
Synthesis of functional 3D COFs with irreversible bond is challenging. Herein, 3D imide-bonded COFs were constructed via the imidization reaction between phthalocyanine-based tetraanhydride and 1,3,5,7-tetra(4-aminophenyl)adamantine. These two 3D COFs are made up of interpenetrated pts networks according to powder X-ray diffraction and gas adsorption analyses. CoPc-PI-COF-3 doped with carbon black has been employed to fabricate the electrocatalytic cathode towards CO2 reduction reaction within KHCO3 aqueous solution, displaying the Faradaic efficiency of 88-96 % for the CO2 -to-CO conversion at the voltage range of ca. -0.60 to -1.00 V (vs. RHE). In particular, the 3D porous structure of CoPc-PI-COF-3 enables the active electrocatalytic centers occupying 32.7 % of total cobalt-phthalocyanine subunits, thus giving a large current density (jCO ) of -31.7 mA cm-2 at -0.90 V. These two parameters are significantly improved than the excellent 2D COF analogue (CoPc-PI-COF-1, 5.1 % and -21.2 mA cm-2 ).


Aziridine biotransformation by microsomes and lethality to hepatocytes isolated from rat.
To clarify the relationship of aziridine biotransformation to their cytotoxic activities, the metabolism of optical isomers of typical cytotoxic and non-cytotoxic aziridines was studied in isolated hepatocytes, rat liver microsomes, mitochondria and L-1210 mouse leukemia cells. Cytotoxic 1-methyl-2-beta-naphthylaziridine (NAZ) gave nitrosomethane as one of the bioactivation products in isolated hepatocytes and simultaneously induced a marked decrease in cellular ATP followed by cell lethality. NAZ itself did not directly affect the respiratory function of mitochondria in isolated hepatocytes or in buffer solution, however, it inhibited the mitochondrial activity in the presence of microsomes in the buffer solution. Nitroso-t-butane or nitrosomethane dimer, used as a substitute for extremely labile nitrosomethane, strongly inhibited the respiration of mitochondria. On the other hand, optical isomers of 2-aziridinecarboxylic acid (AZC) which did not give nitrosomethane in isolated hepatocytes or microsomes also did not show cytotoxicity. Thus, the cytotoxicity of NAZ seems to be induced by bioactivation via cellular oxidases with the nitrosomethane generated being a major toxic component. This may occur with most of the cytotoxic aziridine derivatives.


Scytalidium thermophilum-colonized grain, corncobs and chopped wheat straw substrates for the production of Agaricus bisporus.
We examined the possibility of cultivating Agaricus bisporus (Ab) on various grains and agricultural by-products, with the objective of improving yield capacity of substrate pre-colonized by Scytalidium thermophilum (St). Radial growth rate (RGR) of St at 45 degrees C ranged from no growth on sterile wheat grain to 14.9 mm/d on whole oats. The linear extension rate (LER) of Ab, grown on St-colonized substrate (4 days at 45 degrees C), ranged from a low of 2.7 mm/d on 100% corncobs to 4.7 mm/d on a 50/50 mixture of ground corncobs/millet grain. Several other substrates containing wheat straw+ground corncobs+boiled millet and pre-colonized by St (4 days at 42+/-3 degrees C), were evaluated for production of Ab. The biological efficiency (BE) of production increased linearly with the addition of millet to the formula. However, substrates with millet levels 84% often were contaminated before mushroom harvest. Maximum BE (99%) and yield (21.6 kg/m(2)) were obtained on St-colonized wheat straw+2% hydrated lime supplemented with 9% commercial supplement added both at spawning and at casing.