Reduced performance difference between sexes in master mountain and city marathon running.
The performance in master marathoners has been investigated in flat city marathons but not in mountain marathons. This study examined changes in the sex differences in performance across time in female and male master runners competing in a mountain marathon compared to a flat city marathon. The association between age and performance of finishers in the Jungfrau Marathon, Switzerland, with 1830 meter changes in altitude and a flat city marathon (Lausanne Marathon), Switzerland, were analyzed from 2000 to 2011. In both events, athletes in the 35-44 years age group showed the highest number of finishers. In the mountain marathon, the number of female master runners aged > 35 years increased in contrast to female finishers aged < 35 years, while the number of male finishers was unchanged in all age groups. In the city marathon, the number of female finishers was unchanged while the number of male finishers in the age groups for 25-34-year-olds and 35-44-year-olds decreased. In female marathoners, performance improved in athletes aged 35-44 and 55-64 years in the city marathon. Male marathoners improved race time in age group 45-54 years in both the city marathon and the mountain marathon. Female master runners reduced the sex difference in performance in the 45-54-year age group in both competitions and in the 35-44-year age group in the mountain marathon. The sex difference in performance decreased in the 35-44-year age group from 19.1% ± 4.7% to 16.6% ± 1.9% in the mountain marathon (r(2) = 0.39, P = 0.03). In age groups 45-54 years, the sex difference decreased from 23.4% ± 1.9% to 15.9% ± 6.1% in the mountain marathon (r(2) = 0.39, P < 0.01) and from 34.7% ± 4.6% to 11.8% ± 6.2% in the city marathon (r(2) = 0.39, P < 0.01). These findings suggest that female master runners aged 35-54 years reduced sex differences in their performance in both mountain and city marathon running.


Characteristics of perinatal depression in rural central, India: a cross-sectional study.
Perinatal depression is associated with negative effects on child behavioural, cognitive and emotional development, birth outcomes, and physical growth. In India, increased priority accorded to mental health programs mean it is now possible to reduce the population-level burden of perinatal depression. In this secondary analysis of two studies, we aimed to describe the epidemiological features of depression among community- and facility-based samples of perinatal women from rural central India, and to describe the help-seeking behaviours from those women who screened positive for depression. The Community Study was a multi-round population-based cross-sectional survey (n = 6087). The Facility Study was a multi-round facility-based cross-sectional survey (n = 1577). Both studies were conducted in Sehore District, Madhya Pradesh between 2013 and 2017. Field workers conducted structured interviews with perinatal women. The questionnaire had sections relating to sociodemographic characteristics, depression screening using the Patient's Health Questionnaire (PHQ9), treatment seeking for depression-related symptoms, and disability. Using data pooled from both studies, we tested each characteristic for association with the total screening score and with screening positive for depression. We identified 224 perinatal women from the Community Study and 130 perinatal women from the Facility Study, of whom 8.8% and 18.5% screened positive for depression, respectively. For the continuous PHQ9 score, there was evidence of a "U" shaped association with age, and positive associations with pregnancy, disability score, suicidality and being a health facility attendee. For the binary PHQ9 score, there was evidence of positive associations with pregnancy, disability score, suicidality and being a health facility attendee. This study highlights where the largest population-level variations in perinatal depression symptoms are present in this Indian sample, for which mental health service provision should be made a priority. Epidemiological evidence generated by this study, as well as new evidence on peer-delivered interventions for perinatal depression, must be utilized by policy-makers to prioritize mental health services for mothers along with maternal and child health services.


Platelet-to-lymphocyte ratio but not neutrophil-to-lymphocyte ratio predicts high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndrome.
Dual antiplatelet therapy (DAPT), consisting of clopidogrel and aspirin, is the main-stay treatment of acute coronary syndromes (ACS). However, major adverse cardiovascular events may occur even in patients undergoing DAPT, and this has been related to the variable pharmacodynamic efficacy of these drugs, especially clopidogrel. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers for cardiovascular risk stratification, which may reflect an inflammatory state and thus high on-treatment platelet reactivity (HPR). We investigated the usefulness of PLR and NLR in predicting HPR in clopidogrel-treated patients with ACS. A total of 244 patients were enrolled in this study, and 43 of them were nonresponsive to clopidogrel. Logistic regression analysis indicated that PLR was significantly associated with HPR (P < 0.001). Using a cutoff level of 331, PLR predicted HPR with a sensitivity of 73% and a specificity of 69% (odds ratio: 376.15, 95% confidence interval = 37.813-3741.728 P < 0.001, receiver operating characteristic curve: 0.885). We suggest that more attention should be paid to the PLR values of these patients on admission to identify individuals who may not benefit from clopidogrel during the course of ACS.


[Radionuclide cisternography in the late period of penetrating cranio-cerebral wounds].
An analysis of the radiological signs is presented proceeding from the results of examination of the visualization of the CSF tract in 123 patients in whom radionuclide cisternography with 99mTc-DTPA was performed 1,3,6 and 24 h after administration of a radiopharmaceutical. The radiological appearance of pathology of the CSF system in a long-term period after penetrating craniocerebral wound was developed.


Noninvasive evaluation of coronary flow velocity reserve in homozygous familial hypercholesterolemia by transthoracic Doppler echocardiography.
To evaluate the value of transthoracic Doppler echocardiography (TTDE) of the left anterior descending coronary for the detection of early abnormalities of coronary arteries in asymptomatic patients with homozygous familial hypercholesterolemia (HoFH). Seventeen asymptomatic patients with HoFH and 10 controls had plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides measured and underwent TTDE of their left coronary descending artery to determine peak and mean flow velocities under basal conditions and under hyperemia induced by adenosine infusion. Coronary flow velocity reserve (CFVR) was calculated from the mean flow velocities. The presence of aortic supravalvular stenosis was also determined from supravalvular flow velocity and aortic valve thickening values. HoFH patients had similar basal but significantly lower hyperemic flow velocities and CFVR than control patients. Eight of the 17 HoFH patients had supravalvular aortic stenosis, and these patients had significantly higher LDL cholesterol and lower CFVR than those without this stenosis. Treatment with lipid-lowering drugs lowered lipid levels and increased CFVR values, but neither of these parameters reached normal values. TTDE is a suitable noninvasive technique to detect early abnormalities of coronary arteries and to monitor the clinical efficacy of lipid-lowering treatment in asymptomatic HoFH patients.


Variations of Sexual Scripts Relating to Concurrency by Race, Class, and Gender in South Africa.
It is unclear whether higher rates of sexual partner concurrency in Black South Africans are due to socioeconomic or cultural factors. We used a nationally representative sample of 9,728 individuals aged 16 to 55 from a study conducted in 2009 to examine how the norms pertaining to concurrency and the practice of concurrency vary by race, class, and gender. The percentage of men reporting point concurrency was 14%, 6.5%, and 2.5% in Blacks, coloreds, and Whites, respectively (p < 0.001). These percentages increased to 45.7%, 24.7%, and 11.7%, respectively, for those reporting lifetime concurrency (p < 0.001). In all the racial groups, men exhibited more favorable attitudes toward concurrency than women did. For a range of indicators, White men and women had less favorable attitudes toward concurrency than Black men and women. These differences remained after controlling for a range of confounding variables. In the adjusted logistic regression model, reported concurrency in men was associated with a younger age, Black race, being in the lowest income tertile, not being in a stable relationship, and expressing various positive attitudes toward concurrency.


Learning Impact of a Virtual Brain Electrical Activity Simulator Among Neurophysiology Students: Mixed-Methods Intervention Study.
Virtual simulation is the re-creation of reality depicted on a computer screen. It offers the possibility to exercise motor and psychomotor skills. In biomedical and medical education, there is an attempt to find new ways to support students' learning in neurophysiology. Traditionally, recording electroencephalography (EEG) has been learned through practical hands-on exercises. To date, virtual simulations of EEG measurements have not been used. This study aimed to examine the development of students' theoretical knowledge and practical skills in the EEG measurement when using a virtual EEG simulator in biomedical laboratory science in the context of a neurophysiology course. A computer-based EEG simulator was created. The simulator allowed virtual electrode placement and EEG graph interpretation. The usefulness of the simulator for learning EEG measurement was tested with 35 participants randomly divided into three equal groups. Group 1 (experimental group 1) used the simulator with fuzzy feedback, group 2 (experimental group 2) used the simulator with exact feedback, and group 3 (control group) did not use a simulator. The study comprised pre- and posttests on theoretical knowledge and practical hands-on evaluation of EEG electrode placement. The Wilcoxon signed-rank test indicated that the two groups that utilized a computer-based electrode placement simulator showed significant improvement in both theoretical knowledge (Z=1.79, P=.074) and observed practical skills compared with the group that studied without a simulator. Learning electrode placement using a simulator enhances students' ability to place electrodes and, in combination with practical hands-on training, increases their understanding of EEG measurement.


Rapid assessment of changes in phage bioactivity using dynamic light scattering.
Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity. We then use DLS to optimize phage storage conditions for phages from human clinical trials, predict bioactivity in 50-year-old archival stocks, and evaluate phage samples for use in a phage therapy/wound infection model. We also provide a web-application (Phage-ELF) to facilitate DLS studies of phages. We conclude that DLS provides a rapid, convenient, and non-destructive tool for quality control of phage preparations in academic and commercial settings.


Protein intake and lumbar bone density: the Multi-Ethnic Study of Atherosclerosis (MESA).
Dietary protein has been shown to increase urinary Ca excretion in randomised controlled trials, and diets high in protein may have detrimental effects on bone health; however, studies examining the relationship between dietary protein and bone health have conflicting results. In the present study, we examined the relationship between dietary protein (total, animal and vegetable protein) and lumbar spine trabecular volumetric bone mineral density (vBMD) among participants enrolled in the Multi-Ethnic Study of Atherosclerosis (n 1658). Protein intake was assessed using a FFQ obtained at baseline examination (2000-2). Lumbar spine vBMD was measured using quantitative computed tomography (2002-5), on average 3 years later. Multivariable linear and robust regression techniques were used to examine the associations between dietary protein and vBMD. Sex and race/ethnicity jointly modified the association of dietary protein with vBMD (P for interaction = 0·03). Among white women, higher vegetable protein intake was associated with higher vBMD (P for trend = 0·03), after adjustment for age, BMI, physical activity, alcohol consumption, current smoking, educational level, hormone therapy use, menopause and additional dietary factors. There were no consistently significant associations for total and animal protein intakes among white women or other sex and racial/ethnic groups. In conclusion, data from the present large, multi-ethnic, population-based study suggest that a higher level of protein intake, when substituted for fat, is not associated with poor bone health. Differences in the relationship between protein source and race/ethnicity of study populations may in part explain the inconsistent findings reported previously.


Early Recoil After Balloon Angioplasty of Erection-Related Arteries in Patients With Arteriogenic Erectile Dysfunction.
To evaluate the incidence of elastic recoil in patients presenting with erectile dysfunction (ED) undergoing endovascular revascularization of the pudendal or penile arteries. A consecutive series of 21 ED patients (mean age 58.3±9.3 years) undergoing minimally invasive revascularization of 31 arteries was analyzed. ED lesions included the pudendal arteries (n=27) and the penile artery (n=4). Mean lesion length was 20.6±13.9 mm. Minimal lumen diameter (MLD) measurements were assessed at baseline, immediately after balloon angioplasty, and 10 minutes thereafter. Early recoil was defined as an MLD reduction >10%. Elastic recoil with >10% lumen compromise was treated with drug-coated balloons, while severe elastic recoil (>30%) required drug-eluting stents (DES). The International Index of Erectile Function (IIEF-15) score was obtained prior to and 3 months after the procedure to obtain information on functional outcomes subsequent to angioplasty. Mean MLD at baseline was 0.9±0.6 mm, which improved to 2.0±0.9 mm immediately after balloon dilation. At 10 minutes after dilation, the MLD was 1.7±1.0 mm. Elastic recoil was observed in all 31 lesions and resulted in a mean lumen compromise of 21.2%. Severe (>30%) recoil was observed in 14 arteries, which underwent DES therapy. The IIEF-15 score improved from 31.3±11.2 at baseline to 49.8±16.8 (p<0.001) at the 3-month follow-up. Endovascular revascularization constitutes a safe and feasible treatment modality to restore erectile function in patients with arteriogenic ED and ineffective conservative management. Early elastic recoil is very frequent subsequent to balloon dilation of small-caliber erection-related arteries. Thus, mechanical scaffolding with DES is required in a high subset of ED patients to provide favorable early angiographic and clinical results.


Racial disparities in involuntary outpatient commitment: are they real?
In this paper we explore racial disparities in outpatient civil commitment, using data from Kendra's Law in New York State. Overall, African Americans are more likely than whites to be involuntarily committed for outpatient psychiatric care in New York. However, candidates for outpatient commitment are largely drawn from a population in which blacks are overrepresented: psychiatric patients with multiple involuntary hospitalizations in public facilities. Whether this overrepresentation under court-ordered outpatient treatment is unfair depends on one's view: is it access to treatment and a less restrictive alternative to hospitalization, or a coercive deprivation of personal liberty?


A new plasmid cloning vector for direct detection of recombinant clones, based on inactivation of a bacterial acid phosphatase-encoding gene.
A new plasmid cloning vector for Escherichia coli (pPhoR) suitable for direct detection of recombinant clones has been constructed. The plasmid is a multicopy of a vector which carries a pUC-derived origin of replication and beta-lactamase gene, and the phoN acid phosphatase-encoding gene from Providencia stuartii. Foreign DNA fragments can be cloned into unique restriction sites located within the phoN gene causing a loss of the acid phosphatase activity which is normally overproduced by E. coli strains carrying pPhoR. Since PhoN production can be easily detected by a plate histochemical assay, recombinant clones carrying foreign DNA fragments inserted in the phoN gene can be easily detected as PhoN-negative clolonies on the above medium. The efficiency of the pPhoR-based cloning system for direct cloning of PCR amplimers of a variable region of the HIV-1 genome was comparable to that of conventional cloning systems for direct detection of recombinant based on beta-galactosidase inactivation. Advantage of the pPho-R-based system include reduced costs for histochemical assays and the possibility of being used with any E. coli host.


MICROSCOPE Mission: First Constraints on the Violation of the Weak Equivalence Principle by a Light Scalar Dilaton.
The existence of a light or massive scalar field with a coupling to matter weaker than gravitational strength is a possible source of violation of the weak equivalence principle. We use the first results on the Eötvös parameter by the MICROSCOPE experiment to set new constraints on such scalar fields. For a massive scalar field of mass smaller than 10^{-12} eV (i.e., range larger than a few 10^{5} m), we improve existing constraints by one order of magnitude to |α|<10^{-11} if the scalar field couples to the baryon number and to |α|<10^{-12} if the scalar field couples to the difference between the baryon and the lepton numbers. We also consider a model describing the coupling of a generic dilaton to the standard matter fields with five parameters, for a light field: We find that, for masses smaller than 10^{-12} eV, the constraints on the dilaton coupling parameters are improved by one order of magnitude compared to previous equivalence principle tests.


Extended-spectrum beta-lactamase-producing Gram-negative bacteria causing neonatal sepsis in India in rural and urban settings.
Extended-spectrum β-lactamase (ESBL)-producing Gram-negative bacilli (GNB) are of increasing clinical concern in all age groups worldwide. Whilst sepsis continues to be the leading cause of morbidity and mortality in Indian neonates in the community, identification of microbiological attributes in this population is lacking. This population-based study enrolled 1738 infants with a diagnosis of clinical sepsis at four participating centres in India. Each study site conducted Bactec blood culture, identified bacterial species by API test and stored isolates at -70 °C. From 252 GNB isolates, 155 (113 Klebsiella species, 21 Escherichia coli and 21 other) were subjected to drug susceptibility testing, ESBL phenotyping and testing for clonal relatedness of ESBL strains by PFGE. The results demonstrated that Klebsiella species and E. coli are the most common GNB causes of neonatal sepsis in India, and over one-third are ESBL producers in both community and hospital settings. ESBL-producing strains exhibited frequent co-resistance to aminoglycosides and ciprofloxacin, but remained susceptible to imipenem. PFGE analysis revealed extensive genetic diversity within the ESBL-producing isolates, showing multiple profiles (total of 23). Over 40% of all ESBL-producing isolates formed three pulsed-field profiles (PFP I-III), with PFP-II being the largest cluster (>20% of all ESBL-producing isolates), sharing strains from two distant locations. Identification of a common clone at two geographically distant centres indicated that predominant clones with increased virulence may exist, even in the absence of any clear outbreak. The presence of ESBL-producing strains in community infants with no prior history of hospitalization or antibiotic use dictates heightened vigilance and further studies on the ecology of these organisms.


Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency.
We report two newborns with female external genitalia and bilateral inguinal swelling who were diagnosed with 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low testosterone/androstenedione ratios (0.22 and 0.24, respectively; normal, >0.8) after human chorionic gonadotropin stimulation indicated 17β-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozygous novel mutation (c.464A>C, p.H155P) in exon 6 in the first case and homozygous c.239G>A (p.R80Q) in exon 3 in the second.


O2 and Water Migration Pathways between the Solvent and Heme Pockets of Hemoglobin with Open and Closed Conformations of the Distal HisE7.
Hemoglobin transports O2 by binding the gas at its four hemes. Hydrogen bonding between the distal histidine (HisE7) and heme-bound O2 significantly increases the affinity of human hemoglobin (HbA) for this ligand. HisE7 is also proposed to regulate the release of O2 to the solvent via a transient E7 channel. To reveal the O2 escape routes controlled by HisE7 and to evaluate its role in gating heme access, we compare simulations of O2 diffusion from the distal heme pockets of the T and R states of HbA performed with HisE7 in its open (protonated) and closed (neutral) conformations. Irrespective of HisE7's conformation, we observe the same four or five escape routes leading directly from the α- or β-distal heme pockets to the solvent. Only 21-53% of O2 escapes occur via these routes, with the remainder escaping through routes that encompass multiple internal cavities in HbA. The conformation of the distal HisE7 controls the escape of O2 from the heme by altering the distal pocket architecture in a pH-dependent manner, not by gating the E7 channel. Removal of the HisE7 side chain in the GlyE7 variant exposes the distal pockets to the solvent, and the percentage of O2 escapes to the solvent directly from the α- or β-distal pockets of the mutant increases to 70-88%. In contrast to O2, the dominant water route from the bulk solvent is gated by HisE7 because protonation and opening of this residue dramatically increase the rate of influx of water into the empty distal heme pockets. The occupancy of the distal heme site by a water molecule, which functions as an additional nonprotein barrier to binding of the ligand to the heme, is also controlled by HisE7. Overall, analysis of gas and water diffusion routes in the subunits of HbA and its GlyE7 variant sheds light on the contribution of distal HisE7 in controlling polar and nonpolar ligand movement between the solvent and the hemes.


Corrosion resistant three-dimensional nanotextured silicon for water photo-oxidation.
We demonstrate the ability to chemically transform bulk silicon into a nanotextured surface that exhibits excellent electrochemical stability in aqueous conditions for water photo-oxidation. Conformal defective graphene coatings on nanotextured silicon formed by thermal treatment enable over 50× corrosion resistance in aqueous electrolytes based upon Tafel analysis and impedance spectroscopy. This enables nanotextured silicon as an effective oxygen-evolution photoanode for water splitting with saturation current density measured near 35 mA cm(-2) under 100 mW cm(-2) (1 sun) illumination. Our approach builds upon simple and scalable processing techniques with silicon to develop corrosion resistant electrodes that can benefit a broad range of catalytic and photocatalytic applications.


Helper factor(s) generated by tumor-immune rats for lymphoproliferative responses to syngeneic tumor cells.
New Zealand Black ( NBR ) rats that are innately immune to challenge with a syngeneic 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced fibrosarcoma have spleen cells that produce helper effects for in vitro lymphoproliferative responses in the presence of individual MCA-induced fibrosarcoma cells. Spleen cells from MCA-induced fibrosarcoma progressor rats (which lack innate tumor immunity) do not produce demonstrable helper activity. Supernatants from 48-hour cocultures of spleen cells from tumor-immune (TI) rats and syngeneic MCA-induced fibrosarcoma cells replaced the spleen cell helper activity. Comparable spleen cell supernatants from tumor progressor rats or unchallenged rats (controls) as well as supernatants from MCA-induced fibrosarcoma cells cultured alone did not produce any helper factor activity. Supernatants from TI rat spleen cells following inoculation with MCA-induced fibrosarcoma cells did not affect lymphoproliferative responses of NBR spleen cells induced by concanavalin A or alloantigens. The supernatants also did not contain detectable interleukin 2 activity as determined with the use of the thymocyte costimulator assay. These data indicate that the production of soluble helper factors by TI rat spleen cells may be involved in the augmentation of a protective host antitumor response.


Effect of fatigue on knee kinetics and kinematics in stop-jump tasks.
Altered motor control strategies in landing and jumping maneuvers are a potential mechanism of noncontact anterior cruciate ligament injury. There are biomechanical differences between male and female athletes in the landing phase of stop-jump tasks. Fatigue is a risk factor in musculoskeletal injuries. Lower extremity muscle fatigue alters the knee kinetics and kinematics during the landing phase of 3 stop-jump tasks and increases an athlete's risk of anterior cruciate ligament injury. Controlled laboratory study. Three-dimensional videography and force plate data were collected for 20 recreational athletes (10 male and 10 female athletes) performing 3 stop-jump tasks before and after completing a fatigue exercise. Knee joint angles and resultant forces and moments were calculated. Both male and female subjects had significantly increased peak proximal tibial anterior shear forces (P = .01), increased valgus moments (P = .03), and decreased knee flexion angles (P = .03) during landings of all 3 stop-jump tasks when fatigued. Fatigue did not significantly affect the peak knee extension moment for male or female athletes. Fatigued recreational athletes demonstrate altered motor control strategies, which may increase anterior tibial shear force, strain on the anterior cruciate ligament, and risk of injury for both female and male subjects. CLINIC RELEVANCE: Fatigued athletes may have an increased risk of noncontact anterior cruciate ligament injury.


Determinants of disabling foot pain in retirement village residents.
The aim of this study was to evaluate the relative contribution of structural foot characteristics and comorbidities to the presence of disabling foot pain in older people. One hundred seventy-two people (55 men and 117 women) aged 62 to 96 years (mean +/- SD, 80.1 +/- 6.4 years) who lived in a retirement village underwent tests of foot posture, range of motion, and deformity in addition to completing a medical history questionnaire. Disabling foot pain was determined using the Manchester Foot Pain and Disability Index. Thirty-eight subjects (22%) reported disabling foot pain. Subjects with disabling foot pain had a higher body mass index and were more likely to be female; to report osteoarthritis in the spine, hips, hands or wrists, and feet; and to report pain in the back, hips, and hands or wrists. The only significant difference between the groups regarding structural foot characteristics was that those with disabling foot pain exhibited more severe hallux valgus deformity. The strongest determinants of disabling foot pain revealed by a discriminant function analysis were foot osteoarthritis, pain in the hips, and pain in the hands or wrists. These findings indicate that disabling foot pain in older people is more closely related to pain and osteoarthritis in other body regions than to structural characteristics of the foot, and they suggest that more severe forms of foot pain in older people may be a component of a general chronic pain syndrome or a polyarticular form of osteoarthritis.


Re-assessment of plant carbon dynamics at the Duke free-air CO(2) enrichment site: interactions of atmospheric [CO(2)] with nitrogen and water availability over stand development.
*The potential for elevated [CO(2)]-induced changes to plant carbon (C) storage, through modifications in plant production and allocation of C among plant pools, is an important source of uncertainty when predicting future forest function. Utilizing 10 yr of data from the Duke free-air CO(2) enrichment site, we evaluated the dynamics and distribution of plant C. *Discrepancy between heights measured for this study and previously calculated heights required revision of earlier allometrically based biomass determinations, resulting in higher (up to 50%) estimates of standing biomass and net primary productivity than previous assessments. *Generally, elevated [CO(2)] caused sustained increases in plant biomass production and in standing C, but did not affect the partitioning of C among plant biomass pools. Spatial variation in net primary productivity and its [CO(2)]-induced enhancement was controlled primarily by N availability, with the difference between precipitation and potential evapotranspiration explaining most interannual variability. Consequently, [CO(2)]-induced net primary productivity enhancement ranged from 22 to 30% in different plots and years. *Through quantifying the effects of nutrient and water availability on the forest productivity response to elevated [CO(2)], we show that net primary productivity enhancement by elevated [CO(2)] is not uniform, but rather highly dependent on the availability of other growth resources.


Socioeconomic environment and disparities in cancer survival for 19 solid tumor sites: An analysis of the French Network of Cancer Registries (FRANCIM) data.
Social inequalities are concerning along the cancer continuum. In France, social gradient in health is particularly marked but little is known about social gradient in cancer survival. We aimed to investigate the influence of socioeconomic environment on cancer survival, for all cancers reported in the French Network of Cancer Registries. We analyzed 189,657 solid tumors diagnosed between 2006 and 2009, recorded in 18 registries. The European Deprivation Index (EDI), an ecological index measuring relative poverty in small geographic areas, assessed social environment. The EDI was categorized into quintiles of the national distribution. One- and five-year age-standardized net survival (ASNS) were estimated for each solid tumor site and deprivation quintile, among men and among women. We found that 5-year ASNS was lower among patients living in the most deprived areas compared to those living in the least deprived ones for 14/16 cancers among men and 16/18 cancers among women. The extent of cancer survival disparities according to deprivation varied substantially across the cancer sites. The reduction in ASNS between the least and the most deprived quintile reached 34% for liver cancer among men and 59% for bile duct cancer among women. For pancreas, stomach and esophagus cancer (among men), and ovary and stomach cancer (among women), deprivation gaps were larger at 1-year than 5-year survival. In conclusion, survival was worse in the most deprived areas for almost all cancers. Our results from population-based cancer registries data highlight the need for implementing actions to reduce social inequalities in cancer survival in France.


Crystallographic insights into the pore structures and mechanisms of the EutL and EutM shell proteins of the ethanolamine-utilizing microcompartment of Escherichia coli.
The ethanolamine-utilizing bacterial microcompartment (Eut-BMC) of Escherichia coli is a polyhedral organelle that harbors specific enzymes for the catabolic degradation of ethanolamine. The compartment is composed of a proteinaceous shell structure that maintains a highly specialized environment for the biochemical reactions inside. Recent structural investigations have revealed hexagonal assemblies of shell proteins that form a tightly packed two-dimensional lattice that is likely to function as a selectively permeable protein membrane, wherein small channels are thought to permit controlled exchange of specific solutes. Here, we show with two nonisomorphous crystal structures that EutM also forms a two-dimensional protein membrane. As its architecture is highly similar to the membrane structure of EutL, it is likely that the structure represents a physiologically relevant form. Thus far, of all Eut proteins, only EutM and EutL have been shown to form such proteinaceous membranes. Despite their similar architectures, however, both proteins exhibit dramatically different pore structures. In contrast to EutL, the pore of EutM appears to be positively charged, indicating specificity for different solutes. Furthermore, we also show that the central pore structure of the EutL shell protein can be triggered to open specifically upon exposure to zinc ions, suggesting a specific gating mechanism.


Modelling the effects of copper on soil organisms and processes using the free ion approach: towards a multi-species toxicity model.
The free ion approach has been previously used to calculate critical limit concentrations for soil metals based on point estimates of toxicity. Here, the approach was applied to dose-response data for copper effects on seven biological endpoints in each of 19 European soils. The approach was applied using the concept of an effective dose, comprising a function of the concentrations of free copper and 'protective' major cations, including H(+). A significant influence of H(+) on the toxicity of Cu(2+) was found, while the effects of other cations were inconsistent. The model could be generalised by forcing the effect of H(+) and the slope of the dose-response relationship to be equal for all endpoints. This suggests the possibility of a general bioavailability model for copper effects on organisms. Furthermore, the possibility of such a model could be explored for other cationic metals such as nickel, zinc, cadmium and lead.


Functional variability in the flight phase of one metre springboard forward dives.
In springboard diving, low variability in takeoff conditions and in the somersault orientation angle at water entry is to be expected since consistency and accuracy are necessary for a good dive. A diver's adjustment of body configuration during flight may be a deliberate compensation for variations in takeoff conditions, leading to increased joint angle variability and decreased entry angle variability. The aim of this research was to investigate the extent to which a diver pre-plans the aerial phase and then makes adjustments in flight to control the entry angle in one metre springboard forward dives. Performances of 15 forward pike dives and 15 forward 2½ somersault pike dives, performed by an international diver were video recorded at 250 Hz. Joint centres during flight were digitized and their spatial coordinates were subsequently reconstructed using the Direct Linear Transformation in order to determine orientation and configuration angles. A computer simulation model was used to investigate the effects of variability in takeoff conditions and configuration variability in flight on the variability of the orientation angle at water entry. The amount of variation in the somersault orientation angle at entry as determined using simulations based on the variability in the takeoff conditions was four times greater than the variation in the recorded performances. It was concluded that the diver used open loop control for the first half of the flight phase and subsequently used feedforward and feedback control to make timing adjustments of hip and arm angles to reduce the variability of his entry orientation angle.


Antarctobacter heliothermus gen. nov., sp. nov., a budding bacterium from hypersaline and heliothermal Ekho Lake.
Four Gram-negative, aerobic, pointed and budding bacteria were isolated from various depths of the hypersaline, heliothermal and meromictic Ekho Lake (Vestfold Hills, East Antarctica). The cells contained storage granules and formed rosettes. Daughter cells may be motile. Growth required sodium ions. Nitrate was reduced to nitrite, and dissimilatory reduction of nitrite was possible. DNase and gelatinase were produced. Glutamate was metabolized with and without an additional source of combined nitrogen. The most abundant fatty acid was C18:1; other fatty acids present in lower concentrations were C12:1 3-OH, C16:1, C16:0, C18:0 and C19:0 cyc. The main polar lipids were phosphatidylglycerol and phosphatidylcholine. The DNA base composition was 62.3-62.8 mol% G + C. 16S rDNA sequence comparisons showed the isolates to be phylogenetically related to the genera Sagittula and Roseobacter. Morphological, physiological and genotypic differences to these and distinct characteristics supported the description of a new genus and a new species, Antarctobacter heliothermus gen. nov., sp. nov. The type strain is EL-219T (= DSM 11445T).


[Duodenal angiodysplasia and Turner's syndrome. Case report].
The Turner's syndrome is the most common chromosomic disease in the women and touches 1:2,500 women born live. The most important anomaly is the presence of short stature and ovarian failure. Others disorders are increasing in case reports: osteoporosis, hypothyroidism, renal diseases and gastroenteric diseases. The Authors, after careful review of the literature, that proves rarity of the disease, report a case of duodenal vascular anomaly associated with Turner's syndrome and describe surgical therapy, peculiar to this atypical localization. A 31 years old woman, genotypic XO and female phenotypic, with diabetes mellitus type I, arterial hypertension and hypertransaminasemia. Since three days the patient reports epigastric pain discontinuous, not widespread, not nocturnal, with wretch, bowel open only to gas. The patient underwent Rx abdomen, Rx with gastrografin, TC abdomen. Diagnosed as a high digestive occlusion, the patient underwent explorative laparotomy. As laparotomy she had a necrotic-hemorrhagic lesion in duodenum D3-D4 and first jejunal loop, with stenosis of the jejunal lumen, perforation of serosa and blood in peritoneal cavity. Resection of necrotic loop and reconstruction with Y loop performing manual duodenum jejunal L-L anastomosis, mechanical gastroenterostomy and enteric-enteric L-L mechanical anastomosis. After operation hemorrhage from anastomosis was observed, treated with omeprazole therapy and total parenteral nutrition. The patient was discharged in 14th p. o. day. After two years she is in good health without gastrointestinal symptoms. In patients with Turner's syndrome gastrointestinal vascular anomalies have to be considered as diagnostic hypothesis in cause of abdominal pain.


Direct interaction of eag domains and cyclic nucleotide-binding homology domains regulate deactivation gating in hERG channels.
Human ether-á-go-go (eag)-related gene (hERG) potassium channels play a critical role in cardiac repolarization and are characterized by unusually slow closing (deactivation) kinetics. The N-terminal "eag" domain and a C-terminal C-linker/cyclic nucleotide-binding homology domain (CNBHD) are required for regulation of slow deactivation. The region between the S4 and S5 transmembrane domains (S4-S5 linker) is also implicated in this process, but the mechanism for regulation of slow deactivation is unclear. Here, using an eag domain-deleted channel (hERG Δeag) fused to Citrine fluorescent protein, we found that most channels bearing individual alanine mutations in the S4-S5 linker were directly regulated by recombinant eag domains fused to a cyan fluorescent protein (N-eag-CFP) and had robust Förster resonance energy transfer (FRET). Additionally, a channel bearing a group of eight alanine residues in the S4-S5 linker was not measurably regulated by N-eag-CFP domains, but robust FRET was measured. These findings demonstrate that the eag domain associated with all of the S4-S5 linker mutant channels. In contrast, channels that also lacked the CNBHD (hERG Δeag ΔCNBHD-Citrine) were not measurably regulated by N-eag-CFP nor was FRET detected, suggesting that the C-linker/CNBHD was required for eag domains to directly associate with the channel. In a FRET hybridization assay, N-eag-CFP had robust FRET with a C-linker/CNBHD-Citrine, suggesting a direct and specific interaction between the eag domain and the C-linker/CNBHD. Lastly, coexpression of a hERG subunit lacking the CNBHD and the distal C-terminal region (hERG ΔpCT-Citrine) with hERG Δeag-CFP subunits had FRET and partial restoration of slow deactivation. Collectively, these findings reveal that the C-linker/CNBHD, but not the S4-S5 linker, was necessary for the eag domain to associate with the channel, that the eag domain and the C-linker/CNBHD were sufficient for a direct interaction, and that an intersubunit interaction between the eag domain and the C-linker/CNBHD regulated slow deactivation in hERG channels at the plasma membrane.


Flapping tail membrane in bats produces potentially important thrust during horizontal takeoffs and very slow flight.
Historically, studies concerning bat flight have focused primarily on the wings. By analyzing high-speed video taken on 48 individuals of five species of vespertilionid bats, we show that the capacity to flap the tail-membrane (uropatagium) in order to generate thrust and lift during takeoffs and minimal-speed flight (<1 m (s-1)) was largely underestimated. Indeed, bats flapped the tail-membrane by extensive dorso-ventral fanning motions covering as much as 135 degrees of arc consistent with thrust generation by air displacement. The degree of dorsal extension of the tail-membrane, and thus the potential amount of thrust generated during platform launches, was significantly correlated with body mass (P = 0.02). Adduction of the hind limbs during upstrokes collapsed the tail-membrane thereby reducing its surface area and minimizing negative lift forces. Abduction of the hind limbs during the downstroke fully expanded the tail-membrane as it was swept ventrally. The flapping kinematics of the tail-membrane is thus consistent with expectations for an airfoil. Timing offsets between the wings and tail-membrane during downstrokes was as much as 50%, suggesting that the tail-membrane was providing thrust and perhaps lift when the wings were retracting through the upstoke phase of the wing-beat cycle. The extent to which the tail-membrane was used during takeoffs differed significantly among four vespertilionid species (P = 0.01) and aligned with predictions derived from bat ecomorphology. The extensive fanning motion of the tail membrane by vespertilionid bats has not been reported for other flying vertebrates.


SCORE: a novel multi-criteria decision analysis approach to assessing the sustainability of contaminated land remediation.
The multi-criteria decision analysis (MCDA) method provides for a comprehensive and transparent basis for performing sustainability assessments. Development of a relevant MCDA-method requires consideration of a number of key issues, e.g. (a) definition of assessment boundaries, (b) definition of performance scales, both temporal and spatial, (c) selection of relevant criteria (indicators) that facilitate a comprehensive sustainability assessment while avoiding double-counting of effects, and (d) handling of uncertainties. Adding to the complexity is the typically wide variety of inputs, including quantifications based on existing data, expert judgements, and opinions expressed in interviews. The SCORE (Sustainable Choice Of REmediation) MCDA-method was developed to provide a transparent assessment of the sustainability of possible remediation alternatives for contaminated sites relative to a reference alternative, considering key criteria in the economic, environmental, and social sustainability domains. The criteria were identified based on literature studies, interviews and focus-group meetings. SCORE combines a linear additive model to rank the alternatives with a non-compensatory approach to identify alternatives regarded as non-sustainable. The key strengths of the SCORE method are as follows: a framework that at its core is designed to be flexible and transparent; the possibility to integrate both quantitative and qualitative estimations on criteria; its ability, unlike other sustainability assessment tools used in industry and academia, to allow for the alteration of boundary conditions where necessary; the inclusion of a full uncertainty analysis of the results, using Monte Carlo simulation; and a structure that allows preferences and opinions of involved stakeholders to be openly integrated into the analysis. A major insight from practical application of SCORE is that its most important contribution may be that it initiates a process where criteria otherwise likely ignored are addressed and openly discussed between stakeholders.


Crystal and solution structure of NDRG1, a membrane-binding protein linked to myelination and tumour suppression.
N-myc downstream-regulated gene 1 (NDRG1) is a tumour suppressor involved in vesicular trafficking and stress response. NDRG1 participates in peripheral nerve myelination, and mutations in the NDRG1 gene lead to Charcot-Marie-Tooth neuropathy. The 43-kDa NDRG1 is considered as an inactive member of the α/β hydrolase superfamily. In addition to a central α/β hydrolase fold domain, NDRG1 consists of a short N terminus and a C-terminal region with three 10-residue repeats. We determined the crystal structure of the α/β hydrolase domain of human NDRG1 and characterised the structure and dynamics of full-length NDRG1. The structure of the α/β hydrolase domain resembles the canonical α/β hydrolase fold with a central β sheet surrounded by α helices. Small-angle X-ray scattering and CD spectroscopy indicated a variable conformation for the N- and C-terminal regions. NDRG1 binds to various types of lipid vesicles, and the conformation of the C-terminal region is modulated upon lipid interaction. Intriguingly, NDRG1 interacts with metal ions, such as nickel, but is prone to aggregation in their presence. Our results uncover the structural and dynamic features of NDRG1, as well as elucidate its interactions with metals and lipids, and encourage studies to identify a putative hydrolase activity of NDRG1. DATABASES: The coordinates and structure factors for the crystal structure of human NDRG1 were deposited to PDB (PDB ID: 6ZMM).


Goal setting and feedback for the development of instructional strategies.
This study was done to evaluate the effectiveness of three practice methods, (a) feedback as knowledge of performance (KP), (b) feedback as knowledge of results combined with the goal-setting method, and (c) a combination of knowledge of performance and results with the goal-setting method on the performance and learning of basketball skills of different complexity. Three groups (n = 26) of children followed the practice methods and the performance (result), and technique of simple and complex basketball skills (dribble, pass, shoot, and lay-up) were assessed for their effectiveness. Subjects practiced using four exercises for each skill, three times a week, for eight weeks. A performance and a retention test (two weeks later) were conducted. A multivariate analysis of variance with repeated measures on the last factor indicated that knowledge of performance with results of goal-setting significantly improved the techniques of the more complex skills but it was significantly better than the knowledge of results and goal-setting method for passing. Giving knowledge of results and setting goals improved performance and proved to be better than the knowledge of performance method. Finally, the combined method was as good as the knowledge of performance and as good as the knowledge of results plus goal setting in performance but improvement was delayed mostly for the more complex skills. Attentional needs for the analysis of information given determined the success in skills execution and the effectiveness of the methods. The different content of the information given to the athletes may improve different aspects of motion or execution of the skills.


Genotyping spring viraemia of carp virus and other piscine vesiculo-like viruses using reverse hybridisation.
A simple nylon membrane-based DNA macroarray was developed to genotype spring viraemia of carp virus (SVCV) and related viruses. Twenty-six viruses were genotyped using the array, and the results were confirmed by phylogenetic analysis of a 426 bp partial glycoprotein gene sequence. The array was not only capable of discriminating between the 4 main genogroups of cyprinid vesiculo-type viruses described previously, but also accurately sub-type the SVC viruses assigned to Genogroup I. The assay offers a practical solution for diagnostic laboratories that currently lack a sequencing capability to confirm the nature of PCR products generated in suspected SVCV cases.


Vascular calcification and hypertension: cause and effect.
Vascular calcification is an active and regulated process which is integral to cardiovascular disease and intimately linked to hypertension. Dysfunctional vascular smooth muscle cells, microvesicles, and dysregulated mineralization inhibitors play key roles in the calcification process, which occurs in the vessel intima in association with atherosclerosis as well as in the vessel media during ageing. Historically hypertension was considered a risk factor promoting atherosclerosis and associated intimal calcification. However, it is now recognized that not all vascular calcification occurs with atherosclerosis, and calcification of the vessel media is associated with arterial stiffening and is a major cause of isolated systolic hypertension in the elderly. Importantly, vascular calcification, regardless of its anatomical site, is an independent risk factor for cardiovascular mortality. Therefore, understanding the factors and mechanisms driving these processes will provide novel therapeutic targets for its prevention and perhaps ultimately its regression.


The actin cytoskeleton controls the efficiency of killer Ig-like receptor accumulation at inhibitory NK cell immune synapses.
Killer cell Ig-like receptors (KIRs) are MHC class I-specific receptors expressed in NK and T lymphocytes. KIR antagonism of activation signals occurs at the immune synapse between the effector and target cells. The processes that regulate clustering of KIR are not well defined. We have expressed KIR-GFP receptor chimeras in two human NK-like lines, YTS and NK92. In this study, we show that the frequency of KIR enrichment at the synapse was decreased for a KIR that lacks a portion of the cytoplasmic tail. Strikingly, blocking actin polymerization with a high dose of cytochalasin D also substantially decreased clustering of KIR as well as KIR-induced clustering of HLA-C-GFP in target cells. However, the effect of inhibiting actin polymerization was only clearly evident at the earlier time points after cell mixing, and eventually clustering of KIR and HLA-C occurred independently of actin remodeling. Although treatment with anti-LFA-1 also decreased conjugate formation, the frequency of KIR clustering remained normal within the population of conjugates that did form, suggesting that the effect of cytochalasin D is not solely through LFA-1. Collectively, these data suggest that the actin cytoskeleton and the cytoplasmic tail of KIR regulate the efficiency by which KIR accumulates at inhibitory NK cell synapses.


Computer-assisted design and synthesis of molecularly imprinted polymers for the simultaneous determination of six carbamate pesticides from environmental water.
The computer-assisted design and synthesis of molecularly imprinted polymers for the simultaneous capture of six carbamate pesticides from environmental water are reported in this work. The quantum mechanical computational approach was employed to design the molecularly imprinted polymers with carbofuran as template. The interaction energies between the template molecule and different functional monomers in various solvents were calculated to assist in the selection of the functional monomer and porogen. The optimised molecularly imprinted polymer was subsequently used as a class-selective sorbent in solid-phase extraction for pre-concentration and determination of carbamates from environmental water. The parameters influencing the extraction efficiency of the molecularly imprinted solid-phase extraction procedure were systematically investigated to facilitate the class-selective extraction. For the proposed method, linearity was observed over the range of 2-500 ng/mL with the correlation coefficient ranging from 0.9760 to 1.000. The limits of detection ranged from 0.2 to 1.2 ng/mL, and the limit of quantification was 4 ng/mL. These results confirm that computer-assisted design is an effective evaluation tool for molecularly imprinted polymers synthesis, and that molecularly imprinted solid-phase extraction can be applied to the simultaneous analysis of carbamates in environmental water.


Characterization of verlukast metabolites arising from an epoxide intermediate produced with hepatic microsomes from beta-naphthoflavone-treated rodents (P-4501A1).
Verlukast, (R)3-((((3-(2-(7-chloroquinolin-2-yl)-(E)-ethenyl)phenyl)-3- dimethylamino-3-oxopropylthio)methyl)thio)-propionic acid (also known as MK-0679 and L-668,019), is a potent leukotriene D4 antagonist. Verlukast was incubated with hepatic microsomes from beta-naphthoflavone (beta NF) or isosafrole-treated rodents to evaluate whether P-4501A1 or 1A2 mediated biotransformations could occur. With beta NF-induced mouse or rat microsomes, in which the induction of P-4501A1 had been proven by Western blot analysis, incubations produced new metabolites that were separated by reversed-phase HPLC and were initially characterized by UV (photodiode array). Metabolites were subsequently isolated and characterized by NMR and MS, and were assigned as the 5",6"-dihydrodiol and 6"-phenol (on the quinoline ring). The presumed 5",6"-epoxide intermediate was also detected and was characterized by UV (photodiode array) and MS. Microsomes from isosafrole-treated rodents produced the dihydrodiol to a much lesser extent and did not yield any other new metabolites. alpha-Naphthoflavone inhibited the dihydrodiol formation in incubations with microsomes from isosafrole- and beta NF-treated rats. In incubations with microsomes from beta NF-treated rats, to which the epoxide hydrolase inhibitor 3,3,3-trichloropropene 1,2-oxide had been added, the formation of dihydrodiol was inhibited, consistent with a microsomal epoxide hydrolase hydrolysis of the epoxide intermediate. When glutathione was added to incubations with microsomes from beta NF-treated rats, the dihydrodiol, phenol, and epoxide peaks were reduced in size and a new material, the glutathione adduct, was formed.(ABSTRACT TRUNCATED AT 250 WORDS)


The occurrence of the cold-water coral Lophelia pertusa (Scleractinia) on oil and gas platforms in the North Sea: colony growth, recruitment and environmental controls on distribution.
This study reports a newly established sub-population of Lophelia pertusa, the dominant reef-framework forming coral species in the north-east Atlantic, on oil and gas platforms in the northern North Sea. L. pertusa was positively identified on 13 of 14 platforms examined using existing oil and gas industry visual inspections. Two platforms were inspected in more detail to examine depth and colony size distributions. We recorded 947 colonies occurring between 59 and 132 m depth that coincides with cold Atlantic water at depths below the summer thermocline in the northern North Sea. We suggest that these colonies provide evidence for a planktonic larval stage of L. pertusa with recruits initially originating from populations in the north-east Atlantic and now self recruiting to the platforms. Size class distribution showed a continuous range of size classes, but with few outlying large colonies. The break between the largest colonies and the rest of the population is considered as the point when colonies began self recruiting to the platforms, resulting in greater colonization success. We present the first documented in situ colony growth rate estimate (26 +/- 5 mm yr(-1)) for L. pertusa based on 15 colonies from the Tern Alpha platform with evidence for yearly recruitment events starting the year the platform was installed. Evidence of contamination from drill muds and cuttings was observed on the Heather platform but appeared limited to regions close to drilling discharge points, where colonies experience partial as well as whole colony mortality.


Mortality in women and men in relation to smoking.
Mortality from smoking-related diseases in women is increasing worldwide. Studies comparing hazards associated with smoking in women and men based on a sufficient number of heavy smokers of both genders are lacking. We used pooled data from three prospective population studies conducted in Copenhagen to compare total and cause-specific mortality in relation to smoking habits. A total of 30917 subjects, 44% women, with initial examinations between 1964 and 1992 were followed until 1994 for date and cause of death. During follow up, 2900 women and 5744 men died. Smoking characteristics differed considerably with gender, particularly in the older subjects. Overall mortality rates in smokers were approximately twice those in people who never smoked. Positive associations with smoking in both men and women were confirmed for all-cause mortality as well as mortality from respiratory disease, vascular disease, lung cancer, and other tobacco-related cancers. Despite large gender differences in age at smoking debut, total and cause-specific relative mortality in smokers was similar in men and women. After excluding non-inhalers, relative risks associated with smoking for respiratory and vascular disease were higher for women than men whereas there were no gender differences in smoking related risk of cancers. The relative risks suggest that women may be more sensitive than men to some of the deleterious effects of smoking. However, because of lower baseline mortality rates in women, rate differences may be similar and results should be interpreted with caution.


Biased allelic expression in human primary fibroblast single cells.
The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability.


Molecularly imprinted polymer based micromechanical cantilever sensor system for the selective determination of ciprofloxacin.
The main objective of this study is to develop molecularly imprinted polymer (MIP) based micromechanical cantilever sensor system that has high specificity, fast response time and is easily applicable by user for the detection of ciprofloxacin (CPX) molecule in water resources. Highly specific CPX imprinted nanoparticles were synthesized by miniemulsion polymerization technique. The average size of the synthesized nanoparticles was measured about 160nm with high monodispersivity. Covalent and monolayer binding of the MIP nanoparticles on cantilevers was provided by EDC/NHS activation. Validation of the developed cantilever nanosensor was performed in air with dip-and-dry technique by employing the dynamic sensing mode. According to the results obtained, micromechanical cantilever sensor system worked linearly for the concentration range of 1.5-150.9μM. This concentration range resulted with 18.4-48.9pg mass load on the MIP modified cantilever. The sensitivity of the developed sensor was calculated as 2.6Hz/pg. To control the specificity of MIPs, a different antibiotic enrofloxacin (ENF), with a similar physical and chemical structure with CPX, was used, which showed 7 folds low binding affinity. The developed highly specific microcantilever sensor has a response time of approximately 2min and is reusable up to 4 times. The results indicate that the MIP based AFM nanosensor has high sensitivity for the CPX molecule. This combination of MIP nanoparticles with micromechanical sensors is one of the pioneer studies in the mass sensing applications. This fast, low cost and highly sensitive CPX specific MIP nanoparticle based nanosensor developed in this research have the potential to pave the way for further studies.


Intimate partner violence against women in Nigeria: a multilevel study investigating the effect of women's status and community norms.
Intimate partner violence (IPV) against women has been recognised as a public health problem with far-reaching consequences for the physical, reproductive, and mental health of women. The ecological framework portrays intimate partner violence as a multifaceted phenomenon, demonstrating the interplay of factors at different levels: individual, community, and the larger society. The present study examined the effect of individual- and community-level factors on IPV in Nigeria, with a focus on women's status and community-level norms among men. A cross-sectional study based on the latest Nigerian Demographic Health Survey (2013) was conducted involving 20,802 ever-partnered women aged 15-49 years. Several multilevel logistic regression models were calibrated to assess the association of individual- and community-level factors with IPV. Both measures of association (fixed effect) and measures of variations (random effect) were reported. Almost one in four women in Nigeria reported having ever experienced intimate partner violence. Having adjusted for other relevant covariates, higher women's status reduced the odds of IPV (OR = 0.47; 95% CI = 0.32-0.71). However, community norms among men that justified IPV against women modified the observed protective effect of higher women's status against IPV and reversed the odds (OR = 1.89; 95% CI = 1.26-2.83). Besides women's status, community norms towards IPV are an important factor for the occurrence of IPV. Thus, addressing intimate partner violence against women calls for community-wide approaches aimed at changing norms among men alongside improving women's status.


Stability of benzylpenicillin potassium and ampicillin in an elastomeric infusion pump.
Some infectious diseases, such as infective endocarditis, osteomyelitis, and abscesses, require treatment with long-term intravenous antimicrobial treatment. Therefore, the patient is required to stay in the hospital to receive therapy, which lowers their quality of life. Establishing an outpatient parenteral antimicrobial therapy (OPAT) by continuous infusion pump is desired in Japan to overcome these issues. However, the 24-h stability of antimicrobial agents dissolved in infusion solutions is unclear. Thus, we investigated the stability of antimicrobial agents in five different infusion solutions in a clinical setting. Benzylpenicillin potassium (PCG) and ampicillin (ABPC) were dissolved separately in five different infusion solutions and kept at 25 or 31.1 °C for 24 h. The residual ratios were determined by high-performance liquid chromatography (HPLC). Dissolved PCG in acetate ringer solution remained stable for 24 h at temperatures of 25 and 31.1 °C (101.7 ± 1.4% and 92.9 ± 1.3%, respectively). In addition, the PCG solution did not adsorb onto the elastomeric infusion pump after 24 h at 31.1 °C. PCG dissolved in acetate ringer solution was also stable for 10 days after being kept in an elastomeric infusion pump at 4 °C (99.7 ± 0.5%). ABPC was unstable in all of the tested infusion solutions and temperatures. Based on our results, PCG in acetate ringer solution can be used in OPAT with continuous infusion pumps.


Mycoplasma in periodontal disease. Isolation in juvenile periodontitis.
Mycoplasma have been identified in one case of juvenile periodontitis by size, morphology, hemadsorption and cultural techniques. These microorganisms were found on the surface of the tooth, on the surface of pocket epithelium and invading the gingival epithelium and adjacent connective tissue. These observations suggest the need for further studies on the role of Mycoplasma in the pathogenesis of advanced periodontal infections. The role of Mycoplasma in periodontal disease is discussed.


Von Willebrand factor and the right ventricle (the MESA-Right Ventricle Study).
Elevation in plasma activity of von Willebrand factor (vWF) reflects endothelial dysfunction and predicts death in pulmonary arterial hypertension. Higher vWF activity is also associated with a lower right ventricular (RV) ejection fraction in pulmonary arterial hypertension. Little is known about the relation between vWF and RV structure and function in adults without cardiovascular disease. The present investigation included 1,976 participants with magnetic resonance imaging assessment of RV structure and function and measurement of vWF activity from the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to estimate the associations between vWF activity and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking, diabetes mellitus, hypertension, and the corresponding left ventricular parameter. The average vWF activity was 140.7 ± 57.2%. Elevated vWF activity was independently associated with lower RV mass, RV end-diastolic volume, and RV stroke volume in models with and without adjustment for the corresponding left ventricular parameter (all p values <0.05). There was no association observed between vWF activity and the RV ejection fraction. In conclusion, higher vWF activity is associated with lower RV mass, RV end-diastolic volume, and RV stroke volume. These associations are independent of common cardiovascular risk factors and left ventricular morphologic changes.


Perspective-taking is spontaneous but not automatic.
Data from a range of different experimental paradigms-in particular (but not only) the dot perspective task-have been interpreted as evidence that humans automatically track the perspective of other individuals. Results from other studies, however, have cast doubt on this interpretation, and some researchers have suggested that phenomena that seem like perspective-taking might instead be the products of simpler behavioural rules. The issue remains unsettled in significant part because different schools of thought, with different theoretical perspectives, implement the experimental tasks in subtly different ways, making direct comparisons difficult. Here, we explore the possibility that subtle differences in experimental method explain otherwise irreconcilable findings in the literature. Across five experiments we show that the classic result in the dot perspective task is not automatic (it is not purely stimulus-driven), but nor is it exclusively the product of simple behavioural rules that do not involve mentalising. Instead, participants do compute the perspectives of other individuals rapidly, unconsciously, and involuntarily, but only when attentional systems prompt them to do so (just as, for instance, the visual system puts external objects into focus only as and when required). This finding prompts us to clearly distinguish spontaneity from automaticity. Spontaneous perspective-taking may be a computationally efficient means of navigating the social world.


Effects of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) Trial on Elective Induction and Obstetric Outcomes in Term Nulliparous Patients.
To evaluate the effect of publication of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial on perinatal outcomes in singleton, term, nulliparous patients. An interrupted time series analysis was performed using clinical data for nulliparous singleton births at 39 weeks of gestation or later at 13 hospitals in the Northwest region of the United States (January 2016-December 2020). A modified Poisson regression was used to model time trends and changes after the ARRIVE trial (August 9, 2018). Outcomes of interest were elective induction, unplanned cesarean births, hypertensive disorders of pregnancy, a composite of perinatal adverse outcomes, and neonatal intensive care unit admissions. The analysis included 28,256 births (15,208 pre-ARRIVE and 13,048 post-ARRIVE). The rate of elective labor induction was 3.6% during the pre-ARRIVE period (January 2016-July 2018) and 10.8% post-ARRIVE (August 2018-December 2020). In the interrupted time series analysis, elective induction increased by 42% (relative risk [RR] 1.42; 95% CI 1.18-1.71) immediately after the ARRIVE trial publication. Thereafter, the trend was unchanged compared with the pre-ARRIVE period. There was no statistically significant change in cesarean birth (RR 0.96; 95% CI 0.89-1.04) or hypertensive disorders of pregnancy (RR 0.91; 95% CI 0.79-1.06) immediately after the trial, and no change in trend. After the ARRIVE trial, there was no immediate change in adverse perinatal outcomes, but a statistically significant increase in trend of adverse perinatal events (1.03; 95% CI 1.01-1.05) when compared with a declining trend observed in the pre-ARRIVE period. Publication of the ARRIVE trial was associated with an increase in elective induction, and no change in cesarean birth or hypertensive disorders of pregnancy in singleton nulliparous patients giving birth at 39 weeks or later. There was a flattening of the pre-ARRIVE decreasing trend in perinatal adverse events.


Valve replacement with the Starr-Edwards and Hancock prostheses: comparative analysis of late morbidity and mortality.
Although the Starr-Edwards caged-ball valve remains a standard of comparison for more recently introduced prostheses, a substantial incidence of thromboembolic and hemorrhagic complications prompted our evaluation of the Hancock glutaraldehyde-fixed porcine xenograft. We have compared the results of 435 aortic valve replacements using the Starr- Edwards valve (SE-AVR), 515 mitral valve replacements (SE-MVR), and 121 double-valve replacements (SE-AVRMVR) with 251 aortic valve replacements using the xenograft aortic valve (X-AVR), 338 mitral valve replacements (X-MVR), and 88 double-valve replacements (X-AVR-MVR). The Starr- Edwards valves were used during the period 1963 through 1973 and the xenograft valves between 1971 and 1976. No significant differences in patient age, sex, or preoperative hemodynamic data were noted between comparable groups. All patients with Starr-Edwards valves received long-term anticoagulation while anticoagulants were used only for specific indications in patients with xenograft valves. Total follow up was 3944 patient years for the Starr-Edwards patients and 947 patient years for the xenograft patients. Hospital mortality was not significantly different for comparable groups: SE-AVR 6.9% vs. X-AVR 6.4%, SE-MVR 9.7% vs X-MVR 8.6%, and SE-AVR-MVR 7.5% vs. X-AVR-MVR 10.2%. Linearized mortality and morbidity data expressed as percent per patient- year are tabulated below. Pairs which differ significantly (p < .05) are italicized.


[Dynamics of orotic acid metabolism in chick tissues].
The processes of pyrimidine nucleotides metabolism were analyzed in cells of chicken small intestine mucosa using the kinetic series-parallel model of the first order equations. The rate constants are calculated for absorption of [2-14C]orotic acid by mucosa cells, its accumulation in blood anc conversion to uridine nucleotides. Stages of uridine nucleotides conversion to cytidine ones and their incorporation into RNA are not described by the system of the first order equations based on the series-parallel model with the single-channel utilization of orotic acid through the pyrimidine pathway. The model into two pathways of free nucleotides metabolism and two individual flows of precursors into RNA corresponds qualitatively to the obtained experimental data. Metabolism of orotic acid along two separate channels might be typical of the chicken liver.


Anemia and Iron Deficiency in Children with Chronic Kidney Disease (CKD): Data from the Know-Ped CKD Study.
Children with chronic kidney disease (CKD) are at high risk of anemia, an important risk factor for cardiovascular disease and poor quality of life. The present study used baseline data from the Korean cohort study for Outcome in patients With Pediatric Chronic Kidney Disease (KNOW-PedCKD). A Total of 437 patients was included in the analyses excluding missing data. The characteristics of patients with and without anemia and those of patients with and without iron deficiency were compared. Logistic regression analysis and Pearson correlation were conducted to evaluate associated risk factors and correlations in children with CKD. Anemia in children with CKD was associated with older age, low body weight and body mass index (BMI) z-score, birth age, preceding glomerulonephritis, decreased estimated glomerular filtration rate (eGFR), low levels of serum albumin and calcium, high levels of serum intact parathyroid hormone (iPTH), and serum phosphorus. Anemia was correlated positively with changes in the BMI z-score, body weight, and serum albumin and cholesterol levels, but correlated negatively with serum calcium, iPTH, ferritin levels, and transferrin saturation. Iron deficiency in children with CKD was associated with young age, low hemoglobin and serum ferritin levels, high BMI z-scores, and low levels of serum iPTH. This is the first nationwide cohort study of anemia in Korean children with CKD and the first prospective pediatric CKD cohort study in Asia. The study results demonstrated that anemia and iron deficiency are affected by various factors, including age, BMI, and levels of serum iPTH. To improve the retrospective outcome of affected children, it is important to understand the effect of each of these factors and to attempt an early intervention to prevent anemia and iron deficiency by regular measurement of these parameters in children at risk.


Factors affecting medial temporal lobe engagement for past and future episodic events: an ALE meta-analysis of neuroimaging studies.
Remembering the past and envisioning the future are at the core of one's sense of identity. Neuroimaging studies investigating the neural substrates underlying past and future episodic events have been growing in number. However, the experimental paradigms used to select and elicit episodic events vary greatly, leading to disparate results, especially with respect to the laterality and antero-posterior localization of hippocampal and adjacent medial temporal activations (i.e., parahippocampal, entorhinal and perirhinal cortices, amygdala). Although a central concern in today's literature, the issue of hippocampal and medial temporal lobe laterality and antero-posterior segregation in past and future episodic events has not yet been addressed extensively. Using the activation likelihood estimation (ALE) procedure (Turkeltaub, Eden, Jones, & Zeffiro, 2002), we performed a meta-analysis of hippocampal and adjacent medial temporal coordinates extracted from neuroimaging studies examining past remembering and future envisioning. We questioned whether methodological choices could influence the laterality of activations, namely (1) the type of cue used (generic vs. specific), (2) the type of task performed (recognition vs. recall/imagine), (3) the nature of the information retrieved (episodic vs. "strictly" episodic events) and (4) the age of participants. We consider "strictly" episodic events as events which are not only spatio-temporally unique and personal like episodic events, but are also associated with contextual and phenomenological details. These four factors were compared two-by-two, generating eight whole-brain statistical maps. Results indicate that (1) specific cues tend to activate more the right anterior hippocampus compared to the use of generic cues, (2) recall/imagine tasks tend to recruit more the left posterior parahippocampal gyrus compared to recognition tasks, (3) (re/pre)experiencing strictly episodic events tends to activate more the bilateral posterior hippocampus compared to episodic events and (4) older subjects tend to activate more the right anterior hippocampus compared to younger subjects. Importantly, our results stress that strictly episodic events triggered by specific cues elicit greater left posterior hippocampal activation than episodic events triggered by specific cues. These findings suggest that such basic methodological choices have an impact on the conclusions reached regarding past and future (re/pre)experiencing and their neural substrates.


Clinical trials in traumatic brain injury: lessons for the future.
Thus far, none of the neuroprotective drugs that have been tested to reduce or prevent secondary ischemic brain damage have been shown clear benefit. We will attempt to identify factors that may be responsible for some of these failures. We also will give our thoughts on how to prevent these pitfalls in the usefulness and criteria for use of animal models for traumatic brain injury to depict human head injury are discussed. Clearly, mechanism-driven trials, in which individual pathophysiological mechanisms are targeted, are more likely to show benefit in this heterogeneous patient population. Other factors, such as the effect of brain penetration, safety and tolerability of the compound, and the interface between the pharmaceutical industry and academics are a major influence in the success of these trials. Furthermore, the way trials have been analyzes in the past may not always have been be the most appropriate to show benefits. It is clear that a multi-targeted approach is necessary to address the complicated and closely related mechanisms seen after traumatic and or ischemic brain damage.


Occurrence of Raynaud's phenomenon in children ages 12-15 years: prevalence and association with other common symptoms.
Although Raynaud's phenomenon (RP) in adults is frequently reported as having been present since childhood, there have been no studies on the prevalence of RP in children. This study was undertaken to ascertain the prevalence of RP in children ages 12-15 years and to determine whether, as with other commonly reported symptoms, there were any associations with adverse psychosocial factors. A previously validated self-administered RP questionnaire was distributed to 903 children ages 12-15 years, from 28 schools. The questionnaire also included questions on other common childhood symptoms and on adverse psychosocial factors. Seven hundred twenty children responded (80%), in whom the prevalence of RP was 15%. This was higher in girls (18% versus 12%) and increased with age. After adjustment for age and sex, there was an association with reporting of current pain, both in the arm/shoulder region and elsewhere in the body. There were no associations with psychosocial variables. RP is frequent in children ages 12-15 years. Unlike other common childhood symptoms, RP showed no association with psychosocial factors in this study.


Evaluation of CSF leaks: high-resolution CT compared with contrast-enhanced CT and radionuclide cisternography.
Radiologic evaluation of CSF leaks is a diagnostic challenge that often involves multiple imaging studies with the associated expense and patient discomfort. We evaluated the use of screening noncontrast high-resolution CT in identifying the presence and site of CSF rhinorrhea and otorrhea and compared it with contrast-enhanced CT cisternography and radionuclide cisternography. We retrospectively reviewed the imaging studies and medical records of all patients who were evaluated for CSF leak during a 7-year period. Forty-two patients with rhinorrhea and/or otorrhea underwent high-resolution CT of the face or temporal bone and then had CT cisternography and radionuclide cisternography via lumbar puncture. The results of the three studies were compared and correlated with the surgical findings in 21 patients. High-resolution CT showed bone defects in 30 of 42 patients (71%) with CSF leak. High-resolution, radionuclide cisternography and CT cisternography did not show bone defects or CSF leak for 12 patients (29%) who had clinical evidence of CSF leak. Among the 30 patients with bone defects, 20 (66%) had positive results of their radionuclide cisternography and/or CT cisternography. For the 21 patients who underwent surgical exploration and repair, intraoperative findings correlated with the defects revealed by high-resolution CT in all cases. High-resolution CT identified significantly more patients with CSF leak than did radionuclide cisternography and CT cisternography, with a moderate degree of agreement. Noncontrast high-resolution CT showed a defect in 70% of the patients with CSF leak. No radionuclide cisternography or CT cisternography study produced positive results without previous visualization of a defect on high-resolution CT. CT cisternography and radionuclide cisternography may be reserved for patients in whom initial high-resolution CT does not identify a bone defect or for patients with multiple fractures or postoperative defects.


Parenting and later substance use among Mexican-origin youth: Moderation by preference for a common language.
The primary goal of the current study was to test whether parent and adolescent preference for a common language moderates the association between parenting and rank-order change over time in offspring substance use. A sample of Mexican-origin 7th-grade adolescents (Mage = 12.5 years, N = 194, 52% female) was measured longitudinally on use of tobacco, alcohol, and marijuana. Mothers, fathers, and adolescents all reported on consistent discipline and monitoring of adolescents. Both consistent discipline and monitoring predicted relative decreases in substance use into early adulthood but only among parent-offspring dyads who expressed preference for the same language (either English or Spanish). This moderation held after controlling for parent substance use, family structure, having completed schooling in Mexico, years lived in the United States, family income, and cultural values. An unintended consequence of the immigration process may be the loss of parenting effectiveness that is normally present when parents and adolescents prefer to communicate in a common language. (PsycINFO Database Record


Arthroscopic treatment of greater tuberosity fractures : retrospective review of clinical and radiological outcomes.
The purpose of this retrospective study was to analyze the clinical and radiological outcomes and discuss the value of arthroscopic suture bridge technique in patients with isolated greater tuberosity fractures. Between October 2009 and July 2014, 37 patients with greater tuberosity fractures were analyzed. Thirteen of these patients were treated with arthroscopic reduction and fixation. Analysis of the clinical outcome was performed by comparing final range of motion, UCLA and Constant score. Radiological outcome was analyzed with time for union. Postoperative results were analyzed by range of motion, UCLA and constant score. Each figure resulted as: UCLA from 27 to 35 (average: 29); range of motion in forward flexion from 160° to 180° (average: 173°); Constant score from 69 to 100 (average: 73). Using arthroscopic treatment with a suture-bridge technique can be a useful method in terms of clinical and functional outcomes and be considered as a viable alternative to conventional open techniques.


Phenotypic characterization and whole genome analysis of extended-spectrum beta-lactamase-producing bacteria isolated from dogs in Germany.
Asymptomatic colonization with extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae has been described for humans, various mammal species, and birds. Here, antimicrobial resistant bacteria were recovered from dog feces originating in Germany, Kosovo, Afghanistan, Croatia, and Ukraine, with a subset of mostly E. coli isolates obtained from a longitudinal collection over twelve months. In vitro antimicrobial resistance testing revealed various patterns of resistance against single or all investigated beta-lactam antibiotics, with none of the 101 isolates resistant against two tested carbapenem antibiotics. Whole genome sequence analysis revealed bacteria species-specific patterns for 23 antimicrobial resistance coding DNA sequences (CDS) that were unapparent from the in vitro analysis alone. Phylogenetic analysis of single nucleotide polymorphisms (SNP) revealed clonal bacterial isolates originating from different dogs, suggesting transmission between dogs in the same community. However, individual resistant E. coli clones were not detected over a period longer than seven days. Multi locus sequence typing (MLST) of 85 E. coli isolates revealed 31 different sequence types (ST) with an accumulation of ST744 (n = 9), ST10 (n = 8), and ST648 (n = 6), although the world-wide hospital-associated CTX-M beta-lactamase producing ST131 was not detected. Neither the antimicrobial resistance CDSs patterns nor the phylogenetic analysis revealed an epidemiological correlation among the longitudinal isolates collected from a period longer than seven days. No genetic linkage could be associated with the geographic origin of isolates. In conclusion, healthy dogs frequently carry ESBL-producing bacteria, independent to prior treatment, which may be transmitted between individual dogs of the same community. Otherwise, these antimicrobial resistant bacteria share few commonalities, making their presence eerily unpredictable.


Interaction of CarD with RNA polymerase mediates Mycobacterium tuberculosis viability, rifampin resistance, and pathogenesis.
Mycobacterium tuberculosis infection continues to cause substantial human suffering. New chemotherapeutic strategies, which require insight into the pathways essential for M. tuberculosis pathogenesis, are imperative. We previously reported that depletion of the CarD protein in mycobacteria compromises viability, resistance to oxidative stress and fluoroquinolones, and pathogenesis. CarD associates with the RNA polymerase (RNAP), but it has been unknown which of the diverse functions of CarD are mediated through the RNAP; this question must be answered to understand the CarD mechanism of action. Herein, we describe the interaction between the M. tuberculosis CarD and the RNAP β subunit and identify point mutations that weaken this interaction. The characterization of mycobacterial strains with attenuated CarD/RNAP β interactions demonstrates that the CarD/RNAP β association is required for viability and resistance to oxidative stress but not for fluoroquinolone resistance. Weakening the CarD/RNAP β interaction also increases the sensitivity of mycobacteria to rifampin and streptomycin. Surprisingly, depletion of the CarD protein did not affect sensitivity to rifampin. These findings define the CarD/RNAP interaction as a new target for chemotherapeutic intervention that could also improve the efficacy of rifampin treatment of tuberculosis. In addition, our data demonstrate that weakening the CarD/RNAP β interaction does not completely phenocopy the depletion of CarD and support the existence of functions for CarD independent of direct RNAP binding.


Vasodilation of cat cerebral arterioles by prostaglandins D2, E2, G2, and I2.
To determine the possible role that endogenously produced prostaglandins may play in the regulation of cerebral blood flow, the responses of cerebral precapillary vessels to prostaglandins (PG) D2, E2, G2, and I2 (8.1 X 10(-8) to 2.7 X 10(-5) M) were studied in cats equipped with cranial windows for direct observation of the microvasculature. Local application of PGs induced a dose-dependent dilation of large (greater than or equal to 100 microns) and small (less than 100 microns) arterioles with no effect on arterial blood pressure. The relative vasodilator potency was PGG2 greater than PGE2 greater than PGI2 greater than PGD2. With all PGs, except D2, the percent dilation of small arterioles was greater than the dilation of large arterioles. After application of prostaglandins in a concentration of 2.7 X 10(-5) M, the mean +/- standard error of the percent dilation of large and small arterioles was, respectively, 47.6 +/- 2.7 and 65.3 +/- 6.1 for G2, 34.1 +/- 2.0, and 53.6 +/- 5.5 for E2, 25.4 +/- 1.8, and 40.2 +/- 4.6 for I2, and 20.3 +/- 2.5 and 11.0 +/- 2.2 for D2. Because brain arterioles are strongly responsive to prostaglandins and the brain can synthesize prostaglandins from its large endogenous pool of prostaglandin precursor, prostaglandins may be important mediators of changes in cerebral blood flow under normal and abnormal conditions.


Successful use of daily intravenous infusion of C1 esterase inhibitor concentrate in the treatment of a hereditary angioedema patient with ascites, hypovolemic shock, sepsis, renal and respiratory failure.
Hereditary angioedema (HAE) is a rare autosomal dominant disease most commonly associated with defects in C1 esterase inhibitor (C1-INH). HAE manifests as recurrent episodes of edema in various body locations. Atypical symptoms, such as ascites, acute respiratory distress syndrome, and hypovolemic shock, have also been reported. Management of HAE conventionally involves the treatment of acute attacks, as well as short- and long-term prophylaxis. Since attacks can be triggered by several factors, including stress and physical trauma, prophylactic therapy is recommended for patients undergoing surgery. Human plasma-derived C1-INH (pdC1-INH) concentrate is indicated for the treatment of both acute HAE attacks and pre-procedure prevention of HAE episodes in patients undergoing medical, dental, or surgical procedures. We report the first case of a patient with HAE who experienced an abdominal attack precipitated by a retroperitoneal bleed while being converted from warfarin to heparin in preparation for surgery. Subsequently, the patient had a protracted course in hospital with other complications, which included hypovolemic shock, ascites, severe sepsis from nosocomial pneumonia, renal and respiratory failure. Despite intensive interventions, the patient remained in a critical state for months; however, after a trial of daily intravenous infusion of pdC1-INH concentrate (Berinert®, CSL Behring GmbH, Marburg, Germany), clinical status improved, particularly renal function. Therefore, pdC1-INH concentrate may be an effective treatment option to consider for critically-ill patients with HAE.


Lignin-Based Polyurethanes: Opportunities for Bio-Based Foams, Elastomers, Coatings and Adhesives.
Polyurethane chemistry can yield diverse sets of polymeric materials exhibiting a wide range of properties for various applications and market segments. Utilizing lignin as a polyol presents an opportunity to incorporate a currently underutilized renewable aromatic polymer into these products. In this work, we will review the current state of technology for utilizing lignin as a polyol replacement in different polyurethane products. This will include a discussion of lignin structure, diversity, and modification during chemical pulping and cellulosic biofuels processes, approaches for lignin extraction, recovery, fractionation, and modification/functionalization. We will discuss the potential of incorporation of lignins into polyurethane products that include rigid and flexible foams, adhesives, coatings, and elastomers. Finally, we will discuss challenges in incorporating lignin in polyurethane formulations, potential solutions and approaches that have been taken to resolve those issues.


A proteolytic system that compensates for loss of proteasome function.
Proteolysis is essential for the execution of many cellular functions. These include removal of incorrectly folded or damaged proteins, the activation of transcription factors, the ordered degradation of proteins involved in cell cycle control, and the generation of peptides destined for presentation by class I molecules of the major histocompatibility complex. A multisubunit protease complex, the proteasome, accomplishes these tasks. Here we show that in mammalian cells inactivation of the proteasome by covalent inhibitors allows the outgrowth of inhibitor-resistant cells. The growth of such adapted cells is apparently maintained by the induction of other proteolytic systems that compensate for the loss of proteasomal activity.


Strategies to Offer Uninterrupted Neurosurgical Care at a Tertiary Center in Makka amid COVID-19 Pandemic.
Globally, there is a shooting pandemic that affected many healthcare systems. Healthcare facilities had to set up logistics to avoid being drained while facing a catastrophic health problem. There are currently no available vaccines or perfect therapies and also no certified immunity against that disease. Therefore, it is probable that healthcare systems will face it for an exceptionally long period. That will have a grave effect on the strategy of daily practice of different specialties' services at healthcare centers. Impossible decisions in usual workdays are now forcibly adopted for the sake of patients, care providers, and health resources. We try in a simple way to share tertiary center expertise in managing neurosurgical cases amid a dreadful healthcare crisis. Healthcare workers' safety and patient safety were typical priorities for neurosurgical service at King Abdullah Medical City. We expose the lines of management, triaging cases, the methods of handling confirmed and suspected neurosurgical patients, and strategies for discharging and following up patients. We identified hospital admission and discharge records starting from March 2020 till July to track the neurosurgical case burden and the state of service offered and the rate of infection among healthcare workers who participated in surgeries. At the peak time of the COVID-19 pandemic in Makka starting from March till July, we have admitted 250 neurosurgical patients. About 210 (84%) of them did surgeries according to the triaging protocol described in the article. About 155 (62%) of those who did surgeries were urgent and the rest were borderline or semi-urgent. About 10 (4%) were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive and three of them died due to acute respiratory distress syndrome. Only two mortality cases were reported due to a neurological complication and not related to SARS-CoV-2 infection. The rest of the cases (98%) were discharged for follow-up without grave complications after they were offered the service. No neurosurgeons or anesthesia staff involved in offering the service were infected with SARS-CoV-2. Successful uninterrupted neurosurgical care was available for patients during that health crisis without any healthcare worker being infected. Following the suggested strategies, any center can provide the healthcare service amid any pandemic happening now or in the future without dismantling the normal health system, especially for life-saving cases in a critical specialty as neurosurgery.


[Recurrent European missense mutation in a Hungarian pedigree with Papillon-Lefèvre syndrome].
Papillon-Lefèvre syndrome, a rare disease with autosomal recessive inheritance, is characterized by aggressive periodontitis and palmoplantar hyperkeratosis. Mutations of the cathepsin C gene are responsible for the development of the disease. In this study, we aimed to describe in details the clinical symptoms and to determine the underlying genetic abnormality in two Hungarian siblings affected by Papillon-Lefèvre syndrome. The siblings are under regular dental and dermatological care since their symptoms appeared, but, due to the fact that genetic analysis of Papillon-Lefèvre syndrome has been available for one or two years in Hungary, their mutation screenings were just recently performed. We have identified a homozygous missense mutation on the cathepsin C gene, which is an already published mutation and was originally reported from Germany. Our investigations would like to draw attention to a rare disease, Papillon-Lefèvre syndrome, in which first symptom can be the aggressive periodontitis, and in which genetic testing and for helping child-bearing and family planning is now available.