MoCA Domain Score Analysis and Relation to Mobility Outcomes in Dysvascular Lower Extremity Amputees.
To investigate the association between cognitive functioning, as measured by the Montreal Cognitive Assessment (MoCA), and functional outcomes upon discharge from prosthetic rehabilitation. Retrospective chart audit. Rehabilitation hospital. Consecutive admissions (N=130; mean age, 66.21±11.19y) with lower extremity amputation of dysvascular etiology. Not applicable. Cognitive status was assessed using the MoCA. The L Test of Functional Mobility (L Test) and the 2-minute walk test were used to estimate functional mobility and walking endurance. In multivariable linear regression analysis, those who scored 2 on the visuospatial/executive functioning (out of 5) and language (out of 3) domains had statistically shorter distances walked on the 2-minute walk test than did those who scored the highest on these MoCA domains. These values were not clinically relevant. Time to complete the L Test for those who scored the lowest on the MoCA domains of visuospatial/executive functioning and delayed recall and 3 on the attention domain (out of 6) was significantly longer than that for those who scored the highest. Individuals with lower extremity amputation have an increased risk of cognitive impairment related to amputation etiology. Lower levels of functioning on MoCA domains of visuospatial/executive functioning, delayed recall, and attention were shown to negatively relate to the rehabilitation outcome of functional mobility, as measured by the L Test.


Propylene glycol and Kolliphor as solvents for systemic delivery of cannabinoids via intraperitoneal and subcutaneous routes in preclinical studies: a comparative technical note.
Substance administration to laboratory animals necessitates careful consideration and planning in order to enhance agent distribution while reducing any harmful effects from the technique. There are numerous methods for administering cannabinoids; however, several parameters must be considered, including delivery frequency, volume of administration, vehicle, and the level of competence required for staff to use these routes properly. There is a scarcity of information about the appropriate delivery method for cannabinoids in animal research, particularly those that need the least amount of animal manipulation during the course of the investigation. This study aims to assess the feasibility and potential side effects of intraperitoneal and subcutaneous injection of CBD and THC using propylene glycol or Kolliphor in animal models. By evaluating the ease of use and histopathological side effects of these solvents, this study intends to help researchers better understand an accessible long-term delivery route of administration in animal experiments while minimizing the potential confounding effects of the delivery method on the animal. Intraperitoneal and subcutaneous methods of systemic cannabis administration were tested in rat models. Subcutaneous delivery via needle injection and continuous osmotic pump release were evaluated using propylene glycol or Kolliphor solvents. In addition, the use of a needle injection and a propylene glycol solvent for intraperitoneal (IP) administration was investigated. Skin histopathological changes were evaluated following a trial of subcutaneous injections of cannabinoids utilizing propylene glycol solvent. Although IP delivery of cannabinoids with propylene glycol as solvent is a viable method and is preferable to oral treatment in order to reduce gastrointestinal tract degradation, it has substantial feasibility limitations. We conclude that subcutaneous delivery utilizing osmotic pumps with Kolliphor as a solvent provides viable and consistent route of administration for long-term systemic cannabinoid delivery in the preclinical context.


Children and young people's participation in healthcare consultations in the emergency department.
Approximately 4 million children attend emergency departments (ED) in England, United Kingdom, per annum. It is important for children and young people to have an active say in their assessment and treatment during each emergency care episode. However the reality of hearing the child or young person's voice within active participation in health care consultations remains low at approximately 6% of voices recorded. In the context of policy drivers and patient benefits, there is a need to increase the level of participation by children and young people within the emergency care environment. However, noise, child and parental anxiety and distress, professional time pressure, and severity of child illness or injury add to the inherent complexity of triadic communication (parent, child, healthcare professional) in the ED. Research examining child participation in decision-making in ED is sparse and guidance for all parties is limited. Therefore methods drawn from the wider literature on child participation are discussed which may be implemented, validated and evaluated with an ED context.


Trends and patterns of initial percutaneous nephrolithotomy and subsequent procedures among commercially-insured US adults with urinary system stone disease: a 10-year population-based study.
To describe trends and patterns of initial percutaneous nephrolithotomy (PCNL) and subsequent procedures from 2010 to 2019 among commercially-insured US adults with urinary system stone disease (USSD). Retrospective study of administrative data from the IBM® MarketScan® Database. Eligible patients were aged 18-64 years and underwent PCNL between 1/1/2010 and 12/31/2019. Measures of interest for analysis of trends and patterns included the setting of initial PCNL (inpatient vs. outpatient), percutaneous access (1 vs. 2-step), and the incidence, time course, and type of subsequent procedures (extracorporeal shockwave lithotripsy [SWL], ureteroscopy [URS], and/or PCNL) performed up-to 3 years after initial PCNL. A total of 8,348 patients met the study eligibility criteria. During the study period, there was a substantial shift in the setting of initial PCNL, from 59.9% being inpatient in 2010 to 85.3% being outpatient by 2019 (P < 0.001). The proportion of 1 vs. 2-step initial PCNL fluctuated over time, with a low of 15.1% in 2016 and a high of 22.0% in 2019 but showed no consistent yearly trend (P = 0.137). The Kaplan-Meier estimated probability of subsequent procedures following initial PCNL was 20% at 30 days, 28% at 90 days, and 50% at 3 years, with slight fluctuations by initial PCNL year. From 2010 to 2019, the proportion of subsequent procedures accounted for by URS increased substantially (from 30.8 to 51.8%), whereas SWL decreased substantially (from 39.5 to 14.7%) (P < 0.001). From 2010 to 2019, PCNL procedures largely shifted to the outpatient setting. Subsequent procedures after initial PCNL were common, with most occurring within 90 days. URS has become the most commonly-used subsequent procedure type.


Epipharyngeal Abrasive Therapy Down-regulates the Expression of SARS-CoV-2 Entry Factors ACE2 and TMPRSS2.
The epipharynx, with its high expression of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2), is a primary target for SARS-CoV-2 replication in the early stage of Coronavirus Disease 19 (COVID-19). Epipharyngeal abrasive therapy (EAT) is a treatment for epipharyngitis in Japan which involves applying zinc chloride to the epipharyngeal mucosa. In this study, we evaluated the expression patterns of ACE2 and TMPRSS2 in tissue samples from patients before and after EAT. The study subjects were seven patients that had not been treated with EAT and 11 patients that had. For immunohistochemical assessment of the epipharyngeal mucosa, the staining intensity of ACE2 and TMPRSS2 was described as an immunohistochemical score (IHC score). The IHC scores for ACE2 and TEMPRSS2 in the EAT-treated group were 3.40-fold and 1.81-fold lower, respectively, than those in the non-treated group (p=0.0208 and p=0.0244, respectively). EAT down-regulates the expression of SARS-CoV-2 entry factors ACE2 and TMPRSS2. Thus, EAT has potential as a novel COVID-19 preventative method.


Bullying by peers in childhood and effects on psychopathology, suicidality, and criminality in adulthood.
Bullying is shown to be associated with adverse outcomes in cross-sectional studies, but only a few studies have prospectively examined the effects of childhood bullying on adult outcomes. Our Series paper focuses on prospective longitudinal studies that used large, population-based, community samples analysed through quantitative methods and published between 1960 and 2015. We describe the results of childhood bullying in adulthood in three of the most burdensome areas: psychopathology, suicidality, and criminality. We note that the different groups involved (ie, victims, bullies, and bully-victims) are at risk of difficulties later in life, but their risk profiles differ and the contributions are probably not independent. Controlling for confounders reduces the risk and sometimes eliminates it. Victims are at a high risk of internalising disorders. Bullies seem to be at risk of later externalising disorders and criminality, mainly violent crime and illicit drug misuse. Bully-victims seem to be at risk of internalising disorders, externalising disorders, and criminality, but not all studies examined bully-victims as a separate group. Boys and girls differ in their long-term outcomes. A dose effect exists in which frequent bullying involvement in childhood is most strongly associated with adult adversities. Future studies need to control for additional factors (including genetic, psychosocial, and environmental) to account for the mechanisms behind the reported longitudinal associations.


Hip position influences shear wave elastography measurements of the hamstring muscles in healthy subjects.
Ultrasound shear wave elastography (SWE) has recently emerged as a non-invasive tool for assessing muscle stiffness. The majority of studies utilizing SWE have focused primarily on upper-extremity muscles, with little attention attributed to lower-extremity muscles. In addition, of the studies that have been published, various joint and muscle positions have been examined, rendering it difficult to compare results across studies. Thus, the purpose of this investigation was to examine lower extremity medial hamstring muscles (semitendinosus and semimembranosus) and to determine how hip position (0° versus 90°) and muscle position (knee flexed versus extended) impacted resulting shear modulus values. Ten subjects varying widely in age participated in this study, and their hamstring stiffness was assessed in four separate positions: seated with the knee flexed and extended, and lying prone with the knee flexed and extended. Higher shear modulus values were found at the group-level when participants were seated compared to prone (hip placed at 90° compared to 0°). In addition, higher values were also found when the knee was extended compared to flexed, but only when the hip was placed at 90° (not 0°). These results demonstrate that joint and muscle position, particularly when assessing the hamstrings, largely impact resulting shear modulus values. Therefore, joint and muscle position need to be systematically controlled for and reported when establishing normative ranges for shear modulus values across specific age groups. This will enable physicians to more precisely determine whether patients' shear modulus values indicate clinically meaningful differences in comparison to normative data.


Efficacy and Tolerability of IncobotulinumtoxinA for Treating Glabellar Frown Lines in Korean Adults: A Postmarketing Observational Study.
IncobotulinumtoxinA is safe and effective in Caucasian adults. Its effects have been less documented in Asian adults. To describe the efficacy and tolerability of incobotulinumtoxinA for treating glabellar frown lines (GFLs) in South Korean adults. South Korean adults aged 18 to 65 years with moderate-to-severe GFLs received a single dose of 10 to 28 U incobotulinumtoxinA during routine clinical practice. After 30 ± 14 days, investigators assessed the efficacy using the Global Aesthetic Improvement Scale and rated tolerability using a 4-point scale. Six hundred seventy-three subjects were enrolled, of which 528 completed the study according to protocol. Glabellar frown lines improved in 98.7% (521/528) of subjects, with 30.8% of cases rated as "very much improved" and 47.4% as "much improved." The extent of improvement was unaffected by sex, age, and weight but was greater when the time between GFL identification and treatment was <6 months (p < .001) and when concomitant aesthetic nondrug treatments were used (p < .001). For 94% of subjects, tolerability was good or very good. All reported adverse events were transient and mild or moderate in severity. IncobotulinumtoxinA was well tolerated and effective for treating moderate-to-severe GFLs in Korean adults irrespective of age, sex, or weight.


Partial otubain 1 deficiency compromises fetal well-being in allogeneic pregnancies despite no major changes in the dendritic cell and T cell compartment.
Pregnancy is characterized by well-defined immunological adaptions within the maternal immune cell compartment allowing the survival of a genetically disparate individual in the maternal womb. Phenotype and function of immune cells are largely determined by intracellular processing of external stimuli. Ubiquitinating and deubiquitinating enzymes are known to critically regulate immune signaling either by modulating the stability or the interaction of the signaling molecules. Accordingly, if absent, critical physiological processes may be perturbed such as fetal tolerance induction. Based on previous findings that mice hemizygous for the deubiquitinating enzyme otubain 1 (OTUB1) do not give rise to homozygous progeny, here, we investigated whether partial OTUB1 deficiency influences fetal-wellbeing in a syngeneic or an allogeneic pregnancy context accompanied by changes in the dendritic cell (DC) and T cell compartment. We observed increased fetal rejection rates in allogeneic pregnant OTUB1 heterozygous dams but not syngeneic pregnant OTUB1 heterozygous dams when compared to OTUB1 wildtype dams. Fetal demise in allogeneic pregnancies was not associated with major changes in maternal peripheral and local DC and T cell frequencies. Thus, our results suggest that OTUB1 confers fetal protection, however, this phenotype is independent of immune responses involving DC and T cells.


Histochemical studies on sialic acids in the epididymis during post-natal development of the rat.
A variety of sialic acids contained in the rat epididymis during post-natal development were examined by means of lectin and carbohydrate histochemistry. Epididymides from male Sprague-Dawley rats on post-natal days 14, 21, 30, 39, 49, 56 and 70 were fixed in Bouin's fluid and embedded routinely in paraffin wax. Hydrated sections were subjected either to the lectin methods using biotinylated Sambucus sieboldiana lectin or Maackia amurensis lectin or to the selective periodate oxidation-phenylhydrazine-thiocarbohydrazide-silver protein-physical development technique with or without saponification. The results revealed that sialic acids appeared in the epididymal epithelium at day 14, followed by particular distribution patterns corresponding to cell differentiation during days 21-39. High-level O-acetylation of sialic acids was observed in the principal cells of the initial segment and proximal caput after day 39. These results suggest that sialic acids with different linkages and O-acetylation become adult in distribution at the 'differentiation' period under the influence of androgen, before spermatozoa reach the epididymal lumen. Such carbohydrates may be correlated, at least in part, with sperm-binding sialoproteins, which increase dramatically during the window between days 21 and 39.


Cholesterol esterase in rat adipose tissue and its activation by cyclic adenosine 3':5'-monophosphate-dependent protein kinase.
A high level of cholesterol esterase activity, comparable to that of hormone-sensitive triglyceridase, has been demonstrated in rad adipose tissue. Essentially all of the activity was in the isolated adipocytes, primarily in the 100,000 times g supernatant fraction of the adipocytes. Cholesterol esterase activity in the 100,000 times g supernatant fraction was increased 40 plus or minus 16% by incubation with ATP (0.5 mM), Mg-2+ (1.25 mM), and cyclic adenosine 3':5'-monophosphate (cyclic AMP) (10 muM), conditions which also activated hormone-sensitive triglyceridase. Protein kinase inhibitor (rabbit skeletal muscle) blocked activation, and activation was restored by the addition of excess protein kinase (bovine skeletal muscle). In extracts prepared from adipocytes first incubated for 5 min with 10 muM epinephrine and 1 mM theophylline, there was no cyclic AMP-dependent cholesterol esterase activation, implying that the enzyme had been activated by a similar mechanism in the intact cell. The physiological role of this high level of cholesterol esterase activity in adipose tissue is unclear. Its relationship to hormone-sensitive triglyceride lipase, with which it extensively co-fractionates, and its possible involvement in fat mobilization remain to be determined.


Infrared spectroscopy of glycolipids.
The application of infrared spectroscopy to the physicochemical characterization of glycolipids as biologically important membrane constituents is described. In this contribution, the analysis of diacyl- and sphingosine-based (cerebroside, ganglioside) oligosaccharides and the class of lipid A-anchored lipooligo- and polysaccharides is reviewed. Furthermore, interaction of glycolipids with various agents as well as of sugars with membranes are discussed. The reviewed data prove the capacity of FTIR spectroscopy to monitor intra- and intermolecular interactions under physiologically relevant conditions refering to pH, temperature, and ion concentrations. This includes the characterization of acyl chain order and the beta<-->alpha chain melting transition, cation and drug binding to charged groups, and supramolecular organization of the glycolipid aggregates. In various examples, the biological relevance of IR data analysis are presented.


DNA lesion alters global conformational dynamics of Y-family DNA polymerase during catalysis.
A major product of oxidative damage to DNA, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxoG), can lead to genomic mutations if it is bypassed unfaithfully by DNA polymerases in vivo. However, our pre-steady-state kinetic studies show that DNA polymerase IV (Dpo4), a prototype Y-family enzyme from Sulfolobus solfataricus, can bypass 8-oxoG both efficiently and faithfully. For the first time, our stopped-flow FRET studies revealed that a DNA polymerase altered its synchronized global conformational dynamics in response to a DNA lesion. Relative to nucleotide incorporation into undamaged DNA, three of the four domains of Dpo4 undertook different conformational transitions during 8-oxoG bypass and the subsequent extension step. Moreover, the rapid translocation of Dpo4 along DNA induced by nucleotide binding was significantly hindered by the interactions between the embedded 8-oxoG and Dpo4 during the extension step. These results unprecedentedly demonstrate that a Y-family DNA polymerase employs different global conformational dynamics when replicating undamaged and damaged DNA.


Nifedipine: effects on fetal and maternal hemodynamics in pregnant sheep.
We investigated the effects of nifedipine, a calcium entry blocker, on the fetal and maternal circulation. Nifedipine was administered intravenously for 30 minutes to chronically instrumented pregnant ewes. Infusion of 5 micrograms.kg-1.min-1 resulted in a 30% to 50% increase in total and regional fetal cerebral blood flow to the brain stem, watershed, and subcortical regions (p less than 0.05), without a significant change in fetal oxygenation or cardiac output. Infusion of 10 micrograms.kg-1.min-1 decreased uterine blood flow by 21% (p less than 0.001) and fetal arterial oxygen content by 15% (p less than 0.01), with no further increase in fetal cerebral blood flow. Maternal arterial pressure decreased and heart rate increased (p less than 0.001) without variation of arterial blood gases. Significant plasma levels of nifedipine were detected in the fetal and maternal circulations. In view of the potential adverse effects on the fetus, further studies are needed before nifedipine is considered for use in human pregnancy.


Multicenter evaluation of AYC.2.2 agar for the isolation of mycobacteria from clinical samples.
The aim of this multicenter study is to evaluate AYC.2.2 agar for the isolation of mycobacteria from clinical samples. Totally 5559 media were tested in 7 centers. AYC.2.2 agar media for the study were prepared by C1 and sent to other centers under appropriate conditions. Other media except AYC.2.2 agar were purchased commercially. The media were subjected to routine laboratory operations in the center where they were sent. After the samples received for routine processing (in all centers, samples were processed with the same method (NALC-NaOH)), they were cultivated on routine media and AYC.2.2 agar afterward. C1: Average growth time was determined as 12.74±3.74 days with MGIT 960 system; 24.42±4.75 days with LJ and 24.37±4.96 days with AYC.2.2 agar. C2: Average growth time was determined as 18.25±9.32 days with TK-Medium, 28.73±7.44 days with LJ, and 31.72±6.35 days with AYC.2.2 agar. C3: Average growth time was determined as 20.48±7.24 days with Ogawa medium, 20.74±7.12 days with LJ, and 20.26±7.43 days with AYC.2.2 agar. C4: Average growth time was determined as 15.27±6.37 days with MGIT 960 system, 22.14±9.1 days with LJ, and 22±8.45 days with AYC.2.2 agar. C5: Average growth time was determined as 13±4.24 days with MGIT 960 system, 32.16±6.23 days with LJ, and 33±5.73 days with AYC.2.2 agar. C6: Average growth time was determined as 9±3.11 days with MGIT 960 system, 18.68±5.32 days with LJ, and 18.34±4.63 days AYC.2.2 agar. C7: Average growth time was determined as 14.74±7.65 with MGIT 960 system, 26.01±8.21 days with LJ, and 26.24±7.88 days with AYC.2.2 agar. In conclusion, similar results were obtained with LJ and Ogawa media and AYC.2.2 agar. Furthermore, more studies should be conducted for isolation of M. tuberculosis and performing antibiotic susceptibility tests using AYC.2.2 agar before it can be used as a routine media in the laboratories.


Weight Loss Results in Increased Expression of Anti-Inflammatory Protein CRISPLD2 in Mouse Adipose Tissue.
Obesity is a major risk factor for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus, whereas weight loss is associated with improved health outcomes. It is therefore important to learn how adipose contraction during weight loss contributes to improved health. It was hypothesized that adipose tissue undergoing weight loss would have a unique transcriptomic profile, expressing specific genes that might improve health. This study conducted an RNA-sequencing analysis of the epididymal adipose tissue of mice fed either a high-fat diet (HFD) or a regular rodent chow diet (RD) ad libitum for 10 weeks versus a cohort of mice fed HFD for the first 5 weeks before being swapped to an RD for the remainder of the study (swapped diet [SWAP]). The swapped diet resulted in weight loss, with a parallel improvement in insulin sensitivity. RNA sequencing revealed several transcriptomic signatures distinct to adipose tissue in SWAP mice, distinguished from both RD and HFD adipose tissue. The analysis found a unique upregulated mRNA that encodes a secreted lipopolysaccharide-binding glycoprotein (CRISPLD2) in adipose tissue. Whereas cellular CRISPLD2 protein levels were unchanged, plasma CRIPSLD2 levels increased in SWAP mice following weight loss and could correlate with insulin sensitivity. Taken together, these data demonstrate that CRISPLD2 is a circulating adipokine that may regulate adipocyte remodeling during weight loss.


Willem Hendrik Gispen--an interview.
This text is based on three long interviews in Utrecht University's Faculty Club, and on almost 40 years of working together in the same city, the same department, the same university.


Small-angle x-ray scattering study of insect lipophorin.
The structure of lipophorin in insect blood (hemolymph) was investigated by a small-angle x-ray scattering method over the temperature range 0-45 degrees C. The small-angle x-ray scattering profile of lipophorin exhibited a symmetrical sphere with heterogeneous internal electron density. Cockroach and locust lipophorins, which contain hydrocarbons, demonstrated centrosymmetrical distribution of electron density inside the particles. A previous study suggested that the hydrocarbon-rich region is located in the core of lipophorin particle (Katagiri, C., Kimura, J., and Murase, N. (1985) J. Biol. Chem. 260, 13490-13495). Distance distribution functions, P (r), calculated for a simulated three-layer model (electron-rich shell, middle layer, and electron-deficient core) with radial electron density distribution, show good agreement with those observed experimentally for cockroach and locust lipophorins. The dimensions and electron density obtained for the middle layer reveal that this layer is occupied mainly by diacylglycerol and apolipophorin II. Thus, the present study together with previous reports strongly suggest that insect lipophorin is composed of centrosymmetrical three layers; an outer shell with apolipophorin I and phospholipid, a middle layer with diacylglycerol and apolipophorin II, and a core with hydrocarbons.


Associations between macular retinal vasculature and severity of idiopathic epiretinal membrane.
To demonstrate the associations between the morphology of macular retinal vasculature and disease severity of idiopathic epiretinal membrane (ERM). Macular structures were assessed using optical coherence tomography (OCT), and were classified as "with pseudohole" or "without pseudohole". The 3 × 3 mm macular OCT angiography images were analyzed using the Fiji software to obtain the vessel density, skeleton density, average vessel diameter, vessel tortuosity, fractal dimension, and foveal avascular zone (FAZ)-related parameters. The correlations between these parameters and ERM grading as well as visual acuity were analyzed. For ERM with or without a pseudohole, increased average vessel diameter, decreased skeleton density, and decreased vessel tortuosity were all associated with inner retinal folding and thickened inner nuclear layer, indicating more severe ERM. In 191 eyes without a pseudohole, the average vessel diameter increased, fractal dimension decreased and vessel tortuosity decreased with increasing ERM severity. The FAZ was not associated with ERM severity. Decreased skeleton density (r = -0.37), vessel tortuosity (r = -0.35), and increased average vessel diameter (r = 0.42) were correlated with worse visual acuity (All P < 0.001). In 58 eyes with pseudoholes, a larger FAZ was associated with a smaller average vessel diameter (r = -0.43, P = 0.015), higher skeleton density (r = 0.49, P < 0.001), and vessel tortuosity (r = 0.32, P = 0.015). However, none of the retinal vasculature parameters correlated with visual acuity and central foveal thickness. Increased average vessel diameter, decreased skeleton density, decreased fractal dimension and decreased vessel tortuosity were good indicators of ERM severity and associated visual impairment.


Coenzyme A stimulates collagen production in cultured fibroblasts; possible mechanisms in enzymatic and gene expression.
Coenzyme A, a cofactor in enzymatic acetyl transfer reactions, stimulates collagen production in cultured fibroblasts. The mechanisms involved in this collagen stimulation were investigated. Enzymatic studies using radiolabeled procollagen as substrate revealed that coenzyme A enhanced prolyl hydroxylase activity. Prolyl hydroxylase is a key enzyme in collagen synthesis acting by hydroxylation of proline residues in procollagen peptide, which is necessary for stabilizing collagen. Northern blot analysis demonstrated that coenzyme A also enhanced mRNA levels of both the alpha subunit of prolyl hydroxylase and the alpha1 chain of type I collagen. The levels of protein production of prolyl hydroxylase and type I collagen were also increased in cultured fibroblasts by coenzyme A, which correlated well with observations from Northern blotting. On the other hand, coenzyme A did not stimulate the activity nor the gene expression of two other processing enzymes: lysyl hydroxylase, which provides the sites for glycosylation and crosslinking between collagen peptides, and lysyl oxidase, a fundamental enzyme in intermolecular crosslinking. These results indicate that coenzyme A stimulates collagen production by at least two separate mechanisms: by enhancing prolyl hydroxylase activity as well as stimulating gene expression of the alpha subunit of this enzyme, and by stimulating gene expression of alpha1 chain of type I collagen.


Exploiting RNA as a new biomolecular target for synthetic polyamines.
Anticancer chemotherapy is strongly hampered by the low therapeutic index of most anticancer drugs and the development of chemoresistance. Therefore, there is a continued need for the identification of new molecular targets in order to selectively hit cancer cells. RNA has been recently validated as a cancer target by the use of different specific ligands and/or by different agents able to destroy its diverse forms. The ability of synthetic polyamines to interact and to alter the RNA structure has been already reported. In the present paper the interaction and the ability to damage RNA structure by several synthetic polyamines were evaluated and quantified by microfluid capillary electrophoresis. This technique allowed us to visualize both the RNA impairment through different electropherograms and to assess the RNA integrity number. Finally, the ability to discriminate between RNA and DNA by these synthetic polyamines was also evaluated.


Erosion by an Alpine glacier.
Assessing the impact of glaciation on Earth's surface requires understanding glacial erosion processes. Developing erosion theories is challenging because of the complex nature of the erosion processes and the difficulty of examining the ice/bedrock interface of contemporary glaciers. We demonstrate that the glacial erosion rate is proportional to the ice-sliding velocity squared, by quantifying spatial variations in ice-sliding velocity and the erosion rate of a fast-flowing Alpine glacier. The nonlinear behavior implies a high erosion sensitivity to small variations in topographic slope and precipitation. A nonlinear rate law suggests that abrasion may dominate over other erosion processes in fast-flowing glaciers. It may also explain the wide range of observed glacial erosion rates and, in part, the impact of glaciation on mountainous landscapes during the past few million years.


Performance Effects with Injury Prevention Exercise Programmes in Male Youth Football Players: A Randomised Trial Comparing Two Interventions.
Increased performance from injury prevention exercise programmes (IPEPs) may affect injury risks positively and support the implementation of IPEPs. The primary aim was to study the performance effects of injury prevention exercises from two different IPEPs, the Knee Control IPEP and the further developed Knee Control+ IPEP, in youth male football players, and the secondary aim was to compare potential differences in performance effects between the IPEPs. Four male youth football teams were tested for agility, hop and sprint performance at the start of the second half of the competitive season and after the end of the 8-week season. Per randomisation, two teams used Knee Control and two teams Knee Control+. In total, 47 players executed a median of 13 IPEP sessions (range 11-21 sessions). No improvements in performance were seen in the group as a whole. The intervention groups showed small declines in sprint and agility performance. There was a significant between-group difference in change for the 505 agility test, with improved performance in the Knee Control and worse performance in the Knee Control+ group, ΔKC vs KC+ = - 0.012 (95% CI - 0.19 to -0.04), d = 0.98. No clinically meaningful performance effects were seen from the Knee Control or Knee Control+ IPEP in youth male athletes and no meaningful differences were seen between Knee Control and Knee Control+ regarding effects on performance tests. ClinicalTrials.gov identifier: NCT03251404 . Registered on 16 August 2017.


Feline leukemia virus: survival under home and laboratory conditions.
Feline leukemia virus maintained its infectiousness in cell culture medium at 37 degrees C or lower for at least 48 h. However, virus in saliva or medium was inactivated within a few hours if allowed to dry.


Nickel metallomics: general themes guiding nickel homeostasis.
The nickel metallome describes the distribution and speciation of nickel within the cells of organisms that utilize this element. This distribution is a consequence of nickel homeostasis, which includes import, storage, and export of nickel, incorporation into metalloenzymes, and the modulation of these and associated cellular systems through nickel-regulated transcription. In this chapter, we review the current knowledge of the most common nickel proteins in prokaryotic organisms with a focus on their coordination environments. Several underlying themes emerge upon review of these nickel systems, which illustrate the common principles applied by nature to shape the nickel metallome of the cell.


Leucine to tryptophane substitution in the pore helix IIP1 confer sodium channel resistance to pyrethroids and DDT.
Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.


Computation of solution to fractional order partial reaction diffusion equations.
In this article, the considered problem of Cauchy reaction diffusion equation of fractional order is solved by using integral transform of Laplace coupled with decomposition technique due to Adomian scheme. This combination led us to a hybrid method which has been properly used to handle nonlinear and linear problems. The considered problem is used in modeling spatial effects in engineering, biology and ecology. The fractional derivative is considered in Caputo sense. The results are obtained in series form corresponding to the proposed problem of fractional order. To present the analytical procedure of the proposed method, some test examples are provided. An approximate solution of a fractional order diffusion equation were obtained. This solution was rapidly convergent to the exact solution with less computational cost. For the computation purposes, we used MATLAB.


Correction to: SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016).
Due to a technical issue, the family name of the author.


An aggregating U-Test for a genetic association study of quantitative traits.
We propose a novel aggregating U-test for gene-based association analysis. The method considers both rare and common variants. It adaptively searches for potential disease-susceptibility rare variants and collapses them into a single "supervariant." A forward U-test is then used to assess the joint association of the supervariant and other common variants with quantitative traits. Using 200 simulated replicates from the Genetic Analysis Workshop 17 mini-exome data, we compare the performance of the proposed method with that of a commonly used approach, QuTie. We find that our method has an equivalent or greater power than QuTie to detect nine genes that influence the quantitative trait Q1. This new approach provides a powerful tool for detecting both common and rare variants associated with quantitative traits.


What is the effectiveness of printed educational materials on primary care physician knowledge, behaviour, and patient outcomes: a systematic review and meta-analyses.
Printed educational materials (PEMs) are commonly used simple interventions that can be used alone or with other interventions to disseminate clinical evidence. They have been shown to have a small effect on health professional behaviour. However, we do not know whether they are effective in primary care. We investigated whether PEMs improve primary care physician (PCP) knowledge, behaviour, and patient outcomes. We conducted a systematic review of PEMs developed for PCPs. Electronic databases were searched for randomized controlled trials, quasi randomized controlled trials, controlled before and after studies, and interrupted time series. We combined studies using meta-analyses when possible. Statistical heterogeneity was examined, and meta-analysis was performed using a random effects model when significant statistical heterogeneity was present and a fixed effects model otherwise. The template for intervention description and replication (TIDieR) checklist was used to assess the quality of intervention description. Our search identified 12,439 studies and 40 studies met our inclusion criteria. We combined outcomes from 26 studies in eight meta-analyses. No significant effect was found on clinically important patient outcomes, physician behaviour, or physician cognition when PEMs were compared to usual care. In the 14 studies that could not be included in the meta-analyses, 14 of 71 outcomes were significantly improved following receipt of PEMs compared to usual care. Most studies lacked details needed to replicate the intervention. PEMs were not effective at improving patient outcomes, knowledge, or behaviour of PCPs. Further trials should explore ways to optimize the intervention and provide detailed information on the design of the materials. PROSPERO, CRD42013004356.


Currarino syndrome in an elderly man: Multimodality imaging findings.
Currarino syndrome is a rare congenital disorder characterized by the triad of anorectal anomalies, sacrococcygeal dysgenesis and presacral mass. Because of the anorectal anomalies, the extrinsic compression due to the presacral mass and neurologic deficits, patients usually present with gastrointestinal symptoms, most commonly chronic constipation. Most cases of Currarino syndromes are diagnosed in childhood, at birth or in the pre-birth period and, even if adult presentation has been reported in few sporadic case reports, the diagnosis in the late stages of life remains extremely rare. In this paper, we describe the imaging findings of an elderly man with a past medical history of megacolon surgically treated in his childhood, who was diagnosed with Currarino syndrome at the age of 72.


Role of magnetic resonance spectroscopic imaging ([¹H]MRSI) and dynamic contrast-enhanced MRI (DCE-MRI) in identifying prostate cancer foci in patients with negative biopsy and high levels of prostate-specific antigen (PSA).
The purpose of this study was to evaluate the role of magnetic resonance spectroscopic imaging (MRSI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in detecting tumour foci in patients with elevated prostate-specific antigen (PSA) and negative transrectal ultrasonography (TRUS)-guided biopsy. This prospective randomised trial was conducted on 150 patients who underwent [¹H]MRSI and DCE-MRI and targeted biopsies of suspicious areas on MRI associated with random biopsies. After the second biopsy, the diagnosis of prostate adenocarcinoma was made in 64/150 cases. On a per-patient basis, MRSI had 82.8% sensitivity, 91.8% specificity, 88.3% positive predictive value (PPV), 87.8% negative predictive value (NPV) and 85.7% diagnostic accuracy. The sensitivity, specificity, PPV, NPV and accuracy for DCE-MRI was 76.5%, 89.5%, 84.5%, 83.7% and 82%, respectively. The combination of MRSI and DCE-MRI yielded 93.7% sensitivity, 90.7% specificity, 88.2% PPV, 95.1% NPV and 90.9% accuracy in detecting prostate carcinoma. The combined study with [¹H]MRSI and DCE-MRI showed promising results in guiding the biopsy of cancer foci in patients with an initial negative TRUS-guided biopsy.


Interaction Between Diabetes Mellitus and Platelet Reactivity in Determining Long-Term Outcomes Following Percutaneous Coronary Intervention.
Diabetes mellitus (DM) is an independent predictor of adverse outcomes in patients with coronary artery disease (CAD). We investigated the interaction between DM and high platelet reactivity (HPR) in determining long-term clinical outcomes after percutaneous coronary intervention (PCI). We enrolled 500 patients who were divided based on the presence of DM and HPR. Primary endpoint was the occurrence of major adverse clinical events (MACE) at 5 years. Patients with both DM and HPR showed the highest estimates of MACE (37.9%, log-rank p < 0.001), all-cause death (15.5%, log-rank p = 0.022), and non-fatal myocardial infarction (25.9%, log-rank p < 0.001). At Cox proportional hazard analysis, the coexistence of DM and HPR was an independent predictor of MACE (HR 3.46, 95% CI 1.67-6.06, p < 0.001). Among patients with stable CAD undergoing elective PCI and treated with aspirin and clopidogrel, the combination of DM and HPR identifies a cohort of patients with the highest risk of MACE at 5 years.


Baculovirus as an ideal radionuclide reporter gene vector: a new strategy for monitoring the fate of human stem cells in vivo.
Radionuclide reporter gene imaging holds promise for non-invasive monitoring of transplanted stem cells. Thus, the feasibility of utilizing recombinant baculoviruses carrying the sodium iodide symporter (NIS) reporter gene in monitoring stem cell therapy by radionuclide imaging was explored in this study. Recombinant baculoviruses carrying NIS and green fluorescent protein (GFP) reporter genes (Bac-NIS and Bac-GFP) were constructed and used to infect human induced pluripotent stem cells (hiPSCs), human embryonic stem cells (hESCs) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Infection efficiency, total fluorescence intensity and duration of transgene expression were determined by flow cytometry. Cytotoxicity/proliferative effects of baculovirus on hUCB-MSCs were assessed using CCK-8 assays. ¹²⁵I uptake and perchlorate inhibition assays were performed on Bac-NIS-infected hUCB-MSCs. Radionuclide imaging of mice transplanted with Bac-NIS-infected hUCB-MSCs was performed by NanoSPECT/CT imaging. Infection efficiencies of recombinant baculovirus in hESCs, hiPSCs and hUCB-MSCs increased with increasing MOIs (27.3%, 35.8% and 95.6%, respectively, at MOI = 800). Almost no cytotoxicity and only slight effects on hUCB-MSCs proliferation were observed. Obvious GFP expression (40.6%) remained at 8 days post-infection. The radioiodide was functionally accumulated by NIS gene products and specifically inhibited by perchlorate (ClO₄⁻). Radioiodide uptake, peaking at 30 min and gradually decreasing over time, significantly correlated with hUCB-MSCs cell number (R² = 0.994). Finally, radionuclide imaging showed Bac-NIS-infected hUCB-MSCs effectively accumulated radioiodide in vivo, which gradually weakened over time. Baculovirus as transgenic vector of radionuclide reporter gene imaging technology is a promising strategy for monitoring stem cell transplantation therapy.


Peptide enrichment by microfluidic electrocapture for online analysis by electrospray mass spectrometry.
Identification of peptides from a complex mixture can be difficult because of the wide concentration range and the different ionization efficiencies of peptides during analysis by electrospray ionization (ESI) mass spectrometry (MS). Preconcentration methods are necessary to allow low-abundance and low-intensity peptides to reach the ionization threshold of the mass spectrometer. Here we demonstrate peptide enrichment based on electroimmobilization. Peptides are immobilized without the use of solid support or chemical binding by application of an electric field along a microflow stream in an electrocapture cell. Once enriched/preconcentrated inside the cell, they are released by removal of the electric field and via an interface with an electrospray emitter are submitted to online mass spectrometric analysis. Tandem mass spectrometric analysis of a peptide mixture containing hemoglobin, myoglobin, bovine serum albumin (BSA), and cytochrome c was successful. Amplification factors up to 16-fold were achieved with improvement of the signal-to-noise values for the preconcentrated sample. The limit of detection for one of the preconcentrated peptides was 3.6 fmol.


Are lifestyle changes from online information associated with discussing the information with a doctor? A cross -sectional study.
The prevalence of diabetes and the use of electronic health (eHealth) are increasing. Lifestyle changes in a positive direction may reduce morbidity and mortality in patients with diabetes. The main objective of this study was to test the association between lifestyle changes based on online information seeking and discussing the information with a doctor. In this cross-sectional study we used e-mail survey data from 1250 members of The Norwegian Diabetes Association, collected in 2018. Included in the analyses were 847 men and women aged 18 to 89 years diagnosed with diabetes and who reported use of eHealth within the previous year. We used descriptive statistics to estimate lifestyle changes based on information from the internet. Logistic regressions were used to estimate the associations between lifestyle changes after online information seeking and discussing the information with a doctor. Analyses were adjusted for gender, age, education, and self-rated health. Lifestyle changes accomplished after online information seeking was reported by 46.9% (397/847) of the participants. The odds of changing lifestyle were more than doubled for those who had discussed information from the internet with a doctor (odds ratio 2.54, confidence interval 1.90-3.40). The odds of lifestyle changes were lower in the age groups 30-39 years and 60 years and over, compared to those aged 18-29 years (the reference group). Lifestyle changes were not associated with gender, education, or self-rated health. Our findings indicate that health-care professionals can play an important role in lifestyle changes additional to health-advice found on the internet. This study underlines the importance of easily accessible high-quality online information, as well as the importance of making room for discussing lifestyle in the clinical encounter.


The Effect of a Drug Adherence Enhancement Program on the Drug Adherence Behaviors of Patients With Major Depressive Disorder in Thailand: A Randomized Clinical Trial.
This study aimed to compare drug adherence behaviors during the sixth week between patients with first diagnosed major depressive disorder who received the Drug Adherence Enhancement Program and those who received only the usual care. A randomized clinical trial, post-test only design was conducted in the outpatient-unit of a medical school hospital in Bangkok, Thailand. The experimental and control groups consisted of 30 and 26 participants respectively. Participants in the experimental group exhibited significantly higher drug adherence behaviors than the control group. This is important for nurses in promoting adherence to antidepressant drugs for patients with first diagnosed major depressive disorder.


Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients With Thoracolumbar Spine Trauma: Classification of Injury.
Are there classification systems for fractures of the thoracolumbar spine that have been shown to be internally valid and reliable (ie, do these instruments provide consistent information between different care providers)? A classification scheme that uses readily available clinical data (eg, computed tomography scans with or without magnetic resonance imaging) to convey injury morphology, such as Thoracolumbar Injury Classification and Severity Scale or the AO Spine Thoracolumbar Spine Injury Classification System, should be used to improve characterization of traumatic thoracolumbar injuries and communication among treating physicians. Strength of Recommendation: Grade B. In treating patients with thoracolumbar fractures, does employing a formally tested classification system for treatment decision-making affect clinical outcomes? There is insufficient evidence to recommend a universal classification system or severity score that will readily guide treatment of all injury types and thereby affect outcomes. Strength of Recommendation: Grade Insufficient The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_2.


Knee skin temperature response of patients with bilateral patellofemoral syndrome before and after heat and cold stress.
Patellofemoral Pain Syndrome is characterized by the presence of pain in the front area of the knee, which occurs when performing common activities such as climbing stairs, and bending the knees, among others. The objective of this research was to evaluate the detection capability of infrared thermography in patients with Patellofemoral Pain Syndrome, in the baseline state, as well as after the application of thermal stress. The investigation was conducted in 48 patients, who were subdivided into four groups (n = 12). Two subgroups were healthy patients and two with Patellofemoral Pain Syndrome. For the diagnosis of the syndrome, a manual evaluation was performed using the Zohlen test and Q angle measurement. Subsequently, cold stress was applied for 10 min to a healthy subgroup and an experimental subgroup. The remaining two subgroups were subjected to heat stress for 15 min. Thermographic images of the lower extremities were acquired at seven time points, at baseline, immediately after application of thermal stress and then every 3 min until 15 min were completed. It was observed that patients presented Patellofemoral Pain Syndrome bilaterally. After statistical analysis, it was found that there were no significant differences in baseline temperature between the groups. However, for heat stress, a higher temperature was observed in the group with Patellofemoral Pain Syndrome (p < 0.05) in the recovery period, and in the case of cold stress, only a lower temperature in the left knee immediately after the application. In conclusion, it is not possible to detect patellofemoral syndrome bilaterally in the baseline state by thermography and neither is it evident in cold stress. However, after heat stress, thermal recovery is lower for the PFPS group, so it would be susceptible to detection.


Systemic treatment for hormone receptor-positive/HER2-negative advanced/metastatic breast cancer: A review of European real-world evidence studies.
This review examined patterns of systemic anticancer treatment in patients with HR+ /HER2- metastatic breast cancer in real-world clinical practice in Europe since 2016 to assess whether they reflect clinical guidelines and recent changes in available treatment options. We identified 30 publications for inclusion. In studies evaluating patients up to the end of 2017, endocrine therapy predominated, with endocrine monotherapy typically used in 45-65 % of patients. More recent studies suggested that use of cyclin-dependent kinase 4/6 inhibitor therapy has gained ground since European approval in late 2016, with two studies reporting first-line use in over 55 % of patients. Chemotherapy was typically used first line in 25-45 % of patients, although current guidelines recommend endocrine therapy in the absence of a visceral crisis. In conclusion, our review suggests that the most recent treatment developments for patients with HR+ /HER2 - metastatic breast cancer are being reflected in the changing treatment patterns seen in real-world practice.


Improving the contribution of public health to NHS decision making: development of an instrument.
Recent policy pronouncements have raised expectations that public health practitioners will be increasingly involved in NHS decision making. This is a complex task which requires the bringing together of appropriate data and values. The authors developed an instrument, to aid decision making, which seeks to make explicit the values held by key health decision makers at local level. We report on the evolution of the project and the development of the instrument. This work is then placed within the context of the current renaissance in British public health, as the instrument could be useful when public health issues are being decided by or with partners within the National Health Service (NHS), the local authorities or the wider community.


Idiopathic lipoid pneumonia in an adult treated with prednisolone.
The treatment of lipoid pneumonia, an uncommon chronic lung condition, is generally conservative. We describe a patient with idiopathic lipoid pneumonia who was successfully treated with oral steroids with improvement of chest radiographic abnormalities.


DDeep3M: Docker-powered deep learning for biomedical image segmentation.
Deep learning models are turning out to be increasingly popular in biomedical image processing. The fruitful utilization of these models, in most cases, is substantially restricted by the complicated configuration of computational environments, resulting in the noteworthy increment of the time and endeavors to reproduce the outcomes of the models. We thus present a Docker-based method for better use of deep learning models and quicker reproduction of model performance for multiple data sources, permitting progressively more biomedical scientists to attempt the new technology conveniently in their domain. Here, we introduce a Docker-powered deep learning model, named as DDeep3M and validated it with the electron microscopy data volumes (microscale). DDeep3M is utilized to the 3D optical microscopy image stack in mouse brain for the image segmentation (mesoscale). It achieves high accuracy on both vessels and somata structures with all the recall/precision scores and Dice indexes over 0.96. DDeep3M also reports the state-of-the-art performance in the MRI data (macroscale) for brain tumor segmentation. We compare the performance and efficiency of DDeep3M with three existing models on image datasets varying from micro- to macro-scales. DDeep3M is a friendly, convenient and efficient tool for image segmentations in biomedical research. DDeep3M is open sourced with the codes and pretrained model weights available at https://github.com/cakuba/DDeep3m.


Long-Term Survival of American Joint Committee on Cancer 8th Edition Staging Descriptors for Clinical M1a Non-Small Cell Lung Cancer.
The American Joint Committee on Cancer (AJCC) 8th Edition TNM staging manual for non-small cell lung cancer (NSCLC) M1a descriptors includes tumors seen with malignant pleural or pericardial effusion (ie, M1a-Effusion), pleural or pericardial nodule(s) (ie, M1a-Pleural), or separate tumor nodule(s) in a contralateral lobe (ie, M1a-Contralateral). Is M1a NSCLC seen with malignant pleural or pericardial effusion associated with worse survival compared with other types of M1a NSCLC? Patients with cT1-4, N0-3, M1a NSCLC (satisfying a single M1a descriptor of M1a-Effusion, M1a-Pleural, or M1a-Contralateral), according to AJCC 8th edition staging criteria, in the National Cancer Database from 2010 to 2015 were included. Overall survival was evaluated by using Kaplan-Meier analysis, multivariable-adjusted Cox proportional hazards modeling, and propensity score matching. Of the 25,716 patients who met study eligibility criteria, 12,756 (49.6%) presented with M1a-Effusion tumors, 3,589 (14.0%) with M1a-Pleural tumors, and 9,371 (36.4%) with M1a-Contralateral tumors. In multivariable-adjusted analysis, M1a-Effusion tumors were associated with worse overall survival than M1a-Pleural tumors (hazard ratio [HR], 1.48; 95% CI, 1.40-1.56; P < .001) and M1a-Contralateral tumors (HR: 1.51; 95% CI, 1.46-1.57; P < .001). No significant differences were found in overall survival between patients with M1a-Pleural tumors vs M1a-Contralateral tumors (HR, 0.98; 95% CI, 0.93-1.03; P = .42). In a propensity score-matched analysis of 5,581 patients with M1a-Effusion tumors and 5,581 patients with other M1a tumors (ie, M1a-Contralateral or M1a-Effusion), those with M1a-Effusion tumors had worse 5-year overall survival than patients with other M1a tumors (M1a-Effusion 6.4% [95% CI, 5.7-7.1] vs M1a-Other 10.6% [95% CI, 9.7-11.5]; P < .001). In this national analysis of AJCC 8th Edition cT1-4, N0-3, M1a NSCLC, tumors with malignant pleural or pericardial effusion were associated with worse overall survival than those with either pleural or contralateral pulmonary nodules. These findings may be taken into consideration for the upcoming 9th edition of the lung cancer staging guidelines.


Black carbon in Slovenian alpine lacustrine sediments.
Black carbon (BC) contents were measured in recent sediments in five high altitude remote alpine lakes, i.e. Lake Krisko Sup., Lake Ledvica, Lake Planina, Lake Krn and Lovrensko Lake, and the eutrophic subalpine Lake Bled in Slovenia to follow the history of atmospheric pollution of fossil fuel and local biomass burning in Alps. Organic carbon (OC), its 13C values, total nitrogen and sedimentation rates using 210Pb activity data were also measured. The highest BC contents, reaching 20 mg/gdw, were noted in remote alpine lakes while in the subalpine Lake Bled sediment the concentrations were lower reaching 5 mg/gdw. Lower BC/OC ratios, ranging between 4% and 8%, were typical for remote alpine lakes and increased to about 10% in subalpine Lake Bled. The latter clearly shows the marked importance of local direct pollution sources in comparison to remote atmospheric input which decreases in a W-E direction in parallel with decreasing amounts of precipitation. Based on 210Pb sedimentation data, the minimal BC accumulation rates in sediment cores were detected in the pre-industrialisation period. In the last decades of 20th century the BC contents decreased probably due to reduced emission of pollutants.


A two-site sandwich radioimmunoassay of human fibroblast (beta-) interferon with monoclonal antibodies.
Monoclonal antibodies were produced against human fibroblast (beta-)interferon (IFN-beta). Four of them were directed to the determinant designated a, while the remaining 3 to another determinant named b. An IFN molecule was found to bear one each of a and b determinants arranged in such a manner that the occupation of a with the corresponding antibody did not interfere with the binding of b to its corresponding antibody, and vice versa. This allowed the development of a 2-site sandwich radioimmunoassay in which antibody to b was immobilized on wells of a microtiter plate and the bound antigen was detected by the radiolabeled antibody to a. The 2-site sandwich radioimmunoassay detected, with a high sensitivity, IFN-beta either induced from fibroblast or produced by Escherichia coli harboring the gene of IFN-beta.


The unmet need for birth control in five Asian countries.
The unmet need for family planning services is remarkably constant across all five countries because of the interaction of fertility intentions and fertility control: as more women use contraception, more of them want fewer children.


Lower Extremity Stiffness Predicts Ground Reaction Force Loading Rate in Heel Strike Runners.
High vertical ground reaction force (vGRF) loading rates are thought to contribute to lower extremity injuries in runners. Given that elevated lower extremity stiffness has been reported to be associated with increased GRFs, the purpose of the current study was to determine if overall lower extremity stiffness, individual joint angular excursions and/or torsional stiffness are predictive of the average vGRF loading rate during running. Forty heel strike runners (20 men and 20 women) ran overground at a speed of 3.4 m·s. Average vGRF loading rate, lower extremity stiffness, and hip, knee, and ankle joint excursions and torsional stiffness from initial contact to the first peak of the vGRF were quantified. Stepwise multiple linear regression was performed to determine the best predictor(s) of average vGRF loading rate. Lower extremity stiffness was found to the best predictor of average vGRF loading rate (R = 0.68, P < 0.001). The second variable that entered the stepwise regression model of average vGRF loading rate was knee joint excursion (ΔR = 0.03, P = 0.023). Increased lower extremity stiffness immediately after initial contact may expose heel strike runners to higher vGRF loading rates.


Emergence of different crystal morphologies using the coffee ring effect.
Macroscopic patterns in nature formed during crystal growth e.g. snow crystals have a significant influence on many material properties, such as macroscopic heat conduction, electrical conduction, and mechanical properties, even with the same microscopic crystal structure. Although crystal morphology has been extensively studied in bulk, the formation of patterns induced by re-crystallization during evaporation is still unclear. Here, we find a way to obtain concentric circles, a dendritic pattern, and a lattice pattern by pinning the edge of droplets using the coffee ring effect; only aggregates of crystallites are seen in the absence of pinning. Our systematic study shows that the macroscopic patterns depend both on initial concentration and evaporation rate. In addition, our qualitative analysis suggests that the local concentration of solute at the center of the pattern is related to the macroscopic patterns.


Time of the day for 11beta-HSD1 inhibition plays a role in improving glucose homeostasis in DIO mice.
The physiological effects of glucocorticoids in a given tissue are driven by the local level of the active glucocorticoid, which is determined by two sources: the plasma cortisol in human (or corticosterone in rodents) and the cortisol produced locally through 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity. Because of the circadian variation of plasma glucocorticoids, the pharmacological efficacy of 11beta-HSD1 inhibition may depend on the time of the day for inhibitor administration. The circadian profile of corticosterone was established in lean and diet-induced obesity (DIO) C57BL/6 mice from blood collected at different time of the day. 11beta-HSD1 enzyme activity was also measured throughout the day in DIO mice. To determine the optimal timing for administration of an 11beta-HSD1 inhibitor to obtain maximum efficacy, we used a DIO mouse model and a small molecule inhibitor of 11beta-HSD1 from our thiazolinone series. Based on the circadian profile of corticosterone obtained, we administered the 11beta-HSD1 inhibitor to these animals at different times of the day and evaluated the effects on plasma glucose levels and glucose tolerance. We report that corticosterone circadian rhythm was similar between lean and DIO C57BL/6 mice, and 11beta-HSD1 enzyme activity undergoes minimal variations throughout the day. Interestingly, the compound exhibited maximum efficacy if dosed in the afternoon when plasma corticosterone is high; the morning dosing when plasma corticosterone is low did not lead to efficacy. These data suggest that because of the circadian rhythm of circulating glucocorticoids, the time of the day for 11beta-HSD1 inhibitor administration is important in achieving efficacy.


Inhibition of ascorbic acid uptake by endotoxin: evidence of mediation by serum factor(s).
The effect of bacterial endotoxin on the ascorbic acid uptake by 3T6 fibroblasts was studied. Endotoxin inhibited ascorbic acid uptake by fibroblasts in a dose dependent manner. The inhibition by endotoxin takes place only in the presence of unheated serum; decomplementing serum by heat inactivation at 56 degrees C for 30 minutes eliminates endotoxin's inhibitory effect on ascorbic acid uptake. The effect of endotoxin appears to be instantaneous since the inhibition seen in the cells without any preexposure was similar to the cells preexposed to endotoxin for up to 6 hours. Polymyxin B sulfate which is known to bind the lipid A portion of endotoxin did not reverse the inhibition of ascorbic acid uptake caused by endotoxin.


A soy protein Lunasin can ameliorate amyloid-beta 42 mediated neurodegeneration in Drosophila eye.
Alzheimer's disease (AD), a fatal progressive neurodegenerative disorder, also results from accumulation of amyloid-beta 42 (Aβ42) plaques. These Aβ42 plaques trigger oxidative stress, abnormal signaling, which results in neuronal death by unknown mechanism(s). We misexpress high levels of human Aβ42 in the differentiating retinal neurons of the Drosophila eye, which results in the Alzheimer's like neuropathology. Using our transgenic model, we tested a soy-derived protein Lunasin (Lun) for a possible role in rescuing neurodegeneration in retinal neurons. Lunasin is known to have anti-cancer effect and reduces stress and inflammation. We show that misexpression of Lunasin by transgenic approach can rescue Aβ42 mediated neurodegeneration by blocking cell death in retinal neurons, and results in restoration of axonal targeting from retina to brain. Misexpression of Lunasin downregulates the highly conserved cJun-N-terminal Kinase (JNK) signaling pathway. Activation of JNK signaling can prevent neuroprotective role of Lunasin in Aβ42 mediated neurodegeneration. This neuroprotective function of Lunasin is not dependent on retinal determination gene cascade in the Drosophila eye, and is independent of Wingless (Wg) and Decapentaplegic (Dpp) signaling pathways. Furthermore, Lunasin can significantly reduce mortality rate caused by misexpression of human Aβ42 in flies. Our studies identified the novel neuroprotective role of Lunasin peptide, a potential therapeutic agent that can ameliorate Aβ42 mediated neurodegeneration by downregulating JNK signaling.


Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor.
Epidermal growth factor (EGF) and transforming growth factor type I (TGF) are polypeptides of 53 and 50 amino acid residues, respectively. Both bind to EGF receptor, a 1,200-residue transmembranous glycoprotein, leading to phosphorylation of the receptor, enhancement of its tyrosine-specific kinase activity and ultimately to stimulation of cell growth. We report here that a 140-residue polypeptide encoded by one of the early genes of vaccinia virus (VV) is related closely to EGF and TGF. The presence of putative signal and transmembranous sequences further suggests that the viral protein might be an integral membrane protein, but that, as in the case of EGF itself, the membrane-associated form may be the precursor of a soluble growth factor. Production of EGF-like growth factors by virally infected cells could account for the proliferative diseases associated with members of the poxvirus family such as Shope fibroma virus, Yaba tumour virus, and molluscum contagiosum virus (MCV).


The MFMU Cesarean Registry: uterine atony after primary cesarean delivery.
The purpose of this study was to define independent risk factors for uterine atony after primary cesarean delivery, and to assess their overall association with atony in the study cohort. This was a 13-university center prospective observational study. All women who underwent primary cesarean from January 1, 1999 to December 31, 2000 were eligible. Trained and certified research nurses performed systematic data abstraction. The definition of atony required both the clinical diagnosis and the use of methergine or a prostaglandin preparation. Risk factors for uterine atony were assessed in univariable and multivariable logistic regression analyses, and these analyses then used to inform an assessment of the association of the various risk factors with the occurrence of uterine atony in the overall cohort. Twenty-three thousand, three hundred and ninety pregnancies were analyzed. Uterine atony occurred in 1416 women (6%). Several variables were independently associated with atony in a multivariable model, including multiple gestation (odds ratio [OR] 2.40, 95% CI 1.95-2.93), maternal Hispanic race (2.21, 1.90-2.57), induced or augmented labor for >18 hours (2.23, 1.92-2.60), infant birth weight >4500 g (2.05, 1.53-2.69), and clinically diagnosed chorioamnionitis (1.80, 1.55-2.09). However, because the various risk factors were not very powerful, approximately half of the cases of atony were associated with the 2/3 of women lacking a given risk factor or combination of risk factors. Although certain risk factors and uterine atony were clearly associated, the associations are of limited practical clinical use.


Ruptured aneurysm of a persistent primitive hypoglossal artery treated by endovascular approach--case report and literature review.
A persistent PHA is the second most common of the embryonic carotid-basilar anastomoses that fail to regress in the embryo. The fact that PHA often is functionally a single artery providing blood to the posterior circulation poses challenging therapeutic problems in case of an aneurysm located on the PHA. A 46-year-old woman presented with SAH due to a large ruptured aneurysm of the left PHA. Identification of such an artery by CT angiogram is the proposed cold standard. The aneurysm was obliterated by coil embolization. To our knowledge, this is the first reported case of aneurysm located on a primitive persistent hypoglossal artery that was endovascularly treated. Aneurysms located on a persistent PHA can be treated safely and effectively via an endovascular approach.


Patient Satisfaction Following Level II Oncoplastic Breast Surgery: A Comparison with Mastectomy Utililizing the Breast-Q Questionnaire will be published in Surgical Oncology.
Oncoplastic breast surgery (OBS) is increasingly used to decrease the deformity in breast conserving therapy (BCT) for breast cancer. We aimed to evaluate patient reported satisfaction following level II OBS and mastectomy utilizing the BREAST-Q questionnaire. Patients who underwent level II OBS BCT and those who underwent mastectomies were distributed the BREAST-Q post-reduction/mammoplasty module. Clinicopathological data were collected from review of patient charts. Results were scored using the standardized scoring system (Q-score). Results of the OBS group were compared to those in the mastectomy group. A total of 88 patients who underwent level II OBS and 101 patients who underwent mastectomy completed the questionnaire. Mann-Whitney odds estimator demonstrated higher satisfaction with breasts (1.51, 95% CI [1.04-2.25], p = 0.026) and higher psychosocial well-being (1.51, 95% CI [1.04-2.15], p = 0.022) in those who underwent OBS compared to mastectomy. Results demonstrate a high satisfaction with breasts and improved psychosocial wellbeing in patients who underwent level II OBS compared to those undergoing mastectomy. These results demonstrate that OBS should be considered in patients where mastectomy otherwise would be necessary. Further larger multi-institutional studies are necessary to examine the effect of OBS on the quality of life of breast cancer patients.


Survey of clinical and commensal Escherichia coli from commercial broilers and turkeys, with emphasis on high-risk clones using APECTyper.
Molecular characterization of avian pathogenic Escherichia coli (APEC) is challenging due to the complex nature of its associated disease, colibacillosis, in poultry. Numerous efforts have been made toward defining APEC, and it is becoming clear that certain clonal backgrounds are predictive of an avian E. coli isolate's virulence potential. Thus, APEC can be further differentiated as high-risk APEC based upon their clonal background's virulence potential. However, less clear is the degree of overlap between clinical isolates of differing bird type, and between clinical and gastrointestinal isolates. This study aimed to determine genomic similarities and differences between such populations, comparing commercial broiler vs. turkey isolates, and clinical vs. gastrointestinal isolates. Differences were observed in Clermont phylogenetic groups between isolate populations, with B2 as the dominant group in turkey clinical isolates and G as the dominant group in broiler clinical isolates. Nearly all clinical isolates were classified as APEC using a traditional gene-based typing scheme, whereas 53.4% and 44.1% of broiler and turkey gastrointestinal isolates were classified as APEC, respectively. High-risk APEC were identified among 31.0% and 46.9% of broiler and turkey clinical isolates, compared with 5.7% and 2.9% of broiler and turkey gastrointestinal isolates. As found in previous studies, no specific known virulence or fitness gene sets were identified which universally differentiate between clinical and gastrointestinal isolates. This study further demonstrates the utility of a hybrid APEC typing approach, considering both plasmid content and clonal background, for the identification of dominant and highly virulent APEC clones in poultry production.


The effects of active and passive stretching on muscle length.
Active stretch is necessary for regulating muscle fiber length (ie, the number of series sarcomeres). Elevated cytoplasmic calcium is the proposed component of contractile activity required to activate signaling pathways for sarcomere number regulation. Passive stretch reduces muscle tissue stiffness, most likely by signaling connective tissue remodeling via fibroblasts. Passive stretch may induce sarcomere addition if the muscle fibers are lengthened sufficiently to raise cytoplasmic calcium through stretch-activated calcium channels. The magnitude of stretch in vivo is limited by the physiologic range of movement and stretch pain tolerance. The greatest effect of stretching muscle fibers is expected when the lengthening exceeds the optimum fiber length (Lo).


Green synthesis of novel antifungal 1,2,4-triazoles effective against γ-irradiated Candida parapsilosis.
This study reports the green synthesis of 11 novel 3-substituted-4-amino-5-mercapto-1,2,4-triazole derivatives using water as a readily available nontoxic solvent. Evaluation of their antimicrobial potential against several clinical pathogenic microorganisms was carried out. The newly synthesized cysteine derivative 6 showed promising antifungal activity against both γ-irradiated and nonirradiated Candida parapsilosis 216, with the lowest MIC (minimum inhibitory concentration) value of 3.125 µg/ml, probably through inhibition of 14α-demethylase. In addition, compound 6 showed complete inhibition of gelatinase, a virulence enzyme of C. parapsilosis. Also, scanning electron microscopy was carried out. Interestingly, compound 6 acted as a dual agent as it also showed good antibacterial activity against strains of Gram-positive bacteria used in the study. The synthesized compounds showed no cytotoxicity.


Comprehensive analysis of yacht masters operating in Bodrum district in terms of fatigue, burnout, and job satisfaction.
Yacht tourism is a developing sector in the world and in Turkey as well. Yacht masters are the most important components of this sector. This study aims to investigate the factors affecting the fatigue, job satisfaction, and burnout levels of yacht masters, offer solutions according to the findings, and eliminate this deficiency in the literature. The Maslach Burnout Scale (MBI), Minnesota Job Satisfaction Scale (MSQ) and Piper Fatigue Scale (PFS) were applied to yacht masters who are still actively working on yachts operating in the Bodrum district. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) software. According to the results of the analysis, yacht masters have high emotional burnout perceptions and very high personal success perceptions. In addition, their depersonalisation levels are low and their overall job satisfaction is high. The general fatigue levels of the masters are moderate. As their job satisfaction rate increases, their perceived fatigue level decreases. As their age increases, their fatigue level decreases. As their fatigue level increases, their burnout level also increases.


Changes in cardiac output and total peripheral resistance during the carotid sinus baroreceptor reflex in the pregnant rabbit.
1. The reflex cardiovascular effects of changes in pressure within the isolated carotid sinus have been examined in sixteen anaesthetized pregnant rabbits. 2. Comparison of the mean results at sinus pressures of 40 and 200 mmHg showed that heart rate fell by 32.1 beats min-1 and arterial pressure was reduced by 48.2 mmHg. Cardiac output, measured by thermal dilution, fell by 25.7 ml. min-1.kg-1 and total peripheral resistance was reduced by 0-292 mmHg. ml.-1 min. kg. 3. The corresponding changes previously reported in a group of seventeen non-pregnant female rabbits were a similar fall in heart rate of 34.5 beats min-1 but significantly greater reductions in arterial pressure of 69-8 mmHg and in total peripheral resistance of 0-432 mmHg. ml.-1 min.kg. However, the fall in cardiac output of 12.6 ml.min-1.kg-1 was significantly smaller. 4. These observations show that the smaller blood pressure response of the pregnant rabbit to alterations in sinus pressure is due to a reduced change in total peripheral resistance.


Utilization of two modified layered doubled hydroxides as supports for immobilization of Candida rugosa lipase.
In this study, two synthetic layered doubled hydroxides (LDH), including Mg/Al-CO3-LDH (LDH1) and Zn/Al-CO3-LDH (LDH2), were prepared using the co-precipitation method and modified with sodium dodecyl sulfate to be utilized as carriers for immobilization of Candida rugosa lipase via the adsorption. The activity of prepared biocatalysts was measured in the olive oil hydrolysis. The effects of lipase concentration, pH, storage stability and thermal resistance of the samples were also studied. The maximum activity was obtained at pH 6.0 for immobilized lipase on modified LDHs with monolayer surfactants, including MLDH1 (0.922 U/mg) and MLDH2 (0.744 U/mg), respectively. The remained activities for immobilized lipase on MLDH1 and MLDH2 after 24 h incubation at 60 °C were 85% and 81%, respectively. During the 25days of storage at 4 °C, immobilized lipases on MLDH1, MLDH2, and free lipase kept 87%, 86%, and 70% of their initial activities. The residual activities for immobilized lipase on MLDH1 and MLDH2 after reusing for ten cycles were 72% and 67% of their initial activities. Adsorption parameters for sorption of lipase on all supports were fitted to the Freundlich and Langmuir isotherms. Kinetic parameters obtained from the Michaelis-Menten equation on MLDH1 and MLDH2 were comparable to free enzyme.


Cognitive changes associated with cerebral emboli during coronary intervention.
To investigate factors influencing the frequency and type of microembolic signals (MES) detected using transcranial Doppler (TCD) in patients undergoing elective coronary intervention, and to correlate MES with silent stroke detected using magnetic resonance imaging (MRI) and cognitive dysfunction. The subset study of a randomized clinical trial was conducted on 70 patients (58 males; mean age 59.9 ± 8.4 years) who underwent bilateral TCD monitoring of middle cerebral arteries (MCAs) during elective coronary interventions. Neurologic examination and brain MRI were performed prior to, and 24 h post‑intervention. Cognitive function tests were performed prior to, and on day 30 post‑intervention. The incidence of detected MES was 94.3 %. Eighteen (25.7 %) patients had new clinically asymptomatic ischemic lesions on MRI. The number of solid MES negatively correlated with changes in revised Addenbrooke's Cognitive Examination test (ACE-R) and, the number of solid MES and combinations of solid and gaseous MES negatively correlated with changes in Mini Mental‑State Examination (MMSE) conducted on day 30 after the intervention (p < 0.05 in all cases). Cardiac catheterization was associated with a high risk of cerebral embolism in our patients. A higher number of solid MES and combinations of solid and gaseous MES was associated with the deterioration in cognitive tests (Tab. 5, Fig. 3, Ref. 30).


Beneficial long-term effect of intracoronary perfluorochemical on infarct size and ventricular function in a canine reperfusion model.
The administration of a drug soon after reperfusion that could enhance myocardial salvage would have important clinical application. The aim of this study was to assess the long-term effect of the perfluorochemical, Fluosol DA 20%, on infarct size, infarct morphology, ventricular ectopic activity and serial regional ventricular function in a 2 week closed chest canine model. After 90 minutes of proximal left anterior descending artery occlusion, animals randomly received either oxygenated Fluosol DA (n = 9) or saline solution (n = 9) intracoronary at 15 ml/kg body weight over 20 to 30 minutes. Hemodynamic variables were similar in the two groups except for transient elevation of left ventricular filling pressure immediately after infusion in the treated group. Infarct size was markedly reduced in the perfluorochemical-treated animals when expressed as a percent of the risk region (10.8 +/- 1.8% versus 28.9 +/- 5.5%, p less than 0.02) or as a percent of the total left ventricle (3.7 +/- 1% versus 10.8 +/- 8%, p less than 0.006). This was associated with greater improvement in radial shortening in the jeopardized zone at 2 weeks after reperfusion (15.3 +/- 2.8% versus 5.2 +/- 2.1%, p less than 0.01). Histologic examination revealed adequate healing in the treated animals with an increased number of swollen mononuclear cells in the border zones. Holter electrocardiographic recordings demonstrated a low frequency of ventricular ectopic beats in both groups. This study suggests that the perfluorochemical, Fluosol DA, may be a potentially useful agent in enhancing myocardial salvage after successful reperfusion.


The efficacy of individual treatment of subjective tinnitus with cognitive behavioural therapy.
It has been a long time since subjective tinnitus cases were described for the first time but they still lack a treatment with proven effectiveness. The main goal of this study was to evaluate the effectiveness of cognitive behavioural therapy in these patients. Between 2012 and 2013, 310 patients that suffered from subjective tinnitus were studied. Of these, 267 were included in treatment based on cognitive behavioural therapy. The monitoring period lasted 18 months for most cases, while it lasted 21 months for 11 patients. Considering patients that interrupted their treatment as failures, the percentage of recovery was 95.7%. Cognitive behavioural therapy should always be included in the treatment of people suffering from tinnitus.


Influence of diet and sea ice drift on organochlorine bioaccumulation in Arctic ice-associated amphipods.
The drifting sea ice has been suggested as important in the transport and concentration of organic matter and pollutants in the Arctic. We collected sea ice-associated amphipods in the marginal ice zone north of Svalbard and in the Fram Strait in September 1998 and 1999 to assess contaminant accumulation in ice-associated organisms. Organochlorine concentrations increased from the more herbivorous Apherusa glacialis to the more carnivorous Gammarus wilkitzkii and the more necrophagous Onisimus spp. The relative contribution of compound classes to the sum of organochlorines differed between the amphipod families, with a higher relative contribution of hexachlorocyclohexanes (HCHs) in A. glacialis. The composition of the compound classes HCHs. chlordanes and dichlorodiphenyltrichloroethanes (DDTs) was similar between the amphipod families, whereas the profiles of polychlorinated biphenyls (PCBs) differed. The occurrence of organochlorines differed spatially, with higher alpha-HCH concentrations in amphipods from the Fram Strait in comparison with amphipods collected north of Svalbard. This could be related to the sea ice drift route, since sea ice in the Fram Strait had a drift route across the central Arctic Ocean, while the sea ice north of Svalbard had a western drift route to the sampling stations. Even though marine invertebrates have direct uptake by passive diffusion of contaminants across their gills. our results imply that the species' ecology such as diet is important in the bioaccumulation process of organic pollutants. In addition, the results show that sea ice drift route influences the concentrations of organochlorine pollutants in ice-associated organisms.


The effect of on-site CT-derived fractional flow reserve on the management of decision making for patients with stable chest pain (TARGET trial): objective, rationale, and design.
The diagnostic accuracy of CT-derived fractional flow reserve (CT-FFR) in clinical application has been well validated. This advanced technology focus on evaluating anatomical stenosis and functional ischemia simultaneously. However, the effect of CT-FFR on the management of decision making has not been fully evaluated in randomized controlled design. TARGET study is a pragmatic, multicenter, prospective, open-label, and randomized controlled trial evaluating the effect of a CCTA/CT-FFR strategy (group A) versus usual care (group B) on intermediate-to-high risk patients with suspected CAD who undergo clinically indicated diagnostic evaluation. A total sample size of 1216 subjects will be enrolled and followed up for 12 months. This study will be performed in 6 Chinese hospitals, and the primary endpoint is the planned ICA without significant obstructive CAD within 90 days. The secondary endpoints include MACE, quality of life, medical expenditure, and cumulative radiation exposure during 1-year follow-up. The study will provide information to patients, health care providers, and other stakeholders in China about which strategy could be more effective in the management of intermediate-to-high risk patients with suspect CAD. ClinicalTrials.gov NCT03901326 . Registered on 3 April 2019.


Use of various contraceptive methods and time of conception in a community-based population.
To investigate the association between method of contraception and time to conception in a normal community-based population. Prospective, cross-sectional, survey. Large comprehensive ambulatory women's health center. One thousand pregnant women at their first prenatal obstetrics visit were asked to complete a self-report questionnaire. The return to fertility was analyzed by type of contraceptive method, duration of use, and other sociodemographic variables. Response rate was 80% (n=798). Mean age of the patients was 29.9+/-5 years. Seventy-five percent had used a contraceptive before trying to conceive: 80% oral contraceptives, 8% intrauterine device, and 7% barrier methods. Eighty-six percent conceived spontaneously. Contraceptive users had a significantly higher conception rate than nonusers in the first 3 months from their first attempt at pregnancy. Type of contraception was significantly correlated with time to conception. Pregnancy rates within 6 months of the first attempt was 60% for oral contraceptive users compared to 70 and 81% for the intrauterine device and barrier method groups, respectively. There was no correlation between time to conception and parity or duration of contraceptive use. Other factors found to be significantly related to time to conception were older age of both partners and higher body mass index. Contraception use before a planned pregnancy does not appear to affect ease of conception. Type of method used, although not duration of use, may influence the time required to conceive.


Improving dietary habits of children: effects of nutrition education and correspondence training.
Evidence that a significant number of children are exposed to risk factors associated with coronary heart disease has prompted health care professionals to develop programs designed to encourage the early development of a healthy life style. The present study used a multiple baseline approach to examine the effects of two procedures on the snack selection behavior of 25 third grade children. In children who selected non-nutritious rather than nutritious snacks for more than 40% of the baseline observations, nutrition education alone had little or no impact on their selection of snacks. However, with the implementation of correspondence training, in which a reward was made contingent upon carrying out a stated intent to choose a nutritious snack, the children consistently chose nutritious snacks. These results indicate that correspondence training may be an efficient and cost-effective way to improve dietary habits of young people.


Molecular genetic approach to the study of mammalian choline acetyltransferase.
The enzyme choline acetyltransferase catalyses the biosynthesis of the neurotransmitter acetylcholine and constitutes a specific marker of cholinergic system. To date, there is very limited information about the structure of the mammalian enzyme. More detailed understanding of this enzyme is particularly desirable because of the importance of the cholinergic system in neurotransmission, as well as the possible involvement of this system in certain neurological disorders. In this article, recent studies concerning the isolation of a cDNA encoding the complete sequence of the porcine enzyme are reported and the potential applications of this probe are discussed.


A comparative study of removal of fluoride from contaminated water using shale collected from different coal mines in India.
Low-cost water defluoridation technique is one of the most important issues throughout the world. In the present study, shale, a coal mine waste, is employed as novel and low-cost adsorbent to abate fluoride from simulated solution. Shale samples were collected from Mahabir colliery (MBS) and Sonepur Bazari colliery (SBS) of Raniganj coalfield in West Bengal, India, and used to remove fluoride. To increase the adsorption efficiency, shale samples were heat activated at a higher temperature and samples obtained at 550 °C are denoted as heat-activated Mahabir colliery shale (HAMBS550) and heat-activated Sonepur Bazari colliery shale (HASBS550), respectively. To prove the fluoride adsorption onto different shale samples and ascertain its mechanism, natural shale samples, heat-activated shale samples, and their fluoride-loaded forms were characterized using scanning electron microscopy, energy dispersive X-ray analysis, X-ray diffraction study, and Fourier transform infrared spectroscopy. The effect of different parameters such as pH, adsorbent dose, size of particles, and initial concentration of fluoride was investigated during fluoride removal in a batch contactor. Lower pH shows better adsorption in batch study, but it is acidic in nature and not suitable for direct consumption. However, increase of pH of the solution from 3.2 to 6.8 and 7.2 during fluoride removal process with HAMBS550 and HASBS550, respectively, confirms the applicability of the treated water for domestic purposes. HAMBS550 and HASBS550 show maximum removal of 88.3 and 88.5 %, respectively, at initial fluoride concentration of 10 mg/L, pH 3, and adsorbent dose of 70 g/L.


Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series.
The antibody profile during and after the six-dose primary vaccination series with anthrax vaccine adsorbed (AVA, Biothrax) was characterized in 86 human volunteers. Ninety-three percent of recipients developed IgG antibodies to Bacillus anthracis protective antigen (PA) after two doses, and 100% were seropositive after dose #3. Geometric mean concentrations (GMC) of IgG to PA measured before and after each dose were significantly lower after injection #3 (peak GMC=146.65 microg/mL, trough GMC=15.16 microg/mL) than after injections #4 (peak GMC=430.46 microg/mL, trough GMC=94.57 microg/mL), #5 (peak GMC=415.05 microg/mL, trough GMC=81.94 microg/mL), or #6 (peak GMC=401.16 microg/mL, trough GMC=96.19 microg/mL) (p<or=0.0001 for each); but not between injections #4 and #5, #5 and #6, or #4 and #6 (p>or=0.7923 for each). Decay rates for IgG to PA were significantly faster after injection #3 (half life [T1/2]=39.21 days) than after injections #4 (T1/2=72.03 days), #5 (T1/2=70.14 days), and #6 (T1/2=74.59 days) (p<or=0.0282 for each). Toxin neutralizing assay (TNA) antibody patterns generally paralleled those for IgG to PA. The 6-month dose in the AVA primary series appears to be critical in sustaining IgG to PA concentrations in a substantial proportion of recipients.


Management of cataract in the setting of uveitis: a review of the current literature.
This review aims to cover the preoperative planning, intraoperative considerations, and postoperative management that aids in successful outcomes of patients with cataract and uveitis. Disease-specific management and pediatric management will also be addressed. Dexamethasone implants appear to be a safe and effective addition to standard steroid treatment in decreasing the incidence of postoperative cystoid macular edema (CME). Intravitreal steroids and topical difluprednate have shown utility in CME treatment. Cataract surgery in eyes with uveitis is generally safe and effective if inflammation is well controlled; however, complication rates are still higher than in eyes without uveitis. Future investigations should delineate outcomes for eyes with different etiologies of uveitis, and further research is needed to adequately control inflammation and avoid postoperative complications.


A study on the nature of macroamylase complex. Dissociation of macroamylase by substrates.
Characteristics of a macroamylase that was considered not to be formed by the binding of normal amylase to immunoglobulins were studied. The macroamylase was reversibly dissociated into apparently normal amylase by treating the macroamylasemic serum with guanidine hydrochloride. Concanavalin A precipitated a large portion of the macroamylase. When the macroamylase was purified by affinity chromatography using an insoluble starch polymer at neutral pH, a considerable dissociation of the enzyme into apparently normal amylase was observed with the purified preparation. Such dissociation of the macroamylase was demonstrated by briefly incubating the patient's serum with a low-molecular weight starch, a substrate of the enzyme. This dissociated enzyme showed upon electrophoresis essentially the same isozymic pattern as that of normal serum amylase. When the patient's serum was incubated with the low molecular weight starch for a prolonged period to hydrolyze the starch completely and was dialyzed, reconstitution of macroamylase resulted. The amylase-binding substance(s) that is supposed to be involved in the formation of macroamylase was found to release when the enzyme was adsorbed on the insoluble starch polymer at 0 degrees C. The present results strongly suggest that the amylase-binding substance(s), probably polysaccharide(s) or glycoprotein(s), binds to the substrate-binding site of normal amylase to form a macroamylase complex.


Avoid missing pKas: High-throughput workflow using solution pH-metric in tandem with UV-metric measurements.
We describe a new high-throughput automated pKa workflow using potentiometry starting with 10 mM DMSO stock (solution pH-metric). Two approaches using either neat DMSO stock solution or removal of DMSO were evaluated with different sample amounts and cosolvent schemes. These were validated against traditional potentiometric measurements for optimal conditions. Further, we detail how high throughput solution pH-metric experiments are performed in tandem with established UV-metric measurements to capitalize on the advantages of both approaches. This new workflow maintains the sample and time savings required for measuring a large number of samples in a drug discovery setting, while avoiding "missing pKas" due to lack of sufficient UV chromophores. The combination of the two assays is key to tackle the challenges of low solubility, overlapping pKas, and preliminary assignment of pKas for Structure-Activity Relationship (SAR) understanding.