Development and clinical application of a novel CRISPR-Cas12a based assay for the detection of African swine fever virus.
As no treatment or effective vaccine for African swine fever virus (ASFV) is currently available, a rapid, highly sensitive diagnostic is urgently needed to curb the spread of ASFV. Here we designed a novel CRISPR-Cas12a based assay for ASFV detection. To detect different ASFV genotypes, 19 crRNAs were designed to target the conserved p72 gene in ASFV, and several crRNAs with high activity were identified that could be used as alternatives in the event of new ASFV variants. The results showed that the sensitivity of the CRISPR-Cas12a based assay is about ten times higher than either the commercial quantitative PCR (qPCR) kit or the OIE-recommended qPCR. CRISPR-Cas12a based assay could also detect ASFV specifically without cross-reactivity with other important viruses in pigs and various virus genotypes. We also found that longer incubation times increased the detection limits, which could be applied to improve assay outcomes in the detection of weakly positive samples and new ASFV variants. In addition, both the CRISPR-Cas12a based assay and commercial qPCR showed very good consistency. In summary, the CRISPR-Cas12a based assay offers a feasible approach and a new diagnostic technique for the diagnosis of ASFV, particularly in resource-poor settings.


[Survival of microorganisms on surfaces in relation to moisture and temperature and the effect of desiccation of microorganisms on resistance to disinfectants].
In laboratory tests with carriers (glass, slab, blanket) at a high rel. humidity (95%) the survival was distinctly reduced by S. aureus at 37 degrees C and by Ps. aeruginosa at 21 degrees C and 37 degrees C. Against this after 24 h storing of contaminated carriers (glass) the resistance to disinfectants was higher at 95% rel. humidity as at 35% rel. humidity.


Predictive equations for central obesity via anthropometrics, stereovision imaging and MRI in adults.
Abdominal visceral adiposity is related to risks for insulin resistance and metabolic perturbations. Magnetic resonance imaging (MRI) and computed tomography are advanced instruments that quantify abdominal adiposity; yet field use is constrained by their bulkiness and costliness. The purpose of this study is to develop prediction equations for total abdominal, subcutaneous, and visceral adiposity via anthropometrics, stereovision body imaging (SBI), and MRI. Participants (67 men and 55 women) were measured for anthropometrics and abdominal adiposity volumes evaluated by MRI umbilicus scans. Body circumferences and central obesity were obtained via SBI. Prediction models were developed via multiple linear regression analysis, utilizing body measurements and demographics as independent predictors, and abdominal adiposity as a dependent variable. Cross-validation was performed by the data-splitting method. The final total abdominal adiposity prediction equation was -470.28 + 7.10 waist circumference - 91.01 gender + 5.74 sagittal diameter (R2 = 89.9%), subcutaneous adiposity was -172.37 + 8.57 waist circumference - 62.65 gender - 450.16 stereovision waist-to-hip ratio (R2 =90.4%), and visceral adiposity was -96.76 + 11.48 central obesity depth - 5.09 central obesity width + 204.74 stereovision waist-to-hip ratio - 18.59 gender (R2 = 71.7%). R2 significantly improved for predicting visceral fat when SBI variables were included, but not for total abdominal or subcutaneous adiposity. SBI is effective for predicting visceral adiposity and the prediction equations derived from SBI measurements can assess obesity.


Intravascular embolization versus surgical resection for patients with scalp arteriovenous fistula.
Scalp arteriovenous fistula (sAVF) is a rare vascular disease; so far, the standard guidelines for the treatment of sAVF are still unclear. Since its complex vascular anatomical structure, surgical management of sAVF remains an enormous challenge. Between March 2016 and October 2017, three patients with sAVF admitted to the First Affiliated Hospital of Chongqing Medical University were reviewed, and clinical characteristics, imaging features, and surgical outcomes were analyzed. Three consecutive patients with sAVF were admitted to our hospital during the study period. Two patients received intravascular embolization and one patient received surgical resection. No procedure-related complications occurred after successfully treatment. During the long-term follow-up period, three patients recovered well and had no recurrence of lesion. Either intravascular embolization or surgical resection is an effective therapy method for sAVF. Careful identification of angioarchitecture features contributes to successful treatment for the complex sAVF; therefore, it is recommended that neurosurgeons make the best treatment plan based on the location and number of the fistulas, feeding the artery, and draining the vein.


Early local and systemic innate immune responses in the teleost gilthead seabream after intraperitoneal injection of whole yeast cells.
The early cellular innate immune responses of the teleost gilthead seabream (Sparus aurata L.) against whole yeast cells were studied. Fish received a single intraperitoneal (i.p.) injection of Saccharomyces cerevisiae and leukocyte mobilization, degranulation, peroxidase content, respiratory burst, phagocytic and cytotoxic activities were assayed in both head-kidney leukocytes (HKLs) and peritoneal exudate leukocytes (PELs). The total number of PELs significantly increased from 4 h post-injection until the end of the experiment (3 days). Interestingly, flow cytometric analysis revealed variations in the proportion of cell-types in the PE. Thus, PE acidophilic granulocytes increased to a significant extent 4 h post-injection and were restored thereafter. Moreover, PE monocyte-macrophages started to increase from 24 h, the enhancement being statistically significant after 48 and 72 h. Degranulation was greater in PELs throughout the assay. The peroxidase content of the leukocytes was affected differently in HKLs and PELs. The respiratory burst activity was not affected in HKLs but significantly increased in PELs from 4 to 48 h post-injection with yeast cells. On the other hand, HKL phagocytosis had decreased 72 h post-injection with yeast cells while it increased after 4 and 24 h post-injection in the PELs. Conversely, the cytotoxic activity was significantly enhanced in HKLs from 24 to 72 h post-injection but slightly decreased in PELs. Finally, our data demonstrate that seabream injected with the yeast Saccharomyces cerevisiae show leukocyte mobilization and cellular innate immune response activation at the site of invasion and also in the head-kidney. The implications of the leukocyte-types and the immune responses observed, as well as analogies with other particulated antigens, will be discussed as possible models for investigating the effect of potential pathogens.


Current status of vaccines for substance use disorders: A brief review of human studies.
Substance use is a major public health concern worldwide. In the United States, drug-related deaths have increased many-fold in the past two decades due to the infiltration of more potent and lethal drugs such as fentanyl. Despite significant advancement in medicine, the management of substance use disorders (SUD) continues to be fraught with high attrition, relapse, morbidity, and mortality. The conceptual transition of a SUD from a moral failing to a chronic disease caused by substances facilitated the expansion of biological treatments, including pharmacotherapy, neurostimulation, and immunotherapy. While the quest for vaccines against drugs of abuse had an optimistic start in animal models, clinical trials in humans have yielded disappointing results. This paper provides a brief review on the current progress of vaccines against nicotine, stimulants (cocaine and methamphetamine), opioids including fentanyl, novel psychoactive substances (synthetic cathinones and synthetic cannabis), and discusses prospects for vaccine technology in the treatment of SUD.


Benchtop Assessment of a New Single-Use Flexible Ureteroscope.
Introduction: Single-use flexible ureteroscopes are an increasingly popular alternative to reusable ureteroscopes. In this study, we performed a benchtop examination of the physical and optical properties of the new Dornier Axis™ (Webling, Germany) single-use ureteroscope. Methods: Ten new, never-used Dornier Axis ureteroscopes were assessed for optical performance, maximal tip deflection, and irrigation flow rate with an empty working channel and with insertion of 200 and 365 μm laser fibers, and a 1.9F nitinol basket. All ureteroscopes were then fully deflected 100 times in each direction, and maximal deflection angles were re-measured with and without instruments in the working channel. All measurements were performed in duplicate. In vitro optical testing for resolution, image distortion, and depth of field was performed and compared vs the LithoVue™ (Boston Scientific, Marlborough, MA) single-use ureteroscope. Statistical analyses using paired Wilcoxon rank-sum tests and Kruskal-Wallis multiple-group comparison tests were performed in R. Results: Median maximal deflection angles exceeded 300° in both directions before and after 100 full deflection cycles for all groups except the 365 μm laser fiber group. After 100 deflection cycles, there was no change in the majority of working instruments, except a decrease in upward flexion with an empty channel and 200 μm Moses™ laser fiber, and downward flexion with 200 μm Flexiva™ laser fiber (all <10°). After excluding the 365 μm fiber, there was no difference in multi-group comparison for upward and downward flexion pre- and post-cycling. Median flow rate through an empty channel was 48.0 mL/min, and it decreased significantly with all used instruments (p < 0.001). Compared with the LithoVue, the Axis demonstrated superior resolution at all tested distances and less distortion. Conclusions: The new Dornier Axis single-use ureteroscope demonstrates excellent tip deflection, which remains unchanged after 100 manual flexions in each direction. The Axis also demonstrates superior optical performance compared with the LithoVue in benchtop testing.


Characterization of a novel aphid prenyltransferase displaying dual geranyl/farnesyl diphosphate synthase activity.
We report on the cDNA cloning and characterization of a novel short-chain isoprenyl diphosphate synthase from the aphid Myzus persicae. Of the three IPPS cDNAs we cloned, two yielded prenyltransferase activity following expression in Escherichia coli; these cDNAs encode identical proteins except for the presence, in one of them, of an N-terminal mitochondrial targeting peptide. Although the aphid enzyme was predicted to be a farnesyl diphosphate synthase by BLASTP analysis, rMpIPPS, when isopentenyl diphosphate and dimethylallyl diphosphate are supplied as substrates, typically generated geranyl diphosphate (C10) as its main product, along with significant quantities of farnesyl diphosphate (C15). Analysis of an MpIPPS homology model pointed to substitutions that could confer GPP/FPP synthase activity to the aphid enzyme.


Delimitation and species discovery in the Profundulidae fish family: Using genetic, environmental and morphologic data to address taxonomic uncertainty.
The family Profundulidae includes some one of the most enigmatic freshwater fishes of Mesoamerica: despite many attempts, a robust phylogenetic framework to delimit species is lacking, mainly due to limited morphological variation within the group. The accumulation of molecular data of profundulid fishes has led to advances in the description of new taxa, but relatively less progress has been made estimating evolutionary and phylogenetic relationships for this fish family. Here, we adopt an integrative taxonomy approach including the use of nuclear and mitochondrial DNA sequences, morphometric and ecological data, to test species boundaries in profundulid fishes in the westernmost area of their known distribution range in the states of Guerrero and Oaxaca, Mexico. Using a combination of methods for species discovery and validation based on Bayesian gene tree topologies, our analyses support the delimitation of 15 valid species of profundulid fishes - a combination of previously described species validated by this study, the synonymy of unsupported taxa, and the description of two new species. Using species delimitation methods, examination of phenotypic variation, and ecological niche characterization, we also identify five potentially new lineages which require further evidence to be erected as new species. We demonstrate that the use of an integrative taxonomy approach provides a robust methodology to delimit species in a taxonomically complex group like Profundulidae. Accurate taxonomic and ecological information is crucial for the conservation of these microendemic fishes, as several species are endangered.


Life-time estrogen exposure and cognitive functioning in later life.
While recent studies suggest that exogenous estrogen treatment could help reduce age-related cognitive decline and delay the onset of dementia, this has not been found consistently. Few studies have considered the influence of life-time estrogen exposure which may have an independent effect on cognition and/or modulate treatment response. The aim of this study was to examine whether factors related to estrogen exposure across the life-time were associated with cognitive function in postmenopausal women. A battery of cognitive tests were administered at baseline and at 2 and 4 years of follow-up to evaluate cognitive performance among a population-based cohort of 996 French women aged 65 years or older, who were recruited as part of the ESPRIT study. Detailed reproductive histories were also obtained. Logistic regression models, controlling for an extensive range of potential confounding factors, were generated to determine whether hormone-related factors across a woman's lifetime were associated with poor cognitive performance in later life. Age at first menses was negatively associated with performance on the tasks of visual memory and psychomotor speed, while a longer reproductive period was associated with better verbal fluency. Likewise, women who had their first child at a young age performed significantly worse on each of these tasks, as well as on a measure of global cognitive function. The results also suggest that current hormone therapy may be beneficial for a number of cognitive domains, however, in multivariate analysis, women performed significantly better on the task of visual memory only. In contrast, in analysis adjusted for baseline cognitive performance and a range of other factors, none of the reproductive variables were associated with a decline in cognitive performance or the incidence of dementia during the 4-year follow-up period. In addition to hormone therapy, certain hormone-related events across the lifetime are also associated with cognitive functioning in later life. They were not observed in this study to modulate dementia risk; however, this should be verified over a longer follow-up period. Further studies will also be required to determine whether lifetime hormonal exposure may modify women's response to hormone therapy after the menopause.


Biliary lipid secretion in the rat. The uncoupling of biliary cholesterol and phospholipid secretion from bile acid secretion by sulfated glycolithocholic acid.
Glycolithocholic acid and its sulfated derivative are major metabolites of the secondary bile acid lithocholic acid in man. Both compounds are known to induce cholestasis in experimental animals. We compared the effects of these endogenous hepatotoxins on bile production and biliary lipid composition in rats with chronic biliary drainage. The compounds were administered enterally at relatively low rates (5-50% of the rats' endogenous bile acid secretion in these experiments) to simulate enterohepatic circulation. Both compounds were substantially secreted into bile (more than 90% of dose); sulfated glycolithocholic acid unchanged and glycolithocholic acid after hepatic hydroxylation predominantly in the form of glyco-beta-muricholic acid (cf. Kuipers et al. (1986) Am. J. Physiol. 251, G189-G194). Neither glycolithocholic acid nor its sulfated derivative affected the biliary excretion of endogenous bile acids or bile flow in these experiments. In spite of this, phospholipid and cholesterol secretion were significantly reduced by sulfated glycolithocholic acid but were not altered by glycolithocholic acid. Phospholipid and cholesterol secretion rapidly decreased to 25 and 50% of their initial values, respectively, at biliary output rates of sulfated glycolithocholic acid up to 2 mumol/h, and did not further decrease when this output was increased to 6 mumol/h. Small unilamellar liposomes consisting of cholesterol, [Me-14C]choline-labeled phosphatidylcholine, phosphatidylserine and [3H]cholesteryl oleate in a 5:4:1:0.1 molar ratio were employed to label intrahepatic lipid pools. Administration of sulfated glycolithocholic acid slightly reduced bile acid synthesis from [3H]cholesteryl oleate, but significantly reduced the biliary secretion of [14C]phospholipid. Glycolithocholic acid did not affect the hepatic processing of liposomal lipids. It is concluded that sulfated glycolithocholic acid at low doses causes the uncoupling of biliary lipid secretion from that of bile acids, which might represent in initiating event in sulfated glycolithocholic acid hepatotoxicity.


Physical and biological studies on DNA/anti-DNA immune complex formed in vitro.
In vitro preparation of DNA/anti-DNA immune complex using monoclonal antibody and low molecular weight homogeneous DNA was described and the characteristics of the immune complex were identified. The immune complex was formed by the monoclonal antibody with DNA effectively at high ratios of antibody/DNA. The activation and binding ability of the immune complex to the complement was considerably high, whereas the capacity to bind red blood cells via C3b complement component receptor was shown relatively low. The assay of sucrose density gradient ultracentrifugation indicated that the sedimentation coefficient of the immune complex was between 10S and 23S. Studies of organ distribution and uptake of IC demonstrated a particular affinity to the kidney tissue. The significance of these results with respect to the latent pathogenicity of the immune complex was discussed.


Eosinophilic granuloma of the cervical spine without vertebrae plana.
A case of eosinophilic granuloma of the cervical spine is described. Cervical radiography and computed tomography demonstrated destruction of pedicles and posterior portions of the neural arch. Vertebral body heights were essentially preserved and the importance of this finding is underscored. Computed tomography played an important role in evaluating the extent of this disease.


The marker C-reactive protein is helpful in monitoring the integrity of anastomosis: plasma calprotectin.
Despite improved surgical techniques and materials, anastomotic leakage is a big problem for surgeons. The most frequently used laboratory parameters is leukocyte (white blood cell) and C-reactive protein (CRP). Availability of plasma calprotectin with CRP to detect anastomotic leakage was studied. In this prospective study of 41 (male/female 18/23) patients in the anastomosis group, 30 (male/female 20/10) patients were included in the control group. The anastomosis groups viewed in preoperatively day and postoperatively 1st, 3rd, and 5th day of CRP, white blood cell, and plasma calprotectin values. Anastomosis group with complications and without complications were studied. Statistically significant similarities between plasma calprotectin and CRP levels in the postoperative period were observed. Plasma calprotectin in monitoring the integrity of the anastomosis can be used with a marker CRP.


"I don't know what I'm feeling for": young women's beliefs about breast cancer risk and experiences of breast awareness.
Younger women are often diagnosed with advanced breast cancer. Beliefs about risk are instrumental in motivating many health protective behaviours, but there may be confusion around which behaviour is appropriate to detect breast cancer earlier. Breast awareness, defined as an understanding of how the breasts look and feel so changes can be identified early, is widely recommended. In contrast, breast self-examination involves palpation using a specified method. We aimed to investigate young women's beliefs about their risk and experiences of breast awareness. Thirty-seven women aged 30-39 years residing in a North West region of England with no family or personal history of breast cancer participated in seven focus groups (n = 29) and eight individual interviews. Data were analysed using reflexive thematic analysis. Three themes were generated. "Future me's problem" describes why women perceive breast cancer as an older woman's disease. Uncertainty regarding checking behaviours highlights how confusion about self-checking behaviour advice has resulted in women infrequently performing breast checks. Campaigns as a missed opportunity highlights the potential negative effects of current breast cancer fundraising campaigns and the perceived absence of educational campaigning about breast cancer for this demographic. Young women expressed low perceived susceptibility to developing breast cancer in the near future. Women did not know what breast self-checking behaviours they should be performing and expressed a lack of confidence in how to perform a breast check appropriately due to limited knowledge about what to look and feel for. Consequently, women reported disengagement with breast awareness. Defining and clearly communicating the best strategy for breast awareness and establishing whether it is beneficial or not are essential next steps.


Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53.
Interferon regulatory factors (IRFs) regulate transcription of interferon genes through DNA sequence-specific binding to these targets. Using a differential display method for examining gene expression in p53-defective cells infected with adenovirus containing wild-type p53, we found that expression of interferon regulatory factor 5 (IRF-5) mRNA was increased in the presence of exogenous p53. An electrophoretic mobility-shift assay showed that a potential p53 binding site (p53BS) detected in exon 2 of the IRF-5 gene could in fact bind to p53 protein. Moreover, a heterologous reporter assay revealed that the p53BS possessed p53-dependent transcriptional activity. Expression of IRF-5 was induced in p53+/+ cells (MCF7 and NHDF), but not inp53-/- cells (H1299) when DNA was damaged by gamma-irradiation, UV-radiation, or adriamycin treatment in a wild-type p53-dependent manner. These results suggest that IRF-5 is a novel p53-target, and that it might mediate the p53-dependent immune response.


Fermentation of kiwifruit juice from two cultivars by probiotic bacteria: Bioactive phenolics, antioxidant activities and flavor volatiles.
Three commercial lactic acid bacteria (LAB), namely Lactobacillus acidophilus 85 (La85), Lactobacillus helveticus 76 (Lh76) and Lactobacillus plantarum 90 (Lp90), were employed to investigate the effects on the phenolic compounds, antioxidant capacities and flavor volatiles of kiwifruit juices prepared from two cultivars (Actinidia deliciosa cv. Xuxiang and Actinidia chinensis cv. Hongyang). Results showed that both kiwifruit juices were favorable matrices for LAB growth and the colony counts remained above 9.0 log CFU/mL after fermentation. Total phenolics and flavonoids in Xuxiang and Hongyang juices were increased dramatically by Lh76. Correspondingly, antioxidant capacities based on DPPH, ABTS and FRAP methods were improved significantly and positively correlated with protocatechuic acid and catechin contents (p < 0.05), two newly formed phytochemicals in fermented kiwifruit juices. Furthermore, results of hierarchical cluster analysis revealed that flavor profiles were improved significantly by LAB, and there were noticeable differences between fermented Xuxiang and Hongyang juices.


High density lipoproteinemia due to vigorous physical work inhibits the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture.
The effect of sera from normolipidemic men engaging in normal physical activity and from high density lipoproteinemic lumberjacks engaging in vigorous physical activity on the incorporation of [3H]thymidine and the synthesis of glycosaminoglycans by human aortic smooth muscle cells in culture was measured. At high concentration (15%) high density lipoproteinemic serum inhibited significantly (P less than 0.001) the incorporation of thymidine. The serum inhibited the synthesis of glycosaminoglycans at all concentrations tested (1--15%) with the most marked inhibition at 10 and 15%. At lower concentrations (1--5%) the inhibition was more pronounced for sulphated glycosaminoglycans than for hyaluronic acid. The inhibition was of the same magnitude for the subclasses (chondroitin, dermatan and heparan sulphates) of sulphated glycosaminoglycans studied. High density lipoproteinemia due to vigorous physical work is postulated as a protective factor against the early biochemical reactions of arterial smooth muscle cells in the development of atherosclerosis.


Topological model of membrane domain of the cystic fibrosis transmembrane conductance regulator.
The cystic fibrosis transmembrane conductance regulator is a cAMP-regulated chloride channel. We used molecular modelling to predict 3-D models for the CFTR membrane domain. Hydropathy and residue conservation in all CFTRs as well as in other proteins suggested that the membrane domain is a 12-helix bundle. If the domain is enclosing a channel for chloride, it could be made of five helices. We propose two structural models in which both lumenal and cytoplasmic entrances to the chloride pore have a ring of positively charged residues. The inner surface of the channel is covered with neutral polar plus one or two charged residues. Helices that are not directly involved in the chloride channel could organise to form a second channel; a dimeric symmetrical structure is proposed. Analysis raised interest for helix 5: this hydrophobic fragment is conserved in all CFTRs and aligns with segments present in several different ion channels and transporters. The existence of an FFXXFFXXF motif is proposed. Helix 5 could be an important domain of CFTRs. The models agree with available data from pathological mutations but does not account for the membrane insertion of a hydrophilic fragment of NBDI.


Purification and partial characterization of intact and truncated chitinase from Bacillus thuringiensis HZP7 expressed in Escherichia coli.
To ascertain the effect of chitin-binding domain (ChBD) and fibronectin type III domain (FN3) on the characterization of the intact chitinase from Bacillus thuringiensis. An intact chitinase gene (chi74) from B. thuringiensis HZP7 and its truncated genes (chi54, chi63 and chi66) were expressed in Escherichia coli BL21. The expression products were analyzed after purification. All chitinases were active from pH 4-7.5 and from 20 to 80 °C with identical optimal: pH 5.5 and 60 °C. The activity of colloid chitin degradation for Chi74 was the highest, followed by Chi66, Chi63 and Chi54. Ag(+) reduced the activity of Chi74, Chi54, Chi63 and Chi66, but Mg(2+) enhanced them. The effect of Ag(+) and Mg(2+) was more significant on the activity of Chi54 than on the activities of Chi63, Chi66 and Chi74. ChBDChi74 and FN3Chi74 domains play a role in exerting enzymatic activity and can improve the stability of chitinase.


CFD modeling of ethylene degradation in gas-phase photocatalytic reactors.
Photocatalytic oxidation is a promising technology to degrade volatile organic compounds. The performance of photocatalytic reactors is affected by the hydrodynamics, radiation transfer, mass transfer and reaction kinetics. Baffles may improve the hydrodynamics. The effect of baffles on heterogeneous photocatalytic oxidation of gas-phase ethylene in three annular reactors is simulated using computational fluid dynamics. ANSYS Fluent is used to solve all governing equations. Baffles can improve the uniformity of flow and prolong the residence time. The residence time of the C-type reactor and B-type reactor is 0.5% greater than the unbaffled reactor. Baffles have little effect on the radiation distribution. The concentric arrangement of lamp and the reactor leads to a radial dominance of radiation. The effect of baffles on the diffusion of ethylene is complex. The effective diffusion coefficient at the catalyst surface in the C-type reactor decreases 9.5% and that in the B-type reactor increases 3% with respect to the unbaffled reactor. The outlet ethylene concentration is 4.19 ppmv for the U-type reactor, 3.93 ppmv for the C-type reactor and 3.62 ppmv for the B-type reactor. The optimal performance in the B-type reactor is due to the large diffusion coefficient of ethylene. The arrangement of baffles should enlarge the effective diffusion coefficient at the catalyst surface as far as possible.


Impaired motor skills and atypical functional connectivity of the sensorimotor system in 40- to 65-year-old adults with autism spectrum disorders.
Impairments in fine and gross motor function, coordination, and balance in early development are common in autism spectrum disorders (ASDs). It is unclear whether these deficits persist into adulthood and whether they may be exacerbated by additional motor problems that often emerge in typical aging. We assessed motor skills and used resting-state functional magnetic resonance imaging to study intrinsic functional connectivity of the sensorimotor network in 40- to 65-year-old adults with ASDs (n = 17) and typically developing matched adults (n = 19). Adults with ASDs scored significantly lower on assessments of motor skills compared with an age-matched group of typical control adults. In addition, functional connectivity of the sensorimotor system was reduced and the pattern of connectivity was more heterogeneous in adults with ASDs. A negative correlation between functional connectivity of the motor system and motor skills, however, was only found in the typical control group. Findings suggest behavioral impairment and atypical brain organization of the motor system in middle-age adults with ASDs, accompanied by pronounced heterogeneity.


Differentiation of the various lesions causing an abnormality of the endometrial cavity using MR imaging: emphasis on enhancement patterns on dynamic studies and late contrast-enhanced T1-weighted images.
The objectives of this study were to determine the usefulness of magnetic resonance (MR) imaging in the differentiation of various lesions causing an abnormality of the endometrial cavity by evaluating the imaging features on dynamic contrast-enhanced study and late contrast-enhanced T1-weighted images (T1WI). Contrast-enhanced MR imaging of 59 pathologically proven lesions that showed an abnormality of the endometrial cavity, including 32 endometrial cancers, five sarcomas, nine hyperplastic polyps, nine submucosal myomas, three hyperplasia, and one adenomyoma, were retrospectively reviewed. The enhancement degree and patterns on dynamic contrast-enhanced study and late contrast-enhanced T1WI were compared among different pathologies. On dynamic contrast-enhanced study, 72% (23/32) of endometrial cancers showed early peak enhancement to be reached within 1 min following intravenous administration of contrast material. On late-contrast-enhanced T1WI, lesions showed weak enhancement with gradual washout. Ninety-five percent (21/22) of benign lesions and 100% (5/5) of sarcomas showed late peak enhancement to be reached in 2-3 min following intravenous administration of contrast material. On late contrast-enhanced T1WI, both of these lesions showed persistent strong enhancement. Different enhancement patterns on dynamic contrast-enhanced MR imaging and late contrast-enhanced T1WI can provide a useful clue in the differentiation of various lesions causing an abnormality of the endometrial cavity.


Evaluation of microplastics in Jurujuba Cove, Niterói, RJ, Brazil, an area of mussels farming.
Once non-biodegradable, microplastics remain on the environment absorbing toxic hydrophobic compounds making them a risk to biodiversity when ingested or filtered by organisms and entering in the food chain. To evaluate the potential of the contamination by microplastics in mussels cultivated in Jurujuba Cove, Niterói, RJ, waters of three stations were collected during a rain and dry seasons using a plankton net and later filtered. Microplastics were quantified and characterized morphologically and chemically. The results showed a high concentration of microplastics in both seasons with diversity of colors, types and sizes. Synthetic polymers were present in all samples. The presence of microplastics was probably due to a high and constant load of effluent that this area receives and to the mussel farming activity that use many plastic materials. Areas with high concentrations of microplastics could not be used for mussel cultivation due to the risk of contamination to consumers.


Irrational beliefs, depression and anxiety, in relation to 10-year cardiovascular disease risk: the ATTICA Epidemiological Study.
Various bio-psychosocial mechanisms underlying the link between anxiety, depression and cardiovascular disease risk, remain unknown. We investigated the role of irrational beliefs in conjunction with anxiety and depression in the 10-year cardiovascular disease (CVD) incidence, and the effect of biochemical and socio-behavioral factors. 853[453 men (45 ± 13 years) and 400 women (44 ± 18 years)] from the ATTICA study (2002-2012) and without evidence of CVD were assessed. The Irrational Beliefs Inventory (IBI), the Zung Self-Rating-Depression-Scale (ZDRS) and the State-Trait-Anxiety-Inventory (STAI) were used for the assessments. Incidence of CVD was defined according to the International Coding Diseases (ICD)-10 criteria. Participants with high irrational beliefs and anxiety symptoms had a 138% greater risk of developing CVD during the 10-year follow-up (2.38; 95%CI 1.75, 3.23) as compared to those without anxiety. Among others, C-reactive protein, interleukin-6 and total antioxidant capacity were mediators in the tested association. Interaction of irrational beliefs and depression was not associated with the 10-year CVD in all models. Inflammation and oxidative stress, partially explained the associations between irrational beliefs and anxiety in predicting CVD risk. These findings advance psychological research in the area of primary prevention of mental health and cardiovascular diseases.


Bone formation following carpal interposition arthroplasty.
Two cases of bone formation occurring at the site of carpal excision and soft tissue interposition are presented.


Evaluation and risk stratification of acute coronary syndromes using a low cut-off level of cardiac troponin T, combined with CK-MB mass determination.
To study the usefulness of combined cardiac Troponin T (cTnT) and CK-MB mass determinations in risk stratification of acute coronary syndromes. Blood samples for cTnT and CK-MB mass were collected at arrival and 4, 8, and 12-24 later in 301 consecutive patients with recent acute chest pain (ACP). Data were also collected for cardiac events. Combined cardiac mortality/nonfatal myocardial infarction over a period of 15 months was lowest in patients with <0.04 microg/l cTnT and -<5.0 microg/l CK-MB mass intermediate in those with elevated cTnT but normal CK-MB mass and highest when both markers were elevated, in absence of early reperfusion. The use of a low cut-off point of cTnT, combined wit CK-MB mass determination, offers a good strategy for risk stratification of ACP patients.


Recombination of N Atoms in a Manifold of Electronic States Simulated by Time-Reversed Nonadiabatic Photodissociation Dynamics of N2.
Following a single photon VUV absorption, the N2 molecule dissociates into distinct channels leading to N atoms of different reactivities. The optically accessible singlets are bound, and dissociation occurs through spin-orbit induced transfer to the triplets. There is a forest of coupled electronic states, and we here aim to trace a path along the nonadiabatic couplings toward a particular exit channel. To achieve this, we apply a time-reversed quantum dynamical approach that corresponds to a dissociation running back. It begins with an atom-atom relative motion in a particular product channel. Starting with a Gaussian wave packet at the dissociation region of N2 and propagating it backward in time, one can see the population transferring among the triplets due to a strong nonadiabatic interaction between these states. Simultaneously, the optically active singlets get populated because of spin-orbit coupling to the triplets. Thus, backward propagation traces the nonradiative association of nitrogen atoms.


Laccase-catalyzed removal of the antimicrobials chlorophene and dichlorophen from water: Reaction kinetics, pathway and toxicity evaluation.
As active agents in cleaning and disinfecting products, antimicrobials have been widely spread in the environment and have drawn extensive attention as potential threats to the ecological system and human health. In this study, the laccase-catalyzed removal of two emerging antimicrobials, chlorophene (CP) and dichlorophen (DCP), was investigated under simulated environmental conditions. Intrinsic reaction kinetics showed that the removal of CP and DCP followed second-order reaction kinetics, first-order with respect to both the enzyme and the substrate concentration. It was also found that fulvic acid could suppress the transformation of CP and DCP by reversing the oxidation reactions through its action as a scavenger of the free radical intermediates produced from reactions between laccase and the substrates. Several reaction products were identified by a quadrupole time-of-flight mass spectrometer, and detailed reaction pathways were proposed. For both CP and DCP, direct polymerization was the principal pathway, and the coupling patterns were further corroborated based on molecular modeling. The nucleophilic substitution of chlorine by the hydroxyl group was observed, and further oxidation products capable of coupling with each other were also found. Additionally, toxicity evaluation tests using Scenedesmus obliquus confirmed that the toxicity of CP and DCP was effectively eliminated during the reaction processes.


Mechanism of double-strand DNA cleavage effected by iron-bleomycin.
We have observed that in the absence of hydrogen peroxide the Fe(III)-bleomycin (BLM) complex exhibits high DNA cleavage efficiency, converting supercoiled Form I DNA (pBR322 or phix174) to Form II (nicked, relaxed circular); the present study may give an important clue to elucidate the fact that iron-bleomycin mediated double-strand DNA cleavage requires at least one molecule of oxygen (O2) over the amount required to form 'activated bleomycin."


spoT-mediated stringent response influences environmental and nutritional stress tolerance, biofilm formation and antimicrobial resistance in Klebsiella pneumoniae.
Klebsiella pneumoniae is an important opportunistic pathogen with significant potential for virulence and multidrug resistance. Treatment failure often occurs because the pathogen may couple virulence and drug resistance with the stringent response. This study assessed the role of the spoT gene in environmental and nutritional stress tolerance, exopolysaccharide capsule production and biofilm formation. spoT mutants were constructed using the lambda red recombinase technique, and mutant and wild-type (WT) strains were exposed to limiting concentrations of carbon (glucose), phosphate and aminoacid, and environmental stresses of ethanol, salt and heat. Cell viability, capsule production and cell length were assessed as well as the ability to grow biofilm under antibiotic pressure using gentamicin and ceftazidime. spoT mutants were more susceptible to stresses versus WT; the reverse was true for survival during biofilm susceptibility assay (p < 0.05), especially when carbon and phosphate were present. spoT mutants were elongated and lacked a capsule versus WT and non-starved strains. The inability to produce capsule in mutants before and after starvation was likely a general effect of spoT mutation. These data suggest that the spoT-mediated stringent response is important for K. pneumoniae in conditions of nutrient limitation, environmental stress and antimicrobial pressure.


Musculoskeletal pain and its socioeconomic implications.
Pain is the most common reason for patients seeking advice from their physician. One adult in five suffers from chronic pain. In general, musculoskeletal pain, often in the form of arthritis, non-articular rheumatism, peripheral neuropathies and low back disorders, represents the most common cause of chronic non-malignant pain (CNMP). Exposure to low social support, low social anchorage or low social participation significantly increases the odds of a high level of pain. Most patients do not attribute chronic musculoskeletal pain to injury, but those who do report significantly higher levels of emotional distress. Pain is the third leading reason for absence from work in the United States, where the problem of chronic pain translates into an annual expenditure of at least $50 billion. The effectiveness of opioids for chronic pain goes unchallenged, but issues of potential dependence, abuse, and social and legal concerns have rendered their use in CNMP controversial. Numerous consensus statements, guidelines and policies have been issued by a variety of advocate organisations for the treatment of CNMP with opioids. Undertreatment of chronic pain persists despite the availability of drugs and other therapies for effective pain management.


Synchronization of respiration.
In order to study synchronization of respiration, three different videofragments were presented to 21 normal subjects. Each fragment showed a 'therapeutic interview' specially performed for this purpose, with a 'patient' breathing in a particular way. The respiration of model 1 was deep, slow and clearly audible, the pattern of model 2 was rapid, superficial and slightly audible and that of model 3 was normal and hardly perceptible. The fragments were presented in three different sequences and each sequence was followed by seven subjects. Respiration amplitude (Vt), respiration irregularity (SD of Vt), respiration frequency (RF) and frequency of skin conductance responses (SCRF) were measured. Changes in mean values of these variables were demonstrated during the fragments; an increase in RF was the most pronounced and reliable change. These 'overall' physiological changes did not support the synchronization hypothesis, nor were they at variance with it: they seemed to be effects of attention. A detailed (cycle by cycle) analysis did reveal a synchronization effect in fragment 1. The number of cycles in the subject which were in rhythm with the model's respiration was significantly larger than could have been expected by chance. The effect of synchronization, however, was small and transient as it did not affect the mean RF and Vt of fragment 1.


Spectrum bias, a common unrecognised issue in orthopaedic agreement studies: do CT scans really influence the agreement on treatment plans in fractures of the distal radius?
Current studies on the additional benefit of using computed tomography (CT) in order to evaluate the surgeons' agreement on treatment plans for fracture are inconsistent. This inconsistency can be explained by a methodological phenomenon called 'spectrum bias', defined as the bias inherent when investigators choose a population lacking therapeutic uncertainty for evaluation. The aim of the study is to determine the influence of spectrum bias on the intra-observer agreement of treatment plans for fractures of the distal radius. Four surgeons evaluated 51 patients with displaced fractures of the distal radius at four time points: T1 and T2: conventional radiographs; T3 and T4: radiographs and additional CT scan (radiograph and CT). Choice of treatment plan (operative or non-operative) and therapeutic certainty (five-point scale: very uncertain to very certain) were rated. To determine the influence of spectrum bias, the intra-observer agreement was analysed, using Kappa statistics, for each degree of therapeutic certainty. In cases with high therapeutic certainty, intra-observer agreement based on radiograph was almost perfect (0.86 to 0.90), but decreased to moderate based on a radiograph and CT (0.47 to 0.60). In cases with high therapeutic uncertainty, intra-observer agreement was slight at best (-0.12 to 0.19), but increased to moderate based on the radiograph and CT (0.56 to 0.57). Spectrum bias influenced the outcome of this agreement study on treatment plans. An additional CT scan improves the intra-observer agreement on treatment plans for a fracture of the distal radius only when there is therapeutic uncertainty. Reporting and analysing intra-observer agreement based on the surgeon's level of certainty is an appropriate method to minimise spectrum bias. Cite this article: Bone Joint Res 2015;4:190-194.


Close relationship between the vasodilator response to acetylcholine in the brachial and coronary artery in suspected coronary artery disease.
Vasodilator response to acetylcholine (endothelium-dependent dilation) is impaired in the peripheral and coronary circulation in patients with coronary artery disease (CAD). The purpose of this study is to investigate if the vasodilator response to acetylcholine in the brachial artery (BA) correlates with the same response in the coronary artery (CA). We measured the flow responses of BA and CA in 57 patients with suspected CAD. Doppler guidewire was placed into the proximal portion of the left BA and the major branch of CA. Acetylcholine was infused at 7.5, 15, and 30 mug/min for 5 min into BA and at 10(-8), 10(-7), 10(-6) M for 3 min into CA, respectively. The flow was calculated by multiplying average peak velocity by cross sectional areas obtained from quantitative angiography. Vasodilator response to acetylcholine was assessed by ratio of acetylcholine-induced flow/baseline flow. A total of 33 CAD patients (CAD group, 61+/-8 years old) and 24 normal coronary patients (NL group, 57+/-12 years old) were investigated. A strong correlation between the vasodilator response to acetylcholine in BA and CA was observed in both CAD and NL groups, only at two moderate doses of acetylcholine (CAD group, r=0.64, p<0.001, NL group, r=0.87, p<0.001, 15 microg/min vs. 10(-7) M; CAD group, r=0.68, p<0.001, NL group, r=0.72, p<0.001, 30 microg/min vs. 10(-6) M). No significant correlation was obtained during low dose acetylcholine infusion. The brachial artery vasodilator response to optimal acetylcholine doses is a useful surrogate for coronary endothelial function studies.


Peripheral neuropathy in patients with benign monoclonal gammopathy--a pilot study.
It is well known that peripheral neuropathy occurs in patients with myeloma or macroglobulinaemia, but its pathogenesis is still obscure. In recent years, neuropathy has also been reported in association with benign monoclonal or oligoclonal gammopathy. Modern histo-immunological methods have revealed evidence of antibody production to peripheral nerve tissue, probably the myelin sheath. The present study included 21 unselected, consecutive patients with benign monoclonal gammopathy observed in the Division of Haematology. Clinical and laboratory investigations included electrophysiological examination and analyses of the M components. Of the 21 patients 11 had noticed slight neuropathic symptoms in their extremities; in 5 both clinical and electrophysiological findings were compatible with neuropathy; 6 showed positive clinical signs of neuropathy; 4 had either positive electromyographic or electroneurographic findings. In summary, 15 of 21 patients had some signs of peripheral neuropathy. In spite of the screening design of the study, this strikingly high frequency is comparable with other recent reports. Haematological studies did not reveal any significant differences between the patient groups with positive or negative neurological findings. The findings indicate that even benign gammopathies may be associated with peripheral neuropathy.


Efficacy of washed microbiota transplantation for therapeutic targets of refractory functional constipation and the influencing factors: a single-center, retrospective, 24-week follow-up study.
The efficacy of washed microbiota transplantation (WMT) in terms of refractory functional constipation (FC)-related therapeutic targets and influencing factors have not been elucidated. This study aimed to assess the efficacy and influencing factors of WMT in treating refractory FC-related therapeutic targets. The clinical data of patients diagnosed with refractory FC and received with WMT were retrospectively collected. The therapeutic targets included straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, manual maneuvers, and decreased stool frequency. Each target was recorded as 1 (yes) or 0 (no). All patients were followed up for approximately 24 weeks from the end of the first course of WMT. The primary outcomes were the improvement rates for the individual therapeutic targets and the overall response in respect of the therapeutic targets decreased by 2 at weeks 4, 8, and 24. The secondary outcomes were the clinical remission rate (i.e., the proportion of patients with an average of 3 or more spontaneous complete bowel movements per week), clinical improvement rate (i.e., the proportion of patients with an average increase of 1 or more SCBMs/week or patients with remission), stool frequency, Wexner constipation score, Bristol Stool Form Scale (BSFS) score, and adverse events. The factors influencing the efficacy were also analyzed. Overall, 63 patients with 112 WMT courses were enrolled. The improvement rates at weeks 8 and 24 were 45.6% and 35.0%, 42.9% and 38.6%, 45.0% and 35.7%, 55.6% and 44.4%, and 60.9% and 50.0%, respectively, for straining, hard stools, incomplete evacuation, a sense of anorectal obstruction, and decreased stool frequency. The overall response rates were 49.2%, 50.8%, and 42.9%, respectively, at weeks 4, 8, and 24. The rates of clinical remission and clinical improvement were 54.0% and 68.3%, respectively, at weeks 4. The stool frequency, BSFS score, and Wexner constipation score tended to improve post-WMT. Only 22 mild adverse events were observed during the 112 WMT courses and the follow-up. The number of WMT courses was identified to be the independent factor influencing the efficacy. WMT is efficacious in improving refractory FC-related therapeutic targets. The effectiveness of WMT in the management of FC is enhanced with the administration of multiple courses.


Differences in beliefs about pain control after surgery due to lumbar or cervical discopathy and degenerative spine disease.
Clinical, psychological and demographic variables have been investigated to determine factors involved in quality of life of patients with chronic pain. It has been stressed that chronic pain is more associated with beliefs about pain, than with pain intensity. The main aim of this retrospective cross-sectional study was to examine differences between postoperative beliefs about pain control, perception of pain and mood disturbances in patients treated operatively due to neck or lumbar discopathy and degenerative spine disease. Forty-four patients treated operatively due to lumbar and forty-one patients treated surgically due to cervical discopathy filled in the Visual Analogue Scale (VAS), The Beck Depression Inventory (BDI-PL) and Beliefs about Pain Control Questionnaire (BPCQ-PL). Patients with lumbar and cervical discopathy additionally completed disease-specific outcome measures. The patient groups do not differ significantly in regards to BPCQ-PL, BDI-PL or VAS. Both study samples differ in regards to dependencies related to beliefs that pain is controlled by powerful others and about internal control of pain. Cognitive-behavioral interventions, concerning depression and beliefs about pain control, may be appropriate for both lumbar and cervical surgical populations, to improve post-surgical functioning.


Defining Employment Specialist Competencies: Results of a Participatory Research Study.
The preponderance of research conducted on supported employment has focused on the structure of interventions with little empirical investigation into the contribution of employment specialists to work outcomes. Using a participatory approach, we identified competencies essential to the role of the employment specialists, operationalized and refined those competencies using the perspectives of experts, service recipients, and employment specialists themselves. We conducted an online survey with 34 candidate items and n = 142 respondents. Results suggested good psychometric properties, stability and coherence of the Vocational Practices and Relationship Scale. A total of n = 23 final items tapping the working alliance coalesced into a strong factor, as did strategies for promoting vocational recovery, suggesting that the scale warrants wide-scale testing for predictive validity. We consider these constructs and competencies to be a potential blueprint for training employment specialists, not only in technical skills and strategies, but also to increase the hope for vocational recovery among those they serve.


The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.
Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.


Locus of control in short and long sleepers.
As a test of the hypothesis that consistent short sleepers tend to be less reflective and more conformist in their thinking than long sleepers, the I-E scale scores of 15 short and 15 long sleepers were compared. Consistent with this hypothesis, we found that to a significant degree, short sleepers view themselves as more externally regulated than long sleepers.


A dynamic interaction between the bicarbonate ligand and photosystem II reaction center complexes in chloroplasts.
The binding of HCO-3 to Photosystem II reaction center complexes in broken chloroplasts requires the presence of the oxidized form of the negative charge accumulator 'B'. HCO-3 which is already bound to the reaction center II complex can escape if chloroplasts are illuminated with saturating light in the presence of a Hill oxidant and high concentrations of sodium chloride and sodium formate. These observations are explained in terms of a cyclic dark binding of HCO-3 to the reaction center II complex and a subsequent release in the light.


Assessment of pneumatization of the paranasal sinuses: a comprehensive and validated metric.
The purpose of this study was to develop and validate a radiographic metric for characterizing the degree of paranasal sinus pneumatization. A validated metric for the extent of sinus pneumatization that comprehensively includes the maxillary, ethmoid, frontal, and sphenoid cavities is not currently available. A validation study was performed in which 5 independent reviewers evaluated 49 sinus computed tomography (CT) scans in coronal, sagittal, and axial orientations. Reviewers evaluated each scan, bilaterally, for 18 proposed dichotomous items as part of the Assessment of Pneumatization of the Paranasal Sinuses (APPS) metric. Evaluation of APPS items was independent of sinus opacification, which was simultaneously evaluated using the standard and validated Lund-Mackay scoring system. Interrater and intrarater reliability was assessed for each proposed APPS parameter and Lund-Mackay item using Fleiss kappa statistic. Nine parameters were included in the final APPS metric due to substantial interrater reliability (κ(mean) = 0.61, κ(range) = 0.41-0.81) and intrarater consistency (κ(mean) = 0.64, κ(range) = 0.53-0.77), variable radiographic presence, and unique contribution to the characterization of sinus pneumatization. Kappa values were also calculated for Lund-Mackay interrater reliability (κ(mean) = 0.58, κ(range) = 0.45-0.66) and intrarater consistency (κ(mean) = 0.71, κ(range) = 0.65-0.75). The final APPS metric has comparable interrater and intrarater reliability to Lund-Mackay scoring. APPS scores were normally distributed within the study group by Anderson-Darling normality test (p < 0.005). The APPS score is the first comprehensive and validated metric for quantifying the degree of paranasal sinus pneumatization and anatomic variation. This has important potential utility in standardizing evaluation of sinus CT and researching the relationship of sinus pneumatization with clinical parameters.


[Activity of Enzymes Involved in the Energy and Carbohydrate Metabolism and the Level of Some Molecular-Genetic Characteristics in Young Salmons (Salmo salar L.) with Different Age and Weight].
In order to investigate the metabolic regulation in Atlantic salmon fries (Salmo salar L.) during their growth, development, and in the course of size divergence, age-related changes in the activity of enzymes involved in the energy and carbohydrate metabolism, including myosin heavy chain isoform expression, RNA/DNA ratio in the white muscles and liver of specimens at ages of 0+; 1+, and 2+, as well as correlations of these characteristics with the body weight of fish specimens were analyzed. Multidirectional changes in the activity of enzymes taking part in aerobic and anaerobic energy metabolism, as well as a decrease in the protein synthesis with age, were revealed. There was a positive correlation between the activities of cytochrome oxidase, lactate dehydrogenase, aldolase, and myosin gene expression in the muscles, cytochrome oxidase activity, glucose-6-phosphate dehydrogenase, and glycerol-3-phosphate dehydrogenase in the liver with the body weight of salmon specimens within the age groups.


Introducing problem-based learning into research methods teaching: student and facilitator evaluation.
The evidence base for the effectiveness of problem-based learning (PBL) has never been substantively established, although PBL is a generally accepted approach to learning in health care curricula. PBL is believed to encourage transferable skills, including problem-solving and team-working. PBL was used to deliver a postgraduate research methods module and a small evaluation study to explore its efficacy was conducted amongst the students (n = 51) and facilitators (n = 6). The study comprised of an evaluation questionnaire, distributed after each themed group of PBL sessions, and a group discussion conducted 4 weeks after the conclusion of the module, which was attended by student representatives and the facilitators. Questionnaire data was analysed using SPSS, and a transcript of the interview was subjected to content analysis. The results indicated that students felt that a PBL approach helped to make the subject matter more interesting to them and they believed that they would retain knowledge for a longer period than if their learning had used a more traditional lecture format. Students also perceived that PBL was effective in its ability to enhance students' understanding of the group process. All those involved in the PBL process reinforced the pivotal role of the facilitator. This study indicates that there is potential for PBL to be used beyond the more usual clinical scenarios constructed for health care professional education and further exploration of its use in areas such as building research capability should be undertaken.


Polyandrous females provide sons with more competitive sperm: Support for the sexy-sperm hypothesis in the rattlebox moth (Utetheisa ornatrix).
Given the costs of multiple mating, why has female polyandry evolved? Utetheisa ornatrix moths are well suited for studying multiple mating in females because females are highly polyandrous over their life span, with each male mate transferring a substantial spermatophore with both genetic and nongenetic material. The accumulation of resources might explain the prevalence of polyandry in this species, but another, not mutually exclusive, possibility is that females mate multiply to increase the probability that their sons will inherit more-competitive sperm. This latter "sexy-sperm" hypothesis posits that female multiple mating and male sperm competitiveness coevolve via a Fisherian runaway process. We tested the sexy-sperm hypothesis by using competitive double matings to compare the sperm competition success of sons of polyandrous versus monandrous females. In accordance with sexy-sperm theory, we found that in 511 offspring across 17 families, the male whose polyandrous mother mated once with each of three different males sired significantly more of all total offspring (81%) than did the male whose monandrous mother was mated thrice to a single male. Interestingly, sons of polyandrous mothers had a significantly biased sex ratio of their brood toward sons, also in support of the hypothesis.


Knockdown of tissue nonspecific alkaline phosphatase impairs neural stem cell proliferation and differentiation.
In the adult mammalian brain the subependymal layer of the lateral ventricles houses neural stem cells giving rise to young neurons migrating towards the olfactory bulb. The molecular cues controlling essential functions within the neurogenesis pathway such as proliferation, short and long distance migration, differentiation and functional integration are poorly understood. Neural progenitors in situ express the tissue nonspecific form of alkaline phosphatase (TNAP), a cell surface-located nonspecific phosphomonoesterase capable of hydrolyzing extracellular nucleotides. To gain insight into the functional role of TNAP in cultured multipotent neural stem cells we applied a knockdown protocol using RNA interference with shRNA and retroviral infection. We show that TNAP knockdown reduces cell proliferation and differentiation into neurons or oligodendrocytes. This effect is abrogated by addition of alkaline phosphatase to the culture medium. Our results suggest that TNAP is essential for NSC proliferation and differentiation in vitro and possibly also in vivo.


Identification of a Gene-Expression-Based Surrogate of Genomic Instability during Oral Carcinogenesis.
Our goal was to identify a gene-expression-based surrogate of genomic instability (GI) associated with the transformation of oral potentially malignant disorder (OPMD) into oral squamous cell carcinoma (OSCC). GI was defined as the fraction of genome altered (FGA). Training sets included the CCLE and TCGA databases. The relevance of the enrichment score of the top correlated genes, referred to as the GIN score, was evaluated in eight independent public datasets from the GEO repository, including a cohort of patients with OPMD with available outcome. A set of 20 genes correlated with FGA in head and neck SCC were identified. A significant correlation was found between the 20-gene based GIN score and FGA in 95 esophagus SCC (r = 0.59) and 501 lung SCC (r = 0.63), and in 33 OPMD/OSCC (r = 0.38). A significantly increased GIN score was observed at different stages of oral carcinogenesis (normal-dysplasia -OSCC) in five independent datasets. The GIN score was higher in 10 OPMD that transformed into oral cancer compared to 10 nontransforming OPMD (p = 0.0288), and was associated with oral-cancer-free survival in 86 patients with OPMD (p = 0.0081). The GIN score is a gene-expression surrogate of GI, and is associated with oral carcinogenesis and OPMD malignant transformation.


Managing everyday life: Self-management strategies people use to live well with neurological conditions.
This paper uses the Taxonomy of Everyday Self-management Strategies (TEDSS) to provide insight and understanding into the complex and interdependent self-management strategies people with neurological conditions use to manage everyday life. As part of a national Canadian study, structured telephone interviews were conducted monthly for eleven months, with 117 people living with one or more neurological conditions. Answers to five open-ended questions were analyzed using qualitative content analysis. A total of 7236 statements were analyzed. Findings are presented in two overarching patterns: 1) self-management pervades all aspects of life, and 2) self-management is a chain of decisions and behaviours. Participants emphasized management of daily activities and social relationships as important to maintaining meaning in their lives. Managing everyday life with a neurological condition includes a wide range of diverse strategies that often interact and complement each other. Some people need to intentionally manage every aspect of everyday life. For people living with neurological conditions, there is a need for health providers and systems to go beyond standard advice for self-management. Self-management support is best tailored to each individual, their life context and the realities of their illness trajectory.


Population structure of a hilltopping butterfly.
The hilltopping behavior of individuals in a closed demographic unit ofEuphydryas editha is examined. Both males and females hilltop but the behavior differs between the sexes. Most males appear to hilltop throughout their reproductive lives. Females hilltop only as virgins. The occurrence of hilltopping in a population is influenced by the density and age structure of the population. In addition, some males appear not to hilltop, but instead "patrol" below the hilltop, a strategy which may be favored in periods of high density. We suggest that in order to understand the ecological and evolutionary significance of hilltopping, its populational aspects need to be investigated as well as individual behaviors, such as territoriality, which hilltopping butterflies may also exhibit.


Facile and Cost-effective Synthesis of CoP@N-doped Carbon with High Catalytic Performance for Electrochemical Hydrogen Evolution Reaction.
The manufacture of efficient and low-cost hydrogen evolution reaction (HER) catalysts is regarded as a critical solution to achieve carbon neutrality. Herein, we developed an economical method to synthesize a CoP-anchored N-doped carbon catalyst via one-step pyrolysis using inexpensive starting materials (cobalt ion salt, phytic acid, and glycine). The size of the CoP nanoparticles was controlled by adjusting the Co/P ratio of the catalysts. Nanoscale CoP particles with adequate exposure to active sites were uniformly anchored on the surface of the conductive nitrogen-doped carbon substrate, ensuring the rapid transfer of electrons and species. When Co/P=0.89, the as-made catalyst exhibited outstanding HER activity, with an extraordinarily low overpotential of 202 mV at 10 mA cm-2 and long-term stability.


Insights into urticaria in pediatric and adult populations and its management with fexofenadine hydrochloride.
The present narrative review provides a comprehensive update of the current knowledge on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride (HCl) as a treatment option. A literature search was conducted on Embase and Medline. Clinical studies published in English and published between 1999 and 2020 were selected. Although the exact pathogenesis of urticaria is not fully understood, multiple pathways of mast cell activation are discussed to explain the existence of phenotypically different clinical manifestations of urticaria. An overview of the worldwide prevalence of chronic urticaria, including disease burden and patient's quality of life is provided. The impact of urticaria on patient's life differs on the basis of whether its form is acute or chronic, but pharmacological approaches are most often needed to control the disabling symptoms. A summary of the current management of urticaria recommended by different guidelines across countries (Global; European; American; Australian; Asian; Japanese) is presented. Non-sedating, second-generation H1-antihistamines are the preferred choice of treatment across several guidelines worldwide. Herein, the efficacy and safety of fexofenadine HCl, a representative second-generation H1-antihistamine approved for the treatment of urticaria, is discussed. The occurrence of urticaria manifestations in COVID-19 patients is also briefly presented. The burden of acute and chronic urticaria is high for patients. Second generation anti-histamines such as fexofenadine HCl can help managing the symptoms.


Indicating atmospheric sulfur by means of S-isotope in leaves of the plane, osmanthus and camphor trees.
Foliar δ(34)S values of three soil-growing plant species (Platanus Orientalis L., Osmanthus fragrans L. and Cinnamomum camphora) have been analyzed to indicate atmospheric sulfur. The foliar δ(34)S values of the three plant species averaged -3.11±1.94‰, similar to those of both soil sulfur (-3.73±1.04‰) and rainwater sulfate (-3.07±2.74‰). This may indicate that little isotopic fractionation had taken place in the process of sulfur uptake by root or leaves. The δ(34)S values changed little in the transition from mature leaves to old/senescing leaves for both the plane tree and the osmanthus tree, suggestive of little isotope effect during sulfur redistribution in plant tissues. Significantly linear correlation between δ(34)S values of leaves and rainwater sulfate for the plane and osmanthus trees allowed the tracing of temporal variations of atmospheric sulfur by means of foliar sulfur isotope, while foliage δ(34)S values of the camphor is not an effective indicator of atmospheric sulfur.


Olfactory sensitivity for "green odors" (aliphatic C(6) alcohols and C(6) aldehydes)--a comparative study in male CD-1 mice (Mus musculus) and female spider monkeys (Ateles geoffroyi).
Using a conditioning paradigm, the olfactory sensitivity of six male CD-1 mice for "green odors", a group of eight structurally related aliphatic C(6) alcohols and aldehydes known to exert anxiolytic and stress-reducing effects, was investigated. With all eight stimuli, the animals discriminated concentrations ≤0.03 ppm (parts per million) from the solvent, and with three of the eight stimuli the best-scoring animals were even able to detect concentrations ≤0.03 ppb (parts per billion). Three female spider monkeys tested in parallel were found to detect the same eight stimuli at concentrations <1 ppm, and with six of the eight stimuli the best-scoring animals detected concentrations ≤0.1 ppm. Analysis of odor structure-activity relationships showed that in both species the type of functional group attached to the aliphatic C(6) backbone of the odorant molecules systematically affected their olfactory sensitivity whereas the presence/absence of a double bond did not. In the mice, but not in the spider monkeys, the position of a double bond and the cis/trans-configuration of the odorant molecules also had a systematic effect on detectability of the "green odors". A comparison of the detection thresholds between the two species tested here and those obtained in human subjects suggests that the number of functional olfactory receptor genes is a poor predictor of a species' olfactory sensitivity for "green odors".


Elective total parathyroidectomy without autotransplant in end-stage renal disease.
Ten patients are reported following parathyroidectomy (PTX). In 9 all identifiable parathyroid tissue in the neck was deliberately removed, and in the tenth (operated 14 years ago) the remnant which had been left probably did not function. Their post-operative course resembled that of patients treated conventionally, and their subsequent course was likewise uneventful with disappearance of all symptoms associated with their osteodystrophy. All patients required oral calcium supplementation but none were given vitamin D compounds after the initial period of repletion following surgery. Mean serum values were (before PTX and current) for calcium 2.63 +/- 0.14 and 2.33 +/- 0.08 mmol/liter, P = NS, for phosphorus 1.96 +/- 0.13 and 1.38 +/- 0.09 mmol/liter, P less than 0.01, and for alkaline phosphatase 713 +/- 191 and 101 +/- 14 IU, P less than 0.05. Evidence for residual parathyroid tissue was present in each case; one patient remained mildly hyperparathyroid and several were mildly hypoparathyroid by the IRMA PTH assay. Bone histomorphometry in five subjects post-PTX showed either normal or low turnover. Radiologically, striking remineralization was seen with disappearance of all erosive changes. We suggest that residual areas of parathyroid tissue are stimulated and continue to secrete hormone even when all the discrete glands have been removed. It is recommended that when indicated, and in the absence of aluminum excess, total PTX without autotransplant should be the preferred form of therapy for long-term dialysis patients.


Ambivalence and Anxiety in the Psychiatric Systems of the United States and Japan.
Obsessive-compulsive disorder and the Japanese condition known as taijin kyofusho are classified as 'anxiety disorders' by US and Japanese psychiatrists. While members of the biomedical community might prefer to see this as evidence of a human universal, the similarity between the two is not primarily biological, but cultural and developmental. Both disorders develop out of a conflict between or within cultural significant values, values that refer to and develop from the dynamics of emotional attachment.


Dihydrexidine, a full D1 dopamine receptor agonist, induces rotational asymmetry in hemiparkinsonian monkeys.
Dihydrexidine (trans-10,11-dihydroxy5,6,6a,7,8,12b hexanhyydrobenso- [alpha]phenanthridine) is a full dopamine D1 agonist. In rhesus macaque monkeys rendered hemiparkinsonian by unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), dihydrexidine (0.15-0.9 mg/kg) elicited dose-dependent contralateral rotation. The effects of dihydrexidine were blocked by pretreatment with the D1 antagonist SCH 23390 (0.03 mg/kg), but not by the D2 antagonist raclopride (0.025 mg/kg). These results suggest a functional role for D1 receptors in stimulating motor behavior in a primate model of Parkinson's disease.


The role of striatal glutamate receptors in models of Parkinson's disease.
The aim of the study was to examine the effect of antagonists of the NMDA receptor on the parkinsonian-like muscle rigidity in rats. Reserpine and haloperidol increased the muscle resistance of the hind foot to passive movements, as well as the reflex electromyographic (EMG) activity in the gastroenemius and tibialis anterior muscles. MK-801 (0.32-1.28 mg/kg s.c.), an uncompetitive antagonist of the NMDA receptor, and L-701,324 (5-40 mg/kg i.p.), an antagonist of the glycine site, reduced the muscle tone and the reflex EMG activity enhanced by reserpine or haloperidol. AP-5 (2 and 5 micrograms/0.5 microliter), a competitive antagonist of the NMDA receptor, and 5,7-dichlorokynurenic acid (1.0-4.5 micrograms/0.5 microliter), the glycine site antagonist injected bilaterally into the rostral striatum, inhibited the muscle rigidity induced by haloperidol. In contrast, AP-5, injected alone bilaterally into the intermediate-caudal striatum induced muscle rigidity. The present results suggest that: (1) the inhibitory effect of the NMDA receptor antagonists on the parkinsonian-like muscle rigidity depends, at least partly, on their action on the rostral striatum; (2) the blockade of NMDA receptors in the intermediate-caudal striatum may reduce the beneficial impact of these compounds.


Neurofascin: a novel chick cell-surface glycoprotein involved in neurite-neurite interactions.
We have identified neurofascin, a novel chick cell-surface glycoprotein involved in neurite-neurite interactions. Neurofascin is defined by its reactivity with monoclonal antibody (MAb) F6, which detects two polypeptides (160 and 185 kd) in immunotransfers of brain plasma membrane proteins. Immunoaffinity chromatography using immobilized MAb F6 yields major molecular mass bands at 185, 160, 135-110, and 92 kd. Fingerprint analyses show that these polypeptides are related. Neurofascin is expressed primarily in fiber-rich areas of embryonic cerebellum, spinal cord, and retina. Fab fragments of polyclonal antibodies to neurofascin interfere with the outgrowth of retinal and sympathetic axons in two different in vitro bioassays. Neurofascin is immunologically distinct from other known neurite-associated surface glycoproteins.


A short, simple method for the determination of paraquat in plasma.
Paraquat was measured in plasma after precipitation of plasma proteins by addition of a solvent/salt mixture. The paraquat remaining in the supernatant is measured by its free radical formation after addition of alkaline sodium dithionite. The time required for a single determination is approximately 20 minutes.


cdc7 alleles and the control of induced mutagenesis in yeast.
Four cdc7 alleles have been tested for their effects on the u.v.-induced reversion of arg4-17, a highly u.v.-revertible ochre mutant. The extent to which mutability is suppressed parallels the temperature sensitivity of growth of the mutants. The implication is that the pleiotropic consequences of the cdc7 mutations are different manifestations of a single function activity.


Extension of health and nutrition services via advanced telecommunications.
The present and future technology of telecommunications will revolutionize the promotion and dissemination of health and nutrition services. Telecommunications can extend health and nutrition services because of its communicating and tracking capability. The University Affiliated Cincinnati Center for Developmental Disorders' Federal Project and other selected projects and programs using telecommunications technology illustrate the promotion and dissemination of nutrition and health services and the economic and efficient aspects of teleconferencing, electronic mail, and video imaging. This technology must be incorporated into the field of nutrition and health to meet the changing advances in the world and to improve the nutrition and health of individuals--particularly those who are at high risk, such as children with developmental disorders and chronic diseases.


Kinetics Driven by Hollow Nanoreactors: An Opportunity for Controllable Catalysis.
As a novel class of catalytic materials, hollow nanoreactors offer new opportunities for improving catalytic performance owing to their higher controllability on molecular kinetic behavior. Nevertheless, to achieve controllable catalysis with specific purposes, the catalytic mechanism occurring inside hollow nanoreactors remains to be further understood. In this context, this Review presents a focused discussion about the basic concept of hollow nanoreactors, the underlying theory for hollow nanoreactor-driven kinetics, and the intrinsic correlation between key structural parameters of hollow nanoreactors and molecular kinetic behaviors. We aim to provide in-depth insights into understanding kinetics occurred within typical hollow nanoreactors. The perspectives proposed in this paper may contribute to the development of the fundamental theoretical framework of hollow nanoreactor-driven catalysis.


Resident training and interrater agreements using the ACNS critical care EEG terminology.
Electroencephalography (EEG) remains the gold standard for identifying rhythmic and periodic patterns in critically ill patients. Residents have frequent exposures to EEG and critically ill patients during their training. Our study aimed to assess resident competency in the use of the American Clinical Neurophysiology Society (ACNS) critical care EEG terminology. After self-guided reading and a 2-hour session reviewing the ACNS critical care EEG Terminology training slides, 16 adult neurology residents (PGY 2-4) completed the ACNS certification test. Performance scores were reported as average percent agreement (PA%) with a previously established 5-member expert panel. Interrater agreement was calculated to gauge consensus among peers within the resident cohort. Self-reported comfort levels using the terminology were also obtained. The overall pass rate for our cohort was 50% and the median score was 74%. The terms with the highest PA% were: seizures (86.4%), main term 1 (78%), main term 2 (74%). Interrater agreement scores (kappa values) were almost perfect for seizure, and substantial for main terms 1 and 2. Our data suggests that with minimal investment, adult neurology residents at various stages of training can effectively learn the ACNS critical care EEG Terminology.


Biological pretreatment of corn stover for enhancing enzymatic hydrolysis using Bacillus sp. P3.
The biological pretreatment for the enzymatic hydrolysis of lignocellulosic biomasses depends exclusively on the effective pretreatment process. Herein, we report a significant enhancement of enzymatic saccharification obtained with corn stover using a bacterial strain Bacillus sp. P3. The hemicellulose removal from corn stover by the strain Bacillus sp. P3 was evaluated for enhancing subsequent enzymatic hydrolysis. Therefore, our study revealed that an alkaline-resistant xylanase as well as other enzymes produced by Bacillus sp. P3 in fermentation broth led to a substantially enhanced hemicellulose removal rate from corn stover within pH 9.36-9.68. However, after a 20-day pretreatment of corn stover by the strain P3, the glucan content was increased by 51% and the xylan content was decreased by 35%. After 72 h of saccharification using 20 U/g of commercial cellulase, the yield of reducing sugar released from 20-day pretreated corn stover was increased by 56% in comparison to the untreated corn stover. Therefore, the use of the strain P3 could be a promising approach to pretreat corn stover for enhancing the enzymatic hydrolysis process of industrial bioenergy productions. The online version contains supplementary material available at 10.1186/s40643-021-00445-8.


Ecology of spiders inhabiting abandoned mammal burrows in South African savanna.
In the Nylsvley Nature Reserve, in the South African savanna, the spider community in 320 abandoned mammal burrows was investigated. Three species, Agelena ocellata (Agelenidae), Euprosthenops proximus (Pisauridae) and Smeringopus pallidus (Pholcidae), coexisted in the burrows. The number of individuals and the number of species inhabiting the burrows increased with burrow size. Gerbil burrows were apparently too small to provide space for more than one individual of any of the three species. Only the burrows of springhares, warthogs, and antbears contained more than one spider. When artificial burrows were provided a rapid increase in settlement resulted. Competition for space therefore seems to be the determining factor influencing the population size. A relatively low number of prey items (136, in 119 webs) were found in agelenid webs only. Kleptoparasitic ants were observed stealing prey items from the webs.


Once weekly intraperitoneal therapy for gram-positive peritonitis.
The pharmacokinetics and clinical outcome following a 30 mg/kg/2 L intraperitoneal (IP) dose of vancomycin, which was administered once a week for 3 weeks, was studied in ten continuous ambulatory peritoneal dialysis patients with peritonitis. Vancomycin was 91% absorbed following the first dose and rapidly achieved therapeutic serum concentrations, 19 +/- 8 mcg/mL at 1 hour and a peak of 37 +/- 8 mcg/mL at 6 hours. Vancomycin was eliminated slowly with a mean total clearance of 7 +/- 3 mL/min/70 kg and a distribution volume of 1.2 +/- 0.3 L/kg. The resultant mean serum t1/2 over the first week was 184 hours and the mean serum concentration at 168 hours was 10 +/- 4 mcg/mL. Based on the positive clinical outcome (100% cure) among patients with uncomplicated gram-positive peritonitis, the potential use of this alternative vancomycin dosing regimen is proposed.


Data on beetle-killed and surviving lodgepole pine (Pinus contorta) radial growth from the Beaverhead-Deerlodge National Forest, MT prior to a severe mountain pine beetle outbreak.
This article contains measurements of raw radial growth, distance to pith, and calculated basal area increments (BAI) from 444 5-mm increment cores (237 trees) collected in July 2016 from the Beaverhead-Deerlodge National Forest, MT. These data were used for the study presented in "Mountain pine beetle attack faster growing lodgepole pine at low elevations in western Montana, USA" [1]. Plot locations where increment cores were taken as well as code to calculate BAI are also included. Cores were collected from lodgepole pine (Pinus contorta) trees that were killed during a recent bark beetle outbreak (220 cores; 117 trees) as well as trees that survived the outbreak (210 cores; 113 trees) in twelve stands spanning north and south aspects and three elevational bands along a 600-m gradient. 14 additional cores were collected from 7 strip-attacked trees. Increment cores were prepared and measured using standard dendrochronological techniques, "An Introduction to Tree-Ring Dating" [2]. Master chronologies for each aspect-elevation combination were created using approximately ten cores from surviving trees at each location. Cores were cross-dated, then scanned at 2400 dpi. Annual ring widths were measured using CooRecorder 7.7, "Cybis Electronic, CDendro and CooRecorder V.7.7" [3], and final chronologies were quantitatively validated in COFECHA, "Computer-assisted quality control in tree-ring dating and measurement, Tree-Ring Society" [4].


Screening Strategies and Primary Prevention Interventions in Relatives of People With Coronary Artery Disease: A Systematic Review and Meta-analysis.
Relatives of people with coronary artery disease are at high risk of cardiovascular (CV) disease, but the effect of focused screening and treatment of this population is uncertain. We searched the Cochrane Library, Medline, and Embase from inception until June 30, 2014 for articles that described screening strategies and primary prevention interventions targeting family members of patients with coronary artery disease to reduce CV risk. Results were pooled using a random-effects meta-analysis. We identified 18 studies that reported screening strategies and 15 reporting interventions to reduce CV risk. Proband willingness to refer relatives for screening was high (n = 6 studies, pooled rate = 87%; 95% confidence interval [CI], 80%-95%). Studies using a screening strategy in which the relative was contacted by health care professionals reported a pooled participation rate of 88% (95% CI, 78%-99%). The quality of interventional studies was highly variable. Random-effects meta-analysis of the highest quality randomized studies (n = 6) consisting of a specialized risk factor intervention compared with usual care was consistent with modest improvements in low-density lipoprotein cholesterol control (-0.18 mmol/L low-density lipoprotein cholesterol, 95% CI, -0.35 to -0.001; P = 0.048). Improvements in diet, smoking rates, exercise, and blood pressure were also observed with active intervention; however, reported outcomes were heterogeneous precluding a formal meta-analysis. Screening strategies that target family members, particularly when led by a health care professional, achieve a high participation rate. Although the available evidence is of variable quality, interventions that target individuals with a family history of coronary artery disease appear to be feasible and might be effective in improving certain risk factors or health behaviours but their long-term CV benefits remain uncertain.


Feedback control through cGMP-dependent protein kinase contributes to differential regulation and compartmentation of cGMP in rat cardiac myocytes.
We have shown recently that particulate (pGC) and soluble guanylyl (sGC) cyclases synthesize cGMP in different compartments in adult rat ventricular myocytes (ARVMs). We hypothesized that cGMP-dependent protein kinase (PKG) exerts a feedback control on cGMP concentration contributing to its intracellular compartmentation. Global cGMP levels, cGMP-phosphodiesterase (PDE) and pGC enzymatic activities were determined in purified ARVMs. Subsarcolemmal cGMP signals were monitored in single cells by recording the cGMP-gated current (I(CNG)) in myocytes expressing the wild-type rat olfactory cyclic nucleotide-gated (CNG) channel. Whereas the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) (100 μmol/L) produced little effect on I(CNG), the response increased 2-fold in the presence of the PKG inhibitors KT5823 (50 nmol/L) or DT-2 (2 μmol/L). The effect of KT5823 was abolished in the presence of the nonselective cyclic nucleotide PDE inhibitor 3-isobutyl-1-methylxantine (IBMX) (100 μmol/L) or the selective cGMP-PDE5 inhibitor sildenafil (100 nmol/L). PKG inhibition also potentiated the effect of SNAP on global cGMP levels and fully blocked the increase in cGMP-PDE5 activity. In contrast, PKG inhibition decreased by ≈50% the I(CNG) response to ANP (10 and 100 nmol/L), even in the presence of IBMX. Conversely, PKG activation increased the I(CNG) response to ANP and amplified the stimulatory effect of ANP on pGC activity. PKG activation in adult cardiomyocytes limits the accumulation of cGMP induced by NO donors via PDE5 stimulation but increases that induced by natriuretic peptides. These findings support the paradigm that cGMP is not uniformly distributed in the cytosol and identifies PKG as a key component in this process.


Duty to Warn in the Emergency Department: Three Medical Legal Cases That Illustrate Providers' Broad Risk and Liability.
This article presents three medical-legal cases that define a physician's duty to warn and include caveats on medical practice within the scope of the law. Some physicians may not recognize that these legal and liability requirements extend not only to physical danger, but also to infectious diseases, medical illness, and drug effects.


Outcomes of tracheobronchial stents in patients with malignant airway disease.
Malignant central airway obstruction is difficult to manage and is associated with poor outcome. We sought to identify the short (< 30 days) and intermediate (> 30 days) benefits and risks of tracheobronchial stents in patients with malignant airway disease. Two hundred and twenty-five tracheobronchial stents were placed in 172 patients for benign (n = 32) and malignant (n = 140) disease from January 1, 1997, to May 31, 2003. The records of the patients with malignant disease were retrospectively analyzed to determine complication rate, reintervention rate, and survival. The malignant diagnoses included nonsmall cell cancer, small cell cancer, esophageal cancer, and metastatic disease. There were 172 stents placed in 140 patients with malignant disease, with no intraoperative mortality. The mean follow-up period was 142 +/- 12 days. There were 23 complications, including tumor ingrowth (n = 9), excessive granulation tissue (n = 7), stent migration (n = 5), and restenosis (n = 2). Five of the complications occurred during the short-term period (< 30 days) with the remaining complications (n = 18) occurring after 30 days. The complications required interventions including laser debridement (n = 14), dilation (n = 4), and stent removal (n = 5). Tracheobronchial stents offer minimally invasive palliative therapy for patients with unresectable malignant central airway obstruction. The benefit of airway stents is particularly seen in the short-term period where they provide symptomatic improvement and have low complication risk. The major impediment is excessive granulation tissue and tumor ingrowth, which occur primarily after 30 days.


Cervical intervertebral foramen narrowing and myelographic nerve root sleeve deformities.
Intervertebral foramen narrowing on plain radiographs of the cervical spine was graded from 0 (normal) to 3 according to its severity; myelographic nerve root sleeve deformity was graded from 1 to 3 in 99 consecutive patients with cervical radiculopathy. We thus examined 1118 foramina and root sleeves. Plain radiographs of 684 foramina were normal, changes of one grade were seen in 243, of two grades in 145 and of three grades in 46. Grading of myelographic root sleeves' was normal in 789, changes of one grade in 157, of two grades in 129, and of three grades in 43. The correlations between the foraminal and root sleeve changes were: full correlation in 63.9%, a difference of one grade in 27.4%, a difference of two grades in 7.4% and a difference of three grades in 1.3%. The positive predictive value of the plain radiographs for myelographic root sleeve deformities was 55.5% and the negative value 87.1%.


The use of accelerometry to evaluate the BMX cycling starting hill. Effect of the Q-Ring™ on the acceleration profile.
Accelerometers are becoming popular in sport performance, as they are easy to wear, affordable, and usable in the field. Eccentric chainrings have been commercialised to improve pedalling performance, but little is known about their possible effects in the first pedal strokes (PS) of maximal sprint starts. To analyse the effects of the Q-Ring chainring (Q) on pedalling mechanics and performance in the BMX starting hill, 12 Spanish-National-Team BMX athletes performed 3 maximal sprints comparing Q vs No-Q. Time was measured in the first three meters. Acceleration output was registered with a triaxial 6 g accelerometer (200 Hz) in the first four PS. Discrete time, acceleration and statistical parametric mapping (SPM) were used to compare between conditions. Q showed no improvement in performance, despite a force-application time increasing (p = 0.013, ES = 0.39) and a reduction in the dead spot time (p = 0.028, ES = -0.73). Time after the four PS was greater (p = 0.006, ES = 0.63), and 3-m time did not change. Likewise, SPM 1D comparison showed no differences along the four PS. Therefore, accelerometry confirms its potential to evaluate pedalling technique in BMX, where Q-Ring fails to improve the pedalling mechanics in the starting hill.


[Genetics of congenital deafness].
Congenital deafness is defined as the hearing loss which is present at birth and, consequently, before speech development. It is the most prevalent sensor neural disorder in developed countries, and its incidence is estimated between 1-3 children per 1,000 newborns, of which more than 50% are attributable to genetics causes. Deafness can be classified as syndromic or non-syndromic. In the first case, it is associated with outer ear malformations and/or systemic findings. More than 400 syndromes accompanied of deafness have been described, which represent about 30% of cases of congenital hearing loss. The remaining percentage corresponds to non-syndromic cases: 75-85% are autosomal recessive, 15-24% are autosomal dominant, and 1-2% are X-linked. The evaluation of a child with deafness requires a multidisciplinary collaboration among specialists, who must coordinate themselves and give information to the affected family. The aims of establishing a diagnosis are to predict other manifestations that may suggest some syndrome and to anticipate their management, as well as to perform genetic counseling to parents and affected individuals.


Hemodialysis Water Parameters as Predisposing Factors for Anemia in Patients in Dialytic Treatment: Application of Mixed Regression Models.
Contamination by metals and microbiological agents in hemodialysis water can cause clinical intercurrences in hemodialysis patients. Evaluating and assuring minimum levels of contamination from metals and microorganisms in hemodialysis water can improve patient safety. The objective of this study was to assess hemodialysis water quality in a major tertiary hospital in Brazil and investigate the relationship between hemodialysis water quality and clinical intercurrences in hemodialysis patients. A prospective-observational cohort study for evaluation of water quality parameters and clinical intercurrences present by patients (n = 52) were performed from May 2014 to April 2015. Mixed linear regression models and binary regression models were fitted for water quality parameters and patients' clinical parameters. The increase in the levels of copper and nitrate in hemodialysis water was significant (p < 0.05) to explain anemia. Bone pain was related to age, sex (female), and hemodialysis treatment duration (years). Hypotensive episodes were related to serum sodium decrease. Aluminum in hemodialysis water was present in an average concentration higher than the permitted threshold (15.35 ± 14.53 μg/L). Cadmium, total coliforms, Escherichia coli, and endotoxins in hemodialysis water were not detected and the heterotrophic bacteria count was below the reference limit. These parameters' concentrations varied during the study, evidencing the need for continuous monitoring.