A stable and sensitive testing system for potential carcinogens based on DNA damage-induced gene expression in human HepG2 cell.
In order to analyze potential carcinogenic and genotoxic responses caused by exposure to pollutants existing in environment, a screening method has been established in our laboratory that uses a stably transfected HepG2 cell lines containing gadd153 promoter regions which drive a luciferase reporter gene. Activation of the exogenous gadd153 promoter was quantified using the luciferase activity following drug exposure. Twenty four agents were used to evaluate this screening assay. We selected the agents, ranging from DNA alkylating agents, oxidative agent, radiation, DNA cross-linking agent, nongenotoxic carcinogens, precarcinogenic agents, which included cadmium chloride, chromium trichloride, mercuric chloride, lead nitrate, dichloro-diphenyl-trichloroethane, deltamethrin, biphenylamine, 2-aminofluorene, benzo[a]pyrene, 2,3,7,8,-tetracblorodibenzo-p-dioxin, diethyl-stilbestrol, carbon tetrachloride, mitomycin C, hydroxycamptothecin, UV, sodium fluoride, acrylamide, hydrogen peroxide. In addition, two complex genotoxic agents (water samples) existing in the environment were selected. The results showed that all 20 tested known carcinogenic and genotoxic agents were able to induce gadd153-Luc expression at a sublethal dose. In contrast, four tested non-carcinogens, included 4-acetylaminofluorene, pyrene, benzylpenicillin sodium and vitamin C, were unable to induce gadd153-Luc expression. In conclusion, this reporter system can facilitate in vitro screening for potential carcinogens. Therefore, the gadd153-Luc test system we have developed appears to be a useful and complementary system to existing genotoxic and mutagenic tests.


Baseline achievement of lipid goals and usage of lipid medications in patients with diabetes mellitus (from the Veterans Affairs Diabetes Trial).
The American Diabetes Association has established lipid goals for patients with diabetes. Although diabetic populations historically have poor low-density lipoprotein (LDL) cholesterol goal adherence, little is known about adherence to triglyceride and high-density lipoprotein (HDL) cholesterol goals. To determine the degree of lipid goal attainment among patients with diabetes, and to characterize the patterns of lipid medication use, we evaluated the baseline data from 1,742 enrollees of the national Veterans Affairs Diabetes Trial. Using current American Diabetes Association lipid guidelines, we calculated the proportion of participants achieving a LDL cholesterol level <100 mg/dl, triglyceride level <150 mg/dl, and HDL cholesterol level >40 mg/dl in men (>50 mg/dl in women). We also performed a descriptive analysis of the use of lipid medications in this population. The baseline LDL cholesterol level was 111 +/- 63 mg/dl, triglyceride level was 213 +/- 277 mg/dl, and HDL cholesterol was 36 +/- 10 mg/dl. At enrollment, 44% of veterans met the LDL cholesterol goal, 58% met the triglyceride goal, and 16% met the HDL cholesterol goal, but only 6% met all 3 goals. Of the 1,742 enrollees, 2/3 were receiving lipid therapy, with statins (58%) the most commonly used drug. Combination lipid therapy was used by 11% of enrollees. Although the enrollees of the Veterans Affairs Diabetes Trial demonstrated better adherence to the American Diabetes Association's LDL cholesterol goal than other diabetic populations recently studied, more aggressive and directed lipid medication use is needed to treat the overall lipid profile better.


Technologies of democracy: experiments and demonstrations.
Technologies of democracy are instruments based on material apparatus, social practices and expert knowledge that organize the participation of various publics in the definition and treatment of public problems. Using three examples related to the engagement of publics in nanotechnology in France (a citizen conference, a series of public meetings, and an industrial design process), the paper argues that Science and Technology Studies provide useful tools and methods for the analysis of technologies of democracy. Operations of experiments and public demonstrations can be described, as well as controversies about technologies of democracy giving rise to counter-experiments and counter-demonstrations. The political value of the analysis of public engagement lies in the description of processes of stabilization of democratic orders and in the display of potential alternative political arrangements.


Heparin clearance during continuous veno-venous haemofiltration.
To determine whether premature clotting of haemofiltration circuits could be related to heparin removal across the filter membrane into the ultrafiltrate. Randomised study using either unfractionated (n = 8) or low molecular weight (n = 7) heparin for anticoagulation of the haemofiltration circuit at 1000 and 600 U/h respectively. Samples were drawn at 1 and 2 h from arterial and venous limbs of the haemofilter circuit for measurement of plasma heparin (as anti-Factor Xa activity), antithrombin III and haematocrit. Ultrafiltrate samples were collected at the same time for measurement of anti-Xa activity. Intensive care unit. Patients in acute renal failure requiring haemofiltration. Both unfractionated and low molecular weight heparin plasma levels were within the range required for therapeutic anticoagulation in all but one patient at 2 h. Ultrafiltrate anti-Xa levels were insignificant. Antithrombin III levels in these critically ill patients were subnormal in 11 of the 15 studies. Despite their small sizes, neither unfractionated nor low molecular weight heparins cross the haemofilter membrane into the ultrafiltrate in any measurable quantity. Both heparins were present in plasma at a level suitable for therapeutic anticoagulation. Subnormal levels of antithrombin III may be an important factor in determining filter longevity.


Determining the effect of species composition on temperature fields of tank flames using real-time holographic interferometry.
Interference fringe fields and the visible flame field of a 50 mm diameter n-hexane tank flame were simultaneously measured using a real-time holographic interferometer with special image optics. An inhouse developed image processing method was applied to the holographic images to calculate the interference fringe order profiles. The effect of species composition on temperature profiles was studied by considering three different cases: using the measured species profiles, using an overall reaction mechanism based on stoichiometric combustion, and by assuming that the flame consists of hot air. The results show that species composition has the largest effect on temperature fields in regions near the flame axis at lower axial distances. In the region of the plume zone, the flame consists primarily of hot air due to the increase in total entrained air.


Multiple outbreaks of gastroenteritis that were associated with 16 funerals and a unique caterer and spanned 6 days, 2011, Québec, Canada.
In January 2011, multiple acute gastroenteritis outbreaks that spanned many days and were related to attendance at funerals were reported to public health units in Quebec. An epidemiological investigation was initiated to identify the source of the contamination and to explain the extent of the contamination over time. Thirty-one cohorts of individuals attended different funerals held between 14 and 19 January. All attendees were served a cold buffet made by the same caterer. Of these 31 cohorts, 16 (with a total of about 800 people) contained individuals who reported being ill after the funeral. Symptoms were mainly diarrhea (89 to 94% of individuals), vomiting (63 to 90%,) and fever (26 to 39%), with a median incubation period of 29 to 33 h and a median duration of symptoms of 24 to 33 h, suggesting norovirus-like infection. Among the 16 cohorts, 3 were selected for cohort studies. Among those three cohorts, the mean illness rate was 68%. Associations were found between those who fell ill and those who had consumed pasta salad (relative risk [RR] = 2.4; P = 0.0022) and ham sandwiches (RR = 1.8; P = 0.0096). No food handlers reported being sick. No stool samples were provided by individuals who became ill. Environmental and food samples were all negative for causative agents. Although the causative agent was not clearly identified, this investigation raised many concerns about the importance of preventing foodborne transmission of viral gastroenteritis and generated some recommendations for management of similar outbreaks.


Ovarian cancer in young women in Sweden, 1989-1991.
The present study is an evaluation of the symptoms and gynecological status, at the time of seeking medical advice, among women of reproductive age diagnosed with ovarian malignancies. The study was based on the medical records of all women in Sweden between 15 and 40 years of age who were diagnosed with ovarian malignancies during a 3-year period (1989-1991). The study focused on the diagnosis and panorama of symptoms. These data were compared to the records of more than 10,000 women in this age group during the same period of time who underwent surgery for ovarian changes that resulted in benign diagnoses. The 152 cases of ovarian cancer included only 1 patient who was without symptoms, had normal pelvic status upon manual examination, and a sonographically diagnosed simple cyst. These data support the conclusion that the majority of young women with ovarian cancer have symptoms and/or clinically detectable adnexal masses at the time when medical advice is sought. These studies suggest that diagnosis of ovarian cancer is unlikely in young healthy women lacking subjective symptoms and an adnexal mass upon pelvic examination. In conclusion, programs for the management of simple cysts and development of noninvasive diagnostic methods for ovarian changes found in patients in the reproductive age group are needed in order to reduce the number of patients subjected to operative intervention.


American rural women's exercise self-efficacy and awareness of exercise benefits and safety during pregnancy.
Though the positive link between physical activity and maternal health is well documented, physical activity declines during pregnancy and, internationally, rural mothers are less likely than urban mothers to engage in physical activity. Some evidence suggests that self-efficacy is related to sustained engagement in physical activity. The purpose of this study was to examine self-efficacy, perceived benefits, and knowledge of safe exercise among 88 rural pregnant women in a southeastern region of the United States. Exercise self-efficacy was significantly related to maternal age and gestation. Women over age 26 years, and those in the second and third trimesters, scored significantly higher than younger women or those in the first trimester. Fifty-two percent (n = 46) of participants perceived that activity would decrease energy levels, 37.5% (n = 33) did not know that exercise can decrease the risk of gestational diabetes, and 47.6% (n = 41) were unaware that a mother who is overweight is more likely to have an overweight child. Results confirm a need for education to improve women's knowledge about health benefits and safety information related to physical activity during pregnancy.


Hyperketonemia can increase lipid peroxidation and lower glutathione levels in human erythrocytes in vitro and in type 1 diabetic patients.
Recent studies have suggested that elevated cellular lipid peroxidation may play a role in the development of cellular dysfunction and other complications of diabetes. People with type 1 diabetes frequently encounter elevated levels of the ketone bodies acetoacetate (AA), beta-hydroxybutyrate (BHB), and acetone (ACE). This study was undertaken to test the hypothesis that ketosis might increase lipid peroxidation and lower glutathione (GSH) levels of red blood cells (RBCs) in diabetic patients. This study demonstrates that incubation of AA with normal RBCs in phosphate-buffered saline (37 degrees C for 24 h) resulted in marked GSH depletion, oxidized glutathione accumulation, hydroxyl radical generation, and increased membrane lipid peroxidation. Increases in oxygen radicals and lipid peroxidation and depletion of GSH in RBCs were not observed with BHB or ACE treatments. Similarly, there was a significant generation of superoxide ion radicals even in a cell-free buffer solution of AA, but not in that of BHB. The presence of BHB together with AA did not influence the capacity of AA to generate oxygen radicals in a cell-free solution or the increase in lipid peroxidation of RBCs incubated with AA. The antioxidants vitamin E and N-acetylcysteine (NAC) blocked increase in lipid peroxidation in AA-treated RBCs. To examine the effects of ketone bodies in vivo, studies were performed that showed a significant decrease in GSH and an increase in lipid peroxidation levels in RBCs of hyperketonemic diabetic patients, but not in normoketonemic type 1 diabetic patients, when compared with age-matched normal subjects. This study demonstrates that elevated levels of the ketone body AA can increase lipid peroxidation and lower GSH levels of RBCs in people with type 1 diabetes.


Altered neuroregulation of GH secretion in viscerally obese premenopausal women.
We used deconvolution analysis of 24-h plasma GH concentration profiles (10- min sampling intervals) to appraise GH secretion rates and elimination kinetics in obese (body mass index, approximately 34 kg/m2) premenopausal women with large visceral fat area (LVFA; n = 8) vs. small visceral fat area (SVFA; n = 8) as determined by magnetic resonance imaging. The subjects were matched for body mass index, body fat percentage, and age. The impact of the loss of 50% of prestudy weight excess induced by caloric restriction was assessed as well. The results were compared with those obtained in normal weight control women (n = 8). LVFA subjects manifested markedly (4-fold) reduced mean plasma GH levels, which was brought about by jointly diminished basal and pulsatile GH secretion. Moreover, visceral obesity was associated with loss of regularity of GH release, as established by the approximate entropy statistic. In contrast, SVFA subjects produced normal daily amounts of GH and exhibited mean 24-h plasma GH concentrations that were similar to those in normal weight controls. GH half-life and distribution volume were not different among the study groups. Importantly, weight loss did not affect the daily GH secretion rate in LVFA women, so that their mean plasma GH concentration remained considerably reduced (approximately 50%) compared with controls (despite the loss of approximately 40% of visceral fat). Normal GH kinetics in SVFA women were not significantly influenced by weight reduction. Thus, GH neuroregulation appears to be particularly altered in obese women with a tendency to store fat in their visceral adipose depot. Because weight loss did not reverse GH secretion rate in viscerally obese women, we speculate that relative hyposomatotropism is a primary feature of these women, which could be involved in their tendency to preferentially store excess fat in visceral adipose tissue.


Helping Clients Feel Welcome: Principles of Adapting Treatment Cross-Culturally.
Empirically supported interventions (ESIs) for treating substance problems have seldom been made available to or tested with minority populations. Dissemination of ESIs may help reduce the disproportionate health disparities that exist. However, ESIs may require some adaptation to be effective with minority populations. One ESI, motivational interviewing (MI), appears to be particularly culturally congruent for Native American communities. We worked with Native American community members and treatment providers to adapt MI for Native communities. Reflecting their feedback and suggested amendments, we created and disseminated an intervention manual to improve the accessibility of MI within Native communities. To help guide practitioners working with Native American clients, we used focus-group methodology to explore communication patterns for negotiating change. Native American treatment providers expressed comfort with and enthusiasm for integrating MI into their current practices. Recommendations for adaptations ranged from simple to complex changes. The unique value and challenges of collaboration between academic and community members are presented from each author's perspective. This culturally adapted MI manual will likely improve the accessibility and adoption of MI practices as well as encourage controlled, clinical trials with Native communities.


Laser blepharoplasty in Asians.
Traditional blepharoplasty removes periorbital wrinkles by cutting and stretching the skin. However, this method has a substantial risk of producing ectropion or scleral show. In addition, fine periocular wrinkles may persist because this method does not change skin texture. The pulsed CO2 laser has recently become a primary surgical tool in treating aging eyelids. Periorbital wrinkles vary in depth not only from person to person, but also among different races. Compared with whites, most Asians have a thicker dermis, so more laser passes and a higher power may be required to remove periorbital wrinkles, but concerns about hyperpigmentation and prolonged erythema have limited its use on Asian skin. In this study, 346 patients underwent laser blepharoplasty at the Korea University Medical Center and at Dr Choi's Aesthetic Clinic. They were followed for 12 months on average from September 1995 to September 1999. The CO2 laser was used in resurfacing periorbital wrinkles, transcutaneous skin excision, and transconjunctival blepharoplasty, including fat removal. The authors assessed the benefit of using the UltraPulse CO2 laser in Asian blepharoplasty. They found that 291 patients (84%) had good to excellent results. The incidence of side effects was very low. Prolonged erythema occurred in 19 patients (5%) and hyperpigmentation occurred in 35 patients (10%), but the erythema disappeared spontaneously within 2 months and the hyperpigmentation could be managed readily by the topical use of retinoids and hydroquinone cream. Therefore, the authors conclude that postoperative hyperpigmentation is no longer a problem limiting laser resurfacing in Asian blepharoplasty. The UltraPulse CO2 laser is a safe and effective rejuvenation method for treating aging eyelids in Asians.


Electron beam lithography designed silver nano-disks used as label free nano-biosensors based on localized surface plasmon resonance.
We present a label-free, optical nano-biosensor based on the Localized Surface Plasmon Resonance (LSPR) that is observed at the metal-dielectric interface of silver nano-disk arrays located periodically on a sapphire substrate by Electron-Beam Lithography (EBL). The nano-disk array was designed by finite-difference and time-domain (FDTD) algorithm-based simulations. Refractive index sensitivity was calculated experimentally as 221-354 nm/RIU for different sized arrays. The sensing mechanism was first tested with a biotin-avidin pair, and then a preliminary trial for sensing heat-killed Escherichia coli (E. coli) O157:H7 bacteria was done. Although the study is at an early stage, the results indicate that such a plasmonic structure can be applied to bio-sensing applications and then extended to the detection of specific bacteria species as a fast and low cost alternative.


Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria.
The methylmalonic acidurias are metabolic disorders resulting from deficient methylmalonyl-CoA mutase activity, a vitamin B(12)-dependent enzyme. We have cloned the gene for the cblB complementation group caused by deficient activity of a cob(I)alamin adenosyltransferase. This was accomplished by searching bacterial genomes for genes in close proximity to the methylmalonyl-CoA mutase gene that might encode a protein with the properties of an adenosyltransferase. A candidate was identified in the Archaeoglobus fulgidus genome and was used to probe the human genome database. It yielded a gene on chromosome 12q24 that encodes a predicted protein of 250 amino acids with 45% similarity to PduO in Salmonella enterica, a characterized cob(I)alamin adenosyltransferase. A northern blot revealed an RNA species of 1.1 kb predominating in liver and skeletal muscle. The gene was evaluated for deleterious mutations in cblB patient cell lines. Several mutations were identified including a 5 bp deletion (5del572gggcc576), two splice site mutations (IVS2-1G>T, IVS3-1G>A), andt several point mutations (A135T, R186W, R191W and E193K). Two additional amino acid substitutions (R19Q and M239K) were found in several patient cell lines but were found to be common polymorphisms (36% and 46%) in control alleles. The R186W mutation, which we suggest is disease-linked, is present in four of the six patient cell lines examined (homoallelic in two) and in 4 of 240 alleles in control samples. These data confirm that the identified gene, MMAB, corresponds to the cblB complementation group and has the appearance of a cob(I)alamin adenosyltransferase, as predicted from biochemical data.


Impact of smoking policy on the respiratory health of food and beverage servers.
The purpose of this study was to determine whether workplace smoking policy was associated with respiratory health effects among food and beverage servers. Data were obtained from a postal survey of hospitality workers. The participation rate for the questionnaire was 73.9% of those contacted. Current smokers were excluded from the analysis. Adjustment for differences between groups in age, gender, ex-smoker versus never smoker status, home exposure environmental tobacco smoke, childhood asthma, mail versus telephone questionnaire, and hours worked per week was done using logistic regression. A subset of 88 nonsmokers underwent laboratory evaluation, including spirometry and hair nicotine analysis. The prevalence of irritant and respiratory symptoms among 383 nonsmokers was consistently higher among the participants from premises where smoking was permitted without restrictions on the workplace. In comparison with those from facilities where smoking was prohibited, the highest adjusted odds ratios (OR) were for chronic phlegm for those working where smoking was permitted (OR 8.5 95% confidence interval (95% CI) 2.4-30.0] or where there were partial smoking restrictions (OR 5.7 95% CI 1.7-19.4). Lung function was not reduced apart from the ratio between forced expiratory volume in 1 second and forced vital capacity, which was lower for workers from facilities where smoking was permitted. Hair nicotine levels were lowest for workers from facilities where smoking was prohibited. The results suggest that occupational exposure to environmental tobacco smoke, determined through smoking policies, can adversely affect the respiratory health of nonsmokers who work in the food and beverage service industry.


COVID-19 Lockdown: A Global Study Investigating the Effect of Athletes' Sport Classification and Sex on Training Practices.
To investigate differences in athletes' knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. Athletes (12,526; 66% male; 142 countries) completed an online survey (May-July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%-49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%-28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). Changes in athletes' training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.


Long-term evaluation of fitness and demographic effects of a Chinook Salmon supplementation program.
While the goal of supplementation programs is to provide positive, population-level effects for species of conservation concern, these programs can also present an inherent fitness risk when captive-born individuals are fully integrated into the natural population. In order to evaluate the long-term effects of a supplementation program and estimate the demographic and phenotypic factors influencing the fitness of a threatened population of Chinook Salmon (Oncorhynchus tshawytscha), we genotyped tissue samples spanning a 19-year period (1998-2016) to generate pedigrees from adult fish returning to Johnson Creek, Idaho, USA. We expanded upon previous estimates of relative reproductive success (RRS) to include grandparentage analyses and used generalized linear models to determine whether origin (hatchery or natural) or phenotypic traits (timing of arrival to spawning grounds, body length, and age) significantly predicted reproductive success (RS) across multiple years. Our results provide evidence that this supplementation program with 100% natural-origin broodstock provided a long-term demographic boost to the population (mean of 4.56 times in the first generation and mean of 2.52 times in the second generation). Overall, when spawning in nature, hatchery-origin fish demonstrated a trend toward lower RS compared to natural-origin fish (p < 0.05). However, when hatchery-origin fish successfully spawned with natural-origin fish, they had similar RS compared to natural by natural crosses (first-generation mean hatchery by natural cross RRS = 1.11 females, 1.13 males; second-generation mean hatchery by natural cross RRS = 1.03 females, 1.08 males). While origin, return year, and body length were significant predictors of fitness for both males and females (p < 0.05), return day was significant for males but not females (p > 0.05). These results indicate that supplementation programs that reduce the potential for genetic adaptation to captivity can be effective at increasing population abundance while limiting long-term fitness effects on wild populations.


Transmission degradation and preservation for tapered optical fibers in rubidium vapor.
The use of subwavelength diameter tapered optical fibers (TOFs) in warm rubidium vapor has recently been identified as a promising system for realizing ultralow-power nonlinear optical effects. However, at the relatively high atomic densities needed for many of these experiments, rubidium atoms accumulating on the TOF surface can cause a significant loss of overall transmission through the fiber. Here we report direct measurements of the time scale associated with this transmission degradation for various rubidium density conditions. Transmission is affected almost immediately after the introduction of rubidium vapor into the system, and declines rapidly as the density is increased. More significantly, we show how a heating element designed to raise the TOF temperature can be used to reduce this transmission loss and dramatically extend the effective TOF transmission lifetime.


Trialling Meta-Research in Comparative Cognition: Claims and Statistical Inference in Animal Physical Cognition.
Scientific disciplines face concerns about replicability and statistical inference, and these concerns are also relevant in animal cognition research. This paper presents a first attempt to assess how researchers make and publish claims about animal physical cognition, and the statistical inferences they use to support them. We surveyed 116 published experiments from 63 papers on physical cognition, covering 43 different species. The most common tasks in our sample were trap-tube tasks (14 papers), other tool use tasks (13 papers), means-end understanding and string-pulling tasks (11 papers), object choice and object permanence tasks (9 papers) and access tasks (5 papers). This sample is not representative of the full scope of physical cognition research; however, it does provide data on the types of statistical design and publication decisions researchers have adopted. Across the 116 experiments, the median sample size was 7. Depending on the definitions we used, we estimated that between 44% and 59% of our sample of papers made positive claims about animals' physical cognitive abilities, between 24% and 46% made inconclusive claims, and between 10% and 17% made negative claims. Several failures of animals to pass physical cognition tasks were reported. Although our measures had low inter-observer reliability, these findings show that negative results can and have been published in the field. However, publication bias is still present, and consistent with this, we observed a drop in the frequency of p-values above .05. This suggests that some non-significant results have not been published. More promisingly, we found that researchers are likely making many correct statistical inferences at the individual-level. The strength of evidence of statistical effects at the group-level was weaker, and its p-value distribution was consistent with some effect sizes being overestimated. Studies such as ours can form part of a wider investigation into statistical reliability in comparative cognition. However, future work should focus on developing the validity and reliability of the measurements they use, and we offer some starting points.


Comparing the mRNA expression profile and the genetic determinism of intramuscular fat traits in the porcine gluteus medius and longissimus dorsi muscles.
Intramuscular fat (IMF) content and composition have a strong impact on the nutritional and organoleptic properties of porcine meat. The goal of the current work was to compare the patterns of gene expression and the genetic determinism of IMF traits in the porcine gluteus medius (GM) and longissimus dorsi (LD) muscles. A comparative analysis of the mRNA expression profiles of the pig GM and LD muscles in 16 Duroc pigs with available microarray mRNA expression measurements revealed the existence of 106 differentially expressed probes (fold-change > 1.5 and q-value < 0.05). Amongst the genes displaying the most significant differential expression, several loci belonging to the Hox transcription factor family were either upregulated (HOXA9, HOXA10, HOXB6, HOXB7 and TBX1) or downregulated (ARX) in the GM muscle. Differences in the expression of genes with key roles in carbohydrate and lipid metabolism (e.g. FABP3, ORMDL1 and SLC37A1) were also detected. By performing a GWAS for IMF content and composition traits recorded in the LD and GM muscles of 350 Duroc pigs, we identified the existence of one region on SSC14 (110-114 Mb) displaying significant associations with C18:0, C18:1(n-7), saturated and unsaturated fatty acid contents in both GM and LD muscles. Moreover, we detected several genome-wide significant associations that were not consistently found in both muscles. Further studies should be performed to confirm whether these associations are muscle-specific. Finally, the performance of an eQTL scan for 74 genes, located within GM QTL regions and with available microarray measurements of gene expression, made possible to identify 14 cis-eQTL regulating the expression of 14 loci, and six of them were confirmed by RNA-Seq. We have detected significant differences in the mRNA expression patterns of the porcine LD and GM muscles, evidencing that the transcriptomic profile of the skeletal muscle tissue is affected by anatomical, metabolic and functional factors. A highly significant association with IMF composition on SSC14 was replicated in both muscles, highlighting the existence of a common genetic determinism, but we also observed the existence of a few associations whose magnitude and significance varied between LD and GM muscles.


Connexin 43 plays a role in proliferation and migration of pulmonary arterial fibroblasts in response to hypoxia.
Pulmonary hypertension (PH) is a disease associated with vasoconstriction and remodelling of the pulmonary vasculature. Pulmonary artery fibroblasts (PAFs) play an important role in hypoxic-induced remodelling. Connexin 43 (Cx43) is involved in cellular communication and regulation of the pulmonary vasculature. Using both in vitro and in vivo models of PH, the aims of this study were to (i) investigate the role of Cx43 in hypoxic-induced proliferation and migration of rat PAFs (rPAFs) and rat pulmonary artery smooth muscle cells (rPASMCs) and (ii) determine whether Cx43 expression is dysregulated in the rat sugen5416/hypoxic model of PH. The role of Cx43 in hypoxic-induced proliferation and migration was investigated using Gap27 (a pharmacological inhibitor of Cx43) or genetic knockdown of Cx43 using siRNA. Cx43 protein expression was increased by hypoxia in rPAFs but not rPASMCs. Hypoxic exposure, in the presence of serum, resulted in an increase in proliferation of rPAFs but not rPASMCs. Hypoxic exposure caused migration of rPAFs but not rPASMCs. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) and ERK1/2 were increased by hypoxia in rPAFs. The effects of hypoxia on proliferation, migration and MAPK phosphorylation in rPAFs were attenuated in the presence of Gap27 or Cx43 siRNA. Cx43 protein expression was increased in sugen5416/hypoxic rat lung; this increased expression was not observed in sugen5416/hypoxic rats treated with the MAPK pathway inhibitor GS-444217. In conclusion, Cx43 is involved in the proliferation and migration of rPAFs in response to hypoxia via the MAPK signalling pathway.


P300 amplitude alterations during inhibitory control in persons with Mild Cognitive Impairment.
Deficits in executive function are highly noticeable in Alzheimer's disease, and recent behavioral studies have shown that such deficits - particularly during inhibitory control - can also be found in persons with Mild Cognitive Impairment (MCI). Thus, the objective of this study was to investigate behavioral and electrophysiological correlates of inhibitory control in persons with MCI. A group of persons with MCI and a group healthy older adults performed a Go/NoGo task while electroencephalogram was recorded. Our results revealed that persons with MCI performed less accurately than healthy controls during the Go and NoGo conditions. In addition, we found reduced P300 amplitudes during Go and NoGo conditions relative to healthy older adults. Our results suggest that neurocognitive mechanisms associated with target detection and evaluation (Go P300) and response inhibition (NoGo P300) are compromised in persons with MCI.


Classification of pain in cancer patients--a systematic literature review.
One of the aims of the European Palliative Care Research Collaborative (EPCRC) is to achieve consensus on a classification system for cancer pain. We performed a systematic literature review to identify existing classification systems and domains/items used to classify cancer patients with pain. In a systematic search in the databases Medline and Embase, covering 1986-2006, 692 hits were obtained. 92 papers were evaluated to address pain classification. Six standardised classification systems were identified; three of them systematically developed and partially validated. Both pain characteristics and patient characteristics relevant for cancer pain classification were included in the classification systems. All but one of the standardised systems aim at predicting treatment response or adequacy of treatment. Several domains and items used to describe cancer pain but not formally described as part of a classification system were also identified and systematized. The existing approaches to pain classification in cancer patients are different, mostly not thoroughly validated, and none is widely applied. An internationally accepted classification system for cancer pain could improve research and cancer pain management. This systematic review suggests a need for developing an international consensus on how to classify pain in cancer patients.


Horizontal DNA Transfer Mechanisms of Bacteria as Weapons of Intragenomic Conflict.
Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated.


FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility.
Compartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and myofilament sites, reveals differential kinetics and amplitudes of localized cAMP signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize cardiac contractility upon adrenergic activation. At low adrenergic levels, and those mimicking heart failure, differential local cAMP responses are exacerbated, with near abolition of cAMP signalling at certain locations. This work provides tools and fundamental mechanistic insights into subcellular adrenergic signalling in normal and pathological cardiac function.


Type 2 diabetes can be prevented with early pharmacological intervention.
In the U.S., ∼ 21 × 10(6) individuals have type 2 diabetes, and twice as many have impaired glucose tolerance (IGT). Approximately 40-50% of individuals with IGT will progress to type 2 diabetes over their lifetime. Therefore, treatment of high-risk individuals with IGT to prevent type 2 diabetes has important medical, economic, social, and human implications. Weight loss, although effective in reducing the conversion of IGT to type 2 diabetes, is difficult to achieve and maintain. Moreover, 40-50% of IGT subjects progress to type 2 diabetes despite successful weight reduction. In contrast, pharmacological treatment of IGT with oral antidiabetic agents that improve insulin sensitivity and preserve β-cell function--the characteristic pathophysiological abnormalities present in IGT and type 2 diabetes--uniformly have been shown to prevent progression of IGT to type 2 diabetes. The most consistent results have been observed with the thiazolidinediones (Troglitazone in the Prevention of Diabetes [TRIPOD], Pioglitazone in the Prevention of Diabetes [PIPOD], Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication [DREAM], and Actos Now for the Prevention of Diabetes [ACT NOW]), with a 50-70% reduction in IGT conversion to diabetes. Metformin in the U.S. Diabetes Prevention Program (DPP) reduced the development of type 2 diabetes by 31% and has been recommended by the American Diabetes Association (ADA) for treating high-risk individuals with IGT. The glucagon-like peptide-1 analogs, which augment insulin secretion, preserve β-cell function, and promote weight loss, also would be expected to be efficacious in preventing the progression of IGT to type 2 diabetes. Because individuals in the upper tertile of IGT are maximally/near-maximally insulin resistant, have lost 70-80% of their β-cell function, and have an ∼ 10% incidence of diabetic retinopathy, pharmacological intervention, in combination with diet plus exercise, should be instituted.


Assessment and outcome of pediatric intestinal pseudo-obstruction: A tertiary-care-center experience from Turkey.
Pediatric intestinal pseudo-obstruction (PIPO) is a severe disorder of gut motility. In this rare and difficult-to-manage disease, complex treatment method, such as intestinal transplantation, is sometimes needed. This study evaluated the management and follow-up results of patients with PIPO who received treatment at our center. The cases of 13 patients with PIPO were reviewed retrospectively. Demographic data, clinical features, etiologies, pharmacological and surgical treatments, nutritional support, anthropometric findings, small bowel transplantation (SBT), and survival rates were assessed. Two of the patients were diagnosed at 1 and 5 years of age, while other patients were diagnosed during neonatal period. The etiological cause could not be identified for 5 patients. Pharmacological treatment response was observed in 38.4% of patients. Post-pyloric feeding was applied in 4 patients, but no response was observed. Gastrostomy decreased the clinical symptoms in 3 patients during the abdominal distension period. Total oral nutrition was achieved in 38.4% of the total-parenteral-nutrition (TPN)-dependent patients. It was observed that anthropometric findings improved in patients with total oral nutrition. Liver cirrhosis developed in 1 patient. Venous thrombosis developed in 4 patients. The SBT was performed on 3 patients. One of these patients has been followed up for the last 4 years. Pediatric intestinal pseudo-obstruction is a rare disease that can present with a wide range of clinical symptoms. While some patients require intestinal transplantation, supportive care may be sufficient in others. For this reason, patients with PIPO should be managed individually.


Phytoseiids in Washington commercial apple orchards: biodiversity and factors affecting abundance.
Galendromus occidentalis (Nesbitt) is an important biological control agent of spider mites (Acari: Tetranychidae) in Washington apple orchards. It was thought to be essentially the sole phytoseiid existing in this system, due in part to its resistance to commonly used orchard pesticides, and organophosphates in particular. To test this assumption, we conducted a survey of 102 commercial apple blocks in Washington to characterize the community of phytoseiid species. Seven phytoseiid species were found in our samples; G. occidentalis and Amblydromella caudiglans (Schuster) were found in the greatest abundance. We hypothesized that the gradual shift away from the use of organophosphates in recent decades may have caused the change in phytoseiid community structure. The survey data and information regarding the management, location, and surrounding habitat of each block were used to determine what factors affect phytoseiid abundances. Galendromus occidentalis abundance was positively affected by the use of conventional (vs. organic) spray programs, and the use of the acaricide bifenazate. Amblydromella caudiglans abundance was negatively affected by bifenazate use and positively affected by herbicide strip weediness; it was also less prevalent in 'Golden Delicious' blocks compared to other cultivars. These results indicate that A. caudiglans reaches higher abundances in orchards that lack certain agricultural disturbances, whereas G. occidentalis can survive in more disturbed environments. Surveys of this nature can provide valuable insight to potential drivers of community structure, allowing for the improvement of integrated pest management programs that incorporate conservation of newly recognized biological control agents such as A. caudiglans.


In vivo assessment of diaphragm contraction by ultrasound in normal subjects.
Ultrasound allows observation of the thickness of the diaphragm in the zone of apposition in vivo during relaxation and maximum inspiratory efforts. Changes of diaphragm thickness were studied by B mode (two dimensional) ultrasound in 13 healthy men aged 29-54 years in the seated position. A high resolution 7.5 MHz ultrasound transducer was held perpendicular to the chest wall in the line of a right intercostal space between the anteroaxillary and mid-axillary lines to observe the diaphragm in the zone of apposition 0.5-2 cm below the costophrenic angle. The changes of thickness were observed while breath holding at total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV). At FRC the thickness while relaxing against a closed mouthpiece and during a maximum inspiratory mouth pressure (PImax) manoeuvre was recorded. The thickening ratio (TR) was calculated as TR = thickness during PImax manoeuvre/thickness while relaxing. Mean (SD) thickness was 4.5 (0.9) mm at TLC, 1.7 (0.2) mm at FRC, and 1.6 (0.2) mm at RV. During the PImax manoeuvre at FRC mean thickness increased from 1.7 (0.2) mm during relaxation to 4.4 (1.4) mm, while mean PImax and TR were -104 (33) cm H2O and 2.6 (0.7), respectively. There was a high degree of correlation between TR and the pressure achieved during the maximum inspiratory manoeuvre (r = -0.82). Ultrasound provides a non-invasive assessment of diaphragm thickness with change of lung volume and during the PImax manoeuvre which should prove useful in assessing diaphragm mass and contraction in respiratory and muscle disease.


Hitchhiking of encrusting organisms on floating marine debris along the west coast of Qatar, Arabian/Persian Gulf.
The floating marine debris (FMD) and the associated rafting communities are one of the major stressors to ecosystem services, global biodiversity and economy and human health. In this study, assemblages of encrusting organisms on different types of stranded FMD along the west coast of Qatar, Arabian/Persian Gulf (hereafter referred to as 'Gulf') were examined. The analysis showed 18 fouling species belonging to 5 phyla (Annelida, Anthropoda, Bryozoa, Mollusca and Porifera) on the FMD. The most abundant fouling species were the encrusting Amphibalanus amphitrite, polychaete Spirobranchus kraussii, Bryozoan species and Megabalanus coccopoma. More number of taxa were found on larger size FMD than on smaller FMD. Some of the barnacle rafting types were found to be non-indigenous species. The central and northwest parts of the Qatar had more FMD and fouled species than in other locations. Winds and the prevailing hydrodynamic conditions (waves and currents) played an important role in the transportation and distribution of FMD and associated organisms along the west coast of Qatar. The present study confirmed that huge amount of bio-fouled FMD items, causing great damage to biodiversity, drift in the surface layer of ocean and eventually strand onto the beaches. We propose a simple, but an effective management plan for FMD and associated organisms at regional scale to restore the biodiversity, sustainability and health of the marine ecosystem in the Gulf.


Catalogue of abrupt shifts in Intergovernmental Panel on Climate Change climate models.
Abrupt transitions of regional climate in response to the gradual rise in atmospheric greenhouse gas concentrations are notoriously difficult to foresee. However, such events could be particularly challenging in view of the capacity required for society and ecosystems to adapt to them. We present, to our knowledge, the first systematic screening of the massive climate model ensemble informing the recent Intergovernmental Panel on Climate Change report, and reveal evidence of 37 forced regional abrupt changes in the ocean, sea ice, snow cover, permafrost, and terrestrial biosphere that arise after a certain global temperature increase. Eighteen out of 37 events occur for global warming levels of less than 2°, a threshold sometimes presented as a safe limit. Although most models predict one or more such events, any specific occurrence typically appears in only a few models. We find no compelling evidence for a general relation between the overall number of abrupt shifts and the level of global warming. However, we do note that abrupt changes in ocean circulation occur more often for moderate warming (less than 2°), whereas over land they occur more often for warming larger than 2°. Using a basic proportion test, however, we find that the number of abrupt shifts identified in Representative Concentration Pathway (RCP) 8.5 scenarios is significantly larger than in other scenarios of lower radiative forcing. This suggests the potential for a gradual trend of destabilization of the climate with respect to such shifts, due to increasing global mean temperature change.


Dual oxidase 1 and 2 expression in airway epithelium of smokers and patients with mild/moderate chronic obstructive pulmonary disease.
Dual oxidase (Duox) 1 and Duox2 are important sources of hydrogen peroxide production and play a role in host defense in airways. Little is known about their regulation in association with smoking or chronic obstructive pulmonary disease (COPD). We investigated the epithelial expression of Duox1 and Duox2 in the airways of smokers, and the relationship between this expression and COPD at early stage. First, using bronchoscopy, we harvested tracheal and bronchial epithelium from individuals who have never smoked and current smokers. Duox1 expression in brushed tracheal and bronchial epithelium was significantly downregulated, whereas Duox2 was upregulated, in current smokers as compared to individuals who have never smoked. Second, laser capture microdissection and microscope-assisted manual dissection were performed in surgically resected lung tissues to collect bronchiolar epithelium and alveolar septa. Subjects with mild/moderate COPD, who were all former smokers, exhibited downregulation of bronchiolar Duox1 and Duox2 when compared to individuals who have never smoked, whereas a difference between former smokers, with and without COPD, was observed only for Duox1. Alveolar Duox1 and Duox2 expression was low and did not differ among the groups. These results imply that the airway expression of Duox1 and Duox2 is diversely associated with smoking and COPD.


[Long-term benefit of male circumcision to the reduction of urinary tract infections and genitourinary cancers in China].
Increasingly accumulated results from randomized controlled trials and other clinical studies have demonstrated that male circumcision reduces the risks of acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted infections, and thus has a potential role in preventing cervical cancer, penile cancer and prostate cancer. The prevalence of male circumcision in China is currently less than 5%. The clinical evaluation studies and randomized controlled trials of the Shang Ring device showed excellent safety profiles, extremely high acceptability, and satisfaction among the participants and service providers in Africa and China. Given the recent recommendations by the World Health Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary medical male circumcision should be promoted in China at the national level as an important alternative intervention to reduce reproductive tract infections and prevent both males and females from reproductive tract cancers. More emphasis is required on the studies of the long-term health benefits of male circumcision in uro-andrology.


Atherosclerosis and hypertension induction by lead and cadmium ions: an effect prevented by calcium ion.
In epidemiological studies, both positive and negative correlations have been found between cardiovascular disease and mortality and the presence of several inorganic ions in the drinking water. In an attempt to resolve this apparent disagreement, we exposed White Carneau pigeons to drinking water containing calcium (100 ppm), magnesium (30 ppm), lead (0.8 ppm), or cadmium (0.6 ppm) and used a 2(4)-factorial design to measure the effects of these elements in atherosclerosis and hypertension. The results indicate that (i) lead and cadmium induced aortic atherosclerosis and hypertension, and (ii) calcium protects against the cardiovascular effects of cadmium. Furthermore, the effects of lead and cadmium were promoted by magnesium, and there were indications that magnesium antagonized the atherosclerotic protective effect of calcium. We suggest that, if these results with the pigeon can be applied to humans, the incidence of aortic atherosclerosis and hypertension should be significantly higher in areas where the drinking water contains magnesium, lead, and cadmium with a relatively low calcium concentration. Furthermore, if hard and soft water produce similar levels of lead and cadmium uptakes, the level of magnesium may be an additional factor in aortic atherosclerosis.


Interaction studies of an anticancer alkaloid, (+)-(13aS)-deoxytylophorinine, with calf thymus DNA and four repeated double-helical DNAs.
Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity. The specific biomolecular targets of these alkaloids have not yet been clearly identified. (+)-(13aS)-deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute. (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer activities. The in vivo anticancer effects and toxicity of this compound were investigated in mice, and interactions between this compound and double-helical DNA sequences were studied in detail with circular dichroic spectroscopy and fluorescence spectroscopy. Viscosity measurements were applied to check the interactive mode between this compound and DNA. Potent anticancer effects were observed in vivo. Also, concentration-dependent interactions were observed and this compound seemed to interact in a sequence-specific manner with AT-repeated sequences of double-helical DNA. Such interactions were proved to be intercalating by viscosity measurements. Anticancer alkaloid (+)-(13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an intercalating manner.


Induction of apoptosis after expression of PYK2, a tyrosine kinase structurally related to focal adhesion kinase.
Many cells (e.g., epithelial cells) require attachment to the extracellular matrix (ECM) to survive, a phenomenon known as anchorage-dependent cell survival. Disruption of the cell-ECM interactions mediated by the integrin receptors results in apoptosis. Focal adhesion kinase (FAK), a 125-kD protein tyrosine kinase activated by integrin engagement, appears to be involved in mediating cell attachment and survival. Proline-rich tyrosine kinase 2 (PYK2), also known as cellular adhesion kinase beta (CAKbeta) and related adhesion focal tyrosine kinase, is a second member of the FAK subfamily and is activated by an increase in intracellular calcium levels, or treatment with TNFalpha and UV light. However, the function of PYK2 remains largely unknown. In this study, we show that over-expression of PYK2, but not FAK, in rat and mouse fibroblasts leads to apoptotic cell death. Using a series of deletion mutants and chimeric fusion proteins of PYK2/FAK, we determined that the NH2-terminal domain and tyrosine kinase activity of PYK2 were required for the efficient induction of apoptosis. Furthermore, the apoptosis mediated by PYK2 could be suppressed by over-expressing catalytically active v-Src, c-Src, phosphatidylinositol-3-kinase, or Akt/protein kinase B. In addition, it could also be suppressed by overexpressing an ICE or ICE-like proteinase inhibitor, crmA, but not Bcl2. Collectively, our results suggest that PYK2 and FAK, albeit highly homologous in primary structure, appear to have different functions; FAK is required for cell survival, whereas PYK2 induces apoptosis in fibroblasts.


Serum urate and obstructive sleep apnoea in severe obesity.
Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and predispose to gout. The evidence for the effects of OSA on serum urate in severe obesity is limited. This study investigated whether OSA was associated with serum urate in severe obesity and whether continuous positive airway pressure (CPAP) treatment was associated with a fall in urate. Severely obese subjects without known OSA or gout were recruited. Baseline assessments included urate, metabolic parameters, spirometry and overnight polysomnography. OSA patients were initially naive to treatment and were offered CPAP. At follow-up, change in urate was compared between CPAP-treated and non-CPAP-treated subjects. A high urate was defined as greater than the median. Logistic regression was performed to identify associations between (1) OSA and high urate at baseline and (2) use of CPAP and change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA and 31 (34%) non-OSA). Median urate was 345 μmol/L. OSA was associated with high urate in females at baseline after adjusting for confounders (adjusted odds ratio ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with a fall to a low urate category at follow-up ( = 0.017). Regression revealed a trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95% CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and CPAP may reduce levels in patients with OSA. There may be a need to consider and assess for OSA in obese patients with hyperuricaemia and recurrent attacks of gout.


Case Series: Redefining Severe Grade 5 Vaginismus.
Vaginismus is poorly understood and relatively unknown among health care providers. For those who understand and treat vaginismus, few make an assessment of the severity of this condition. The importance of classifying the severity of vaginismus impacts the clinician's ability to diagnose and treat vaginismus, and understanding of the patient's experience. The aims of this paper are to identify the distinguishing features of severe grade 5 vaginismus, determine if vaginal spasm is present in severe grade vaginismus, and to establish qualifications for the Pacik grade 5 classification. Assessment of 553 referred or self-referred women who were unable to tolerate intercourse completed a comprehensive pretreatment questionnaire. Of those women, 391 underwent a vaginal examination in a certified surgicenter using sedation and anesthesia as needed. The main outcome measures were to detect the presence of a visceral reaction with an intended or actual gynecologic examination in Grade 5 patients, and to identify vaginal spasm on examination. A visceral response reaction to routine gynecologic examinations, as well as spasm of the bulbocavernosum, occurred in patients with severe vaginismus. Severe vaginismus with visceral response manifestations to routine gynecologic examinations, inability to have intercourse, and spasm of the bulbocavernosum is newly defined as severe grade 5 vaginismus. Pacik PT, Babb CR, Polio A, et al. Redefining Severe Grade 5 Vaginismus. Sex Med 2019;7:489-497.


Imaging Bone-Cartilage Interactions in Osteoarthritis Using [18F]-NaF PET-MRI.
Simultaneous positron emission tomography-magnetic resonance imaging (PET-MRI) is an emerging technology providing both anatomical and functional images without increasing the scan time. Compared to the traditional PET/computed tomography imaging, it also exposes the patient to significantly less radiation and provides better anatomical images as MRI provides superior soft tissue characterization. Using PET-MRI, we aim to study interactions between cartilage composition and bone function simultaneously, in knee osteoarthritis (OA). In this article, bone turnover and remodeling was studied using [18F]-sodium fluoride (NaF) PET data. Quantitative MR-derived T1ρ relaxation times characterized the biochemical cartilage degeneration. Sixteen participants with early signs of OA of the knee received intravenous injections of [18F]-NaF at the onset of PET-MR image acquisition. Regions of interest were identified, and kinetic analysis of dynamic PET data provided the rate of uptake ( Ki) and the normalized uptake (standardized uptake value) of [18F]-NaF in the bone. Morphological MR images and quantitative voxel-based T1ρ maps of cartilage were obtained using an atlas-based registration technique to segment cartilage automatically. Voxel-by-voxel statistical parameter mapping was used to investigate the relationship between bone and cartilage. Increases in cartilage T1ρ, indicating degenerative changes, were associated with increased turnover in the adjoining bone but reduced turnover in the nonadjoining compartments. Associations between pain and increased bone uptake were seen in the absence of morphological lesions in cartilage, but the relationship was reversed in the presence of incident cartilage lesions. This study shows significant cartilage and bone interactions in OA of the knee joint using simultaneous [18F]-NaF PET-MR, the first in human study. These observations highlight the complex biomechanical and biochemical interactions in the whole knee joint in OA, which potentially could help assess therapeutic targets in treating OA.


Concentrations of thioredoxin, a redox-regulating protein, in umbilical cord blood and breast milk.
Growing evidence indicates that oxidative stress occurs during the fetal-to-neonatal transition. Such stress plays an important role in the pathogenesis of many neonatal diseases. Thioredoxin (TRX), a redox-regulating protein with antioxidant activity, is induced in various cells against oxidative stress and is secreted extracellularly. This study was undertaken to examine the clinical and biological importance of TRX in the perinatal setting. We measured concentrations of TRX in umbilical cord blood and breast milk using a sandwich ELISA. Our study demonstrated that concentrations of TRX in umbilical cord blood were six to seven times higher than those in blood of healthy adults. This study also showed that umbilical concentrations of TRX were correlated significantly with the extent of prematurity of the newborn, and that they were elevated significantly in newborns of mothers with preeclampsia compared to those of mothers without preeclampsia. In contrast, concentrations of coenzyme Q(10) and vitamin E in umbilical blood were lower than adult blood levels. Breast milk concentrations of TRX during the early postpartum period were seven to eight times higher than those in blood of lactating women. Those of the coenzyme Q(10) were lower than adult blood levels, while those of vitamin E were comparable to adult blood levels. Our findings suggest that the systemic release of TRX is enhanced at birth, and that early breast milk is a rich source of this protein. Consequent high levels of TRX in newborns may provide a unique protective mechanism that allows the maintenance of redox balance during the fetal-to-neonatal transition.


Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.
Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected correlation between the mutated gene and the associated phenotype. This provides a good rationale for examining patients with apparent distal myopathy for a neuromuscular transmission disorder and agrin mutations.


Ovarian activity in beef and dairy cows with prolonged postpartum period and heifers that fail to conceive.
The primary objectives of this study were to investigate incidence of abnormal ovarian cyclicity (AOC) and its type in dairy and beef cows with prolonged postpartum period (>90 days) and in heifers that fail to conceive. A total of 53 animals were included in the study: 17 Friesian crosses, 16 Braford crosses, eight Brangus crosses, and 12 local Kedah-Kelantan (KKX) crosses. These animals were initially checked for absence of pregnancy via palpation per rectum. Blood samples for progesterone analysis were obtained twice a week for 2 to 3 months following their spontaneous oestrous cycle, and all animals were rechecked for pregnancy at the end of the study. Progesterone analysis indicated that 33.9% of the total animals were having AOC: 18.9% with cessation of ovarian cyclicity, 9.4% with prolonged luteal phases (PLP), and 5.7% short luteal phases. The highest incidence was observed in Brangus crosses (62.5%), followed by Braford crosses (43.8%), and Friesian crosses (35.3%). In contrast, no AOC was observed in the local KKX breeds, and all of them were found to be pregnant at the end of the study. A significant difference (p < 0.05) in the incidence of AOC and its type was observed between Kedah-Kelantan crosses and the other breeds. Although not significant (p > 0.05), Friesian crosses showed a higher percentage incidence of AOC than beef cows (40% vs 36.4%), with major types being PLP (26.7%) in dairy and cessation of ovarian cycle (27.3%) in beef cows. Compared with beef heifers, beef cows showed a higher percentage of AOC (36.4% vs 28.6%) where again, cessation of cyclicity was the predominant abnormality. In conclusion, AOC reflected by abnormal endocrine pattern is a possible cause of reduction in fertility for dairy and beef cows beyond 90 days postpartum and heifers that fail to conceive.


Study of particle size effects on an optical fiber sensor response examined with Monte Carlo simulation.
Optical fiber sensors based on the total light transmittance are widely used to measure the volume fraction of particles in suspensions. However, the sensor response depends not only on the volume fraction but also on the particle size. The particle size effect is studied for a sensor configuration consisting of two linear arrays of fibers on each of two blocks: the emitting and receiving blocks. These two linear arrays are arranged with three adjacent fibers (one fiber on the first array, two fibers on the second array) forming a perfect triangle. The almost superimposition of the calculated sensor response versus the extinction factor for different particle sizes allows for the application of single- curve models. Two single-curve models that describe the sensor response for all particle sizes ranging from 36 to 200 microm are proposed. The models are validated by Monte Carlo simulation for different particle sizes and are valid within a detectable volume fraction. The single-curve models proposed provide an easier approach to creating a database for sensor calibration for suspended sediment concentration measurements.


Cross-Sectional Study of Swallowing Phases in Cases of Megaesophagus Caused by Chagas Disease.
Chagas disease, caused by the flagellate protozoan Trypanosoma cruzi, is an infectious cause of secondary achalasia and megaesophagus. Moreover, the oral and pharyngeal phases of swallowing may also be affected, which may contribute to dysphagia and increase the possibility of airway aspiration during and/or after swallowing. This cross-sectional study evaluated, with videofluoroscopy, the oral, pharyngeal, and esophageal phases of swallowing in patients with megaesophagus caused by Chagas disease. The hypothesis is that there is impairment of the pharyngeal phase of swallowing that may increase the risk of airway aspiration. A total of 29 patients, aged 48 - 73 years (mean: 63.8 ± 5.1 years), with dysphagia, radiological changes in the esophagus, and positive serologic test for Chagas disease, participated in the study. They were submitted to the videofluoroscopic evaluation of oral, pharyngeal, and esophageal phases, swallowing twice 10 mL of liquid and 10 mL of thickened barium boluses. The most frequent findings were: oral residues and ineffective ejection in the oral phase; residues in vallecula, pharynx, and pyriform sinuses in the pharyngeal phase; abnormal esophageal motility, longer clearance, and longer transit in the esophageal phase. Laryngeal penetration was seen in 28% of the patients. Patients with increased esophageal diameter had more pharyngeal residues than patients without increased esophageal diameter. None of the patients had airway aspiration. Megaesophagus caused by Chagas disease may affect all phases of swallowing, with an increase in oral and pharyngeal residues which suggest the impairment of oral and pharyngeal efficiency. None of the patients had airway aspiration.


Ionomics and the study of the plant ionome.
The ionome is defined as the mineral nutrient and trace element composition of an organism and represents the inorganic component of cellular and organismal systems. Ionomics, the study of the ionome, involves the quantitative and simultaneous measurement of the elemental composition of living organisms and changes in this composition in response to physiological stimuli, developmental state, and genetic modifications. Ionomics requires the application of high-throughput elemental analysis technologies and their integration with both bioinformatic and genetic tools. Ionomics has the ability to capture information about the functional state of an organism under different conditions, driven by genetic and developmental differences and by biotic and abiotic factors. The relatively high throughput and low cost of ionomic analysis means that it has the potential to provide a powerful approach to not only the functional analysis of the genes and gene networks that directly control the ionome, but also to the more extended gene networks that control developmental and physiological processes that affect the ionome indirectly. In this review we describe the analytical and bioinformatics aspects of ionomics, as well as its application as a functional genomics tool.


Crown ether complexes of actinyls: a computational assessment of AnO2(15-crown-5)2+ (An = U, Np, Pu, Am, Cm).
For further fundamental understanding of the nature and extent of covalency in actinyl-ligand bonding, and the benefits that this may have in the design of new ligands for nuclear waste separation, there is burgeoning interest in the nature of actinyl complexes with polydentate or multiple-point-donor ligands, such as crown ethers. There are few cases of structurally authenticated molecular actinyl-crown bonds under ambient conditions. We report here the computational characterization of AnO22+-(15-crown-5) complexes, where An = U, Np, Pu, Am, and Cm, and 15-crown-5 is the cyclic polyether ligand with five ether oxygen atoms. In the gas-phase complex, the actinyl group is located inside of the crown ether, tilted slightly out of the plane of the five equatorial oxygen atoms that coordinate the actinide metal center. The actinyl-cyclic ether complexes are found to exhibit a conventional conformation, with typical An-Oaxial and An-Oequatorial distances and angles. A striking result is the enhanced stability of the insertion complex for UO22+versus NpO22+, PuO22+, AmO22+ and CmO22+, which is evaluated in the context of An-O binding strengths (esp. bonding covalency), and may have ramifications for the utility of actinyl-crown complexes in separation applications.


Point mutations of the P53 gene, human hepatocellular carcinoma and aflatoxins.
The tumor suppressor p53 exerts important protective functions towards DNA-damaging agents. Its inactivation by allelic deletions or point mutations within the P53 gene as well as complex formation of wildtype p53 with cellular or viral proteins is a common and crucial event in carcinogenesis. Mutations increase the half-life of the p53 protein allowing the immunohistochemical detection and anti-p53 antibody formation. Distinct G to T point mutations in codon 249 leading to a substitution of the basic amino acid arginine by the neutral amino acid serine are responsible for the altered functionality of the mutant gene product and were originally identified in 8 of 16 Chinese and 5 of 10 African HCC patients. Both groups are frequently exposed to mycotoxin contaminations of their food. Today an average P53 gene mutation rate of 25% is assumed for high-aflatoxin B1-exposure regions. This is double the rate observed in low-aflatoxin B1-exposure countries. Although many HCC patients displaying P53 mutations also suffer from HBV infection, which itself can lead to rearrangements of P53 coding regions or induce the synthesis of viral proteins possibly interacting with p53, the specific G to T transversion within codon 249 of the P53 gene seems to directly reflect the extent of aflatoxin B1 exposure.


Natural variation of hormone levels in Arabidopsis roots and correlations with complex root architecture.
Studies on natural variation are an important tool to unravel the genetic basis of quantitative traits in plants. Despite the significant roles of phytohormones in plant development, including root architecture, hardly any studies have been done to investigate natural variation in endogenous hormone levels in plants. Therefore, in the present study a range of hormones were quantified in root extracts of thirteen Arabidopsis thaliana accessions using a ultra performance liquid chromatography triple quadrupole mass spectrometer. Root system architecture of the set of accessions was quantified, using a new parameter (mature root unit) for complex root systems, and correlated with the phytohormone data. Significant variations in phytohormone levels among the accessions were detected, but were remarkably small, namely less than three-fold difference between extremes. For cytokinins, relatively larger variations were found for ribosides and glucosides, as compared to the free bases. For root phenotyping, length-related traits-lateral root length and total root length-showed larger variations than lateral root number-related ones. For root architecture, antagonistic interactions between hormones, for example, indole-3-acetic acid to trans-zeatin were detected in correlation analysis. These findings provide conclusive evidence for the presence of natural variation in phytohormone levels in Arabidopsis roots, suggesting that quantitative genetic analyses are feasible.


Relationship between healthy lifestyle behaviors and health related quality of life in turkish school-going adolescents.
The aim of this study is to determine the relationship between healthy lifestyles behaviours and health-related quality of life (HRQOL) among Turkish school-going adolescents. This cross-sectional study was conducted among 413 students studying in a secondary school of Istanbul, Turkey. Data were collected using a questionnaire containing socio-demographic characteristics, health promoting lifestyle behaviors and the Turkish generic health-related quality of life questionnaire for children (Kid-KINDL). Data were analyzed using descriptive statistics, t-test, Pearson's product-moment correlation, and a hierarchical multiple regression analysis. Univariate statistics showed that gender, school grade, parental education level, monthly income, and all healthy lifestyles behaviours except for fruit and vegetable intake were associated with adolescents' HRQOL. Multivariate statistics indicated that participation in social activities and talking about their problems were the most important predictors of better HRQOL. Healthy lifestyles behaviours, especially talking about their problems to close friends and/or family members and participation in leisure-time social activity were related to better HRQOL of Turkish adolescents, independently of socio-demographic factors. Collaborative efforts among providers of school health and counseling services are urgently needed to improve all aspects of adolescent health.


Replication confirms the association of loci in FOXE1, PDE8B, CAPZB and PDE10A with thyroid traits: a Genetics of Diabetes Audit and Research Tayside study (GoDARTS).
Replication of associations in genome-wide association studies is desirable to ensure that such signals are potentially clinically meaningful. This study aimed to replicate associations of selected single-nucleotide polymorphisms (SNPs) with hypothyroidism and serum thyroid-stimulating hormone (TSH) using electronic medical records (EMRs). A cross-sectional study was carried out among patients of European Caucasian ethnicity from the Genetics of Diabetes Audit and Research Tayside recruited in Tayside (Scotland, UK). EMRs (biochemistry, prescribing, hospital admissions and demographics) were used to ascertain patients with hypothyroidism and their controls as well as average serum TSH concentration, and linked to genetic biobank data. Genetic tests of association were performed using logistic and linear regression models. We analysed 1703 cases of hypothyroidism and 9457 controls. All four SNPs located on chromosome 9 at FOXE1 were associated with hypothyroidism with similar effect estimates (odds ratio=0.75-0.76, P<5e-08). Also, loci on chromosomes 1 (PTPN22), six (HLA-E/HLA-C) and 12 (SH2B3) were replicated. For serum TSH, we confirmed 12 SNPs previously reported at PDE8B, CAPZB, PDE10A, LOC105371356, NR3C2, VEGFA, IGFBP5, INSR, PRDM11, NFIA, ITPK1 and ABO. Overall, these SNPs accounted for 6.8% of the serum TSH variation (P<1e-04). EMRs linked to genomic data in large populations enable validation of genome-wide association studies discoveries without additional genotyping costs. Our replication confirmed at genome-wide significance the association of loci at FOXE1 with hypothyroidism, and PDE8B, CAPZB and PDE10A with serum TSH. A total of 12 SNPs seemed to explain nearly 7% of the serum TSH variation.


Ensuring sample quality for blood biomarker studies in clinical trials: a multicenter international study for plasma and serum sample preparation.
Sample quality is critical for biomarker detection in oncology, and platelet degradation and contamination in plasma have a remarkable impact on the ability to accurately quantify many blood-based biomarkers. Platelet factor 4 (PF4) can be used as an indicator to monitor sample quality. This multicenter study aimed to determine the impact of critical components of the blood sample handling process on platelet degradation/contamination and to establish an optimal method for collecting platelet-poor plasma samples. At each of six participating centers, blood samples were drawn from 12-13 healthy volunteers. Serum and plasma samples were prepared from whole blood samples using nine different methods that have been commonly used in ongoing multicenter trials. PF4 levels in the prepared samples were measured by enzyme-linked immunosorbent assay (ELISA). Paired t-tests were used for statistical analysis. Blood samples were collected from 74 subjects enrolled in six centers. PF4 levels were significantly higher in serum samples than in plasma samples (P<0.001), in plasma samples from blood that sat at room temperature for 5 minutes (P=0.021), in plasma samples prepared at an insufficient centrifugal force (P<0.001), and in plasma samples prepared from blood that sat for longer than 4 hours on ice (P=0.001). For each method, the PF4 levels did not differ significantly among the centers or between Chinese and American subjects. The methods that resulted in normal levels of PF4 involved keeping blood samples on ice for 30 minutes to <4 hours and centrifugation at 2,500-3,000 ×g for 30 min. This multicenter study evaluated multiple blood sample handling conditions for minimizing platelet degradation during plasma serum preparation and determined an optimal method for preparing platelet-poor plasma. The findings of this study can be applied in future blood biomarker studies.


Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy.
Radiotherapy and chemotherapeutic agents that damage DNA are the current major non-surgical means of treating cancer. However, many patients develop resistances to chemotherapy drugs in their later lives. The PI3K and Ras signaling pathways are deregulated in most cancers, so molecularly targeting PI3K-Akt or Ras-MAPK signaling sensitizes many cancer types to radiotherapy and chemotherapy, but the underlying molecular mechanisms have yet to be determined. During the multi-step processes of tumorigenesis, cancer cells gain the capability to disrupt the cell cycle checkpoint and increase the activity of CDK4/6 by disrupting the PI3K, Ras, p53, and Rb signaling circuits. Recent advances have demonstrated that PI3K-Akt-mTOR signaling controls FANCD2 and ribonucleotide reductase (RNR). FANCD2 plays an important role in the resistance of cells to DNA damage agents and the activation of DNA damage checkpoints, while RNR is critical for the completion of DNA replication and repair in response to DNA damage and replication stress. Regulation of FANCD2 and RNR suggests that cancer cells depend on PI3K-Akt-mTOR signaling for survival in response to DNA damage, indicating that the PI3K-AktmTOR pathway promotes resistance to chemotherapy and radiotherapy by enhancing DNA damage repair.


Synaptic responses and electrical properties of cells in brain slices of the mouse anteroventral cochlear nucleus.
Intracellular recordings were made from cells in brain slices of the anteroventral cochlear nucleus. Responses to electrical stimulation of the stump of the auditory nerve were: (1) all-or-none, following the stimulus with no delay, and insensitive to the removal of extracellular Ca2+, probably representing the firing of directly stimulated auditory nerve fibers, or (2) graded, excitatory postsynaptic potentials, with synaptic delays of about 0.7 msec, which were often followed by graded, inhibitory synaptic potentials with synaptic delays of 1.2 msec or longer. The excitatory and inhibitory synaptic potentials were abolished by the removal of extracellular Ca2+. The result that delays of inhibitory synaptic responses were at least 2 times as long as those of excitatory ones indicates that probably an additional synapse was interposed. Responses to intracellularly injected current pulses show that cells in the anteroventral cochlear nucleus have one of two types of electrical characteristics. Type I properties are characterized by linear current-voltage relationships in the subthreshold voltage range and large, regularly firing action potentials in the suprathreshold range. Type II properties are characterized by nonlinear current-voltage relationships; suprathreshold depolarization elicits only one or two small action potentials. Type II characteristics are particularly well suited for maintaining the information contained in the timing and patterns of firing of the auditory nerve fibers.


Clinical comparison of the efficacy and tolerability of once daily Canesten with twice daily Nizoral (clotrimazole 1% cream vs. ketoconazole 2% cream) during a 28-day topical treatment of interdigital tinea pedis.
The effects of two topical cream formulations containing clotrimazole 1% and ketoconazole 2%, respectively, were clinically compared in a double-blind, randomized manner for a 28-day therapy of interdigital tinea pedis in 106 treated patients. Ketoconazole was to be used twice daily whereas clotrimazole was administered only once daily. The primary response criterion defined as the number of patients with cure or improvement after 28 treatment days was comparable with 62.0% vs. 64.0% (clotrimazole vs. ketoconazole) for the full analysis set of 100 (50 vs. 50) patients. The mycological response revealed a negative culture and microscopy in 53.1% vs. 52.1% of the patients after 14, in 76.0% vs. 79.2% after 28, and in 83.7% vs. 76.9% after 56 days of observation, indicating a possibly better long-term efficacy of clotrimazole. The development of the overall score of tinea-related signs and symptoms did not show relevant differences between the two drugs and continuously decreased from 11+/-5 in both groups at baseline to 2+/-2 vs. 2+/-1 at day 56. As to the remission and improvement rates of single symptoms, better results were obtained under clotrimazole than under ketoconazole particularly for pruritus (97.8 vs. 89.6%) and burning/stinging (97.5 vs. 89.4%) which both are perceived as most bothersome by the patients. Furthermore, both substances appeared as comparably safe and well tolerable (8 vs. 7 adverse events with only 1 vs. 3 drug related). In conclusion, a successful therapy of tinea pedis can be achieved with both clotrimazole and ketoconazole within 28 days of treatment and once-daily clotrimazole is equally effective as twice-daily ketoconazole with favourable influences on the most irritating symptoms of the disease. Mycological and reliable clinical cure cannot be observed during two weeks after start of treatment.


Embedment of anodized p-type Cu₂O thin films with CuO nanowires for improvement in photoelectrochemical stability.
A highly stable p-type cuprous oxide (Cu2O) photoelectrode has been fabricated by direct anodization of the Cu foil, followed by a thermal treatment to introduce a protective layer of copper oxide (CuO) nanowires penetrating the surface of the Cu2O layer. The anodized Cu2O served as the seeding sites for the growth of CuO nanowires. The embedment of CuO nanowires within the Cu2O matrix enhanced the adhesion of the nanowires onto the Cu substrate. In addition, the presence of CuO nanowires on the outer layer of the composite film, in turn stabilized the Cu2O layer by passivating the redox activities of Cu2O when exposed to the environment. This nanostructured p-type Cu2O photoelectrode generated 360 μA cm(-2) of photocathodic current density upon visible light illumination and managed to retain its photocathodic current density after being used and kept for one month. The improvement in photoelectrochemical (PEC) stability by introducing a passive layer of CuO nanowires provides useful insights into the development of a Cu2O photoelectrode, as its stability remained as the main challenge.


Characterisation of K+ channels in human fetoplacental vascular smooth muscle cells.
Adequate blood flow through placental chorionic plate resistance arteries (CPAs) is necessary for oxygen and nutrient transfer to the fetus and a successful pregnancy. In non-placental vascular smooth muscle cells (SMCs), K(+) channels regulate contraction, vascular tone and blood flow. Previous studies showed that K(+) channel modulators alter CPA tone, but did not distinguish between effects on K(+) channels in endothelial cells and SMCs. In this study, we developed a preparation of freshly isolated CPASMCs of normal pregnancy and investigated K(+) channel expression and function. CPASMCs were isolated from normal human term placentas using enzymatic digestion. Purity and phenotype was confirmed with immunocytochemistry. Whole-cell patch clamp was used to assess K(+) channel currents, and mRNA and protein expression was determined in intact CPAs and isolated SMCs with RT-PCR and immunostaining. Isolated SMCs expressed α-actin but not CD31, a marker of endothelial cells. CPASMCs and intact CPAs expressed h-caldesmon and non-muscle myosin heavy chain-2; phenotypic markers of contractile and synthetic SMCs respectively. Whole-cell currents were inhibited by 4-AP, TEA, charybdotoxin and iberiotoxin implicating functional K(v) and BK(Ca) channels. 1-EBIO enhanced whole cell currents which were abolished by TRAM-34 and reduced by apamin indicating activation of IK(Ca) and SK(Ca) respectively. BK(Ca), IK(Ca) and SK(Ca)3 mRNA and/or protein were expressed in CPASMCs and intact CPAs. This study provides the first direct evidence for functional K(v), BK(Ca,) IK(Ca) and SK(Ca) channels in CPASMCs. These cells display a mixed phenotype implicating a dual role for CPASMCs in controlling both fetoplacental vascular resistance and vasculogenesis.


[Comparison of three methods for detecting Campylobacter pylori and measurement of human antibody titers against the whole organisms].
In order to detect Campylobacter pylori in the gastric mucosa, three different methods as 1) culture of the organisms, 2) immunostaining by monoclonal antibody against the cells, and 3) urease test were compared. In the disease group, positive % of each methods was 64, 75 and 74. However, positive % common to the three methods was only 48. The corresponding rate of culture and urease tests, and that of culture and staining methods was 81% and 60%, respectively. Therefore, it was concluded that urease test was a useful method, and that the three methods were necessary to confirm the existence of the organisms in the gastric mucosa. Total positive % of culture and staining methods in disease and control groups was 77 and 31, respectively, indicating that positive % of the disease group was much higher than that of the control group. Anti C. pylori titer was compared between culture-positive and culture-negative patients by ELISA. The titer of the former was significantly higher than that of the latter.


Weight in infancy and adult calcium absorption as determinants of bone mineral density in adult men: the Hertfordshire cohort study.
Adult bone mass is modified by early life environmental influences, but the mechanism of this association is uncertain. Data support an inverse relationship between intestinal calcium absorption (αCa) and birth weight in women. However, little is known regarding determinants in men. This study examines the association between weight in infancy and adult αCa in healthy men and whether this could be a mechanism by which the early life environment may influence bone mass. Men were recruited from the MRC Hertfordshire Cohort Study, for whom detailed early life records were available. Areal bone mineral density (aBMD) was measured using a Hologic QDR 4500 at the femoral neck (FN) and lumbar spine. We randomly selected 123 men stratified by birth weight and assessed αCa using the stable strontium absorption test. The mean age was 63.6 (SD 2.5) years. αCa was not associated with birth weight or weight at 1 year. FN aBMD was associated with both weight at 1 year (r = 0.20, p = 0.03) and αCa (r = 0.20, p = 0.03). Both of these associations remained statistically significant in a mutually adjusted, multivariable model but would account for only ~4 % variance in BMD. We demonstrated a positive association between weight at 1 year and aBMD and between αCa and FN BMD, but no association was found between birth weight and αCa. This suggests that in men, although αCa is a contributing factor in FN bone density, it is not the main mechanism whereby the early environment modifies adult BMD.


Differences in microRNA detection levels are technology and sequence dependent.
Identification and quantification of small RNAs are challenging because of their short length, high sequence similarities within microRNA (miRNA) families, and the existence of miRNA isoforms and O-methyl 3' modifications. In this study, the detection performance of three high-throughput commercial platforms, Agilent and Affymetrix microarrays and Illumina next-generation sequencing, was systematically and comprehensively compared. The ability to detect miRNAs was shown to depend strongly on the platform and on miRNA modifications and sequence. Using synthetic transcripts, including mature, precursor, and O-methyl-modified miRNAs spiked into human RNA, a large intensity variation in all spiked-in miRNAs and a reduced capacity in detecting O-methyl-modified miRNAs were observed between the tested platforms. In addition, endogenous human miRNA expression levels were assessed across the platforms. Detected miRNA expression levels were not consistent between platforms. Although biases in miRNA detection were previously described, here the end-point result, i.e., detection intensity, of these biases was investigated on multiple platforms in a controlled fashion. A detailed exploration of a large number of attributes, including base composition, sequence structure, and isoform miRNA attributes, suggests their impact on miRNA expression detection level. This study provides a basis for understanding the attributes that should be considered to adjust platform-dependent detection biases.


[The effect of deprenil on the dopaminergic system of the brain in mice of different genotypes during aging].
Effects of aging on brain dopaminergic system, e.g., neurotransmitter metabolism and different kinds of dopamine-dependent behaviour, were studied in mice of three inbred strains. Homovanillic acid concentrations in structures of both nigrostriatal (striatum) and mesolimbic (n. accumbens with tuberculum olfactorium) systems were found to be increased in the aged animals. Aged mice of the strains studied were characterized by decreased locomotor activity and stereotypic climbing; CC57Br mice, in contrast to A/He and C3H/He, demonstrated significantly diminished level of investigatory activity. However, genotypic differences in these kinds of behaviour were less pronounced in the aged animals in comparison to the young adults, but interstrain differences in swimming activity (Porsolt's "despair test") which was almost unchanged in aged mice, remained enough pronounced. In the aged mice postsynaptic dopamine receptor sensitivity, assessed after administration of a high dose of the mixed agonist apomorphine, was markedly decreased. Chronic treatment with deprenyl, a specific MAO-B inhibitor, produced a clear-cut genotype-dependent effect on investigatory activity in the aged animals. High level of this activity, characteristic for the young adults, was restored in CC57Br, in A/He it was elevated in comparison both with young and old untreated animals, and the same tendency was observed in C3H/He. This fact seems to reflect an interesting property of deprenyl to increase general adaptation in the aged organism, that might have valuable clinical implications.