Circulatory system disease mortality and occupational exposure to radon progeny in the cohort of Newfoundland Fluorspar Miners between 1950 and 2016.
Exposure to ionizing radiation may increase the risk of circulatory diseases, including heart disease. A limited number of cohort studies of underground miners have investigated these associations. We previously reported a positive but non-statistically significant association between radon progeny and heart disease in a cohort of Newfoundland fluorspar miners. In this study, we report updated findings that incorporate 15 additional years of follow-up. The cohort included 2050 miners who worked in the fluorspar mines from 1933 to 1978. Statistics Canada linked the personal identifying data of the miners to Canadian mortality data to identify deaths from 1950 to 2016. We used previously derived individual-level estimates of annual radon progeny exposure in working-level months. Cumulative exposure was categorized into quantiles. We estimated relative risks and their 95% confidence intervals using Poisson regression for deaths from circulatory, ischemic heart disease and acute myocardial infarction. Relative risks were adjusted for attained age, calendar year, and the average number of cigarettes smoked daily. Relative to the Newfoundland male population, the standardized mortality ratio for circulatory disease in this cohort was 0.82 (95% CI 0.74-0.91). Those in the highest quantile of cumulative radon progeny exposure had a relative risk of circulatory disease mortality of 1.03 (95% CI 0.76-1.40) compared to those in the lowest quantile. The corresponding estimates for ischemic disease and acute myocardial infarction were 0.99 (95% CI 0.66-1.48), and 1.39 (95% CI 0.84-2.30), respectively. Our findings do not support the hypothesis that occupational exposure to radon progeny increases the risk of circulatory disease.


Breakdown of prothrombin and proconvertin in rats with experimental extrahepatic cholestasis.
Changes in the half-life of prothrombin and proconvertin were studied in rats with experimental extraphepatic cholestasis induced by ligation of the common bile duct. By the end of the second week of cholestasis the prothrombin activity was reduced almost by half and the proconvertin activity by more than two-thirds compared with the control. Meanwhile the half-life of prothrombin after cholestatsis for 14 days was increased by 1.f h and that of proconvertin by 4.7 h compared with the control. The slower breakdown of prothrombin and proconvertin during cholestasis is regarded as a compensatory reation.


Long-term bone remodeling after definitive decompression for jaw cysts based on a three-dimensional analysis.
Decompression is an effective treatment for jaw cysts. Many studies have reported its effectiveness as a preliminary treatment followed by secondary enucleation. This study aimed to explore long-term bone remodeling after definitive decompression for jaw cysts based on a three-dimensional (3D) analysis. This was a retrospective study. The clinical and radiological data of patients with jaw cysts who underwent decompression and were followed up for two years or more at Peking Union Medical College Hospital between January 2015 and December 2020 were reviewed. The 3D radiological data before and after decompression were analyzed to study the long-term reduction in cysts, especially after one year of decompression. A total of 17 patients with jaw cysts were included in this study. The radiological data showed a mean reduction rate of 78% one year after decompression. At the final examination, which was 36.1 months after decompression on average, the mean reduction rate was 86%. The unossified lesions could still ossify slowly after one year of decompression. The recurrence rate was 5.9% (1/17). Bone remodeling continued for a long time after decompression. Definitive decompression could be an option for most patients with jaw cysts. Long-term follow-up is required.


Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of 51 Cr-EDTA.
We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of 51 Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 μmol l-1 entered the study. 51 Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg-1 body weight (150 mg ml-1 ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for 51 Cr-EDTA was 59·7 ± 18·8 ml min-1 . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min-1 and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min-1 , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min-1 . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and 51 Cr-EDTA for the assessment of GFR.


Methodology for the evaluation of vascular surgery manpower in France.
The French population is growing and ageing. It is expected to increase by 2.7% by 2020, and the number of individuals over 65 years of age is expected to increase by 3.3 million, a 33% increase, between 2005 and 2020. As the number of vascular surgery procedures is closely associated with the age of a population, it is anticipated that there will be a significant increase in the workload of vascular surgeons. A model is presented to predict changes in vascular surgery activity according to population ageing, including other parameters that could affect workload evolution. Three types of arterial procedures were studied: infrarenal abdominal aortic aneurysm (AAA) surgery, peripheral arterial occlusive disease (PAOD) procedures and carotid artery (CEA) procedures. Data were selected and extracted from the national PMSI (Medical Information System Program) database. Data obtained from 2000 were used to predict data based on an ageing population for 2008. From this model, a weighted index was defined for each group by comparing expected and observed workloads. According to the model, over this 8-year period, there was an overall increase in vascular procedures of 52.2%, with an increase of 89% in PAOD procedures. Between 2000 and 2009, the total increase was 58.0%, with 3.9% for AAA procedures, 101.7% for PAOD procedures and 13.2% for CEA procedures. The weighted model based on an ageing population and corrected by a weighted factor predicted this increase. This weighted model is able to predict the workload of vascular surgeons over the coming years. An ageing population and other factors could result in a significant increase in demand for vascular surgical services.


A rapid and simple PCR-based method for analysis of transgenic fish using a restricted amount of fin tissue.
The protocol described in this paper offers a simple and rapid method for PCR analysis of transgenes using a restricted amount of fin tissue from small-sized transgenic fish. A simple preparation of fin lysate using a buffer containing a low concentration of an ionic detergent, SDS (0.01%), followed by neutralization with a second buffer containing higher concentrations of non-ionic detergents NP40 (2%) and Tween 20 (2%) consistently provides a reliable quantity of high-quality DNA template for PCR amplification of transgenes. Based on this protocol, transgenic fish can be clearly distinguished from non-transgenic fish using PCR in a rapid and reproducible manner. Tedious DNA purifications are avoided while fidelity of amplification and efficient identification of transgenic fish are maintained.


Enzymatic reduction of fatty acids and acyl-CoAs to long chain aldehydes and alcohols.
The properties of enzymatic systems involved in the synthesis of long chain aldehydes and alcohols have been reviewed. Fatty acid and acyl-CoA reductases are widely distributed and generate fatty alcohols for ether lipid and wax ester synthesis as well as fatty aldehydes for bacterial bioluminescence. Fatty alcohol is generally the major product of fatty acid reduction in crude or membrane systems, although reductases which release fatty aldehydes as products have also been purified. The reduction of fatty acid proceeds through the ATP-dependent formation of acyl intermediates such as acyl-CoA and acyl protein, followed by reduction to aldehyde and alcohol with NAD(P)H. In most cases, both the rate of fatty acid conversion and acyl chain specificity of the reaction are determined at the level of reduction of the intermediate. The reduction of fatty acids represents the major pathway for the control of the synthesis of fatty aldehydes and alcohols. Several other enzymatic reactions involved in lipid degradation also release fatty aldehydes but do not appear to play an important role in long chain alcohol synthesis.


Copper-catalyzed oxidative coupling between quinazoline 3-oxides and unactivated aldehydes: an efficient approach to functionalized quinazolines.
A copper-catalyzed oxidative coupling between quinazoline 3-oxides and unactivated aldehydes was described. The reaction worked well for both aliphatic and aromatic aldehydes and produced not only the direct oxidative coupling ketones but also cyclic hydroxamic esters derived from quinazolines.


Significance of anti-HBc screening of blood donors and its association with occult hepatitis B virus infection: Implications for blood transfusion.
Expansions of blood donor screening and improved laboratory detection of viral markers have remarkably reduced the risk for infection with transfusion-transmitted viruses. This study was aimed to evaluate the presence of anti-HBc and to determine the presence or absence of HBV DNA in the serum samples from HBsAg negative, anti-HBc positive blood donors in a tertiary care hospital blood bank from Delhi. A total of 2175 HBsAg negative, first time volunteer blood donors were included in the study from blood bank, Lok Nayak Hospital, New Delhi. The blood specimens from all these subjects were evaluated for anti-HBV-core antigen (anti-HBc) serology, anti-HBV-surface antigen (anti-HBs) titres and HBeAg. The presence of HBV DNA was evaluated by testing, through polymerase chain reaction (PCR) techniques. Of the 2175 HBsAg negative voluntary blood donors, 413 (19.8%) were tested to be positive for anti-HBc alone. Of these, 153 (group-I) were anti-HBs negative whereas group-II comprises a total of 260 anti-HBs positive cases i.e. 89 out of 413 had anti-HBs titres of 10-99 IU/l and the remaining 171 had anti-HBs titres of 100-500 IU/l. HBV DNA was detected in 7.5 per cent anti-HBc positive samples irrespective of anti-HBs status. Our results showed that 18.9 per cent of our donor population was anti-HBc reactive, and hence inclusion of anti-HBc testing will lead to a high discard rate. The presence of HBV DNA in fairly high percentage of anti-HBc positive samples highlighted the need for a stringent and better screening system to prevent occult HBV infection.


Hemodynamic and symptomatic consequences of ventricular pacing.
After implantation of a ventricular demand pacemaker (VVI), occasional patients continue to have dizziness, syncope, or near syncope ("pacemaker syndrome"). To identify patients in whom VVI pacing may have deleterious effects, we compared cuff blood pressure responses to VVI pacing with blood pressure responses to atrioventricular sequential pacing (DVI) or sinus rhythm in 50 consecutive patients. Patients with intact ventriculoatrial conduction had a much greater decrease in systolic blood pressure with VVI pacing (24 +/- 11 mm Hg) than those with ventriculoatrial dissociation (-4 +/- 15 mm Hg) (P less than 0.005). Patients who were in heart failure had a lesser decrease in blood pressure with VVI pacing than did those without failure (P less than 0.05); 13 of the 14 heart failure patients lacked ventriculoatrial conduction. Ten patients had symptomatic dizziness after VVI pacing; the incidence of symptoms was higher in patients with ventriculoatrial conduction (9 of 23) than in those without ventriculoatrial conduction (1 of 27) (P less than 0.003). We conclude that the presence of intact ventriculoatrial conduction appears to be a crucial determinant of the hemodynamic response to VVI pacing, and its presence may identify patients who are at risk for "pacemaker syndrome."


Cell-Free Synthesis of Natural Compounds from Genomic DNA of Biosynthetic Gene Clusters.
A variety of chemicals can be produced in a living host cell via optimized and engineered biosynthetic pathways. Despite the successes, pathway engineering remains demanding because of the lack of specific functions or substrates in the host cell, the cell's sensitivity in vital physiological processes to the heterologous components, or constrained mass transfer across the membrane. In this study, we show that complex multidomain proteins involved in natural compound biosynthesis can be produced from encoding DNA in vitro in a minimal complex PURE system to directly run multistep reactions. Specifically, we synthesize indigoidine and rhabdopeptides with the in vitro produced multidomain nonribosomal peptide synthetases BpsA and KJ12ABC from the organisms Streptomyces lavendulae and Xenorhabdus KJ12.1, respectively. These in vitro produced proteins are analyzed in yield, post-translational modification and in their ability to synthesize the natural compounds, and compared to recombinantly produced proteins. Our study highlights cell-free PURE system as suitable setting for the characterization of biosynthetic gene clusters that can potentially be harnessed for the rapid engineering of biosynthetic pathways.


[Mycosis fungoides associated with chronic myelomonocytic leukemia with specific skin lesions].
A 77 year old man, who presented cutaneous T cell lymphoma, was treated with polychemotherapy and cyclosporine. After one year, erythemato-papulonodules were seen on the face, neck and trunk. Histologic examination showed specific infiltration myelomonocytic, bone marrow examination revealed the same characteristics. The patient died one month after the diagnosis. We comment the association between these two hemoproliferative processus.


In vitro cytogenotoxic evaluation of sertraline.
Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 μg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=-0.979, p<0.01; r=-0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 μg/mL in the 24-h and at the highest concentration (5 μg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.


Fibroblast matrix and surface components that mediate cell-to-cell interaction with lymphocytes.
The interaction between lymphocytes and fibroblasts in vitro has been examined using a quantitative ELISA assay to measure the binding of T and B cells to monolayer cultures of human dermal fibroblasts. This was carried out on microtiter culture plates, using an anti-Thy-1 monoclonal antibody, to determine the attachment of murine T lymphocytes and an affinity-purified polyclonal anti-IgM antibody to measure B cell binding. Both types of lymphocyte were found to adhere strongly to intact human fibroblasts, and also had high levels of attachment to purified fibroblast plasma membranes and extracts of the fibroblast extracellular matrix. Attachment, particularly of B lymphocytes, also took place onto plastic surfaces coated with fibronectin, but not to collagens or to intact fibroblasts that had been fixed with a low concentration of paraformaldehyde. Lymphocyte binding to fibroblasts was partially prevented by a monoclonal antibody against fibroblast MHC class II antigens, but not against the class I membrane complex, or by polyclonal antiserum to the cell surface mannose 6-phosphate receptor. In addition, although both lymphocyte types were able to adhere to fibro-nectin, the presence of antibody against fibronectin or the synthetic peptide Arg-Gly-Asp-Ser, had no effect on their attachment to fibroblasts. Thus, lymphocyte adhesion may occur by fibronectin, but other types of interactions with fibroblasts also appear to take place.


Cerebellar hemorrhage: diagnosis and treatment.
We have reviewed the records of 22 patients with spontaneous cerebellar hemorrhage. One question that we considered was whether the increased recognition of this disorder, since the introduction of computed tomography (CT) scanning, had brought about a change in the associated signs and symptoms, as compared with previous series. No such change was found. Nine patients died, four after operation (ventricular shunting in one, clot evacuation in one, both procedures in two patients). The five other patients were considered inoperable, because they showed signs of compression of the caudal brainstem. It is improbable that any of these five could have been saved by immediate ventricular drainage, advocated by some as the only treatment. Thirteen patients were treated conservatively and recovered, although four had a hematoma larger than 3 cm. All these patients had a Glasgow coma scale score of 11 points or more. The level of consciousness may be a better guide in management than the size of the clot.


Mobile health application for remote oral cancer surveillance.
To determine the effectiveness of a mobile phone-based remote oral cancer surveillance program (Oncogrid) connecting primary care dental practitioners and frontline health care workers (FHW) with oral cancer specialists. The study population (N = 3,440) included a targeted cohort (n = 2,000) and an opportunistic cohort (n = 1,440) screened by FHW and dental professionals, respectively. The authors compared the screening efficacy in both groups, with specialist diagnosis considered the reference standard. The outcomes measured were lesion detection and capture of interpretable images of the oral cavity. In the targeted cohort, among 51 of 81 (61%) interpretable images, 23 of 51 (45%) of the lesions were confirmed by specialists, while the opportunistic cohort showed 100% concordance with the specialists (106 of 106). Sixty-two of 129 (48%) of the recommended patients underwent biopsy; 1 of 23 (4%) were in the targeted cohort, and 61 of 106 (57%) were in the opportunistic cohort. Ninety percent of the lesions were confirmed to be malignant or potentially malignant. The mobile health-based approach adopted in this study aided remote early detection of oral cancer by primary care dental practitioners in a resource-constrained setting. Further optimization of this program is required to adopt the system for FHW. Evaluation of its efficacy in a larger population is also warranted. The increased efficiency of early detection by dentists, when assisted by a remote mobile health-based approach, is a step toward a more effective oral cancer screening program.


[Comparative analysis of the biophysical characteristics of influenza A virus variants with differing pathogenicity for mice].
Variants of influenza A virus: A/PR8/34 Pm-, nonpathogenic for mice and A/PR8/34 Pm+, pathogenic for mice, obtained after 5 passages in mice, were studied. Both variants showed close similarities in the antigenic specificity, high reproductive activity at optimal temperature and reduced activity at low and high temperatures, similar plaque-producing activity in chick fibroblast cell cultures. Differences in their polypeptide composition were found. The A/PR8/34 Pm+ variant had no HAO and a lower molecular weight of HA1. In the mapping of HA1 and NP proteins, differences in the oligopeptide compositions were observed.


Programmed anti-inflammatory macrophages protect against AKI and promote repair through trophic actions.
Because pharmacological interventions for the treatment of acute kidney injury (AKI) have remained ineffective, cell-based therapies have been developed. Marrow stromal cells have been found to be safe and potentially effective in study subjects. Jung et al. demonstrate that macrophages made to overexpress anti-inflammatory interleukin-10 protect rats with AKI through iron-mediated upregulation of lipocalin-2 and its receptors, eliciting both anti-inflammatory and proliferative responses. These data further advance our understanding of cell-based therapies for AKI.


Pratylenchus thornei: The Relationship Between Presowing Nematode Density and Yield Loss in Wheat and Barley.
The root lesion nematode Pratylenchus thornei causes economic losses in wheat and barley internationally through both reduced grain yield and grain quality. This study investigated the relationships between the presowing P. thornei density and grain yield and the postharvest nematode densities. Four field experiments were conducted at the same site between 2010 and 2014. A range of presowing P. thornei densities was established in the first year by growing three cereal cultivars that ranged from resistant to susceptible. In the following year, plots were sown with the five same cereal cultivars. A linear relationship was observed between the natural log of the presowing P. thornei density and grain yield across all seasons. The results showed that grain yield losses varied between cultivars and seasons. The importance of season was significant, with this study conducted over several seasons, and it highlighted the variability in yield losses between seasons, which will need further investigation. The greatest yield losses observed were 25 to 28% when the maximum presowing P. thornei densities ranged between 150 and 250 P. thornei g of soil-1. An analysis of the relationship between the presowing and postharvest nematode densities revealed that increased presowing nematode densities resulted in decreased multiplication rates in all seasons and in all cultivars. Nematode multiplication rates also varied between seasons. These results explain why it is difficult to predict nematode levels based on cropping history, and additionally, they highlight the importance of growing resistant cultivars to maintain low levels of P. thornei to minimize risk of yield losses.


Phosphatidylinositol availability and polyphosphoinositide synthesis in pancreatic islet cell membranes.
Polyphosphoinositide synthesis in isolated islets of the rat was determined by the phosphorylation of endogenous phosphatidylinositol (PtdIns) by PtdIns kinase and [gamma-32P]ATP to form [32P]-phosphatidylinositol 4-phosphate (PtdInsP) in cell homogenates. Glucose stimulation of intact islets resulted in a time- and concentration-dependent reduction in PtdInsP synthesis. Similarly, the stimulation of intact islets with carbachol (CCh), cholecystokinin (CCK-8S), or tolbutamide for 15 min reduced PtdInsP production in a concentration-dependent manner. The effects of glucose, tolbutamide and CCh were reversible. PtdInsP hydrolysis did not account for the reduction in PtdInsP recovery. The addition of exogenous PtdIns to the PtdIns kinase assay significantly increased basal PtdInsP levels. In addition, exogenous PtdIns completely reversed the inhibitory effects of glucose and increased PtdIns kinase activity in homogenates of glucose-stimulated islets to levels found in control homogenate with PtdIns. Exogenous PtdIns also increased PtdIns kinase activity in CCK-8S-treated islets, although exogenous PtdIns did not overcome the tolbutamide-induced inhibition of PtdIns kinase. The Vmax of PtdIns kinase in homogenates of islets treated with tolbutamide was reduced significantly, although glucose did not affect the Vmax. In addition, the Km values for ATP and PtdIns were not altered by exposure of the islets to cell stimuli. The results suggest that the level of PtdIns in islet cell membranes is rate limiting for PtdInsP synthesis, and that tolbutamide is a noncompetitive inhibitor of PtdIns kinase.


Influence of period length of light/dark cycles on the body weight and food intake of young rats.
The purpose of this work is to test whether physiological factors, such as body weight or food intake, are related to the period of environmental cycles under which animals are kept. We studied body weight increase, daily food intake and efficiency (i.e. relationship between body weight increase and food intake) of 7 groups each containing 20-24 male rats. Measurements were recorded every 4 days from the day of weaning (25 days old) during 64 days. Each group of rats was kept under a symmetrical LD cycle. The period of the cycles studied were: 22, 23, 24, 25, 26, 27 and 28 hours (T22, T23 ... T28). Results show differences in the three variables studied for groups T25 and T26. These animals show an inferior body weight, less food intake and less efficiency. It would seem that the difference between the period of the external LD cycle and the endogenous period of the animals rhythm induces changes in the energetic needs of the organism.


Risk of fracture of the acromion depends on size and orientation of acromial bone tunnels when performing acromioclavicular reconstruction.
Current techniques for anatomic repair of the dislocated acromioclavicular (AC) joint aim on reconstruction of the AC ligaments and utilize tunnels drilled through the acromion . This improves the stability of the reconstruction but might also increase the risk of fractures at the acromion. The purpose of this study was to evaluate the fracture risk for the acromion after transacromial tunnel placement for anatomic AC joint stabilization procedure. It was hypothesized that the risk of fracture of the acromion is correlated to size and orientation of bone tunnels commonly used for anatomic AC joint reconstruction. A finite element analysis was used to simulate multiple bone tunnels and incoming force vectors (lateral vs. superior). Different tunnels were analysed, horizontal meaning an anterior-posterior orientation versus a vertical inferior-superior orientation through the acromion. Two tunnel diameters were simulated (2.4 vs. 4.5 mm). Furthermore, the tunnel length and distance between tunnels were altered. Forty-five cadaveric specimens (median age: 64 years, range 33-71 years) were utilized for data acquisition. Out of these, 30 specimens were used to evaluate basic tunnel orientations and drill diameters using a MTS 858 servohydraulic test system. With regard to the tunnel orientation and drill hole size, the loads to failure were limited. The acromion is at higher fracture risk, with a superior to inferior directed incoming force. Position, size and direction of bone tunnels influenced the loads to failure. Horizontal tunnels with a higher diameter (4.5 mm) had the most impact on load to failure reduction. A long horizontal tunnel with a diameter of 4.5 mm reduced the load to failure with medial direction of force to 25% of the native acromion. The identical tunnel with a diameter of 2.4 mm reduced the load to failure to 61%. Both 2.4-mm horizontal tunnels with a medium and short length did not reduce the load to failure. Tunnels placed at the acromion did not result in an increased risk of fracture. However, descriptive data showed a tendency for an increased fracture risk if tunnels are placed at the acromion, especially in horizontal direction with diameters of 4.5 mm. In addition, the pattern of fracture was dependent on the orientation of the bone tunnels and the size. However, the results indicate a "safe zone" for the placement of bone tunnels within the anterior half of the acromion, which does not affect the loads to failure at the acromion. Therefore, current techniques for anatomic AC joint reconstruction which utilize fixation of grafts or sutures at the acromion are safe within current ranges of tunnel placement and sizes.


Biomarkers of renal function in preterm neonates at 72h and 3weeks of life.
Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72h and 3 weeks of life. Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. The preterm neonates included 55% of males with gestational age of 30±1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.


Immunological cross-reactivity of the histidine-rich protein of Plasmodium lophurae and the knob protein of Plasmodium falciparum.
Rabbits were immunized with the histidine-rich protein (HRP) of the avian malaria parasite, Plasmodium lophurae. The anti-HRP immunoprecipitated the knob protein (KP) from extracts of the human parasite, Plasmodium falciparum. The anti-HRP did not react with any antigens of a laboratory-derived strain of P. falciparum (K-) that does not form knobs. Antisera raised against a membrane-enriched fraction of P. falciparum-infected erythrocytes as well as sera from humans exposed to P. falciparum infections immunoprecipitated HRP from P. lophurae extracts.


Relationship between prey consumption and colony size in an orb spider.
I studied the relationship between prey consumption and colony size in the orb spiderPhiloponella semiplumosa. Observations of unmanipulated colonies showed that prey biomass per juvenile spider was positively correlated with colony size, indicating that prey consumption was highest in the largest colonies observed. In contrast, the relationship between prey biomass per adult female and colony size was curvilinear; prey consumption tended to be highest in intermediatesized colonies. Adult female cephalothorax width was positively correlated with colony size. Number of egg sacs per adult female tended to be highest in intermediate-sized colonies. Prey biomass per juvenile was lower in experimentally reduced colonies than in large control colonies. Aerial-arthropod abundance was not correlated with colony size, and experimental prey supplementation did not affect colony size. Thus, the relationship between prey consumption and colony size was influenced by coloniality directly, rather than by a correlation between prey abundance at a site and colony size.


Cortical Beta Oscillatory Activity Evoked during Reactive Balance Recovery Scales with Perturbation Difficulty and Individual Balance Ability.
Cortical beta oscillations (13-30 Hz) reflect sensorimotor processing, but are not well understood in balance recovery. We hypothesized that sensorimotor cortical activity would increase under challenging balance conditions. We predicted greater beta power when balance was challenged, either by more difficult perturbations or by lower balance ability. In 19 young adults, we measured beta power over motor cortical areas (electroencephalography, Cz electrode) during three magnitudes of backward support -surface translations. Peak beta power was measured during early (50-150 ms), late (150-250 ms), and overall (0-400 ms) time bins, and wavelet-based analyses quantified the time course of evoked beta power. An ANOVA was used to compare peak beta power across perturbation magnitudes in each time bin. We further tested the association between perturbation-evoked beta power and individual balance ability measured in a challenging beam walking task. Beta power increased ~50 ms after perturbation, and to a greater extent in larger perturbations. Lower individual balance ability was associated with greater beta power in only the late (150-250 ms) time bin. These findings demonstrate greater sensorimotor cortical engagement under more challenging balance conditions, which may provide a biomarker for reduced automaticity in balance control that could be used in populations with neurological impairments.


Ventral pallidum self-stimulation: a moveable electrode mapping study.
The distribution of electrical self-stimulation (ESS) foci within the ventral pallidum (VP) was mapped using moveable electrodes in rats. The function relating ESS bar-pressing rate to the frequency of cathodal rectangular pulses (0.4 mA and 0.1 ms) was obtained for several positions of a moveable electrode in the VP and in the various adjacent to VP nuclei. The rate-frequency functions were fitted to a sigmoid model to obtain the asymptotic rate and threshold frequency. ESS was found in almost all (98%) VP sites tested and to a lesser degree (66%) in the surrounding areas (namely globus pallidus and caudate). Depending on the VP site, maximum rates varied from 14 to 85 bar presses/min, whereas threshold frequencies varied from 10.2 to 36.4 pulses/train; no correlation between these two aspects of ESS was found. Extra-pallidal areas contained less low-frequency threshold sites compared to VP. The lowest threshold found in the VP was slightly higher than that usually obtained for the most rewarding brain areas (VTA, dorsal raphé, LH, amygdala), which suggests that the VP represents an important structure for reward. Furthermore the threshold frequencies were found to decline along the rostrocaudal axis of the VP which supports the view that the VP is heterogeneous in regard to reward related functions.


Antiviral antibody responses: the two extremes of a wide spectrum.
Viruses elicit a diverse spectrum of antiviral antibody responses. In this review, we discuss two widely used experimental model systems for viral infections - non-cytopathic lymphocytic choriomeningitis virus (LCMV) and acutely cytopathic vesicular stomatitis virus (VSV) - to analyse two fundamentally different types of antiviral antibody response. The basic principles found in these model infections are discussed in the context of other viral infections, and with regard to protective neutralizing versus non-protective enzyme-linked immunosorbent assay (ELISA)-detected antibody responses. Issues of antibody specificity, affinity and avidity, maturation and escape are discussed in the context of co-evolution of the host and viruses.


Evaluation of a university course aimed at promoting exercise behavior.
This study assessed a 10-week, university-required lifetime fitness for health (LFH) course on students' leisure-time exercise behavior and advancement through the stages of change for exercise. a quasi-experimental design was employed. public university located in the United States. a total of 540 students who were enrolled in an LFH course or selected psychology courses volunteered to participate in this study. a 30-hour LFH course administered over 10 weeks. The course was delivered both in a lecture and lab format. The control condition consisted of psychology courses. weekly leisure-time exercise behavior and stage of change for exercise behavior were assessed using valid and reliable self-report questionnaires at pre- and post-intervention. Regardless of course, students' showed minimal changes in their exercise levels from pre- to post-intervention. Moreover, students in the LFH course did not improve their stage of change for exercise behavior as much students in the psychology courses. Regardless of course, participants' stage of change for exercise was an important moderator variable associated with exercise behavior change. As was taught, the LFH course did little to change the participants' exercise levels outside of class, and did little to positively influence the participants' stage of change for exercise behavior.


Complement C1q subunit molecules from Xenopus laevis possess conserved function in C1q-immunoglobulin interaction.
Complement component 1q (C1q), together with C1r and C1s to form C1, recognize and bind immune complex to initiate the classical complement pathway. In this study, C1q subunit molecules (XlC1qA, XlC1qB, XlC1qC) were cloned and analyzed from Xenopus laevis (X. laevis). The open reading frame (ORF) of XlC1qA is 819 bp of nucleotide sequence encoding 272 amino acids, the ORF of XlC1qB is 711 bp encoding 236 aa, and the XlC1qC is consists of 732 bp encoding 243 aa. The deduced amino acid sequences contain a collagen-like region (CLR), Gly-X-Y repeats in the N-terminus and a C1q family domain at the C-terminus. Phylogenetic analysis revealed that the XlC1qs are clustered with the amphibian clade. Expression analysis indicated that the XlC1qs exhibited constitutive expression in all examined tissues, with the highest expression in liver. Additionally, XlC1q could interact with heat-aggregated mouse IgG and IgM, Xenopus IgM and Nile tilapia IgM, respectively, indicating the functional conservation of XlC1q binding to immunoglobulins. Further, XlC1qs can inhibit C1q-dependent hemolysis of sensitized sheep red blood cells with concentration-dependent manner. These data collectively suggest that the function of C1qs in X. laevis may be conserved in interaction with immunoglobulins, as that of mammals and teleosts.


Docking protein 1 and free fatty acids are associated with insulin resistance in patients with type 2 diabetes mellitus.
Insulin resistance (IR) is a key defect in type 2 diabetes mellitus (T2DM); therefore, effective means of ameliorating IR are sought. We performed a retrospective cohort study of 154 patients with T2DM and 39 with pre-diabetes (pre-DM). The effects of IR and a high concentration of FFA on gene expression were determined using microarray analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR) in patients with T2DM or pre-DM. Serum FFA concentration and homeostasis model assessment of IR (HOMA-IR) were significantly higher in patients with T2DM but no obesity and in those with pre-DM than in controls. HOMA-IR was significantly associated with T2DM. RT-qPCR showed that the expression of FBJ murine osteosarcoma viral oncogene homolog (FOS) and AE binding protein 1 (AEBP1) was much lower in the circulation of participants with obesity and diabetes. RT-qPCR showed that the expression of docking protein 1 (DOK1) was significantly lower in the blood of participants with diabetes but no obesity and in those with pre-DM than in controls. FFA and DOK1 are associated with IR in patients with T2DM but no obesity or pre-DM. The downregulation of DOK1 might inhibit lipid synthesis and induce lipolysis, inducing or worsening IR.


Developmental expression and intracellular location of P400 protein characteristic of Purkinje cells in the mouse cerebellum.
The developmental expression and intracellular localization of a cerebellum-characteristic 250-kDa glycoprotein, P400 protein, were studied by immunohistochemical and immunoblot methods using a monoclonal antibody against P400 protein. In the cerebellum of normal mouse, the expression of P400 protein increased from Postnatal Day 3 to Day 21. This enhancement of P400 protein expression occurred only in the Purkinje cells and proceeded with the growth of their dendritic arborization. Electron microscopic analysis indicated that P400 protein is present at the plasma membrane, the endoplasmic reticulum, and the postsynaptic densities of Purkinje cells. Immunohistochemistry of the cerebella of neurological mutant mice indicated that the Purkinje cells of reeler, weaver, and pcd mutant mice retain the ability to produce a large amount of P400 protein. However, the Purkinje cells of staggerer mutant mouse proved to be incapable of enhanced P400 protein expression. These results indicate that P400 protein is a Purkinje cell-characteristic plasma membrane-associated glycoprotein, which is also present at the postsynaptic density and endoplasmic reticulum and that the expression of P400 protein in Purkinje cells is closely associated with the growth of their dendritic arborization.


MANF is indispensable for the proliferation and survival of pancreatic β cells.
All forms of diabetes mellitus (DM) are characterized by the loss of functional pancreatic β cell mass, leading to insufficient insulin secretion. Thus, identification of novel approaches to protect and restore β cells is essential for the development of DM therapies. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER)-stress-inducible protein, but its physiological role in mammals has remained obscure. We generated MANF-deficient mice that strikingly develop severe diabetes due to progressive postnatal reduction of β cell mass, caused by decreased proliferation and increased apoptosis. Additionally, we show that lack of MANF in vivo in mouse leads to chronic unfolded protein response (UPR) activation in pancreatic islets. Importantly, MANF protein enhanced β cell proliferation in vitro and overexpression of MANF in the pancreas of diabetic mice enhanced β cell regeneration. We demonstrate that MANF specifically promotes β cell proliferation and survival, thereby constituting a therapeutic candidate for β cell protection and regeneration.


Divergent molecular evolution in glutathione S-transferase conferring malathion resistance in the oriental fruit fly, Bactrocera dorsalis (Hendel).
Insect glutathione S-transferases (GSTs) are important in insecticide detoxification and Insect-specific GSTs, Epsilon and Delta, have largely expanded in insects. In this study, we functionally expressed and characterized an epsilon class GST gene (BdGSTe8), predominant in the adult Malpighian tubules of Bactrocera dorsalis. This gene may be associated with malathion resistance based on transcriptional studies of resistant and susceptible strains. RNA interference-mediated knockdown of this gene significantly recovered malathion susceptibility in the adults of a malathion-resistant strain, and overexpression of BdGSTe8 enhanced resistance in transgenic Drosophila. Analysis of BdGSTe8 polymorphism showed that several point mutations may be associated with metabolic resistance to malathion. A cytotoxicity assay in Escherichia coli indicated that both of the recombinant BdGSTe8 proteins may play a functional role in protecting cells from toxicity. The allele of BdGSTe8-B conferred higher levels of malathion detoxification capability. Liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry analysis showed that the BdGSTe8-A allele did not metabolize malathion directly. However, the BdGSTe8-B allele was involved in the direct metabolism of malathion, which was caused by a mutation in V128A. Further analysis of the sequence suggests that BdGSTe8 evolved rapidly. It maybe play the role of a backup gene and could become a new gene in the future in order to retain the ability of detoxification of malathion, which was driven by positive selection. These results suggest that divergent molecular evolution in BdGSTe8 has played a role in metabolic resistance to malathion in B. dorsalis.


Effects of secobarbital on human aggressive and non-aggressive responding.
This study examined the effects of secobarbital on human aggressive responding in a controlled laboratory setting. Sixty minutes prior to experimental sessions, male subjects were administered either placebo or 50, 100 or 200 mg per 70 kg of body weight doses of secobarbital double-blind. During these sessions, subjects could press a button to accumulate points exchangeable for money (non-aggressive response) or press another button ostensibly to subtract points from a fictitious person (aggressive response). Aggressive responding was occasioned by subtracting points from the subject. Subjects were instructed that points were subtracted by another person. Aggressive responding was maintained by contingent presentation of periods free of point subtractions, i.e., provocations. Acute secobarbital administration produced dose-dependent decreases in non-aggressive responding, and increases in aggressive responding.


Experiences in treating cancer of the bladder.
Experience in the treatment of urinary bladder cancer based upon observation of 306 cases has been presented. Two hundred and thirteen patients were treated surgically by performing in 151 cases partial cystectomy and in 62 cases total cystectomy. Conservative treatment was applied in 75 patients. In the authors' opinion the best method of treating bladder cancer is its radical excision. A simple and easy method of implantation of the ureters into the rectum is described.


Prevalence of hearing impairment amongst school going children in the rural field practice area of the institution.
Worldwide, over 275 million people are estimated to have moderate to profound hearing loss in both ears. Children with hearing impairment often experience delayed development of speech and cognitive skills, which may result in slower learning and difficulty in progressing at school. Adequate hearing is one of the main factors for good psychosocial development, by which individuals may express their thoughts, feelings, and wishes, and acquire life experience and knowledge. Therefore, hearing impairment needs to be diagnosed early for prompt therapy. Primary objectives of this study was to know prevalence of hearing impairment amongst primary school children and secondary objective was to identify the common causes of hearing impairment amongst primary school children. The cross sectional study was conducted in the government and private schools of our rural field practice area in 2013-2014 for the duration of 4 months from November 2013 to February 2014. Prevalence of Hearing loss was 8.8%. Most common cause of Hearing loss was Impacted wax and Retracted Tympanic membrane. Otological conditions-Wax followed by otitis media with effusion and chronic suppurative otitis media were the common ear problems found in our study.


Phox2b mutation mediated by Atoh1 expression impaired respiratory rhythm and ventilatory responses to hypoxia and hypercapnia.
Mutations in the transcription factor Phox2b cause congenital central hypoventilation syndrome (CCHS). The syndrome is characterized by hypoventilation and inability to regulate breathing to maintain adequate O2 and CO2 levels. The mechanism by which CCHS impact respiratory control is incompletely understood, and even less is known about the impact of the non-polyalanine repeat expansion mutations (NPARM) form. Our goal was to investigate the extent by which NPARM Phox2b mutation affect (a) respiratory rhythm; (b) ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR); and (c) number of chemosensitive neurons in mice. We used a transgenic mouse line carrying a conditional Phox2bΔ8 mutation (same found in humans with NPARM CCHS). We crossed them with Atoh1cre mice to introduce mutation in regions involved with respiratory function and central chemoreflex control. Ventilation was measured by plethysmograph during neonatal and adult life. In room air, mutation in neonates and adult did not greatly impact basal ventilation. However, Phox2bΔ8, Atoh1cre increased breath irregularity in adults. The HVR and HCVR were impaired in neonates. The HVR, but not HCVR, was still partially compromised in adults. The mutation reduced the number of Phox2b+/TH--expressing neurons as well as the number of fos-activated cells within the ventral parafacial region (also named retrotrapezoid nucleus [RTN] region) induced by hypercapnia. Our data indicates that Phox2bΔ8 mutation in Atoh1-expressing cells impaired RTN neurons, as well as chemoreflex under hypoxia and hypercapnia specially early in life. This study provided new evidence for mechanisms related to NPARM form of CCHS neuropathology.


Cognitive function and platelet membrane fluidity in Alzheimer's disease.
Increased platelet membrane fluidity, as reflected by a decrease in the fluorescence anisotropy of diphenylhexatriene in labeled membranes, identifies a clinically distinct subgroup of approximately 50% of patients at our center who meet NINCDS-ADRDA clinical criteria for Alzheimer's disease. In the current study, we compared the cognitive impairments of patients in this subgroup to those observed in the residual subgroup of patients with Alzheimer's disease who had normal platelet membrane fluidity. No significant differences in the number or distribution of deficits in six cognitive domains were observed between the two subgroups. However, in the subgroup with increased platelet membrane fluidity, there were significantly more patients who exhibited dissociation of deficits on tests related to left and right parietal lobe function than in the residual subgroup. Moreover, the cases with dissociation of deficits consisted almost entirely of patients with deficits on tests reflecting left parietal lobe function and no deficit on tests of right parietal lobe function.


Human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide.
In order to determine the human in vivo percutaneous absorption of pyrethrin and piperonyl butoxide, a commercial formulation containing either [14C]pyrethrin (3.8 mCi/mmol) or [14C]piperonyl butoxide (3.4 mCi/mmol) was applied to the ventral forearm of six human volunteers. The formulation contained 0.3% pyrethrin and 3.0% piperonyl butoxide. Spreadability studies showed that concentrations of 5.5 micrograms pyrethrin/cm2 and 75.8 micrograms piperonyl butoxide/cm2 (used in this study) would be consistent with levels found in actual use. The forearms were thoroughly cleansed with soap and water 30 min after application (as recommended for actual use). Percutaneous absorption was determined by urinary cumulative excretion following dose application. With a 7-day urinary accumulation, 1.9 +/- 1.2% (SD) of the dose of pyrethrin and 2.1 +/- 0.6% of the dose of piperonyl butoxide applied was absorbed through the forearm skin. 1 hr after application blood samples contained no detectable radioactivity. The percutaneous absorption of pyrethrin and piperonyl butoxide from the scalp was calculated to be 7.5% of the applied dose for pyrethrin and 8.3% for piperonyl butoxide. The calculated half-life of 14C excretion was 50 hr for pyrethrin and 32 hr for piperonyl butoxide. The data should be of relevance to appropriate risk assessment in extrapolating animal data to humans.


P-value, compatibility, and S-value.
Misinterpretations of P-values and 95% confidence intervals are ubiquitous in medical research. Specifically, the terms significance or confidence, extensively used in medical papers, ignore biases and violations of statistical assumptions and hence should be called overconfidence terms. In this paper, we present the compatibility view of P-values and confidence intervals; the P-value is interpreted as an index of compatibility between data and the model, including the test hypothesis and background assumptions, whereas a confidence interval is interpreted as the range of parameter values that are compatible with the data under background assumptions. We also suggest the use of a surprisal measure, often referred to as the S-value, a novel metric that transforms the P-value, for gauging compatibility in terms of an intuitive experiment of coin tossing.


The Sensitivity of Scalp EEG at Detecting Seizures-A Simultaneous Scalp and Stereo EEG Study.
Compare the detection rate of seizures on scalp EEG with simultaneous intracranial stereo EEG (SEEG) recordings. Twenty-seven drug-resistant epilepsy patients undergoing SEEG with simultaneous scalp EEG as part of their surgical work-up were included. A total of 172 seizures were captured. Of the 172 seizures detected on SEEG, 100 demonstrated scalp ictal patterns. Focal aware and subclinical seizures were less likely to be seen on scalp, with 33% of each observed when compared with focal impaired aware (97%) and focal to bilateral tonic-clonic seizures (100%) (P < 0.001). Of the 72 seizures without ictal scalp correlate, 32 demonstrated an abnormality during the SEEG seizure that was identical to an interictal abnormality. Seizures from patients with MRI lesions were statistically less likely to be seen on scalp than seizures from nonlesional patients (P = 0.0162). Stereo EEG seizures not seen on scalp were shorter in duration (49 seconds) compared with SEEG seizures seen on scalp (108.6 seconds) (P < 0.001). Scalp EEG is not a sensitive tool for the detection of focal aware and subclinical seizures but is highly sensitive for the detection of focal impaired aware and focal to bilateral tonic-clonic seizures. Longer duration of seizure and seizures from patients without MRI lesions were more likely to be apparent on scalp. Abnormalities seen interictally may at times represent an underlying seizure. The cognitive, affective, and behavioral long-term effects of ongoing difficult-to-detect seizures are not known.


Value of dual-phase multislice CT prior to minimally invasive therapy of iatrogenic renal injuries.
To evaluate the diagnostic impact of multislice computed tomography (MSCT) in treatment planning prior to transarterial coil embolization of iatrogenic renal injuries. Nine patients (median age 54 years, range 36-66) with iatrogenic renal vascular injury were treated with superselective coil embolization. Prior to therapy, a dual-phase (40 and 120 seconds) contrast-enhanced MSCT was applied in 6 patients. Seven patients underwent renal ultrasonography. Multiplanar reconstructions of the MSCT scans were used to affirm ongoing bleeding and to localize the bleeding site at the level of the segmental or interlobar artery. MSCT and angiographic findings were compared to evaluate the accuracy of MSCT in the detection of the bleeding source prior to therapy. Multiplanar reconstructions of early-phase MSCT scans allowed precise identification of the bleeding interlobar or segmental artery in all 6 cases prior to angiography. In one case, MSCT was even able to detect a source of bleeding that was not revealed by selective renal angiography. Multiplanar reconstructions of MSCT data demonstrate not only the presence of hematoma but also confirm ongoing bleeding and the location of the feeder artery prior to minimally invasive therapy.


Teleconsultations by primary care physicians of Belo Horizonte: challenges in the diffusion of innovation.
Telemedicine is the provision of health services by professionals who use information and communications technology in the exchange of information for the diagnosis, treatment, and prevention of diseases. Since 2004, the Municipal Department of Health of Belo Horizonte, MG, Brazil, has been implementing telehealth initiatives with the goal of increasing the ability of primary care providers to resolve problems by providing them with clinical support and with continuing education using information and communications technologies. This study characterized the primary care physicians who used the Belo Horizonte telehealth store-and-forward teleconsultation. A descriptive study was conducted of the frequency of use of store-and-forward teleconsultation and characteristics of physician users. We analyzed 737 store-and-forward teleconsultations in the period 2006-2010. The number of store-and-forward teleconsultations grew from 2006 to 2009, and 85 physicians used the tool. The physician users were predominantly women, specialists in family and community medicine, those employed under a stable contract, and older and with more time in the profession and in public service. The adoption rate was 6.0%, 4.8%, and 1.2% in 2008, 2009, and 2010, respectively. Context variables and individual variables may be influencing the adoption of store-and-forward teleconsultation in Belo Horizonte. It would be useful to further study the factors that constitute barriers to using teleconsultations and to improve the training in use of the tool.


Quantitatively understanding reduced xylose fermentation performance in AFEX™ treated corn stover hydrolysate using Saccharomyces cerevisiae 424A (LNH-ST) and Escherichia coli KO11.
Reduced xylose fermentation performance has been an issue during fermentation of AFEX™ hydrolysate using Saccharomyces cerevisiae 424A (LNH-ST) or Escherichia coli KO11. To better understand why fermentation performance is reduced, we quantitatively studied the effects of compounds present in the fermentation broth on xylose consumption. The compounds include biomass degradation products, ethanol and fermentation metabolites. The xylose consumption capability of E. coli KO11 was almost totally inhibited by the presence of both degradation products and ethanol. On the other hand, for S. cerevisiae 424A, 89% reduction of xylose consumption rate was found during hydrolysate fermentation. Degradation products, ethanol and fermentation metabolites were responsible for 32%, 24% and 33% of such reduction, respectively. Those results suggest that to further improve the xylose fermentation in hydrolysate, strains should be selected not only for degradation products tolerance but also for ethanol and fermentation metabolites tolerance.


Relationships between the chemical structure and the biological properties of some eremophilane compounds related to PR toxin.
The problem of the chemical structure--biological effects relationships has been studied for various eremophilane compounds related to PR toxin (PRT), a mycotoxin synthesized by Penicillium roqueforti. The biological tests were based on in vivo toxicity for male Swiss mice and inhibition of in vitro transcription and tranlation. The results showed a good correlation between the responses obtained for the three tests by the different compounds; thus, the toxic potency and the capacity of inhibiting transcription and translation should be directed by a common chemical structure. The data also indicated that the biological properties are related to the existence of an aldehyde group in position 12. In addition, evidence has been obtained demonstrating the hydrolysis of PRT imine with formation of a PRT-like compound.


Barium content of Archaean continental crust reveals the onset of subduction was not global.
Earth's earliest continental crust is dominated by tonalite-trondhjemite-granodiorite (TTG) suites, making these rocks key to unlocking the global geodynamic regime operating during the Archaean (4.0-2.5 billion years ago [Ga]). The tectonic setting of TTG magmatism is controversial, with hypotheses arguing both for and against subduction. Here we conduct petrological modeling over a range of pressure-temperature conditions relevant to the Archaean geothermal gradient. Using an average enriched Archaean basaltic source composition, we predict Ba concentrations in TTG suites, which is difficult to increase after magma generated in the source. The results indicate only low geothermal gradients corresponding to hot subduction zones produce Ba-rich TTG, thus Ba represents a proxy for the onset of subduction. We then identify statistically significant increases in the Ba contents of TTG suites worldwide as recording the diachronous onset of subduction from regional at 4 Ga to globally complete sometime after 2.7 Ga.


Adrenal, kidney, and heart angiotensins in female murine Ren-2 transfected hypertensive rats.
We analyzed by high-performance liquid chromatography and radioimmunoassay angiotensin I (Ang I), Ang II, Ang-(1-7), and metabolites in the adrenal, kidney and heart of normotensive female Sprague-Dawley (SD) and transgenic hypertensive [TGR(mRen-2)27] rats carrying the murine Ren-2d renin gene. The monogenetic model of hypertensive rats had significant increases in adrenal Ang II; whereas in the kidney Ang II was unchanged, but Ang I and Ang-(1-7) were significantly lower. Cardiac Ang I, Ang II, and Ang-(2-10) were significantly reduced in transgenic rats, while Ang-(2-7) was increased. In SD and transgenic rats kidney and adrenal angiotensins increased primarily during estrus or proestrus. In female transgenic rats the increased adrenal Ang II and the sustained renal Ang II may contribute to the established phase of hypertension.


[Primary cysts and tumors of the mediastinum].
To assess results in patients with primary cysts and tumours of the mediastinum who under- went surgery. A retrospective single-centre study was undertaken into patients with primary cysts and tumours of the mediastinum who underwent surgery between January 1992 and December 2004. We analysed demographic data, clinical presentation, type of surgery carried out and procedure, lesion location and histological diagnosis. Predictive malignancy factors were also evaluated. Postoperative morbidity and mortality were noted, as was medium-term results. 171 patients underwent surgery over a 13-year period; 73 female (43%) and 98 male (57%). Mean age was 40.3+/-19.7 years (20 days-78 years). A primary cystic lesion was present in 15 patients (9%). The pri- mary tumours included thymic neoplasms (31%), lymphoma (22%), neurogenic tumours (16%), germ cell tumours (9%) and a miscellaneous group (13%). Malignant neoplasms were present in 78 patients (46%). The antero-superior mediastinum was the most commonly involved site to have a primary cyst or tumour (58%), followed by the posterior mediastinum (24%) and the middle mediastinum (18%). Symptoms were present in 68% of the patients and included chest pain (20%), fever and chills (13%), myasthenia gravis (11%), cough (10%), dyspnoea (10%), and superior vena caval syndrome (7%). Univariate analysis identified symptoms as a predictive factors of malignancy (p<0.001). Types of surgery carried out included postero-lateral thoracotomy (64 patients), median sternotomy (51 patients), anterior mediastinostomy (27 patients), antero-lateral thoracotomy (18 patients), video-assisted thoracic surgery (9 patients) and mediastinoscopy (2 patients). Total excision was performed in 116 patients, enlarged resection in 8 patients, subtotal re- section in 7 patients and biopsy in 40 patients. There was one postoperative death (0.6%). Follow-up was available in 165 patients (96.5%) and ranged from 34 days to 13.4 years (mean 5.7+/-4.0 years). Complementary treatment with chemo and/or radiotherapy was provided in 75 patients. Six patients had to be reoperated on for local recurrence (3) or metastasis (3) of the primary lesion. Fifteen patients died of their disease during the follow-up period. Actuarial survival at five years was 97.6% for benign lesions and 76.4% for malignant tumours. Results support surgical resection for benign lesions and an aggressive multimodal approach for malignant tumours.


A novel protein immunoassay with predetermined specificity using monoclonal antibodies against tryptic fragments: application to HIV P24 antigen.
We have developed a new protein immunoassay method which uses antibodies raised against synthetic peptides. These synthetic peptides are selected to correspond to fragments of the protein that can be obtained by proteolytic treatment of the protein by trypsin. Just before assay, biological samples are treated with trypsin to liberate the fragments which bind to the anti-peptide antibodies with high affinity. The exact specificity of the assay is predetermined by the amino acid sequence of the fragment which may be either conserved within a family of antigens or, conversely, entirely specific for a particular protein. This method has been successfully employed in the development of an immunoassay for HIV P24 antigen. In that case, peptides were selected that were strongly conserved among the different HIV-1 and HIV-2 strains. This methodology has permitted the development of a sensitive immunoassay with a broad specificity despite many amino acid variations between HIV strains. The methodology could be extended to other protein antigens.


An Exploratory Study of Hyoid Visibility, Position, and Swallowing-Related Displacement in a Pediatric Population.
Hyoid position and swallowing-related displacement has been studied in healthy adults and adults with dysphagia, but research is limited in children. The aim of this study was to investigate feasibility of visualizing and measuring position and swallowing-related displacement of the hyoid bone in children. We explored relationships between hyoid displacement, age and aspiration risk scores. Pediatric swallowing data were extracted from a videofluoroscopy database containing recordings from 133 children aged 9 days to 21 years (mean 36 months, SD 3 years) referred for videofluoroscopy due to concerns regarding their feeding. Children presented with varying etiologies: neurological, structural, respiratory, and other diagnoses. Still shot images were extracted for the frame of hyoid peak position and a frame showing the hyoid at rest. Pixel-based image analysis software was used to measure hyoid position in three directions (X = anterior, Y = superior, XY = hypotenuse) relative to C4 vertebra. Difference between rest and peak position was used to measure hyoid displacement (X, Y and XY). The hyoid was not visible in children < 9 months, but could be reliably visualized and measured in 49 children. Descriptive statistics were collected for hyoid parameters. Age was significantly associated with rest (Y and XY) and peak (Y and XY) hyoid position parameters as well as anterior displacement. No significant associations were observed between hyoid parameters and aspiration risk scores. This study successfully explored hyoid visibility, position and swallowing-related displacement in a pediatric population. Hyoid can be reliably visualized and tracked through videofluoroscopy in children > 9 months of age.


Overexpression, crystallization and preliminary X-ray crystallographic analysis of the RNA polymerase domain of primase from Streptococcus mutans strain UA159.
Primase is the enzyme that synthesizes RNA primers on single-stranded DNA during normal DNA replication. In this study, the catalytic core domain of primase from Streptococcus mutans UA159 was overexpressed in Escherichia coli, purified and crystallized. Diffraction data were collected to 1.60 Å resolution using a synchrotron-radiation source. The crystal belonged to space group P4(1) or P4(3), with unit-cell parameters a = b = 52.63, c = 110.31 Å. The asymmetric unit is likely to contain one molecule, with a corresponding V(M) of 1.77 Å(3) Da(-1) and a solvent content of 30.7%.


Examining the influences on the use of behavioural science within UK local authority public health: Qualitative thematic analysis and deductive mapping to the COM-B model and Theoretical Domains Framework.
Behavioural science and its contribution towards improving public health is receiving increased recognition. Yet, the translation of these insights into public health practice is under-researched. This study explored the factors influencing the use of behavioural science within public health at a local authority level. Fourteen local authority staff (n = 13 female) in the south of England participated in semi-structured interviews, which were analysed inductively to identify key themes. These were later mapped deductively to the COM-B model and Theoretical Domains Framework. Nine themes were identified as factors that influence the use of behavioural science in local authority public health: (1) "Limited past experience," (2) "Narrow understanding," (3) "Perceived value of behavioural science," (4) "Translational gap from theory-to-practice," (5) "No protected time," (6) "Old ways of working," (7) "Political influence and organisational culture," (8) "Relationships with key stakeholders," (9) "Access to behavioural science resources". Deductive mapping of these themes revealed that five of the COM constructs (excluding Physical Capability) and eleven of the TDF domains influenced behavioural science use, with "Social influences" and "Knowledge" being the most prominent. Use of behavioural science within local authority public health practice is limited and inconsistent. For it to be successfully implemented, there must be an understanding of its role and value, alongside strategies to overcome a translational gap from theory to practice. Public health teams would benefit from protected time to enable application and strategies to break old habits of using a common-sense approach. System-wide buy-in, particularly related to senior leadership and system partners is needed, which would benefit from organisational and political culture change. Training opportunities, practical resources and expert in-house support should be considered a priority across public health teams.


Discovery of a new cyclooxygenase-2 lead compound through 3-D database searching and combinatorial chemistry.
Using a combination of computational and combinatorial chemistry methodologies, a phenothiazine compound was discovered that is a selective inhibitor of cyclooxygenase-2 and serves as a lead compound for a potentially novel series of anti-inflammatory compounds.


Bacteremia following intraoral suture removal.
Following dental extractions, prophylactic antibiotic protection of patients at high risk of cardiovalvular infection is usually discontinued before suture removal. To determine whether bacteremia is created upon removal of intraoral sutures, twenty healthy patients who required extractions of at least five erupted teeth and placement of several sutures were selected without regard to sex, age, or race. Blood samples were drawn preoperatively, immediately after the extractions, before suture removal, and immediately following removal of the intraoral silk sutures. The samples were cultured in prereduced and aerobic media suitable for quantitative colony counts. Fourteen of 16 patients yielded positive blood cultures following tooth extractions. One of 20 patients yielded a positive blood culture following suture removal. Even though the incidence of bacteremia following intraoral suture removal is relatively low (5%), this study suggests that intraoral suture removal is not a benign procedure for those persons who are considered high-risk cardiac patients.


Sequence and expression of mouse gamma-renin.
Mouse gamma-renin is a member of the group of serine proteases known as glandular kallikreins. These highly homologous proteins process a diverse range of growth factors and hormones to their biologically active form, usually by cleavage at a basic residue. gamma-Renin, however, cleaves at a Leu-Leu bond in a similar fashion to renin. We have identified and sequenced the gene and a cDNA encoding gamma-renin. The complete predicted amino acid sequence was determined, and residues that may be important in the unusual cleavage pattern exhibited by gamma-renin are discussed. The nucleotide sequence enabled design of a gene-specific oligodeoxyribonucleotide which was used to determine in which mouse tissues gamma-renin is expressed.


Vitamin D status of females in an elite gymnastics program.
Vitamin D plays an important role in calcium and bone metabolism. In Australia it has been assumed that all young athletes have good vitamin D levels. A survey of females in an elite gymnastics program was undertaken to determine their vitamin D and dietary calcium status. Cross-sectional survey. Females in an elite gymnastics program at the Australian Institute of Sport. Eighteen female gymnasts aged 10-17 years were assessed for vitamin D status (serum 25[OH]D) and dietary calcium intake. Fifteen were found to have levels below current recommended guidelines for optimal bone health (<75 nmol/L). Six had vitamin D levels below 50 nmol/L. Thirteen of the gymnasts also had daily dietary calcium intakes below the daily recommended intake for their age. Gymnasts and possibly other indoor athletes should be carefully reviewed for vitamin D and calcium status.


A new nanobody-enzyme fusion protein-linked immunoassay for detecting antibodies against influenza A virus in different species.
Circulation of influenza A virus (IAV), especially within poultry and pigs, continues to threaten public health. A simple and universal detecting method is important for monitoring IAV infection in different species. Recently, nanobodies, which show advantages of easy gene editing and low cost of production, are a promising novel diagnostic tool for the monitoring and control of global IAVs. In the present study, five nanobodies against the nucleoprotein of H9N2 IAV were screened from the immunized Bactrian camel by phage display and modified with horseradish peroxidase (HRP) tags. Out of which, we determined that H9N2-NP-Nb5-HRP can crossreact with different subtypes of IAVs, and this reaction is also blocked by positive sera for antibodies against different IAV subtypes. Epitope mapping showed that the nanobody-HRP fusion recognized a conserved conformational epitope in all subtypes of IAVs. Subsequently, we developed a nanobody-based competitive ELISA (cELISA) for detecting anti-IAV antibodies in different species. The optimized amount of coating antigen and dilutions of the fusion and testing sera were 100 ng/well, 1:4000, and 1:10, respectively. The time for operating the cELISA was approximately 35 min. The cELISA showed high sensitivity, specificity, reproducibility, and stability. In addition, we found that the cELISA and hemagglutination inhibition test showed a consistency of 100% and 87.91% for clinical and challenged chicken sera, respectively. Furthermore, the agreement rates were 90.4% and 85.7% between the cELISA and commercial IEDXX ELISA kit. Collectively, our developed nanobody-HRP fusion-based cELISA is an ideal method for monitoring IAV infection in different species.


Effects of a cyanobacterial bloom sample containing microcystin-LR on the ecophysiology of Daphnia similis.
Cyanobacterial blooms can affect a wide range of aquatic organisms due to the presence of toxic compounds. However, no study so far has shown the effects of natural blooms samples on the physiological parameters related to the ecology of Daphnia. In this study we used a natural bloom sample obtained from a reservoir in Colombia to evaluate its effects on five parameters related to Daphnia's feeding behavior, swimming movements and physiology: second antennae movement (swimming), mandible movement (feeding), thoracic appendages (feeding), postabdomen movement (rejection of food particles) and heart rate (physiology). The results revealed significant changes in all parameters evaluated at two different concentrations of aqueous extracts of the bloom: second antennae movements increased significantly and there were significant reductions in mandibular movements, thoracic movements and heart rate. Although postabdominal movements showed high variability with no distinctive pattern between control and treatments, the reduction in the other parameters (such as heart rate over time) could possibly reflect an intoxication by microcystins or a behavioral response (e.g., feeding inhibition).


Capacity for thermal adaptation in Nile tilapia (Oreochromis niloticus): Effects on oxygen uptake and ventilation.
Standard metabolic rate (SMR) and maximum metabolic rate (MMR) were determined for Nile tilapia acclimated to six different experimental temperatures from 18 °C to 38 °C. SMR increased exponentially with temperature, from 79.8 mg O2 kg-1 h-1 at 18 °C, to 255.1 mg O2 kg-1 h-1 at 38 °C (Q10 = 1.79). The main increase in Q10 occurred within the highest temperature range, whereas in the lower temperature from 18 °C to 22 °C, temperature did not significantly affect SMR. MMR showed a hyperbolic correlation with increasing temperature, rising from 240.5 mg O2 kg-1 h-1 at 18 °C to a peak of 373.8 mg O2 kg-1 h-1 at 30 °C, before decreasing again at higher temperatures. Absolute aerobic scope (AAS) peaked at 26.0 °C, which we conclude to be the optimal temperature for Nile tilapia. The optimal temperature range, defined as the thermal range where 80% or more of the metabolic scope (MS) can be maintained, occurred between 19.5 and 32.1 °C. The lower (TCMIN) and upper (TCMAX) critical temperatures occurred at 13.1 °C and 38.8 °C. Nile tilapia showed a 4-fold scope for increasing ventilation frequency from 24 opercular beats min-1 (OB min-1) during SMR at 18 °C, to a maximum of 100 OB min-1 which occurred during MMR at 34 °C. fV during MMR increased with temperature, but above 30 °C became uncoupled with MO2, as fish were unable to sustain their rates of oxygen consumption despite a high fV. There was a strong correlation between fV and SMR (r2 = 0.83) across all temperatures indicating that fV is a good predictor of SMR. However, the correlation between MMR and fV was weak (r2 = 0.06), due to a strong interacting effect of temperature. When selecting data from the thermal optimum range, a good correlation between fV and MO2 was obtained (r2 = 0.74).


[The use of clostridial antigens for a serological and autoradiographical early diagnosis of tumours (author's transl)].
In continuation of the examinations on the usefulness of Cl. oncolyticum M 55 spores reported by Möse new experiments with an auto-radiographical method are plannes. After the isolation, chemical characterization of the cell wall antigens and the exo-antigens and the formation of antibodies, these antibodies should be at first labelled with 125 J and henceforth with 131 J. The iodine-labelled antibodies should allow the diagnosis and localization of the tumours.


High serological response to pneumococcal vaccine in nephrotic children at disease onset on high-dose prednisone.
Our objective was to demonstrate that nephrotic children at disease onset and under high-dose prednisone respond to vaccination with 23-valent pneumococcal vaccine (PV). We compared the serological response after PV in 30 children with nephrotic syndrome, directly after initiation of prednisone therapy (60 mg/m2 body surface area) at disease onset (group 1), with the response in 13 patients who received the vaccine while in remission (group 2). Safety was studied, comparing disease course in group 1 with those in patients who did not receive any PV (group 3). In group 1, 23-valent PV antibody (Ab) levels increased tenfold after 1 month and remained increased after 1 year (P < 0.01). Ab response in the short term and in the long term was not different from that of patients in group 2. Serum albumin, age, or immunosuppressive drugs did not influence Ab response. Disease courses in groups 1 and 3 were not different. In conclusion, nephrotic children on high-dose glucocorticoid therapy respond to a 23-valent anti-PV. Children with steroid dependent/resistant forms acquire high Ab levels, even if early relapses delay the tapering of steroids or if immunosuppressive agents are introduced. Patients who relapse during the tapering of steroids already have increased anti-pneumococcal Ab at the time of relapse.


Comparative study of metals accumulation in cultured in vitro mycelium and naturally grown fruiting bodies of Boletus badius and Cantharellus cibarius.
Cantharellus cibarius Fr. (chanterelle) and Boletus badius Pers. (bay bolete) harvested from natural sites in Poland were used to derive in vitro cultures. The optimal medium composition for cultures was developed. Concentrations of the chosen elements (Zn, Cu, Fe, Mg, Ni, and Cd) in mycelium samples were measured by means of atomic absorption spectrometry. Fe concentration in the analyzed mushroom materials was in the range 215.4-680.3 μg/g dry weight. Mean values of Mg were respectively (in micrograms per gram dry weight) 541.8 for mycelium of C. cibarius cultured in vitro and 1,004.1 for C. cibarius fruiting bodies and 928.9 for the mycelium of B. badius cultured in vitro and 906.4 for B. badius fruiting bodies. The mean concentrations of Zn were 442.7 μg/g dry weight in mycelium from in vitro cultures of B. badius and 172.1 in B. badius fruiting bodies and 131.9 in the case of C. cibarius in mycelium from in vitro cultures and 95.5 for the C. cibarius fruiting bodies. Cu exhibited a reversal tendency, i.e., the element concentrations in naturally grown mushrooms were significantly higher (43.57 μg/g dry weight for C. cibarius and 43.54 μg/g for B. badius) than in cultured in vitro mycelium (12.47 μg/g for C. cibarius and 4.17 μg/g for B. badius). Ni was found in lowest concentrations ranging from 0.33 to 1.88 μg/g dry weight. Toxic metal Cd was found in relatively high concentrations in naturally grown species (0.79 μg/g dry weight-1.02). The lowest was the concentration of Cd in C. cibarius mycelium from in vitro culture-0.06 μg/g dry weight-a bit higher than it was in the B. badius mycelium (0.21 μg/g).


Efficacy and safety of intrapartum electronic fetal monitoring: an update.
To compare the efficacy and safety of routine electronic fetal monitoring (EFM) of labor with intermittent auscultation, using the results of published randomized controlled trials (RCTs). We identified RCTs by searching the MED-LINE data base for the period 1966-1994, contacting experts, and reviewing published references. Our search identified 12 published RCTs addressing the efficacy and safety of EFM; no unpublished studies were found. The studies included 58,855 pregnant women and their 59,324 infants in both high- and low-risk pregnancies from ten clinical centers in the United States, Europe, Australia, and Africa. Data were abstracted, and their accuracy was confirmed independently. A single reviewer assessed study quality based on criteria developed by others for RCTs. Data reported from similar studies were used to calculate a combined risk estimate for each of nine outcomes. Overall, a statistically significant decrease was associated with routine EFM for a 1-minute Apgar score less than 4 (relative risk [RR] 0.82, 95% confidence interval [CI] 0.65-0.98) and neonatal seizures (RR 0.5, 95% CI 0.30-0.82). The protective effect of EFM for a 1-minute Apgar score less than 4 was apparent only in the non-United States studies, and the protective effect for neonatal seizures was evident only in studies with high-quality scores. No significant differences were observed in 1-minute Apgar scores less than 7, rate of admissions to neonatal intensive care units, and perinatal death. An increase associated with the use of EFM was observed in the rate of cesarean delivery (RR 1.33, 95% CI 1.08-1.59) and total operative delivery (RR 1.23, 95% CI 1.15-1.31). Risk of cesarean delivery was greatest in low-risk pregnancies. The only clinically significant benefit from the use of routine EFM was in the reduction of neonatal seizures. Because of the increase in cesarean and operative vaginal deliveries, the long-term benefit of this reduction must be evaluated in the decision reached jointly by the pregnant woman and her clinician to use EFM or intermittent auscultation during labor.


Differences of vascular endothelial growth factor (VEGF) expression between liver and abdominal metastases from colon cancer. Implications for the treatment with VEGF inhibitors.
The vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis, and it is the target of innovative anti-cancer therapies. In colorectal carcinomas, differences in the VEGF expression have been found between the primary tumor and its metastases. We postulated that differences in the VEGF expression may also exist between liver and abdominal metastases from colon cancer. Consecutive colon cancer patients with liver or abdominal metastases were considered eligible for the study. Biopsies had to be performed before chemotherapy and the VEGF analysis were conducted through immunohistochemistry. The staining results were correlated to the metastatic pattern. The study population consisted of 41 patients with a metastatic site in the liver in 19 patients and the abdomen in 22 patients. A positive VEGF staining was found in 19 of the 41 metastatic samples (46%). Cases with positive VEGF expression were found more frequently in abdominal (15 out of 22 patients; 68%) than in liver metastases (4 out of 19 patients; 21%). Also, the degree of VEGF immunoreactivity was significantly higher in abdominal than in liver metastases. Evidence is supported that the VEGF expression may be different between colon cancer metastatic sites. The efficacy of anti-VEGF treatments may depend on the VEGF expression status, and this finding deserves further investigation.


Antioxidant effect of red wine anthocyanins in normal and catalase-inactive human erythrocytes.
Previous studies reported that aged red wine, but not novel red wine or white wine protects human red blood cells from oxidative damage induced in vitro by H(2)O(2.) Here, we demonstrate that the beneficial properties of aged red wine are due, at least in part, to the presence of anthocyanins. We firstly measured the "antioxidant power" of an Italian red wine (Taurasi, Avellino) and that of its anthocyanin fractions by using Ferric Reducing Antioxidant Power Assay. Subsequently, we demonstrate that fractions containing anthocyanins lower ROS (reactive oxygen species) and methemoglobin production in human erythrocytes treated with H(2)O(2.) Finally, we reported that the protective effects of anthocyanins were also confirmed in an experimental model in which RBCs were deprived of catalase activity by treatment with 4 mM sodium azide. The results obtained clearly demonstrate that red wine anthocyanins protect human RBCs from oxidative stress.


Synergistic Effect of Zinc Oxide Nanoparticles and Heat Stress on the Alleviation of Transcriptional Gene Silencing in Arabidopsis thaliana.
Phytotoxicity is an inevitable consideration in evaluating the potential ecological effects of nanoparticles (NPs). Natural ecosystems are complex and accompanied by many other environmental factors. Thus understanding the impact of NPs on plant response to other environmental stresses is crucial to assess the comprehensive toxicity of NPs in ecosystem. In the present study, Arabidopsis thaliana seedlings were cultured in medium containing zinc oxide NPs (ZnO-NPs) then subjected to heat stress at 37°C. Alleviation of transcriptional gene silencing (TGS) in aerial leafy tissues was assessed as an epi-genotoxic endpoint. Results showed that 1 µg/mL ZnO-NPs alone can not alleviate GUS gene (β-glucuronidase) which silenced by TGS (TGS-GUS), but it significantly enhanced heat stress-induced alleviation of TGS-GUS, suggesting an synergistic effect of ZnO-NPs and heat stress on genomic instability. Further study showed that the initiation of synergistic effect could be regulated by plant developmental stage, heat duration and temperature, and heat shock related genes might be involved in.


Adult and infant pharmacokinetic profiling of dihydrocodeine using physiologically based pharmacokinetic modeling.
We previously analysed the serum concentrations of dihydrocodeine in a 1-month-old infant with respiratory depression after being prescribed dihydrocodeine phosphate 2.0 mg/day divided t.i.d. for 2 days. The purpose was to develop a full physiologically based pharmacokinetic (PBPK) model that could account for these and other drug monitoring results. Based on experiments in Caco-2 cell monolayers, the effective permeability of dihydrocodeine in human jejunum was established as 1.28 × 10-4 cm/s. The in vitro Vmax /Km values for dihydrocodeine demethylation mediated by recombinant cytochrome P450 2D6 and 3A4 were 0.19 and 0.066 μl/min/pmol, respectively, and for dihydrocodeine 6-O-glucuronidation mediated by recombinant UGT2B4 and 2B7, the Vmax /Km values were 0.14 and 0.22 μl/min/mg protein, respectively. Renal clearance was calculated as 5.37 L/h on the total clearance value multiplied by the fraction recovered in urine. The reported plasma concentration-time profiles of dihydrocodeine after intravenous administration in healthy volunteers were used to adjust the tissue partitioning ratios. The developed model simulated the pharmacokinetic profiles of dihydrocodeine after single and multiple oral administrations reasonably well in the same population. Subsequently, the validated model was used to simulate pharmacokinetic profiles for five pediatric cases, including the 1-month-old Japanese boy and a 14-year-old Japanese girl who took an overdose of dihydrocodeine phosphate (37 mg). The simulated pharmacokinetic profiles for five virtual pediatric subjects matching the age, gender, and P450 2D6 phenotype of each case approximately reflected the observed values. These results suggested that our dihydrocodeine PBPK model reproduced the results of clinical cases reasonably well for subjects.


Community pharmacist workflow and medication therapy management delegation: An assessment of preferences and barriers.
The role of community pharmacists continues to evolve to meet the changing medication-related needs of patients in the United States, requiring a fundamental shift in the pharmacist's workflow and tasks including medication dispensing and medication therapy management (MTM). To compare community pharmacists' current and idealized time allocation. Barriers to, and potential facilitators of, typical and specific pharmacist functions are also reported, with an emphasis on MTM practices. A secondary objective included interpreting how pharmacists perceived the value of social determinants of health to the MTM process. Community pharmacists practicing in Tennessee were surveyed online with 3 distinct foci: time allocation and delegation, MTM barriers, and the perceived value of health-related and social data to the MTM process. For the first 2 sections, the respondents provided responses in 2 different scenarios: (1) current workflow and (2) an idealized workflow. Paired Wilcoxon signed-rank and chi-square tests compared the responses to workday items, and Spearman correlations assessed the relationships between preferences and perceived barriers. The pharmacists reported spending the largest share of time verifying product (32.8% [SD 19.28]), and most indicated that they spent no time in either point-of-care testing (POCT) or physical patient assessment. In an ideal work environment, more patient-focused roles would be preferred (e.g., health screening, POCT, MTM, and vaccinations), with more than 80% indicating that they would delegate register activities, data entry, and product verification to technicians. In performing MTM, the pharmacists indicated that they would prefer delegating more data collection and patient management activities to technicians to reserve time for patient assessment and care plan creation. Key barriers to MTM included a lack of time, staff support, and patients' willingness to participate. Ideally, pharmacists would prefer to do no prescription filling or selling or register activities. Facilitating community pharmacy practice evolution will require focusing on building teams around support personnel.


Associations between rs965513/rs944289 and papillary thyroid carcinoma risk: a meta-analysis.
Single-nucleotide polymorphisms of rs965513 (9q22.33) and rs944289 (14q13.3) may be involved in the pathogenesis of papillary thyroid carcinoma (PTC). But, relevant genetic studies reported different results. The aim of this meta-analysis was to derive a more precise assessment of the association of rs965513/rs944289 polymorphism with PTC risk. Relevant studies were identified using PubMed, ISI Web of knowledge, Medline, Embase, Google Scholar Search database, SinoMed (Chinese), CNKI (Chinese), GeNii (Japanese) and ICHUSHI (Japanese) (update to December, 2013). A total of eight case-control studies with 52,363 subjects for rs965513 and 51,120 subjects for rs944289 were included. The results showed significant associations of rs965513/rs944289 with PTC risk existed in overall population (for rs965513, A vs. G: OR 1.71 (1.56-1.86); for rs944289, T vs. C: OR 1.29 (1.23-1.37)). Subgroup analysis by ethnicity showed that there were significant associations in Asians (for rs965513, A vs. G: OR 1.48 (1.27-1.73); for rs944289, T vs. C: OR 1.35 (1.18-1.55)), in Europeans (for rs965513, A vs. G: OR 1.74 (1.61-1.88); for rs944289, T vs. C: OR 1.24 (1.14-1.34)), and in Americans (for rs965513, A vs. G: OR 2.00 (1.76-2.27); for rs944289, T vs. C: OR 1.29 (1.14-1.47)). In conclusion, Rs965513 [A] and rs944289 [T] are risk factors of PTC. Effect estimate for rs965513 polymorphism is higher in Americans than in Asians.


Regulatory mechanism of CaMKII δ mediated by RIPK3 on myocardial fibrosis and reversal effects of RIPK3 inhibitor GSK'872.
Myocardial fibrosis (MF) remains a prominent challenge in heart disease. The role of receptor-interacting protein kinase 3 (RIPK3)-mediated necroptosis is evident in the pathogenesis of numerous heart diseases. Concurrently, the activation of Ca2+/calmodulin-dependent protein kinase (CaMKII) is pivotal in cardiovascular disease (CVD). This study aimed to evaluate the impact and underlying mechanisms of RIPK3 on myocardial injury in MF and to elucidate the potential involvement of CaMKII. Building upon our previous research methods [1], wild-type (WT) mice and RIPK3 knockout (RIPK3 -/-) mice underwent random assignment for transverse aortic constriction (TAC) in vivo. Four weeks post-procedure, the MF model was effectively established. Parameters such as the extent of MF, myocardial injury, RIPK3 expression, necroptosis, CaMKII activity, phosphorylation of mixed lineage kinase domain-like protein (MLKL), mitochondrial ultrastructural details, and oxidative stress levels were examined. Cardiomyocyte fibrosis was simulated in vitro using angiotensin II on cardiac fibroblasts. TAC reliably produced MF, myocardial injury, CaMKII activation, and necroptosis in mice. RIPK3 depletion ameliorated these conditions. The RIPK3 inhibitor, GSK'872, suppressed the expression of RIPK3 in myocardial fibroblasts, leading to improved fibrosis and inflammation, diminished CaMKII oxidation and phosphorylation levels, and the rectification of CaMKIIδ alternative splicing anomalies. Furthermore, GSK'872 downregulated the expressions of RIPK1, RIPK3, and MLKL phosphorylation, attenuated necroptosis, and bolstered the oxidative stress response. Our data suggested that in MF mice, necroptosis was augmented in a RIPK3-dependent fashion. There seemed to be a positive correlation between CaMKII activation and RIPK3 expression. The adverse effects on myocardial fibrosis mediated by CaMKII δ through RIPK3 could potentially be mitigated by the RIPK3 inhibitor, GSK'872. This offered a fresh perspective on the amelioration and treatment of MF and myocardial injury.


Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation.
Natriuretic peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMP), but the mechanism of cGMP action is unclear. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP; however, this mechanism is not involved in the action of cGMP on other channels or on Ca2+ channels in other cells. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium. In an electrophysiological study on rat pituitary tumour cells, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems.


Facile synthesis of 2-[(3-aminopropyl)thio]adenosine 5'-diphosphate: a key intermediate for the synthesis of molecular probes of adenosine 5'-diphosphate function.
Adenosine 5'-diphosphate (ADP) and, uniquely, its C-2 derivatized analogues are able to induce platelet activation. We here report the synthesis of 2-[(3-aminopropyl)thio]-ADP from ADP itself via 1,N6-etheno-ADP. 2-[(3-Aminopropyl)thio]-ADP induced platelet aggregation with a potency about one-seventh that of ADP itself and should prove a useful intermediate in the synthesis of other probes of platelet function.