Cleavage stage versus blastocyst stage embryo transfer in assisted conception.
Despite numerous advances in the field of in vitro fertilisation (IVF), many of the widely applied embryo culture techniques and resulting implantation rates have remained relatively unchanged since the first treatment was performed in the mid 1970's. Recent advances in the understanding of nutrient requirements of embryos, have led to a renaissance of extending their culture from the standard procedure of 2-3 days (early cleavage embryo transfer) to 5-6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Numerous reports on the clinical benefits of blastocyst culture have led to the worldwide introduction of this technique, despite a deficiency of conclusive evidence to do so. Primary: To determine if blastocyst stage embryo transfers (ET's) result in higher success rates, than cleavage stage embryo transfers. Secondary: To assess the overall embryo utilisation rate of both techniques. Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information. Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. Of the 29 trials that were identified, ten trials met the inclusion criteria and were reviewed. Primary outcomes were rates of; live birth, clinical pregnancy and implantation per woman. Secondary outcomes were rates of; miscarriage, monozygotic twinning, embryo freezing, embryo utilisation, cancellation, multiple pregnancy and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. There was no significant difference between the two treatment groups in live birth rate, although this was reported by only one quasi-random trial (Peto OR 1.59, 95% CI 0.80, 3.15). There was also no evidence of a difference in pregnancy rate (both overall and subgroups) between the two groups for pregnancy rate per couple randomised (4 RCTs: Peto OR 0.86, 95% CI 0.57, 1.29). There was also no suggestion of an overall difference in implantation rates per embryo's transferred although it was impossible to calculate valid confidence intervals from published data (Day 2/3 17.1% vs Day 5/6 18.9%). The subgroup of sequential media trials suggested higher implantation rate for blastocyst transfer (Day 2/3 22.6% vs Day 5/6 32%). The miscarriage rate was no different between the two groups (1 RCT, Peto OR 1.66, 95% CI 0.41, 6.81). The RCTs reporting embryo freezing showed no difference (Peto OR 1.71, 95% CI 1.00, 2.94), however the two quasi-random trials showed a significant difference in favour of the Day 2/3 group (Peto OR 2.99, 95% CI 1.88, 4.75). Embryo transfer cancellation rates were significantly higher in the Day 5/6 group (5 RCTs: Peto OR 0.57, 95% CI 0.40, 0.83). There was no significant difference in the rate of multiple pregnancies or the rate of high order pregnancies (3 RCTs, Peto OR 0.58, 95% CI 0.30, 1.12)(2 RCTs, Peto OR 7.88, 95% CI 0.49, 126.30 respectively). Overall this review of the best available evidence based on data from randomised controlled trials, suggests that to date little difference in the major outcome parameters has been demonstrated between early embryo transfer and blastocyst culture. Collectively, the increase in cancellation and the possible decrease in cryopreservation rates suggest that the routine practice of blastocyst culture should be offered to patients with caution. The subgroup of trials employing sequential media, did however demonstrate a substantial improvement in implantation rates and similar pregnancy rates, despite the transfer of less embryos. Whether this trend will culminate in convincing higher live birth rates per woman, has yet to be validated.


[Clinical value of TS90% in evaluation of hypoxemia in patients with obstructive sleep apnea/hypoventilation syndrome].
To explore the appropriate study how to properly evaluate the hypoxemia degree in patients with obstructive sleep apnea/hypoventilation syndrome (OSAHS). polysomnography was conducted on 108 OSAHS patients and 37 simple snorers to record the minimum oxygen saturation level (MiO(2)) and the total recorded time spent below 90% oxygen saturation (TS90%). The correlation between MiO(2) and the percent of the total recorded time spent below 90% oxygen saturation (TS90%) with the AHI were calculated. The value of TS90% was significantly increased, and the value of MiO(2) was significantly decreased as the severity of OSAHS increased (all P < 0.001). The correlation coefficients of TS90% with AHI and with Epworth sleepiness scale (ESS) were both much higher than those of MiO(2). TS90% can express the severity of hypoxemia of the OSAHS patients more correctly than MiO(2). TS90% combined with MiO(2) can comprehensively and objectively reflect the severity of hypoxia of the OSAHS patients.


iso-caracurine V, a novel unexpected decomposition product of caracurine V.
The structure of iso-caracurine V (3), an unexpected decomposition product of the Strychnos alkaloid caracurine V (1), was determined by NMR spectroscopy. Compound 3, which was probably previously regarded as bisnortoxiferine I (2), is a one-sided ring closed product of 2.


Screening of putative oxygenase genes in the Fusarium graminearum genome sequence database for their role in trichothecene biosynthesis.
In the biosynthesis of type B trichothecenes, four oxygenation steps remain to have genes functionally assigned to them. On the basis of the complete genome sequence of Fusarium graminearum, expression patterns of all oxygenase genes were investigated in Fusarium asiaticum (F. graminearum lineage 6). As a result, we identified five cytochrome P450 monooxygenase (CYP) genes that are specifically expressed under trichothecene-producing conditions and are unique to the toxin-producing strains. The entire coding regions of four of these genes were identified in F. asiaticum. When expressed in Saccharomyces cerevisiae, none of the oxygenases were able to transform trichodiene-11-one to expected products. However, one of the oxygenases catalyzed the 2beta-hydroxylation rather than the expected 2alpha-hydroxylation. Targeted disruption of the five CYP genes did not alter the trichothecene profiles of F. asiaticum. The results are discussed in relation to the presence of as-yet-unidentified oxygenation genes that are necessary for the biosynthesis of trichothecenes.


Parapharyngeal abscess associated with the second pharyngeal pouch.
Peritonsillar or parapharyngeal abscess is not at all a rare disease. Usually the abscess is recognized as the underlying consequence of acute tonsillitis. However, the abscess may be caused by an internal fistula related to the second pharyngeal pouch. Presented here are the clinical, radiological and pathological aspects of an internal fistula with a parapharyngeal abscess related to the second pharyngeal pouch.


Expanding the role of PAs in the treatment of severe and persistent mental illness.
Patients with severe and persistent mental illness often face limited access to psychiatric and primary care. This exploratory qualitative analysis studied the effect of introducing a PA into a comprehensive outpatient psychiatric team. Early results suggest this model improves the quality and access to primary and psychiatric care.


Regulation of canine jejunal transit.
The aim of this study was to determine what factors influence the direction of movement of canine jejunal chyme. In four dogs, pacing electrodes were implanted near each end of a 50-cm jejunal Vella loop, while recording electrodes and intraluminal pressure catheters were spaced along the loop. After recovery, the loop was perfused from either the proximal stoma (forward flow) or the distal stoma (reversed flow), and effluent was collected from the nonperfused stoma. The pacesetter potentials were paced electrically in a forward (aborad) or a reverse (orad) direction. During control conditions (forward flow-forward pacing), the mean transit time of liquids was 2.6 +/- 0.1 min (mean +/- SE) and the static volume of the loop was 8.8 +/- 0.3 ml. Reversing both direction of flow and direction of pacesetter potential propagation slowed transit (4.4 +/- 0.4 min; P less than 0.05) and increased loop volume (16.0 +/- 1.0 ml; P less than 0.01). Reversing flow with forward pacing resulted in even slower transit (7.5 +/- 1.2 min; P less than 0.05), maintained a large volume (33 +/- 10 ml), and increased basal pressure in the loop from -1.2 +/- 1.7 (control) to 2.3 +/- 1.6 mmHg (P less than 0.05). These observations suggest that the direction of propagation of jejunal pacesetter potentials influences the direction of movement of jejunal chyme but that other factors have a role as well.


The effects of model selection on confidence intervals for the size of a closed population.
One encounters in the literature estimates of some rates of genetic and congenital disorders based on log-linear methods to model possible interactions among sources. Often the analyst chooses the simplest model consistent with the data for estimation of the size of a closed population and calculates confidence intervals on the assumption that this simple model is correct. However, despite an apparent excellent fit of the data to such a model, we note here that the resulting confidence intervals may well be misleading in that they can fail to provide an adequate coverage probability. We illustrate this with a simulation for a hypothetical population based on data reported in the literature from three sources. The simulated nominal 95 per cent confidence intervals contained the modelled population size only 30 per cent of the time. Only if external considerations justify the assumption of plausible interactions of sources would use of the simpler model's interval be justified.


Analysis of CO2 adsorption in different lytotypes of lignite.
The problem of reducing CO2 emissions in the atmosphere is indirectly related to the potential storage options in different environments in the earth's crust. One of the promising possibilities for reducing emissions of carbon dioxide (CO2) into the atmosphere is the geological storage of CO2 in deep, unminable coal seams. Measurements of the CO2 adsorption of 10 lignite samples from the Velenje Coal Mine and different rocks and soils from surrounding areas were carried out using Langmuir isotherm principles. Adsorption measurements were taken using the gravimetric method, where exposed samples at a selected temperature to different CO2 pressures were done. Also, the measures of mass changes in the measuring and reference cells were the basis of calculations for the mass and volume of the adsorbed CO2. Measurements were taken at a temperature of 23 degrees C and at CO2 pressures varying from 18 to 38 bars. The results of laboratory investigations of the lignite from the Velenje Coal Mine have shown the capacity adsorption from 9 to 14 m3 CO2/ton (at measuring pressures up to 4 MPa) of coal in the given conditions, which cannot compare with other rocks and soils.


Screening for breast cancer: current recommendations and future directions.
Breast cancer is one of the most significant health concerns in the United States. Recent reviews have questioned the value of traditional breast cancer screening methods. Breast self-examination has been shown not to improve cancer-specific or all-cause mortality in large studies, but it is commonly advocated as a noninvasive screen. Patients who choose to perform self-examination should be trained in appropriate technique and follow-up. The contribution of the clinical breast examination to early detection is difficult to determine, but studies show that sensitivity is highly dependent on time taken to do the examination. Up to 10 percent of cancers are mammographically silent but evident on clinical breast examination. The U.S. Preventive Services Task Force recommends mammography for women older than 40 years who are in good health, but physicians should consider that sensitivity is lower for younger women. Digital mammography is somewhat more sensitive in younger women and women with dense breasts, but outcome studies are lacking. Although magnetic resonance imaging shows promise as a screening tool in some high-risk women, it is not currently recommended for general screening because of high false-positive rates and cost. The American Cancer Society recommends annual magnetic resonance imaging as an adjunct to screening mammography in high-risk women 30 years and older.


The hyperthermic phase of histamine action in rats.
Intracerebroventricular injections of histamine in rats at ambient temperature of 32 degrees C induced a hyperthermic response, but depressed the body temperature at low and room temperatures. Agonists of H1 receptors caused hyperthermia at all ambient temperatures studied (9, 22 and 32 degrees C). The action of histamine and of H1 receptor agonists was inhibited by mepyramine and abolished by sodium salicylate. The involvement of both H1 receptors and prostaglandins in hyperthermia is suggested.


[Innovation in pharmaceutical and health biotechnology industries: challenges for a virtuous agenda].
Pharmaceutical and biotechnology industries comprise a major production subsystem of the health industrial complex in Brazil. It stands out for both its economic importance and its prominent role in developing new technologies in strategic areas. Strengthening the local production of generic drugs in the last decade has significantly increased the number of Brazilian companies in the local pharmaceutical market and has been an important turning point for this industry's growth. However, there remain major structural bottlenecks both in terms of production and continuous innovation. These bottlenecks reveal the high vulnerability of the Brazilian National Health System and point to the need of public policies that promote strengthening the production base and innovation in the pharmaceutical industry and that at the same time meet health-related social demands in health in Brazil.


DNA sequencing reveals AMELX, ODAM and MMP20 variations in dental fluorosis.
Dental fluorosis (DF) is a dental development disorder caused by chronic fluoride overconsumption. There are differences in the susceptibility to and severity of DF in studied populations. The objective of the present study was to determine if single-nucleotide variations (SNVs) in the genes Amelogenin (AMELX), Odontogenic Ameloblast Associated (ODAM) and Matrix Metalloproteinase 20 (MMP20) are associated with DF by evaluating the relationship between variations in these genes and the degree of DF severity. Schoolchildren from two regions of Durango State and Mexico City, Mexico, were studied. The DF phenotype was determined using the Thylstrup and Fejerskov (TF) index. DNA was obtained from the buccal mucosa of each participant, and the presence of the variations rs946252 in AMELX, rs1514392 in ODAM and rs1784418 in MMP20 was determined by bidirectional DNA sequencing. A total of 180 DNA samples from 30 schoolchildren from 2 areas of Durango State were sequenced and analyzed. Differences in the severity of DF were found between the study areas (p = 0.006). SNVs in theMMP20 gene were present in 76.9 % of the participants in the high fluoride concentration and lower DF severity area. AMELX and ODAM variations was not different between the two populations with respect to DF severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF and may serve as a protective marker.


[Proper use of antibiotics--what is that?].
Antibiotics are one of the cornerstones of modern medicine. During the last 20 years there has been an alarming world-wide spread of multiple-resistant bacteria. One of the main reasons is the overuse of all types of antibiotics, especially broad-spectrum drugs. This paper gives general advice on antibiotic therapy in Norway. We adovcate the use of drugs with little ecological impact, such as the penicillins. Whenever possible, empiric treatment with macrolides, tetracyclines cefalosporines, imipenem and fluoroquinolones should be avoided.


Personal, situational and organizational aspects that influence the impact of patient safety incidents: A qualitative study.
When a patient safety incident (PSI) occurs, not only the patient, but also the involved health professional can suffer. This study focused on this so-called "second victim" of a patient safety incident and aimed to examine: (1) experienced symptoms in the aftermath of a patient safety incident; (2) applied coping strategies; (3) the received versus needed support and (4) the aspects that influenced whether one becomes a second victim. Thirty-one in-depth interviews were performed with physicians, nurses and midwives who have been involved in a patient safety incident. The symptoms were categorized under personal and professional impact. Both problem focused and emotion focused coping strategies were used in the aftermath of a PSI. Problem focused strategies such as performing a root cause analysis and the opportunity to learn from what happened were the most appreciated, but negative emotional responses such as repression and flight were common. Support from colleagues and supervisors who were involved in the same event, peer supporters or professional experts were the most needed. A few individuals described emotional support from the healthcare institution as unwanted. Rendered support was largely dependent on the organizational culture, a stigma remained among healthcare professionals to openly discuss patient safety incidents. Three aspects influenced the extent to which a healthcare professional became a second victim: personal, situational and organizational aspects. These findings indicated that a multifactorial approach including individual and emotional support to second victims is crucial.


Identification of candidates for coronary artery bypass grafting admitted with STEMI and Multivessel Disease.
The optimal management of patients with multivessel coronary artery disease (MVD) admitted with STEMI is under debate. CABG is rarely performed, even on ideal candidates. A provisional PCI without stent implantation may allow complete surgical revascularization (CSR) in a subset of patient that we sought to identify in this study. Patients with STEMI from April 2014 to October 2016 were evaluated and those with a TIMI flow <3 in the culprit vessel, and an additional stenosis of >70% in an epicardial vessel or sidebranch >2.5 mm were selected. Epidemiological variables, surgical risk scores and SYNTAX and SYNTAX II scores were analyzed. All the selected patients were discussed in a post hoc heart-team, and predictors of 12-month events were also analyzed. Seventy-two (19.0%) accomplished MVD criteria. Mean SYNTAX was 19 ± 13 points and SYNTAX II score recommended CABG in 12 patients (16.7%) and heart-team discussion in 60 (83.3%). All patients were discussed in a post hoc heart-team, which concluded that 21 (29.2%) patients could have been good candidates for CSR. After one year follow-up, SYNTAX II PCI > 40 was found to be the sole independent predictor for 12-month events (OR 12.9 [2.7-62.1], p = 0.001). MVD and STEMI with a SYNTAX II PCI > 40 should be discussed in an ad-hoc heart team, after a provisional revascularization of the culprit vessel, and should be considered for CSR, especially when the RCA is the culprit artery and there is a complex disease in the left coronary artery.


Nicotine withdrawal and dependence among smokers with a history of childhood abuse.
Previous studies have found that those with a history of childhood abuse are more likely to smoke cigarettes than those without a history of abuse. Mechanisms underlying this greater prevalence are unclear. We examined whether current smokers with a history of childhood abuse reported greater levels of nicotine dependence and more severe nicotine withdrawal symptoms. We analyzed data from a 2-wave, national, random-digit-dial survey of adult cigarette smokers (n = 751). We examined whether childhood physical, emotional, and sexual abuse were associated with greater levels of nicotine dependence. Among those who made a quit attempt (n = 368), we examined whether abuse was associated with more severe withdrawal symptoms recalled during the 14 months between surveys. For both dependence and withdrawal, we tested a mediation pathway through current serious mental illness (SMI). All 3 types of childhood abuse were associated with more severe withdrawal symptoms. These associations were partially mediated by SMI. Sexual abuse and physical abuse were directly associated with dependence, whereas emotional abuse was indirectly associated with dependence through SMI. All 3 forms of childhood abuse were associated with both dependence and withdrawal. The greater prevalence of smoking found among those with a history of childhood abuse may be explained by heightened vulnerability to nicotine dependence and withdrawal and may be partially due to comorbid mental illness.


Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma.
Patients with T-cell lymphomas face a poorer prognosis compared with patients with B-cell lymphomas. New therapeutic approaches need to be developed to improve outcomes for these patients. Forty patients with recurrent and refractory T-cell lymphomas other than mycosis fungoides and patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy were prescribed oral lenalidomide at a dose of 25 mg daily on days 1 to 21 of each 28-day cycle, with standardized dose reductions for toxicity. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete and partial response rates, progression-free survival (PFS), overall survival (OS), and safety. The authors also determined duration of response (DoR). A total of 40 patients were enrolled in the current study; 1 patient was subsequently deemed ineligible. The ORR was 10 of 39 patients (26%); 3 patients (8%) achieved complete responses and 7 patients achieved partial responses. Three patients had stable disease for ≥5 cycles. The median OS was 12 months (range <1 month to ≥69 months), the median PFS was 4 months (range, <1 month to ≥50 months), and the median DoR was 13 months (range 2 months to ≥37 months), including 5 responses that lasted >1 year. Toxicity was in keeping with the known safety profile of lenalidomide. Among the patients who had recurrent/refractory peripheral T-cell lymphoma (29 patients), the ORR was 24%, the median OS was 12 months, the median PFS was 4 months, and the median DoR was 5 months (range, 2 months to ≥37 months). In the current study, the use of oral lenalidomide monotherapy demonstrated clinically relevant efficacy among patients with systemic T-cell lymphomas. It appears to have excellent potential as an agent in combination therapy for patients with T-cell lymphoma.


Abnormalities in the structural covariance of emotion regulation networks in major depressive disorder.
Major depressive disorder (MDD) is a common psychiatric disorder that is characterized by cognitive deficits and affective symptoms. To date, an increasing number of neuroimaging studies have focused on emotion regulation and have consistently shown that emotion dysregulation is one of the central features and underlying mechanisms of MDD. Although gray matter morphological abnormalities in regions within emotion regulation networks have been identified in MDD, the interactions and relationships between these gray matter structures remain largely unknown. Thus, in this study, we adopted a structural covariance method based on gray matter volume to investigate the brain morphological abnormalities within the emotion regulation networks in a large cohort of 65 MDD patients and 65 age- and gender-matched healthy controls. A permutation test with p < 0.05 was used to identify the significant changes in covariance connectivity strengths between MDD patients and healthy controls. The structural covariance analysis revealed an increased correlation strength of gray matter volume between the left angular gyrus and the left amygdala and between the right angular gyrus and the right amygdala, as well as a decreased correlation strength of the gray matter volume between the right angular gyrus and the posterior cingulate cortex in MDD. Our findings support the notion that emotion dysregulation is an underlying mechanism of MDD by revealing disrupted structural covariance patterns in the emotion regulation network.


AVI-7288 for Marburg Virus in Nonhuman Primates and Humans.
AVI-7288 is a phosphorodiamidate morpholino oligomer with positive charges that targets the viral messenger RNA that encodes Marburg virus (MARV) nucleoprotein. Its safety in humans is undetermined. We assessed the efficacy of AVI-7288 in a series of studies involving a lethal challenge with MARV in nonhuman primates. The safety of AVI-7288 was evaluated in a randomized, multiple-ascending-dose study in which 40 healthy humans (8 humans per dose group) received 14 once-daily infusions of AVI-7288 (1 mg, 4 mg, 8 mg, 12 mg, or 16 mg per kilogram of body weight) or placebo, in a 3:1 ratio. We estimated the protective dose in humans by comparing pharmacokinetic variables in infected nonhuman primates, uninfected nonhuman primates, and uninfected humans. Survival in infected nonhuman primates was dose-dependent, with survival rates of 0%, 30%, 59%, 87%, 100%, and 100% among monkeys treated with 0 mg, 3.75 mg, 7.5 mg, 15 mg, 20 mg, and 30 mg of AVI-7288 per kilogram, respectively (P<0.001 with the use of the log-rank test for the comparison of survival across groups). No safety concern was identified at doses up to 16 mg per kilogram per day in humans. No serious adverse events were reported. Drug exposure (the area under the curve) was dose-dependent in both nonhuman primates and humans; drug clearance was independent of dose but was higher in nonhuman primates than in humans. The protective dose in humans was initially estimated, on the basis of exposure, to be 9.6 mg per kilogram per day (95% confidence interval, 6.6 to 12.5) for 14 days. Monte Carlo simulations supported a dose of 11 mg per kilogram per day to match the geometric mean protective exposure in nonhuman primates. This study shows that, on the basis of efficacy in nonhuman primates and pharmacokinetic data in humans, AVI-7288 has potential as postexposure prophylaxis for MARV infection in humans. (Funded by the Department of Defense; ClinicalTrials.gov number, NCT01566877.).


Parent and adolescent knowledge of HPV and subsequent vaccination.
Human papillomavirus (HPV) vaccination has been shown to have important health benefits, but vaccination rates are low. Parental and adolescent knowledge could possibly promote vaccination, but the relationship between knowledge and subsequent vaccination is unclear. This study examines how strongly HPV vaccination among high-risk adolescents is related to their or their parents' previous knowledge. A longitudinal cohort study enrolled participants from low-income, predominantly African American neighborhoods. Baseline questionnaires measuring knowledge of HPV and HPV vaccination, as well other variables, were completed by 211 adolescents and 149 parents of another adolescent sample. Adolescent vaccination was tracked prospectively for 12 months after baseline by using clinic reporting data. Analyses tested if parent or adolescent knowledge was associated with or predictive of adolescent HPV vaccination. On average, parents and adolescents answered slightly less than 50% of knowledge items correctly at baseline, with 5% of parents and 10% of adolescents not answering any knowledge items correctly. Within 12 months, 20 of 149 (13.4%) of the parents' daughters received an HPV vaccination and 32 of 211 (15.2%) of the other adolescent sample did so. Neither parental nor adolescent knowledge was associated with or predictive of adolescent vaccination. For example, when testing the relationship between adolescent vaccination and parental knowledge scores, all R(2) values were <0.005. Results were independent of available potential confounders. Those with higher levels of knowledge were not more likely to obtain vaccination for themselves or their daughters. Ideally, future interventions will target factors related to vaccination.


Kinetics and mechanism of erythrocyte anion exchange.
Steady state velocities for the rate of exchange of extracellular dithionite for intracellular sulfate through the red cell inorganic anion transport protein, known as band 3, were measured at increasing trans-sulfate concentrations at constant cis-sulfate concentration in order to directly discriminate between single and double displacement classes of mechanism. A 7-fold increase in trans-sulfate concentration resulted in intersecting Lineweaver-Burk plots under iso-osmotic conditions. This result argues against a double displacement or ping-pong mechanism. The specificity of the trans-anion effect for band 3 was illustrated by studying reversible 4-acetamido-4'-isothiocyano-2,2'-stilbene disulfonate inhibition of anion exchange. The increase in trans-sulfate increased 4-acetamido-4'-isothiocyano-2,2'-stilbene disulfonate affinity at the outer surface by about 4-fold under conditions where outside anion concentration was constant. A possible two-site ordered sequential mechanism for erythrocyte inorganic anion exchange is briefly discussed.


Characterization of nucleotide-free uncoating ATPase and its binding to ATP, ADP, and ATP analogues.
The interactions of the 70-kDa heat-shock proteins (hsp70s) with their protein substrates appear to be regulated by bound nucleotide. Previous work has shown that the nucleotide binding site of the bovine brain uncoating ATPase, a constitutive member of the hsp70 family, crystallographically resembles the nucleotide binding site of actin and, like actin, the uncoating ATPase has a strongly bound ADP which cannot be removed by dialysis or treatment with ethylenediaminetetraacetic acid (EDTA). This suggests that, like the bound nucleotide of actin, it may be required for the enzyme to retain its native structure. In this study, the strongly bound ADP was removed by first replacing it with 5'-adenylyl imidodiphosphate (AMP-PNP) and then removing the bound AMP-PNP by dialysis. Following this treatment, more than 95% of the uncoating ATPase becomes nucleotide-free. The nucleotide-free uncoating ATPase retains its ability to bind and hydrolyze ATP and to uncoat clathrin-coated vesicles, even after 10 days of storage at 4 degrees C. Therefore, in contrast to actin, the bound nucleotide of the uncoating ATPase is not required to prevent denaturation of the enzyme. Using nucleotide-free uncoating ATPase, we were able to accurately measure the dissociation constants of ATP, ADP, and the nucleotide analogues AMP-PNP and 2'-deoxyadenosine 5'-triphosphate (dATP). The dissociation constants of both ATP and ADP are about 10(-8) M, more than 1-2 orders of magnitude stronger than previously reported, while AMP-PNP and dATP bind 2-3 orders of magnitude more weakly than ATP.


Differential mechanisms of Ca(2+) release from vascular smooth muscle cell microsomes.
The release of Ca(2+) from intracellular stores is a fundamental element of signaling pathways involved in regulation of vascular tone, proliferation, apoptosis, and gene expression. Studies of sea urchin eggs have led to the identification of three functionally distinct Ca(2+) signaling pathways triggered by IP3, cADPR, and NAADP. The coexistence and functional relevance of these distinct intracellular Ca(2+) release systems has only been described in a few mammalian cell types. The purpose of this study was to determine whether the IP3, cADPR, and NAADP Ca(2+) release systems coexist in smooth muscle cells (SMC) and to determine the specificity of these intracellular Ca(2+) release pathways. Microsomes were prepared from rat aortic SMC (VSMC) and were loaded with 45Ca(2+). cADPR, NAADP, and IP3 induced Ca(2+) release from VSMC microsomes in a dose-dependent fashion. Heparin blocked only IP3-mediated Ca(2+) release, whereas the ryanodine channel inhibitors 8-Br-cADPR and ruthenium red blocked only cADPR-induced Ca(2+) release. Nifedipine, an L-type Ca(2+) channel blocker, inhibited NAADP elicited Ca(2+) release, but had no effect on IP3- or cADPR-mediated Ca(2+) release. An increase in pH from 7.2 to 8.2 inhibited cADPR-mediated Ca(2+) release, but had no effect on IP3- or NAADP-induced Ca(2+) release. By RT-PCR, VSMC expressed ryanodine receptor types 1, 2, and 3. Ca(2+)-dependent binding of [3H]-ryanodine to VSMC microsomes was enhanced by the ryanodine receptor agonists 4-chloro-methyl-phenol (CMP) and caffeine, but was inhibited by ruthenium red and cADPR. We conclude that VSMC possess at least three functionally distinct pathways that promote intracellular Ca(2+) release. IP3-, cADPR-, and NAADP-induced intracellular Ca(2+) release may play a critical role in the maladaptive responses of VSMC to environmental stimuli that are characteristically associated with hypertension and/or atherogenesis.


European position paper on drug-induced sedation endoscopy (DISE).
Although drug-induced sedation endoscopy (DISE) represents the most widespread diagnostic tool for upper airway endoscopic evaluation of snoring and obstructive sleep apnea hypopnea syndrome (OSAHS), many controversies exist about how to perform the sedation, the indications for DISE, and how to report DISE findings. The present position paper reports on a consensus as proposed by a group of European experts in the field of DISE after discussion during a recent dedicated meeting. The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centers in order to provide a standardization of the DISE procedure and an in-depth insight in the main aspects of this technique. A proposal of the DISE procedure standardization has been achieved with a general agreement concerning the terminology, indications, contraindications, required preliminary examinations, setting, technical equipment required, staffing, local anesthesia and nasal decongestion, patient positioning, basis and special diagnostic maneuvers, and the applied sedation drugs and observation windows. Otherwise, no consensus has been reached on a scoring and classification system. Although consensus has been reached on several aspects of the DISE procedure, some topics remain open to future research, such as a better analysis of the importance of positional aspects during DISE and a further comparison of the differences in degree, level and pattern of upper airway collapse observed during DISE versus during natural sleep and awake endoscopy. Finally, a universally accepted scoring and classification system is lacking.


[Polyacrylamide gel electrophoresis of proteins of Anomalocers patersoni (Copepods, Pontellidea) and evidence for esterase activity. Elements of biochemical sexual dimorphism].
Electrophoresis on polyacrylamide gel of total proteins and esterases of the Copepod Anomalocera patersoni shows the existence of intraspecific variability. Some of these variations represent sexual differences which are an expression of a biochemical sexual dimorphism.


A Survey of Injuries Affecting Pre-Professional Ballet Dancers.
A cross-sectional design was employed retrospectively to evaluate injuries self-reported by 71 pre-professional ballet dancers over one season. Some of the descriptive findings of this survey were consistent with those of previous research and suggest particular demographic and injury trends in pre-professional ballet. These results include gender distribution, mean age and age range of participants, training hours, injury location, acute versus overuse injuries, as well as average number of physiotherapy treatments per dancer. Other results provide information that was heretofore unreported or inconsistent with previous investigations. These findings involved proportion of dancers injured, average number of injuries per dancer, overall injury incidence during an 8.5 month period, incidence rate by technique level, mean time loss per injury, proportion of recurrent injury, and activity practiced at time of injury. The results of univariate analyses revealed several significant findings, including a decrease in incidence rate of injury with increased months of experience in the pre-professional program, dancers having lower injury risk in rehearsal and performance than in class, and a reduced risk of injury for dancers at certain technique levels. However, only this latter finding remained significant in multivariate analysis. The results of this study underscore the importance of determining injury rates by gender, technique level, and activity setting in addition to overall injury rates. They also point to the necessity of looking at both overall and individual dancer-based injury risks.


Structures of silicon cluster cations in the gas phase.
We present gas-phase infrared spectra for small silicon cluster cations possessing between 6 and 21 atoms. Infrared multiple photon dissociation (IR-MPD) of these clusters complexed with a xenon atom is employed to obtain their vibrational spectra. These vibrational spectra give for the first time experimental data capable of distinguishing the exact internal structures of the silicon cluster cations. By comparing the experimental spectra with theoretical predictions based on density functional theory (DFT), unambiguous structural assignments for most of the Si(n)(+) clusters in this size range have been made. In particular, for Si(8)(+) an edge-capped pentagonal bypriamid structure, hitherto not considered, was assigned. These structural assignments provide direct experimental evidence for a cluster growth motif starting with a pentagonal bipyramid building block and changing to a trigonal prism for larger clusters.


Solitary pancreatic metastasis occurring 20 years after nephrectomy for carcinoma of the kidney.
This report describes a case observed in December 1983: a woman who underwent right nephrectomy in 1963 for kidney carcinoma, developed a solitary metastasis to the pancreas, and was operated on again. She is disease free more than one year after.


[Budd-Chiari syndrome: a contribution to surgical therapy].
The commonest cause of Budd-Chiari syndrome is stenosis of the inferior vena cava and hepatic veins. Improved venous draining can be achieved by resection of a dorso-cranial portion of the liver and the anterior aspect of the vena cava wall. A complex case is reported.


Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development.
Epithelial-mesenchymal transitions (EMTs) are an important mechanism for reorganizing germ layers and tissues during embryonic development. They have both a morphogenic function in shaping the embryo and a patterning function in bringing about new juxtapositions of tissues, which allow further inductive patterning events to occur [Genesis 28 (2000) 23]. Whereas the mechanics of EMT in cultured cells is relatively well understood [reviewed in Biochem. Pharmacol. 60 (2000) 1091; Cell 105 (2001) 425; Bioessays 23 (2001) 912], surprisingly little is known about EMTs during embryonic development [reviewed in Acta Anat. 154 (1995) 8], and nowhere is the entire process well characterized within a single species. Embryonic (developmental) EMTs have properties that are not seen or are not obvious in culture systems or cancer cells. Developmental EMTs are part of a specific differentiative path and occur at a particular time and place. In some types of embryos, a relatively intact epithelium must be maintained while some of its cells de-epithelialize during EMT. In most cases de-epithelialization (loss of apical junctions) must occur in an orderly, patterned fashion in order that the proper morphogenesis results. Interestingly, we find that de-epithelialization is not always necessarily tightly coupled to the expression of mesenchymal phenotypes.Developmental EMTs are multi-step processes, though the interdependence and obligate order of the steps is not clear. The particulars of the process vary between tissues, species, and specific embryonic context. We will focus on 'primary' developmental EMTs, which are those occurring in the initial epiblast or embryonic epithelium. 'Secondary' developmental EMT events are those occurring in epithelial tissues that have reassembled within the embryo from mesenchymal cells. We will review and compare a number of primary EMT events from across the metazoans, and point out some of the many open questions that remain in this field.


Photosynthesis of ATP-electrons, proton pumps, rotors, and poise.
Light-driven electron transport is coupled to ATP synthesis in chloroplasts. While the nature of the coupling and the structures of key components are now known, there has long been disagreement over pathways of electron transport. Recent results now put an old idea back on the agenda-cyclic electron transport around photosystem I.


Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection.
Phagocytosis, bactericidal capacity and some selected parameters of oxygen-dependent bactericidal mechanisms were evaluated in 20 patients with type 2 diabetes being in similar (intermediate) state of metabolic control and in 15 healthy individuals. Polymorphonuclear neutrophils (PMNs) from diabetics showed normal ability to phagocytose staphylococci, a decreased Intracellular bacteria killing, the impaired stimulated superoxide anion (O2-) and hydrogen peroxide (H2O2) production and the low intracellular myeloperoxidase activity. The obtained data seem to indicate that the decreased bacterial killing by PMNs isolated from diabetics are partly at least related to an impairment of the oxygen-dependent bactericidal mechanisms. Since none of the diabetic patients suffered from recurrent infection the clinical significance of our finding is still uncertain.


How meta-analytic evidence impacts clinical decision making in oral implantology: a Delphi opinion poll.
To investigate the impact of meta-analytic evidence in scientific literature on clinical decision making in the field of oral implantology. A Delphi opinion poll was performed at the meeting of the "Next Generation" Committees of the Austrian, German and Swiss Societies for Implantology (ÖGI, DGI and SGI). First, the experts gave their opinion on 20 questions regarding routine implant treatment (uninformed decisions), then they were confronted with up-to-date Level I evidence from scientific literature on these topics and again asked to give their opinion (informed decisions) as well as to rate the available evidence as satisfactory or insufficient. Topics involved surgical issues, such as immediate implant placement, flapless surgery, tilted and short implants and bone substitute materials, as well as opinions on prosthodontic paradigms, such as immediate loading, abutment materials and platform switching. Compared to their uninformed decisions prior to confrontation with recent scientific literature, on average, 37% of experts (range: 15-50%) changed their opinion on the topic. When originally favoring one treatment alternative, less than half were still convinced after review of meta-analytic evidence. Discrepancy between uninformed and informed decisions was significantly associated with insufficient evidence (P = 0.014, 49% change of opinion vs. 26% on topics rated as sufficiently backed with evidence). Agreement regarding strength of evidence could be reached for eight topics (40%), in three issues toward sufficiency and in five issues toward lack of evidence. Confrontation with literature results significantly changes clinical decisions of implantologists, particularly in cases of ambiguous or lacking meta-analytic evidence.


A differentiation stage-specific factor interacts with mouse carbonic anhydrase form I gene and a conserved sequence in mammalian beta-globin genes.
We have identified in mouse erythroleukemic (MEL) cells a novel factor which binds to the 3' flanking region of beta-globin genes. Upon induction, this DNA binding factor disappears as beta-globin gene transcription increases. The factor protects 20-30 base pairs (bp) of a sequence which is tightly conserved in beta-globin genes including chicken, human, mouse and rabbit. A very similar sequence binds the factor in the mouse carbonic anhydrase form I gene, whose transcription diminishes upon induction of MEL cells. The factor, or a closely related form, is detected in nonerythroid cells and binding sites have been detected in other genes, including c-myb and immunoglobulin heavy chain-enhancer. We suggest that this factor could play a role in determining the timing of gene expression in several differentiating cell types.


Delayed gratification: A grey parrot (Psittacus erithacus) will wait for a better reward.
Delay of gratification, the ability to forgo an immediate reward to gain either better quality or quantity, has been used as a metric for temporal discounting, self-control, and the ability to plan for the future in both humans (particularly children) and nonhumans. The task involved can be parsed in several ways, such that the subjects can be required to wait, not only for a better or a larger reward, but also such that the rewards can either be in view or hidden during the delay interval. We have demonstrated that a Grey parrot (Psittacus erithacus) trained in the use of English speech could respond to the label "wait" for up to 15 min, in a task that has many similarities to those used with young children, to receive a better quality reward, whether or not the better quality reward or the experimenter was in view.


The content validity index: are you sure you know what's being reported? Critique and recommendations.
Scale developers often provide evidence of content validity by computing a content validity index (CVI), using ratings of item relevance by content experts. We analyzed how nurse researchers have defined and calculated the CVI, and found considerable consistency for item-level CVIs (I-CVIs). However, there are two alternative, but unacknowledged, methods of computing the scale-level index (S-CVI). One method requires universal agreement among experts, but a less conservative method averages the item-level CVIs. Using backward inference with a purposive sample of scale development studies, we found that both methods are being used by nurse researchers, although it was not always possible to infer the calculation method. The two approaches can lead to different values, making it risky to draw conclusions about content validity. Scale developers should indicate which method was used to provide readers with interpretable content validity information.


They also serve: Chamorro male fertility in the pre-world war ii period.
Male fertility, a generally overlooked aspect in studies of human reproductive patterns, is examined from the reproductive life histories of Chamorro males with essential completed fertility by 1941. Males in this "natural fertility" indigenous population of the Pacific island of Guam exhibit low levels of couple infertility which are counteracted by high levels of adult male mortality, while new unions formed after the death of female partners tend to reduce completed fertility by only about one child. Delayed age at the time of union formation is largely compensated by reduction in birthspacing intervals among offspring of older fathers. Early terminators, formerly fertile couples of reproductive age who fail for unspecified biological or behavioral reasons to continue reproducing, affect an equal or even larger impact than adult male mortality on failure to attain theoretical male fertility maxima in this population. Am. J. Hum. Biol. 10:23-35, 1998. © 1998 Wiley-Liss, Inc.


PAF-acether-induced mortality in mice: protection by benzodiazepines.
Intraperitoneal injection to mice of platelet-activating factor (PAF) induces severe shock symptoms, leading to death. The effects of various drugs which are potential specific or non-specific PAF inhibitors were tested. Salbutamol, a beta 2-agonist, showed a partial protection, whereas the specific PAF antagonists CV 3988 or BN 52021 induced an important beneficial action against PAF-induced lethal effects. The effects of drugs related to benzodiazepines were also studied: alprazolam administered p.o. prior to PAF challenge provides almost complete protection against PAF toxicity. Thus PAF-induced death in mice represents a useful model of systemic anaphylaxis; moreover, studies of benzodiazepine-related compounds may be interesting for investigating the mechanisms of the biological actions of PAF.


Diplomatic and operational adaptations to global health programmes in post-conflict settings: contributions of monitoring and evaluation systems to health sector development and 'nation-building' in South Sudan.
Monitoring and evaluation (M&E) systems are an essential element of functioning and accountable global health programmes. In post-conflict settings, the role of M&E systems is also critical to ensure that health services are being delivered to those populations and regions most in need. Given the inherent challenges of health service delivery in such environments, a range of both diplomatic and operational adaptations to M&E procedures are necessary. Using the '12 components' of a functioning M&E system as a conceptual and analytical framework, we observed and reviewed the key challenges to M&E systems in South Sudan as part of a broader review of United Nations Development Programme (UNDP) activities supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria. Based on additional interview-based reviews and analyses of M&E activities, a list of adaptations to standardized M&E procedures in response to post-conflict environmental challenges was developed. The study concludes that development and implementation of M&E systems in post-conflict environments requires extensive adaptations to conventional procedures. Flexible and adaptable as well as 'diplomatically sensitized' M&E systems are considered to be essential to the successful completion of M&E-related activities, and may also contribute to broader international relations, 'nation-building', and peace-keeping goals.


Interferon-alpha and lamivudine combination therapy of children with chronic hepatitis b infection who were interferon-alpha nonresponders.
Greater than one-half of children with chronic hepatitis B infection are nonresponders to interferon-alpha (IFN-alpha). The aim of this study was to investigate the efficacy of lamivudine (LMV) and IFN-alpha combination therapy in these children. Nineteen children were given LMV alone for 3 months; then IFN-alpha was added to LMV for 6 months. Virologic response was achieved in seven (36.8%) patients. LMV and IFN-alpha combination therapy may represent an effective treatment option.


Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial.
Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. Randomised controlled study. Single university teaching hospital, from March 2015 to January 2016. A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. Patients were randomised to receive a single intravenous bolus of 0.1 mg kg dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100β protein levels. Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P < 0.001) and postoperative C-reactive protein levels (P < 0.001). Postoperative S100β levels were insignificantly lower (P = 0.56) in the dexamethasone group. Preoperative administration of dexamethasone reduced the inflammatory response and thereby decreased the risk of early POCD after cardiac surgery. Clinicaltrials.gov identifier: NCT02767713.


Clinical conference in pulmonary disease. Factors influencing upper airway closure.
The factors which produce closure of the upper airway (UAW) in patients with the sleep apnea syndrome are still poorly understood. A distinction should be made between the factors which induce closure and those which reopen the UAW. Neurologic factors include arousal phenomena, the magnitude and timing of various motor outputs, and postsynaptic inhibition. Mechanical factors include the anatomy of the UAW, especially that above the tongue, the position of the neck and jaw, and mucosal adherence once occlusion has occurred. Muscle factors include the type of myosin isozyme, the forces generated by the large number of UAW muscles and the diaphragm, and the possibility of high-frequency fatigue occurring during occlusion. Hypoxia and acidosis probably play a critical role in making the UAW less stable. Currently, the best method to prevent UAW closure is by nasal CPAP. Patients with life-threatening arrhythmias due to sleep apnea should have a tracheostomy. The role of drugs is controversial. Respiratory or muscle stimulants should probably be avoided; oxygen, medroxyprogesterone, and protriptyline may be useful adjuncts.


A retrospective study of the risk factors for ridge expansion with self-tapping osteotomes in dental implant surgery.
To analyze the risk factors associated with the survival of self-threading implants placed with the ridge expansion technique using self-tapping osteotomes after at least 24 months. This retrospective study followed patients for at least 2 years in whom implants had been inserted by means of the ridge expansion technique. The patient was taken as the unit of analysis, and the loss of any implant as a result of mobility at any time during the follow-up period was considered as a failure. A number of patient variables were recorded: sociodemographic (age/sex), anatomical (bone quantity/quality, expansion zone), infection history (prior antibiotic therapy for active infection), prosthodontic (type of provisional prosthesis and type of definitive rehabilitation), and surgical (number of surgical stages, the use of biomaterials or atraumatic maxillary sinus elevation). Risk factors were expressed as values of relative risk (RR) and the odds ratio. Seventy-four patients (157 implants) were followed over a mean period of 38.8 ± 7.7 months. Most patients (91.9%) did not lose any implants, and failures occurred mainly after implant loading (5.4%). Sociodemographic factors (sex and age) were not associated with a significant risk of implant failure. However, the existence of previous local infection (RR = 34.0), the use of an immediate fixed provisional prosthesis (RR = 15.0), and type D3 bone (RR = 5.1) were seen to be the main risk factors involved in this technique for the period assessed. The risk of failure when implants are placed using self-tapping osteotomes was highest in patients who had active local infection; immediate provisionalization and less dense bone were also associated with additional risk of failure.


[Histopathological study of the aging process in the human sacroiliac joint].
It has not been well defined the morphologic characteristics of the aging process of the sacroiliac joints in man. We have, therefore, studied the sacroiliac joints of human subjects by light and scanning electron microscopy. The joints were collected from 55 Japanese fetuses and adult cadavers. The articular cartilages on both sacral and iliac sides were composed of hyaline cartilage in the fetuses and adults. In fetuses, loose fibrous strands were found in the articular space and appeared to represent a residue of the intermediate layer during formation of the articular space. In adults who were older than 30, the joints showed definite degeneration which was more severe on the cartilage at the iliac side than that of sacral side. Scanning electron microscopic observations supported the light microscopic findings. Fusion of the two articular surfaces was observed in 24% of the adult joints. These findings strongly suggest that the buffering capacity of the sacroiliac joints decreases with aging which appears to relate to the clinical symptom of low back pain.


Nontransplant surgical options for congestive heart failure.
A wide array of surgical options are currently available for the treatment of congestive heart failure ranging from traditional coronary artery bypass grafting to total artificial heart implantation. The indications for each procedure depend on the severity of disease and the individual patients desires. Some surgical options are indicated for patients with moderate disease and prevent worsening heart failure, whereas other procedures are limited to patients who will only survive with high-risk surgery. Ongoing technologic advances are increasing the number of patients that benefit from the reparative surgical treatment of congestive heart failure.


Performance and microbial community variations in thermophilic anaerobic digesters treating OTC medicated cow manure under different operational conditions.
This study aimed to determine the fate and effect of oxytetracycline (OTC) and its metabolites during thermophilic anaerobic digestion of cow manure. OTC-medicated and non-medicated digesters were operated at 55°C with different volatile solids (VS) concentrations (4% and 6%) and mixing rates (90 and 120rpm). OTC and its metabolites were measured by HPLC and LC/MS/MS, respectively. Microbial community dynamics were monitored by denaturing gradient gel electrophoresis (DGGE) and real-time PCR (qPCR). Approximately 2mg/L initial OTC concentration caused 10-30% inhibition on biogas production and higher inhibition was observed as mixing rate increased. DGGE results indicated that OTC caused a shift in bacterial community structure and several species became dominant with time. Archaeal community decreased throughout the digestion period. RNA based qPCR analyses showed that gene copy numbers of bacteria and Methanomicrobiales declined in all digesters whereas gene copy numbers of Methanobacteriales and Methanosarcinales increased in high mixing rate digesters.


Transcriptional profiling of the endosymbiont Blochmannia floridanus during different developmental stages of its holometabolous ant host.
The transcriptome of Blochmannia floridanus, the endosymbiont of the carpenter ant Camponotus floridanus, is presented during various developmental stages of its holometabolous host by use of a whole-genome DNA macroarray. The detected transcription patterns indicate the presence of local transcription units as well as global regulatory mechanisms. Yet, the overall regulation scale is very modest, rarely exceeding a factor of three. A large number of genes show differential expression in different life stages and a distinct expression pattern of genes possibly involved in symbiotic function as compared with housekeeping genes is apparent. However, these transcriptional changes are small as compared with the changes in the number of bacteria during host development, which is the highest in pupae and in young imagines. Control of replication of the bacteria in certain life stages may therefore be the decisive parameter influencing the overall level of gene expression of Blochmannia in the animal. The few highly expressed genes like those encoding molecular chaperones exhibit a significantly higher G+C content than moderately expressed genes.


Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies.
Pre-clinical data in non-M3 AML supports the use of differentiation therapy, but clinical activity has been limited. Myeloid growth factors can enhance anti-leukemic activity of differentiating agents in vitro. We conducted companion phase II trials investigating sargramostim (GM-CSF) 125μg/m(2)/day plus 1) bexarotene (BEX) 300mg/m(2)/day or 2) entinostat (ENT) 4-8mg/m(2)/week in patients with MDS or relapsed/refractory AML. Primary endpoints were response after at least two treatment cycles and toxicity. 26 patients enrolled on the BEX trial had a median of 2 prior treatments and 24 enrolled on the ENT trial had a median of 1. Of 13 response-evaluable patients treated with BEX, the best response noted was hematologic improvement in neutrophils (HI-N) seen in 4 (31%) patients; none achieved complete (CR) or partial remission (PR). Of 10 treated with ENT, there was 1 (10%) partial remission (PR) and 2 (20%) with HI-N. The secondary endpoint responses of HI-N with each combination were accompanied by a numerical increase in ANC (BEX: 524 to 931 cells/mm(3), p=0.096; ENT: 578 to 1 137 cells/mm(3), p=0.15) without increasing marrow blasts. Shared grade 3-4 non-hematologic toxicities included febrile neutropenia, bone pain, fatigue, and dyspnea. GM-CSF plus either BEX or ENT are well tolerated in resistant and refractory MDS and AML and showed modest clinical and biologic activity, most commonly HI-N.


Monitoring the dynamics of coastal vegetation in southwestern Taiwan.
This study analyzes the results of the first 5 years of long-term environmental monitoring of the dynamics of coastal vegetation communities in southwestern Taiwan. Seven permanent plots were established in major vegetation communities, including grassland, windbreak forest, and secondary succession forest. Results showed that species richness decreased yearly in grasslands but fluctuated moderately in the forest plots. A Jaccard similarity coefficient was used to evaluate the similarities of species composition between different monitoring years. Species composition changed rapidly in grassland sites, with the similarity coefficient dropping from 82 to 29% in 5 years. The similarity coefficient of vegetation in the composite hardwood forest dropped from 80 to 50%, indicating that at least half the species were the same as those in the beginning and that the composition of forest communities was more stable than that of grassland communities. Dominant species in the forest community changed gradually during the monitoring period. The original planting of Casuarina equisetifolia in windbreak forests decreased year by year in most of the plots, while Cerbera manghas and Ficus microcarpa became the dominant species. The trend of replacement of dominant species indicates that most of the vegetation communities are still in successional stages.


Modeling and performance improvement of an anaerobic-anoxic/nitrifying-induced crystallization process via the multi-objective optimization method.
The trade-off between energy savings and emission reductions of an activated sludge process is a multi-objective problem relating to several potentially conflicting objectives. Therefore, the optimal modification of an anaerobic-anoxic/nitrifying/induced crystallization (A2N-IC) process by multi-objective optimization method was studied in this work. The multi-objective optimization model comprised three evaluative indices, (effluent quality (EQ), operation cost (OC), and total volume (TV) of structures), and 14 process parameters (decision variables) solving by non-dominated sorting genetic algorithm II (NSGA-II) in MATLAB. The trade-off relationships among EQ, OC, and TV were investigated under 30 days of dynamic influent with different constraint conditions. A series of Pareto solutions were obtained, and one Pareto solution was selected for further analysis. Results showed improved effluent concentrations of chemical oxygen demand (COD), total nitrogen (TN), ammonia-nitrogen (NH4+-N), and total phosphorous (TP) under the optimized strategy compared to the original strategy, where the average effluent concentrations decreased by 2.22, 0.47, 0.13, and 0.02 mg/L, respectively. The values of EQ and OC decreased from 0.015 kg/day and 0.15 ¥/m3 to 0.0023 kg/day and 0.12 ¥/m3, respectively, while the TV increased from 0.31 to 0.33 m3. These results indicated that the multi-objective optimization method is useful for modifying activated sludge processes.


Review of challenges in optimizing oral anticoagulation therapy for stroke prevention in atrial fibrillation.
Oral anticoagulant therapy is the mainstay of stroke prevention in patients with atrial fibrillation; it is highly effective at reducing stroke risk, but its use can be limited by increased risk of bleeding. As new oral anticoagulants are available, barriers to optimal use of oral anticoagulation therapy warrant consideration by healthcare professionals and administrators who are seeking to optimize the quality of care for patients with atrial fibrillation. Suboptimal use of oral anticoagulation therapy constitutes an important health problem with significant humanistic and economic consequences. Based on a review of the medical literature published between 2000 and 2011, this article summarizes the literature on the barriers to optimal use of oral anticoagulation therapy, describes the clinical and economic burdens that these barriers add to the burden of atrial fibrillation, and discusses how well the new oral anticoagulants may address some of these issues.


A multicentred cohort evaluation of a chitosan gelling fibre dressing.
A multicentre cohort evaluation was undertaken by 15 clinicans in 11 centres across Staffordshire community care on chitosan gelling fibre dressing (Kytocel(®)). The aim of this evaluation was to examine whether the new fibre dressing improved healing outcomes for patients with chronic non-healing wounds of 6 weeks or more, observations were made regarding tissue type, fluid handling, haemostasis in bleeding friable wounds and increased granulation. Quality of life observations regarding leaking, strikethrough, pain, wear time and malodour were observed over a 4-week period or until healed. A total of 18 patients took part; 13 women and 5 men, with a mean age of 60.7 years. Fifteen (83%) had wounds in excess of 12 weeks and nine (50%) received care within wound clinics compared to home visits. Eleven (61%) patients' wounds healed within 4 weeks. A number of quality-of-life issues were addressed successfully, namely reduction in malodour and fluid handling. Sixteen (89%) rated the dressing's overall performance as very good to good.


Study of water migration by micro MR imaging.
Magnetic Resonance (MR) microscopy is a noninvasive tool that enables high resolution imaging of water concentration in non-magnetic materials. In this study, water migration in a dense porous material (dental cement) was monitored by 1D MR microscopy. The measured concentration profiles were later analyzed via three different migration models: an imbibition model, a diffusion model and a combined model. From the best fit to the experimental data, model parameters were obtained.


Obstacle training programme for individuals post stroke: feasibility study.
The purposes were threefold: to develop an obstacle ambulation training programme, to recruit and retain individuals post chronic stroke and to assess the effectiveness of the obstacle ambulation training programme. Intervention study; case series; baseline to post-intervention measures and one month follow-up after intervention. An outpatient department. Five individuals with chronic stroke with mild to moderate functional limitations; convenience sample. Therapy consisted of twice weekly sessions for four weeks during which subjects walked along a walkway and over obstacles. Motor Assessment Scale--walking section (MAS--time), Six-minute Walk Test distance, walking velocity, and Medical Outcomes Study-36 Health Status Measurement (SF-36). Significant improvements were seen baseline to post intervention for walking velocity, Six-minute Walk Test, MAS and SF-36 physical function score (p < or = 0.025 for all measures). Most improvements noted at the end of training were retained one month later. The effect sizes ranged from 0.33 to 1.20. Substantial improvement in ambulation function and disability level were seen as a result of the obstacle training programme for individuals with chronic stroke. Further investigation is warranted.


Mononuclear cell-modulation of granulosa cell steroidogenesis in rat: influence of ovarian cycle.
The mononuclear cells exert a paracrine influence on the ovarian function, including steroidogenesis. This study examines the ability of the conditioned medium from the cultures of splenic mononuclear cells, obtained during various phases of the ovarian cycle, on progesterone accumulation by the granulosa cells in the culture medium. Female Wistar rats, aged twenty-five days, were made pseudopregnant by an injection of pregnant mare's serum gonadotropin. The splenic mononuclear cells were isolated at follicular phase, early luteal phase, mid luteal phase and late luteal phase and cultured for 48 h. The ammonium sulphate precipitated fraction of the conditioned medium was added to the granulosa cells obtained from immature rats treated with diethylstillboestrol. The granulosa cells were cultured for 48 h, and the progesterone accumulated in the medium was assayed. The conditioned medium from the cultures of the mononuclear cells obtained during follicular phase and late luteal phase inhibited FSH-induced progesterone secretion, whereas conditioned medium obtained from mid luteal phase mononuclear cells enhanced the effect of FSH. The stimulatory effect of db-cAMP on progesterone accumulation in the culture medium is inhibited by conditioned medium obtained from all the phases of the ovarian cycle. This study demonstrates a cyclicity in the behaviour of the splenic mononuclear cells on ovarian steroidogenesis, suggesting a bi-directional paracrine and/or endocrine relationship between ovary and the mononuclear cells.


Cardiovascular effect of V1 vasopressinergic blockade during acute hypercapnia in conscious rats.
Experiments were performed to test the possible involvement of arginine vasopressin (AVP) in the systemic cardiovascular responses to acute hypercapnic acidosis in conscious chronically instrumented rats. Exposure to 6% CO2 caused arterial PCO2 to rise from 34 +/- 2 to 53 +/- 1 Torr. This level of hypercapnia was associated with a consistent bradycardia; however, cardiac output, blood pressure, and total peripheral resistance were not significantly affected. Administration of 10 micrograms/kg iv of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP during 6% CO2 had no effect on any of the measured hemodynamic variables. Furthermore, d(CH2)5Tyr(Me)AVP also had no effect in normocapnic control animals. Exposure to a more severe level of hypercapnia (10% CO2, arterial PCO2 = 89 +/- 1 Torr) resulted in marked hemodynamic alterations. Profound bradycardia and decreased cardiac output in addition to increases in mean arterial blood pressure and total peripheral resistance were observed. V1 vasopressinergic antagonism during 10% CO2 had no effect on heart rate but greatly increased cardiac output. In addition, blood pressure fell and resistance was decreased below prehypercapnic levels. These data suggest that a number of the hemodynamic alterations associated with severe hypercapnic acidosis in the conscious rat may be mediated by the peripheral cardiovascular effects of enhanced AVP release.


Curative effects of Distemonanthus benthamianus Baillon. Trunk-bark extracts on enteropathogenic Escherichia coli 31-induced diarrhea in rats.
Background Distemonanthus benthamianus is used in the Western part of Cameroon to treat diarrheal episodes and infections. This study assessed its trunk-bark extracts activity against enteropathogenic Escherichia coli 31 (EPEC 31)-induced diarrhea in rats. Methods Aqueous and methanolic extracts were analyzed through high-performance liquid chromatography (HPLC). In vitro minimum inhibitory and bactericidal concentrations (MICs/MBCs) were evaluated on Enterococcus faecalis (ATCC 10,541), E. coli (ATCC 6539), Klebsiella pneumoniae (ATCC 13,883), Salmonella typhi (ATCC 6539) strains and on Proteus mirabilis, Pseudomonas aeruginosa (PA 01) and Shigella flexneri isolates using the microdilution method. Diarrhea was induced by inoculating rats with EPEC 31 (1.5 × 108 CFU/mL; p.o). Serum transaminases level assay and enzyme-linked immunosorbent assay (ELISA) for cytokines determination were performed. Hematoxylin-eosin (H-E) staining was used for intestinal tissue analysis. Results HPLC fingerprints of extracts showed presence of gallic acid and other unidentified compounds. The lowest MIC of 256 µg/mL was obtained with methanolic extract. At 100 mg/kg, both extracts significantly (p<0.001) inhibited diarrhea, with the methanolic extract being the most active. In addition, the methanolic extract significantly (p<0.001) increased the relative mass of the liver compared to negative control (Tween-DMSO 8%). The aqueous extract (100 mg/kg) significantly (p<0.01) increased alanine aminotransferase (ALT) serum concentration; while the methanolic extract (100 mg/kg) exhibited similar effect over aspartate aminotransferase (AST). At 50 and 100 mg/kg, the methanolic extract significantly (p<0.05 and p<0.01) decreased the Interleukin-1β (IL-1β) serum level, compared to negative control (Tween-DMSO 8%). Serum level of tumor necrosis factor alpha (TNF-α) significantly (p<0.001) decreased with 100 mg/kg of aqueous extract and all doses of methanolic extract. Inhibition of inflammatory cells tissue infiltration and epithelial regeneration was highly noticed in the ileum and colon of extracts-treated rats than in ciprofloxacin-treated animals. Conclusion These findings suggest that D. benthamianus trunk-bark extracts displayed therapeutic effects against infectious diarrhea in rats.


Simultaneous determination of cis-trans isomeric retinals by high-performance liquid chromatography.
A high-performance liquid chromatographic method for the simultaneous determination of geometric isomers of retinal in a mixture has been developed. The method can be applied to problems such as determination of optimal conditions for the preparation of a particular isomer, or the investigation of novel photoproducts from retinal. Aprotic solvent effects on cis-trans isomerization are discussed.


Persistent placoid maculopathy: a new clinical entity.
To describe a previously unreported clinical entity superficially resembling macular serpiginous choroiditis but with a distinct presentation and clinical course. Retrospective observational case series. Six patients, 50 to 68 years old, exhibiting this entity who were seen at 5 different centers from 1984 to 2006. Review of medical records. Best-corrected visual acuity (VA) and clinical and angiographic findings. The lesions in our patients are similar to those of acute macular serpiginous choroiditis. Our patients had well-delineated whitish plaquelike lesions involving the macula and sparing the peripapillary areas of both eyes. In contrast to serpiginous choroiditis, VA remained good despite early involvement of the fovea until complications related to choroidal neovascularization or pigmentary mottling developed. Angiographic characteristics and the clinical course were also atypical. Fluorescein angiography revealed well-defined early hypofluorescent areas that partially filled in in the late phase. Indocyanine green angiography showed the hypofluorescence to be persistent. Unlike serpiginous choroiditis, the white macular lesions faded over a period of months to years, whereas the characteristic angiographic findings often persisted longer. Choroidal neovascularization developed in 11 of 12 eyes, with subsequent conversion to disciform macular scars in 9 of 12 eyes. Unlike serpiginous choroiditis, none of the eyes showed chorioretinal scar formation unless related to choroidal neovascularization. Persistent placoid maculopathy has features resembling macular serpiginous choroiditis but differs in its clinical course and effect on VA. It appears to be a new entity. The majority of eyes develop choroidal neovascularization that results in loss of central vision.


Assessing the performance of fold recognition methods by means of a comprehensive benchmark.
Recently there has been an explosion of methods for fold recognition. These methods seek to align a protein sequence to a three-dimensional structure and measure the compatibility of the sequence to the structure. In this work, we present a benchmark to assess the performance of such methods. The benchmark consists of a set of protein sequences matched by superposition to known structures. This set covers a wide range of protein families, and includes matching proteins with insignificant sequence similarity. To demonstrate the usefulness of this benchmark, we apply it here to compare different fold-recognition methods developed through the years in our group as well as several sequence-sequence substitution matrices. The results show that "global-local" alignments are superior to either local or global alignments. The most effective sequence-sequence matching matrix is the Gonnet table. The best performance overall is obtained by a method which combines the 3D-1D profiles of Bowie et al. with a substitution matrix and takes into account residue pairwise interactions.


The effects of intensive, moderate and downhill treadmill running on human blood lymphocytes expressing the adhesion/activation molecules CD54 (ICAM-1), CD18 (beta2 integrin) and CD53.
This study examined the effects of intensive, moderate and downhill treadmill running on blood lymphocyte expression of adhesion/activation (AA) molecules. Trained subjects completed three treadmill-running protocols of identical duration: (1) an intensive protocol at 80% VO2max to volitional exhaustion, (2) a moderate protocol at 60% VO2max and (3) a -10% downhill (eccentric) protocol at 80% VO2max. Blood samples were taken before, immediately after, 1 and 24 h after exercise. Isolated lymphocytes were assessed for expression of the AA molecules CD54, CD18 and CD53 by flow cytometry. Lymphocyte counts increased immediately after all running protocols. Lymphocytopenia was observed 1 h after the intensive and eccentric protocols only. Plasma creatine kinase increased 24 h after the downhill protocol only. Increases in the number and percentage of CD54+, CD18bright and CD53bright lymphocytes were observed immediately after the intensive and eccentric protocols, with the numbers falling below pre-exercise values at 1 h post-exercise for all protocols. No differences were found between the intensive protocol and the eccentric protocol at the same relative intensity. Analysis of lymphocyte subsets showed that the total number of CD3+, CD4+, CD8+ and CD56+ lymphocytes increased after the intensive protocol before falling below pre-exercise values at 1 h post-exercise. A relatively greater mobilisation of CD56+ and CD8+ cells accounts for the changes in CD54+, CD18bright and CD53bright cell populations. Lymphocytes that enter and exit the circulation following exercise express high levels of AA molecules, which may mediate extravasation and post-exercise lymphocytopenia. This effect appears to be influenced by exercise intensity and not muscle damage.


Dietary intake and blood lipid profile survey of fighter pilots at Tyndall Air Force Base.
A 24-hour dietary recall, a food frequency checklist, and a blood lipid profile were collected from 30 USAF fighter pilots. Sample mean intakes of nutrients studied met U.S. military recommended dietary allowances, except for folic acid, which was 78%. Mean percentages of energy derived from carbohydrate, protein and fat were 48.3, 16.1 and 34.2%, respectively. Of the pilot sample, 63% reported they did not eat breakfast daily. Sample mean blood lipid profile values were: total cholesterol = 218 mg/dl, HDL-cholesterol = 45 mg/dl, triglycerides = 109 mg/dl. Based on total cholesterol level, 40% of the pilot sample should have follow-up according to the National Cholesterol Education Program. A significant negative relationship was found between reported exercise frequency and total cholesterol/HDL-cholesterol ratio. Some fighter pilots could benefit from counseling with a dietitian regarding dietary intake patterns, decreasing dietary fats, and the advantages of regular exercise.


Elements of plant physiology in theophrastus' botany.
For thousands of years the plants were considered only as a source of food and medicine, and as ornamental objects. Only from the fifth century BC, some philosophers of Ancient Greece realized that the plants were living organisms but, unfortunately, their works have come to us as fragments that we often know from the biological works of Aristotle. This eminent philosopher and man of science, however, did not give us a complete work on the plants, which he often promised to write. From scattered fragments of his conspicuous biological work, it emerges a concept of nutritive soul that, in the presence of heat and moisture, allows plants to grow and reproduce. The task of writing a comprehensive botanical work was delegated to his first pupil, Theophrastus, who left us two treatises over time translated into the various languages up to the current versions (Enquiry into plants, On the causes of plants). The plant life is described and interpreted on the basis of highly accurate observations. The physiological part of his botany is essentially the nutrition: According to Theophrastus, plants get matter and moisture from the soil through root uptake and process the absorbed substances transforming them into food, thanks to the heat. The processing (pepsis, coction) of matter into the food represents an extraordinary physiological intuition because individual organs of a plant appear to perform its specific transformation. Despite that Theophrastus did not do scientific experiments or use special methods other than the sharpness of his observations, he can be considered the forerunner of a plant physiology that would take rebirth only after two millennia.


Arginine-vasotocin influence on aggressive behavior and dominance in rainbow trout.
The mammalian neuropeptide arginine-vasopressin (AVP) and its non-mammalian homologue arginine-vasotocin (AVT) are involved in social behavior including aggression in vertebrates. Juvenile rainbow trout (Onchorhynchus mykiss) are highly territorial and we tested the effect of two different doses each of AVT and Manning compound, an AVP V(1A) receptor antagonist, on aggressive behavior and the outcome of staged fights for social dominance in size matched pairs. Each pair consisted of one fish receiving AVT or Manning compound through an intracerebroventricular (icv) injection and one fish receiving a similar icv injection of saline. In addition, plasma cortisol and brain serotonergic activity were monitored. Fish receiving AVT at a dose of 200 ng became subordinate whereas AVT at a dose of 20 ng had no effect on the outcome of fights for social dominance. Further, Manning compound had no effect on the outcome of fights for dominance but at a dose of 200 ng it had an effect on fight duration. Fish receiving 200 ng Manning compound and losing dyadic fights appeared to take longer to become subordinate. Neither AVT nor Manning compound had any effects on plasma cortisol levels or brainstem serotonergic activity. The apparent inhibiting effect of AVT on aggression could be centrally mediated.


Dental caries and pulpal disease.
This article reviews the diagnostic process, from the first clinically evident stages of the caries process to development of pulpal pathosis. The caries diagnostic process includes 4 interconnected components-staging caries lesion severity, assessing caries lesion activity, and risk assessments at the patient and tooth surface level - which modify treatment decisions for the patient. Pulpal pathosis is diagnosed as reversible pulpitis, irreversible pulpitis (asymptomatic), irreversible pulpitis (symptomatic), and pulp necrosis. Periapical disease is diagnosed as symptomatic apical periodontitis, asymptomatic apical periodontitis, acute apical abscess, and chronic apical abscess. Ultimately, the goal of any diagnosis should be to achieve better treatment decisions and health outcomes for the patient.


Cell mediated immunity in Antarctic wintering personnel; 1984-1992.
Cell-mediated immune responses were studied in 12 Antarctic and sub-Antarctic wintering groups at quarterly intervals over the period 1984-1992, using the cutaneous CMI Multitest. These populations are among the most isolated on earth. While the sub-Antarctic population at Macquarie Island had levels of responsiveness and hypoergy (9%) comparable to healthy populations in temperate zones, the Antarctic Continental group showed a level of hypoergy of 36%. There was no seasonal variation in the pattern of responses. It is concluded that the extreme and isolated environment and stress factors are responsible for the decreased immunological responsiveness but the mechanisms are presently unclear. On review, one factor appears to be perceived anxiety. The high rate of hypoergy in Antarctica, where medical care is limited, may have health implications. These groups provide an excellent analogue for immunological investigations in longer term space flight.


[Aims and realizations in the manufacture of articulators].
The various designs of the most familiar articulators are described. Also the different concepts important to comprehending the stomatognathic functions are discussed. Their impact on the designs of various articulators are shown. The purpose of this study is not to given a complete review of the history and development of different articulators, rather, the purpose is to present the application of various stomatognathic philosophies to the design of various articulators.


[Willem Kouwenaar, editor-in-chief of the Dutch Journal of Medicine 1950-1954].
Willem Kouwenaar (1891-1954) spent the first part of his career in the Dutch East Indies as a physician of tropical medicine and tropical hygienist. He conducted many comparative epidemiological studies. After returning to The Netherlands in 1946, he became a professor of tropical medicine. Among other accomplishments, he developed a vaccine against yellow fever. In 1950 he became editor-in-chief of the Nederlandsch Tijdschrift voor Geneeskunde (Dutch Journal ofMedicine). He was of the opinion that 'everything that Dutch physicians are dealing with should also be presented for the information of the subscribers to our Journal,' which also applied to the controversial topics of birth control and contraceptive agents. He died in an airplane accident in 1954.


Vetrabutine clorhydrate use in dystocic farrowings minimizes hemodynamic sequels in piglets.
The objective was to measure the effects of VC (a uterotonic drug with vasodilator effects) in eutocic and dystocic sows, on the acid-base balance and some vitality traits of piglets at birth. Farrowing was induced with prostaglandin F2α. Four groups of sows (20 sows/group) were monitored; Groups 1 and 2 were eutocic sows, whereas Groups 3 and 4 were dam-fetal dystocic sows. Groups 1 and 3 (control) were given saline, whereas Groups 2 and 4 were given VC im (1.66 mg/kg of body weight) after the first piglet was born. Piglets' physio-metabolic performance was monitored peripartum. Treatment with VC reduced (P<0.0001) the percentage of intrapartum stillbirths in sows either with eutocic (5.2 vs. 10.0%) and dystocic (7.6 vs. 16.7%) farrowings and increased (P<0.0001) the number of pigs born alive without any evidence of AFS (89.9 vs. 79.9%, eutocic and 81.6 vs. 65.2%, dystocic). In addition, for the group of pigs with no acute fetal suffering (AFS), VC treatment enhanced survival responses with a half point grater vitality score in Group 4; it also reduced the latency to first teat contact by 6 min (P<0.05) in both treated groups compared to controls; and it improved the condition of the pigs' umbilical cord, with more adhered (98 vs. 86% in eutocic and 88 vs. 80% in dystocic; P<0.05) and less ruptured cords. Moreover, VC reduced the severity of adverse physio-metabolic indicators and the acid-base balance of piglets with AFS at birth by lowering blood lactate (89.8 vs. 93.5 mmol/L in eutocic groups and 94.6 vs. 100.2 mmol/L in dystocic groups; P<0.05), PaCO2 and Ca2+, and by increasing blood pH, HCO3 and PaO2 levels (P<0.05).


Development of a novel digestion chamber for human and porcine islet isolation.
The current technique of human pancreas digestion for islet isolation relies on selective distribution of collagenase delivered via the pancreatic duct to produce digestion and removal of peri-acinar fibrous tissue. However, the collagenase has relatively little effect on the interlobular fibrous tissue, which must therefore be broken down by mechanical means within the digestion chamber so as to release the contained acini and islets. The current way of achieving this in the Ricordi chamber is to place five or six stainless steel balls within the chamber and shake vigorously. The shaking presumably breaks down the interlobular fibrous tissue by a combination of shear force induced by the movement of tissue through the shaking process, assisted by numerous blows from the steel balls. Intuitively, one would expect some islets would be destroyed rather than released by such a battering. In an attempt to improve the efficiency of islet isolation we have designed a new digestion/filtration chamber that consists of a glass cylinder, sealed with Teflon plates holding in mesh filters at each end, secured in place by a central threaded tie-rod and external knurled nuts. A ring-shaped piston within the cylinder can be pushed up and down the travel by two rods passing out through sealed ports in the Teflon disk at one end and connected to an external handle. The handle is used to gently push the piston up and down the travel of the cylinder, which pushes the fluid and tissue through the central lumen of the ring-piston. A series of hooks attached to the central tie-rod catch the fibrous strands of the passing tissue; the shearing forces produced cause disruption by a process thought to be similar to teasing the tissue apart with fine forceps. A series of initial experiments with human pancreas showed the prototype to be too large, causing temperature control problems, and a redesigned smaller chamber was produced, maintaining the crucial design features. Experience processing five human pancreata has now demonstrated that in three of five pancreata the new chamber produced a good yield (>200,000 I.E.) of remarkably well separated and intact islets, the entire dispersion process being under 1 hour. However, in two isolations the collagenase digestion was poor, with few free islets. A copy of the new chamber (reserved for porcine work only) has been produced, as well as a copy of the Ricordi chamber. We have confirmed that the new chamber can isolate porcine islets in large numbers (>5000 islets/g pancreas [n = 2], but note that pig islets are small). These preliminary studies are sufficiently encouraging to justify further direct comparison with the Ricordi chamber for the purpose of animal and human islet isolation.


Repair of dental resin-based composites.
The study analyzed the reparability and compatibility of light-curing resin-based composites (RBCs) of the categories "microhybrid," "nanohybrid," and "packable." Six RBCs with different matrix and filler formulation--purely methacrylate-based composites (MBCs), ormocer-based composites (OBCs), and silorane-based composites (SBCs)--were used for the specimens. Every material was combined with itself and with the other five RBCs, resulting in a total of 36 combination groups (n = 20). The specimens were polymerized, aged for 8 weeks in distilled water at 37 °C, and then repaired by means of a repair kit. Shear bond strength and fracture mode were measured after aging of the specimens, undergoing storage for 24 h in distilled water at 37 °C followed by thermocycling (5,000 cycles, 5-55 °C) and an additional 4-week storage in distilled water at 37 °C. Data were statistically analyzed using ANOVA with TUKEY HSD post hoc test (α = 0.05). On average, the OBC Admira reached the highest value as a substrate material (30.41 MPa), and the SBC Filtek Silorane reached the lowest value (8.14 MPa). Filtek Silorane was identified as the repair material with the highest bond strength value (28.70 MPa), while a packable composite reached the lowest bond strength value (15.55 MPa). The analysis of the break modes showed that adhesive breaks are typical when strength is at its lowest (6.27 MPa). A large number of cohesive fractures are conspicuous when identical materials are used for repair, except Filtek Silorane (2 % cohesive fractures). The study demonstrated that the effect of the different materials on bond strength varies strongly, depending on whether the material is used as filling or as repair material. It is generally advisable but not compulsory to combine identical RBCs.


The Elder's Right to Sight Collaborative: a new model of eye care delivery for the elderly.
Vision and visual impairment have a significant impact on older adults' daily function and safety within their homes and communities. Yet many do not seek out the necessary care to address their visual health. Many older adults want to age in places that require a supportive environment to compensate for changes in abilities and to promote healthy aging and quality of life. The Elder's Right to Sight Collaborative (ERTS) was established to gain insight into the role of the environment in maintaining the functional independence and safety of older adults with visual impairment and to understand the barriers to obtaining the necessary eye care services. The ERTS provides education, screening, environmental assessments, and simple tools to complete daily activities. The screening results indicate significant need for eye care services to this population. However, service delivery needs to be flexible to meet the needs of this population. A team approach to address education, eye care services, rehabilitation, environmental assessment, and social services is needed. Through education, accessible services, rehabilitation, and environmental modifications, a significant impact on an older adult's independence and quality of life can be attained.


Porous zirconium metal-organic framework constructed from 2D → 3D interpenetration based on a 3,6-connected kgd net.
A new porous zirconium metal-organic framework (Zr MOF), Zr6(μ3-O)4(μ3-OH)4(OH)6(H2O)6(BTB)2·6DMF·H2O (1; H3BTB = 5'-(4-carboxyphenyl)[1,1':3',1″-terphenyl]-4,4″-dicarboxylic acid), based on Zr6 clusters and tricarboxylate ligands has been constructed and characterized. The Zr6 clusters were linked by BTB ligands to generate a 2D network of kgd topology. The interpenetrations among the 2D networks gave rise to a 3D porous framework, which represents the first Zr MOF constructed from 2D → 3D interpenetration. The gas uptake and catalytic properties for 1 have also been studied.


Comparison of granulosa cell proliferation in small follicles of hypophysectomized, prepubertal, and mature rats.
The factors that control the rate of granulosa cell proliferation during follicular development are unknown. The object of this study was to test the hypothesis that growth rates of small and medium follicles may be modulated by cyclic alterations in endogenous hormone concentrations. Follicular growth in adult cycling rats was compared with hypophysectomized rats, untreated prepubertal rats, and prepubertal rats treated with exogenous gonadotropins. Cell kinetics was studied using a metaphase arrest technique and by long-term infusion of [3H]thymidine. Many follicles of hypophysectomized rats showed evidence of continued cell proliferation despite the absence of gonadotropins. In hypophysectomized rats, follicular growth was able to proceed to the size of the largest healthy non-preovulatory follicles in the proestrous rat ovary. Follicular growth in prepubertal rats progressed little beyond this same size range. Granulosa cell proliferation rates differed in immature rats and cycling rats. Granulosa cells in small follicles (80-180 cells in the largest cross-section) of cycling rats grew slowly. However, granulosa cells in small follicles of immature rats were among the fastest growing in the ovary. These results suggest that, although gonadotropins are not absolutely required to maintain granulosa cell proliferation in small follicles, the rate at which these follicles grow varies under different hormonal conditions.