[Serial whole-body cryotherapy in the criostream for inflammatory rheumatic diseases. A pilot study].
Local as well as whole-body cryotherapy is used to relieve pain and inflammation in rheumatic diseases. In comparison with a chamber-based whole-body cryotherapy, the novel criostream whole-body therapy (single-person cabin with cold air cooled by liquid nitrogen) as an innovative technique offers not only a rapid therapeutic effect but also a considerable reduction in costs. The aim of this study was to compare the effect of whole-body cryotherapy in the criostream on pain reduction, disease activity and pro-inflammatory cytokines (tumor necrosis factor-[TNF-]alpha and interleukin-[IL-]1), and improvement in functional scores. Ten patients with different active inflammatory rheumatic diseases (four patients with rheumatoid arthritis, three patients with ankylosing spondylitis, and three patients with psoriatic arthritis/spondylitis) underwent nine sessions of whole-body cryotherapy in 5 days for a short time period (at first 90 s, with step-up in each application to 2.5 min total time). Pain and disease activity scores decreased significantly, and, subsequently, also the functional scores showed a significant amelioration. Furthermore, there was a significant reduction in TNF-alpha (p < 0.01) and IL-1 (p < 0.05). Side effects were reported only after the first application in two cases (headache and sensation of cold). The criostream offers an elegant and, from the patient's point of view, attractive therapeutic agent in the multimodal treatment concept for inflammatory rheumatic diseases.


Atrial natriuretic factor inhibits maximal tubuloglomerular feedback response.
The effect of atrial natriuretic factor (ANF) on maximal tubuloglomerular feedback was assessed in 16 Munich-Wistar rats. When the loop of Henle was not perfused, ANF increased single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) from 32 +/- 2 nl/min and 32 +/- 2 mmHg in the control period to 37 +/- 2 nl/min (P less than 0.05) and 40 +/- 2 mmHg (P less than 0.025) after ANF administration, respectively. Because ANF caused SFP to rise but did not significantly alter plasma protein concentration, the estimated glomerular capillary hydraulic pressure increased. Maximal tubuloglomerular feedback response (examined by increasing orthograde microperfusion of the loop from 0 to 50 nl/min) was significantly inhibited by ANF; changes in SNGFR and SFP during the control state, -9 +/- 2 nl/min and -9 +/- 1 mmHg, were reduced to -4 +/- 2 nl/min (P less than 0.05) and -5 +/- 1 mmHg (P less than 0.05), respectively, after ANF administration. In conclusion, the increase in SNGFR caused by ANF is associated with an increase in glomerular capillary hydraulic pressure and with a blunted maximal tubuloglomerular feedback response.


Mitochondrial DNA analysis of the presumptive remains of Jesse James.
We report here the results of mtDNA analysis of remains exhumed in July, 1995 from Mt. Olivet Cemetery in Kearney, Nebraska, that are thought to be those of Jesse James. The remains were poorly preserved, presumably due to wet and slightly acidic soil conditions, and insufficient DNA for analysis was obtained from two bone samples. However, two of four teeth, and two hairs recovered in 1978 from the original burial site on the James Farm, did yield reproducible mtDNA sequences. These mtDNA sequences from the teeth and hairs were all identical, suggesting that they came from the same individual; furthermore, this mtDNA sequence was identical to mtDNA sequences determined from blood samples from two maternal relatives of Jesse James. Therefore, either the remains are indeed those of Jesse James, or they are from an unrelated individual who, by chance, happens to have the same mtDNA sequence. To assess the probability that an unrelated individual would have the same sequence, we searched the forensic mtDNA database, and found that this sequence does not appear among the 2426 mtDNA sequences therein. Hence, the mtDNA analysis supports the identification of the exhumed remains from Mt. Olivet Cemetery as those of Jesse James.


Medicine use and safety while breastfeeding: investigating the perspectives of community pharmacists in Australia.
Consumers and health professionals rely on community pharmacists for accurate information about the safety of medicines. Many breastfeeding women require medications, yet we know little about the advice provided to them by pharmacists in Australia. The aim of this study therefore was to investigate the perspectives of community pharmacists in Australia on medication use and safety in breastfeeding using a postal survey of a national random sample of 1166 community pharmacies in 2011. One hundred and seventy-six pharmacists responded (51% female). Of the 52% of participants with children, many (70%) had a total breastfeeding duration (self or partner) of 27 weeks or more. The majority (92%) were confident about supplying or counselling on medication during breastfeeding. The most commonly used resources were drug company information, Australian Medicines Handbook and the Royal Women's Pregnancy and Breastfeeding Medicine Guide. Most (80%) believed the available information to be adequate and 86% thought it accessible. Over one-third were unaware that ibuprofen and metronidazole are compatible with breastfeeding. Most (80%) were able to name at least one medicine that may decrease milk supply. We found that community pharmacists discuss medicine use in lactation and are confident of their ability to do so; however, their knowledge may be variable.


The Understanding of Death in Terminally Ill Cancer Patients in China: An Initial Study.
Patient's needs and rights are the key to delivering state-of-the-art modern nursing care. It is especially challenging to provide proper nursing care for patients who are reaching the end of life (EOL). In Chinese culture nursing practice, the perception and expectations of these EOL patients are not well known. This article explores the feelings and wishes of 16 terminally ill Chinese cancer patients who are going through the dying process. An open-ended questionnaire with eight items was used to interview 16 terminally ill Chinese cancer patients, and was then analyzed by a combined approach employing grounded theory and interpretive phenomenological analysis. Four dimensions were explored: first, patient's attitudes towards death, such as accepting the fact calmly, striving to survive, and the desire for control; second, the care desired during the dying process, including avoiding excessive treatment and dying with dignity; third, the degree of the patient's acceptance of death; and fourth, the consequences of death. This cognitive study offers a fundamental understanding of perceptions of death of terminally ill cancer patients from the Chinese culture. Their attitude toward death was complex. They did not prefer aggressive treatment and most of them had given a great deal of thought to their death.


[The use of stents in benign oesophageal conditions].
In recent years, self-expanding stents have been used to treat benign perforations and strictures of the oesophagus. We conducted a PubMed search of literature from January 1st 1993 to February 7th 2005 on the use of self-expanding stents in benign oesophageal conditions. Only case reports and minor series are published in the literature; further studies are needed in order to define the future role of stents in benign disease. Present experience indicates that self-expanding metal stents can be used in benign perforations of the oesophagus, provided that the stent is removed once the perforation has healed. Removing such stents may, however, require significant endoscopic experience. When stents are used in benign strictures, a high number of complications should be expected; the literature is more ambiguous as to whether or not this procedure should be recommended. The development of retrievable plastic stents and bio-absorbable stents could alter the use of stents in the future.


Bioactive glass-gelatin hybrids: building scaffolds with enhanced calcium incorporation and controlled porosity for bone regeneration.
Thanks to their active promotion of bone formation, bioactive glasses (BG) offer unique properties for bone regeneration, but their brittleness prevents them from being used in a wide range of applications. Combining BG with polymers into a true hybrid system is therefore an ideal solution to associate toughness from the polymer and stimulation of bone mineralization from the glass. In this work, we report the synthesis and characterization of hybrid scaffolds based on SiO2-CaO bioactive glass and gelatin, a hydrolyzed form of bone type-I collagen. Incorporation of calcium ions, known to trigger bone formation and cellular activity, into the hybrid structure was achieved at ambient temperature through careful control of chemistry of the sol-gel process. Thorough characterization of the materials highlights the effect of grafting an organoalkoxysilane coupling molecule to covalently link networks of BG and gelatin, and proves it a successful means to take control over the degradation and bioactive properties of hybrids. Importantly, BG-gelatin hybrids are synthesized in a process fully conducted at ambient temperature that allows obtaining open-porous scaffolding structures, with well-controlled and tuneable porosity with regards to both pore and interconnection sizes. Mechanical properties of the scaffolds under compression are similar to that of trabecular bone and their apatite-forming ability is even higher than that of pure BG scaffold foams.


Neural correlates of giving support to a loved one.
Social support may benefit mental and physical well-being, but most research has focused on the receipt, rather than the provision, of social support. We explored the potentially beneficial effects of support giving by examining the neural substrates of giving support to a loved one. We focused on a priori regions of interest in the ventral striatum and septal area (SA) because of their role in maternal caregiving behavior in animals. Twenty romantic couples completed a functional magnetic resonance imaging session in which the female partner underwent a scan while her partner stood just outside the scanner and received unpleasant electric shocks. Support giving (holding a partner's arm while they experienced physical pain), compared with other control conditions, led to significantly more activity in the ventral striatum, a reward-related region also involved in maternal behavior (p values < .05). Similar effects were observed for the SA, a region involved in both maternal behavior and fear attenuation. Greater activity in each of these regions during support giving was associated with greater self-reported support giving effectiveness and social connection (r values = 0.55-0.64, p values < .05). In addition, in line with the SA's role in fear attenuation (presumably to facilitate caregiving during stress), increased SA activity during support giving was associated with reduced left (r = -0.44, p < .05) and right (r = -0.42, p < .05) amygdala activity. Results suggest that support giving may be beneficial not only for the receiver but also for the giver. Implications for the possible stress-reducing effects of support giving are discussed.


Air Pollution Particulate Matter Exposure and Chronic Cerebral Hypoperfusion and Measures of White Matter Injury in a Murine Model.
Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM. This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameter ≤200 nm) and CCH secondary to bilateral carotid artery stenosis (BCAS) in a murine model to produce white matter injury. Based on other air pollution interactions, we predicted synergies of nPM with BCAS. nPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms: a) FA, b) nPM, c) FA + BCAS, and d) nPM + BCAS. Behavioral outcomes, white matter injury, glial cell activation, inflammation, and oxidative stress were assessed. The joint nPM + BCAS group exhibited synergistic effects on white matter injury (2.3× the additive nPM and FA + BCAS scores) with greater loss of corpus callosum volume on T2 magnetic resonance imaging (MRI) (30% smaller than FA group). Histochemical analyses suggested potential microglial-specific inflammatory responses with synergistic effects on corpus callosum C5 immunofluorescent density and whole brain nitrate concentrations (2.1× and 3.9× the additive nPM and FA + BCAS effects, respectively) in the joint exposure group. Transcriptomic responses (RNA-Seq) showed greater impact of nPM + BCAS than individual additive effects, consistent with changes in proinflammatory pathways. Although nPM exposure alone did not alter working memory, the nPM + BCAS cohort demonstrated impaired working memory when compared to the FA + BCAS group. Our data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.


Patterns and trends in opioid use among individuals with back pain in the United States.
Secondary analysis of Medical Expenditure Panel Survey from 1996 to 1999. To examine patterns in opioid use in 1996, 1997, 1998, and 1999 among individuals with back pain in the United States and to investigate trends in the use of overall and individual opioid category. To the authors' best knowledge, no study has examined at a national level the patterns and trends in opioid use among individuals with back pain in the United States. Individuals with back pain were stratified by sociodemographic characteristics and geographic regions. Rates of overall opioid use were compared among different strata by the use of simple and multivariate logistic regression models. To investigate trends in opioid use, use rates of the overall and individual opioid category in each year were calculated and compared. From 1996 to 1999, wide variations in overall opioid use were consistently observed among individuals with different educational levels, family income, and health insurance status. Regional variation in opioid use was also observed for most of the 4 years. After adjustment for covariates, health insurance status and geographic regions were consistent predictors of opioid use from 1997 to 1999. Trend analysis indicated that the rates of overall opioid use increased slightly across the 4-year span. Among individual opioid categories, the use of oxycodone or hydrocodone increased, whereas the use of propoxyphene decreased. The variation in overall opioid use among individuals with back pain with different sociodemographic characteristics and from different geographic regions suggested an opportunity to improve opioid prescribing patterns. The increase in the use of hydrocodone and oxycodone indicated a need to better assess the efficacy and safety associated with these drugs among individuals with back pain.


Water quality and plankton in the United States nearshore waters of Lake Huron.
Our goal in the development of a nearshore monitoring method has been to evaluate and refine an in situ mapping approach to assess the nearshore waters across the Great Lakes. The report here for Lake Huron is part of a broader effort being conducted across all five Great Lakes. We conducted an intensive survey for the United States nearshore of Lake Huron along a continuous shoreline transect (523 km) from Port Huron, Michigan, to Detour Passage. A depth contour of 20 m was towed with a conductivity-temperature depth profiler, fluorometer, transmissometer, and laser optical plankton counter. Multiple cross-contour tows (10-30 m) on the cruise dates were used to characterize the variability across a broader range of the nearshore. The cross-contour tows were comparable with the alongshore contour indicating that the 20-m contour does a good job of representing the nearshore region (10-30 m). Strong correlations were observed between water quality and spatially associated watershed land use. A repeat tow separated by several weeks investigated temporal variability in spatial patterns within a summer season. Strong correlations were observed across each variable for the temporal repeat across broad- and fine-scale spatial dimensions. The survey results for Lake Huron nearshore are briefly compared with a similar nearshore survey in Lake Superior. The biomass concentrations of lower food web components of Lake Huron were notably approximately 54-59 % of those in Lake Superior. The towed instrumentation survey supported the recent view of a change in Lake Huron to an ultra-oligotrophic state, which has been uncharacteristic in recent history.


The major, N2-dG adduct of (+)-anti-B[a]PDE induces G-->A mutations in a 5'-AGA-3' sequence context.
Previously, in a random mutagenesis study, the (+)-anti diol epoxide of benzo[a]pyrene [(+)-anti-B[a]PDE] was shown to induce a complex mutational spectrum in the supF gene of an Escherichia coli plasmid, which included insertions, deletions and base substitution mutations, notably a significant fraction of GC-->TA, GC-->AT and GC-->CG mutations. At some sites, a single type of mutation dominated and to understand individual mutagenic pathways these sites were chosen for study by site-specific means to determine whether the major adduct, [+ta]-B[a]P-N2-dG, was responsible. [+ta]-B[a]P-N2-dG was shown to induce approximately 95% G-->T mutations in a 5'-TGC-3' sequence context and approximately 80% G-->A mutations in a 5'-CGT-3' sequence context. (+)-anti-B[a]PDE induced principally GC-->CG mutations in the G133 sequence context (5'-AGA-3') in studies using both SOS-uninduced or SOS-induced E. coli. Herein, [+ta]-B[a]P-N2-dG is shown to induce principally G-->A mutations (>90%) either without or with SOS induction in a closely related 5'-AGA-3' sequence context (identical over 7 bp). This is the first time that there has been a discrepancy between the mutagenic specificity of (+)-anti-B[a]PDE versus [+ta]-B[a]P-N2-dG. Eight explanations for this discordance are considered. Four are ruled out; e.g. the second most prevalent adduct [+ca]-B[a]P-N2-dG also induces a preponderance of G-->A mutations (>90%), so it also is not responsible for (+)-anti-B[a]PDE-induced G133-->C mutations. The four explanations not ruled out are discussed and include that another minor adduct might be responsible and that the 5'-AGA-3' sequence context differed slightly in the studies with [+ta]-B[a]P-N2-dG versus (+)-anti-B[a]PDE. In spite of the discordance, [+ta]-B[a]P-N2-dG induces G-->A mutations in the context studied herein and this result has proven useful in generating a hypothesis for what conformations of [+ta]-B[a]P-N2-dG are responsible for G-->T versus G-->A mutations.


Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention.
Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005-2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P<0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups. Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.


Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma.
Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.


Annual glyphosate treatments alter growth of unaffected bentgrass (Agrostis) weeds and plant community composition.
Herbicide resistance is becoming more common in weed ecotypes and crop species including turfgrasses, but current gaps in knowledge limit predictive ecological risk assessments and risk management plans. This project examined the effect of annual glyphosate applications on the vegetative growth and reproductive potential of two weedy bentgrasses, creeping bentgrass (CB) and redtop (RT), where the glyphosate resistance (GR) trait was mimicked by covering the bentgrass plants during glyphosate application. Five field plots were studied in habitats commonly inhabited by weedy bentgrasses including an agricultural hayfield, natural meadow, and wasteland. Results showed that annual glyphosate treatment improved bentgrass survivorship, vegetative growth, and reproductive potential compared with bentgrass in unsprayed subplots. In the second year of growth, RT plants had an 86-fold increase in flower number in glyphosate-treated subplots versus controls, while CB plants had a 20-fold increase. At the end of the three year study, plant community composition had changed in glyphosate-treated subplots in hayfield and meadow plots compared to controls. Soils in subplots receiving glyphosate had higher nitrate concentrations than controls. This is the first study to mimic the GR trait in bentgrass plants with the goal of quantifying bentgrass response to glyphosate selection pressure and understanding the impacts on surrounding plant communities.


Creating the market under managed competition: getting there will not be half the fun.
To develop a framework for managed competition, implementers of health care reform will need to encourage the development of a large number of new AHPs. If experience with the rapid growth in HMOs that occurred in the late 1980s can serve as a guide, it would be expected that many new IPAs will form and that their development will occur at different rates in different communities, depending in part on the supply of medical resources and population demographics. There is evidence from past studies that new IPA entrants can stimulate the price competition desired by health care reformers. Lower bid prices were submitted by plans in the AHCCCS program in markets where new IPAs were competitors. IPAs also can fail, however, particularly at low enrollment levels. Implementers need to be concerned about the political and operational consequences of AHP failures during the early stages of health reform. If managed competition is to contain costs, implementers will need to develop effective policies to stimulate AHP entry, to oversee the performance of new AHPs during initial periods of low enrollment, and to protect consumers from any adverse consequences of AHP failures. It is possible that a large number of failures could occur among newly formed AHPs and that such failures could undermine the confidence of the public in managed competition. This would probably lead to calls for the replacement of managed competition with a more centrally managed and closely regulated health care system.


[Effects of beta-blockers on transmitral, pulmonary venous flows, and spontaneous echo-contrast grades in heart failure].
In this study, we aimed to investigate effects of metoprolol treatment on transmitral, pulmonary venous flows and spontaneous echo contrast in patients with heart failure. Twenty-four patients (mean age: 55+/-8 years) with heart failure were enrolled to the study. All were given metoprolol succinate with titrated target dose of 50 mg/d controlled release tablets for 1 month. Transmitral flow and pulmonary venous flow, systolic, diastolic and atrial reversal flow velocities were measured, and compared with the pretreatment values. Heart rate significantly decreased. No significant change was observed in ejection fraction. When the post treatment values were compared with the pretreatment values, it was detected that isovolumetric relaxation time significantly decreased (p<0.05), mitral E wave and E/A ratio were significantly increased (p<0.05 and p<0.05, respectively) after the treatment. A significant increase was observed in pulmonary vein systolic velocity after metoprolol treatment (p<0.05). Metoprolol treatment can cause an improvement in transmitral and pulmonary venous flows.


Older onset essential tremor: More rapid progression and more degenerative pathology.
There are few data on rate of progression in essential tremor (ET). To quantify the rate of tremor progression in a cross-sectional sample of 348 ET cases in an epidemiological study; characterize the relationship between age of tremor onset and rate of tremor progression in that sample; and characterize the relationship between age of tremor onset, rate of tremor progression, and severity of underlying brain changes in 9 cases from a brain repository. Rate of tremor progression was defined as tremor severity / duration. The degeneration index = number of torpedoes per section / Purkinje cell linear density. In the epidemiological study, older age of tremor onset was associated with faster rate of tremor progression (P < 0.001). In the brain repository, older age of tremor onset was associated with higher degeneration index (P = 0.037), and higher degeneration index was associated with faster rate of tremor progression (P = 0.018). In a large clinical sample, older age of onset was associated with more rapid tremor progression. In a brain bank, older age of onset was associated with more degenerative pathology in the cerebellum. As in several neurodegenerative disorders, in older onset cases, it is possible that the disease advances more rapidly.


Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).
Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume-Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. Primary-Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary-Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.


Alkaline ribonuclease and ribonuclease inhibitor in mammary gland during the lactation cycle and in the R3230AC mammary tumour.
Alkaline RNAase (ribonuclease) and RNAase inhibitor were assayed to determine the potential role of the degradative process in regulating the amount of RNA in the mammary gland and mammary tumour. Very little free alkaline RNAase activity was found in the cytosol fraction of the mammary gland of virgin, pregnant, lactating or involuting Fischer rats. However, addition of p-chloromercuribenzoate to the assay medium revealed latent RNAase which, when expressed on a DNA basis, decreased during pregnancy and lactation. The cytosol latent RNAase is stable in 0.125 M-H2SO4. The non-cytosol RNAase activity also decreased during pregnancy and lactation. Addition of Triton X-100 produced slightly higher activity at all stages tested. The inhibitor activity in rat mammary gland was very low before pregnancy, increased gradually during pregnancy and more dramatically at parturition, continued to increase throughout lactation and returned to resting-gland values by the sixth day of involution. The increase during pregnancy may be due to the increased cellularity of the gland, whereas the gain during lactation was more than could be accounted for by increases in cell number. The R3230AC transplantable mammary tumour resembles the normal gland in early lactation with respect to both its cytosol and non-cytosol alkaline RNAase activities and its moderately high content of RNAase inhibitor. The relatively high inhibitor and low RNAase activities in both the gland of the lactating rat and in the tumour are of potential significance in maintaining high amounts of RNA and increased rates of protein synthesis in these tissues.


Artificial insemination for oligospermia. A critical review.
The study concerns the review of the literature concerning the effectiveness of artificial insemination in cases of oligospermia. Differences in AIH techniques, the lack of standardized methodology explain the wide range of discrepancies in the resulting pregnancy rates. Still, in the course of time, a few certainties have been acquires: A detailed and thorough investigation of the female partner is mandatory. The use of fresh ejaculates is today totally obsolete, even with the help of cups, intra-cervical or eventual intra-uterine insemination. The standardization of seminal parameters still remains an unsolved problem. At the present time, intrauterine insemination with capacitated sperm is the method of choice. Still a basic condition is mandatory: a minimum of 1 M motile capacitated spermatozoa is required. Timing of insemination determined by the LH peak seems the most valuable procedure. The overall benefit is low, +/- 5% conception rate per cycle, and short lived because of the strain involved in an optimalized procedure. The policy to plan 3 to 6 AIH cycles before going over to an IVF procedure is the more debatable.


Dental visiting behaviours among primary schoolchildren: Application of the health belief model.
This study aimed to develop and validate a new instrument based on the health belief model and to use the instrument to investigate the determinants of regular dental attendance among primary schoolchildren. A cross-sectional study was conducted using a newly developed measurement scale based on the HBM, 4 health-promoting schools participated in the study and 958 students studying in grades 4-6 completed the questionnaire. The psychometric properties of the instrument were analysed, and a path analysis model was used to identify the determinants of regular dental attendance. The instrument had good internal consistency (Cronbach's α = 0.826-0.925) and a factor structure identical to HBM. Overall, the schoolchildren's health beliefs on caries treatment were positive. The determinants of regular dental visit were school location (β = -0.13), mother's education level (β = 0.15), susceptibility (β = -0.18) and barriers (β = -0.11). This study provided evidence that HBM is applicable to children's dental visiting behaviour and their health beliefs towards adherence to caries treatment. Although children had a positive attitude towards dental visits, environmental obstacles would interfere with dental visits. The newly developed instrument could be used to identify high-risk children and help design oral health interventions for these children. Moreover, policy makers should increase the accessibility of dental resources to enhance the utilization of dental care among schoolchildren.


The effect of temperature on the coupled slow and fast dynamics of an electrochemical oscillator.
The coupling among disparate time-scales is ubiquitous in many chemical and biological systems. We have recently investigated the effect of fast and, long-term, slow dynamics in surface processes underlying some electrocatalytic reactions. Herein we report on the effect of temperature on the coupled slow and fast dynamics of a model system, namely the electro-oxidation of formic acid on platinum studied at five temperatures between 5 and 45 °C. The main result was a turning point found at 25 °C, which clearly defines two regions for the temperature dependency on the overall kinetics. In addition, the long-term evolution allowed us to compare reaction steps related to fast and slow evolutions. Results were discussed in terms of the key role of PtO species, which chemically couple slow and fast dynamics. In summary we were able to: (a) identify the competition between two reaction steps as responsible for the occurrence of two temperature domains; (b) compare the relative activation energies of these two steps; and (c) suggest the role of a given reaction step on the period-increasing set of reactions involved in the oscillatory dynamics. The introduced methodology could be applied to other systems to uncover the temperature dependence of complex chemical networks.


Product variability of the 'cineole cassette' monoterpene synthases of related Nicotiana species.
Nicotiana species of the section Alatae characteristically emit the floral scent compounds of the 'cineole cassette' comprising 1,8-cineole, limonene, myrcene, α-pinene, β-pinene, sabinene, and α-terpineol. We successfully isolated genes of Nicotiana alata and Nicotiana langsdorfii that encoded enzymes, which produced the characteristic monoterpenes of this 'cineole cassette' with α-terpineol being most abundant in the volatile spectra. The amino acid sequences of both terpineol synthases were 99% identical. The enzymes cluster in a monophyletic branch together with the closely related cineole synthase of Nicotiana suaveolens and monoterpene synthase 1 of Solanum lycopersicum. The cyclization reactions (α-terpineol to 1,8-cineole) of the terpineol synthases of N. alata and N. langsdorfii were less efficient compared to the 'cineole cassette' monoterpene synthases of Arabidopsis thaliana, N. suaveolens, Salvia fruticosa, Salvia officinalis, and Citrus unshiu. The terpineol synthases of N. alata and N. langsdorfii were localized in pistils and in the adaxial and abaxial epidermis of the petals. The enzyme activities reached their maxima at the second day after anthesis when flowers were fully opened and the enzyme activity in N. alata was highest at the transition from day to night (diurnal rhythm).


Nef promotes evasion of human immunodeficiency virus type 1-infected cells from the CTLA-4-mediated inhibition of T-cell activation.
CTLA-4 is a negative regulator of T-cell receptor-mediated CD4(+) T-cell activation and function. Upregulation of CTLA-4 during human immunodeficiency virus type 1 (HIV-1) infection on activated T cells, particularly on HIV-specific CD4(+) T cells, correlates with immune dysfunction and disease progression. As HIV-1 infects and replicates in activated CD4(+) T cells, we investigated mechanisms by which HIV-1 modulates CTLA-4 expression to establish productive viral infection in these cells. Here, we demonstrate that HIV-1 infection in activated CD4(+) T cells was followed by Nef-mediated downregulation of CTLA-4. This was associated with a decreased T-cell activation threshold and significant resistance to CTLA-4 triggering. In line with these in vitro results, quantification of pro-viral HIV DNA from treatment-naive HIV-infected subjects demonstrated a preferential infection of memory CD4(+)CTLA-4(+) T cells, thus identifying CTLA-4 as a biomarker for HIV-infected cells in vivo. As transcriptionally active HIV-1 and Nef expression in vivo were previously shown to take place mainly in the CD3(+)CD4(-)CD8(-) [double-negative (DN)] cells, we further quantified HIV DNA in the CTLA-4(+) and CTLA-4(-) subpopulations of these cells. Our results showed that DN T cells lacking CTLA-4 expression were enriched in HIV DNA compared with DN CTLA-4(+) cells. Together, these results suggested that HIV-1 preferential infection of CD4(+)CTLA-4(+) T cells in vivo was followed by Nef-mediated concomitant downregulation of both CD4 and CTLA-4 upon transition to productive infection. This also highlights the propensity of HIV-1 to evade restriction of the key negative immune regulator CTLA-4 on cell activation and viral replication, and therefore contributes to the overall HIV-1 pathogenesis.


Reversible optical control of conjugated polymer solubility with sub-micrometer resolution.
Organic electronics promise to provide flexible, large-area circuitry such as photovoltaics, displays, and light emitting diodes that can be fabricated inexpensively from solutions. A major obstacle to this vision is that most conjugated organic materials are miscible, making solution-based fabrication of multilayer or micro- to nanoscale patterned films problematic. Here we demonstrate that the solubility of prototypical conductive polymer poly(3-hexylthiophene) (P3HT) can be reversibly "switched off" using high electron affinity molecular dopants, then later recovered with light or a suitable dedoping solution. Using this technique, we are able to stack mutually soluble materials and laterally pattern polymer films by evaporation or with light, achieving sub-micrometer, optically limited feature sizes. After forming these structures, the films can be dedoped without disrupting the patterned features; dedoped films have identical optical characteristics, charge carrier mobilities, and NMR spectra as as-cast P3HT films. This method greatly simplifies solution-based device fabrication, is easily adaptable to current manufacturing workflows, and is potentially generalizable to other classes of materials.


Is high serum uric acid a risk marker or a target for treatment? Examination of its independent effect in a large cohort with low cardiovascular risk.
Cohort studies evaluating increased uric acid level as a cardiovascular disease (CVD) risk factor have shown variable results; studies are particularly lacking in lower risk populations. Prospective cohort study. 484,568 adults participating in a medical screening program in Taiwan since 1994 were followed up for a median of 8.5 years. Two subgroups were constructed: the first (n = 246,697; 51%) excluded participants with either overt CVD or overt CVD risk factors (including hypertension, diabetes, obesity, and hypertriglyceridemia) and the second (n = 157,238; 32%) further excluded individuals with early-stage CVD risk factors (including prehypertension, prediabetes, overweight, and borderline hypertriglyceridemia). Serum uric acid. All-cause and CVD mortality risk assessed using Cox proportional hazards models for categorical and continuous serum uric acid levels. As applicable, models adjusted for 14 variables. Population-attributable fraction was applied to compare contributions to mortality between high uric acid level and other CVD risk factors. In the total cohort, mean age was 41.4 +/- 14.0 years and 26.2% had serum uric acid levels >or=7 mg/dL. Through 2007, there were 16,246 deaths (3.4% of all participants), with 35.2% of deaths occurring in individuals with hyperuricemia. Adjusted HRs associated with serum uric acid levels >or=7 mg/dL for all-cause and CVD mortality were 1.10 (95% CI, 1.04-1.17) and 1.38 (95% CI, 1.20-1.58), respectively. In individuals with hyperuricemia, 64.3% had overt CVD risk factors and 82.5% had either overt or early-stage CVD risk factors. Individuals with serum uric acid levels >or=8 mg/dL without overt CVD risk factors constituted 13.5% of the total study population with hyperuricemia; in analyses excluding those with overt CVD risk factors, serum uric acid level >or=8 mg/dL was significantly associated with all-cause and CVD mortality, with HRs of 1.37 (95% CI, 1.18-1.60) and 2.30 (95% CI, 1.51-3.49), respectively. In the subgroup of those with serum uric acid levels >or=8 mg/dL but who lacked both overt and early-stage CVD risk factors, the HRs for all-cause and CVD mortality were also significant and were 1.39 (95% CI, 1.08-1.78) and 2.38 (95% CI, 1.24-4.54), respectively. HRs for individuals with the same risk profiles but with serum uric acid of 7.0-7.9 mg/dL were not significant. In all groups, inclusion of proteinuria and glomerular filtration rate in models substantially attenuated the association between uric acid level and outcomes. High uric acid levels contributed a relatively insignificant portion to mortality (1.2%) and CVD deaths (4.5%) in this population. A single measurement of uric acid was used. Increased serum uric acid level is a minor, but significant, risk factor for all-cause and CVD mortality. However, except for a small proportion (13.5%), increased serum uric acid level is more a risk marker than a target for treatment and is not an independent risk. Determining appropriate groups to target in clinical trials for uric acid-lowering therapy is critical.


Ntdin, a tobacco senescence-associated gene, is involved in molybdenum cofactor biosynthesis.
To date, dozens of genes have been reported to be up-regulated with senescence in higher plants. Radish din1 and its ortholog sen1 of Arabidopsis are known as such, but their function is not clear yet. Here we have isolated their counterpart cDNA from tobacco and designated it as NTDIN: Its product, Ntdin, a 185 amino acid polypeptide with 56.8% and 54.2% identity to Atsen1 and Rsdin1, respectively, is localized in chloroplasts. Transcripts of Ntdin are induced by sulfate or nitrate but not by phosphate, suggesting its involvement in sulfur and nitrogen metabolism. A database search revealed that Ntdin shows similarity with the C-terminal region of Nicotiana plumbaginifolia Cnx5, which functions in molybdenum cofactor (Moco) biosynthesis. Transgenic tobacco plants with suppressed Ntdin are more tolerant to chlorate, a substrate analog of nitrate reductase, than controls, implying low nitrate reductase activity in the transgenic plants due to a deficiency of Moco. Indeed, enzymatic activities of two molybdoenzymes, nitrate reductase and xanthine dehydrogenase, in transgenic plants are found to be significantly lower than in control plants. Direct measurement of Moco contents reveals that those transgenic plants contain about 5% Moco of those of the control plants. Abscisic acid and indole-3-acidic acid, whose biosynthetic pathways require Moco, up-regulated Ntdin expression. Taken together, it is concluded that Ntdin functions in a certain step in Moco biosynthesis.


Clonal preservation of human pancreatic cell line derived from primary pancreatic adenocarcinoma.
Adenocarcinoma of the pancreas generally remains an incurable disease by available treatment modalities, demanding the development of a suitable cell-culture/animal model and the discovery and evaluation of novel therapeutic agents. We report the clonal preservation of a human pancreatic cell line (KCI-MOH1) established from a 74-year-old African-American man diagnosed with pancreatic cancer. Initially the human primary tumor was grown as a xenograft in SCID mice and, subsequently, a cell line was established from tumors grown as a xenograft as reported in our earlier publication. The molecular characterization of the primary tumor, the tumors grown as xenograft, and the cell line all revealed similar genotypic properties. By using an automated DNA sequencer, a K-ras mutation (codon 12, GGT to CGT, Gly to Arg) was detected in the pancreatic tumor tissue taken from the patient, whereas no p53 mutation was detected. The same K-ras mutation and unaltered p53 was also found in the xenograft tumor and in the KCI-MOH1 cell line. Chromosome analysis of the cultured cells revealed: 42,XY,add(3)(p11.2),der(7)t(7;12) (p22;q12),-10,-12,add (14)(p11),-18,add (20)(q13),-22/84, idemx2, which is the same chromosome complement found in xenograft tumors. The KCI-MOH1 cell line grows well in tissue culture and forms tumors in the SCID mice when implanted subcutaneously, as well as in orthotopic sites. The KCI-MOH1 cell line-derived SCID mouse xenograft model was used for efficacy evaluation of bryostatin 1, auristatin-PE, spongistatin 1, and gemcitabine alone and in combination. Tumor growth inhibition (T/C expressed as percentage), tumor growth delay (T - C), and log 10 kill for these agents were 38%, 22 days, and 0.53; 15%, 30 days, and 0.80; 24%, 25 days, and 0.66; and 10%, 33 days, and 0.90, respectively. When given in combination, two of seven gemcitabine + auristatin-PE-treated animals were free of tumors for 150 days and were considered cured. Animals treated with a combination of bryostatin 1 and gemcitabine and a combination of spongistatin and gemcitabine produced remissions in only one of seven mice. From these results, we conclude that (a) this is the first study illustrating that clonal characteristics of primary pancreatic tumors remained unchanged when implanted in mice and as a permanent cell line grown in vitro; and (b) there is a synergistic effect between gemcitabine and selected marine products tested in this study, which is more apparent in the gemcitabine and auristatin-PE combination. The results of this preliminary study suggest that these agents should be explored clinically in the treatment of pancreatic cancer.


Dental practitioner rural work movements: a systematic review.
There is a globally observed unequal distribution of dental and other health practitioners between urban and rural areas in OECD countries. Dental practitioners provide important primary healthcare services to rural populations. Workforce shortages and stability issues in underserved areas can have negative effects on rural communities. Strategies used to fix the dental practitioner workforce maldistribution need to be investigated. The study had primary focus on Australia and included relevant international literature. Databases used were PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Informit, Web of Science, Scopus and Summon. Search terms included dental practitioner, rural, remote, retention, recruitment and strategies. Sixteen articles met the inclusion criteria. The articles described a total of eight different positive factors and 12 negative factors towards rural practice. The positive factors related to the nature of the type of clinical work being a 'challenge', close social and professional support networks, enjoyment of rural lifestyle and successful integration into the rural community. The negative factors mentioned included social and professional isolation, workload and type of clinical work, access to further education opportunities, access to facilities, education for children and job opportunities for a partner, and inability to integrate into the rural community. The articles that analysed recruitment incentives described three strategies currently used to influence recruitment, all of which were financial or contractual in nature. Articles mentioning retention factors described seven long-term retention motivators; of these, six of them were personal reasons. The most commonly mentioned motivational factor for recruitment and retention of the rural dental practitioner workforce was the effect of prior rural exposure for dental practitioners. The results of this review indicate that the most important influences on rural dental practitioner workforce recruitment and retention were a combination of financial reimbursement and personal reasons. There was also a large influence of rural medical workforce research on untested assumptions and drivers of the rural dental practitioner workforce. The high recruitment rate compared with the low retention rate indicates that current strategies were not effective in addressing rural dental practitioner workforce shortages in the long term.


Stabilization of cell wall proteins in Bacillus subtilis: a proteomic approach.
Even though cell wall proteins of Bacillus subtilis are characterized by specific cell wall retention signals, some of these are also components of the extracellular proteome. In contrast to the majority of extracellular proteins, wall binding proteins disappeared from the extracellular proteome during the stationary phase and are subjected to proteolysis. Thus, the extracellular proteome of the multiple protease-deficient strain WB700 was analyzed which showed an increased stability of secreted WapA processing products during the stationary phase. In addition, stabilization of the WapA processing products was observed also in a sigD mutant strain which is impaired in motility and cell wall turnover. Next, we analyzed if proteins that can be extracted from B. subtilis cell walls are stabilized in the WB700 strain as well as in the sigD mutant. Thus, the cell wall proteome of B. subtilis wild type was defined showing most abundantly cell wall binding proteins (CWBPs) resulting from the WapA and WprA precursor processing. The inactivation of extracellular proteases as well as SigmaD caused an increase of CWBP105 and a decrease of CWBP62 in the cell wall proteome. We conclude that WapA processing products are substrates for the extracellular proteases which are stabilized in the absence of sigD due to an impaired cell wall turnover.


The effect of streptozotocin induced diabetes on sperm function: a closer look at AGEs, RAGEs, MAPKs and activation of the apoptotic pathway.
This study was designed to (1) investigate the possible mechanisms through which diabetes-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) activation can affect male reproductive function; and (2) corroborate the interaction of previously established independent pathways. Male albino Wistar rats (14-weeks old) weighing 250-300 g received either a single intraperitoneal injection of streptozotocin (30 mg/kg or 60 mg/kg), represented as STZ30 or STZ60 respectively, or citrate buffer (control). Diabetes mellitus (DM) was confirmed if plasma glucose levels were ≥ 14 mmol/L after 1 week. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160 mg/kg body weight). The testes and epididymides were harvested. The testes were used for biochemical and Western blot analysis, while sperm was retrieved from the epididymis and analysed with computer-aided sperm analysis. The blood glucose levels of STZ60 animals were above the cut-off point and hence these animals were regarded as diabetic. Diabetic animals presented with a non-significant increase in AGE and RAGE expression. Diabetic animals showed a significant increase in the expression of cleaved caspase 3 compared to control (p < 0.001), and these animals also presented with an increase in the expression of JNK (p < 0.05), PARP (p = 0.059) and p38 MAPK (p = 0.1). Diabetic animals also displayed decreased catalase activity accompanied by a non-significant increase in malondialdehyde levels. Additionally, there was a significant decrease in the percentage of progressively motile spermatozoa (p < 0.05) in diabetic animals. This study has shed some light on the interplay between DM, AGE, RAGE and mitogen-activated protein kinase signalling in the testes of diabetic rats, which can result in altered sperm function and contribute to male infertility. However, more studies are needed to better understand this complicated process.


Cladocerans (Branchiopoda) of a tropical estuary in Brazil.
The study was conducted in the Capibaribe river estuary in Recife (Brazil) to assess the role played by cladocerans in a eutrophic environment. Samplings were carried out monthly at 4 fixed stations along the estuary from July 1987 to June 1988. Collections were made with a plankton net of 65 micrometers mesh size. Six cladocerans species were registered: Penilia avirostris, Diaphanosoma spinulosum, Chlydorus barroisi, Ceriodaphnia rigaudi, Ilyocryptus spinifer, and Moina micrura. The most frequent species was Moina micrura with 49%. The only true marine species was Penilia avirostris, which was registered at station 1 (close to the river mouth), during high and low tide and in the dry season. The Cladocera average density decreased from 329 ind.m'3 (August 1987, high tide) to 2 ind.m(-3) (March 1988, high tide) due to the high load of organic and chemical pollution received by the estuary. At all stations, D. spinulosum, M. micrura, and C. barroisi occurred with a wide distribution, mainly during the rainy season. C. rigaudi and I. spinifer were rare, occurring only during the rainy season. Cladocerans played an important role in the food webs of the plankton community of the Capibaribe tropical estuary and the dominance of a few small species indicated a hypereutrophic environment. A high level of disturbance was indicated by the decline in diversity of specialized species and the increase in abundance of opportunistic species like M. micrura.


Combination of ginsenoside Rb1 and Rd protects the retina against bright light-induced degeneration.
Photoreceptor degeneration is a central pathology of various retinal degenerative diseases which currently lack effective therapies. Antioxidant and anti-inflammatory activities are noted for Panax notoginsenoside saponins (PNS) and related saponin compound(s). However, the photoreceptor protective potentials of PNS or related saponin compound(s) remain unknown. The current study revealed that PNS protected against photoreceptor loss in bright light-exposed BALB/c mice. Combination of ginsenoside Rb1 and Rd, two major saponin compounds of PNS, recapitulated the retinal protection of PNS and attenuated retinal oxidative stress and inflammatory changes. Rb1 or Rd partially alleviated all-trans-Retinal-induced oxidative stress in ARPE19 cells. Rb1 or Rd suppressed lipopolysaccharides (LPS)-induced proinflammatory gene expression in ARPE19 and RAW264.7 cells. Rb1 or Rd also modulated the expression of proinflammatory microRNA, miR-155 and its direct target, anti-inflammatory SHIP1, in LPS-stimulated RAW264.7 cells. The retinal expression of miR-155 and SHIP1 was altered preceding extensive retinal damage, which was maintained at normal level by Rb1 and Rd combination. This work shows for the first time that altered expression of miR-155 and SHIP1 are involved in photoreceptor degeneration. Most importantly, novel retinal protective activities of combination of Rb1 and Rd justify further evaluation for the treatment of related retinal degenerative disorders.


Association between organic food consumption and metabolic syndrome: cross-sectional results from the NutriNet-Santé study.
Metabolic syndrome (MetS), a multicomponent condition, is a cardiovascular disease predictor. Although exposure to agricultural pesticides has been suggested as a potential contributor to the rising rates of obesity, type 2 diabetes, and other features of metabolic disorders, no studies have focused on the association between consumption of organic food (produced without synthetic pesticides) and MetS. We aimed to investigate the cross-sectional association between organic food consumption and MetS in French adults to determine whether it would be worth conducting further studies, particularly large prospective and randomised trials. A total of 8174 participants from the NutriNet-Santé study who attended a clinical visit and completed an organic food frequency questionnaire were included in this cross-sectional analysis. We evaluated the association between the proportion of organic food in the diet (overall and by food group) and MetS using Poisson regression models while adjusting for potential confounders. Higher organic food consumption was negatively associated with the prevalence of MetS: adjusted prevalence ratio was 0.69 (95% CI 0.61, 0.78) when comparing the third tertile of proportion of organic food in the diet with the first one (p value <0.0001). Higher consumption of organic plant-based foods was also related to a lower probability of having MetS. In addition, when stratifying by lifestyle factors (nutritional quality of the diet, smoking status, and physical activity), a significant negative association was detected in each subgroup (p values <0.05), except among smokers. Our results showed that a higher organic food consumption was associated with a lower probability of having MetS. Additional prospective studies and randomised trials are required to ascertain the relationship between organic food consumption and metabolic disorders.


Evaluation of Airway Volume in Cleft Lip and Palate Following Nasoalveolar Molding.
Patients with cleft lip and palate (CLP) have commonly reduced nasal airways and are more prone to snoring, mouth breathing and hypopnea during sleep. Therefore, the morphometric evaluation of pharyngeal airway in patients with CLP is crucial. The purpose of this study is to evaluate the pharyngeal airway volumes of patients with CLP who underwent nasoalveolar molding (NAM) and to compare them with a well-matched control group without NAM. The study consisted of 40 patients with CLP divided into 2 main groups (26 with NAM; 14 without NAM) and 4 subgroups (15 unilateral CLP [UCLP] with NAM, mean age: 10.13 ± 1.30 years; 11 bilateral CLP [BCLP] with NAM, mean age: 10.55 ± 1.51 years; 7 UCLP without NAM, mean age: 9.86 ± 1.68 years; 7 BCLP without NAM, mean age: 10.28 ± 1.89 years). Nasopharyngeal, oropharyngeal, and total airway volumes of all the patients were calculated 3-dimensionally with cone-beam computed tomography. There were statistically significant differences in nasopharyngeal volume (P < 0.05) of NAM group compared to control group; however, volumetric differences in oropharyngeal and total pharyngeal airway were not significant (P > 0.05). The amount of nasopharyngeal, oropharyngeal, and total pharyngeal airway size in the BCLP with NAM group was significantly larger compared to BCLP without NAM group (P < 0.05). However, UCLP did not show any significant difference in NAM group (P > 0.05). This study implies that NAM can effectively enlarge the nasopharyngeal airway size in patient with CLP. In addition, the pharyngeal airway volume enlargement is more apparent in BCLP than UCLP individuals.


Continuum of care in maternal, newborn and child health in Indonesia: Evidence from the Indonesia Demographic and Health Survey.
Maternal and child health improved considerably due to the Sustainable Development Goals of the United Nations. However, the rate of preventable death worldwide remains high. Nevertheless, implementation was insufficient in low- and middle-income countries, including Indonesia. The study aims to assess the relationships between continuum of care (CoC) in maternal, neonatal and child health (MNCH) services and levels of care in Indonesia, examine the distribution of utilisation and investigate the associations between CoC in MNCH. Data were derived from the recent 2017 Indonesia Demographic and Health Survey. Fieldwork took place from July 24 to September 30, 2017. The sample included ever-married women aged 15-49 years who had given birth in the last 5 years prior to the survey. The total sample size is 15,288. Only 52.6% (n = 8038) continued to receive the three levels of MNCH services. Multivariate analysis revealed that variables, such as socioeconomic status, parity and distance from health facilities were statistically significantly associated with the continuum from antenatal to postnatal care (PNC). The use of each level of MNCH care is correlated with the next level of care. Antenatal care is associated with delivery care which is subsequently associated with postnatal care. Identifying populations that contribute significantly to overall health inequalities and a well-established follow-up system from pregnancy to PNC may enhance maternal and child health and equity outcomes.


Soccer Small-Sided Games Activities Vary According to the Interval Regime and their Order of Presentation within the Session.
In order to investigate the physical demands of widely used in soccer small-sided games (SSGs), we compared game variations performed under different interval (fixed or variable) and timing regimens (beginning or end of a training session). Twelve male players wore GPS devices during the SSGs to record total distance, relative distance, distance at different speeds, and maximum velocity variables. Four variations of SSGs (4x4) were randomly applied: beginning of a training session with fixed and variable recovery, or end of a training session with fixed and variable recovery. During the beginning or end of a training session settings with fixed recovery duration, 2-min of playing and 2-min of recovery were provided. During the beginning and end of a training session settings with variable recovery, athletes kept playing until a goal was scored, or up to 2-min if no goals were scored. Results were analysed using MANOVA. Total distance and relative distance were higher in the beginning compared to end of training sessions for both fixed and variable recovery duration (small to moderate effect sizes). Distance at various speed ranges (i.e., 13-18 km/h and >18 km/h) was higher (p ≤ 0.01) at the beginning than at the end of training sessions with variable recovery. In addition, distance >18 km/h was higher at the beginning of a training session with variable recovery than fixed recovery and at the end of a training session with variable recovery than fixed recovery. In conclusion, several physical demand characteristics are affected by the moment of SSG application, while others respond to the recovery regime during SSGs, thus providing indications to the coaches to prescribe the intended training intensity by manipulating the context.


Genome-Wide Identification of Splicing Quantitative Trait Loci (sQTLs) in Diverse Ecotypes of Arabidopsis thaliana.
Alternative splicing (AS) of pre-mRNAs contributes to transcriptome diversity and enables plants to generate different protein isoforms from a single gene and/or fine-tune gene expression during different development stages and environmental changes. Although AS is pervasive, the genetic basis for differential isoform usage in plants is still emerging. In this study, we performed genome-wide analysis in 666 geographically distributed diverse ecotypes of Arabidopsis thaliana to identify genomic regions [splicing quantitative trait loci (sQTLs)] that may regulate differential AS. These ecotypes belong to different microclimatic conditions and are part of the relict and non-relict populations. Although sQTLs were spread across the genome, we observed enrichment for trans-sQTL (trans-sQTLs hotspots) on chromosome one. Furthermore, we identified several sQTL (911) that co-localized with trait-linked single nucleotide polymorphisms (SNP) identified in the Arabidopsis genome-wide association studies (AraGWAS). Many sQTLs were enriched among circadian clock, flowering, and stress-responsive genes, suggesting a role for differential isoform usage in regulating these important processes in diverse ecotypes of Arabidopsis. In conclusion, the current study provides a deep insight into SNPs affecting isoform ratios/genes and facilitates a better mechanistic understanding of trait-associated SNPs in GWAS studies. To the best of our knowledge, this is the first report of sQTL analysis in a large set of Arabidopsis ecotypes and can be used as a reference to perform sQTL analysis in the Brassicaceae family. Since whole genome and transcriptome datasets are available for these diverse ecotypes, it could serve as a powerful resource for the biological interpretation of trait-associated loci, splice isoform ratios, and their phenotypic consequences to help produce more resilient and high yield crop varieties.


Optimal antenna locations of the VLBI Global Observing System for the estimation of Earth orientation parameters.
To support monitoring subtle effects in the Earth system such as a mean sea level rise of 3 mm/year, a next-generation VLBI system, the VLBI Global Observing System (VGOS), has been developed and a new VGOS station network is being built. However, the geometry of the current VGOS network and its planned extension suffer from a lack of stations in the southern hemisphere. In this investigation, we identify optimal locations for additional VGOS radio telescopes with a new method based on bulk observing schedule generation and subsequent large-scale Monte-Carlo simulations. The location of the additional station is varied over 477 possible locations, homogeneously distributed over land areas on the globe. For each antenna location, several schedules have been generated and simulated to minimize the effects of scheduling and the randomness of simulations. Thereby, it is possible to judge, in which regions an additional VGOS station would have the biggest impact on the precision of the estimated geodetic parameters, in our case assessed by the repeatabilities of the estimated Earth orientation parameters (EOPs). To generate highly optimized schedules and to remove effects due to non-optimized scheduling, a total of 93 thousand schedules were iteratively generated, investigating over 300 billion scans and 2.4 trillion observations. Each schedule was further simulated 1000 times, leading to over 5 trillion simulated and analyzed observations. Although the optimum location of a future VLBI station depends on the EOP of interest and the geometry of the existing network, it is shown that the more the VGOS network grows, the more the lack of southern stations becomes prominent. The best location for an additional VGOS station for most EOP components and especially in the case of future VGOS networks would be the southern part of South America. It is further shown that the location of the additional antenna highly determines the expectable precision of the EOP estimates. For a 6-station network, the location of an additional seventh antenna can improve the precision of the EOP by a factor of 2.4 to 3.8. For an 18-station network, the location of an additional 19th station still improves the repeatability by a factor of 1.6. It is also found that adding a station at some locations will not improve the precision at all.


Magnitude of and risk factors for in-hospital and postdischarge stroke in patients with acute coronary syndromes: findings from a Global Registry of Acute Coronary Events.
Stroke is a recognized complication after acute myocardial infarction, but few studies have investigated the incidence and outcome of stroke in patients with acute coronary syndrome (ACS). This study examined the incidence and outcomes of hemorrhagic and nonhemorrhagic stroke and risk factors associated with stroke in patients with ACS. Data were obtained from 35,233 patients enrolled in the Global Registry of Acute Coronary Events (GRACE) with an ACS. In-hospital strokes occurred in 310 patients (0.9%), of which 100 (32.6%) were fatal. The incidence of in-hospital stroke was significantly higher in patients with ST-segment-elevation myocardial infarction than in non-ST-segment myocardial infarction or unstable angina (1.3%, 0.9%, 0.5%, respectively; P<0.001). Overall, 35.5% of in-hospital strokes occurred within 6 days of hospitalization. The strongest risk factor for in-hospital nonhemorrhagic stroke was in-hospital CABG, followed by in-hospital atrial fibrillation, previous stroke, initial enzyme elevation, and advanced age. Prior statin use was a protective factor. After controlling for potential confounders, in-hospital mortality was significantly higher among patients who experienced an in-hospital stroke (adjusted odds ratio, 8.3; 95% CI, 6.0 to 11.4). A total of 269 additional strokes (1.1%) occurred within 6 months after discharge from hospital, of which 56 (20.9%) were fatal. The most important risk factor for postdischarge stroke was the occurrence of an in-hospital stroke. Stroke is an uncommon event in patients with ACS but is associated with high mortality. Despite current therapy, the incidence of postdischarge stroke is not low. New approaches are warranted to reduce the risk of stroke in patients with ACS.


Effect of Stenting Strategy on the Outcome in Patients with Non-Left Main Bifurcation Lesions.
Previous studies have not compared outcomes between different percutaneous coronary intervention (PCI) strategies and lesion locations in non-left main (LM) bifurcation lesions. We enrolled 2044 patients from a multicenter registry with an LAD bifurcation lesion (n = 1551) or non-LAD bifurcation lesion (n = 493). The primary outcome was target lesion failure (TLF), a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). During a median follow-up period of 38 months, non-LAD bifurcation lesions treated with the two-stent strategy, compared with the one-stent strategy, were associated with more frequent TLF (20.7% vs. 6.3%, p < 0.01), TLR (16.7% vs. 4.7%, p < 0.01), and target vessel revascularization (TVR; 18.2% vs. 6.3%, p < 0.01). There was no significant difference in outcome among LAD bifurcation lesions treated with different PCI strategies. The two-stent strategy was associated with a higher risk of TLF (adjusted HR 4.34, CI 1.93−9.76, p < 0.01), TLR (adjusted HR 4.30, CI 1.64−11.27, p < 0.01), and TVR (adjusted HR 5.07, CI 1.69−9.74, p < 0.01) in the non-LAD bifurcation lesions. The planned one-stent strategy is preferable to the two-stent strategy for the treatment of non-LAD bifurcation lesions.


AChE mRNA expression as a possible novel biomarker for the diagnosis of coronary artery disease and Alzheimer's disease, and its association with oxidative stress.
Oxidative metabolic reactions and their by products have played a role in coronary artery disease (CAD) and Alzheimer's disease (AD) pathogenesis. This study was carried out on 28 patients with AD, 21 patients with CAD, and 28 healthy as control. Oxidative stress biomarkers and acetylcholinesterase (AChE) activity were assayed in plasma. mRNA expression of AChE was investigated in leukocytes of patients with CAD and AD. Thus, Alzheimer's and coronary artery patients were observed that the protein carbonyl levels and mRNA expression of AChE were increased (p<.05, p<.01, respectively). The plasma total thiol levels were decreased compared to the control group (p<.05). There was a significant relationship between amyloid β (Aβ) accumulation and oxidative stress, cholinergic gene expression. AChE gene expression and protein oxidation were increased in patients with AD and CAD. These results suggest that increased release of AChE from cells produces neurotoxic β-amyloid plaques and may cause neurodegenerative diseases.


The carboxyl terminal domain regulates the unitary conductance and voltage dependence of connexin40 gap junction channels.
Chemical regulation of connexin (Cx) 40 and Cx43 follows a ball-and-chain model, in which the carboxyl terminal (CT) domain acts as a gating particle that binds to a receptor affiliated with the pore. Moreover, Cx40 channels can be closed by a heterodomain interaction with the CT domain of Cx43 and vice versa. Here, we report similar interactions in the establishment of the unitary conductance and voltage-dependent profile of Cx40 in N2A cells. Two mean unitary conductance values ("lower conductance" and "main") were detected in wild-type Cx40. Truncation of the CT domain at amino acid 248 (Cx40tr248) caused the disappearance of the lower-conductance state. Coexpression of Cx40tr248 with the CT fragment of either Cx40 (homodomain interactions) or Cx43 (heterodomain interactions) rescued the unitary conductance profile of Cx40. In the N2A cells, the time course of macroscopic junctional current relaxation was best described by a biexponential function in the wild-type Cx40 channels, but it was reduced to a single-exponential function after truncation. However, macroscopic junctional currents recorded in the oocyte expression system were not significantly different between the wild-type and mutant channels. Concatenation of the CT domain of Cx43 to amino acids 1 to 248 of Cx40 yielded a chimeric channel with unitary conductance and voltage-gating profile indistinguishable from that of wild-type Cx40. We conclude that residence of Cx40 channels in the lower-conductance state involves a ball-and-chain type of interaction between the CT domain and the pore-forming region. This interaction can be either homologous (Cx40 truncation with Cx40CT) or heterologous (with the Cx43CT).


The physical properties of lipid monolayers and bilayers containing calixarenes sensitive to cytochrome c.
We studied physical properties of the monolayers and bilayer lipid membranes (BLM) formed by calix[6]arene carboxylic acid derivative (CX) and its mixtures with diphytanoylphosphatidylcholine (DPhPC) by means of measurement surface pressure, surface dipole potential and electrostriction. CX forms stable monolayers at an air-water interface and complexes in mixed monolayers contained DPhPC. Calixarenes increase the elastic moduli of lipid monolayers as well as BLM. Cytochrome c (cyt c) specifically binds to CX by incorporation of the amino groups of lysine residues at the protein surface. This binding affected the physical properties of CX monolayers depending on their initial surface pressure. Addition of cyt c into the water subphase induced increase of surface pressure of CX monolayers at relatively low initial pressure (15 mN/m) when monolayer was in liquid expanded state (LE). This may be due interaction of positively charged cyt c with negatively charged carboxylic groups of CX and also by its penetration into the air-water interface. However, much subtle changes were observed for higher initial surface pressure (20 and 35 mN/m) when monolayer is in liquid condensed (LC) and solid (S) state, respectively. Lysine induced substantially lower changes in surface pressure in comparison with that of cyt c.


Relationship between abnormal sperm chromatin packing and IVF results.
This study was initiated to determine the relationship between the fertilizing potential of spermatozoa and abnormalities in the compact packing of their chromatin which occurs in the final stage of male germ cell differentiation. Chromatin packing involves disulphide bridge covalent cross-linking. The degree of packing was determined from the accessibility of DNA to a fluorescent dye, ethidium bromide, following detergent treatment of the spermatozoa. The amount of dye bound was determined by flow cytometry in the presence or absence of heparin, a polyanion which removes only non-disulphide bridge-linked proteins. The results of a number of different sperm samples were compared with their results following in-vitro fertilization, and a relationship between disordered sperm chromatin packing and rates of embryo cleavage was observed. This study suggests that abnormal chromatin packing in spermatozoa may contribute to male fertility.


Dynamic changes of hepatitis B virus polymerase gene including YMDD motif in lamivudine-treated patients with chronic hepatitis B.
The mutation of YMDD motif of hepatitis B virus (HBV) polymerase gene is the most frequent cause in HBV resistant to lamivudine. The aim of the study was to investigate variation features of HBV polymerase gene in chronic hepatitis B (CHB) patients before and after lamivudine treatment. From the serum samples of five CHB patients before and after 12 months of lamivudine treatment, HBV polymerase gene was amplificated and positive DNA fragments were cloned into JM105 competent cell. Twenty positive clones of every sample were checked with mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and YMDD variants were sequenced. Among five patients after 12 months of lamivudine treatment, M552I mutations in two patients with HBV DNA rebounding and D553G mutation in one non-responder were detected except two patients with negative HBV DNA consecutively. In summary, D553G mutation is probably one of the reasons that caused non-responders during lamivudine treatment. The mutations of YMDD motif occurred after lamivudine treatment are caused by the induction of lamivudine.


The immunologic considerations in human head transplantation.
The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient.


Laparoscopic findings in primary sclerosing cholangitis.
Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by segmental narrowing and dilatation of bile ducts. Few studies have been performed on the laparoscopic findings associated with this disease, and the present study was intended to assess the usefulness of laparoscopy for the diagnosis and staging of PSC. Six patients were examined by laparoscopy with liver biopsy. Repeated laparoscopy was performed in three patients. Laparoscopy revealed coarse surface irregularity and discoloration. Surface irregularity was classified into four grades: smooth, shallowly depressed, undulated, and nodular. The affected area showed whitish yellow discoloration. The discolored area was demonstrated as a poorly stained area by intravenous injection of indocyanine green (ICG). Lobular markings became apparent because of the yellow color change in the portal tract, resulting in a leopardskin-like appearance. Lymph-vessel dilatation was seen in advanced stages. Repeated laparoscopy of a patient without treatment demonstrated a progression from a smooth surface to a shallow depression with leopardskin-like markings. On the other hand, the two patients treated with immunosuppressive agents showed improvement of liver swelling and disappearance of the leopardskin-like markings and lymph-vessel dilatation. Laparoscopy may provide useful information for the diagnosis and staging of PSC.


The role played by salts in the formation of SBA-15, an in situ small-angle X-ray scattering/diffraction study.
The influence of salts (NaCl, NaBr, and NaI) on the formation of mesoporous silica SBA-15 was studied in situ by small-angle X-ray scattering and diffraction. Pluronic P104 was used as structure director. The micellar properties and the dynamics of formation were clearly dependent on the presence of salt. It was also shown that the kinetics of mesophase formation, the initial value of the cell parameters, and the extent of long-range order were all influenced by salt additions. The observations are explained to primarily originate from the influence of the anions on the ethylene oxide part of the polymer, i.e., the corona region of the Pluronic micelles. Two effects are identified: a general ion effect causing dehydration of the ethylene oxide part and consequently inducing micellar growth, and a specific ion effect that counterbalances this. The study provides the basis for understanding the means by which addition of simple Na-salts influence the formation of mesoscopically ordered silicas synthesized using nonionic surfactants as structure directors, hence advancing the knowledge base toward a more rational design of mesoporous materials.


Medical therapies for prevention of cardiovascular and renal events in patients with atrial fibrillation and diabetes mellitus.
Atrial fibrillation (AF), type 2 diabetes mellitus (DM), and chronic kidney disease (CKD) are three global epidemics with significant effects on morbidity and mortality. Diabetes is a risk factor for AF, and a risk factor for thromboembolism, comorbidity, and mortality when AF is present. The pathophysiology of diabetes-related AF and interrelationships with cardiovascular events and renal events is not fully understood but is in part related to structural, electrical, electromechanical, and autonomic remodelling. The current practice guidelines offer limited recommendations on the management of patients with AF (or risk of AF) and diabetes with its own heterogeneity for the prevention of cardiovascular and renal events. This document discusses possible clinical approaches for these patients. In the last decade, there have been major improvements for the prevention of stroke in AF patients with direct oral anticoagulants, which are preferable to vitamin K antagonists for stroke prevention in DM. Because of the increased risk rate for several cardiovascular adverse events in diabetic patients, a similar relative risk reduction generally translates into greater absolute risk reduction in the diabetic population. Recent trials with non-insulin diabetes drugs using glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors showed a significant reduction for the risk of major adverse cardiovascular events in patients with type 2 DM. Sodium-glucose cotransporter-2 inhibitors also showed a large reduction in hospitalization for heart failure and renal events, which need to be more completely evaluated in patients with AF. Mechanisms, risks, and optimal management of AF patients with DM who have or are under risk of developing heart failure or CKD are also discussed in this document. The benefits of medical therapies for these patients still need to be put into perspective, and gaps in evidence on some of these issues are likely to be addressed in future years.


An examination of the relationship between sunlight exposure and hot flush in working women.
We examined whether sunlight affects hot flushes in working menopausal women and explored effect modification by shift work and season. In this prospective cohort study, daily hot flush score (outcome) was measured by the 7-day North Central Cancer Treatment Group Daily Vasomotor Symptoms Diary. Daily duration of sunlight (≥2000 lux) was recorded by the HOBO MX2202 pendant. Both variables were measured in two 7-day data collection phases. T0 data were collected during the Australian Summer (December 2017, January and February 2018); and T1 data were collected in the Australian winter (June, July and August 2018). Linear mixed effects model was used. Shift work and season were both confounders and effect modifiers. To detect a median effect size of R2 = 0.2, 34 women were required to achieve an effective sample size of 41. A total of 49 menopausal women were recruited, 11 shift and 38 day workers. Some 13 women had various missing observations. For shift workers, an hour increase in sunlight exposure was associated with a 1.4-point reduction in hot flush score (p = .016). This relationship was not significant for day workers (p = .185). The finding of this study suggests increased sunlight exposure might improve hot flushes in menopausal shift workers who are moderately bothered by hot flushes, but probably not in day workers. The possible role of shift-work associated circadian disruption on estrogen level in regard to elevated intensity and frequency of hot flush in menopausal women is discussed.


Effect of caffeic acid phenethyl ester on bone formation in the expanded inter-premaxillary suture.
Narrow maxilla is a common problem in orthodontics and dentofacial orthopedics. To solve this problem, a procedure called rapid maxillary expansion (RME) has been used. However, relapse tendency is a major problem of RME. Although relapse tendency is not clearly understood, various treatment procedures and new applications have been investigated. The present study aimed to investigate the possible effectiveness of caffeic acid phenethyl ester (CAPE) on new bone formation in rat midpalatal suture after RME. Twenty male Sprague Dawley rats were used in this study. The animals were randomly divided into two groups as control and CAPE group. In the CAPE group, CAPE was administered systemically via intraperitoneal injection. RME procedure was performed on all animals. For this purpose, the springs were placed on the maxillary incisors of rats and activated for 5 days. After then, the springs were removed and replaced with short lengths of rectangular retaining wire for consolidation period of 15 days. At the end of the study, histomorphometric analysis was carried out to assess new bone formation. New bone formation was significantly greater in the CAPE group than the control group (P<0.05). CAPE enhances new bone formation in midpalatal suture after RME. These results show that CAPE may decrease the time needed for retention.


Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.
Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2) (KD) AMPK mice and wild type (WT) littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.


Effects of pistachio by-products on digestibility, milk production, milk fatty acid profile and blood metabolites in Saanen dairy goats.
The objective of this study was to investigate the effects of pistachio by-products (PBP) on nutrient digestibility, blood metabolites and milk fatty acid (FA) profile in Saanen dairy goats. Nine multiparous lactating Saanen goats (on day 90 post-partum, 45 ± 2/kg BW) were randomly assigned to a 3 × 3 Latin square design with three treatment diets: 1) control diet (alfalfa hay based), 2) 32% PBP and 3) 32% PBP + polyethylene glycol (PEG-4000; 1 g/kg dry matter). Each period lasted 21 days, including 14 day for treatment adaptation and 7 day for data collection. Pistachio by-products significantly decreased (p < 0.01) crude protein (CP) digestibility compared with the control diet (64.4% vs. 58.7%), but PEG addition did not differ for CP digestibility of goats fed 32% PBP + PEG and those fed the two other diets. The digestibility of NDF tended (p = 0.06) to decrease for goats fed PBP compared with those fed the control diet. Yields of milk and 4% fat-corrected milk were not affected by dietary treatments. Compared with the control diet, PBP supplementation appreciably changed the proportions of almost all the milk FA measured; the main effects were decreases (p < 0.01) in FA from 8:0 to 16:0 and increases (p < 0.01) proportions of cis-9, trans-11 18:2 and trans-11 18:1, monounsaturated FA, polyunsaturated FA and long-chain FA. The saturated FA, short-chain FA and medium-chain FA proportions were lower (p < 0.01) in goats fed the two PBP supplemented diet than in those fed the control diet and PEG addition led to intermediate proportions of saturated FA, unsaturated and monounsaturated FA. Inclusion of PBP in the diet decreased (p < 0.01) plasma concentrations of glucose and urea nitrogen compared with the control diet. It was concluded that PBP can be used as forage in the diet of dairy goats without interfering with milk yield. Inclusion of 32% PBP in the diet of dairy goats had beneficial effects on milk FA profile but PEG addition to PBP did not contribute to enhance further milk FA profile.


Microbacterium luticocti sp. nov., isolated from sewage sludge compost.
Strain SC-087B(T), isolated from sewage sludge compost during a study of bacterial diversity in composts, was characterized. The isolate was a Gram-positive, short rod that was motile, catalase- and oxidase-negative and able to grow at 27-45 degrees C, pH 5.5-9.7 and in up to 10 % NaCl. The peptidoglycan was of the B2beta type, containing the characteristic amino acids ornithine, homoserine and hydroxyglutamic acid. The muramic acid residues of the peptidoglycan were partially glycolylated. The major cell-wall sugar was mannose; traces of xylose were also detected. The predominant fatty acids, comprising more than 70 % of the total, were anteiso-C(17 : 0) and anteiso-C(15 : 0), the major respiratory quinone was menaquinone-12 (MK-12) and the G+C content of the genomic DNA was 72 mol%. Based on analysis of the 16S rRNA gene sequence, the closest phylogenetic neighbours of strain SC-087B(T) were members of the family Microbacteriaceae, showing sequence similarity values of around 96 % with members of the species Microbacterium barkeri (96.0 %), Microbacterium gubbeenense (95.6 %) and Microbacterium indicum (95.7 %). The chemotaxonomic and phenotypic traits analysed supported the inclusion of this strain within the genus Microbacterium and the proposal of a novel species. The name Microbacterium luticocti sp. nov. is proposed and the type strain is SC-087B(T) (=DSM 19459(T)=CCUG 54537(T)).


Extracting fetal heart beats from maternal abdominal recordings: selection of the optimal principal components.
This study presents a systematic comparison of different approaches to the automated selection of the principal components (PC) which optimise the detection of maternal and fetal heart beats from non-invasive maternal abdominal recordings.A public database of 75 4-channel non-invasive maternal abdominal recordings was used for training the algorithm. Four methods were developed and assessed to determine the optimal PC: (1) power spectral distribution, (2) root mean square, (3) sample entropy, and (4) QRS template. The sensitivity of the performance of the algorithm to large-amplitude noise removal (by wavelet de-noising) and maternal beat cancellation methods were also assessed. The accuracy of maternal and fetal beat detection was assessed against reference annotations and quantified using the detection accuracy score F1 [2*PPV*Se / (PPV + Se)], sensitivity (Se), and positive predictive value (PPV). The best performing implementation was assessed on a test dataset of 100 recordings and the agreement between the computed and the reference fetal heart rate (fHR) and fetal RR (fRR) time series quantified.The best performance for detecting maternal beats (F1 99.3%, Se 99.0%, PPV 99.7%) was obtained when using the QRS template method to select the optimal maternal PC and applying wavelet de-noising. The best performance for detecting fetal beats (F1 89.8%, Se 89.3%, PPV 90.5%) was obtained when the optimal fetal PC was selected using the sample entropy method and utilising a fixed-length time window for the cancellation of the maternal beats. The performance on the test dataset was 142.7 beats(2)/min(2) for fHR and 19.9 ms for fRR, ranking respectively 14 and 17 (out of 29) when compared to the other algorithms presented at the Physionet Challenge 2013.


Simultaneous overexpression of enzymes of the lower part of glycolysis can enhance the fermentative capacity of Saccharomyces cerevisiae.
Recombinant S. cerevisiae strains, with elevated levels of the enzymes of lower glycolysis (glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase, phosphoglycerate kinase, enolase, pyruvate kinase, pyruvate decarboxylase and alcohol dehydrogenase) were physiologically characterized. During growth on glucose the enzyme levels in the recombinant strains (YHM4 and YHM7) were 1.1-3.4-fold higher than in the host strain (CEN.PK.K45). The recombinant strains were grown in aerobic or anaerobic batch cultures on glucose or a mixture of glucose and galactose. The specific ethanol production rates in the recombinant strains were the same as for the host strain and the physiological behaviour of the recombinant strains and the host strain was similar. When the cellular demand for ATP was increased by means of glucose pulses (final concentrations of 3.9 g/l or 2.0 g/l, respectively) to aerobic chemostat cultures maintained at a dilution rate of 0.08/h, the specific carbon dioxide production rate (qCO(2)) of CEN.PK.K45 accelerated at 6x10(-3) mmol/g/min(2) during the first 15 min, whereas during the same time period the qCO(2) of YHM7 accelerated twice as fast at 12x10(-3) mmol/g/min(2), indicating a higher fermentative capacity in the recombinant strain.


Deep crustal drilling in the north atlantic ocean.
Oceanic crustal drilling by R. V. Glomar Challenger at 15 sites in the North Atlantic has led to a complex picture of the upper half kilometer of the crust. Elements of the picture include the absence of the source for linear magnetic anomalies, marked episodicity of volcanic activity, ubiquitous low temperature alteration and evidence for large scale tectonic disturbance. Comparison sections in the Pacific and much deeper crustal drilling are needed to attack problems arising from the North Atlantic results.