Nurses' use of mobile devices to access information in health care environments in australia: a survey of undergraduate students.
The growth of digital technology has created challenges for safe and appropriate use of mobile or portable devices during work-integrated learning (WIL) in health care environments. Personal and professional use of technology has outpaced the development of policy or codes of practice for guiding its use at the workplace. There is a perceived risk that portable devices may distract from provision of patient or client care if used by health professionals or students during employment or WIL. This study aimed to identify differences in behavior of undergraduate nurses in accessing information, using a portable or mobile device, when undertaking WIL compared to other non-work situations. A validated online survey was administered to students while on placement in a range of health care settings in two Australian states. There were 84 respondents, with 56% (n=47) reporting access to a mobile or portable device. Differences in use of a mobile device away from, compared with during WIL, were observed for non-work related activities such as messaging (P<.001), social networking (P<.001), shopping on the Internet (P=.01), conducting personal business online (P=.01), and checking or sending non-work related texts or emails to co-workers (P=.04). Study-related activities were conducted more regularly away from the workplace and included accessing University sites for information (P=.03) and checking or sending study-related text messages or emails to friends or co-workers (P=.01). Students continued to access nursing, medical, professional development, and study-related information away from the workplace. Undergraduate nurses limit their access to non-work or non-patient centered information while undertaking WIL. Work-related mobile learning is being undertaken, in situ, by the next generation of nurses who expect easy access to mobile or portable devices at the workplace, to ensure safe and competent care is delivered to their patients.


A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease.
The association between low serum testosterone levels, visceral adipose tissue (VAT), and metabolic syndrome is now well known. However, the relationship between hepatic steatosis and serum testosterone levels has not been extensively studied. Our aim was to investigate the association of serum total testosterone levels with nonalcoholic fatty liver disease (NAFLD), adjusting for the influence of VAT and insulin resistance. This study is a retrospective observational cross-sectional one of healthy Korean men and was conducted at the Seoul National University Hospital Healthcare System Gangnam Center. We used data obtained from 495 men who were at least 20 years of age and who had undergone blood testing, abdominal computed tomography, and ultrasonography. Multiple logistic regression analysis was used to explore the association of serum total testosterone levels with NAFLD. Men in the low serum testosterone quintile were at a higher risk for NAFLD than men in the highest serum testosterone quintile. After adjusting for age, smoking, diabetes, exercise, BMI, triglycerides, and high-density-lipoprotein cholesterol, subjects with serum testosterone levels in the lowest quintile had an odds ratio (OR) (95% confidence interval (CI)) of 5.12 (2.43-10.77) for NAFLD (p value, 0.0004). The inverse association between serum testosterone and NAFLD was attenuated by further adjustment for variables including VAT; however, it remained statistically significant (OR (95% CI): 4.52 (2.09-9.80) in the lowest quintile; p value=0.004). A low serum total testosterone level was independently associated with NAFLD. This report is the first one suggesting the association remains unchanged even after controlling for VAT and insulin resistance.


Phosphotyrosyl protein phosphatases: potential regulators of cell proliferation and differentiation.
Tyrosyl phosphorylated proteins have been associated with the regulation of cellular activities, including proliferation, differentiation, and transformation. The overall cellular levels of tyrosyl phosphorylated proteins are regulated by the balance of the activities of both tyrosyl protein kinases and phosphotyrosyl protein phosphatases. Until recently, it was generally assumed that the kinase reaction was the key regulatory process for determining the level of tyrosyl phosphorylated proteins and that the dephosphorylation reaction was an unregulated event. However, recent evidence strongly suggest a regulatory role for phosphotyrosyl protein phosphatases for determination of the overall level of tyrosyl phosphorylated proteins. This review focuses on the discussion of the properties, the regulation, and the primary structure of phosphotyrosyl protein phosphatases. Evidence that supports an important role for phosphotyrosyl protein phosphatases on cell proliferation and differentiation also is presented.


[Technical features of intestinal ureteroplasty. part 5: bilateral ureteroplasty].
To present the results and the technical features of the various methods of bilateral ileal ureteroplasty. From 2001 to 2016, 154 patients (mean age 52+/-9.2 years) underwent ileal and appendicular substitution of the ureter and urinary bladder. Study participants comprised 70 (45.4%) men and 84 (54.6%) women. All patients underwent comprehensive examination, including ultrasound, X-ray, radioisotope and endoscopic tests. Bilateral isolated ileal ureteroplasty was performed in 20 patients (40 substituted ureters) whereof in 14, 5 and 1 cases U-shaped, 7-shaped and two separate grafts were used, respectively. Postoperative complications occurred in 2 (10%) of 20 patients who underwent bilateral intestinal ureteroplasty. Acute small bowel obstruction occurred in a patient after a U-shaped substitution of extended defects of both ureters. He underwent relaparotomy, bypass ileotransverse side-to-side anastomosis. Another patient developed right-sided ureteral-intestinal anastomotic leak following bilateral 7-shaped ureteroplasty. After relaparotomy and right ureter ligation, the breakdown site of the graft was closed with suturing. Repeat operations were successful; there were no deaths. Bilateral ileal ureteroplasty is much more complicated surgery than a unilateral operation. For proper collection and preparation of ileal graft in isoperistaltic position without mesenteric torsion, one should know how to place it in relation to intestinal anastomosis. Depending on this, several types of bilateral ileal ureteroplasty may be used: U-shaped, bilateral 7-, J- or L-shaped or separate isoperistaltic ileoureteroplasty.


Thalamo-cortical connectivity in children born preterm mapped using probabilistic magnetic resonance tractography.
Our aim was to investigate the feasibility of studying white matter tracts and connections between the thalamus and the cortex in 2-year-old infants who were born preterm by probabilistic magnetic resonance (MR) tractography. Using this approach, we were able to visualize and quantify connectivity distributions in a number of white matter tracts, including the corticospinal tracts, optic radiations, fibers of the genu and splenium of the corpus callosum, superior longitudinal fasciculus and inferior fronto-occipital fasciculus, and to map the distribution within thalamus of fibers connecting to specific cortical regions. In eleven infants with no MR evidence of focal cerebral lesions and appropriate neurodevelopment as shown by general quotient (GQ) scores above 100, we mapped cortical connections to the thalamus that appeared similar to those reported in adults. However, in a proof-of-principle experiment, we examined one further child with marked white matter abnormalities and found that the volume and pattern of thalamo-cortical connections were severely disrupted. This technique promises to be a useful tool for assessing connectivity in the developing brain and in infants with lesions.


Stimulatory effects of insulin on DNA synthesis in suckling mouse colon.
The influence of insulin on the postnatal development of DNA synthesis and epithelial and muscular cell proliferation has been studied in suckling mice. Daily administration of insulin (12.5 mU/g body weight) during 3 days to 8-day-old mice induced a significant increase of the incorporation of [3H]-thymidine into DNA in the small intestine and the proximal and distal halves of the colon. The esophagus and the glandular portion of the stomach did not respond. A detailed analysis of the proximal and distal colon between 4 and 30 days revealed a decrease of [3H]-thymidine incorporation into total DNA during this period. However, the establishment of the labeling indices in specific compartments such as the epithelium and the muscularis externa revealed that the epithelial cellular proliferation increased around weaning period in both segments while a drastic reduction of cellular proliferation occurred in the muscle layer. A premature rise of the circulating insulin level induced a significant increase of the epithelial labeling indices in both colonic segments but remained without effects on the muscular layer. These results suggest an important role of insulin in the modulation of the ontogenic changes in epithelial cell proliferation of the mouse colon.


Does the volume of supplemental intraligamentary injections affect the anaesthetic success rate after a failed primary inferior alveolar nerve block? A randomized-double blind clinical trial.
To investigate the efficacy of 0.2 mL vs. 0.6 mL of 2% lidocaine when given as a supplementary intraligamentary injection after a failed inferior alveolar nerve block (IANB). Ninety-seven adult patients with symptomatic irreversible pulpits received an IANB and root canal treatment was initiated. Pain during treatment was recorded using a visual analogue scale (Heft-Parker VAS). Patients with unsuccessful anaesthesia (n = 78) randomly received intraligamentary injection of either 0.2 mL or 0.6 mL of 2% lidocaine with 1 : 80 000 epinephrine. Root canal treatment was reinitiated. Success after primary injection or supplementary injection was defined as no or mild pain (HP VAS score ≤54 mm) during access preparation and root canal instrumentation. Heart rate was monitored using a finger pulse oximeter. The anaesthetic success rates were analysed with Pearson chi-square test at 5% significance levels. The heart rate changes were analysed using t-tests. The intraligamentary injections with 0.2 mL solution gave an anaesthetic success rate of 64%, whilst the 0.6 mL was successful in 84% of cases with failed primary IANB. (χ2 = 4.3, P = 0.03). There was no significant effect of the volume of intraligamentary injection on the change in heart rate. Increasing the volume of intraligamentary injection improved the success rates after a failed primary anaesthetic injection.


Ground- and Excited-State Interactions of a Psoralen Derivative with Human Telomeric G-Quadruplex DNA.
G-quadruplex DNA has been a recent target for anticancer agents, and its binding interactions with small molecules, often used as anticancer drugs, have become an important area of research. Considering that psoralens have long been studied in the context of duplex DNA but that very little is known about their potential as G-quadruplex binders and their excited-state interaction with the latter has not been explored, we have studied herein the binding of a planar water-soluble psoralen derivative, 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), with the 22-mer human telomeric G-quadruplex-forming sequence, AGGG(TTAGGG)3, labeled here as (hTel22), and investigated the consequences of photoexcitation of AMT by calorimetric and spectroscopic techniques. The results show an enthalpy-driven 1:1 binding of AMT with hTel22 via end-stacking mode. Fluorescence quenching experiments on 6-fluorescein amidite-labeled oligomers indicate that the binding site is nearer to the 3' end of hTel22 in the diagonal loop region. Femtosecond time-resolved transient absorption measurements indicate electron transfer from the guanine moiety of hTel22 to photoexcited AMT, leading to the formation of a radical pair species (AMT•-G•+), which survives for 30 ps and is favored by a parallel/quasi-parallel orientation between the two. The findings reveal psoralens as a prospective class of compounds for the development of anticancer therapeutics by targeting the G-quadruplex DNA.


Potential use of an antagonist of cAMP-dependent protein kinase to block inhibition and modulate T-cell receptor-triggered activation of cytotoxic T-lymphocytes.
It was recently established that cAMP-dependent protein kinase (PK-A) inhibits both early and late stages of T-cell receptor-mediated cytotoxic T-lymphocyte (CTL) activation. We suggested that PK-A may function as a part of a biochemical down-regulating "off" signal in regulation of CTL activities. It is proposed here to use antagonists of PK-A to block such an inhibitory pathway, thereby enhancing immune response. We explored this possibility using the diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a recently described PK-A antagonist. It is shown that Rp-cAMPS blocks cAMP-induced inhibition of lytic activity and of exocytosis of granules from CTL. The immunomodulating potential of cAMP analogues which inhibit PK-A is discussed.


Substance P neurokinin 1 receptor activation within the dorsal raphe nucleus controls serotonin release in the mouse frontal cortex.
Preclinical studies suggest that substance P (SP) neurokinin 1 (NK1) receptor antagonists are efficient in the treatment of anxiety and depression. This therapeutic activity could be mediated via stimulation of serotonin (5-HT) neurons located in the dorsal raphe nucleus (DRN), which receive important SP-NK1 receptor immunoreactive innervations. The present study examined the effects of intraraphe injection of SP on extracellular 5-HT levels in the frontal cortex, ventral hippocampus, and DRN by using intracerebral microdialysis in conscious mice. Intraraphe SP injection dose dependently decreased cortical 5-HT release, whereas no effects were detected in the ventral hippocampus. Cortical effects were blocked by the selective NK1 receptor antagonist N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine (GR205171) and completely dampened in mice lacking NK1 receptors. Furthermore, genetic (in knockout 5-HT1A(-/-) mice) or pharmacological inactivation of 5-HT1A autoreceptors blocked cortical responses to SP. Contrasting with its cortical effects, intraraphe SP injection increased 5-HT outflow in the DRN in wild-type mice; this effect was potentiated by a local perfusion of the selective 5-HT1A antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Finally, SP-induced changes in frontal cortex and DRN dialysate 5-HT levels were blocked by the DRN perfusion of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate ionotropic receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). These data support the hypothesis that SP-induced over-activation of 5-HT1A autoreceptors within the DRN limits cortical 5-HT release. A better knowledge of the complex relationship between tachykininergic, serotonergic, and glutamatergic systems within the DRN might help better understand the pathophysiology and subsequent treatment of depression.


Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factor.
A clonal cell line (Saos-2/B-10) derived from human osteosarcoma Saos-2 cells had the same osteoblastic characteristics as the mother line, but lacked sensitivity to parathyroid hormone (PTH) at early passages. At later passages (greater than 70) the cells became very sensitive to PTH (0.1 nmol/l). The absence of PTH-stimulatable adenylate cyclase correlated with the secretion of an adenylate cyclase-stimulatory activity which had the properties of the recently characterized PTH-like peptide (PTH-LP). This activity was inhibited by the PTH antagonist [8norleucyl,18norleucyl,34tyrosinyl]bovine PTH-(3-34)amide and could be neutralized by an antiserum raised against the synthetic PTH-LP-(1-34). Hybridization with a human PTH-LP cDNA showed that these cells produce two PTH-LP mRNAs of approximately 1.5 and 1.8 kb. The production of PTH-LP was stimulated by 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 150 nmol/l) and epidermal growth factor (EGF; 10 ng/ml). The increased accumulation of PTH-LP in conditioned media in response to TPA was seen after 1 h and levelled off at 6 h. In contrast, EGF stimulation was lower at 3 and 6 h but continued for 24 h. Both agents increased PTH-LP mRNA levels in Saos-2/B-10 cells. A TPA analogue which does not stimulate protein kinase C had no effect on PTH-LP production. Cycloheximide blocked the stimulatory effect of both TPA and EGF and the TPA effect was blocked by actinomycin D, suggesting transcriptional control. The regulation of PTH-LP by these agents may offer clues regarding the association of this protein with malignancy.


In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells.
To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro. Rat pancreatic tissue was submitted to digestion by collegenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XlHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulin-producing cells were detected by dithizone-staining. XlHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were significantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 +/- 0.43 vs 3.48 +/- 0.81, P < 0.01 at 5.6 mmol/L; 4.86 +/- 1.15 vs 10.25 +/- 1.32, P < 0.01 at 16.7 mmol/L). PDX-1 can differentiate rat pancreatic ductal epithelial cells into insulin-producing cells in vitro. In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells.


The drug treatment of panic disorder.
Reviews current information about panic disorder that establishes its prevalence, heritable nature, course and complications. With this brief introduction, develops a general strategy for the management of panic disorder that entails careful diagnostic assessment, recognition of the risk of complications (i.e. major depression, phobic avoidance, substance abuse), education, supportive psychotherapy and the use of medication in the acute control of symptoms and the long term management of the vulnerability to panic attacks.


Idealized glass transitions for a system of dumbbell molecules.
The mode-coupling theory for ideal glass transitions in simple systems is generalized to a theory for the glassy dynamics of molecular liquids using the density fluctuations of the sites of the molecule's constituent atoms as the basic structure variables. The theory is applied to calculate the liquid-glass phase diagram and the form factors for the arrested structure of a system of symmetric dumbbells of fused hard spheres. The static structure factors, which enter the equations of motion as input, are calculated as function of the packing fraction phi and the molecule's elongation zeta within the reference-interaction-site-model and Percus-Yevick theories. The critical packing fraction phi(c) for the glass transition is obtained as nonmonotone function of zeta with a maximum near zeta=0.43. A transition line is calculated separating a small-zeta-glass phase with ergodic dipole motion from a large-zeta-glass phase where also the reorientational motion is arrested. The Debye-Waller factors at the transition are found to be somewhat larger for sufficiently elongated systems than those for the simple hard-sphere system, but the wave-number dependence of the glass-form factors is quite similar. The dipole reorientations for zeta> or =0.6 are arrested as strongly as density fluctuations with wave vectors at the position of the first sharp diffraction peak.


Psychopathology in children of alcoholic and antisocial parents.
In this controlled family study the frequency of psychiatric disorder in children of alcoholic parents was found to be higher than in children of nonalcoholic parents. The rate in children of two alcoholic parents was distinctly higher than in those of one alcoholic parent. Comparison was also made between children of antisocial parents (usually coexisting with alcoholism) and children of parents with alcoholism only; no significant differences in the rates of childhood disorder were found between these two groups. Structured diagnostic interviews independently administered to both parents and children between 6 and 17 years old were used to assess psychopathology in the children. The types of disorders in the children of alcoholic parents reflected a mixed diagnostic picture with the reports of both parents and children yielding similar results.


In eHealth in India today, the nature of work, the challenges and the finances: an interview-based study.
India is a country with vast unmet medical needs. eHealth has the potential to improve the quality of health care and reach the unreached. We have sought to understand the kinds of eHealth programmes being offered in India today, the challenges they face and the nature of their financing. We have adopted an interview-based methodology. The 30 interviews represent 28 organizations, and include designers, implementers, evaluators and technology providers for eHealth programmes. A range of programmes is being run, including point-of-care in rural and urban areas, treatment compliance, data collection and disease surveillance, and distant medical education. Most programmes provide point-of-care to patients or other beneficiaries in rural areas. Technology is not a limiting factor but the unavailability of suitable health personnel is a major challenge, especially in rural areas. We have identified a few factors that help this situation. Financial sustainability is also a concern for most programmes, which have rarely been scaled up. There are recent for-profit efforts in urban areas, but no reliable business model has been identified yet. Government facilities have not been very effective in eHealth on their own, but collaborations between the government and non-profit (in particular) and for-profit organisations have led to impactful programmes. It is unlikely that eHealth will have widespread and sustainable impact without government involvement, especially in rural areas. Nevertheless, programmes run solely by the government are unlikely to be the most effective.


Targeting AMPK/eNOS pathway and mitochondria by sonlicromanol protects myocardial cells against ischemia-reperfusion injury.
This work evaluated the cardioprotective effects of sonlicromanol, a new mitochondrial-directed drug, on cardiac ischemia/reperfusion (I/R) injury and explored the involvement of inflammatory and oxidative responses via activation of AMPK-eNOS-mitochondrial pathway. Male Sprague-Dawley rats underwent regional I/R injury through in vivo left anterior descending (LAD) coronary artery ligation for 40 minutes followed by 24 hours of reperfusion. Pretreatment of rats with sonlicromanol considerably reduced cardiac I/R injury in a dose-dependent manner, as indicated by lower infarct size and serum creatine-kinase levels, and improved cardiac function after reperfusion. Sonlicromanol (50 mg/kg) significantly reduced TNF-α, interleukin-1β, NF-κB-p65, and 8-isoprostane levels while increased manganese-superoxide dismutase and nitric-oxide levels and expression of eNOS and AMPK protein. It significantly reduced mitochondrial membrane depolarization and reactive oxygen species (ROS) levels. However, AMPK inhibition significantly reduced sonlicromanol protective actions. Cardioprotection by sonlicromanol was achieved by moderating inflammatory and oxidative responses, and AMPK/eNOS/mitochondrial signaling is a crucial regulator of these actions.


Near real-time flood inundation and hazard mapping of Baitarani River Basin using Google Earth Engine and SAR imagery.
Flood inundation mapping and satellite imagery monitoring are critical and effective responses during flood events. Mapping of a flood using optical data is limited due to the unavailability of cloud-free images. Because of its capacity to penetrate clouds and operate in all kinds of weather, synthetic aperture radar is preferred for water inundation mapping. Flood mapping in Eastern India's Baitarani River Basin for 2018, 2019, 2020, 2021, and 2022 was performed in this study using Sentinel-1 imagery and Google Earth Engine with Otsu's algorithm. Different machine-learning algorithms were used to map the LULC of the study region. Dual polarizations VH and VV and their combinations VV×VH, VV+VH, VH-VV, VV-VH, VV/VH, and VH/VV were examined to identify non-water and water bodies. The normalized difference water index (NDWI) map derived from Sentinel-2 data validated the surface water inundation with 80% accuracy. The total inundated areas were identified as 440.3 km2 in 2018, 268.58 km2 in 2019, 178.40 km2 in 2020, 203.79 km2 in 2021, and 321.33 km2 in 2022, respectively. The overlap of flood maps on the LULC map indicated that flooding highly affected agriculture and urban areas in these years. The approach using the near-real-time Sentinel-1 SAR imagery and GEE platform can be operationalized for periodic flood mapping, helps develop flood control measures, and helps enhance flood management. The generated annual flood inundation maps are also useful for policy development, agriculture yield estimation, crop insurance framing, etc.


A comparative study of minimally invasive percutaneous nephrolithotomy and retrograde intrarenal surgery for solitary renal stone of 1-2 cm.
PCNL is the treatment of choice for renal stones. But wide array of complications due to larger tract size(>20 Fr) has lead to development of improved techniques like miniPCNL(<20 Fr) and RIRS(Retrograde intrarenal surgery). To perform a study comparing miniPCNL with RIRS for renal stones 1-2 cm with respect to stone free rate , complications and quality of life. A prospective, randomised study was carried out our tertiary care centre, recruiting 40 patients in each group from Dec 2016 to Oct 2018. Patients demographic characteristics, operative findings, surgical outcomes and quality of life( SF-36 questionnaire) were recorded with 3 months of follow-up. RIRS has longer operative time (69.75 min > 51.58 min; p=0.003), lesser radiation exposure (p=0.012), shorter hospital stay (p =0.15), lesser blood loss and lesser post operative pain on POD1 and POD2 (p =0.005, p=0.001 respectively). RIRS group patients sufferred more post op complications (p=0.03 )of which urosepsis was most common. Stone free rate is significantly better(p =0.003) in miniPCNL group on POD1 , while SFR's at 1 month (miniPCNL-90% and RIRS -85%) and 3 month (miniPCNL- 92.5% and RIRS -87.5%) was better in miniPCNL group, but statistically insignificant.On subgroup analysis SFR in lower pole calculus was better in miniPCNL group at 1month and 3 month (p=0.008). Second intervention for stone clearance was required in 3 patients of miniPCNL and 5 patients of RIRS, out of which 4 had lower pole stone.No significant differnce was found in quality of life in both groups at 1 month. MiniPCNL is a better treatment modality for higher single step stone free rate, shorter operative time and fewer postop complication. RIRS has SFR slightly less than miniPCNL but has less radiation exposure and much less post operative pain. There is no significant difference in quality of life in both groups.


Accelerating cardiac cine 3D imaging using k-t BLAST.
By exploiting spatiotemporal correlations in cardiac acquisitions using k-t BLAST, gated cine 3D acquisitions of the heart were accelerated by a net factor of 4.3, making single breathhold acquisitions possible. Sparse sampling of k-t space along a sheared grid pattern was implemented into a cine 3D SSFP sequence. The acquisition of low-resolution training data, which was required to resolve aliasing in the k-t BLAST method, was either interleaved into the sampling process or obtained in a separate prescan to allow for shorter breathhold durations in patients with heart disease. Volumetric datasets covering the heart with 20 slices at a spatial resolution of 2 x 2 x 5 mm3 were recorded with 20 cardiac phases in a total breathhold duration of 25-27 sec, or 18 sec if partial Fourier sampling was additionally employed. The feasibility of the method was demonstrated on healthy volunteers and on patients. The comparison of endocardial area derived from single slices of the 3D dataset with values extracted from separate single-slice acquisitions showed no significant differences. By shortening the acquisition substantially, k-t BLAST may greatly facilitate volumetric imaging of the heart for evaluation of regional wall motion and the assessment of ventricular volume and ejection fraction.


The influence of reading ability on subsequent changes in verbal IQ in the teenage years.
Intelligence Quotient (IQ) is regularly used in both education and employment as a measure of cognitive ability. Although an individual's IQ is generally assumed to stay constant across the lifespan, a few studies have suggested that there may be substantial variation at the individual level. Motivated by previous reports that reading quality/quantity has a positive influence on vocabulary acquisition, we hypothesised that reading ability in the early teenage years might contribute to changes in verbal IQ (VIQ) over the next few years. We found that good readers were more likely to experience relative improvements in VIQ over time, with the reverse true for poor readers. These effects were largest when there was a discrepancy between Time 1 reading ability and Time 1 VIQ. In other words, VIQ increases tended to be greatest when reading ability was high relative to VIQ. Additional analyses supported these findings by showing that variance in VIQ change associated with Time 1 behaviour was also associated with independent measurements of brain structure. Our finding that reading in the early teenage years can predict a significant proportion of the variance in subsequent VIQ change has implications for targeted education in both home and school environments.


Sensitive electrochemical biosensing of H2O2 based on cobalt nanoparticles synthesised in iron storage protein molecules, ferritin.
In this report, a highly sensitive electrochemical biosensor based on cobaltferritin immobilised on a self-assembled monolayer modified gold electrode for determination of hydrogen peroxide (H2O2) in phosphate buffer solution (pH 7.5) was investigated. The modified electrode showed excellent electrochemical activity for oxidation of H2O2. The response to H2O2 on the modified electrode was examined using linear sweep and differential pulse voltammetries. In phosphate buffer (pH 7.5, 0.1 M), the fabricated biosensor exhibited a linear dependence (R = 0.989) on the concentration of H2O2 from 2.49 × 10(-9) to 1.91 × 10(-8) M, a high sensitivity of -0.4099 µA/nM and detection limit of 2.48 × 10(-9) based on a signal-to-noise ratio of 3. Charge transfer coefficient (α) and the exchange current (i0) of oxidation for H2O2 were found to be 0.57 and 7.55 A, respectively. It has been shown that, this modified electrode is able to determine H2O2 with a high sensitivity, low detection limit and high selectivity.


Impact of Water Management on Efficacy of Insecticide Seed Treatments Against Rice Water Weevil (Coleoptera: Curculionidae) in Mississippi Rice.
Two experiments were conducted at the Delta Research and Extension Center in Stoneville, MS, during 2011 and 2012 to determine the impact of water management practices on the efficacy of insecticidal seed treatments targeting rice water weevil, Lissorhoptrus oryzophilus Kuschel. Larval densities and yield were compared for plots treated with labeled rates of thiamethoxam, chlorantraniliprole, and clothianidin and an untreated control. In the first experiment, plots were subjected to flood initiated at 6 and 8 wk after planting. Seed treatments significantly reduced larval densities with the 8-wk flood timing, but not the 6-wk flood timing. Overall, the treated plots yielded higher than the control plots. In the second experiment, the impact of multiple flushes on the efficacy of insecticidal seed treatments was evaluated. Plots were subjected to zero, one, or two flushes with water. All seed treatments reduced larval densities compared with the untreated control. Significantly fewer larvae were observed in plots that received one or two flushes compared with plots that did not receive a flush. All seed treatments resulted in higher yields compared to the untreated control in the zero and one flush treatments. When two flushes were applied, yield from the thiamethoxam and clothianidin treated plots was not significantly different from those of the control plots, while the chlorantraniliprole treated plots yielded significantly higher than the control. These data suggest that time from planting to flood did not impact the efficacy of seed treatments, but multiple flushes reduced the efficacy of thiamethoxam and clothianidin.


Real-Life Management of Diabetic Macular Edema with Dexamethasone Intravitreal Implant: A Retrospective Analysis of Long-Term Clinical Outcomes.
Inflammation plays a key role in the pathogenesis of diabetic macular edema (DME), and intravitreal corticosteroids are among the recommended therapies. The goal of this retrospective analysis was to describe outcomes with dexamethasone intravitreal implant (DEX implant) in real life. Medical digital records of DME patients treated with DEX implant and followed up for 3 years were analyzed. Treatment with DEX implant was started either as first-line therapy in pseudophakic patients and in patients with cardiovascular comorbidities or as second-line therapy in patients refractory to the inhibitor of the vascular endothelial growth factor (anti-VEGF) therapy. Analyzed outcomes included central macular thickness (CMT) and best-corrected visual acuity (BCVA). Mean number of implant injections per patient and mean duration of the interval between injections were also estimated. Seventy-five patients (mean age 65.7 (±12.3) years; 53 phakic and 22 pseudophakic) with DME were included. Overall, 84 eyes were treated. Mean CMT improved from 380.1 (±100.3) µm at baseline to 306.8 (±77.0) µm at 36 months (p=0.0003). Mean BCVA improved for up to 6 months (p=0.08) and then started to decrease reaching values lower than baseline after 24 months. In pseudophakic patients, BCVA improvements were more pronounced and sustained up to 36 months (p=0.6). Over 36 months, each patient received on average 2.4 (±1.6) intravitreal injections of DEX implant. The time interval between consecutive injections was included between 180 and 240 days. No unexpected safety issues were reported. With fewer than 3 injections per patient over a 3-year period, DEX implant was able to improve anatomic outcomes in DME patients. Only pseudophakic eyes showed also a long lasting functional benefit at 36 months.


Cellular mechanisms of atracurium-induced tetanic fade in the isolated rat muscle.
Although atracurium is a widely used neuromuscular blocker, we still lack knowledge regarding some of its cellular mechanisms of action. Thus, similar to other clinically used blockers atracurium induces, both in vivo and in vitro, fade of the tetanic contraction. However, the cellular mechanisms underlying this tetanic fade have never been systematically studied. In the present work these mechanisms were investigated in vitro. A sciatic nerve extensor digitorum longus muscle preparation of the rat was used. A combination of myographical and electrophysiological techniques was employed. Indirect twitches were evoked at 0.1 Hz and tetanic contractions at 50 Hz. Trains of end-plate potentials were evoked at a frequency of 50 Hz. The electrophysiological variables used in the analysis of the trains of end-plate potentials were: peak amplitude of the first end-plate potential in the train, peak amplitude of plateau end-plate potentials in the train, tetanic run-down of the end-plate potentials' train, quantal content of first and plateau end-plate potentials in the train, quantal size. In the myographical study atracurium, at a concentration of 2.4 microM, induced a complete fade of the tetanic contraction while only slightly affected the twitch. In the electrophysiological study atracurium, at the same 2.4 microM concentration, significantly decreased the amplitude of both first end-plate potentials in the train (control: 14.4 mV; atracurium: 3.2 mV) and plateau end-plate potentials (control: 10.8 mV; atracurium: 2.4 mV) and reinforced the tetanic run-down of the train of end-plate potentials, evaluated as the percent loss in amplitude of plateau end-plate potentials compared to first end-plate potentials in the trains (control: 25.2%; atracurium: 33.2%). Atracurium also significantly decreased the quantal content of first end-plate potentials in the train (control: 231; atracurium: 68), the quantal content of plateau end-plate potentials (control: 159; atracurium: 42) and the quantal size (control: 0.119 mV; atracurium: 0.075 mV). In relative terms the decrease in quantal content was about twice as large as the decrease in quantal size. This indicates that the fade of the tetanic contraction induced by atracurium (2.4 microM) is due to both pre- and postsynaptic blocking effects, the presynaptic one being stronger.


Coronary artery anomaly with congenital factor V deficiency.
The case of a 60-years-old woman with coronary artery anomaly and factor V deficiency is reported. She presented with right radial artery pseudoaneurysm after coronary angiography. Her coronary angiography revealed aberrant origin of left anterior descending artery from right coronary cusp. On preliminary investigations her prothrombin time and activated partial thromboplastin time were prolonged. Her plasma factor V level was found out to be 4%, a moderate deficiency of factor V.


Quantifying Differences in Responses of Aquatic Insects to Trace Metal Exposure in Field Studies and Short-Term Stream Mesocosm Experiments.
Characterizing macroinvertebrate taxa as either sensitive or tolerant is of critical importance for investigating impacts of anthropogenic stressors in aquatic ecosystems and for inferring causality. However, our understanding of relative sensitivity of aquatic insects to metals in the field and under controlled conditions in the laboratory or mesocosm experiments is limited. In this study, we compared the response of 16 lotic macroinvertebrate families to metals in short-term (10-day) stream mesocosm experiments and in a spatially extensive field study of 154 Colorado streams. Comparisons of field and mesocosm-derived EC20 (effect concentration of 20%) values showed that aquatic insects were generally more sensitive to metals in the field. Although the ranked sensitivity to metals was similar for many families, we observed large differences between field and mesocosm responses for some groups (e.g., Baetidae and Heptageniidae). These differences most likely resulted from the inability of short-term experiments to account for factors such as dietary exposure to metals, rapid recolonization in the field, and effects of metals on sensitive life stages. Understanding mechanisms responsible for differences among field, mesocosm, and laboratory approaches would improve our ability to predict contaminant effects and establish ecologically meaningful water-quality criteria.


Prosopagnosia: current perspectives.
Prosopagnosia is a selective visual agnosia characterized by the inability to recognize the identity of faces. There are both acquired forms secondary to brain damage and developmental forms without obvious structural lesions. In this review, we first discuss the diagnosis of acquired and developmental prosopagnosia, and the challenges present in the latter case. Second, we discuss the evidence regarding the selectivity of the prosopagnosic defect, particularly in relation to the recognition of other objects, written words (another visual object category requiring high expertise), and voices. Third, we summarize recent findings about the structural and functional basis of prosopagnosia from studies using magnetic resonance imaging, functional magnetic resonance imaging, and event-related potentials. Finally, we discuss recent attempts at rehabilitation of face recognition in prosopagnosia.


[New possibilities of treatment of low back pain].
Low back pain (LBP) is a syndrome caused by degenerative spine diseases and a common reason for referral for medical care. LBP is mostly often caused by osteoarthritis (OA) that needs long-term treatment with nonsteroidal anti-inflammatory drugs. The treatment is associated with a risk of side-effects. The authors consider the possibility of using slow-acting drugs for symptomatic treatment of OA (SYSADOA) in patients with LBP and present the data on anti-inflammatory effects of chondroitin sulfate on the chondral tissue in OA. The results of the studies on the use of SYSADOA in LBP are analyzed.


Homeostasis--the key concept to physiological control.
Immunity is a response to the invasion of the body by non-self antigens (Figure 8). Immunity is characterised by being: Xenophobic--it distinguishes self from non-self components. Adaptive--it produces a response to an antigenic invasion. Highly specific--its response is personal for different antigenic insults. Anamnestic--its memory component allows the occurrence of primary and secondary responses.


The fuzzy math of solid tumor stem cells: a perspective.
Apparently effective therapeutic agents very often fail to cure cancer patients. It is therefore attractive to wonder whether a specific resistant cell subset should be recognized and separately targeted. In solid tumors, such as carcinomas, a minor population of "cancer stem cells" has been proposed and sought experimentally in human tumors and isolated cell populations. It is often overlooked that the rationale and supportive data are essentially numerical and can be evaluated as such. A reevaluation of the published studies and related claims within awarded U.S. patents suggests that the mathematical support for the concept of therapeutically useful stem cells is weak and may even invalidate the foundations of these publications and patent claims. Mathematical arguments should be used more consistently, because they can serve as a guide for interpreting studies into cancer stem cells of solid tumors.


Herpes zoster in HIV-1-infected patients in the era of highly active antiretroviral therapy: a prospective observational study.
Between June 1994 and May 2003, 93 of 716 (13.0%) HIV-infected patients with a median baseline cell differentiation CD4+ count of 61 x 10(6) cells/L (range, 1-1206 x 10(6) cells/L) developed 103 episodes of herpes zoster [HZ], with an incidence of 5.67 per 100 person-years (PY). The incidence of HZ in the pre-highly active antiretroviral therapy (HAART) era (17.21 per 100 PY) was significantly higher than that in the post-HAART era (5.05 per 100 PY) (P < 0.0001). In the first six months of enrollment, the incidence of HZ was significantly higher than that between six and 12 months both in the pre-HAART (27.65 per 100 PY versus 8.43 per 100 PY, P = 0.02) and post-HAART era (17.79 per 100 PY versus 3.39 per 100 PY, P < 0.0001). In multivariate analyses, only baseline CD4+ count remained a significant risk factor associated with HZ. HZ did not increase mortality rate either in the pre-HAART or post-HAART era, although the risk for HIV progression was significantly higher in patients with HZ (adjusted odds ratio [OR], 1.747, 95% confidence interval, 1.037-2.943). We conclude that the incidence of HZ was highest in the first six months of enrollment in patients at late stage of HIV infection, which did not increase with the introduction of HAART. Baseline CD4+ lymphocyte count was the most significant risk factor associated with development of HZ. HZ was associated with increased risk for HIV progression, but not mortality.


The use of handheld technology in nursing research and practice.
Use of handheld devices with electronic patient diaries (EPDs) can improve the quality of patient-reported information collected in clinical and research settings. EPDs have advantages compared with traditional paper-based instruments that include decreased data entry error and decreased time spent on data management. Orthopaedic pain management, which is often dependent on patient-reported pain levels, can benefit from the use of EPDs. A pilot survey was conducted to compare two self-report pain diary methods in shoulder surgery patients: (a) EPD or (b) paper entry. Compliance was lower in the EPD group, which was attributed to insufficient ease of use. Handheld technology can be used by nurses to improve and streamline patient care by capturing clinical data, by organizing and reporting home health services, and by providing references for evidence-based practice. Handheld technology can facilitate the transformation of clinical documentation of assessments, interventions, and outcomes into evidence-based decision making in orthopaedic nursing.


Variation in feeding behavior and milk production among dairy cows when supplemented with 2 amounts of mixed ration in combination with 2 amounts of pasture.
Variation in feeding behavior and milk production of grazing dairy cows fed a mixed ration was measured. Experiments were conducted in spring (early lactation) and autumn (late lactation) with 48 Holstein-Friesian dairy cows. Pasture allowance (low vs. high) and amounts of supplement (low vs. high) were applied to determine the effect on variation among cows in feeding behavior and milk production. The experiments investigated 4 dietary treatments in a 2×2 factorial arrangement of treatments. Daily pasture allowances were 15kg of DM/cow per day (low) and 37kg of DM/cow per day (high; to ground level); and 12kg of DM/cow per day (low) and 31kg of DM/cow per day (high; to ground level), for the spring and autumn experiments, respectively. Supplements were offered at 6kg of DM/cow per day (low) and 14kg of DM/cow per day (high); and 6kg of DM/cow per day (low) and 12kg of DM/cow per day (high), for the spring and autumn experiments, respectively. There were 2groups of 6 cows per treatment. All treatments received a partial mixed ration, defined as a total mixed ration fed between periods of grazing that contained wheat grain, corn grain, alfalfa hay, and canola meal. The grain-to-forage ratio of the supplements was 78:22 (DM basis) in both spring and autumn. In both experiments, the pre-experimental period was 14d followed by a 10-d experimental period. The variation among cows within a group in feeding behavior was influenced by the amount of supplement but not the amount of pasture offered. The variation among cows in pasture eating time approximately doubled when the amount of supplement offered increased, indicating that to reduce the variability among cows, supplement feeding management strategies need to be considered. Increasing pasture allowance had no effect on pasture eating time although pasture intake increased as a result of increased grazing intensity compared with the low pasture allowance. However, increasing the amount of supplement in the partial mixed ration feeding system reduced pasture eating time by 51min/cow per day.


The role of human prolactin and its antagonist, G129R, in mammary gland development and DMBA-initiated tumorigenesis in transgenic mice.
Human prolactin (hPRL) has been implicated to have a pathological role in breast cancer and play a critical role in mammary gland development. The hPRL antagonist, G129R, has been shown to induce breast cancer cell apoptosis. 9,10-Dimethyl-1,2-benzanthracene (DMBA), a potent mammary gland carcinogen, induces hormone responsive mammary tumor formation in rodents. To investigate the effects of hPRL and its counterpart, G129R, on mammary gland development and tumorigenesis, transgenic mice that express hPRL or G129R under the regulation of the metallothionein (Mt) promoter were generated. Mammary glands from virgin female transgenic mice at the ages of 12, 24, and 36 weeks were used to compare the effect of hPRL and G129R in various developmental stages. Mammary gland whole mount comparisons between transgenic mice and their littermates revealed a significant increase in ductal branching and lobular bud formation in hPRL transgenic mice; whereas a drastic decrease in ductal branching and lobular bud formation was observed in the mammary glands of G129R transgenic mice. In addition, total RNA isolated from the mammary glands of transgenic mice at the three different ages was analyzed on Affymetrix GeneChip Mouse Expression 430A chips (MOE430A). Microarray data revealed alteration to the gene expression levels, greatest at 12 and 36 weeks. Furthermore, hPRL and G129R transgenic mice, as well as their littermates, were treated with multiple doses of DMBA and the rate of mammary tumor formation and survival were compared. The tumor rates in the G129R transgenic mice were significantly reduced (18% at 28 weeks) as compared to that of either NTG (39%) or hPRL (40%). On the other hand, the tumor appearance is significantly earlier in the PRL transgenic group as compared to that of controls. Taken together, the data further confirmed the inhibitory effects of G129R in mammary gland development, which translates to a resistance to DMBA-initiated breast tumorigenesis.


Soil organisms shape the competition between grassland plant species.
Decomposers and arbuscular mycorrhizal fungi (AMF) both determine plant nutrition; however, little is known about their interactive effects on plant communities. We set up a greenhouse experiment to study effects of plant competition (one- and two-species treatments), Collembola (Heteromurus nitidus and Protaphorura armata), and AMF (Glomus intraradices) on the performance (above- and belowground productivity and nutrient uptake) of three grassland plant species (Lolium perenne, Trifolium pratense, and Plantago lanceolata) belonging to three dominant plant functional groups (grasses, legumes, and herbs). Generally, L. perenne benefited from being released from intraspecific competition in the presence of T. pratense and P. lanceolata. However, the presence of AMF increased the competitive strength of P. lanceolata and T. pratense against L. perenne and also modified the effects of Collembola on plant productivity. The colonization of roots by AMF was reduced in treatments with two plant species suggesting that plant infection by AMF was modified by interspecific plant interactions. Collembola did not affect total colonization of roots by AMF, but increased the number of mycorrhizal vesicles in P. lanceolata. AMF and Collembola both enhanced the amount of N and P in plant shoot tissue, but impacts of Collembola were less pronounced in the presence of AMF. Overall, the results suggest that, by differentially affecting the nutrient acquisition and performance of plant species, AMF and Collembola interactively modify plant competition and shape the composition of grassland plant communities. The results suggest that mechanisms shaping plant community composition can only be understood when complex belowground interactions are considered.


Alzheimer's disease and oral care.
Alzheimer's disease (AD) is the commonest form of dementia, closely associated with age, but also with other causative factors. AD affects half a million people in the UK, and presents dentists with numerous behavioural and clinical challenges. The aetiology, diagnosis and medical treatment for persons with AD are discussed, together with communication strategies and issues related to families and care-givers. Realistic dental treatment planning for patients in early, moderate and late stage AD is considered in conjunction with relevant ethical issues. Dentists have the potential to improve markedly the quality of life for people with AD.


Development of clindamycin-loaded wound dressing with polyvinyl alcohol and sodium alginate.
To develop a clindamycin-loaded wound dressing, cross-linked hydrogel films were prepared using freeze-thawing method with various mixtures of polyvinyl alcohol (PVA) and sodium alginate (SA). The physicochemical properties such as swelling ratio, tensile strength and elongation of hydrogels were evaluated. The drug release from this clindamycin-loaded hydrogel, in vitro protein adsorption test and in vivo wound healing observations in rats were then performed. Increased SA concentration decreased the gelation %, maximum strength and break elongation, but it resulted into an increment in the swelling ability, elasticity and thermal stability of hydrogel film. However, SA had insignificant effect on the release of clindamycin. This hydrogel improved the healing rate of artificial wounds in rats. Thus, a clindamycin-loaded wound dressing with PVA and SA hydrogel should be a candidate for wound care.


Cranium-Penetrating Mass Detected by Ultrasound Expedited Management of Langerhans Cell Histiocytosis.
A 6-year-old boy presented to the pediatric emergency department with a unilateral 5 × 3-cm superficial mass on the postauricular region growing for 1 month. Point-of-care ultrasound was used to evaluate the mass, which revealed a complex cystic mass penetrating the temporal bone. After confirmatory magnetic resonance imaging, the patient was transferred for neurosurgical evaluation, and the tumor was excised. Pathology revealed Langerhans cell histiocytosis.


Air Pollution and Preterm Birth in the U.S. State of Georgia (2002-2006): Associations with Concentrations of 11 Ambient Air Pollutants Estimated by Combining Community Multiscale Air Quality Model (CMAQ) Simulations with Stationary Monitor Measurements.
Previous epidemiologic studies suggest associations between preterm birth and ambient air pollution. We investigated associations between 11 ambient air pollutants, estimated by combining Community Multiscale Air Quality model (CMAQ) simulations with measurements from stationary monitors, and risk of preterm birth (< 37 weeks of gestation) in the U.S. state of Georgia. Birth records for singleton births ≥ 27 weeks of gestation with complete covariate information and estimated dates of conception between 1 January 2002 and 28 February 2006 were obtained from the Office of Health Indicators for Planning, Georgia Department of Public Health (n = 511,658 births). Daily pollutant concentrations at 12-km resolution were estimated for 11 ambient air pollutants. We used logistic regression with county-level fixed effects to estimate associations between preterm birth and average pollutant concentrations during the first and second trimester. Discrete-time survival models were used to estimate third-trimester and total pregnancy associations. Effect modification was investigated by maternal education, race, census tract poverty level, and county-level urbanicity. Trimester-specific and total pregnancy associations (p < 0.05) were observed for several pollutants. All the traffic-related pollutants (carbon monoxide, nitrogen dioxide, PM2.5 elemental carbon) were associated with preterm birth [e.g., odds ratios for interquartile range increases in carbon monoxide during the first, second, and third trimesters and total pregnancy were 1.005 (95% CI: 1.001, 1.009), 1.007 (95% CI: 1.002, 1.011), 1.010 (95% CI: 1.006, 1.014), and 1.011 (95% CI: 1.006, 1.017)]. Associations tended to be higher for mothers with low educational attainment and African American mothers. Several ambient air pollutants were associated with preterm birth; associations were observed in all exposure windows. Hao H, Chang HH, Holmes HA, Mulholland JA, Klein M, Darrow LA, Strickland MJ. 2016. Air pollution and preterm birth in the U.S. state of Georgia (2002-2006): associations with concentrations of 11 ambient air pollutants estimated by combining Community Multiscale Air Quality Model (CMAQ) simulations with stationary monitor measurements. Environ Health Perspect 124:875-880; http://dx.doi.org/10.1289/ehp.1409651.


Nonsurgical correction of cleft lip nasal deformity in the early neonate.
Auricular cartilage is soft and plastic, and congenital auricular deformities are easily corrected nonsurgically in the early neonatal period. Alar cartilage is the same kind of elastic cartilage as auricular cartilage. Therefore, alar cartilage is also malleable in the early neonate. When cleft lip repair is performed around the age of three months, it is difficult to obtain good nasal shape without surgical correction. In the early neonate, there is a fair possibility for success in the nonsurgical correction of cleft lip nasal deformity. We performed cleft lip repair accompanied with nonsurgical correction of nasal deformity in 48 neonates aged two to seven days. A special retainer was placed in the affected nostril during the postoperative period for three months. In 10 cases, preoperative nonsurgical correction with a special retainer began in the early neonatal period and the lip repair was done at about three months of age. Following observation of 40 infants for 12 months or longer, their nasal shapes and symmetry were considered superior to those conventionally operated on at about three months of age without nonsurgical correction of their nasal deformity during the early neonatal period. Except for one case of nasal infection, there were no other complications.


Regiodivergent Photocyclization of Dearomatized Acylphloroglucinols: Asymmetric Syntheses of (-)-Nemorosone and (-)-6-epi-Garcimultiflorone A.
Regiodivergent photocyclization of dearomatized acylphloroglucinol substrates has been developed to produce type A polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives using an excited-state intramolecular proton transfer (ESIPT) process. Using this strategy, we achieved the enantioselective total syntheses of the type A PPAPs (-)-nemorosone and (-)-6-epi-garcimultiflorone A. Diverse photocyclization substrates have been investigated leading to divergent photocyclization processes as a function of tether length. Photophysical studies were performed, and photocyclization mechanisms were proposed based on investigation of various substrates as well as deuterium-labeling experiments.


Inflammation, cytokines and anti-inflammatory therapies in heart failure.
Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Certain categories in patients with dilated cardiomyopathy have shown the presence of humoral and cellular immunity activation suggesting a possible relation between myocarditis and dilated cardiomyopathy. Recent studies suggest a link between the circulating levels of cytokines (TNF alpha IL-1 et IL-6), the clinical status and prognostic. However, the mechanisms connecting heart failure and cytokine activation are unclear and the sites of cytokines production remain controversial. In the clinical setting, specific measurements of cytokines are not available. As tests of inflammation, erythrocyte sedimentation rate and C-reactive protein concentration appear to have interesting pronostic values. Current conventional therapy i.e. ACE inhibitors, type I angiotensin II antagonist and beta-blockers have shown some anti-cytokine properties. Recently, immunosuppressive therapies have shown their ability to improve symptoms and LV ejection in selected patients with dilated cardiomyopathy and clear sign of myocardium inflammation. Specific anti-cytokine therapy have been developed and showed interesting results in preliminary clinical studies. However large clinical trials testing this new therapy have been stoppel prematurely because of deterious effects.


[Clinical and laboratory features of acute monocytic leukemia with B lymphoproliferative disorders].
To identify the clinical and pathological features of acute myeloid leukemia with B lymphoproliferative disorders. The characteristics of 3 cases of acute monocytic leukemia with untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis were reported with literatures review. The patients presented with a history of anemia, bleeding and/or fever. Acute monocytic leukemia was diagnosed by bone marrow morphology, cytochemistry and pathology studies. Immunophenotyping by flow cytometry analysis showed a significant population of absolute B-lymphocyte count of > 5×10(9)/L in a patients, similar to that of chronic lymphocytic leukemia. The association of acute monocytic leukemia and untreated chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis was a rare event. The abnormal B lymphocytes was likely to be misdiagnosis. Thus, it was important to combine several kinds of laboratory studies, especially flow cytometry to identify this rare disorder.


Bromocriptine in cocaine withdrawal--does it work?
Heavy cocaine use has been reported to lead to dopamine depletion in the brain, which in turn may be responsible for strong cocaine craving after withdrawal. Bromocriptine, a dopaminergic agonist, was used on that basis to prevent relapses in the withdrawal period. In an uncontrolled trial of 25 heavy cocaine users, measurements of pre- and post-bromocriptine serum prolactin levels-as indicators of inhibitory dopaminergic control-did not suggest dopamine depletion. Moreover, in 13 of these 25 patients, an assessment scale for craving and for other subjective discomforts indicated some improvement in only a slight majority, which is probably inseparable from placebo effect.


[Clinical examination of children with tooth aplasia. Correlations between dental symptoms and the whole organism].
The characteristic abnormalities of jaws, teeth, and salivation can be measured and expressed by numbers. The possible etiological factors, like the positive family history of noxas during the pregnancy can be explored. In our study we examined the symptoms of general organic system and teeth trait--jaw relation, seriousness of aplasia, abnormalities of teeth in size--defect of salivary glands and the presence of possible etiological factors. Thirty children were examined. The symptoms of general organic system were diagnosed. 60% of tooth agenesis occurs in the maxilla, the size of teeth reduced also in the upper jaw. Pseudoprogenia can be explained by these facts. The size reduction of extant teeth appeared stronger in the labiolingual direction. The salivary secretion rate in examined children proved significantly lower than in the control group. Seven siblings and eight parents were identified by examining the etiological factors. We did not find any noxas during the pregnancy by our questionnaire method.


Contemporary Imaging of Cerebral Arteriovenous Malformations.
Brain arteriovenous malformation (AVM) rupture results in substantial morbidity and mortality. The goal of AVM treatment is eradication of the AVM, but the risk of treatment must be weighed against the risk of future hemorrhage. Imaging plays a vital role by providing the information necessary for AVM management. Here, we discuss the background, natural history, clinical presentation, and imaging of AVMs. In addition, we explain advances in techniques for imaging AVMs.


Strategy development and learning differences in supervised and unsupervised categorization.
The processes that determine unsupervised categorization, the task of classifying stimuli without guidance or feedback, are poorly understood. Two experiments examined the emergence and plasticity of unsupervised strategies using perceptual stimuli that varied along two separable dimensions. In the first experiment, participants either classified stimuli into any two categories of their choice or learned identical classifications by supervised categorization. Irrespective of the complexity of classification, supervised and unsupervised learning rates differed little when both modes of learning were maximally comparable. The second experiment examined the plasticity of unsupervised classifications by introducing novel stimuli halfway through training. Whether or not people altered their strategies, they responded to novel stimuli in a gradual manner. The gradual and continuous evolution and adaptation of strategies suggests that unsupervised categorization involves true learning which shares many properties of supervised category learning. We also show that the choice of unsupervised strategy cannot be predicted from the properties of early learning trials, but is best understood as a function of the initial distribution of dimensional attention.


Association of Self-Perceived Physical Competence and Leisure-Time Physical Activity in Childhood-A Follow-Up Study.
The basis of self-perceived physical competence is built in childhood and school personnel have an important role in this developmental process. We investigated the association between initial self-perceived physical competence and reported leisure-time physical activity (LTPA) longitudinally in 10-, 12-, and 15-year-old children. This longitudinal follow-up study comprises pupils from an elementary school cohort (N = 1346) in the city of Turku, Finland (175,000 inhabitants). The self-perceived physical competence (fitness and appearance) and LTPA data were collected with questionnaires. The full longitudinal data were available from 571 pupils based on repeated studies at the ages of 10, 12, and 15 years in 2004, 2006, and 2010. We analyzed the association of self-perceived physical competence and LTPA using regression models. Self-perceived physical competence was positively associated with LTPA at all ages (10 years p < .05, 12 years p < .0001, 15 years p < .0001). Increase in the self-perceived physical fitness scores was likely to associate with higher LTPA at each age point (10 years [odds ratio, OR] = 1.18, 95% confidence interval, CI: 1.09-1.27; 12 years [OR] = 1.27, 95% CI: 1.18-1.37; and 15 years [OR] = 1.28, 95% CI: 1.19-1.38). Self-perceived physical competence is associated with LTPA in children and adolescents, and the association is strengthened with age.


Minimally invasive periapical curettage of foreign materials in periapical lesions using a fiberscope.
The design and development of a new fine fiberscope (1.0 mm outer diameter) is described, that includes an irrigation system for endoscopic use. This effectively allows visualisation of fields involved in periodontal disease. This fiberscope has been used in our clinic for seven years to diagnose and treat periapical and periodontal lesions through fistulae and periodontal pockets. The fiberscope has been applied to endodontic surgery for the inspection of root apices and the denuded root surfaces, in addition to the cut root face, rootend cavity and root-end filling after root-end resection. The advantages of endoscopy compared to surgical microscopy are portability and easy adjustment of direct viewing angle to examine around corners without the use of additional mirrors. Furthermore, the fiberscope can be utilised through the sinus tract or a minimal incision without the need for surgical flaps to observe the root surface, periapical tissue and foreign materials before, during and after curettage. The system requires little local anaesthesia, no large incisions, no opening flaps and no sutures. As a result, postoperative symptoms are minimised. Periapical curettage using a fiberscope represents a useful and minimally invasive surgical procedure.


Field-programmable-gate-array-based digital frequency stabilization of low-phase-noise diode lasers.
We present the comparison of a field-programmable-gate-array (FPGA) based digital servo module with an analog counterpart for the purpose of laser frequency stabilization to a high-finesse optical cavity. The transfer functions of both the digital and analog modules for proportional-integral-derivative control are measured. For the lasers stabilized to the cavity, we measure the singe-sideband power spectral density of fast phase noise by means of an optical beat with filtered light transmitted through the cavity. The comparison between the digital and analog modules is performed for two low-phase-noise diode lasers at 1120 and 665 nm wavelengths. The performance of the digital servo module compares well to the analog one for the lowest attained levels of 30 mrad for the integrated phase noise and 10-3 for the relative noise power. The laser linewidth is determined to be in the sub-kHz regime, only limited by the high-finesse cavity. Our work exploits the versatility of the FPGA-based servo module (STEMlab) when used with open-source software and hardware modifications. We demonstrated that such modules are suitable candidates for remote-controlled low-phase-noise applications in the fields of laser spectroscopy and atomic, molecular, and optical physics.


Role of oxidative stress from mitochondria on aging and cancer.
Much attention has been focused on the hypothesis that oxidative damage plays a part in cellular and organismal aging. Oxygen is initially converted to superoxide anion (O2), one of the reactive oxygen species (ROS), by electrons mainly leaked from complex III in the electron transport system present in mitochondria, where it is the major endogenous source of ROS. We have shown that a mutation in a subunit, cytochrome b large subunit (SDHC), of complex II, also results in increasing O2 production and therefore leads to apoptosis and precocious aging in Caenorhabditis elegans. Recently, individuals with an inherited propensity for vascularized head and neck tumors (ie, paragangliomas) have been shown to possess one of several mutations in complex II. To further explore the role of oxidative stress from mitochondria on apoptosis and cancer, we established a transgenic cell line with a point mutation at the ubiquinone binding region in the SDHC gene. As expected, this mutation increased O2 production from complex II and led to excess apoptosis. Moreover, a significant fraction of the surviving cells from the apoptosis were transformed, as evidenced by increased tumor formation, after injection into mice. Oxidative stress results in damage to the cellular components including mitochondria and therefore leads to apoptosis. Furthermore, oxidative stress seems to cause mutations in DNA and leads to cancer. It is suggested that oxidative stress from mitochondria plays an important role in apoptosis, which leads to precocious aging and cancer.


Successful use of rocuronium and sugammadex in an anticipated difficult airway scenario.
Neuromuscular blocking agents are often avoided in anticipated difficult airway scenarios. However to facilitate jet ventilation, muscle relaxants are useful. We report a case of a potentially threatened airway in a 21-year-old with a large infraglottic pedunculated polyp. In this case rocuronium was used on induction to facilitate subsequent jet ventilation and periglottic laser ablation of the tumour As the duration of the surgery was not predictable, the intention was to use sugammadex at the end to ensure complete reversal of muscle relaxation. This strategy also provided a quick rescue option if there was a sudden loss of the airway.


Efficacy of the epilepsy nurse: Results of a randomized controlled study.
We investigated the efficacy of epilepsy nurses on satisfaction with counseling about epilepsy in a randomized, controlled, prospective trial. Patients with epilepsy treated by neurologists in outpatient clinics were consecutively enrolled and randomly allocated to either the epilepsy nurse (EN) group (n = 92) or the control group (n = 95). Patients in the EN group were advised according to their needs by epilepsy nurses. The control group received routine care without additional counseling. The EN group completed the questionnaires before the first consultation (T1) and 6 months later (T2); the control group completed the questionnaires twice with an interval of 6 months. Primary outcome measure was satisfaction of patients with information and support. Secondary outcome measures were satisfaction with patient-doctor relationship, organization of treatment, epilepsy knowledge, coping, and restrictions in daily life. Anxiety and depression (Hospital Anxiety and Depression Scale) and global Quality of Life (item from QOLIE-31) were also assessed. Statistical analysis included generalized estimating equation (GEE) and nonparametric tests. Satisfaction with information and support improved significantly in the EN group compared to the control group (GEE, interaction group × time, p = 0.001). In addition, Epilepsy Knowledge (p = 0.014) and Coping (subscale Information Seeking) (p = 0.023) improved. Increase in satisfaction with counseling was dependent on patients' needs for information and on the amount of received information (Jonckheere-Terpstra test, p < 0.001). No differences between the groups were observed on other epilepsy-specific scales. A reliable questionnaire for satisfaction with epilepsy care has been developed. Epilepsy nurses improve the satisfaction of patients with counseling and information about epilepsy and concomitant problems.


Effects of nicotine exposure on in vitro metabolism of chlorpyrifos in male Sprague-Dawley rats.
The routine use of tobacco products may modify key metabolizing systems, which will further impact the metabolism of environmental contaminants. The objective of this study was to quantify the effect of repeated in vivo exposures to nicotine, a major pharmacologically active component of cigarette smoke, on in vitro metabolism of chlorpyrifos (CPF). CPF is an organophosphorus (OP) insecticide that is metabolized by cytochrome P-450 (CYP450) to its major metabolites, chlorpyrifos-oxon (CPF-oxon) and 3,5,6-trichloro-2-pyridinol (TCP). Male Sprague-Dawley rats were dosed subcutaneously with 1 mg nicotine/kg for 1, 7, or 10 d. Rats were sacrificed 4 or 24 h after the last nicotine treatment, and liver microsomes were prepared. The microsomes were incubated with varying concentrations of CPF and the production of the metabolites CPF-oxon and TCP were measured. The metabolism of CPF to the active oxon metabolite did not show significant changes following repeated nicotine treatments, evidenced by the unchanged pseudo first-order clearance rate of V(max)/K(mapp). The V(max) describing the metabolism of CPF to the inactive metabolite, TCP was increased in 24-h postdosing groups, after both single and repeated treatments of nicotine. In contrast, the metabolism to TCP was unchanged in groups evaluated at 4 h (single or repeated) post nicotine dosing. Some basic marker substrate activities were also investigated to ensure that nicotine exerted effects on CYP450 activities. Total P450 reduced spectra were not altered by nicotine treatment, but marker substrate activities for CYP1A and CYP2E1 were increased at 24 h after the single treatment, and marker substrate activity for CYP2B was decreased 4 h after 7 d of treatment. Results of this in vitro study suggest that repeated nicotine exposure may result in altered metabolism of CPF. Future in vivo experiments based on these results need to be conducted to ascertain the impact of in vivo nicotine exposures on CPF metabolism in rats.


Use of industrial amino acids to allow low protein concentrations in finishing diets for growing Muscovy ducks.
1. Three experiments were performed to assess the effects of decreasing protein concentration in the finishing diets for growing Muscovy ducks (8 to 12 weeks of age) by adding 4 essential amino acids (AAs, lysine, methionine, threonine and tryptophan). Experimental diets with crude protein (CP) contents from 105 to 142 g/kg, were compared with control diets providing 150 to 160 g/kg CP. In each trial, all diets were isocaloric. No significant modification in growth or carcase quality was observed when CP was greater than 124 g/kg in diets supplemented with the 4 essential AAs. 2. There was no advantages in supplying more than 4.3 g of digestible lysine per kg of diet (12.75 MJ ME/kg). When threonine was not added, breast yield decreased significantly (-4.3%), while omitting tryptophan supplementation did not influence performance. 3. Furthermore, the experiments confirmed that reducing CP had little or no effect on food conversion efficiency and fatness in Muscovy ducklings, unlike the observed situation in broiler chickens.


Bleomycin and cyclophosphamide increase pulmonary type IV procollagen mRNA in mice.
Constant 7-day subcutaneous infusion of bleomycin (100 mg/kg) induces pulmonary fibrosis in C57Bl/6N mice, whereas BALB/cN mice are relatively resistant. In contrast, cyclophosphamide (200 mg/kg, ip) induces fibrosis in BALB/cN mice, whereas C57Bl/6N mice are resistant. The effect of these drugs on the pulmonary levels of mRNA encoding the major basement membrane components, laminin and type IV collagen, relative to poly (A+)RNA was determined in both C57Bl/6N and BALB/cN mice. In the sensitive C57Bl/6N mice, bleomycin increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the absence of increases in laminin A, B1, and B2 mRNA/poly (A+)RNA. In the relatively resistant BALB/cN mice, bleomycin did not alter alpha 1IV procollagen mRNA/poly (A+)RNA and only transiently increased laminin A, B1, B2, and alpha 2IV procollagen mRNA/poly (A+)RNA. Similarly, cyclophosphamide increased alpha 1IV and alpha 2IV procollagen mRNA/poly (A+)RNA twofold in the sensitive BALB/cN mice and not in C57Bl/6N mice. Laminin mRNAs/poly (A+)RNA were not increased by cyclophosphamide in either strain. Thus, in these models, pulmonary fibrosis is preceded by a coordinate increase in steady-state levels of mRNA encoding basement membrane procollagen but is not associated with an increase in laminin gene expression.


The phenotypic manifestations of rare genic CNVs in autism spectrum disorder.
Significant evidence exists for the association between copy number variants (CNVs) and Autism Spectrum Disorder (ASD); however, most of this work has focused solely on the diagnosis of ASD. There is limited understanding of the impact of CNVs on the 'sub-phenotypes' of ASD. The objective of this paper is to evaluate associations between CNVs in differentially brain expressed (DBE) genes or genes previously implicated in ASD/intellectual disability (ASD/ID) and specific sub-phenotypes of ASD. The sample consisted of 1590 cases of European ancestry from the Autism Genome Project (AGP) with a diagnosis of an ASD and at least one rare CNV impacting any gene and a core set of phenotypic measures, including symptom severity, language impairments, seizures, gait disturbances, intelligence quotient (IQ) and adaptive function, as well as paternal and maternal age. Classification analyses using a non-parametric recursive partitioning method (random forests) were employed to define sets of phenotypic characteristics that best classify the CNV-defined groups. There was substantial variation in the classification accuracy of the two sets of genes. The best variables for classification were verbal IQ for the ASD/ID genes, paternal age at birth for the DBE genes and adaptive function for de novo CNVs. CNVs in the ASD/ID list were primarily associated with communication and language domains, whereas CNVs in DBE genes were related to broader manifestations of adaptive function. To our knowledge, this is the first study to examine the associations between sub-phenotypes and CNVs genome-wide in ASD. This work highlights the importance of examining the diverse sub-phenotypic manifestations of CNVs in ASD, including the specific features, comorbid conditions and clinical correlates of ASD that comprise underlying characteristics of the disorder.


Modeling aquifer storage and recovery in the eastern district of the United Arab Emirates using MODFLOW.
The Emirate of Abu Dhabi has relied on groundwater as a source of fresh water for several decades, which has resulted in the deterioration of non-renewable groundwater aquifers. This has led to the installation of desalination plants for fresh water supply. This research aims to increase strategic water reserves in the eastern district of Abu Dhabi by analyzing the best locations for aquifer storage and recovery (ASR). The ASR technology offers an opportunity to store large volumes of water for later beneficial use. This study explores an option of using excess desalination water for ASR recharge in the eastern district Al Ain region of Abu Dhabi. A limiting factor in the application of the ASR technology is the lack of suitable sites. Detailed hydrogeological and operational knowledge of the studied areas helped in identifying potential sites for ASR based on a scoring system. Determining best locations for managed aquifer recharge is a crucial design step. Five scenarios were studied at Al-Khrair and Al-Shuwaib sites in Al Ain region. Results show that a wider distribution of injection wells with intervals more than 1200 m is more suitable to overcome the excessive head buildup. Based on the adopted criteria, Al-Khrair was the best site for recharge followed by Al-Shuwaib. Al-Khrair site can be recharged at 64,000 m3 d-1 for seven years, while Al-Shuwaib site can be recharged at 64,000 m3 d-1 for only two years.


[Clinical and electrophysiologic findings following operative therapy of ventricular tachycardias].
40 patients with sustained ventricular tachycardia underwent either complete (n = 12) or partial (n = 28) endomyocardial encircling ventriculotomy ( EEV ). All patients had coronary artery disease, mean age 54 years. Aneurysmectomy was performed in 35 patients. 30 patients also received coronary artery bypass grafts. There were 3 perioperative deaths (7.5%): 1/12 with complete and 2/28 with partial EEV . All survivors underwent programmed right ventricular stimulation postoperatively. Ventricular tachycardia was not inducible in 23 of 36 patients (64%). One patient was not studied postoperatively. In contrast, sustained ventricular tachycardia was still inducible in 13 patients. Ventricular tachycardia was considered as "clinical" tachycardia in 9 patients whereas it was a "non-clinical" form in another 4 patients. Thus the electrophysiological failure rate with regard to "clinical" forms was 25%. In 2 of 4 patients with spontaneous recurrences during the first postoperative week, sustained ventricular tachycardia could not be induced during the postoperative electrophysiological study. During follow-up (mean 18 months), spontaneous recurrence of ventricular tachycardia occurred in 2 patients. Cardiac arrest possibly due to coronary bypass occlusion occurred in 1 patient who could be resuscitated. 6 patients died late postoperatively: 4 of congestive heart failure, 1 of re-infarction and 1 of fulminant pneumonia. 3/11 patients (27.3%) with complete and 1/26 (3.8%) with partial EEV died because of congestive heart failure (p less than .03). Thus abolition of spontaneous sustained ventricular tachycardia was successfully achieved in 94.6% of cases surviving surgery (91.9% if the patient with cardiac arrest is included.(ABSTRACT TRUNCATED AT 250 WORDS)


Molecular basis of retinol anti-ageing properties in naturally aged human skin in vivo.
Retinoic acid has been shown to improve the aged-appearing skin. However, less is known about the anti-ageing effects of retinol (ROL, vitamin A), a precursor of retinoic acid, in aged human skin in vivo. This study aimed to investigate the molecular basis of ROL anti-ageing properties in naturally aged human skin in vivo. Sun-protected buttock skin (76 ± 6 years old, n = 12) was topically treated with 0.4% ROL and its vehicle for 7 days. The effects of topical ROL on skin epidermis and dermis were evaluated by immunohistochemistry, in situ hybridization, Northern analysis, real-time RT-PCR and Western analysis. Collagen fibrils nanoscale structure and surface topology were analysed by atomic force microscopy. Topical ROL shows remarkable anti-ageing effects through three major types of skin cells: epidermal keratinocytes, dermal endothelial cells and fibroblasts. Topical ROL significantly increased epidermal thickness by stimulating keratinocytes proliferation and upregulation of c-Jun transcription factor. In addition to epidermal changes, topical ROL significantly improved dermal extracellular matrix (ECM) microenvironment; increasing dermal vascularity by stimulating endothelial cells proliferation and ECM production (type I collagen, fibronectin and elastin) by activating dermal fibroblasts. Topical ROL also stimulates TGF-β/CTGF pathway, the major regulator of ECM homeostasis, and thus enriched the deposition of ECM in aged human skin in vivo. 0.4% topical ROL achieved similar results as seen with topical retinoic acid, the biologically active form of ROL, without causing noticeable signs of retinoid side effects. 0.4% topical ROL shows remarkable anti-ageing effects through improvement of the homeostasis of epidermis and dermis by stimulating the proliferation of keratinocytes and endothelial cells, and activating dermal fibroblasts. These data provide evidence that 0.4% topical ROL is a promising and safe treatment to improve the naturally aged human skin.


Ureteral penetration caused by drilling during internal pelvic bone fixation: delayed recognition.
A 49-year-old man was referred to our department with profuse serous fluid discharge from a Penrose drain after undergoing internal fixation with metal screws for multiple pelvic bone fractures. A definite ureteral penetration was identified that was orientated from the lateral to the medial aspect of the right distal ureter. The patient was surgically treated with excision of the 2-cm injured ureteral segment, end-to-end ureteroureterostomy, and double J ureteral stent placement. To our knowledge, a penetrating ureteral injury caused by bone drilling has not been reported previously in the published literature. This case shows that surgeons who do pelvic surgery, including orthopedic surgeons, should be familiar with the anatomical relationship of the ureter and its potential injuries.


In vitro and ex vivo effects of erythromycin A, azithromycin and josamycin on the splenic response to specific antigens and mitogens.
The immunomodulatory properties of antimicrobial agents and their clinical impact have been the focus of worldwide interest in recent years. In this study, the effects of different treatments with 14-, 15- and 16-membered ring macrolides on the mitogen-induced proliferative response of lymphocytes and the splenic response to immunization with sheep erythrocytes have been tested by in vitro and ex vivo assays in a murine experimental model. We observed that the in vivo administration of these antibiotics to mice induces a compensatory mechanism that abrogates the suppression observed by in vitro assays. Thus, physiological parameters may be important when testing the immunopharmacological effects of antibiotics.


Functional neuroimaging of avoidance habits in obsessive-compulsive disorder.
The purpose of this study was to determine the neural correlates of excessive habit formation in obsessive-compulsive disorder (OCD). The authors aimed to test for neurobiological convergence with the known pathophysiology of OCD and to infer, based on abnormalities in brain activation, whether these habits arise from dysfunction in the goal-directed or habit system. Thirty-seven OCD patients and 33 healthy comparison subjects learned to avoid shocks while undergoing a functional MRI scan. Following four blocks of training, the authors tested whether the avoidance response had become a habit by removing the threat of shock and measuring continued avoidance. Task-related differences in brain activity in three regions of interest (the caudate, the putamen, and the medial orbitofrontal cortex) were tested at a statistical threshold set at <0.05 (family-wise-error corrected). Excessive habit formation in OCD patients, which was associated with hyperactivation in the caudate, was observed. Activation in this region was also associated with subjective ratings of increased urge to perform habits. The OCD group, as a whole, showed hyperactivation in the medial orbitofrontal cortex during the acquisition of avoidance; however, this did not relate directly to habit formation. OCD patients exhibited excessive habits that were associated with hyperactivation in a key region implicated in the pathophysiology of OCD, the caudate nucleus. Previous studies indicate that this region is important for goal-directed behavior, suggesting that habit-forming biases in OCD may be a result of impairments in this system, rather than differences in the buildup of stimulus-response habits themselves.


Gas phase hydrogen/deuterium exchange of arginine and arginine dipeptides complexed with alkali metals.
The hydrogen/deuterium (H/D) exchange of protonated and alkali-metal cationized Arg-Gly and Gly-Arg peptides with D(2)O in the gas phase was studied using electrospray ionization quadropole ion trap mass spectrometry. The Arg-Gly and Gly-Arg alkali metal complexes exchange significantly more hydrogens than protonated Arg-Gly and Gly-Arg. We propose a mechanism where the peptide shifts between a zwitterionic salt bridge and nonzwitterionic charge solvated conformations. The increased rate of H/D exchange of the alkali metal complexes is attributed to the peptide metal complexes' small energy difference between the salt-bridge conformation and the nonzwitterionic charge-solvated conformation. Implications for the applicability of this mechanism to other zwitterionic systems are discussed.


Absinthin, an agonist of the bitter taste receptor hTAS2R46, uncovers an ER-to-mitochondria Ca2+-shuttling event.
Type 2 taste receptors (TAS2R) are G protein-coupled receptors first described in the gustatory system, but have also been shown to have extraoral localizations, including airway smooth muscle (ASM) cells, in which TAS2R have been reported to induce relaxation. TAS2R46 is an unexplored subtype that responds to its highly specific agonist absinthin. Here, we first demonstrate that, unlike other bitter-taste receptor agonists, absinthin alone (1 μm) in ASM cells does not induce Ca2+ signals but reduces histamine-induced cytosolic Ca2+ increases. To investigate this mechanism, we introduced into ASM cells aequorin-based Ca2+ probes targeted to the cytosol, subplasma membrane domain, or the mitochondrial matrix. We show that absinthin reduces cytosolic histamine-induced Ca2+ rises and simultaneously increases Ca2+ influx into mitochondria. We found that this effect is inhibited by the potent human TAS2R46 (hTAS2R46) antagonist 3β-hydroxydihydrocostunolide and is no longer evident in hTAS2R46-silenced ASM cells, indicating that it is hTAS2R46-dependent. Furthermore, these changes were sensitive to the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenyl-hydrazone (FCCP); the mitochondrial calcium uniporter inhibitor KB-R7943 (carbamimidothioic acid); the cytoskeletal disrupter latrunculin; and an inhibitor of the exchange protein directly activated by cAMP (EPAC), ESI-09. Similarly, the β2 agonist salbutamol also could induce Ca2+ shuttling from cytoplasm to mitochondria, suggesting that this new mechanism might be generalizable. Moreover, forskolin and an EPAC activator mimicked this effect in HeLa cells. Our findings support the hypothesis that plasma membrane receptors can positively regulate mitochondrial Ca2+ uptake, adding a further facet to the ability of cells to encode complex Ca2+ signals.


Effect of local structures on structural evolution during crystallization in undercooled metallic glass-forming liquids.
The effect of local structures on structural evolution during the crystallization of undercooled ZrCu metallic glass-forming liquid was studied via molecular dynamics simulations. It is found that body-centered-cubic (bcc)-like clusters play a key role in structural evolution during crystallization. In contrast to previous speculations, the number of bcc-like crystal nuclei does not change much before the onset of crystallization. Instead, the development of a bcc-like critical nucleus during annealing leads to a strong spatial correlation with other nuclei in its surroundings, forming a crystalline structure template. It is also found that the size distribution of bcc-like nuclei follows a power-law form with an exponential cutoff in the early stage of annealing, but changes to a pure power-law behavior just before the onset of crystallization. This implies that the crystalline structure template has fractal feature and the undercooled liquids evolve to a self-organized critical state before the onset of crystallization, which might trigger the subsequent rapid crystallization. According to the graph theory analysis, it is also found that the observed large scatter of the onset time of crystallization in different liquid samples results from the connectivity of the bcc-like clusters.


Synaptic and temporal ensemble interpretation of spike-timing-dependent plasticity.
We postulate that a simple, three-state synaptic switch governs changes in synaptic strength at individual synapses. Under this switch rule, we show that a variety of experimental results on timing-dependent plasticity can emerge from temporal and spatial averaging over multiple synapses and multiple spike pairings. In particular, we show that a critical window for the interaction of pre- and postsynaptic spikes emerges as an ensemble property of the collective system, with individual synapses exhibiting only a minimal form of spike coincidence detection. In addition, we show that a Bienenstock-Cooper-Munro-like, rate-based plasticity rule emerges directly from such a model. This demonstrates that two apparently separate forms of neuronal plasticity can emerge from a much simpler rule governing the plasticity of individual synapses.


Screening for amnestic mild cognitive impairment and early Alzheimer's disease with M@T (Memory Alteration Test) in the primary care population.
To design and validate a new screening test for amnestic Mild Cognitive Impairment (A-MCI) and early stage Alzheimer's disease (AD). We develop a verbal episodic and semantic memory test: the Memory Alteration Test (M@T). Discriminative validity was assessed in a population sample of 400 aged individuals from primary care population centres in Barcelona, Spain, 50 patients with A-MCI according to Petersen et al. criteria, and 66 with early AD (Global Deterioration Scale-4 stage) according to the NINCDS-ADRDA criteria. The M@T is quick, 5-min, and easy to administer and to score. M@T mean scores were significantly different between all groups: 41.4 (SD = 4.9) in the primary care population, 31.5 (SD = 3.9) in the A-MCI group and 21.8 (SD = 4.9) in early AD. A cut-off score of 37 points had a sensitivity of 96% and a specificity of 79% for A-MCI diagnosis (AUC = 0.932). A cut-off score of 28 points had a sensitivity of 92% and a specificity of 98% for early AD diagnosis (AUC = 0.99) and a sensitivity of 87 % and specificity of 82% to differentiate between A-MCI and AD patients. The M@T provides efficient and valid screening for A-MCI and early stage AD, and discriminates between A-MCI and early AD patients.


Potential for modulation of the hydrophobic effect inside chaperonins.
Despite the spontaneity of some in vitro protein-folding reactions, native folding in vivo often requires the participation of barrel-shaped multimeric complexes known as chaperonins. Although it has long been known that chaperonin substrates fold upon sequestration inside the chaperonin barrel, the precise mechanism by which confinement within this space facilitates folding remains unknown. We examine the possibility that the chaperonin mediates a favorable reorganization of the solvent for the folding reaction. We discuss the effect of electrostatic charge on solvent-mediated hydrophobic forces in an aqueous environment. Based on these physical arguments, we construct a simple, phenomenological theory for the thermodynamics of density and hydrogen-bond order fluctuations in liquid water. Within the framework of this model, we investigate the effect of confinement inside a chaperonin-like cavity on the configurational free energy of water by calculating solvent free energies for cavities corresponding to the different conformational states in the ATP-driven catalytic cycle of the prokaryotic chaperonin GroEL. Our findings suggest that one function of chaperonins may involve trapping unfolded proteins and subsequently exposing them to a microenvironment in which the hydrophobic effect, a crucial thermodynamic driving force for folding, is enhanced.