Health education alone and health education plus advance provision of emergency contraceptive pills on knowledge and attitudes among university female students in Enugu, Nigeria.
This was an intervention study to compare the effects of health education alone and health education plus advance provision of emergency contraception (EC) pills on the knowledge and attitudes to EC by female students of University of Nigeria in South-East Nigeria. A structured questionnaire was used to collect data in February, 2009 from 290 female students of a tertiary educational institution (140 in the study group and 150 from the control group) who were selected by multistage sampling. Subsequently, health education was conducted among all the students. In addition, a pack containing 2 tablets of EC pills (Postinor) was given only to the students in the study group. Three months after this intervention, its effects were assessed through a survey using the same structured questionnaire employed in the baseline survey. knowledge of EC was significantly higher among the study group than the controls at post-intervention, P < 0.05. Attitudes to EC were also more favorable at post-intervention survey among the study group, P < 0.05 in most of the variables. Health education plus advance provision of EC pills effectively improved knowledge and attitudes to EC among female students of tertiary institutions more than health education alone and this should be promoted.


Divergent gonadotropin-gonadal dose-responsive coupling in healthy young and aging men.
The present study extends a recent composite model of in vivo interglandular signaling to assess the impact of age on 1) nonequilibrium exchange among diffusible and protein-bound testosterone (Te); 2) elimination of total and free Te; 3) basal and pulsatile Te secretion (sec); 4) the implicit feedforward function mediating luteinizing hormone (LH) concentration (con) drive of instantaneous Te sec; and 5) possible stochastic variability of the predicted LH con-Te sec dose-response linkage. To this end, we measured LH and Te con every 10 min for 24 h in healthy young (n = 13) and older men (n = 13). Statistical comparisons of analytic estimates revealed that elderly subjects manifest 1) reduced maximal burstlike LH-stimulated Te sec (impaired stimulus efficacy); 2) depressed half-maximally LH-stimulated Te sec (lower Leydig-cell responsivity); 3) decreased pulsatile and total Te sec; 4) elevated basal Te sec; 5) a prolonged half-life of total but not free Te con; and 6) delayed time evolution of LH and Te sec bursts. In contradistinction, age did not influence estimated LH-pulse potency (ED50), steroidogenic sensitivity (slope term), or stochastic variability of LH-Te coupling. On the basis of these data, we postulate that aging in the human male alters specific dose-response attributes linking LH con and Te sec and disrupts the time waveform of LH and Te sec bursts.


Advanced Cellulose Fibers for Efficient Immobilization of Enzymes.
Biocatalytic pulp fibers were prepared using surface functionalization of bleached kraft pulp with amino groups (F) and further immobilization of a cross-linked glucose oxidase (G*) from Aspergillus niger. The cross-linked enzymes (G*) were characterized using X-ray spectroscopy, Fourier transform infrared spectroscopy, dynamic scanning calorimetry, and dynamic light scattering. According to standard assays, the G* content on the resulting fibers (FG*) was of 11 mg/g of fiber, and enzyme activity was of 215 U/g. The results from confocal- and stimulated emission depletion microscopy techniques demonstrated that glucose oxidase do not penetrate the interlayers of fibers. The benefit of pulp fiber functionalization was evident in the present case, as the introduction of amino groups allowed the immobilization of larger amount of enzymes and rendered more efficient systems. Using the approach described on this paper, several advanced materials from wood pulp fibers and new bioprocesses might be developed by selecting the correct enzyme for the target applications.


Health effects of exposure to isocyanates in a car factory.
Isocyanates are known to induce occupational diseases. The aim of this work was to assess the health effects of exposure to isocyanates and to test the sensitivity of selected parameters for early detection of isocyanate-related allergic diseases. In total, 35 employees from one factory were tested: 26 workers exposed to isocyanates (exposed group) and nine office workers (control group). All subjects filled in a questionnaire regarding possible health problems. Fractional exhaled nitric oxide (FeNO) and spirometry were measured for each subject at the same time during two consecutive working days. A urine sample was taken for a biological exposure test (BET). No significant difference was found between the exposed and control groups for spirometry parameters and FeNO. However, in the exposed group, FeNO was highly elevated (> 50 ppb) in five subjects (all reporting health problems at the workplace, all with normal spirometry and non-smokers). The BET revealed a significant difference (p < 0.001) between the exposed and control groups for 4,4´-methylenediphenyl diamine (MDA) in the urine. Our examination showed the usefulness of the BET in monitoring of workplace exposure to isocyanates and the importance of FeNO in monitoring of allergic inflammation of airways in non-smoking employees with normal spirometry.


[Effect of antidepressants with different chemical structures on the uptake and release of norepinephrine in sections of the rat cerebral cortex].
Experiments with slices of the rat cortex were made to study the interaction between the ability of the antidepressants to inhibit the reverse uptake of 14C-noradrenaline and to inhibit its presynaptic release. The antidepressants studied are distributed into 3 groups according to the ratio of effective concentrations that block the uptake and enhance the release of 14C-noradrenaline from the slices. The first group includes the antidepressants (melipramine, chlorimipramine, Lu 5-003, Lu 3-010, S-394, pyrazidol) that have a ratio close to I and in whose mechanism of aminopotentiating action the main component is unlikely to be distinguished. The second group with a ratio less than I is represented by the substances (nortryptyline, desipramine) whose mechanism of the aminopotentiating action is determined by the inhibitory effect on the neurotransmitter reverse uptake. As to the 3d group antidepressants (thyroliberin, iprindol, noveril, C-356, C-395, amitryptyline), of great importance is their effect on the presynaptic neurotransmitter release from the terminals of the axons of noradrenergic neurons.


Identification of regional climatic conditions favorable for development of European canker of apple.
Months of the year with high risk of European canker (Neonectria galligena) development in areas of the United States, Chile, England, and Northern Ireland were determined from published data. Moving-window analysis of long-term climatic data was used to classify disease risk in these areas in relation to rainfall and temperature conditions using the degree of agreement statistic. Greatest agreement occurred when it both rained on >30% of days/month and there was an average of >8 h/day with temperature of 11 to 16°C. When these thresholds were applied in eight validation areas in New Zealand, Australia, the United States, The Netherlands, and Denmark, areas with reported higher risk of disease tended to be areas where the thresholds were exceeded more often and by greater amounts. Areas at higher latitudes (>52°) with frequent summer rainfall appeared to be most prone to European canker, including the fruit rot phase of the disease, probably because summer temperatures were more favorable than at lower latitudes. The climatic thresholds derived for European canker could be useful for studies of disease establishment risk, surveillance, eradication, climate change impact assessment, and, possibly, for disease risk forecasting. The methods used in this study allowed conditions favorable for disease development to be identified even though quantitative regional disease data were lacking, and they could be useful for similar geoclimatic studies of other diseases.


Simple unity among the fundamental equations of science.
The Price equation describes the change in populations. Change concerns some value, such as biological fitness, information or physical work. The Price equation reveals universal aspects for the nature of change, independently of the meaning ascribed to values. By understanding those universal aspects, we can see more clearly why fundamental mathematical results in different disciplines often share a common form. We can also interpret more clearly the meaning of key results within each discipline. For example, the mathematics of natural selection in biology has a form closely related to information theory and physical entropy. Does that mean that natural selection is about information or entropy? Or do natural selection, information and entropy arise as interpretations of a common underlying abstraction? The Price equation suggests the latter. The Price equation achieves its abstract generality by partitioning change into two terms. The first term naturally associates with the direct forces that cause change. The second term naturally associates with the changing frame of reference. In the Price equation's canonical form, total change remains zero because the conservation of total probability requires that all probabilities invariantly sum to one. Much of the shared common form for the mathematics of different disciplines may arise from that seemingly trivial invariance of total probability, which leads to the partitioning of total change into equal and opposite components of the direct forces and the changing frame of reference. This article is part of the theme issue 'Fifty years of the Price equation'.


Validation of an ultra-sensitive detection method for steroid esters in plasma for doping analysis using positive chemical ionization GC-MS/MS.
The standard approach to detect misuse with testosterone in sport is based on the determination and evaluation of the urinary steroid profile followed by the confirmation of atypical profiles using isotope ratio mass spectrometry. The detection capacity of these methods can be attenuated by confounding factors or testosterone preparations with endogenous isotopic fingerprints. An alternative detection method for misuse of an endogenous steroid in sports is the direct detection of the administered steroid ester present in most preparations. Thus unambiguous proof for doping misuse can be delivered. In this work, the sensitivity of gas chromatography coupled to a triple quadrupole with chemical ionization (GC-CI-MS/MS) is applied to detect trace levels of 10 testosterone and 2 nandrolone esters in plasma for in human doping analysis. The detection method was developed employing a liquid-liquid extraction and HPLC cleanup step before analysis on the GC-CI-MS/MS. The quantitative method was validated in a linear range of 100-2000 pg/ml and proved to be selective, reproducible and very sensitive with limits of detection as low as to 10 pg/ml. A clinical study with the administration of testosterone undecanoate in 3 volunteers was carried out and the compound was detectable up to 86 days after administration.


Synergic PDE3 and PDE4 control intracellular cAMP and cardiac excitation-contraction coupling in a porcine model.
Cyclic AMP phosphodiesterases (PDEs) are important modulators of the cardiac response to β-adrenergic receptor (β-AR) stimulation. PDE3 is classically considered as the major cardiac PDE in large mammals and human, while PDE4 is preponderant in rodents. However, it remains unclear whether PDE4 also plays a functional role in large mammals. Our purpose was to understand the role of PDE4 in cAMP hydrolysis and excitation-contraction coupling (ECC) in the pig heart, a relevant pre-clinical model. Real-time cAMP variations were measured in isolated adult pig right ventricular myocytes (APVMs) using a Förster resonance energy transfer (FRET) biosensor. ECC was investigated in APVMs loaded with Fura-2 and paced at 1 Hz allowing simultaneous measurement of intracellular Ca2+ and sarcomere shortening. The expression of the different PDE4 subfamilies was assessed by Western blot in pig right ventricles and APVMs. Similarly to PDE3 inhibition with cilostamide (Cil), PDE4 inhibition with Ro 20-1724 (Ro) increased cAMP levels and inotropy under basal conditions. PDE4 inhibition enhanced the effects of the non-selective β-AR agonist isoprenaline (Iso) and the effects of Cil, and increased spontaneous diastolic Ca2+ waves (SCWs) in these conditions. PDE3A, PDE4A, PDE4B and PDE4D subfamilies are expressed in pig ventricles. In APVMs isolated from a porcine model of repaired tetralogy of Fallot which leads to right ventricular failure, PDE4 inhibition also exerts inotropic and pro-arrhythmic effects. Our results show that PDE4 controls ECC in APVMs and suggest that PDE4 inhibitors exert inotropic and pro-arrhythmic effects upon PDE3 inhibition or β-AR stimulation in our pre-clinical model. Thus, PDE4 inhibitors should be used with caution in clinics as they may lead to arrhythmogenic events upon stress.


Study protocol for a cluster randomised controlled trial to assess the effectiveness of user-driven intervention to prevent aggressive events in psychiatric services.
People admitted to psychiatric hospitals with a diagnosis of schizophrenia may display behavioural problems. These may require management approaches such as use of coercive practices, which impact the well-being of staff members, visiting families and friends, peers, as well as patients themselves. Studies have proposed that not only patients' conditions, but also treatment environment and ward culture may affect patients' behaviour. Seclusion and restraint could possibly be prevented with staff education about user-centred, more humane approaches. Staff education could also increase collaboration between patients, family members and staff, which may further positively affect treatment culture and lower the need for using coercive treatment methods. This is a single-blind, two-arm cluster randomised controlled trial involving 28 psychiatric hospital wards across Finland. Units will be randomised to receive either a staff educational programme delivered by the team of researchers, or standard care. The primary outcome is the incidence of use of patient seclusion rooms, assessed from the local/national health registers. Secondary outcomes include use of other coercive methods (limb restraint, forced injection, and physical restraint), service use, treatment satisfaction, general functioning among patients, and team climate and employee turn-over (nursing staff). The study, designed in close collaboration with staff members, patients and their relatives, will provide evidence for a co-operative and user-centred educational intervention aiming to decrease the prevalence of coercive methods and service use in the units, increase the functional status of patients and improve team climate in the units. We have identified no similar trials. ClinicalTrials.gov NCT02724748 . Registered on 25th of April 2016.


Research status and development potential of composite hemostatic materials.
Bleeding is a serious incident that can occur in people's daily lives or clinics. Bleeding can be caused by accidental trauma, surgery, congenital diseases, or blood disorders caused by drugs. Excessive bleeding in the body can lead to illness or death. Adequate hemostasis is an essential strategy to prevent bleeding to avoid death and is the first step in wound healing. With rapid developments in science and technology, various hemostatic materials have been developed with the hope of enhancing the hemostatic effect by activating different coagulation mechanisms. Some examples are the formation of physical barriers, platelet aggregation, concentration of blood components, and release of clotting factors. The design of composite hemostatic materials should conform to the requirement according to which multiple coagulation mechanisms can be simultaneously activated in order to enhance the hemostatic effect. Combined with the research status of composite hemostatic materials, it has been found that there is still a lack of materials that exhibit high biocompatibility, shape variability, simultaneous usability for both internal and external bleeding, in vivo degradability, ability to camouflage platelets or blood cells, and other clotting-related factors. Therefore, the future development potential and optimization direction for composite hemostatic materials have been proposed through an in-depth discussion on their characteristics and coagulation mechanisms. It is hoped that this review can provide a worthwhile reference for research into hemostatic materials.


Organic anion and cation transporters are possibly involved in renal excretion of entecavir in rats.
The purpose of the present study was to investigate the roles of transporters in the renal excretion of entecavir. We analyzed the effect of probenecid, cimetidine, sulfobromophthalein sodium (BSP), verapamil, inhibitors of organic anion transporter (OAT), organic cation transporter (OCT), multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein respectively, on the excretion of entecavir. The area under plasma concentration-time curve (AUC), body clearance, and renal clearance of entecavir was examined in each group. After intravenous coadministration with entecavir in conscious rats, cimetidine, probenecid, BSP and verapamil significantly increased the AUC of entecavir by 40.07%, 48.78%, 37.49%, and 54.58%, and reduced the body clearance by 27.14%, 31.69%, 29.79%, and 42.17%, respectively. Then the effects of these inhibitors on the renal clearance of entecavir in unconscious rats were studied. Coadministration of cimetidine and probenecid increased the steady plasma concentration of entecavir by 127.61% and 169.46%, reduced the renal clearance by 50.47% and 67.76%, and decreased the excretion ratio by 44.81% and 64.16% compared to initial values. However, the effects of BSP and verapamil were slight. Cimetidine and probenecid also increased the concentration of entecavir in kidney from 34.00±0.80ng/mL to 55.19±4.92ng/mL and 49.92±1.53ng/mL, while the concentration of entecavir in kidney from BSP and verapamil groups was 30.96±0.81ng/mL and 35.72±7.30ng/mL, respectively. These results suggest that cimetidine and probenecid inhibit the renal excretion of entecavir in rats, which indicates the most likely involvement of organic anion and cation transporters in the renal excretion of entecavir.


Surgical techniques for the removal of mandibular wisdom teeth.
The surgical removal of mandibular wisdom teeth is one of the most common operations undertaken in oral and maxillofacial surgery. The most common indication for surgery is infection about a partially erupted tooth that is impacted against bone or soft tissues. Other indications include unrestorable caries, pulpal and periapical pathology, fracture of the tooth and cyst development, amongst others. Most commonly the benefits of surgical removal of a wisdom tooth include alleviation of the symptoms and signs of pericoronitis and its potential consequences. However, surgery is frequently associated with postoperative pain, swelling and trismus. Less commonly complications include infection, including dry socket, trigeminal nerve injuries and rarely fracture of the mandible. To compare the relative benefits and risks of different techniques for undertaking various aspects or stages of the surgical extraction of mandibular wisdom teeth. We searched the Cochrane Oral Health Group's Trials Register (to 21 March 2014), CENTRAL (The Cochrane Library 2014, Issue 1), MEDLINE (OVID) (1946 to 21 March 2014) and EMBASE (OVID) (1980 to 21 March 2014). We searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. There were no restrictions regarding language or date of publication in the electronic searches. RCTs comparing surgical techniques for removal of mandibular wisdom teeth. Two review authors conducted assessment of relevance, risk of bias and data extraction. Study authors were contacted for additional information. RRs were used for dichotomous data and MDs for continuous data, unless the event rate was very low and Peto ORs were used. The pairing of the split-mouth studies was taken into account in the analysis for both dichotomous and continuous outcomes, and parallel group and split-mouth studies were combined using the generic inverse variance method. Random-effects models were used provided there were more than three studies (fixed-effect models otherwise). A total of 35 trials (2569 patients) were included. The interventions under consideration fell into seven broad categories, with many comparisons including only a small number of trials. Twenty-one of the trials were assessed at high risk of bias, the remaining 14 as unclear. The results are described in the summary of findings tables.Triangular flaps were associated with a 71% reduction in alveolar osteitis at one week (RR 0.29, 95% CI 0.11 to 0.78; three trials, moderate quality) and reduction in pain at 24 hours (MD -0.21, 95% CI -0.32 to -0.10; two trials, moderate quality) compared with envelope flaps. There was no evidence of a difference in overall infection rates, in maximum mouth opening or in permanent sensation. However, there was some evidence that residual swelling after one week was slightly increased in the triangular flap groups compared to envelope flap types (MD 0.66 mm, 95% CI 0.26 to 1.07; two trials, low quality). We found no data on temporary sensation, or adverse events.There was low quality evidence from two studies, looking at the use of a retractor during third molar surgery, to indicate more cases of temporary altered sensation (up to one month) when a retractor was used (Peto OR 5.19, 95% CI 1.38 to 19.49; two trials, low quality). One study reported that this did not persist for more than six months in either group. We found no data for use of a retractor on other primary outcomes or adverse effects (including fracture of the mandible).Due to the small number of studies, the different comparisons evaluated, the variable outcomes reported and the paucity of useful data for all primary outcomes we were not able to draw any conclusions concerning bone removal in third molar surgery.There was insufficient evidence from single studies of very low quality on irrigation method (manual versus mechanical) or irrigation volume (low or high) to determine whether there were differences or not for the outcomes of alveolar osteitis or postoperative infection. We found no data for any of the other primary outcomes.There was insufficient evidence (low to very low quality) that any wound closure technique (primary versus secondary) was superior to another for the outcomes of alveolar osteitis, postoperative infection or maximum mouth opening achieved after seven days, or reactionary bleeding. There was evidence that secondary wound closure was associated with reduced pain at 24 hours (MD 0.79, 95% CI 0.35 to 1.24; four trials, moderate quality) and slightly reduced swelling after one week (MD 0.33, 95% CI 0.09 to 0.57; seven trials, moderate quality).We found no data on other primary outcomes.There was some evidence that the use of a surgical drain was associated with less postoperative swelling (MD -0.90, 95% CI -1.62 to -0.19; five trials, moderate quality) and greater maximum mouth opening one week after surgery (MD 3.72 mm, 95% CI 2.84 to 4.59; two trials, moderate quality). There was insufficient evidence from a single study (low quality) to determine whether the presence of a drain made any difference to pain at 24 hours postoperation. There were no data for the other primary outcomes.Although two RCTs compared coronectomy with complete extraction, flaws in the design and the unit of analysis of these studies meant that there were no reliable data available for inclusion. The thirty-five included trials looked at a range of different surgical techniques. The comparisons related to seven broad aspects of the surgical procedures for impacted mandibular third molars: type of surgical flap raised, use of retractors, techniques for bone removal, wound irrigation, wound closure, wound drainage, and complete/incomplete tooth removal. The quality of the body of evidence for each of these comparisons was very low to moderate due to the small number of trials and patients, and the majority of the trials being at high risk of bias (65%) with the remainder at unclear risk of bias.The evidence for making changes to surgical practice is therefore limited. However, it is useful to describe the state of the research evidence supporting practice so that surgeons can make an informed choice in adopting new techniques, or continuing with established techniques.


Egr3-dependent muscle spindle stretch receptor intrafusal muscle fiber differentiation and fusimotor innervation homeostasis.
Muscle stretch proprioceptors (muscle spindles) are required for stretch reflexes and locomotor control. Proprioception abnormalities are observed in many human neuropathies, but the mechanisms involved in establishing and maintaining muscle spindle innervation and function are still poorly understood. During skeletal muscle development, sensory (Ia-afferent) innervation induces contacted myotubes to transform into intrafusal muscle fibers that form the stretch receptor core. The transcriptional regulator Egr3 is induced in Ia-afferent contacted myotubes by Neuregulin1 (Nrg1)/ErbB receptor signaling and it has an essential role in spindle morphogenesis and function. Because Egr3 is widely expressed during development and has a pleiotropic function, whether Egr3 functions primarily in skeletal muscle, Ia-afferent neurons, or in Schwann cells that myelinate Ia-afferent axons remains unresolved. In the present studies, cell-specific ablation of Egr3 in mice showed that it has a skeletal muscle autonomous function in stretch receptor development. Moreover, using genetic tracing, we found that Ia-afferent contacted Egr3-deficient myotubes were induced in normal numbers, but their development was blocked to generate one to two shortened fibers that failed to express some characteristic myosin heavy chain (MyHC) proteins. These "spindle remnants" persisted into adulthood, remained innervated by Ia-afferents, and expressed neurotrophin3 (NT3), which is required for Ia-afferent neuron survival. However, they were not innervated by fusimotor axons and they did not express glial derived neurotrophic factor (GDNF), which is essential for fusimotor neuron survival. These results demonstrate that Egr3 has an essential role in regulating gene expression that promotes normal intrafusal muscle fiber differentiation and fusimotor innervation homeostasis.


[Clinical use of ventilation measurement during early phase of exercise in patients with chronic heart failure].
In patients with chronic heart failure (CHF) augmented exercise ventilation is related to functional severity and increased mortality. Nevertheless, the optimal approach to the assessment of ventilatory response to controlled exercise has not been established. The study was carried out to evaluate the clinical application of the measurement of ventilatory response to the early phase of exercise in the non-selected group of patients with CHF. We investigated 180 consecutive patients with CHF (155 men, age: 59 +/- 11 years, left ventricle ejection fraction: 31 +/- 7%; NYHA class I/II/III/IV: 13/90/60/17). All patients underwent the cardiopulmonary exercise testing (CPX) with RER > 1.0 (mean peak oxygen consumption [peakVO2]: 15.5 +/- 4.8 ml/kg/min). Ventilatory response to exercise was assessed: 1) during the whole exercise--expressed as a correlation coefficient of linear regression describing the relationship between minute ventilation (VE) and carbon dioxide production (VCO2) during the whole exercise (VE-VCO2 100%); 2) during the early phase of exercise--expressed as VE-VCO2 derived from VE and VCO2 during first 180 seconds of exercise (VE-VCO2 180 s). Ventilatory responses to early and maximal exercise were significantly augmented in CHF patients (VE-VCO2 100% -36.1 +/- 9.8, VE-VCO2 180% -34.4 +/- 10.3; p < 0.0001 vs values in the reference group without CHF). Ventilatory responses to early and whole exercise were strongly interrelated (r = 0.88, p < 0.0001). Indices of exercise ventilation correlated with the severity of CHF expressed as NYHA class (for VE-VCO2 100% and VE-VCO2 180 s -r = 0.52 and r = 0.51) and peak VO2 (for VE-VCO2 100% and VE-VCO2 180 s, r = -0.49 and r = -0.47, respectively) (p < 0.0001 for all correlations). Among echocardiographic parameters only right ventricular systolic pressure correlated with indices of exercise ventilation (for VE-VCO2 100% -r = 0.45, p = 0.001; for VE-VCO2 180 s -r = 0.35, p = 0.01). The reproducibility of indices of exercise ventilation was assessed in 19 CHF patients (another CPX during 2-9 days), and variability coefficients reached 7.8% for VE-VCO2 100% and 8.5% for VE-VCO2 180 s. Indices of ventilatory response to both early and maximal exercise can significantly differentiate the CHF patients with regard to their exercise capacity, are highly reproducible, and may therefore constitute useful parameters carrying an important clinical message. The assessment of ventilatory response during the early stage of exercise seems to be of a particular significance in CHF patients who are unable to perform the maximal exercise effort, as diagnostic data obtained during first 180 seconds of exercise are in accordance to those derived from the standard maximal CPX.


Food Insecurity Is Associated With Lower Levels of Antiretroviral Drug Concentrations in Hair Among a Cohort of Women Living With Human Immunodeficiency Virus in the United States.
Food insecurity is a well-established determinant of suboptimal, self-reported antiretroviral therapy (ART) adherence, but few studies have investigated this association using objective adherence measures. We examined the association of food insecurity with levels of ART concentrations in hair among women living with human immunodeficiency virus (WLHIV) in the United States. We analyzed longitudinal data collected semiannually from 2013 through 2015 from the Women's Interagency HIV Study, a multisite, prospective, cohort study of WLHIV and controls not living with HIV. Our sample comprised 1944 person-visits from 677 WLHIV. Food insecurity was measured using the US Household Food Security Survey Module. ART concentrations in hair, an objective and validated measure of drug adherence and exposure, were measured using high-performance liquid chromatography with mass spectrometry detection for regimens that included darunavir, atazanavir, raltegravir, or dolutegravir. We conducted multiple 3-level linear regressions that accounted for repeated measures and the ART medication(s) taken at each visit, adjusting for sociodemographic and clinical characteristics. At baseline, 67% of participants were virally suppressed and 35% reported food insecurity. In the base multivariable model, each 3-point increase in food insecurity was associated with 0.94-fold lower ART concentration in hair (95% confidence interval, 0.89 to 0.99). This effect remained unchanged after adjusting for self-reported adherence. Food insecurity was associated with lower ART concentrations in hair, suggesting that food insecurity may be associated with suboptimal ART adherence and/or drug absorption. Interventions seeking to improve ART adherence among WLHIV should consider and address the role of food insecurity.


In vivo imaging of carbon nanotube biodistribution using magnetic resonance imaging.
As novel engineered nanoparticles such as carbon nanotubes (CNTs) are extensively used in nanotechnology due to their superior properties, it becomes critical to fully understand their biodistribution and effect when accidently inhaled. A noninvasive follow-up study would be beneficial to evaluate the biodistribution and effect of nanotube deposition after exposure directly in vivo. Combined helium-3 and proton magnetic resonance resonance (MRI) were used in a rat model to evaluate the biodistribution and biological impact of raw single-wall CNTs (raw-SWCNTs) and superpurified SWCNTs (SP-SWCNTs). The susceptibility effects induced by metal impurity in the intrapulmonary instilled raw-SWCNT samples were large enough to induce a significant drop in magnetic field homogeneity detected in 3He MR image acquired under spontaneous breathing conditions using a multiecho radial sequence. No MRI susceptibility variation was observed with SP-SWCNT exposition even though histological analysis confirmed their presence in instilled lungs. Proton MRI allowed detection of intravenously injected raw-SWCNTs in spleen and kidneys using gradient echo sequence sensitive to changes of relaxation time values. No signal modifications were observed in the SP-SWCNT injected group. In instilled groups, the contrast-to-noise ratio in liver, spleen, and kidneys stayed unchanged and were comparable to values obtained in the control group. Histological analysis confirms the absence of SWCNTs in systemic organs when SWCNTs were intrapulmonary instilled. In conclusion, the presence of SWCNTs with associated metal impurities can be detected in vivo by noninvasive MR techniques. Hyperpolarized 3He can be used for the investigation of CNT pulmonary biodistribution while standard proton MR can be performed for systemic investigation following injection of CNT solution.


Self-socialization: a case study of a parachute child.
The theoretical concept of self-socialization suggests that an individual is able to reflect on the self, formulate a vision of a future self, set goals, and take actions that create or alter the developmental trajectory. This case study of a parachute child illustrates how a person constructs her life from a very young age, drawing on a profound capacity for personal agency to overcome obstacles, identify resources, and internalize values to build a life structure. A model of the psychosocial process of self-socialization emerges from this case. Following the disruption of a well-defined trajectory, self-socialization is observed as a sequence of actions, reflection, correction, and new actions. Self-socialization is possible when a strong sense of self-efficacy is applied to attaining internalized values and goals.


Improved peripheral nerve regeneration with sustained release nerve growth factor microspheres in small gap tubulization.
To evaluate the long-term results of the use of nerve growth factor (NGF)-loaded poly-D, L-lactide-co-glycolide (PLGA) microspheres for improve nerve regeneration with small gap tubulization. NGF microspheres were prepared by a modified W/O/W emulsion solvent evaporation method. Forty-eight male SD rats were separated into 4 groups and received a chitin conduit to bridge a sciatic nerve injury left a 2 mm gap. Saline (Group A), 20 ng/ml NGF solution (Group B), blank PLGA microspheres (Group C), or 40 ng/ml NGF-loaded microspheres (Group D) was injected in the gap. Each group had two study endpoints, 3 months subgroup and 1 year subgroup. The myelinated fiber count at 2 mm distal to the conduit at 1 year was slightly less than at 3 months in all groups (P>0.05). However, the maturity of the myelinated nerves at 1 year was obviously improved. The fiber count, myelin sheath thickness, axon area of NGF microsphere group were significantly higher than the saline groups at 3 months (P=0.05, P<0.05, and P<0.05, respectively). The SFI was significantly improved in NGF microspheres group compared to the saline group and NGF solution group at 1 year (P<0.05, and P<0.05, respectively). The results demonstrated that the release of NGF microspheres in small gap tubulization benefit on peripheral nerve injury facilitated nerve regeneration histologically, especially for the maturity of early regenerative nerve fibers and also had an effect on functional recovery in the long term.


In vivo and in vitro osmotic regulation of HSP-70 and prostaglandin synthase gene expression in kidney cells.
As a function of the urinary concentrating mechanism, the cells of the renal medulla are exposed to elevated and constantly varying osmolalities and adapt to this environment by selectively expressing certain mRNAs. We evaluated the expression and regulation of two RNAs that may be important in adaptation of rental medullary cells to hyperosmolality. We demonstrate selective, modulated expression in the renal medulla of heat shock protein HSP-70 mRNA and prostaglandin synthase-1 mRNA, with the abundance of these two mRNAs regulated in vivo in concert with changes in medullary sodium and urea. We also determined the abundance of these mRNAs in cultured kidney cells (MDCK) in response to an increase in extracellular osmolality due to selected osmotic agents. HSP-70 and prostaglandin synthase-2 mRNA levels increased when extracellular osmolality was increased to 400-600 mosmol/kg by the addition of NaCl. At 500 mosmol/kg this response was evident at 6 h, was maximal near 24 h, and persisted for a total of 90 days. Prostaglandin synthase-1 mRNA levels in MDCK cells were also increased after chronic exposure to extracellular osmolality. Increased extracellular osmolality caused by agents to which cells are impermeable caused increased levels of HSP-70 and prostaglandin synthase-2 mRNAs, whereas increased extracellular osmolality caused by agents to which cells are permeable did not; thus osmotic regulation involved osmotic water movement. We conclude that the abundance of HSP-70 and prostaglandin synthase-1 mRNAs in the renal medulla is regulated in response to renal medullary osmolality and suggest that this may also be true for other medullary mRNAs yet to be described.


Pulsed and cw photothermal phase shift spectroscopy in a fluid medium: theory.
A theoretical treatment of photothermal phase shift spectroscopy in a fluid medium for the most general conditions is given. The medium is assumed to be flowing. Results for a stationary medium appear as a special case. Both pulsed and cw excitation are considered. For pulsed excitation, the results are valid for excitation pulses of arbitrary length. For the cw case, modulated excitation is explicitly considered, and the results for unmodulated excitation appear as a special case.


Quantification of endotoxin inhibition in serum and plasma using a turbidimetric LAL assay.
A modified Limulus amebocyte lysate (LAL) test was developed which quantifies the inhibition associated with lipopolysaccharide (LPS) in serum and plasma. The assay utilized the LR50 value to determine relative inhibition. The LR50, measured in ng/ml, represented the concentration of endotoxin needed to elicit a turbidimetric response equal to 50% of the maximum above the control (no added endotoxin). The LR50 concept was used to compare plasma and serum from a normal donor population. Plasma LR50 values ranged from 115 to 5000 ng/ml, while serum samples ranged from 48 to 615 ng/ml. Endotoxin in saline measured in a similar manner yielded values averaging 0.07 ng/ml (LAL sensitivity). Various means to remove inhibition were also tested by this method. Heating, dilution, and chloroform extraction of serum were all found to be efficient in removing inhibition. Although no direct attempt was made to elucidate the biochemical nature of the inhibitor(s) present in serum and plasma, the results presented were consistent with other studies and indicate the involvement of a heat labile component(s). The LR50 may provide a tool for the elaboration of these components. It also was suggested that LR50 may be the best in vitro indicator of the overall ability of serum or plasma to neutralize endotoxin.


Multilevel Analysis of Urban-Rural Variations of Body Weights and Individual-Level Factors among Women of Childbearing Age in Nigeria and South Africa: A Cross-Sectional Survey.
Background: An unhealthy body weight is an adverse effect of malnutrition associated with morbidity among women of childbearing age. While there is increasing attention being paid to the body weights of children and adolescents in Nigeria and South Africa, a major surge of unhealthy body weight in women has received less attention in both countries despite its predominance. The purpose of this study was to explore the prevalence of body weights (underweight, normal, overweight, and obese) and individual-level factors among women of childbearing age by urban-rural variations in Nigeria and South Africa. Methods: This study used the 2018 Nigeria Demographic Health Survey data (n = 41,821) and 2016 South Africa Demographic Health Survey (n = 8514). Bivariate, multilevel, and intracluster correlation coefficient analyses were used to determine individual-level factors associated with body weights across urban-rural variations. Results: The prevalence of being overweight or obese among women was 28.2% and 44.9%, respectively, in South Africa and 20.2% and 11.4% in Nigeria. A majority, 6.8%, of underweight women were rural residents in Nigeria compared to 0.8% in South Africa. The odds of being underweight were higher among women in Nigeria who were unemployed, with regional differences and according to breastfeeding status, while higher odds of being underweight were found among women from poorer households, with differences between provinces and according to cigarette smoking status in South Africa. On the other hand, significant odds of being overweight or obese among women in both Nigeria and South Africa were associated with increasing age, higher education, higher wealth index, weight above average, and traditional/modern contraceptive use. Unhealthy body weights were higher among women in clustering areas in Nigeria who were underweight (intracluster correlation coefficient (ICC = 0.0127), overweight (ICC = 0.0289), and obese (ICC = 0.1040). Similarly, women of childbearing age in clustering areas in South Africa had a lower risk of experiencing underweight (ICC = 0.0102), overweight (ICC = 0.0127), and obesity (ICC = 0.0819). Conclusions: These findings offer a deeper understanding of the close connection between body weights variations and individual factors. Addressing unhealthy body weights among women of childbearing age in Nigeria and South Africa is important in preventing disease burdens associated with body weights in promoting Sustainable Development Goal 3. Strategies for developing preventive sensitization interventions are imperative to extend the perspectives of the clustering effect of body weights on a country level when establishing social and behavioral modifications for body weight concerns in both countries.


AVP reduces transepithelial resistance across IMCD cell monolayers.
The inner medullary collecting duct (IMCD) is an important site of action for arginine vasopressin (AVP). To examine the mode of action of AVP in this segment, we measured the change in transepithelial resistance of cultured rat IMCD cells grown to confluence on collagen-coated Millicell culture plate inserts in response to AVP. Resistance was measured by use of an EVOM voltage-ohm meter. AVP at 10(-11)-10(-8) M caused a fall in resistance of 6.9 +/- 1.3 to 14.0 +/- 1.4 omega.cm2 (P less than 0.05 to less than 0.01 vs. no AVP), which was reversed by removal of AVP or addition of 10(-6) M amiloride. Pretreating the apical surface of IMCD cells with trypsin had no effect on resistance but totally prevented the antidiuretic hormone-induced fall in resistance. Pretreating the apical surface with trypsin and amiloride did not prevent the fall in resistance to AVP. Addition of 10(-9) M AVP or 10(-6) M forskolin increased 2-min adenosine 3',5'-cyclic monophosphate (cAMP) accumulation by 55 or 96%, respectively. Stimulation of endogenous cAMP accumulation by forskolin or the addition of exogenous 8-bromo-cAMP caused no change in resistance. To examine the relationship between intracellular calcium [( Ca2+]i) and AVP action, the response of [Ca2+]i to AVP was measured by use of fura-2. AVP induced no change in [Ca2+]i in IMCD cells in suspension, on glass cover slips, or on permeable supports. Ionomycin (25 nM) increased [Ca2+]i in IMCD cells and lowered resistance across monolayers, but the fall in resistance was not blocked by amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)


Psychiatrists' and internists' knowledge and attitudes about delivery of clinical preventive medical services.
Changes in the health care environment have placed a greater responsibility on psychiatrists to deliver basic primary care services. The study assessed baseline knowledge and attitudes about clinical preventive medical services among psychiatric faculty and psychiatric residents at a tertiary care medical center. Residents and faculty in psychiatry and general internal medicine completed a structured questionnaire, including 20 case scenarios, that assessed their baseline knowledge of clinical preventive medical services, their attitudes concerning delivery of those services, and their beliefs about the effectiveness of those services in changing patients' behavior. The case scenarios and knowledge questions were based on the clinical preventive medical services recommendations outlined by the U. S. Preventive Services Task Force. Psychiatrists reported more frequent assessment of and counseling about the use of illicit drugs and weapons, and internists were more likely to query about measures related to physical health such as cancer screening and immunizations. The two groups reported similar attitudes toward the need for and the efficacy of preventive medical services. Commonly cited barriers to the delivery of preventive care included lack of time and education. Psychiatrists scored reasonably well on baseline knowledge about guidelines for preventive medical services, particularly given their recent lack of specific education in these matters. Psychiatrists believe clinical preventive services are important and express interest in their delivery. Additional educational interventions are needed to train psychiatrists in clinical preventive services to avoid missed clinical opportunities for intervention in psychiatric populations that may have poor access to other medical care.


Controlling assembly of paired gold clusters within apoferritin nanoreactor for in vivo kidney targeting and biomedical imaging.
Functional nanostructures with high biocompatibility and stability, low toxicity, and specificity of targeting to desired organs or cells are of great interest in nanobiology and medicine. However, the challenge is to integrate all of these desired features into a single nanobiostructure, which can be applied to biomedical applications and eventually in clinical settings. In this context, we designed a strategy to assemble two gold nanoclusters at the ferroxidase active sites of ferritin heavy chain. Our studies showed that the resulting nanostructures (Au-Ft) retain not only the intrinsic fluorescence properties of noble metal, but gain enhanced intensity, show a red-shift, and exhibit tunable emissions due to the coupling interaction between the paired Au clusters. Furthermore, Au-Ft possessed the well-defined nanostructure of native ferritin, showed organ-specific targeting ability, high biocompatibility, and low cytotoxicity. The current study demonstrates that an integrated multimodal assembly strategy is able to generate stable and effective biomolecule-noble metal complexes of controllable size and with desirable fluorescence emission characteristics. Such agents are ideal for targeted in vitro and in vivo imaging. These results thus open new opportunities for biomolecule-guided nanostructure assembly with great potential for biomedical applications.


Systemic mastocytosis with review of gastrointestinal manifestations.
A 63-year-old man presented with fever, splenomegaly, steatorrhea, diarrhea, and weight loss. A tissue diagnosis of systemic mastocytosis was made. This case is unusual in that diarrhea and steatorrhea were present in the absence of skin lesions and because fever was a prominent symptom. Thus, systemic mastocytosis should be included in the differential diagnosis of intestinal malabsorption even when the skin shows no abnormalities. The gastrointestinal manifestations of systemic mastocytosis are reviewed.


Randomized Controlled Trial of Intensive Versus Conservative Glucose Control in Patients Undergoing Coronary Artery Bypass Graft Surgery: GLUCO-CABG Trial.
The optimal level of glycemic control needed to improve outcomes in cardiac surgery patients remains controversial. We randomized patients with diabetes (n = 152) and without diabetes (n = 150) with hyperglycemia to an intensive glucose target of 100-140 mg/dL (n = 151) or to a conservative target of 141-180 mg/dL (n = 151) after coronary artery bypass surgery (CABG) surgery. After the intensive care unit (ICU), patients received a single treatment regimen in the hospital and 90 days postdischarge. Primary outcome was differences in a composite of complications, including mortality, wound infection, pneumonia, bacteremia, respiratory failure, acute kidney injury, and major cardiovascular events. Mean glucose in the ICU was 132 ± 14 mg/dL (interquartile range [IQR] 124-139) in the intensive and 154 ± 17 mg/dL (IQR 142-164) in the conservative group (P < 0.001). There were no significant differences in the composite of complications between intensive and conservative groups (42 vs. 52%, P = 0.08). We observed heterogeneity in treatment effect according to diabetes status, with no differences in complications among patients with diabetes treated with intensive or conservative regimens (49 vs. 48%, P = 0.87), but a significant lower rate of complications in patients without diabetes treated with intensive compared with conservative treatment regimen (34 vs. 55%, P = 0.008). Intensive insulin therapy to target glucose of 100 and 140 mg/dL in the ICU did not significantly reduce perioperative complications compared with target glucose of 141 and 180 mg/dL after CABG surgery. Subgroup analysis showed a lower number of complications in patients without diabetes, but not in patients with diabetes treated with the intensive regimen. Large prospective randomized studies are needed to confirm these findings.


[Detection of rubella antibodies in blood samples collected on filter paper].
Congenital rubella syndrome (CRS) could be prevented if young women knew their immune status before pregnancy, contributing in this way to decrease the birth morbidity rate due to CRS among the children. Our objective was to optimize the detection of rubella virus-antibodies by HAI, using an easier and safer method to collect samples of big populations. One hundred specimens, obtained from patients in a pediatric hospital and pregnant women in an institute of Virology were used for this work. Venous blood was drawn and collected in a test tube, and few drops were spotted onto filter paper circles. These samples were kept in envelopes and stored at room temperature until analysis. Seventy two percent of dried blood samples had titers identical to those of the corresponding serum samples, and 28% dried blood samples showed 1 dilution of difference. Storage of dried blood at room temperature for 30 days did not affect the HAI titers. Up to 60 days post attainment, 59% dried blood samples had identical titers to those of the corresponding serum samples, and 41% dried blood samples showed one dilution of difference. At 100 days of storage 51% dried blood samples had identical titers to those of the corresponding serum samples, 38% dried blood samples showed 1 dilution of difference and 11% and more than 1 dilution of difference. In conclusion, dried blood on filter paper is an easier method to transport and store blood samples for the determination of rubella virus immunity, for as long as 30 days. It could be used for large-scale epidemiological studies. The sensitivity and specificity of HAI performed on dried blood samples was 100%. Only 0.25 ml of whole blood is needed and the samples are stable at room temperature, without air or sterile conditioning. The proposed methodology is a practical approach to collect, transport and store blood samples. Moreover the blood dried on paper spots can be placed in a plastic bag and mailed to a reference laboratory. This is an appropriate alternative method for serological screenings in developing countries.


The mouse intestinal microflora with emphasis on the strict anaerobes.
The various components of the intestinal microflora in the mouse become established according to a definite time sequence; the strict anaerobes are the last groups of bacteria to reach their maximum population levels, 14-16 days after birth. The multiplication of these strict anaerobes in the mouse intestine seems to depend upon the prior multiplication of other bacterial species, and coincides with the ingestion of food other than maternal milk. These two conditioning factors may correspond to the establishment of a suitably reduced Eh potential and to the provision of certain metabolites. Once established, the strict anaerobes constitute by far the largest percentage of the total intestinal microflora; most of them are associated in a viable form with the mucosa. In normal animals they persist at very high levels throughout the life span. However, their populations can be drastically reduced by dietary manipulation of the animal, by administration of vancomycin, or by certain disease processes of the intestine. The strict anaerobic bacteria seem to play an important, and perhaps essential role in the maintenance of the anatomic structures and physiological functions of the intestine. They also seem to hold in check several species of intestinal bacteria, in particular the coliform bacilli.


[The physical capacity of Bulgarian boys from homes for children and youth].
The educational effects and living conditions' impact on the physical activity of boys with unequal social status have been investigated. Children from under school age to secondary school age, living in different towns and regions of the country have been studied. The indicators used for physical activity are 60 meters sprint, long jump, right and left hand small ball throw. A comprehensive analysis of the studied indicators is made. It has been found out that the boys from the asylums aged from 3 to 6 years living in town have significantly poorer results in the sprint events compared to the mean standards for the age.


Prevalence and predictive factors of left atrial tachycardia occurring after second-generation cryoballoon ablation of atrial fibrillation.
Assess the prevalence and predictors of left atrial tachycardia (LAT) after cryoballoon ablation of pulmonary veins. Patients who underwent catheter ablation of pulmonary veins with a second-generation cryoballoon for symptomatic paroxysmal (151 of 270, 56%) or persistent (119 of 270, 44%) atrial fibrillation were entered in a single-center prospective registry. Patients who experienced postcryoballoon LAT (pcryo-LAT) were selected on the basis of 12-lead ECG characteristics. Left atrial origin was confirmed during conventional EP study and electroanatomical activation mapping, and patients were treated by RF catheter ablation. Pcryo-LAT was observed in 15 (5.6%) of 270 patients and was attributed to a reentrant mechanism in 11 patients (73%). The other four cases of pcryo-LAT were due to focal atrial tachycardia associated with reconnection of one pulmonary vein. In comparison with patients who remained in sinus rhythm, LA area (HR = 1.09; CI 1.01, 1.2; P = 0.02), LVEF (HR = 0.94; CI 0.90, 0.97; P < 0.001), and LVEF <50% (HR = 8.5; CI 3.1, 23.6; P < 0.001) were predictors of pcryo-LAT. After multivariate Cox analysis, only left ventricular ejection fraction < 50% remained predictive of pcryo-LAT, (HR = 7.8, CI 2.3 26.7, P = 0.002). With a mean survival of 23 months, 73% of patients who experienced pcryo-LAT were in sinus rhythm versus 78% of patients without pcryo-LAT (log rank P = 0.85). The prevalence of pcryo-LAT in patients with atrial fibrillation is low. Left ventricular ejection fraction < 50% is associated with an increased risk of pcryo-LAT. When treated by RF catheter ablation, the presence of pcryo-LAT is not a predictive factor of subsequent recurrence of atrial fibrillation during follow-up.


Copper Pollution Increases the Relative Importance of Predation Risk in an Aquatic Food Web.
Although the cascading impact of predators depends critically on the relative role of lethal predation and predation risk, we lack an understanding of how human-caused stressors may shift this balance. Emergent evidence suggests that pollution may increase the importance of predator consumptive effects by weakening the effects of fear perceived by prey. However, this oversimplification ignores the possibility that pollution may also alter predator consumptive effects. In particular, contaminants may impair the consumptive effects of predators by altering density-dependent interactions among prey conspecifics. No study has directly compared predator consumptive and non-consumptive effects in polluted versus non-polluted settings. We addressed this issue by using laboratory mesocosms to examine the impact of sublethal doses of copper on tri-trophic interactions among estuarine predator crabs Cancer productus, carnivorous whelk prey Urosalpinx cinerea, and the basal resource barnacles Balanus glandula. We investigated crab consumptive effects (whelks culled without crab chemical cues), non-consumptive effects (whelks not culled with crab chemical cues), and total effects (whelks culled with crab chemical cues) on whelks in copper polluted and non-polluted waters. Realistic copper concentrations suppressed the effects of simulated crab lethal predation (whelk culling) by removing density-dependent feeding by whelks. Specifically, reductions in conspecific density occurring in elevated copper levels did not trigger the normal increase in whelk consumption rates of barnacles. Weakened effects of fear were only observed at extremely high copper levels, suggesting consumptive effects were more sensitive to pollution. Thus, pollution may shape communities by altering the roles of predators and interactions among prey.


Fast determination of anthocyanins and free pelargonidin in fruits, fruit juices, and fruit wines by high-performance liquid chromatography using a core-shell column.
Anthocyanins are water-soluble pigments that are liable for colors ranging from red to blue of most fruits, vegetables, and flowers. A novel and fast method was developed for the determination of five anthocyanins and free pelargonidin by high-performance liquid chromatography coupled to photodiode array detection. A 10% formic acid and acetonitrile mixture was employed as mobile phase in the gradient elution mode. Mobile phase composition, column temperature, flow rate, injection volume, and column conditioning time were optimized by employing a stepwise strategy. Using a C18 core-shell column (100 × 4.6 mm, 2.7 μm), the separation of six analytes was accomplished in less than 9.5 min with a run-to-run analysis time of 19 min. The developed method was validated with respect to linearity (r > 0.9999), limit of detection, limit of quantification, intra-/interday precision (<2%), accuracy (98.6-104.4%), and specificity. Afterwards, the method was applied to the determination of anthocyanins present in 15 different samples including fruits, fruit juices, and fruit wines.


Transport of ADP/ATP carrier into mitochondria. Precursor imported in vitro acquires functional properties of the mature protein.
Precursor to ADP/ATP carrier synthesized in vitro is transferred into isolated mitochondria to a protease-resistant location. This process requires an electrical potential across the inner membrane. We show now that precursor imported in a cell-free system exhibits the same resistance to protease as the mature endogenous carrier. Furthermore, transferred protein, but not receptor-associated precursor, binds carboxy-atractyloside, a specific inhibitor of the mature carrier and can be isolated by the purification procedure for the mature carrier. At least 70% of the precursor associated with mitochondria in the presence of a membrane potential acquires this functional characteristic. Finally, the binding of carboxyatractyloside can be modulated by treatment of the imported protein with sulfhydryl reagents in a manner indistinguishable from the authentic carrier protein. We conclude that import in vitro leads to correct assembly and orientation of the ADP/ATP carrier in the mitochondria.


Kinetics of solid state photodimerization of 1,4-dimethyl-2-pyridinone in its molecular compound.
The [4 + 4] photodimerization of 1,4-dimethyl-2-pyridinone (A) in its molecular compound with 1,1,6,6-tetraphenyl-2,4-hexadiyne-1,6-diol (I) was investigated by irradiation of a single crystal of the compound. The conversion to the product in a single-crystal to single-crystal transformation enabled the determination of its crystal structure after each exposure cycle of 10-20 min with a pulsed 355 nm laser light. The unit cell changes as a function of the conversion were monitored and showed monotonic changes. The kinetics of the reaction was studied at two different temperatures (230 and 280 K) and revealed a sigmoidal behavior that could be explained by the JMAK model for crystal growth with a mechanism that is intermediate between random distribution of products in the crystal and the existence of growing nuclei. The Arrhenius plot provided calculated activation energy of 32.5 kJ/mol.


The thermal index: its strengths, weaknesses, and proposed improvements.
The thermal index (TI) has been used as a relative indicator of thermal risk during diagnostic ultrasound examinations for many years. It is useful in providing feedback to the clinician or sonographer, allowing assessment of relative, potential risks to the patient of an adverse effect due to a thermal mechanism. Recently, several shortcomings of the TI formulations in quantifying the risk to the patient have been identified by members of the basic scientific community, and possible improvements to address these shortcomings have been proposed. For this reason, the Output Standards Subcommittee of the American Institute of Ultrasound in Medicine convened a subcommittee to review the strengths of the TI formulations as well as their weaknesses and proposed improvements. This article summarizes the findings of this subcommittee. After a careful review of the literature and an assessment of the cost of updating the TI formulations while maximizing the quality of patient care, the Output Standards Subcommittee makes the following recommendations: (1) some inconsistencies in the current TI formulations should be resolved, and the break point distance should be redefined to take focusing into consideration; (2) an entirely new indicator of thermal risk that incorporates the time dependence not be implemented at this time but be included in continuing efforts toward standards or consensus documents; (3) the exponential dependence of risk on temperature not be incorporated into a new definition of the TI formulations at this time but be included in continuing efforts toward standards or consensus documents; (4) the TI formulations not be altered to include nonlinear propagation at this time but be included in continuing efforts toward standards or consensus documents; and (5) a new indicator for risk from thermal mechanisms should be developed, distinct from the traditional TI formulations, for new imaging modalities such as acoustic radiation force impulse imaging, which have more complicated pulsing sequences than traditional imaging.


Emission tomography in embolic lung disease.
Ventilation-perfusion lung scans and emission tomography studies were performed in 84 patients with suspected embolic lung disease. Concordant data were obtained in 72 patients (57 positive, 15 negative); results were discordant in ten patients and indeterminate in two. Although the diagnosis of pulmonary embolism with the conventional two-dimensional planar projections of standard ventilation-perfusion lung scans is still the mainstay, a greater sensitivity in lesion detection can be expected with multiplane detection imaging.


Polydimethylsiloxane Polymerized Emulsions for Acoustic Materials Prepared Using Reactive Triblock Copolymer Surfactants.
Porous polymers have interesting acoustic properties including wave dampening and acoustic impedance matching and may be used in numerous acoustic applications, e.g., waveguiding or acoustic cloaking. These materials can be prepared by the inclusion of gas-filled voids, or pores, within an elastic polymer network; therefore, porous polymers that have controlled porosity values and a wide range of possible mechanical properties are needed, as these are key factors that impact the sound-dampening properties. Here, the synthesis of acoustic materials with varying porosities and mechanical properties that could be controlled independent of the pore morphology using emulsion-templated polymerizations is described. Polydimethylsiloxane-based ABA triblock copolymer surfactants were prepared using reversible addition-fragmentation chain transfer polymerizations to control the emulsion template and act as an additional cross-linker in the polymerization. Acoustic materials prepared with reactive surfactants possessed a storage modulus of ∼300 kPa at a total porosity of 71% compared to materials prepared using analogous nonreactive surfactants that possessed storage modulus values of ∼150 kPa at similar porosities. These materials display very low longitudinal sound speeds of ∼35 m/s at ultrasonic frequencies, making them excellent candidates in the preparation of acoustic devices such as metasurfaces or lenses.


Monitoring genome evolution ex vivo: reversible chromosomal integration of a 106 kb plasmid at two tRNA(Lys) gene loci in sequential Pseudomonas aeruginosa airway isolates.
The genome rearrangements in sequential Pseudomonas aeruginosa clone K isolates from the airways of a patient with cystic fibrosis were determined by an integrated approach of mapping, sequencing and bioinformatics. Restriction mapping uncovered an 8.9 kb deletion of PAO sequence between phnAB and oprL in clone K, and two 106 kb insertions either adjacent to this deletion or several hundred kilobases away, close to the pilA locus. These 106 kb blocks of extra DNA also co-existed as the circular plasmid pKLK106 in several clone K isolates and were found to be closely related to plasmid pKLC102 in P. aeruginosa clone C isolates. The breakpoints of the deletion in clone K and the attB-attP sequences for the reversible integration of the plasmid in clones C and K were located within the 3' end of the lysine tRNA structural genes (att site). pKLK106 sequentially recombined with either of the two tRNA(Lys) genes in clone K isolates. The att site of the pilA hypervariable region has been utilized by clone C to target its plasmid pKLC102 into the chromosome; the att site of the phnAB-oprL region has been employed by strain PAO to incorporate a DNA block encoding pyocin, transposases and IS elements. The use of typical phage attachment sites by conjugative genetic elements could be one of the major mechanisms used by P. aeruginosa to generate the mosaic genome structure of blocks of species-, clone- and strain-specific DNA. The example described here demonstrates the potential impact of systematic genome analysis of sequential isolates from the same habitat on our understanding of the evolution of microbial genomes.


Are accumulated sulfide-bound metals metabolically available in the benthic oligochaete Tubifex tubifex?
The present study evaluates the relationship between metal-binding sediment characteristics like acid volatile sulfides (AVS), metal accumulation, and internal metal distribution in the benthic oligochaete Tubifex tubifex and relates this accumulation to the induction of metallothionein-like proteins (MTLPs). In total, 15 Flemish lowland rivers were sampled. Cd, Cu, Zn, Pb, Ni, As, Cr, Co, and Ag concentrations were measured in environmental fractions (water and sediment) and worm tissue (both total and subcellular fractions). Furthermore, total cytosolic MTLP concentrations were measured in the worm tissue. Our results showed that Cd, Pb, Ni, and Cr were mainly stored as biological detoxified metal (BDM) while Cu, Zn, As, and Ag were mostly available in the metal sensitive fraction (MSF). A remarkable difference in the subcellular distribution of accumulated Cd, Ni, and Co between anoxic (SEMMe-AVS<0; mostly stored as BDM) and oxic (SEMMe-AVS>0; mostly stored in the MSF) sediments was noticed. Moreover, a rapid increase in MTLP induction was found when SEMTot-AVS>0. Our results indicate that the accumulated sulfide-bound metals were detoxified and little available to the metabolism of T. tubifex under anoxic conditions.


[Marital feedback behavior: relations between feedback activity of the partner and feedback quality, duration of the marriage and ability of the marriage to function].
The effect of the quality of feedback and the feedback activity of partners on the feedback behavior of married controls, who differed with regard to the duration and the functioning of their marriages, was investigated. 106 married couples were divided into a group of disturbed marriages in the first half of life (GJE), a group of disturbed marriages in the second half of life (GAE), and harmonious marriages (HAE). During a conflict-conversation that was structured according to the technique of revealed differences the partners exchanged positive and negative feedback optically and acoustically. Corresponding to the frequency of the feedback active and less active partners were differentiated. In comparison with the couples of the HAE group, couples of the GAE group gave less feedback, especially less positive feedback. The less active partner of the GAE group gave significantly more negative feedback than the comparable partner of the HAE group. Differences between the GAE and the GJE group that can be called statistically significant do not exist. The results have been discussed with respect to their application.


Increased stability of galactosyltransferase on immobilization.
The stability of galactosyltransferase was greatly enhanced on immobilization. The immobilized enzyme was demonstrated to be insensitive to mechanical stirring for several hours, whereas its soluble counterpart was totally inactivated in less than 60 min under the same conditions. Immobilization also conferred increased thermostability to the enzyme. The Arrhenius energy of inactivation was raised from 13 kcal/mol for the soluble enzyme to 30 kcal/mol for the immobilized protein. The gel-bound enzyme could be stored at 4 degrees C for over 10 months without apparent loss of activity.


The effects of HIV disease and older age on laboratory-based, naturalistic, and self-perceived symptoms of prospective memory: does retrieval cue type and delay interval matter?
There is a rising prevalence of older HIV+ adults who are at risk of deficits in higher order neurocognitive functions and associated problems in everyday functioning. The current study applied multiprocess theory to examine the effects of HIV and aging on measures of laboratory-based, naturalistic, and self-perceived symptoms of prospective memory (PM). Participants included 125 Younger (48 with HIV, age = 32 ± 4.6 years) and 189 Older (112 with HIV, age = 56 ± 4.9 years) adults. Controlling for global neurocognitive functioning, mood, and other demographics, older age and HIV had independent effects on long-delay time-based PM in the laboratory, whereas on a naturalistic PM task older HIV- adults performed better than older HIV+ adults and younger persons. In line with the naturalistic findings, older age, but not HIV, was associated with a relative sparing of self-perceived PM failures in daily life across longer delay self-cued intervals. Findings suggest that, even in relatively younger aging cohorts, the effects of HIV and older age on PM can vary across PM delay intervals by the strategic demands of the retrieval cue type, are expressed differently in the laboratory and in daily life, and are independent of other higher order neurocognitive functions (e.g., retrospective memory).


[Diagnostics of inflammation activity in infectious endocarditis].
This work was designed to analyse dynamics of inflammation markers (C-reactive protein, TNF-alpha) and procalcitonin in 66 patients with infectious endocarditis (IE) followed up during 6 months. Comparison of clinical observations and laboratory data revealed specific trends in these parameters in patients with different clinical course of IE and at its different stages. Some of the changes are shown to be responsible for the unfavourable prognosis of IE. TNF-alpha levels are considered to be a sensitive and informative index of the patients" clinical conditions throughout the entire period of IE evolvement.


Differential Fourier transform technique for the inverse scattering problem.
An inversion technique was developed for determining the size distribution of randomly distributed tenuous scatterers from the forward scattering pattern. This technique is applicable for 1-D, 2-D, and 3-D scatterers. It does not require matrix inversion or a priori knowledge of functional forms of the size distribution, and it takes advantage of the fast Fourier transform and digital filtering techniques in spectral analysis. A typical error for 10% noise was within a few percent in the estimation of Gaussian size distribution using 1024-point FFT. The usefulness of this technique in practice was shown in experiments with latex spheres and bacteria.


The effectiveness of personalized coronary heart disease and stroke risk communication.
Current guidelines recommend global risk assessment to guide vascular risk factor management; however, most provider-patient communication focuses on individual risk factors in isolation. We sought to evaluate the impact of personalized coronary heart disease and stroke risk communication on patients' knowledge, beliefs, and health behavior. We conducted a randomized controlled trial testing personalized risk communication based on Framingham stroke and coronary heart disease risk scores compared with a standard risk factor education. A total of 89 patients were recruited from primary care clinics and followed up for 3 months. Outcomes included the following: risk perception and worry, risk factor knowledge, risk reduction preferences and decision conflict, medication adherence, health behaviors, and blood pressure. Participants had a very low understanding of numeric information, high perceived risk for stroke or myocardial infarction, and high proportion of medication nonadherence. Patients' ability to identify vascular risk factors increased with personalized risk communication (mean 1.8 additional risk factors, 95% CI 1.3-2.2) and standard risk factor education (mean 1.6 additional risk factors, 95% CI 1.1-2.1) immediately after the intervention but was not sustained at 3 months. Patients in the personalized group had less decision conflict than the standard risk factor education group over intended risk reduction strategies (5.9 vs 10.1, P = .003). There was no appreciable impact of either communication strategy on medication adherence, exercise, smoking cessation, or blood pressure. Personalized risk communication was preferred by patients and had a small impact on risk reduction preferences and decision conflict but had no impact on patient beliefs or behavior compared with standard risk factor education.


The down-regulation of hsa_circ_0012919, the sponge for miR-125a-3p, contributes to DNA methylation of CD11a and CD70 in CD4+ T cells of systemic lupus erythematous.
Systemic lupus erythematous (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against various autoantigens. But the expression profiles and functions of circular RNAs (circRNAs) in SLE are still scarce. To explore the roles of circRNA in SLE and its potential diagnostic potential in SLE. SLE patients and healthy control subjects were recruited. CD4+ T cells were isolated, circRNA microarray analysis were used to screen for circRNA candidate in CD4+ T cells. Expression of DNMT1, CD11a and CD70, and methylation level of CD11a and CD70 were detected after transfecting hsa_circ_0012919-targetted siRNA. The network analysis of hsa_circ_0012919 was used by bioinformatics. Luciferase reporter assay and fluorescence in situ hybridization (FISH) assay were used for screening for which miRNAs could bind with hsa_circ_0012919. Twelve circRNAs were up-regulated and two circRNAs were down-regulated in SLE patients group after circRNA microarray analysis. Hsa_circ_0012919 was further confirmed to be significantly different between healthy control and SLE patients (P<0.05) and associated with SLE characters (P<0.05). Down-regulation of hsa_circ_0012919 (i) increased the expression of DNMT1 and reduced the expression of CD70, CD11a, (ii) reversed the DNA hypomethylation of CD11a and CD70 in CD4+ T cells of SLE, but it could be reversed by down-regulation of DNMT1. Hsa_circ_0012919 regulated KLF13 and RANTES by miR-125a Conclusion: Hsa_circ_0012919 could be regarded as a biomarker for SLE and hsa_circ_0012919 was the competitive endogenous RNA (ceRNA) for miR-125a-3p.


Group housing in row cages: an alternative housing system for juvenile mink.
We studied a group housing system as an alternative to the traditional pair housing of juvenile mink. The focus was on both the welfare and production of mink. The pairs were housed in standard mink cages, whereas the groups were in row cage systems consisting of three standard mink cages connected to each other. The welfare of the mink was evaluated by behavioural observations (stereotypies and social contacts), evaluation of the incidence of scars assumed to be caused by biting, and adrenal function (serum cortisol level after adrenocorticotropic hormone (ACTH) administration and adrenal mass). Feed consumption, pelt length, quality and price were used for comparing the two housing systems from the economic point of view. Although the incidence of scars showed that there might have been more aggressive behaviour among the group-housed than among the pair-housed mink, this was not observed unambiguously in behavioural observations, and, at least, aggression did not cause mortality or serious injuries to the animals as has been observed in some earlier studies. In addition, the housing system did not affect pelt size, and, although the quality of the pelts was slightly lower in the group than in pair-housed mink, there was only a tendency for lower pelt prices. The lower pelt prices in the group-housed mink might even be partially compensated for by the group-housed mink eating 10% to 20% less in the late autumn, due to thermoregulatory benefits, than their pair-housed conspecifics. The results on the frequency of stereotypic behaviour (but not adrenal function) suggest that the group-housed animals were possibly less stressed than the pair-housed animals. Group housing of juvenile farmed mink in a row cage system cannot be recommended before the effects on welfare and production are clarified in further studies.


Very low versus undetectable maternal serum alpha-fetoprotein values and fetal death.
Very low maternal serum alpha-fetoprotein (MSAFP) levels (less than 10 ng/mL) are known to be associated with non-viable pregnancies, including conditions such as fetal death, molar pregnancies, and non-pregnancies. There has not been agreement, however, as to whether very low MSAFP levels indicate already existing fetal deaths or are actually predictive. We analysed 230 pregnancies with MSAFP levels less than 10 ng/mL from among 15,807 women (1.5 per cent) screened consecutively during a three-year period and identified 26 non-viable pregnancies, 22 of which were diagnosed sonographically as part of the screening process (17 missed abortions, 3 blighted ova, 2 non-pregnancies). Furthermore, 20 of these 22 pregnancies were associated with essentially undetectable MSAFP levels (less than 5 ng/mL). Our data indicate that pregnancies with MSAFP values less than 5 ng/mL are the group most strongly associated with fetal non-viability and that very low MSAFP values are not strongly predictive for fetal death.


Cerebellar hemangioblastoma associated with diffuse neonatal hemangiomatosis in an infant.
Hemangioblastomas (HBLs) comprise approximately 2% of all primary central nervous system (CNS) tumors. Although histological features of this rare tumor are generally benign, its outcome is often unfavorable due to high risk of recurrence and multifocal localization. HBLs can be detected as sporadic or associated with Von Hippel-Lindau disease. Diffuse neonatal hemangiomatosis (DNH) presents with multiple, progressive, rapidly growing cutaneous hemangiomas associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges. DNH with predominant CNS involvement is rarely reported. Herein, we present a neonatal case of cerebellar HBL associated with DNH. A 5-day-old male baby was referred with complaints of multiple cutaneous lesions. Purple papules were noted on the trunk, extremities, and the head. Thoracic magnetic resonance imaging demonstrated multiple hyperintense lesions on the chest wall and apex of the right lung. On MRI, a 3×2-cm mass lesion in the right cerebellar hemisphere was detected. Total resection of the mass and ventriculoperitoneal shunting was performed. Histopathologic examination confirmed the diagnosis of HBL. Steroid therapy was administered for disseminated hemangiomatosis, and the lesions showed regression; the patient showed good clinical recovery. The parents refused further treatment, and he was out of our control when he was 9 months old. According to our knowledge, the presented newborn is the second case of cerebellar HBL associated with diffuse skin and visceral hemangiomas in the English medical literature. Clinicians must be vigilant about the predictive value of visceral and/or cutaneous hemangioma for an associated intracranial HBL.


Genetic mapping of mutation in Escherichia coli leading to a temperature-sensitive RNase D.
In order to determine the metabolic role of RNase D in Escherichia coli, we have attempted to isolate strains deficient in this enzyme. One strain containing a temperature-sensitive RNase D was found among a heavily mutagenized stock of strain temperature-sensitive for growth. Genetic mapping of the mutation responsible for the altered RNAse D enabled us to define the rnd locus, at 39.5-40.0 min on the E. coli map, which apparently specifies the RNase D structural gene. Using a Tn10 insertion near the rnd locus, we constructed isogenic strains containing RNase D and Rnase II mutations, alone or in combination. Although the original mutant isolate displayed temperature-sensitive growth. no growth phenotype was associated with the rnd mutation in wild type background, possibly because a substantial amount of RNase D remained in cells grown at 45 degrees C. However, elucidation of the map position of the rnd locus should prove useful for the isolation of other mutant strains with lower levels of RNase D.


Does funded research reflect the priorities of people living with type 1 diabetes? A secondary analysis of research questions.
This study explored the divergence and convergence between funded research about type 1 diabetes and the research agenda of people living with the condition and their carers. A secondary analysis was undertaken of existing data from two UK organisations who regularly work with patients and carers to identify research priorities. The research ideas of people with diabetes were identified in two ways: in 15 research question generation workshops involving approximately 100 patients and carers, and in a James Lind Alliance Type 1 Diabetes Priority Setting Partnership with approximately 580 patients, carers and clinicians (clinician question submissions were excluded from analysis). A total of 859 individual research questions were collected from patients and carers. Diabetes research funding activity was identified through extensive online searches which provided a total of 172 relevant research projects for analysis. The data were thematically analysed and areas of priority for research identified and compared between the patient and funded research agendas. The overall finding of this study is that there is substantial convergence between the two research agendas, alongside some important areas of divergence. The key areas of divergence were found in care delivery, injection issues, psychosocial impacts and women's health. We also demonstrate how an apparently convergent priority can host significant differences in emphasis between patient-generated and funded research agendas. We offer a comparison of a funded research agenda with one that has been derived directly from people with type 1 diabetes without initial framing by researchers. This provided a rare opportunity to explore the viewpoints of the end-users of research and compare them to realised research as determined by researchers and research organisations.


Renal function and renal afferent and efferent nerve activity.
Recent microperfusion studies have fully substantiated the direct action of catecholamines on renal tubular reabsorptive rates. Surprisingly, these techniques have not provided consistent information on the nature of the adrenoceptor responsible for the stimulation of proximal tubular reabsorption. Both alpha- and beta-receptors have been favored for this role. These techniques have confirmed earlier reports that dopamine may have a direct natriuretic action on the renal tubules. The demonstration that renal efferent nerves contain both noradrenergic and dopaminergic fibers lends further support for the participation of dopamine in the regulation of salt and water excretion. Efferent renal nerve activity is modulated by a number of different afferent inputs to the central nervous system. One of these is the renal afferent innervation, which is composed of both chemoreceptor and mechanoreceptor fibers. A number of different reflexes that affect efferent renal nerve activity have been identified by electrical stimulation of renal afferent nerves or by selective stimulation of renal mechanoreceptors and chemoreceptors. These renorenal reflexes may have importance in the coordination of excretory activity between the two kidneys. Studies of these aspects of renal nerve function are reviewed. The importance of the renal nerves in conscious animals is also discussed in the light of evidence that their influence on renal function may be more apparent in abnormal or pathological circumstances.


Classification of three airborne bacteria and proposal of Hymenobacter aerophilus sp. nov.
Three aerobic, gram-negative, rod-shaped, non-spore-forming, red-pigmented, airborne bacteria (I/26-Cor1T, I/32A-Cor1 and I/74-Cor2) collected in the Museo Correr (Venice, Italy) were investigated to determine their taxonomic status by analysing their biochemical, physiological and chemotaxonomic features and the G+C content of genomic DNA and by comparing their genomic fingerprints. Additionally, the almost complete 16S rRNA gene sequence of strain I/26-Cor1T was analysed. The three strains were nearly identical in their morphological, physiological, biochemical and chemotaxonomic properties. The strains contained a menaquinone system with the predominant menaquinone MK-7 and a fatty acid profile with C15:0 anteiso, C15:0 iso and C16:1 predominant. Phosphatidylethanolamine and several unidentified lipids were detected in the polar lipid profiles. The polyamine pattern consisted of sym-homospermidine as the major compound. meso-Diaminopimelic acid was found as the characteristic cell-wall diamino acid. The DNA base composition of the three strains ranged from 60 to 63 mol% G+C. Phylogenetically, strain I/26-Cor1T was most closely related to Hymenobacter actinosclerus (95.8% 16S rRNA gene sequence similarity). Physiological and genomic characteristics indicated that the two strains I/26-Cor1T and I/32A-Cor1 are representatives of the same species. The phylogenetic distance to any validly described taxon as indicated by 16S rRNA gene sequence similarities demonstrates that I/26-Cor1T and I/32A-Cor1 represent a novel species, for which the name Hymenobacter aerophilus sp. nov. is proposed, with the type strain I/26-Cor1T (= DSM 13606T = LMG 19657T). I/32A-Cor1 (= DSM 13607 = LMG 19658) is another strain of the species Hymenobacter aerophilus. Since the taxonomic status of strain I/74-Cor2 within the genus Hymenobacter was not determined unambiguously, it is designated Hymenobacter sp. I/74-Cor2 (= DSM 13611 = LMG 19659).


Druggable Transcriptional Networks in the Human Neurogenic Epigenome.
Chromosome conformation capture methods have revealed the dynamics of genome architecture which is spatially organized into topologically associated domains, with gene regulation mediated by enhancer-promoter pairs in chromatin space. New evidence shows that endogenous hormones and several xenobiotics act within circumscribed topological domains of the spatial genome, impacting subsets of the chromatin contacts of enhancer-gene promoter pairs in cis and trans Results from the National Institutes of Health-funded PsychENCODE project and the study of chromatin remodeling complexes have converged to provide a clearer understanding of the organization of the neurogenic epigenome in humans. Neuropsychiatric diseases, including schizophrenia, bipolar spectrum disorder, autism spectrum disorder, attention deficit hyperactivity disorder, and other neuropsychiatric disorders are significantly associated with mutations in neurogenic transcriptional networks. In this review, we have reanalyzed the results from publications of the PsychENCODE Consortium using pharmacoinformatics network analysis to better understand druggable targets that control neurogenic transcriptional networks. We found that valproic acid and other psychotropic drugs directly alter these networks, including chromatin remodeling complexes, transcription factors, and other epigenetic modifiers. We envision a new generation of CNS therapeutics targeted at neurogenic transcriptional control networks, including druggable parts of chromatin remodeling complexes and master transcription factor-controlled pharmacogenomic networks. This may provide a route to the modification of interconnected gene pathways impacted by disease in patients with neuropsychiatric and neurodegenerative disorders. Direct and indirect therapeutic strategies to modify the master regulators of neurogenic transcriptional control networks may ultimately help extend the life span of CNS neurons impacted by disease.


[Biosynthesis and secretion of insulin under the effect of an antibiotic of the tetracycline group].
Formation and secretion of insulin during administration of tetracycline hydrochloride in vivo and in vitro were studied in experimental rat Langerhans islets isolated by enzymatic digestion with collagenase. Insulin secretion was determined by radioimmunoassay, insulin biosynthesis was assessed from 3H-leucin incorporation into the de novo formed proteins of the islets with insulin immunoreactivity (proinsulin plus insulin). Injection of the antibiotic in a dose of 25 mg/kg intraperitoneally for 10 days did not change the functional activity of beta-cells--the rate of insulin formation and secretion at low and high glucose concentrations in the incubation medium. Higher doses of the antibiotic applied in vivo (100 mg/kg intraperitoneally for 10 days) and in vitro (100 mumol, 2-hour incubation) inhibited the glucose-stimulated (15 mmol) insulin secretion but exerted no effect on insulin biosynthesis. The possible importance of ionophore properties of the antibiotic, that changes the concentration of intracellular Ca2+ in the mechanism of dissociated action of tetracycline hydrochloride on insulin formation and secretion, as well as the practical significance of the data obtained are discussed.


Low-level laser therapy in the prevention and treatment of cancer therapy-induced mucositis: 2012 state of the art based on literature review and meta-analysis.
To discuss the promising state of the art low-level laser therapy (LLLT) for preventive and therapeutic usage in oral mucositis due to cancer therapy. Photomedicine using LLLT is very effective with intraoral and extraoral devices in the management of oral mucositis, based on several studies including randomized control studies. A systematic review identified 33 relevant articles that were subjected to meta-analysis based on which laser parameters in routine practice are being defined. Meta-analysis showed that LLLT reduced risk of oral mucositis with relative risk (RR) 2.45 [confidence interval (CI) 1.85-3.18], reduced duration, severity of oral mucositis and reduced number of days with oral mucositis (4.38 days, P = 0.0009). RR was similar between the red (630-670 nm) and infrared (780-830 nm) LLLT. Pain-relieving effect based on the Cohen scale was at 1.22 (CI 0.19-2.25). No adverse side effects of LLLT were reported; hence, we recommend red or infrared LLLT with diode output between 10-100 mW, dose of 2-3 J/cm2/cm2 for prophylaxis and 4 J/cm2 (maximum limit) for therapeutic effect, application on single spot rather than scanning motion. Lesions must be evaluated by a trained clinician and therapy should be repeated daily or every other day or a minimum of three times per week until resolution. There is moderate-to-strong evidence in favor of LLLT at optimal doses as a well tolerated, relatively inexpensive intervention for cancer therapy-induced oral mucositis. It is envisaged that LLLT will soon become part of routine oral supportive care in cancer.


Steric control of dioxygen activation pathways for MnII complexes supported by pentadentate, amide-containing ligands.
Dioxygen activation at manganese centers is well known in nature, but synthetic manganese systems capable of utilizing O2 as an oxidant are relatively uncommon. These present investigations probe the dioxygen activation pathways of two mononuclear MnII complexes supported by pentacoordinate amide-containing ligands, [MnII(dpaq)](OTf) and the sterically modified [MnII(dpaq2Me)](OTf). Dioxygen titration experiments demonstrate that [MnII(dpaq)](OTf) reacts with O2 to form [MnIII(OH)(dpaq)](OTf) according to a 4 : 1 Mn : O2 stoichiometry. This stoichiometry is consistent with a pathway involving comproportionation between a MnIV-oxo species and residual MnII complex to form a (μ-oxo)dimanganese(iii,iii) species that is hydrolyzed by water to give the MnIII-hydroxo product. In contrast, the sterically modified [MnII(dpaq2Me)](OTf) complex was found to react with O2 according to a 2 : 1 Mn : O2 stoichiometry. This stoichiometry is indicative of a pathway in which a MnIV-oxo intermediate abstracts a hydrogen atom from solvent instead of undergoing comproportionation with the MnII starting complex. Isotopic labeling experiments, in which the oxygenation of the MnII complexes was carried out in deuterated solvent, supported this change in pathway. The oxygenation of [MnII(dpaq)](OTf) did not result in any deuterium incorporation in the MnIII-hydroxo product, while the oxygenation of [MnII(dpaq2Me)](OTf) in d3-MeCN showed [MnIII(OD)(dpaq2Me)]+ formation. Taken together, these observations highlight the use of steric effects as a means to select which intermediates form along dioxygen activation pathways.


Prevalence of Musculoskeletal Diseases of the Upper Extremity Among Dental Professionals in Germany.
Although many findings on occupational musculoskeletal complaints are available from American and European dentists, the corresponding data from Germany are still scarce. Therefore, the aim of this study was to provide additional information on the prevalence of and risk factors for musculoskeletal disorders of the upper extremity, particularly the shoulder in this specific population. A written survey was carried out among 600 dentists in the state of North Rhine-Westphalia, Germany. Questionnaire items included physical and psychosocial workload, general health, and the occurrence of musculoskeletal symptoms during the previous 12 months that led to sick leave and medical care according to a modified version of the Nordic Musculoskeletal Questionnaire (NMQ). Regression analysis was used to evaluate relevant risk factors for severe musculoskeletal disorders. A total of 229 dentists were participated in the study (response rate 38%). Overall, 92.6% of the participants had already suffered from musculoskeletal symptoms in at least one body region. Symptoms were mostly reported in the neck (65.1%) and in the shoulder (58.1%). Limitations in daily activities were experienced by 15.9% due to neck pain and by 15.4% due to shoulder pain. Medical care was sought by 23.7% because of neck pain and by 21.1% due to shoulder pain. Risk factors for symptoms in the upper extremity regions were gender (female), increased physical load, and numerous comorbidities. There is a high prevalence of musculoskeletal disorders among dentists. Suitable interventions are therefore needed to prevent musculoskeletal diseases and pain among dental professionals, with particular attention to female dentists.


Dual field effects in electrolyte-gated spinel ferrite: electrostatic carrier doping and redox reactions.
Controlling the electronic properties of functional oxide materials via external electric fields has attracted increasing attention as a key technology for next-generation electronics. For transition-metal oxides with metallic carrier densities, the electric-field effect with ionic liquid electrolytes has been widely used because of the enormous carrier doping capabilities. The gate-induced redox reactions revealed by recent investigations have, however, highlighted the complex nature of the electric-field effect. Here, we use the gate-induced conductance modulation of spinel ZnxFe₃₋xO₄ to demonstrate the dual contributions of volatile and non-volatile field effects arising from electronic carrier doping and redox reactions. These two contributions are found to change in opposite senses depending on the Zn content x; virtual electronic and chemical field effects are observed at appropriate Zn compositions. The tuning of field-effect characteristics via composition engineering should be extremely useful for fabricating high-performance oxide field-effect devices.