Identification of a novel kinase-like gene induced during neuronal cell death.
When deprived of neurotrophic factors, neuronal cells undergo a form of programmed cell death that involves a cascade of gene expression. To better understand this cascade, we screened the genes induced during programmed cell death evoked in neuronal PC6-3 cells by NGF-depletion and discovered a novel gene, NIPK (Neuronal cell death Inducible Putative Kinase), that contains a kinase-like domain. Expression of NIPK was also induced in cultured sympathetic neurons by NGF deprivation and in cortical neurons exposed to the Ca2+ ionophore, A23187. In contrast, NIPK was not induced during non-neuronal cell death evoked by serum or growth factor deprivation, or by treatment with methyl methanesulfonate, an agent that causes cell death by damaging DNA. Taken together, these findings suggest that NIPK is involved in programmed cell death via a pathway that is present in neurons but is absent in non-neurons.


Seminal plasma zinc level may be associated with the effect of cigarette smoking on sperm parameters.
The aim of this study was to investigate the effect of cigarette smoking on seminal plasma zinc levels and sperm parameters, and to examine the role of seminal plasma zinc. Semen samples from 79 non-smokers and 68 smokers were obtained. There was a significant decrease in seminal plasma zinc in smokers and a clear correlation between seminal plasma zinc levels and the extent of smoking. Sperm parameters (concentration, motility and morphology) among smokers were significantly lower in comparison to non-smokers. These parameters were also significantly decreased among smokers with abnormal zinc levels, while there was no significant difference between non-smokers with normal zinc and non-smokers with abnormal zinc levels. As previous studies have shown that seminal plasma zinc is associated with a decrease of anti-oxidant defences, seminal plasma zinc could be a contributor to the effects of cigarette smoking on sperm parameters. In conclusion, cigarette smoking can affect sperm parameters and this study may help towards providing a mechanistic explanation.


RAB-6.2 and the retromer regulate glutamate receptor recycling through a retrograde pathway.
Regulated membrane trafficking of AMPA-type glutamate receptors (AMPARs) is a key mechanism underlying synaptic plasticity, yet the pathways used by AMPARs are not well understood. In this paper, we show that the AMPAR subunit GLR-1 in Caenorhabditis elegans utilizes the retrograde transport pathway to regulate AMPAR synaptic abundance. Mutants for rab-6.2, the retromer genes vps-35 and snx-1, and rme-8 failed to recycle GLR-1 receptors, resulting in GLR-1 turnover and behavioral defects indicative of diminished GLR-1 function. In contrast, expression of constitutively active RAB-6.2 drove the retrograde transport of GLR-1 from dendrites back to cell body Golgi. We also find that activated RAB-6.2 bound to and colocalized with the PDZ/phosphotyrosine binding domain protein LIN-10. RAB-6.2 recruited LIN-10. Moreover, the regulation of GLR-1 transport by RAB-6.2 required LIN-10 activity. Our results demonstrate a novel role for RAB-6.2, its effector LIN-10, and the retromer complex in maintaining synaptic strength by recycling AMPARs along the retrograde transport pathway.


Analysis of spirometry results in hospitalized patients aged over 65 years.
The growing population of the elderly, as well as the occurrence of coexisting diseases and polypharmacy, is the reason why diseases of patients aged $65 years belong to the major issues of the contemporary medicine. Among the most frequent diseases of the elderly, there are respiratory system diseases. They are difficult to diagnose because of the patient group specificity, which is the reason for increased mortality among seniors, caused by underdiagnosis. The study objective was to assess the factors influencing spirometry results in hospitalized patients aged ≥65 years with respiratory system disorders. In the research, 217 (100%) patients aged ≥65 years who underwent spirometry at the Regional Medical Center of the Jelenia Góra Valley Hospital in Poland were analyzed. In the statistical analysis, the STATISTICA 9.1 program, the t-test, the Shapiro-Wilk test, the ANOVA test, and the Scheffé's test were applied. The majority of the patients (59.4%) were treated in the hospital. The most frequent diagnosis was malignant neoplasm (18%). The study showed a statistically significant dependence between the forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC parameters and the time of hospitalization, as well as between the FVC and FEV1 parameters and the age of patients. The FVC parameter values turned out to be dependent on the main diagnosis. Highest results were noted in patients with the diagnosis of sleep apnea or benign neoplasm. A low FVC index can reflect restrictive ventilation defects, which was supported by the performed analyses. Highest FEV1/FVC values were observed in nonsmokers, which confirms the influence of nicotine addiction on the incidence of respiratory system diseases. The respondents' sex and the established diagnosis statistically significantly influenced the FVC index result, and the diet influenced the FEV1/FVC parameter result.


A method for making estimates of the benefit of the late use of letrozole in patients completing 5 years of tamoxifen.
This article discusses the rationale for 2 methods of making estimates of the benefit of letrozole as extended adjuvant hormonal therapy after 5 years of tamoxifen. It uses information from the Overview metaanalyses to develop general rules for making estimates of remaining risk of relapse for women completing 5 years of adjuvant tamoxifen without relapse. The first derived method shows that the expected benefit for such a woman is approximately one tenth of her risk of relapse in years 0-10 if untreated. The second method uses a modification of Adjuvant!, a decision support tool, and makes similar estimates. The decision tool supplies needed estimates of initial risk and allows adjustment for competing mortality. Uncertainties involved in making these estimates are also discussed.


Skeletal Muscle for Endomyocardial Biopsy: Comparable Stress Response in Doxorubicin Cardio-myopathy.
In the present study, we compared the cell damage response in skeletal and cardiac muscle tissue when exposed to doxorubicin. This was carried out by means of a less invasive informative substitute to endomyocardiac biopsy based on Hsp70 immunodetection and a subcellular analysis of the nucleolus. Male Sprague Dawley rats (62 g body weight) were randomly distributed into 3 group, the control and doxorubicin I and doxorubicin II groups, in which 15 and 25 mg/kg body weight of doxorubicin (0.1 ml, i.v.) was administered, respectively. After 15, 30, 45 and 60 minutes, portions of the left and right ventricle wall and interventricle wall, together with skeletal muscle from the posterior and anterior member, were prepared for Hsp70 immunodetection by Western blot analysis and ultrastructural study using the thin cut technique. Differential cell response between the control and treated groups was observed in Hsp70 immunodetection and at the subcellular level. In the control group, the Hsp70 recognition levels and typical normal nucleolar morphology were similar, while the treated groups showed variable-dependent Hsp70 recognition and segregation of nucleolar components, forming ring-like figures of a variable-independent nature. Comparison of cardiac and skeletal muscle tissue cell response to doxorubicin toxic aggression revealed parallelism in terms of Hsp70 accumulation in certain regions of both tissues (15 mg/kg body weight of doxorubicin), which suggests that replacing endomyocardiac biopsy analysis with skeletal muscle analysis may be a safe option.


Slow Waves Promote Sleep-Dependent Plasticity and Functional Recovery after Stroke.
Functional recovery after stroke is associated with a remapping of neural circuits. This reorganization is often associated with low-frequency, high-amplitude oscillations in the peri-infarct zone in both rodents and humans. These oscillations are reminiscent of sleep slow waves (SW) and suggestive of a role for sleep in brain plasticity that occur during stroke recovery; however, direct evidence is missing. Using a stroke model in male mice, we showed that stroke was followed by a transient increase in NREM sleep accompanied by reduced amplitude and slope of ipsilateral NREM sleep SW. We next used 5 ms optical activation of Channelrhodopsin 2-expressing pyramidal neurons, or 200 ms silencing of Archeorhodopsin T-expressing pyramidal neurons, to generate local cortical UP, or DOWN, states, respectively, both sharing similarities with spontaneous NREM SW in freely moving mice. Importantly, we found that single optogenetically evoked SW (SWopto) in the peri-infarct zone, randomly distributed during sleep, significantly improved fine motor movements of the limb corresponding to the sensorimotor stroke lesion site compared with spontaneous recovery and control conditions, while motor strength remained unchanged. In contrast, SWopto during wakefulness had no effect. Furthermore, chronic SWopto during sleep were associated with local axonal sprouting as revealed by the increase of anatomic presynaptic and postsynaptic markers in the peri-infarct zone and corresponding contralesional areas to cortical circuit reorganization during stroke recovery. These results support a role for sleep SW in cortical circuit plasticity and sensorimotor recovery after stroke and provide a clinically relevant framework for rehabilitation strategies using neuromodulation during sleep.SIGNIFICANCE STATEMENT Brain stroke is one of the leading causes of death and major disabilities in the elderly worldwide. A better understanding of the pathophysiological mechanisms underlying spontaneous brain plasticity after stroke, together with an optimization of rehabilitative strategies, are essential to improve stroke treatments. Here, we investigate the role of optogenetically induced sleep slow waves in an animal model of ischemic stroke and identify sleep as a window for poststroke intervention that promotes neuroplasticity and facilitates sensorimotor recovery.


Breakthrough curves and column design parameters for sorption of lead ions by natural zeolite.
Sorption of lead ions, by natural phillipsite (zeolite) has been studied in a laboratory-scale packed-bed column. Breakthrough curves were obtained under different operating conditions. Bed depth- service time (BDST) model was applied and parameters for column design were determined for lead ions at 5% breakthrough yielding BDST sorption capacity of 24.27-35.73 mg x g(-1), rate constant 2.80 x 10(-4) - 4.16 x 10(-4) dm3 x mg(-1) x min(-1), critical bed depth 4.02-10.37 cm and sorbent exhaustion rate of 12-51.3 g zeolite per dm3 of treated solution over a flow-rate range of 14.15-36.80 cm x min(-1). Breakthrough times at C/Co = 0.05 ranged from 5-100 min depending on flow rate and bed depth. External mass transfer is rate limiting in the initial stages of adsorption as indicated by agreement between Wolborska model and the experimental data in the low C/Co region of the breakthrough curve.


Clonidine distribution in the rat: temporal relationship between tissue levels and blood pressure response.
1. The time course of the distribution of clonidine (20 microgram/kg, i.v.) was determined in the rat by use of a sensitive and specific radioimmunoassay, and was compared with the hypotensive response following this dose. 2. Levels of clonidine were determined in tissues at 2 min, corresponding to the beginning of the hypotensive phase of the drug, and then at 10, 30 and 120 min during recovery of blood pressure to the pre-dose level. The peak tissue concentrations of clonidine were found at 2 min, after which they declined in a mono-exponential manner. The half-lives of clonidine in the various tissues were similar to the half-life of the recovery of blood pressure. 3. Regional variations in clonidine distribution in the brain were not very great; however, the half-life was longer in the corpus striatum and shorter in the cerebellum than in other brain regions. 4. Clonidine concentrations were highest in the kidney and similarly distributed between the cortex and medulla. Concentrations of the drug in other tissues approximated those in brain. 5. Although clonidine is thought to act primarily through the central nervous system, this distribution study shows that at the peak of the hypotensive response less than 2% of the injected dose is present in brain and at least equal concentrations of the drug are found in most peripheral tissues. Thus the possibility of peripheral mechanisms contributing to the hypotensive effect cannot be dismissed.


Evidence that microRNAs are part of the molecular toolkit regulating adult reproductive diapause in the mosquito, Culex pipiens.
For many insects, diapause is the primary mechanism for surviving unfavorable seasons. Some aspects of diapause regulation are well known, but we still lack a mechanistic understanding of molecular mechanisms that control the diapause pathway. Accumulating evidence suggests microRNAs regulate diapause in evolutionarily diverse insect species including flesh flies and moths, and, it is likely that microRNAs regulate multiple characteristics of diapause, including arrested egg follicle development and fat hypertrophy, in females of the Northern house mosquito, Culex pipiens. To investigate microRNA regulation of diapause in this species, we measured changes in egg follicle development and total lipid content over 22 days following adult emergence. We also evaluated changes in the abundance of candidate microRNAs associated with these physical changes during the same time frame. We found egg follicle size and lipid content were nearly the same in diapausing and nondiapausing females on the day of adult emergence, and then diverged over time such that by day 22 diapausing females had significantly smaller egg follicles and higher total lipids than their nondiapausing counterparts. Several microRNAs associated with lipid metabolism in insects, including miR-14-3p, miR-277-3p, and miR-305-5p, were underexpressed in diapausing females compared to nondiapausing females on the day of adult emergence, which suggests microRNA regulation occurs ahead of observed changes in these two features of the diapause phenotype. We also found miR-309-3p, miR-375-3p which stimulate ovarian development in other mosquito species, were underexpressed in diapausing females of Cx. pipiens at times after diapause is fully established and may be responsible for the arrest in ovarian development in this species. Taken together, our results demonstrate that changes in the abundance of some microRNAs is associated with phenotypic changes in diapause Cx. pipiens and suggests this epigenetic mechanism is part of the molecular toolkit regulating diapause.


A review on bio-cooperative control in gait rehabilitation.
While gait rehabilitation robots have become increasingly common to automate treadmill training, their efficacy is still controversial. Current robots lack the ability to react compliantly to the user's voluntary effort and cognitive intention. Bio-cooperative control concepts allow integrating the patient into the control loop as part of the plant rather than seeing him as a source of disturbance. Closed loop control is thereby performed on a physiological and psychological level. In this paper, we review the concept of bio-cooperative control implemented with neurological patients during robot-assisted gait rehabilitation. We highlight its clinical importance and review our work on control strategies that allow bio-cooperative control. We finish by discussing the future potential of bio-cooperative control in rehabilitation robotics.


Design and Modeling of Bioreactor Utilizing Electrophoresis and Di-Electrophoresis Techniques for Regenerating Reabsorption Function of Human Kidney PCT in Microfluidics Environment.
The need for innovation in medical device technology is immense; especially to replace dialysis techniques the necessity is extremely high. Available techniques that promised to replace dialysis have not yet geared up to the marketization level. The utilization of live kidney cells makes these devices costly, delicate, and unreliable. This paper aims to design a bioreactor to mimic the reabsorption function of the kidney that is fully artificial and highly controllable, which can be one step forward to the emerging Kidney-on-Chip (KOC) technology. The additional benefit of the proposed design is that it utilizes size-dependent reabsorption along with charge-dependent reabsorption phenomena to make it more compatible with human kidney function. The electrophoresis (EP), and di-electrophoresis (DEP) techniques are utilized to mimic the reabsorption function in this report. The structure utilized in the present design exactly replicates the proximal convoluted tubule (PCT) dimensions and functions as well. The whole setup is implemented in the COMSOL Multiphysics FEM benchmark tool for simulation, and analysis with appropriate boundary conditions. The device when excited by an electric field, Electrophoresis has produced a maximum velocity of 1.07 m/s for DC excitation and di-electrophoresis has produced a maximum flow velocity of 1.23 m/s, where both the offset voltages are the same (0.7 V). The flow velocity obtained utilizing both EP and DEP produced a reabsorption rate of 50-58% depending on the voltage applied and dimensions considered which is close to 60% reabsorption rate of the normal human kidney PCT. In accordance with the outcomes produced, the di-electrophoresis technique proved to be more efficient in realizing bioreactor as compared to electrophoresis. The novelty of the present work lies in the creation of a simulation environment, rigorous analysis, and optimization of the bioreactor supported by compact mathematical model.


Community violence and childhood asthma prevalence in peripheral neighborhoods in Salvador, Bahia State, Brazil.
This study aimed to identify degrees of exposure to community violence reported by parents and guardians of children from four to 12 years of age and the association with childhood asthma symptoms. A cross-sectional study was conducted with 1,232 parents/guardians in 24 peripheral neighborhoods in Salvador, the capital of Bahia State, Brazil. The authors investigated asthma symptoms in children and acts of violence in the community. More than 75% of parents/guardians had been exposed to community violence in the previous year, with 20% reporting high levels of exposure. Children that were more exposed to violence showed higher asthma prevalence (28.4%) as compared to non-exposed children (16.4%). Children exposed to maximum levels of violence were nearly twice as likely to present asthma symptoms (adjusted OR = 1.94; 95%CI: 1.12-3.36). The study highlighted the relevance of community violence as a risk factor for asthma and the need for further research to elucidate methodological issues.


[Microbiological quality of indoor air in dentist's offices].
It's a well-known fact that water-air aerosol can be a result of some dentist's activity during regular dental surgery and can contain broad range of microorganisms from dental plaque, saliva and pus. Assessment of dentist's activity impact on bacteria concentration in air of dentist surgery was a main purpose of this assay. Presented data contains results of four total number of bacteria and fungi in air assays made with fifty minutes intervals. Air samples was taken in dentist's office during regular dental surgery of patients afflicted with oral cavity infection with pus. Due to defective ventilation system, bacteria's concentration in air samples increased from less than thousand cfu/m3 to almost three thousands cfu/m3. Obtained results demonstrated that aerosol containing bacteria is released during regular dental surgery so the concentration of potentially infectious bacteria around patient and dentist can increase up to three thousands cfu/m3.


Increased cavernosal relaxation by Phoneutria nigriventer toxin, PnTx2-6, via activation at NO/cGMP signaling.
Erectile dysfunction (ED) mechanisms in diabetic patients are multifactorial and often lead to resistance to current therapy. Animal toxins have been used as pharmacological tools to study penile erection. Human accidents involving the venom of Phoneutria nigriventer spider are characterized by priapism. We hypothesize that PnTx2-6 potentiates cavernosal relaxation in diabetic mice by increasing cyclic guanosine monophosphate (cGMP). This effect is neuronal nitric oxide synthase (nNOS) dependent. Cavernosal strips were contracted with phenylephrine (10(-5) M) and relaxed by electrical field stimulation (20 V, 1-32 Hz) in the presence or absence of PnTx2-6 (10(-8) M). Cavernosal strips from nNOS- and endothelial nitric oxide synthase (eNOS)-knockout (KO) mice, besides nNOS inhibitor (10(-5) M), were used to evaluate the role of this enzyme in the potentiation effect evoked by PnTx2-6. Tissue cGMP levels were determined after stimulation with PnTx2-6 in presence or absence of N-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) and ω-conotoxin GVIA (10(-6) M), an N-type calcium channel inhibitor. Results showed that PnTx2-6 enhanced cavernosal relaxation in diabetic mice (65%) and eNOS KO mice, but not in nNOS KO mice. The toxin effect in the cavernosal relaxation was abolished by nNOS inhibitor. cGMP levels are increased by PnTx2-6, however, L-NAME abolished this enhancement as well as ω-conotoxin GVIA. We conclude that PnTx2-6 facilitates penile relaxation in diabetic mice through a mechanism dependent on nNOS, probably via increasing nitric oxide/cGMP production.


Breaking the myths: new treatment approaches for chronic depression.
Chronic depressive disorders are common, accounting for approximately one-third of all cases of depression and posing a major public health problem. In the past, chronic depression has been thought to be treatment-resistant, and evidence suggests that it is currently underdiagnosed, misdiagnosed, and suboptimally treated. To review the subtypes of chronic depression and the evidence-base concerning their optimal treatment and to discuss some key clinical issues and areas of future research. We identified key studies and randomized controlled trials (RCTs) by systematically searching electronic databases and hand searching specialist journals and bibliographies. Chronic depressive disorders respond well to standard pharmacologic interventions in the acute and maintenance phases of treatment. Standard psychotherapies alone may not be efficacious for chronic depression (especially dysthymia). Recent evidence suggests that treatment combining psychotherapy and medications may be superior to either treatment alone. Chronic depressive disorders are amenable to treatment, provided that intervention is both thorough and intensive. Although our knowledge about the optimal treatment of chronic depression has developed rapidly, changes in clinical practice have been slower to evolve. Further research is required to assess the effectiveness of multimodal interventions for chronic depression in more naturalistic settings.


Biological properties of olive oil phytochemicals.
Olive oil is the principal source of fat in the Mediterranean diet, which has been associated with a lower incidence of coronary heart disease and certain cancers. Extra-virgin olive oil contains a considerable amount of phenolic compounds, for example, hydroxytyrosol and oleuropein, that are responsible for its peculiar taste and for its high stability. Evidence is accumulating to demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and in vivo; also, they exert other potent biological activities that could partially account for the observed healthful effects of the Mediterranean diet.


Functional and intracellular localization properties of U6 promoter-expressed siRNAs, shRNAs, and chimeric VA1 shRNAs in mammalian cells.
RNA polymerase III (Pol III) expression systems for short hairpin RNAs (U6 shRNAs or chimeric VA1 shRNAs) or individually expressed sense/antisense small interfering RNA (siRNA) strands have been used to trigger RNA interference (RNAi) in mammalian cells. Here we show that individually expressed siRNA expression constructs produce 21-nucleotide siRNAs that strongly accumulate as duplex siRNAs in the nucleus of human cells, exerting sequence-specific silencing activity similar to cytoplasmic siRNAs derived from U6 or VA1-expressed hairpin precursors. In contrast, 29-mer siRNAs separately expressed as sense/antisense strands fail to elicit RNAi activity, despite accumulation of these RNAs in the nucleus. Our findings delineate different intracellular accumulation patterns for the three expression strategies and suggest the possibility of a nuclear RNAi pathway that requires 21-mer duplexes.


The Long-Term and Late Effects of the Diagnosis and Treatment of Colorectal Cancer.
Colorectal cancer is the 3rd most common cancer in the UK. Through early detection and improved treatments more people than ever are surviving this disease. Surgery, chemotherapy and radiotherapy are the cornerstones of management, but these invasive treatments can cause a number of long-term and late effects. Using qualitative methods this study aimed to; explore peoples experiences with long-term and late effects of colorectal cancer, how these effects impacted on their lives and how participants managed them. Semi-structured qualitative interviews were conducted with 15 participants who had completed curative treatment. Interviews were transcribed and analysed using the Framework approach to identify themes and categorise text data. Many long-term and late effects of colorectal cancer were explored including bowel dysfunction, sexual dysfunction, pain, metastatic disease and cognitive dysfunction. These effects caused distress for many and were linked to depression and social limitation. Previously unidentified long-term effects included decreased libido and joint pain which respondents attributed to chemotherapy. Anxiety and depression were found predominantly to be late effects. Management of long-term and late effects was varied with healthcare services often ineffective. Insight gained into long-term and late effects and their treatment, indicated that many participants suffered because of their after-effects and had unmet health needs. It adds a qualitative insight into an area where quantitative research has already been conducted. Improvements in cancer follow-up could offer opportunities to effectively identify, manage and monitor these effects. Further interventional studies are required to develop effective care pathways to achieve optimal care.


Changes in sub-nuclear structures and functional perturbations: implications for radiotherapy.
The eukaryotic cell nucleus is required to accomplish its functions (e.g., replicating transcription, DNA repair, hmRNA processing, etc.) within the context of a highly organized structure [Wei X, Samarabandu J, Devdhar RS, Siegel AJ, Acharya R, Berezney R. 1998. Science 281:1502-1506.], since many cancer-therapeutic modalities utilize the nucleus as target for a cytotoxic outcome. A better understanding of the organizational disruption of sub-nuclear structures and subsequent loss of nuclear function is the key to knowing both the mechanism of action of, and the basis of cellular sensitivity to, therapeutic agents such as ionizing radiation. With this prospect, we examine four examples in which changes in specific nuclear structures or functions lead to significant therapeutic end points, e.g. cell death, radiosensitization, or the intrinsic radioresistance of tumor cells. The inter-relationships delineated in these examples provide a paradigm that delineates a relationship between disruption of nuclear organization, loss of function and a point of intervention that affects a therapeutic outcome. The examples specifically address issues related to radiation and thermal therapy. However, the concepts that result from these studies are translatable to other cancer therapeutic modalities. In addition, the results echo a basic principle that proper nuclear organization is critical to the maintenance of cellular viability and genomic stability. J. Cell. Biochem. Suppl. 35:142-150, 2000.


Inclusion of coherence in Monte Carlo models for simulation of x-ray phase contrast imaging.
Interest in phase contrast imaging methods based on electromagnetic wave coherence has increased significantly recently, particularly at X-ray energies. This is giving rise to a demand for effective simulation methods. Coherent imaging approaches are usually based on wave optics, which require significant computational resources, particularly for producing 2D images. Monte Carlo (MC) methods, used to track individual particles/photons for particle physics, are not considered appropriate for describing coherence effects. Previous preliminary work has evaluated the possibility of incorporating coherence in Monte Carlo codes. However, in this paper, we present the implementation of refraction in a model that is based on time of flight calculations and the Huygens-Fresnel principle, which allow reproducing the formation of phase contrast images in partially and fully coherent experimental conditions. The model is implemented in the FLUKA Monte Carlo code and X-ray phase contrast imaging simulations are compared with experiments and wave optics calculations.


Application of the scatter diagram technique to the scanning electron microscope: preliminary results from diamond.
Using primary beam energies E0 ranging from 0.2 to 15 keV and an in-lens detector, a series of images of the same region of an artificial microstructured diamond sample have been acquired in scanning electron microscopy. Next, the images were analysed by using a scatter diagram technique to underline the topographic contrast change and contrast reversal. The results obtained from 0.5 to 15 keV are discussed with the help of an expression derived from the constant loss model for the secondary electron yield delta of diamond, but including the respective roles of the angle of incidence, i, and of the angle of detection, alpha. More surprising is the quality of images obtained at a beam energy as low as 0.2 keV, and more difficult to explain is the significant contrast change between 0.2 keV and 0.5 keV. For the first time, scatter diagrams are used as a diagnostic tool in scanning electron microscopy, and after some improvements it is hoped that the experimental approach followed here may lead to quantitative estimates of the local tilts of a specimen surface.


Stomatal Behavior and Water Status of Maize, Sorghum, and Tobacco under Field Conditions: II. At Low Soil Water Potential.
Diurnal changes in the vertical profiles of irradiance incident upon the adaxial leaf surface (I), leaf resistance (r(1)), leaf water potential (psi), osmotic potential (pi), and turgor potential (P) were followed concurrently in crops of maize (Zea mays L. cv. Pa602A), sorghum (Sorghum bicolor [L.] Moench cv. RS 610), and tobacco (Nicotiana tabacum L. cv. Havanna Seed 211) on several days in 1968 to 1970 when soil water potentials were low. The r(1), measured with a ventilated diffusion porometer, of the leaves in the upper canopy decreased temporarily after sunrise [ approximately 0530 hours Eastern Standard Time] as I increased, but then r(1) increased again between 0700 and 0830 hr Eastern Standard Time as the psi, measured with a pressure chamber, decreased rapidly from the values of -7, -4 and -6 bars at sunrise to minimal values of -18, -22 and -15 bars near midday in the maize, sorghum, and tobacco, respectively. The pi, measured with a vapor pressure osmometer, also decreased after sunrise, but not to the same degree as the decrease in psi, so that a P of zero was reached in some leaves between 0730 and 0800 hours. The lower (more negative) pi of leaves in the upper canopy than those in the lower canopy gave the upper leaves a higher P at a given psi than the lower leaves in all three species; leaves at intermediate heights had an intermediate P. This difference between leaves at the three heights in the canopy was maintained at all values of psi. The r(1) remained unchanged over a wide range of P and then increased markedly at a P of 2 bars in maize, -1 bar in sorghum, and near zero P in tobacco: r(1) also remained constant until psi decreased to -17, -20, and -13 bars in leaves at intermediate heights in maize, sorghum, and tobacco, respectively. In all three species r(1) of leaves in the upper canopy increased at more negative values of psi than those at the base of the canopy, and in tobacco, leaves in the upper canopy wilted at more negative values of psi than those in the lower canopy.


Croatian indications for hyperbaric oxygenation: doubts of the world projected in a small country.
The recently issued "Croatian List of Indications for Hyperbaric Oxygen Treatment" (HBO2T) includes indications from the Undersea and Hyperbaric Medical Society List of Indications and the European Consensus List of Indication for Hyperbaric Oxygen, but also several considered by many as "off-label." Now approved by Croatian national health authorities, these indications are no longer "off-label" in Croatia. This represents a real controversy, confronting administrative vs. scientific/professional issues. Few systematic reviews have been published in The Cochrane Library so far on the subject of HBO2T, and most of them did not result in definitive recommendations for clinical practice. Croatian patients might benefit from the current list of indications because they will have the opportunity to be treated at the government's expense. Researchers will have easier access to potential subjects for clinical studies, subjects that are urgently needed to establish whether standard and off-label indications for HBO2T are in accordance with the principles of evidence-based medicine.


An outbreak of hepatitis A associated with a contaminated well in a middle school, Guangxi, China.
In May 2012, an outbreak of viral hepatitis A was reported to the Guangxi Center for Disease Control and Prevention from a middle school in Liujiang County. An investigation was conducted to identify the cause and mode of transmission and to recommend control and prevention measures. A case was defined as any person from the middle school with onset of fatigue, anorexia, abdominal pain, diarrhoea or jaundice from 20 February to 20 May 2012. We compared attack rates (AR) between boys and girls, assuming that only boys used well water and girls used pipeline water. We then selected 133 students from three classes in each of the three grades to compare AR by reported water source and drinking history. There were 22 cases, an AR of 3.8% (21/553) for students and 1.5% for teachers (1/65). Those who used well water were 8.7 (95% confidence interval [CI] = 2.1-37.2) times more likely to be ill than those using pipeline water. The cohort study showed that students who reported using well water daily were 5.2 (95% CI = 0.7-41.8) times more likely to be ill than those that reported using the pipeline water daily. Eighteen cases were confirmed as hepatitis A. This hepatitis A outbreak was potentially caused by a contaminated school well. We recommended that the school discontinue using the well and that the students should drink boiled water. As there is a vaccine for hepatitis A, we recommended that several doses of the vaccine be stored for controlling outbreaks and for immunizing susceptible populations in future outbreaks.


Public perceptions on Controlled Human Infection Model (CHIM) studies-a qualitative pilot study from South India.
Research using Controlled Human Infection Models is yet to be attempted in India. This study was conducted to understand the perceptions of the lay public and key opinion makers prior to the possible introduction of such studies in the country. 110 respondents from urban and rural Bangalore district were interviewed using qualitative research methods of Focus Group Discussions and In-depth Interviews. The data was analyzed using grounded theory. Safety was a key concern of the lay public, expressed in terms of fear of death. The notion of infecting a healthy volunteer, the possibility of continued effects beyond the study duration and the likelihood of vulnerable populations volunteering solely for monetary benefit, were ethical concerns. Public good outcomes such as effective treatments, targeted vaccines and prevention of diseases was necessary justification for such studies. However, the comprehension of this benefit was not clear among non-medical, non-technical respondents and suggestions to seek alternatives to CHIMs repeatedly arose. There was a great deal of deflection-with each constituency feeling that people other than themselves may be ideally suited as participants. Risk takers, those without dependents, the more health and research literate, financially sound and those with an altruistic bent of mind emerged as possible CHIM volunteers. While widespread awareness and advocacy about CHIM is essential, listening to plural voices is the first step in public engagement in ethically contentious areas. Continued engagement and inclusive deliberative processes are required to redeem the mistrust of the public in research and rebuild faith in regulatory systems.


Glycogen phosphorolysis can form a metabolic shuttle to support Ca2+ uptake by sarcoplasmic reticulum membranes in skeletal muscle.
In the presence of glycogen, ADP, phosphoglucomutase and hexokinase, the glycogen phosphorylase b activity associated to sarcoplasmic reticulum (SR) membranes stimulates Ca2+ uptake by SR membrane fragments in the absence of added ATP. Phosphoglucomutase and hexokinase lead to the formation of glucose 6-phosphate which in turn is used as an ATP regenerating system by the Ca2+ pump. It is proposed that a raise of cytosolic AMP and ADP concentrations after muscle contraction can activate an alternative metabolic route which would be used to ensure the maintenance of a low cytosolic Ca2+ concentration and avoid unnecessary metabolic energy depletion in muscle cells.


The role of the isothermal bulk modulus in the molecular dynamics of super-cooled liquids.
Elastic models imply that the energy expended for a flow event in ultra-viscous matter coincides with the elastic work required for deforming and re-arranging the environment of the moving entity. This is quite promising for explaining the strong non-Arrhenius behavior of dynamic quantities of fragile super-cooled liquids. We argue that the activation volume obtained from dielectric relaxation and light-scattering experiments for super-cooled liquids should scale with the Gibbs free energy of activation, with a proportionality constant determined by the isothermal bulk modulus and its pressure derivative, as described by an earlier thermodynamic elastic model. For certain super-cooled liquids the bulk compression transpiring in the local environment, as governed by the isothermal bulk modulus, play a significant role in the reorientational dynamics, with far-field density fluctuations and volume changes avoided by shear deformation.


Ultrasensitive probing of the protein resistance of PEG surfaces by secondary ion mass spectrometry.
The highly sensitive surface analytical techniques X-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-SIMS) were used to test the resistance of poly(ethylene glycol) (PEG) coatings towards adsorption of lysozyme (LYS) and fibronectin (FN). PEG coatings were prepared by grafting methoxy-terminated aldehyde-PEG (MW 5000 Da) onto two amino-functionalised surfaces with different amine group densities, generated by radio frequency glow discharge polymerisation of n-heptylamine and allylamine. Grafting was performed at the lower critical solution temperature to maximise the graft density of the PEG chains. XPS showed that the grafted density of PEG chains was slightly higher on the allylamine surface. XPS detected no adsorption of either protein on either PEG coating. ToF-SIMS analysis, on the other hand, found, in the positive ion spectra, minute but statistically significant signals assignable to amino acid fragment ions from both proteins adsorbed to the lower density PEG coating and from LYS but not FN on the higher density PEG coating. Negative ion spectra contained relatively more intense protein fragment ion signals for the lower density PEG coating but no changes assignable to adsorbed proteins on the higher density PEG coating. These results demonstrate the importance of utilising highly sensitive techniques to study protein adsorption on surfaces intended to be protein resistant, and that both positive and negative ion ToF-SIMS spectra should be acquired to probe for possible very low levels of protein adsorption.


Dual effect of halides in the Stille reaction: in situ halide metathesis and catalyst stabilization.
Halide anions can increase or decrease the transmetallation rate of the Stille reaction through in situ halide metathesis. Although the influence of the halogen present in oxidative addition complexes on the transmetallation rate with organostannanes was already known, the application of in situ halide metathesis to accelerate cross-coupling reactions with organometallic reagents is not described in the literature yet. In addition a second unprecedented role of halides was discovered. Halide anions stabilize the [Pd(0)(L)(2)] catalyst in Stille reactions, by means of [Pd(0)X(L)(2)](-) formation (X=Cl, I), hereby preventing its leaching from the catalytic cycle. Both arene (iodobenzene) and azaheteroarene (2-halopyridine, halopyrazine, 2-halopyrimidine) substrates were used.


[Influence factors of dislocation after bipolar prosthetic replacement].
To discuss the influence factors of dislocation after bipolar prosthetic replacement. A total of 374 patients who received bipolar prosthetic replacement in our hospital from October 2001 to October 2015 were retrospectively studied. The clinic data of patients with dislocation after operation was summarized to analyze the causes. Dislocation happened in 12 patients among all the 374 patients.10 cases received manual relocation, 2 cases open relocation. Most of the 12 patients were accompanied with neurological and psychiatric disorders, such as Alzheimer's disease, Parkinson's disease, sequelae of cerebral infarction, etc. Some factors like improper body position caused by these complications were the main influence factors of dislocation. Accompanied with neurological and psychiatric disorders is the important influence factor of dislocation after bipolar prosthetic replacement.


Cost-effectiveness of a quality improvement collaborative focusing on patients with diabetes.
To investigate the lifelong health effects, costs, and cost-effectiveness of a quality improvement collaborative focusing on improving diabetes management in an integrated care setting. Economic evaluation from a healthcare perspective with lifetime horizon alongside a nonrandomized, controlled, before-after study in the Netherlands. Analyses were based on 1861 diabetes patients in 6 intervention and 9 control regions, representing 37 general practices and 13 out-patient clinics. Change in the United Kingdom Prospective Diabetes Study score, remaining lifetime, and costs per quality-adjusted life year gained were calculated. Probabilistic life tables were constructed using the United Kingdom Prospective Diabetes Study risk engine, a validated diabetes model, and nonparametric bootstrapping of individual patient data. Annual United Kingdom Prospective Diabetes Study risk scores reduced for cardiovascular events (hazard ratio: 0.83 and 0.98) and cardiovascular mortality (hazard ratio: 0.78 and 0.88) for men and women, respectively. Life expectancy improved by 0.97 and 0.76 years for men and women, and quality-adjusted life years by 0.44 and 0.37, respectively. Higher life expectancy in the intervention group increased lifelong costs by &OV0556;860 for men and &OV0556;645 for women. Initial program costs were about &OV0556;22 per patient. The incremental costs per quality-adjusted life year were &OV0556;1937 for men and &OV0556;1751 for women compared with usual care costs. There is a probability >95% that the collaborative is cost-effective, using a threshold of &OV0556;20,000 per quality-adjusted life year. Optimizing integrated and patient-centered diabetes care through a quality-improvement collaborative is cost-effective compared with usual care.


Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma.
Previous studies in advanced-stage neuroblastoma (NB) have shown a link between the silencing of caspase-8 and methylation of a regulatory region at the boundary between caspase-8 exon 3 and intron 3. However, a number of recent studies from NB cell lines have shown that the transcriptional regulation of caspase-8 may reside with interferon gamma-sensitive promoters through the action of transcription factors, such as signal transducer and activator of transcription 1 (STAT-1). In this study, the authors tested the hypothesis that there is a correlation between caspase-8 and STAT-1 protein expression levels that may be linked to methylation of the regulatory elements of either of these genes. Thirty clinical tumor samples of all stages, including 13 samples from patients with Stage 4 disease, were analyzed by quantitative immunoblotting for caspase-8 and STAT-1. The DNA methylation status of putative caspase-8 and STAT-1 regulatory elements were determined by bisulfite-modified sequencing analysis. A significant correlation was observed between caspase-8 and STAT-1 protein levels in Stage 4 NB samples but not in lower stage NB samples. Caspase-8 and STAT-1 protein levels varied widely across all stages of NB and did not correlate with methylation of these genes. A strong correlation was observed between STAT-1 levels and caspase-8 levels in clinical Stage 4 NB. This suggests that STAT-1 or similar transcription factors, and not methylation, may play a role in controlling caspase-8 levels in this illness. No evidence of such a correlation between caspase-8 and STAT-1 levels was observed in lower clinical stages, suggesting that mechanisms controlling caspase-8 expression in NB vary with clinical stage.


Reticulated platelets in uremic patients: effect of hemodialysis and continuous ambulatory peritoneal dialysis.
Platelet RNA content can be detected by flow cytometry using thiazole orange staining to identify platelets recently released into the circulation. We studied platelet RNA content and platelet function in uremic patients under different treatment regimens. Four groups were studied: (I) 15 end-stage renal disease (ESRD) patients (10M/5F) on maintenance hemodialysis (HD); (II) 11 ESRD patients (6M/5F) on continuous ambulatory peritoneal dialysis (CAPD); (III) 8 patients with chronic renal failure managed conservatively (5M/3F); and (IV) 34 controls (20M/14F). A double color labeling technique using a phycoerythrin-tagged antibody against glycoprotein Ib (CD42b) and RNA labeling by thiazole orange was performed and read by flow cytometry. Aggregation studies were made in platelet-rich plasma using ADP, epinephrine, collagen, arachidonic acid, and ristocetin. In group I, samples were also obtained after HD. Platelet counts did not differ among the groups. Aggregation studies showed a lower response to ADP and ristocetin in the HD patients, but not in the CAPD or in the chronic renal failure patients. The percentage of platelets with high RNA content in group I was significantly lower than in controls (3.72 +/- 1.72% vs. 9.05 +/- 3.53%, P < 0.01), but was also lower than in the remaining groups (I vs. II P < 0.01, and I vs. III P < 0.01). No differences were seen in platelet RNA content among groups II (8.67 +/- 2.73%), III (9.14 +/- 3.04%) and IV. In group I, the percentage of reticulated platelets decreased further after HD (2.14 +/- 1.09%, P < 0.01). Aggregation studies showed a significantly lower response to ADP and ristocetin in group I (P < 0.05), but not in groups II or III in comparison with controls. Aggregation response to ADP and ristocetin decreased after HD (P < 0.05). In conclusion, HD may decrease the percentage of RNA-rich platelets through elimination of the younger and more active platelets and worsen the thrombopathy present in uremic patients.


Protective effect of melatonin against hippocampal DNA damage induced by intraperitoneal administration of kainate to rats.
The pineal hormone melatonin protects neurons in vitro from excitotoxicity mediated by kainate-sensitive glutamate receptors and from oxidative stress-induced DNA damage and apoptosis. Intraperitoneal injection on kainate into experimental animals triggers DNA damage in several brain areas, including the hippocampus. It is not clear whether melatonin is neuroprotective in vivo. In this study, we tested the in vivo efficacy of melatonin in preventing kainate-induced DNA damage in the hippocampus of adult male Wistar rats. Melatonin and kainate were injected i.p. Rats were killed six to 72 h later and their hippocampi were examined for evidence of DNA damage (in situ dUTP-end-labeling, i.e. TUNEL staining) and for cell viability (Nissl staining). Quantitative assay was performed using computerized image analysis. At 48 and 72 h after kainate we found TUNEL-positive cells in the CA1 region of the hippocampus; in the adjacent sections that were Nissl-stained, we found evidence of cell loss. Both the number of TUNEL-positive cells and the loss of Nissl staining were reduced by i.p. administration of melatonin (4 x 2.5 mg/kg; i.e. 20 min before kainate, immediately after, and 1 and 2 h after the kainate). Our results suggest that melatonin might reduce the extent of cell damage associated with pathologies such as epilepsy that involve the activation of kainate-sensitive glutamate receptors.


Asymptotics for metamaterials and photonic crystals.
Metamaterial and photonic crystal structures are central to modern optics and are typically created from multiple elementary repeating cells. We demonstrate how one replaces such structures asymptotically by a continuum, and therefore by a set of equations, that captures the behaviour of potentially high-frequency waves propagating through a periodic medium. The high-frequency homogenization that we use recovers the classical homogenization coefficients in the low-frequency long-wavelength limit. The theory is specifically developed in electromagnetics for two-dimensional square lattices where every cell contains an arbitrary hole with Neumann boundary conditions at its surface and implemented numerically for cylinders and split-ring resonators. Illustrative numerical examples include lensing via all-angle negative refraction, as well as omni-directive antenna, endoscope and cloaking effects. We also highlight the importance of choosing the correct Brillouin zone and the potential of missing interesting physical effects depending upon the path chosen.


Autophagy induction by low-dose cisplatin: the role of p53 in autophagy.
The majority of chemotherapy treatments for lung cancer use cisplatin; however, its use is limited as it has several side-effects. Autophagy (or type II cell death) is an important mechanism by which programmed cell death occurs. The purpose of this study was to determine whether low-dose cisplatin treatment induces autophagy in lung cancer cells. We also examined whether autophagy inhibition results in p53-mediated apoptosis. NCI-H460 (wild-type p53) and NCI-H1299 (null-type p53) cells were treated with 5 or 20 µM cisplatin for 12, 24 or 48 h. An MTT assay was performed to measure the cell viability following cisplatin treatment. To detect cisplatin-induced autophagy, cell morphology (autophagic vacuole) and LC3 localization were examined. The outcome of autophagy inhibition was determined using 3-methyladenine (3-MA) to detect Annexin V (+), propidium iodide (PI) (-) and acridine orange (+) cells by FACS analysis. To determine whether cisplatin induced autophagy, we examined the role of p53 as a cell survival regulator in autophagy. Low-doses of cisplatin (5 µM) induced cell death and this was augmented by 3-MA in both cell lines. Autophagic vacuoles and cytoplasmic LC3 formation was more evident in H460 cells than in H1299 cells. The induction of autophagy by low-dose cisplatin was increased by 2-fold in H460 compared to H1299 cells. However, the tests for apoptosis showed no difference between the 2 cell lines. Following 3-MA pretreatment, cisplatin-induced autophagy was found to be markedly reduced (a 3-fold reduction) in wild-type p53 compared to null-type p53 cells. However, cisplatin-induced apoptosis increased in wild-type p53 compared to null-type p53 cells. Autophagy induction and apoptotic shift after autophagy inhibition may be mediated by p53 activation in lung cancer cells treated with low-dose cisplatin.


Biohybrid networks of selectively desulfated glycosaminoglycans for tunable growth factor delivery.
Sulfation patterns of glycosaminoglycans (GAG) govern the electrostatic complexation of biomolecules and thus allow for modulating the release profiles of growth factors from GAG-based hydrogels. To explore options related to this, selectively desulfated heparin derivatives were prepared, thoroughly characterized, and covalently converted with star-shaped poly(ethylene glycol) into binary polymer networks. The impact of the GAG sulfation pattern on the network characteristics of the obtained hydrogels was theoretically evaluated by mean field methods and experimentally analyzed by rheometry and swelling measurements. Sulfation-dependent differences of reactivity and miscibility of the heparin derivatives were shown to determine network formation. A theory-based design concept for customizing growth factor affinity and physical characteristics was introduced and validated by quantifying the release of fibroblast growth factor 2 from a set of biohybrid gels. The resulting new class of cell-instructive polymer matrices with tunable GAG sulfation will be instrumental for multiple applications in biotechnology and medicine.


Electrophysiological correlates of hierarchical stimulus processing: dissociation between onset and later stages of global and local target processing.
In the discussion of whether the processing of hierarchically structured stimuli proceeds from the more global to the more local level or vice versa, it is frequently assumed that the relative speed of global/local target identification (response time (RT) advantage) and the direction of interference from local/global distractors reflect the order of processing. Studies both in brain-injured patients and in normals, however, have demonstrated that RT advantage and interference are dissociable, leading to the conclusion that they do not provide a valid index of the order of global/local processing. The aim of the present event-related brain potential (ERP) study was to assess electrophysiological correlates of global/local processing and to determine how the relative speed of responding to global and local targets is related to these ERP measurements. In a divided-attention paradigm, subjects were asked to respond to hierarchically structured letter stimuli that contained a target letter either at the global or at the local level. The behavioral results confirmed a dissociation between RT advantage and interference. ERP analysis revealed an early posterior negative component (denoted as N250) as a sign of early global/local target perception. It was found that RT advantage is not a valid measure of the onset nor of the time course of this component. Furthermore, the N250 components to global and local targets exhibited a different time course and a different topographical distribution, suggesting that they are determined by separate processing structures. Together, the behavioral and electrophysiological results support the view that global and local target perception may be mediated by separate brain systems acting, at least initially, in parallel.


Rational Polyelectrolyte Design Enables Multifunctional Polyion Complex Vesicles.
Polyion complex (PIC) vesicles prepared by polyelectrolyte assembly have attracted extensive attention as distinctive carriers and nanoreactors, particularly for biological cargoes. However, the constrained regulation of their structure and functionality at this stage hinder the application of PIC vesicles. Herein, we design a new asymmetric assembly system, namely cationic-neutral-cationic triblock copolymer co-assembly with a supramolecular ionic coordination polymer. The former creates poly(ethylene oxide) (PEO) loops upon complexation, which are favorable for vesicle fabrication, while the coordination polyelectrolyte composed of metal ions and a dipicolinic acid (DPA)-based bis-ligand features well-defined functionalities depending on the incorporated metal ions. Thus, the rational combination allows controlled fabrication of PIC vesicles with a modulated structure and functionalities. Moreover, the encapsulation and release of hydrophilic dextran based on different PIC vesicles has been realized. Our design integrates the advantages of both triblock and coordination polymers, and therefore demonstrates a novel strategy for harmonious regulation of the structure and functionality of PIC vesicles. The revealed findings and achieved properties shall be inspirational for developing functional PIC vesicles and boosting their applications towards demand encapsulation and delivery.


Safety and pharmacokinetics of lisdexamfetamine dimesylate in adults with clinically stable schizophrenia: a randomized, double-blind, placebo-controlled trial of ascending multiple doses.
To assess the safety and pharmacokinetics of lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, this double-blind study enrolled adults with clinically stable schizophrenia who were adherent (≥12 weeks) to antipsychotic pharmacotherapy. The participants received placebo or ascending LDX doses (50, 70, 100, 150, 200, and 250 mg) daily for 5 days at each dose (dose periods, 1-6; days, 1-5). Of the 31 enrolled participants, 27 completed the study (placebo, n = 6; LDX, n = 21). Treatment-emergent adverse events (AEs) were reported by 4 participants receiving placebo and by 23 participants receiving LDX (all doses) with no serious AEs while on active treatment. For all periods, the mean postdose change on day 5 (up to 12 hours postdose) in systolic and diastolic blood pressure and pulse, respectively, ranged from -4.62 to 8.05 mm Hg, -3.67 to 4.43 mm Hg, and -3.57 to 14.43 beats per minute for placebo and -3.83 to 11.25 mm Hg, -1.55 to 5.80 mm Hg, and -0.36 to 21.26 beats per minute for LDX. With ascending LDX dose, the mean (SD) maximum plasma concentration for LDX-derived d-amphetamine ranged from 51.68 (10.28) to 266.27 (56.55) ng/mL. The area under the plasma concentration-time curve for 24 hours ranged from 801.8 (170.2) to 4397.9 (1085.9) ng[BULLET OPERATOR]h/mL. The d-amphetamine maximum plasma concentration and area under the plasma concentration-time curve increased linearly with ascending LDX dose. Antipsychotic agents did not markedly affect d-amphetamine pharmacokinetics. Over a wide range of ascending doses, LDX safety profile in adults with schizophrenia was consistent with previous findings with no unexpected treatment-emergent AEs. Pulse tended to increase with LDX dose; overall, blood pressure did not increase with LDX dose. Consistent with previous studies, pharmacokinetic parameters increased linearly with increasing LDX dose.


Structure of the cysteine-rich intestinal protein, CRIP.
LIM domains are Zn-binding arrays found in a number of proteins involved in the control of cell differentiation, including several developmentally regulated transcription factors and a human proto-oncogene product. The rat cysteine-rich intestinal protein, CRIP, is a 76-residue polypeptide which contains a LIM motif. The solution structure of CRIP has been determined by homonuclear and 1H-15N heteronuclear correlated nuclear magnetic resonance spectroscopy. Structures with individual distance violations of < or = 0.03 angstrom and penalties (squared sum of distance violations) of < or = 0.06 angstrom2 were generated with a total of 500 nuclear Overhauser effect (NOE)-derived distance restraints (averaging 15.6 restraints per refined residue). Superposition of backbone heavy atoms of ordered residues relative to mean atom positions is achieved with pairwise rms deviations of 0.54(+/-0.14) angstrom. As observed previously for a peptide with the sequence of the C-terminal LIM domain from the avian cysteine-rich protein, CRP (cCRP-LIM2), CRIP binds two equivalents of zinc, forming N-terminal CCHC (Cys3, Cys6, His24, Cys27) and C-terminal CCCC (Cys30, Cys33, Cys51, Cys55) modules. The CCHC and CCCC modules in CRIP contain two orthogonally-arrayed antiparallel beta-sheets. The C-terminal end of the CCHC module contains a tight turn and the C terminus of the CCCC module forms an alpha-helix. The modules pack via hydrophobic interactions, forming a compact structure that is similar to that observed for cCRP-LIM2. The most significant differences between the structures occur at the CCHC module-CCCC module interface, which results in a difference in the relative orientations of the modules, and at the C terminus where the alpha-helix appears to be packed more tightly against the preceding antiparallel beta-sheet. The greater abundance of NOE information obtained for CRIP relative to cCRP-LIM2, combined with the analysis of J-coupling and proton chemical shift data, have allowed a more detailed evaluation of the molecular level interactions that stabilize the fold of the LIM motif.


Influence of blood collection techniques on platelet function.
For investigations of platelet function it is recommended that venipuncture should be performed using ordinary needle systems instead of butterfly cannulae systems. Platelets might be activated in the long plastic tubes of butterfly systems. The aim of this study was to investigate the dependency of platelet function results on blood sampling using different collection systems. Therefore, blood of 25 healthy volunteers was collected from both arms using at the same time on one side a 21-gauge needle and on the other side a 21-gauge butterfly cannula system. Both samples of each volunteer were analyzed on the PFA-100. Platelet aggregation was performed on the Behring Coagulation Timer (BCT) and the optical aggregometer PAP-4 using ADP, collagen and arachidonic acid to induce platelet aggregation in platelet-rich plasma. No significant prolongation of the closure times on the PFA-100 with the COL/EPI cartridge and the COL/ADP cartridge was observed when using butterfly cannulae. The results of optical aggregometry were not significantly different. The maximum aggregation response did not differ significantly for both collection systems. Aggregometry and the PFA-100 system are not affected by different blood collection systems. Therefore butterfly cannulae can be used for sample collection to investigate platelet function.


Enhanced Performance of Nanoporous Titanium Dioxide Solar Cells Using Cadmium Sulfide and Poly(3-hexylthiophene) Co-Sensitizers.
This work reports the effect of co-sensitization of nanoporous titanium dioxide using Cadmium Sulfide (CdS) and poly(3-hexylthiophene) (P3HT) on the performance of hybrid solar cells. CdS nanolayer with different thicknesses was grown on Titanium Dioxide (TiO₂) nanoparticles by chemical bath deposition technique with varying deposition times. Both atomic force microscopy (AFM) and UV⁻Vis⁻NIR spectroscopy measurements of TiO₂ electrode sensitized with and without CdS layer confirm that the existence of CdS layer on TiO₂ nanoparticles. AFM images of CdS-coated TiO₂ nanoparticles show that the surface roughness of the TiO₂ nanoparticle samples decreases with increasing CdS deposition times. Current density⁻voltage and external quantum efficiency (EQE) measurements were carried out for corresponding solar cells. Both short circuit current density (JSC) and fill factor were optimized at the CdS deposition time of 12 min. On the other hand, a steady and continuous increment in the open circuit voltage (VOC) was observed with increasing CdS deposition time and increased up to 0.81 V when the deposition time was 24 min. This may be attributed to the increased gradual separation of P3HT and TiO₂ phases and their isolation at the interfaces. The higher VOC of 0.81 V was due to the higher built-in voltage at the CdS⁻P3HT interface when compared to that at the TiO₂⁻P3HT interface. Optimized nanoporous TiO₂ solar cells with CdS and P3HT co-sensitizers showed external quantum efficiency (EQE) of over 40% and 80% at the wavelengths corresponding to strong absorption of the polymer and CdS, respectively. The cells showed an overall average efficiency of over 2.4% under the illumination of 70 mW/cm² at AM 1.5 condition.


A rank based social norms model of how people judge their levels of drunkenness whilst intoxicated.
A rank based social norms model predicts that drinkers' judgements about their drinking will be based on the rank of their breath alcohol level amongst that of others in the immediate environment, rather than their actual breath alcohol level, with lower relative rank associated with greater feelings of safety. This study tested this hypothesis and examined how people judge their levels of drunkenness and the health consequences of their drinking whilst they are intoxicated in social drinking environments. Breath alcohol testing of 1,862 people (mean age = 26.96 years; 61.86 % male) in drinking environments. A subset (N = 400) also answered four questions asking about their perceptions of their drunkenness and the health consequences of their drinking (plus background measures). Perceptions of drunkenness and the health consequences of drinking were regressed on: (a) breath alcohol level, (b) the rank of the breath alcohol level amongst that of others in the same environment, and (c) covariates. Only rank of breath alcohol level predicted perceptions: How drunk they felt (b 3.78, 95 % CI 1.69 5.87), how extreme they regarded their drinking that night (b 3.7, 95 % CI 1.3 6.20), how at risk their long-term health was due to their current level of drinking (b 4.1, 95 % CI 0.2 8.0) and how likely they felt they would experience liver cirrhosis (b 4.8. 95 % CI 0.7 8.8). People were more influenced by more sober others than by more drunk others. Whilst intoxicated and in drinking environments, people base judgements regarding their drinking on how their level of intoxication ranks relative to that of others of the same gender around them, not on their actual levels of intoxication. Thus, when in the company of others who are intoxicated, drinkers were found to be more likely to underestimate their own level of drinking, drunkenness and associated risks. The implications of these results, for example that increasing the numbers of sober people in night time environments could improve subjective assessments of drunkenness, are discussed.


Replication of the multidimensionality of activities of daily living.
We attempted to replicate the three-dimensional factor structure of a previously proposed ADL scale and demonstrate an association between the advanced ADL dimension and cognitive function. Data used in these analyses were baseline assessments of health and functional status of hospitalized patients enrolled in a randomized controlled trial of case managers as a means of reducing health care utilization. We submitted 14 items from the OARS to a two-stage process of principal components factor analysis. Four significant dimensions emerged that were remarkably similar to the advanced, basic, and household ADL dimensions reported by Wolinsky and Johnson (1991). In this sample of hospitalized patients, however, incontinence emerged as a weak fourth dimension. Multiple regression of SPMSQ mental status examination scores on these ADL dimensions demonstrates the association between cognitive function and the advanced ADL dimension. These data confirm that the underlying structure of ADLs consists of at least three separate dimensions, one of which is aligned with cognitive capacity.


Pathophysiological aspects of the low anterior resection syndrome for treatment of rectal cancer.
The number of patients with bowel dysfunction due to the treatment of rectal cancer has increased during the recent decades. Anatomical and functional disorders after the removal of the rectum are followed by increased stool frequency, urgency, multiple evacuations and flatus or stool incontinence characterizing the low anterior resection syndrome - LARS. The purpose of this article is to present a review of the literature on current concepts and pathophysiological aspects of bowel dysfunction after resection of rectal cancer. It is essential to understand these mechanisms for a better management of patients and recovery of their quality of life.


New and emerging therapies for diseases of the oral cavity.
It is obvious from the review of the literature that most treatments for oral diseases such as lichen planus, pemphigoid, and pemphigus are based on case reports, anecdotes, and small uncontrolled studies. Efforts must be made to perform more controlled studies to evaluate the efficacy of new treatments. Small numbers of patients at each site and multiple-drug therapy make this task difficult. Dermatologists should familiarize themselves with the newer immunosuppressive agents available. Use of these drugs requires knowledge of their pharmacokinetics and potential side effects, so that they may be used effectively and safely. Relatively low doses of azathioprine, cyclophosphamide, and cyclosporine should then be added to the dermatologist's armamentarium for the treatment of severe or recalcitrant diseases. Old drugs are resurfacing with new (but often off-label) uses as the underlying mechanisms of disease become understood. Thalidomide and mycophenolate mofetil are two examples of promising drugs for the future of dermatology.


Phytochrome action on chlorophyll synthesis-a study of the escape from photoreversibility.
A brief red light pretreatment (pulse), operating through phytochrome, stimulates the synthesis of chlorophyll a and b in Sorghum vulgare shoots that are placed in continuous saturating white light. The red light effect is fully reversible by a far-red (756 nanometers) light pulse for 45 minutes. Thereafter, escape from reversibility is fast, being completed within 2 hours. It is shown here that physiologically active phytochrome (Pfr) is required continuously during these first 45 minutes if the onset of the loss of photoreversibility is to begin 45 minutes after the red light treatment. Thus, the initial action of Pfr consists of two distinct processes: the first process is to overcome the lag prior to escape from photoreversibility; the second process is the actual stimulation of chlorophyll synthesis by Pfr. The duration of the lag prior to escape from photoreversibility depends on the level of Pfr established by the light pulse. The duration increases with increasing Pfr levels from nondetectable to 45 minutes. Above approximately 15% Pfr (Pfr/P(lot) approximately 0.15), the duration of the lag prior to escape from photoreversibility remains constant at 45 minutes.


Increased incidence of bladder cancer, lymphoid leukaemia, and myeloma in a cohort of Queensland melanoma families.
Familial cancer risk has been proposed as a shared feature of many cancers, and overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Clustering of melanoma occurs in approximately 10 % of families, and an over-representation of additional cancers has been noticed in some 'melanoma' families. The degree to which other cancers aggregate in families affected by melanoma has not been well defined. Therefore, this study aimed to assess the risk of cancers other than melanoma in a cohort of 178 'intermediate risk' melanoma families, not selected for specific genetic mutations. Families designated as 'intermediate risk' had two first degree relatives (FDRs) affected by melanoma when ascertained between 1982 and 1990, and were followed up over a 33 year period to assess new occurrences of cancer. We included 414 melanoma cases and 529 FDRs, comprising 25,264 person years of observation. Standardised incidence ratios and their 95 % confidence intervals were calculated for all invasive cancers, comparing observed to expected cases of cancer based on age and sex specific incidence rates for the Queensland population. Statistically significant increases were found for bladder cancer in females (observed, 7; expected, 1.99; SIR, 3.52; 95 % CI 1.41-7.25), lymphoid leukaemia in females (observed, 6; expected, 1.75; SIR, 3.43; 95 % CI 1.26-7.46), and myeloma in female melanoma cases (observed, 4; expected, 0.82; SIR, 4.89; 95 % CI 1.33-12.52). Over-representation of bladder cancer, lymphoid leukaemia, and myeloma in females of the cohort may suggest sex-dependent co-modifiers, and it is possible that specific combinations of polymorphisms predispose to certain cancer types.


Noncovalent protein--oligonucleotide interactions monitored by matrix-assisted laser desorption/ionization mass spectrometry.
Positive ion mode matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was used to explore nonspecific interactions between proteins and oligonucleotides. The formation of noncovalent complexes showed correlation with the type of oligonucleotide bases and with the amino acid composition of the proteins. Among the four DNA homooligomers, abundant protein-nucleic acid complexes were detected for pd(T)n, whereas negligible attachment was evident for pd(A)n, pd(C)n, and pd(G)n. Mixed base sequence nucleic acids (pd(AGCTCAGCTT) and d(TTAGCAGCTT) also showed affinity to Arg-Lys. The protein affinity of pd(T)n turned out to be nonspecific and produced a larger variety of complexes when the number of basic residues in the protein was increased. Complexation of pd(T)n with small basic dipeptides (Arg-Lys or His-His) led to significant improvement in the mass resolution for positive ions. For example, the mass resolution of the pd(T)20/Arg-Lys complex exhibited about 4 times improvement over pd(T)20 alone. The protein--oligonucleotide interactions were also pH and matrix dependent. Lowering the pH from its original value (pH = 1.7) led to diminishing complex related signal, whereas increasing the pH resulted in the appearance of a larger variety of complexes. 2,5-Dihydroxybenzoic acid matrix demonstrated much greater tendency to produce complex ions than did the three other matrix materials we tested. A possible explanation of the observed phenomena was based on pH-controlled ion pair formation between oligonucleotides and proteins.


Genetic determination of coagulation factor VIIc levels among healthy middle-aged women.
A recent study (1) reported variation among men in clotting factor VIIc levels is associated with a genetic polymorphism detected by the restriction enzyme Msp I. The present study determined the Msp I genotype (Arg353, Gln353 alleles) for 189 women (mean age 53) who were subjects in the Healthy Women Study, a population study of CHD risk factor change at menopause. Women with the Arg/Arg genotype (n = 147) had an 16% higher (geometric) mean FVIIc level than those with the Arg/Gln (n = 41) genotype (1.21 vs 1.04 U/ml, p < 0.01), while the one subject with the Gln/Gln genotype had an FVIIc level of 1.00 U/ml. These results are consistent with those previously found in healthy men (1). In addition, women carrying the Gln allele did not exhibit the elevation in FVIIc with menopause and use of hormone therapy found among those with the Arg allele, suggesting that genotype may modify the observed rise in factor VIIc at menopause. Possibly because of the small sample size this interaction did not reach conventional levels of statistical significance. Results of multiple linear regression analyses controlling for age, hormone use, obesity, (ln) triglyceride levels, and family history of CHD found FVIIc levels to be significantly (p < 0.001) related to genotype. Thus, genotype appears to be a major determinant of FVIIc levels among women.


Evaluation of published clinical studies for reproducibility, comparability and adherence to evidence-based methods.
To evaluate the "Materials and Methods" of long-term clinical studies in relation to documentation, reproducibility and comparability with and without employing the systematic methods of evidence-based medicine. The "Materials and Methods" sections in 45 clinical long-term published studies of direct posterior resin-based composite restorations were evaluated for their use of systematic methods of evidence-based medicine. The search was limited to the years 1988-1997, using the key words "clinical study/evaluation/results/report, long-term, in vivo, posterior, Class I/II, composite, restoration". Special attention was directed to comparisons of the underlying documentation, descriptions of the operative techniques used, and their reproducibility. In addition, an evidence-based search was carried out using the Internet PubMed interface for MEDLINE, using identical synonyms, to identify studies with high levels of quality of evidence. Documentation, reproducibility, and comparability of "Materials and Methods" were also evaluated. Results revealed how difficult it is to interpret results based on tenuous premises, subjective standards, and inadequate study designs. Only one article could be identified when the search was limited to "humans" and "randomized clinical trials". None of the articles, even when fulfilling the highest quality of evidence, showed sufficient or satisfactory quality of reproducibility in their descriptions in Materials and Methods.


Efficient Isolation and Functional Characterization of Niche Cells from Human Corneal Limbus.
The fate decision of limbal epithelial progenitor cells (LEPC) at the human corneal limbus is determined by the surrounding microenvironment with limbal niche cells (LNC) as one of its essential components. Research on freshly isolated LNC which mainly include limbal mesenchymal stromal cells (LMSC) and limbal melanocytes (LM) has been hampered by a lack of efficient protocols to isolate and purify these cells. We devised a protocol for rapid retrieval of pure LMSC, LM and LEPC populations by collagenase digestion of limbal tissue and subsequent fluorescence-activated cell sorting (FACS) using antibodies against CD90 and CD117. The sorted cells were characterized by immunophenotyping and functional assays. The effects of LMSC and LM on LEPC were studied in 3D co-cultures and LEPC differentiation status was assessed by immunohistochemistry. Enzymatic digestion and flow sorting yielded pure populations of LMSC (CD117-CD90+), LM (CD117+CD90-), and LEPC (CD117-CD90-). The LMSC exhibited self-renewal capacity (55.0 ± 4.6 population doublings), expressed mesenchymal stem cell markers (CD73, CD90, CD105, and CD44), and transdifferentiated to adipocytes, osteocytes, or chondrocytes. The LM exhibited self-renewal capacity and sustained melanin production. The sorted LEPC expressed epithelial progenitor markers (CK14, CK19, and CK15) and showed a colony-forming ability. Co-cultivation of LMSC and LM with LEPC resulted in a 4-5-layered stratified epithelium and supported the preservation of a LEPC phenotype, as reflected by increased p63+ and Ki67+ cells and decreased CK12+ cells compared with LEPC monocultures. A highly efficient isolation of pure LM, LMSC, and LEPC populations from a single preparation may allow for direct transcriptomic and proteomic profiling as well as functional studies on native unpassaged LNC, which can be considered as proper equivalents of LNC in vivo. The developed biomimetic 3D co-culture method could provide an experimental model for investigating the functional role of LNC in the limbal stem cell niche.


Associations Between Independent Assessments of Child Appetite Self-Regulation: A Narrative Review.
A variety of eating behaviors among children have been associated with obesity risk and are thought to broadly reflect child appetite self-regulation (ASR). While ASR is thought to occur on cognitive, emotional, motivational, biological, and behavioral levels, the inter-relatedness of ASR constructs as assessed by different methods/measures is not well-characterized. This narrative review describes the correspondence between different methods/measures of child ASR constructs as assessed by self-report questionnaires and/or observational tasks and their relationship to child standardized body mass index (BMIz). Research involving at least two different methods/measures is presented including observational tasks such as the Eating in the Absence of Hunger task, compensation trials, and eating rate, as well as various child eating behavior self-report questionnaires. Keyword searches in the PubMed and PsycINFO databases for articles published between 2000 and July 2021 identified 21,042 articles. Eighteen articles met the inclusion criteria and examined at least two of the targeted measures. Studies comparing questionnaire data with other questionnaire data showed the most evidence of significant associations (r values ranging from -0.45 to 0.49), whereas studies comparing questionnaires with observational tasks mostly showed weak (r values ranging from -0.17 to 0.19) or not significant associations, with only few studies finding moderate associations (r values ranging from -0.38 to 0.33). Studies comparing different observational tasks showed no significant associations. Overall, studies comparing self-report questionnaires showed the most correspondence, whereas those comparing observational tasks showed no correspondence. Studies across methods (questionnaires with tasks) showed less correspondence. Significant associations were found between ASR constructs and child BMIz across five studies using self-report questionnaires and two studies using observational tasks. Future research is needed to clearly define the various ASR constructs, their expected correspondence, and the strength of that correspondence, as well as the relations between ASR constructs and child weight among youth with and without overweight/obesity.


[The biological and diagnostic implication of the comparative data on expression of the same protein, obtained by Western blotting and surface plasmone resonance tests].
The comparative analysis of the data on the expression of the same modulating protein MX, obtained on the same biological materials by Western blotting and surface plasmone resonance tests was shown to provide in most cases a semiquantitative opinion as to modulation of MX affinity to its specific target (effector X protein) under the experimental action of F. This is doubtlessly to offer additional possibilities for the prediction and differential diagnosis of a number of diseases, including cancer.


Combination therapies in the management of type 2 diabetes: the use of insulin degludec/liraglutide.
The global burden of type 2 diabetes is estimated to currently affect over 350 million people worldwide and is anticipated to continue increasing over the next 20 years. Current treatment guidelines recommend the choice of pharmacotherapy based upon patient-specific parameters, with combination therapy for patients with a hemoglobin A1c level ≥9%. A new combination therapy of insulin degludec + liraglutide provides a long-acting basal insulin with a glucagon-like peptide agonist. In clinical trials, this combination product has reduced hemoglobin A1c and fasting plasma glucose more than the individual agents alone. Further advantages observed with this combination include weight loss and decrease in hypoglycemia compared to basal insulin alone.


Role of the Wilms' tumor 1 gene in the aberrant biological behavior of leukemic cells and the related mechanisms.
The Wilms' tumor 1 (WT1) gene is one of the regulating factors in cell proliferation and development. It is a double-functional gene: an oncogene and a tumor suppressor. This gene was found to be highly expressed in many leukemic cell lines and in patients with acute myeloid leukemia. In the present study, we demonstrated that the WT1 gene was commonly expressed in leukemic cell lines apart from U937 cells. The K562 cell line which expresses WT1 at a high level (mRNA and protein) was used in the entire experiment. By MTT and colony formation assays, we found that curcumin, an inhibitor of the WT1 protein, inhibited cell proliferation and clonogenicity in a time- and dose-dependent manner. It also caused cell cycle arrest at the G2/M phase. We then designed specific short hairpin RNAs (shRNAs) which could downregulate WT1 by 70-80% at the mRNA and protein levels. Reduction in the WT1 levels attenuated the proliferative ability and clonogenicity. Cell cycle progression analysis indicated that the proportion of cells in the G0/G1 phase increased while the proportion in the S phase decreased distinctively. ChIP-DNA selection and ligation (DSL) experiment identified a cohort of genes whose promoters are targeted by WT1. These genes were classified into different cellular signaling pathways using MAS software and included the Wnt/β-catenin pathway, MAPK signaling pathway, apoptosis pathway, and the cell cycle. We focused on the Wnt/β-catenin signaling pathway, and compared expression of several genes in the K562 cells transfected with the control shRNA and WT1-specific shRNA. β-catenin, an important gene in the Wnt canonical pathway, was downregulated after WT1 RNAi. Target genes of β-catenin which participate in cell proliferation and cell cycle regulation, such as CCND1 and MYC, were also significantly downregulated. Collectively, these data suggest that WT1 functions as an oncogene in leukemia cells, and one important mechanism is regulation of the Wnt/β-catenin pathway.


A conditional lethal mutant in the fission yeast 26 S protease subunit mts3+ is defective in metaphase to anaphase transition.
We have isolated a conditional lethal mutant mts3 in the fission yeast Schizosaccharomyces pombe which at the permissive temperature is resistant to the mitotic poison MBC and at the restrictive temperature is defective in metaphase to anaphase transition. The predicted amino acid sequence of mts3+ is 36% identical with the budding yeast gene NIN1. NIN1 cloned into a fission yeast expression vector can rescue both mts3 temperature-sensitive and null alleles demonstrating that NIN1 is the budding yeast homologue of the fission yeast mts3+ gene. The phenotype of the mts3 null is identical with the mts3 ts mutant demonstrating that the phenotype of the mts3 ts mutant is due to loss of mts3+ function. The deduced amino acid sequences of both mts3+ and NIN1 show homology to peptide sequences obtained from subunit 14 of the 26 S protease purified from bovine or human cells.


Joint Statement of the German Radiological Society and the German Respiratory Society on a Quality-Assured Early Detection Program for Lung Cancer with Low-Dose CT.
Substantial new data on the early detection of lung cancer with low-dose CT has become available since the last joint statement of the German Radiological Society and the German Respiratory Society was published in 2011. The German S3 guideline on lung cancer was revised in 2018 and now contains a weak recommendation regarding the early detection of lung cancer with low-dose CT in a quality-assured early detection program. These new developments required a change in the position of the involved professional societies. This joint statement describes the main features of a quality-assured program for the early detection of lung cancer with low-dose CT in Germany. KEY POINTS:: · New study data on early detection of lung cancer with low-dose CT and the new German S3 guideline on lung cancer required a new positioning of the involved professional societies.. · The involved professional societies strongly recommend that low-dose CT examinations for early detection of lung cancer should only be performed within a quality-assured program.. · The article describes some fundamentals of such a quality-assured early detection program.. CITATION FORMAT: · Wormanns D, Kauczor H, Antoch G et al. Joint Statement of the German Radiological Society and the German Respiratory Society on a Quality-Assured Early Detection Program for Lung Cancer with Low-Dose CT. Fortschr Röntgenstr 2019; 191: 993 - 997.


Traumatic stress responses in treatment-seeking earthquake survivors in Turkey.
This study examined the incidence of posttraumatic stress disorder (PTSD) and depression in 1,027 earthquake survivors who were consecutively referred to a community center at a mean of 14 months after the August 1999 earthquake in Turkey. Seventy-seven percent of referrals were women. The estimated rates of PTSD and major depression were 63% and 42%, respectively. More severe PTSD symptoms related to greater fear during the earthquake, female gender, lower education, loss of friends, shorter time since the earthquake, and material loss. More severe depression symptoms related to female gender, longer time since the earthquake, lower educational level, loss of a family member, and past psychiatric illness. In conclusion, long-term public mental health policies are needed for postearthquake psychological problems. These policies need to take into account the risk factors for traumatic stress and the gender differences in referral patterns. The differential stressor-response relationship may have important implications for treatment.


Improving the yield of mono-DNA-functionalized gold nanoparticles through dual steric hindrance.
A novel strategy of dual steric hindrance, which was obtained by Janus modification of gold nanoparticles (Au NPs) and volume exclusion of DNA, was adopted to prepare mono-DNA-modified Au NPs. The yield of mono-DNA-functionalized Au NPs significantly improved from 44 to 70% in the reaction between Au NPs and thiolated DNA. Furthermore, the specificity of mono-DNA-functionalized Au NPs was enhanced from 57 to 95%. The as-prepared Au NPs without postsynthetic treatment showed good controllability in self-assembly fabrication of complex nanostructures.


Vaccination strategies and transmission of COVID-19: Evidence across advanced countries.
Given limited supply of approved vaccines and constrained medical resources, design of a vaccination strategy to control a pandemic is an economic problem. We use time-series and panel methods with real-world country-level data to estimate effects on COVID-19 cases and deaths of two key elements of mass vaccination - time between doses and vaccine type. We find that new infections and deaths are both significantly negatively associated with the fraction of the population vaccinated with at least one dose. Conditional on first-dose coverage, an increased fraction with two doses appears to offer no further reductions in new cases and deaths. For vaccines from China, however, we find significant effects on both health outcomes only after two doses. Our results support a policy of extending the interval between first and second doses of vaccines developed in Europe and the US. As vaccination progresses, population mobility increases, which partially offsets the direct effects of vaccination. This suggests that non-pharmaceutical interventions remain important to contain transmission as vaccination is rolled out.


Magnetic resonance imaging of the fetal central nervous system, head, neck, and chest.
Magnetic resonance imaging (MRI) has become an important tool in the assessment of fetal anomalies. Although ultrasound remains the modality of choice for screening, MRI offers several advantages that permit optimal characterization of anomalies in certain situations. Accurate recognition and characterization of fetal anomalies guides decisions about pregnancy management and coordination of postnatal care. This article will briefly review safety and practical aspects of fetal MRI. We will then provide a concise summary of the most common indications for fetal MRI, and discuss the differential diagnosis and role of MRI in assessment of fetal brain, head, neck, spine, and chest anomalies.


Mucoadhesive tablets for buccal administration containing sodium nimesulide.
The possibility of improving the flux of nimesulide across the buccal mucosa using the drug in the form of a sodium salt was investigated in our study. The salt form may increase to flux across buccal membrane, starting from a suspension; its lower permeation coefficient is compensated by a higher concentration gradient. The salt was inserted into a mucoadhesive tablet for buccal administration. The tablets were designed to prevent the loss of the drug into the saliva by means of a protective layer and placed on the area not in contact with the mucosa. Ten volunteers were used. The in vitro release from mucoadhesive tablets was examined through a porcine buccal mucosa, using a standard Franz cell, modified for present purposes. The advantages of a higher concentration gradient for the flux, related to a higher solubility of the salt, and to a sufficiently high permeation coefficient of the drug, despite the ionized form, could not be completely exploited, because the composition of the formulation destroys the chemical form of the drug.


The measurement of exhaled nitric oxide in routine practice.
Exhaled nitric oxide (NO) is considered the most easily available clinical test to indirectly assess the level of eosinophilic airway inflammation in asthma, and to predict the efficacy of anti-inflammatory treatment with inhaled corticosteroids (ICS). It is possible to measure the level of exhaled NO using online or offline methods. The most widely used online method employs techniques that enable NO in exhaled air to be measured in a single exhalation, calculating the value at the end-expiratory plateau. Because of the correlation between the level of exhaled NO with the level of eosinophilic inflammation in the airway of asthmatic patients, it has been proposed as a clinical marker in the practice of respiratory and allergy physicians with differing targets. In particular it is considered to be highly effective in the diagnosis of allergic asthma, to be capable of identifying those patients with a higher response probability to inhaled corticosteroids, and to a lesser extent, to be of value in contributing to the management of the disease. The possibility of easily taking measurements of FeNO in an office setting even by relatively young children, and the availability of a portable device, opens a significant perspective for the routine use of FeNO evaluation in daily practice.


Energy-conserving dimethyl sulfoxide reduction in the acetogenic bacterium Moorella thermoacetica.
Moorella thermoacetica is one of the well-studied thermophilic acetogenic bacteria. It grows by oxidation of organic substrates, CO or H2 coupled to CO2 reduction to acetate. Here, we describe that M. thermoacetica can also use dimethyl sulfoxide as terminal electron acceptor. Growth of M. thermoacetica on glucose or H2 + CO2 was stimulated by dimethyl sulfoxide (DMSO). Membranes showed a DMSO reductase activity, that was induced by growing cells in presence of DMSO. The enzyme used reduced anthraquinone-2,6-disulfonate, benzyl- and methyl viologen as electron donor, but not NAD(P)H. Activity was highest at pH 5 and 60°C, the Km for DMSO was 2.4 mM. Potential DMSO reductase subunits were identified by peptide mass fingerprinting; they are encoded in a genomic region that contains three potential dmsA genes, three dmsB genes and one dmsC gene. Transcriptome analysis revealed that two different dmsAB gene clusters were induced in the presence of DMSO. The function of these two and their predicted biochemical features are discussed. In addition, the data are in line with the hypothesis that M. thermoacetica can use DMSO alongside CO2 as electron acceptor and DMSO reduction is catalysed by an energy-conserving, membrane-bound electron transport chain with DMSO as final electron acceptor.


Lung cancer resection with concurrent off-pump coronary artery bypasses: safety and efficiency.
To assess the safety and efficacy of combined surgery for patients with concurrent lung cancer and severe coronary heart disease (CHD). Between 2003 and 2014, 34 patients with stage I or II lung cancer and simultaneous severe CHD underwent combined off-pump coronary artery bypass (OPCAB) grafting and lung resection. Surgically, myocardial revascularization was performed first and followed by lobectomies through the same or a second incision. Video-assisted thoracoscopes were used in some cases. Five patients also received chemotherapy before or after combined surgery in an effort to improve the long-term survival. All patients survived the operation and no new myocardial infarctions (MIs) occurred in the perioperative period. The most frequent complications were cardiac arrhythmias (5 cases), atelectasis (4 cases), and pulmonary infections (2 cases). All patients were followed up for 5-60 months. Within this period, 6 patients (17.6%) died due to cancer recurrence. The 3- and 5-year survivals were 75% and 67% for these lung cancer patients, respectively. Combined OPCAB and pulmonary resection for early stage lung cancer patients with concurrent severe CHD is a relatively safe and effective treatment with satisfactory long-term survival rates, especially for those patients with three-vessel disease who are not usually candidates for percutaneous coronary intervention (PCI) before open surgery.