Quality of life and radiological outcome after cervical cage fusion and cervical disc arthroplasty.
In this retrospective comparative study, 42 patients with single-level cervical radiculopathy were operated upon, either with Shell cage fusion (23 patients) or with Prestige cervical disc arthroplasty (19 patients). The mean follow-up (FU) was 17.5 months (range: 5.6-42.1 months). Both treatments significantly improved all clinical parameters (VAS, ODI, SF36) (p < 0.001), without statistically relevant differences between the two groups. From a radiological viewpoint there was an obvious but statistically non-significant increase in the segmental height for both treatment groups. Segmental angle also increased in both groups, and the increase was significant (p < 0.05). As expected, range of motion (ROM) decreased significantly (p < 0.05) in the fusion group, while it was preserved in the arthroplasty group. Significantly more (p < 0.05) adjacent level degeneration class 1 to 4 was evident in the fusion group (8/23 or 34.8%) than in the arthroplasty group (3/19 or 15.8%). Two fusion patients (2/23 or 8.7%) developed painful clinical adjacent level disease requiring arthroplasty. The major conclusion was that significant adjacent level degenerative changes occurred in the cage group. Retained motion at the operative site seems to decrease the incidence of adjacent level degeneration. Implant subsidence was recorded at FU in 8 out of 42 patients (19%). It occurred significantly (p < 0.05) more often in the fusion group (6/23 or 26.1%) than in the arthroplasty group (2/19 or 10.5%), but it did not cause clinical symptoms. As in other studies, there is no explanation as to why better radiological results did not translate into better clinical outcomes within the time limits of the study.


Specific developmental window for establishment of an insect-microbe gut symbiosis.
The alydid stinkbug Riptortus pedestris is specifically associated with a beneficial Burkholderia symbiont in the midgut crypts. Exceptional among insect-microbe mutualistic associations, the Burkholderia symbiont is not vertically transmitted but orally acquired by nymphal insects from the environment every generation. Here we experimentally investigated the process of symbiont acquisition during the nymphal development of R. pedestris. In a field population, many 2nd instar nymphs were Burkholderia free, while all 3rd, 4th, and 5th instar nymphs were infected. When reared on soil-grown potted soybean plants, Burkholderia acquisition occurred at a drastically higher frequency in the 2nd instar than in the other instars. Oral administration of cultured Burkholderia cells showed that 2nd and 3rd instar nymphs are significantly more susceptible to the symbiont infection than 1st, 4th, and 5th instar nymphs. Histological observations revealed rudimentary midgut crypts in the 1st instar, in contrast to well-developed midgut crypts in the 2nd and later instars. These results indicate that R. pedestris acquires the Burkholderia symbiont from the environment mainly during the 2nd instar period and strongly suggest that the competence for the symbiont infection is developmentally regulated by the host side. Potential mechanisms involved in infection competence and possible reasons why the infection preferentially occurs in the 2nd instar are discussed.


Correctional policy for offenders with mental illness: creating a new paradigm for recidivism reduction.
Offenders with mental illness have attracted substantial attention over the recent years, given their prevalence and poor outcomes. A number of interventions have been developed for this population (e.g., mental health courts). They share an emphasis on one dimension as the source of the problem: mental illness. Their focus on psychiatric services may poorly match the policy goal of reducing recidivism. In this article, we use research to evaluate (a) the effectiveness of current interventions, and(b) the larger viability of psychiatric, criminological, and social psychological models of the link between mental illness and criminal justice involvement. We integrate theory and research to offer a multidimensional conceptual framework that may guide further research and the development of efficient interventions that meaningfully reduce recidivism. We hypothesize that the effect of mental illness on criminal behavior reflects moderated mediation (i.e., the effect is direct in the case of one subgroup, but fully mediated in another); and that the effect of mental illness on other "recidivism" is partially mediated by system bias and stigma. We use this framework to propose three priorities for advancing research, articulating policy, and improving practice.


The sexual and reproductive health of young people in Latin America: evidence from WHO case studies.
This original article addresses the sexual and reproductive health needs of young people aged 15 to 24 in Latin America. It introduces five articles from original research projects in three countries: Argentina, Brazil, and Peru. These projects were funded by the World Health Organization. This article explains the importance of studies that address the sexual and reproductive health of young people in developing countries. It provides an overview of sexual and reproductive health issues in Latin America and a discussion these issues in the three study countries. The five articles deal with difficult and challenging issues, including: knowledge of STIs and HIV/AIDS; pregnancy related practices; quality of care; the role of young men in couple formation, pregnancy and adoption of contraceptive practice; and, the role of obstetricians and gynecologists in public policy debate about family planning and abortion. The four articles in this special section help to improve our understanding of the factors that contribute to risky sexual behavior and negative reproductive health outcomes among youth in Latin America. The findings are useful to help inform and improve health care interventions in various contexts.


Differential sensitivity of genetically Fast vs. Slow kindling rats strains to GABAergic convulsive agents.
Following selective breeding for seizure-proneness vs. seizure-resistance to amygdala kindling, two strains of rats were developed with non-overlapping kindling rates, i.e. the number of stimulations required to develop fully generalized convulsive seizures (Epilepsy Res. 35 (1999) 183). In the temporal cortices of these two strains, the local seizure thresholds to electrical stimulation have been reported to be approximately two times lower in the seizure-prone (Fast kindling) compared to the seizure-resistant (Slow kindling) strain (McIntyre et al., 1999). In the present experiment, the pharmacological sensitivities of the two strains to three GABAergic antagonists, pentylenetetrazol, bicuculline and picrotoxin, were determined, and compared to the glycine antagonist, strychnine. Paralleling kindling epileptogenesis, naïve rats of the Fast kindling strain developed convulsive seizures to doses of the GABAergic antagonists that were significantly (approximately 30%) lower than the naïve Slow kindling strain. In contrast, there were no strain differences in their response to strychnine. These data indicate substantial GABAergic sensitivity differences between the two strains with an emphasis on forebrain mechanisms, which is consistent with other physiological and molecular data related to their differential profiles of epileptogenesis.


[Primary outcome of disability as a result of femur neck fractures].
The authors propose the strategy of surgical treatment of patients with fractures of the neck of the femur with due consideration for patient's age, disorders of local circulation, and terms of operation. As a result of this strategy, the share of good outcomes and social rehabilitation improved appreciably. Anatomic physiological classification of disorders of local circulation at the femoral bone neck has been developed, which helps assess the rehabilitation potential of the invalids with consequences of fractures of the neck of the femur.


[Excretion of 5-hydroxyindole-3-acetic and 5-methoxyindole-3-acetic acids in cancer patients].
Daily urinary excretion of 5-hydroxy-3-indoleacetic acid (5-HIAA) and 5-methoxyindole-3-acetic acid (5-MIAA) was studied by chromatography-mass-spectrometry in patients with cancer and healthy subjects. A considerable increase in urinary 5-MIAA-excretion was shown in patients with cancer of the stomach, rectum and lung. In some cases, a correlation was found between high urine levels of carcinogenic 5-MIAA and similarly high levels of 5-HIAA excretion with urine.


Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.
Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (p<0.001) brain- reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) significantly increased (p<0.001) the level of malondialdehyde (MDA), nitric oxide and the activity of cytokines in the brain. MEAR supplementation resulted in normalization of brain GSH and CAT and SOD and decreases in the levels of MDA with reduction of nitric oxide and cytokines in the brain. The action of the extract at dose of 200 mg/kg was almost similar to the standard drug, quercetin (100mg/kg, p.o.). These present study conclude that MEAR administration significantly (P<0.05) reduced LPS- induced oxidative-stress and intensely suggest that Asparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.


Excess feeding increases adipogenesis but lowers leptin transcript abundance in zebrafish larvae.
Although fish exposed to municipal wastewater effluents (MWWE) show higher lipid accumulation, whether this is due to adipogenesis is unclear. The objective here was to identify molecular markers of adipogenesis in zebrafish (Danio rerio) larvae for use as high throughput screening tools for environmental contaminants, including obesogens in MWWE. Zebrafish larvae were fed a commercial diet at a maintenance level (5 % body mass) or in excess (25 or 50 % body mass) from day 6 to 30 days post-fertilization (dpf) to stimulate adipogenesis. We monitored fat accumulation and markers of lipid metabolism, including peroxisome proliferator-activated receptor γ (ppar γ), fatty acid synthase (fas), ELOVL fatty acid elongase 2 (elovl2), diacylglycerol O-acyltransferase 2 (dgat2), leptin (lepa and lepb), leptin receptor (lepr), and lipoprotein lipase (lpl). Excess feeding led to a higher growth rate, protein content and an increase in igf1 transcript abundance. Also, these larvae had higher triglyceride levels and accumulated lipids droplets in the abdominal cavity and viscera. The molecular markers of adipogenesis, including fas, elovl2, and dgat2, were upregulated, while the transcript abundance of lpl, a lipolytic gene, were transiently lower due to excess feeding. The increased adiposity seen at 30 dpf due to excess feeding coincided with a lower lep but not lepr transcript abundance in zebrafish. Our results demonstrate that excess feeding alters the developmental programming of key genes involved in lipid homeostasis, leading to excess lipid accumulation in zebrafish larvae. Overall, fas, elovl2, lpl, and dgat2, but not lep or ppar γ, have the potential as biomarkers of adipogenesis in zebrafish larvae.


Activation-inactivation of potassium channels and development of the potassium-channel spike in internally perfused squid giant axons.
A spike that is the result of calcium permeability through potassium channels was separated from the action potential is squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution by blocking sodium channels with tetrodotoxin. Currents through potassium channels were studied under voltage clamp. The records showed a clear voltage-dependent inactivation of the currents. The inactivation was composed of at least two components; one relatively fast, having a time constant of 20--30 ms, and the other very slow, having a time constant of 5--10 s. Voltage clamp was carried out with a variety of salt compositions in both the internal and external solutions. A similar voltage-dependent inactivation, also composed of the two components, was recognized in all the current through potassium channels. Although the direction and intensity of current strongly depended on the salt composition of the solutions, the time-courses of these currents at corresponding voltages were very similar. These results strongly suggest that the inactivation of the currents in attributable to an essential, dynamic property of potassium channels themselves. Thus, the generation of a potassium-channel spike can be understood as an event that occurs when the equilibrium potential across the potassium channel becomes positive.


Catalytic activity, thermal stability and structural evolution of PdCu single-atom alloy catalysts: the effects of size and morphology.
Single-atom alloys (SAAs) have been emerging as an important field of research in electrocatalysis owing to extremely high atom utilization, unique structure and high catalytic activity. In this work, the catalytic properties and thermal stability of PdCu SAAs with a crown-jewel (CJ) structure are studied by density functional theory (DFT) calculations and the molecular dynamics (MD) simulation method. The DFT results reveal that CJ-structured PdCu SAAs show excellent HER and ORR catalytic performance, and can be regarded as a promising alternative to Pt catalysts towards the ORR or HER. Additionally, we attempt to explain the high catalytic activity of PdCu SAAs by electronic structure analysis. In addition, MD simulation results confirm the thermal stability of CJ-structured PdCu. More importantly, we found that CJ-structured PdCu clusters undergo a structural transformation from cuboctahedral (Cubo) to icosahedral (Ico) structure by heating or after the adsorption of reaction intermediate, which indicates that Cubo is less stable than the Ico structure. Besides, Cubo-Ico transformation is size-dependent and only found in small clusters. Furthermore, the effects of size and morphology on melting properties are discussed. The melting point increases as cluster size increases, which agrees well with Pawlow's law.


Differential elastic electron scattering cross sections for CCl4 by 1.5-100 eV energy electron impact.
We report absolute elastic differential, integral and momentum transfer cross sections for electron interactions with CCl(4). The incident electron energy range is 1.5-100 eV, and the scattered electron angular range for the differential measurements varies from 15°-130°. The absolute scale of the differential cross section was set using the relative flow technique with helium as the reference species. Comparison with previous total cross sections shows good agreement. Atomic-like behaviour in this scattering system is shown here for the first time, and is further investigated by comparing the CCl(4) elastic cross sections to recent results on the halomethanes and atomic chlorine at higher impact energies [H. Kato, T. Asahina, H. Masui, M. Hoshino, H. Tanaka, H. Cho, O. Ingólfsson, F. Blanco, G. Garcia, S. J. Buckman, and M. J. Brunger, J. Chem. Phys. 132, 074309 (2010)].


Role of vegetation (Typha latifolia) on nutrient removal in a horizontal subsurface-flow constructed wetland treating UASB reactor-trickling filter effluent.
The main objective of the work is to characterize the role of plants in a constructed wetland in the removal of nitrogen (N) and phosphorus (P). The experiments were carried out in a full-scale system in the city of Belo Horizonte, Brazil, with two parallel horizontal subsurface-flow constructed wetland units (one planted with Typha latifolia and one unplanted) treating the effluent from a system composed of an upflow anaerobic sludge blanket reactor and a trickling filter (TF). Each wetland unit received a mean flow of approximately 8.5 m³ d⁻¹ (population equivalent around 60 inhabitants each), with a surface hydraulic loading rate 0.12 m³m⁻²d⁻¹. The experiments were conducted from September 2011 to July 2013. Mean effluent concentrations from the wetlands were: (a) planted unit total nitrogen (TN) 22 mg L⁻¹, ammonia-N 19 mg L⁻¹, nitrite-N 0.10 mg L⁻¹, nitrate-N 0.25 mg L⁻¹, P-total 1.31 mg L⁻¹; and (b) unplanted unit TN 24 mg L⁻¹, ammonia-N 20 mg L⁻¹, nitrite-N 0.54 mg mL⁻¹, nitrate-N 0.15 mg L⁻¹, P-total 1.31 mg L⁻¹. The aerial part of the plant contained mean values of 24.1 gN (kg dry matter)⁻¹ and 4.4 gP (kg dry matter)⁻¹, and the plant root zone was composed of 16.5 gN (kg dry matter)⁻¹ and 4.1 gP (kg dry matter)⁻¹. The mean extraction of N by the plant biomass was 726 kgN ha⁻¹y⁻¹, corresponding to 17% of the N load removed. For P, the extraction by the plant biomass was 105 kgP ha⁻¹y⁻¹, corresponding to 9% of the P load removed. These results reinforce the reports that N and P removal due to plant uptake is a minor mechanism in horizontal subsurface-flow constructed wetlands operating under similar loading rates, typical for polishing of sanitary effluent.


Non-traumatic subdural hemorrhage: beware of ruptured intracranial aneurysm.
Acute subdural hemorrhage (SDH) is commonly encountered by emergency radiologists in the setting of trauma. When history or imaging evidence of trauma is absent, the differential diagnosis for SDH should be expanded. Intracranial aneurysm rupture is a rare and underrecognized cause of SDH which may present without concurrent subarachnoid hemorrhage. The mechanism of aneurysmal SDH is controversial, but understanding the anatomic microenvironment of the aneurysm provides insight and clarifies aneurysm features predisposing to subdural compartment rupture. Aneurysmal SDH is a neurosurgical emergency and its treatment strategies differ from traumatic SDH. Outcomes are poor if treatment is delayed; thus, radiologists play a central role in recognizing this uncommon but potentially devastating complication of aneurysm rupture. The goal of this article is to familiarize radiologists with clinical and imaging characteristics of aneurysmal SDH and review pertinent anatomy, risk factors, and potential etiologies. Aneurysmal rupture can easily be overlooked in the routine workup of atraumatic SDH, and radiologists must know when to recommend vascular imaging to avoid the catastrophic consequences of a missed diagnosis.


The effects of simulated microgravity on avian embryonic development.
Based on the few reports available, microgravity (MG) can have adverse effects on the early development of vascularised extra-embryonic membranes in avian eggs. Whether gravity or oxygen availability is the stimulus for development of the blood vessels in the chorioallantoic membranes (CAM) remains unclear. Under gravity the blastoderm forms on top of the yolk sac, closest to the oxygen rich region beneath the shell membranes, and from there the CAM buds from an abdominal extension subsequently to form a close contact with shell membranes. Then as the embryo develops it spreads beneath the eggshell surface to maximise the surface area of the CAM vascular bed available for O2 uptake. To investigate how simulated MG influences development of the CAM and embryo we conducted experiments on chicken embryos during incubation in a 3D-clinostat (control or continuous MG treatment at 5 rpm). Further, to determine if CAM angiogenesis is directed towards regions of high O2 tension or gravity we investigated the effects of wax treatment (50% shell surface area) on development in MG. We found that clinostat MG caused embryonic failure between day 0-5 by preventing normal development of CAM-shell membrane complex. Thereafter acute MG promoted increases in CAM mass, but did not affect embryo mass. Preliminary findings suggest that combined acute MG and wax treatment did not significantly affect embryonic growth in either MG or control groups, but retarded CAM growth in control embryos only. Finally, we will present evidence to show that acute and prolonged exposure to MG does not prevent normal growth and hatching, but might have more subtle effects on hatchling physiology, including reduced heart mass.


Bee venom phospholipase A2 ameliorates Alzheimer's disease pathology in Aβ vaccination treatment without inducing neuro-inflammation in a 3xTg-AD mouse model.
Alzheimer's disease (AD) is the most common form of dementia and is characterized by an imbalance between the production and clearance of amyloid-beta (Aβ) and tau proteins. Although vaccination against Aβ peptide results in a dramatic reduction in Aβ pathology in experimental mouse models, the initial clinical trial for an active Aβ vaccine was halted early due to the development of acute meningoencephalitis in 6% of the immunized patients, which likely involved a T-cell mediated pro-inflammatory response. In this study, we aimed to determine whether bee venom phospholipase A2 (bvPLA2) treatment would induce Tregs and ameliorate AD pathology without unwanted T cell-mediated inflammation. First, we investigated the effects of bvPLA2 on the inflammatory infiltration caused by Aβ vaccination. Inflammatory aggregates of CD3+ T lymphocytes and macrophages were found in the brains and spinal cords of mice treated with Aβ. However, administration of bvPLA2 dramatically eliminated central nervous system inflammation following Aβ immunization. In AD model mice (3xTg-AD mice), bvPLA2 administration significantly ameliorated cognitive deficits and reduced Aβ burdens in the brains of Aβ-vaccinated 3xTg-AD mice. Additionally, we examined brain glucose metabolism using positron emission tomography with 18F-2 fluoro-2-deoxy-D-glucose. Cerebral glucose uptake was considerably higher in the brains of Aβ-vaccinated 3xTg-AD mice that received bvPLA2 than those that did not. The present study suggests that the modulation of Treg populations via bvPLA2 treatment may be a new therapeutic approach to attenuate the progression of AD in conjunction with Aβ vaccination therapy without an adverse inflammatory response.


Consensus statement of the European Heart Rhythm Association: updated recommendations for driving by patients with implantable cardioverter defibrillators.
Patients with an implantable cardioverter defibrillator (ICD) have an ongoing risk of sudden incapacitation that might cause harm to others while driving a car. Driving restrictions vary across different countries in Europe. The most recent recommendations for driving of ICD patients in Europe were published in 1997 and focused mainly on patients implanted for secondary prevention. In recent years there has been a vast increase in the number of patients with an ICD and in the percentage of patients implanted for primary prevention. The EHRA task force on ICD and driving was formed to reassess the risk of driving for ICD patients based on the literature available. The recommendations are summarized in the following table and are further explained in the document, (Table see text). Driving restrictions are perceived as difficult for patients and their families, and have an immediate consequence for their lifestyle. To increase the adherence to the driving restrictions, adequate discharge of education and follow-up of patients and family are pivotal. The task force members hope this document may serve as an instrument for European and national regulatory authorities to formulate uniform driving regulations.


Learning from the Epidemiological Response to the 2014/15 Ebola Virus Disease Outbreak.
A large international response was needed to bring the 2014/15 West African Ebola virus disease outbreak under control. This study sought to learn lessons from this epidemic to strengthen the response to future outbreaks of international significance by identifying priorities for future epidemiology training and response. Epidemiologists who were deployed to West Africa were recruited through a snowball sampling method and surveyed using an online anonymous questionnaire. Associations between demographics, training, qualifications, and role while in-country were explored alongside respondents' experience during deployment. Of 128 responses, 105 met the inclusion criteria. Respondents originated from 25 countries worldwide, for many (62%), this was their first deployment abroad. The most common tasks carried out while deployed were surveillance, training, contact tracing, and cluster investigation. Epidemiologists would value more detailed predeployment briefings including organizational aspects of the response. Gaps in technical skills reported were mostly about geographical information systems; however, epidemiologists identified the need for those deployed in future to have greater knowledge about roles and responsibilities of organizations involved in the response, better cultural awareness, and leadership and management skills. Respondents felt that the public health community must improve the timeliness of the response in future outbreaks and strengthen collaboration and coordination between organizations.


Binding, internalization, and processing of bombesin by rat pancreatic acini.
The binding and subsequent fate of 125I-labeled bombesin was studied in rat pancreatic acini. At both 37 degrees C and 4 degrees C binding occurred to a single saturable site, with Kd equal to 1.7 nM. The amount of steady-state tracer binding was reduced at 4 degrees C (5.7%/mg protein) compared with 37 degrees C (8.7%/mg), with a similar relative change in calculated binding capacity. With the use of an acid wash procedure to remove surface bound ligand, 55% of cell-associated 125I-bombesin was internalized in the steady state at 37 degrees C but only 5% at 4 degrees C. Preincubation at 4 degrees C followed by an increase to 37 degrees C led to rapid internalization of bound bombesin, which was blocked by the metabolic inhibitor antimycin. 125I-bombesin was found to be degraded by two acinar systems. One was not related to receptor binding but could be inhibited with bacitracin. The other occurred after internalization and was partially blocked with chloroquine. Thus, after binding, bombesin is internalized, and the degradation products are released from the cell. Exposure to bombesin is also accompanied by a subsequent decrease in cell surface binding (54% after 1 h exposure to 100 nM bombesin), suggesting that the bombesin receptor may also be internalized in a ligand-dependent manner.


Prevention of postdural puncture headache after accidental dural puncture: a quantitative systematic review.
No clear consensus exists on how to best prevent severe headache from occurring after accidental dural puncture. We conducted a quantitative systematic review to identify all available evidence for the prevention of postdural puncture headache (PDPH) and included 17 studies with 1264 patients investigating prophylactic epidural blood patch (PEBP), epidural morphine, intrathecal catheters, and epidural or intrathecal saline. The relative risk (RR) for headache after PEBP was 0.48 [95% confidence interval (CI): 0.23-0.99] in five non-randomized controlled trials (non-RCTs) and 0.32 (0.10-1.03) in four randomized controlled trials (RCTs). The RR for epidural morphine (based on a single RCT) was 0.25 (0.08-0.78). All other interventions were based on non-RCTs and failed statistical significance, including long-term intrathecal catheters with an RR of 0.21 (0.02-2.65). There are a number of promising options to prevent PDPH, yet heterogeneity between the studies and publication bias towards small non-RCTs with positive results limits the available evidence. Thus, a large multicentre RCT is needed to determine the best preventative practices.


Global Sensitivity Estimates for Neural Network Classifiers.
Artificial neural networks (ANNs) have traditionally been seen as black-box models, because, although they are able to find ``hidden'' relations between inputs and outputs with a high approximation capacity, their structure seldom provides any insights on the structure of the functions being approximated. Several research papers have tried to debunk the black-box nature of ANNs, since it limits the potential use of ANNs in many research areas. This paper is framed in this context and proposes a methodology to determine the individual and collective effects of the input variables on the outputs for classification problems based on the ANOVA-functional decomposition. The method is applied after the training phase of the ANN and allows researchers to rank the input variables according to their importance in the variance of the ANN output. The computation of the sensitivity indices for product unit neural networks is straightforward as those indices can be calculated analytically by evaluating the integrals in the ANOVA decomposition. Unfortunately, the sensitivity indices associated with ANNs based on sigmoidal basis functions or radial basis functions cannot be calculated analytically. In this paper, the indices for those kinds of ANNs are proposed to be estimated by the (quasi-) Monte Carlo method.


UROSCAN and UROSCANSEQ: a large-scale multicenter effort towards translation of molecular bladder cancer subtypes into clinical practice - from biobank to RNA-sequencing in real time.
Bladder cancer is molecularly one of the most heterogenous malignancies characterized by equally heterogenous clinical outcomes. Standard morphological assessment with pathology and added immunohistochemical analyses is unable to fully address the heterogeneity, but up to now treatment decisions have been made based on such information only. Bladder cancer molecular subtypes will likely provide means for a more personalized bladder cancer care. To facilitate further development of bladder cancer molecular subtypes and clinical translation, the UROSCAN-biobank was initiated in 2013 to achieve systematic biobanking of preoperative blood and fresh frozen tumor tissue in a population-based setting. In a second phase, we established in 2018 a parallel logistic pipeline for molecular profiling by RNA-sequencing, to develop and validate clinical implementation of molecular subtyping and actionable molecular target identification in real-time. Until June 2021, 1825 individuals were included in the UROSCAN-biobank, of which 1650 (90%) had primary bladder cancer, 127 (7%) recurrent tumors, and 48 (3%) unknown tumor status. In 159 patients, multiple tumors were sampled, and metachronous tumors were collected in 83 patients. Between 2016 and 2020 the UROSCAN-biobanking included 1122/2999 (37%) of all primary bladder cancer patients in the Southern Healthcare Region. Until June 2021, the corresponding numbers subjected to RNA-sequencing and molecular subtyping was 605 (UROSCANSEQ), of which 52 (9%) samples were not sequenced due to inadequate RNA-quality (n = 47) or technical failure/lost sample (n = 5). The UROSCAN-biobanking and UROSCANSEQ-infrastructure for molecular subtyping by real-time RNA-sequencing represents, to our knowledge, the largest effort of evaluating population-wide molecular classification of bladder cancer.


Comparison Between the 2021 USPSTF Lung Cancer Screening Criteria and Other Lung Cancer Screening Criteria for Racial Disparity in Eligibility.
In 2021, the US Preventive Services Task Force (USPSTF) broadened its age and smoking pack-year requirement for lung cancer screening. To compare the 2021 USPSTF lung cancer screening criteria with other lung cancer screening criteria and evaluate whether the sensitivity and specificity of these criteria differ by race. This study included 912 patients with lung cancer and 1457 controls without lung cancer enrolled in an epidemiology study (INHALE [Inflammation, Health, Ancestry, and Lung Epidemiology]) in the Detroit metropolitan area between May 15, 2012, and March 31, 2018. Patients with lung cancer and controls were 21 to 89 years of age; patients with lung cancer who were never smokers and controls who were never smokers were not included in these analyses. Statistical analysis was performed from August 31, 2020, to April 13, 2021. The study assessed whether patients with lung cancer and controls would have qualified for lung cancer screening using the 2013 USPSTF, 2021 USPSTF, and 2012 modification of the model from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCOm2012) screening criteria. Sensitivity was defined as the percentage of patients with lung cancer who qualified for screening, while specificity was defined as the percentage of controls who did not qualify for lung cancer screening. Participants included 912 patients with a lung cancer diagnosis (493 women [54%]; mean [SD] age, 63.7 [9.5] years) and 1457 control participants without lung cancer at enrollment (795 women [55%]; mean [SD] age, 60.4 [9.6] years). With the use of 2021 USPSTF criteria, 590 patients with lung cancer (65%) were eligible for screening compared with 619 patients (68%) per the PLCOm2012 criteria and 445 patients (49%) per the 2013 USPSTF criteria. With the use of 2013 USPSTF criteria, significantly more White patients than African American patients with lung cancer (324 of 625 [52%] vs 121 of 287 [42%]) would have been eligible for screening. This racial disparity was absent when using 2021 USPSTF criteria (408 of 625 [65%] White patients vs 182 of 287 [63%] African American patients) and PLCOm2012 criteria (427 of 625 [68%] White patients vs 192 of 287 [67%] African American patients). The 2013 USPSTF criteria excluded 950 control participants (65%), while the PLCOm2012 criteria excluded 843 control participants (58%), and the 2021 USPSTF criteria excluded 709 control participants (49%). The 2013 USPSTF criteria excluded fewer White control participants than African American control participants (514 of 838 [61%] vs 436 of 619 [70%]). This racial disparity is again absent when using 2021 USPSTF criteria (401 of 838 [48%] White patients vs 308 of 619 [50%] African American patients) and PLCOm2012 guidelines (475 of 838 [57%] White patients vs 368 of 619 [60%] African American patients). This study suggests that the USPSTF 2021 guideline changes improve on earlier, fixed screening criteria for lung cancer, broadening eligibility and reducing the racial disparity in access to screening.


Computed tomography and cross-sectional anatomy of the metatarsus and digits of the one-humped camel (Camelus dromedarius) and buffalo ( Bos bubalis).
The purpose of the present study was to provide a detailed computed tomography (CT) and cross-sectional anatomic reference of the normal metatarsus and digits for the camel and buffalo, as well as to compare between metatarsus and digits in these animals to outstand a basis for diagnosis of their diseases. Advantages, including depiction of detailed cross-sectional anatomy, improved contrast resolution and computer reformatting, make it a potentially valuable diagnostic technique. The hind limbs of 12 healthy adult camel and buffalo were used. Clinically relevant anatomic structures were identified and labelled at each level in the corresponding images (CT and anatomic slices). CT images were used to identify the bony and soft tissue structures of the metatarsus and digits. The knowledge of normal anatomy of the camel and buffalo metatarsus and digits would serve as initial reference to the evaluation of CT images in these species.


Disordered labor: objective evaluation and management.
Simplified techniques for analyzing the graphic patterns of dilatation and descent allow the practitioner to define aberrant labor using objective criteria for diagnosis. Six major disorders of labor are readily characterized. Once diagnosed, details concerning etiologic factors, efficacy of modalities of treatment, and prognostic outlook can be readily evolved. Programs of management are presented for each group of dysfunctional patterns based on such data. Introduction of the graphic analytic technique for diagnosing and managing labor adds a significant new dimension to our diagnostic potential and therapeutic capabilities.


Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains.
Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.


The structure of the ITS2-proximal stem is required for pre-rRNA processing in yeast.
Accurate and efficient processing of pre-rRNA is critical to the accumulation of mature functional ribosomal subunits for maintenance of cell growth. Processing requires numerous factors which act in trans as well as RNA sequence/ structural elements which function in cis. To examine the latter, we have used directed mutagenesis and expression of mutated pre-rRNAs in yeast. Specifically, we tested requirements for formation of an ITS2-proximal stem on processing, a structure formed by an interaction between sequences corresponding to the 3' end of 5.8S rRNA and the 5' end of 25S. Pre-rRNA processing is inhibited in templates encoding mutations that prevent the formation of the ITS2-proximal stem. Compensatory, double mutations, which alter the sequence of this region but restore the structure of the stem, also restore processing, although at lower efficiency. This reduction in efficiency is reflected in decreased levels of mature 5.8S and 25S rRNA and increased levels of 35S pre-rRNA and certain processing intermediates. This phenotype is reminiscent of the biochemical depletion of U8 snoRNA in vertebrates for which the ITS2-proximal stem has been proposed as a potential site for interaction with U8 RNP. Thus, formation of the ITS2-proximal stem may be a requirement common to yeast and vertebrate pre-rRNA processing.


Coherent Spin Control of Single Molecules on a Surface.
Control of single electron spins constitutes one of the most promising platforms for spintronics, quantum sensing, and quantum information processing. Utilizing single molecular magnets as their hosts establishes an interesting framework since their molecular structure is highly flexible and chemistry-based large-scale synthesis directly provides a way toward scalability. Here, we demonstrate coherent spin manipulation of single molecules on a surface, which we control individually using a scanning tunneling microscope in combination with electron spin resonance. We previously found that iron phthalocyanine (FePc) molecules form a spin-1/2 system when placed on an insulating thin film of magnesium oxide (MgO). Performing Rabi oscillation and Hahn echo measurements, we show that the FePc spin can be coherently manipulated with a phase coherence time T2Echo of several hundreds of nanoseconds. Tunneling current-dependent measurements demonstrate that interaction with the tunneling electrons is the dominating source of decoherence. In addition, we perform Hahn echo measurements on small self-assembled arrays of FePc molecules. We show that, despite additional intermolecular magnetic coupling, spin resonance and T2Echo are much less perturbed by T1 spin flip events of neighboring spins than by the tunneling current. This will potentially allow for individual addressable molecular spins in self-assemblies and with application for quantum information processing.


Interpopulation hybridization generates meiotically stable rDNA epigenetic variants in allotetraploid Tragopogon mirus.
Uniparental silencing of 35S rRNA genes (rDNA), known as nucleolar dominance (ND), is common in interspecific hybrids. Allotetraploid Tragopogon mirus composed of Tragopogon dubius (d) and Tragopogon porrifolius (p) genomes shows highly variable ND. To examine the molecular basis of such variation, we studied the genetic and epigenetic features of rDNA homeologs in several lines derived from recently and independently formed natural populations. Inbred lines derived from T. mirus with a dominant d-rDNA homeolog transmitted this expression pattern over generations, which may explain why it is prevalent among natural populations. In contrast, lines derived from the p-rDNA dominant progenitor were meiotically unstable, frequently switching to co-dominance. Interpopulation crosses between progenitors displaying reciprocal ND resulted in d-rDNA dominance, indicating immediate suppression of p-homeologs in F1 hybrids. Original p-rDNA dominance was not restored in later generations, even in those segregants that inherited the corresponding parental rDNA genotype, thus indicating the generation of additional p-rDNA and d-rDNA epigenetic variants. Despite preserved intergenic spacer (IGS) structure, they showed altered cytosine methylation and chromatin condensation patterns, and a correlation between expression, hypomethylation of RNA Pol I promoters and chromatin decondensation was apparent. Reversion of such epigenetic variants occurred rarely, resulting in co-dominance maintained in individuals with distinct genotypes. Generally, interpopulation crosses may generate epialleles that are not present in natural populations, underlying epigenetic dynamics in young allopolyploids. We hypothesize that highly expressed variants with distinct IGS features may induce heritable epigenetic reprogramming of the partner rDNA arrays, harmonizing the expression of thousands of genes in allopolyploids.


Harnessing Hypoxia-Dependent Cyanine Photocages for In Vivo Precision Drug Release.
Photocaging holds promise for the precise manipulation of biological events in space and time. However, current near-infrared (NIR) photocages are oxygen-dependent for their photolysis and lack of timely feedback regulation, which has proven to be the major bottleneck for targeted therapy. Herein, we present a hypoxia-dependent photo-activation mechanism of dialkylamine-substituted cyanine (Cy-NH) accompanied by emissive fragments generation, which was validated with retrosynthesis and spectral analysis. For the first time, we have realized the orthogonal manipulation of this hypoxia-dependent photocaging and dual-modal optical signals in living cells and tumor-bearing mice, making a breakthrough in the direct spatiotemporal control and in vivo feedback regulation. This unique photoactivation mechanism overcomes the limitation of hypoxia, which allows site-specific remote control for targeted therapy, and expands the photo-trigger toolbox for on-demand drug release, especially in a physiological context with dual-mode optical imaging under hypoxia.


Effect of organic amendments obtained from different pretreatment technologies on soil microbial community.
The application of organic amendments (OAs) obtained from biological treatment technologies is a common agricultural practice to increase soil functionality and fertility. OAs and their respective pretreatment processes have been extensively studied. However, comparing the properties of OAs obtained from different pretreatment processes remains challenging. In most cases, the organic residues used to produce OAs exhibit intrinsic variability and differ in origin and composition. In addition, few studies have focused on comparing OAs from different pretreatment processes in the soil microbiome, and the extent to which OAs affect the soil microbial community remains unclear. This limits the design and implementation of effective pretreatments aimed at reusing organic residues and facilitating sustainable agricultural practices. In this study, we used the same model residues to produce OAs to enable meaningful comparisons among compost, digestate, and ferment. These three OAs contained different microbial communities. Compost had higher bacterial but lower fungal alpha diversity than ferment and digestate. Compost-associated microbes were more prevalent in the soil than ferment- and digestate-associated microbes. More than 80% of the bacterial ASVs and fungal OTUs from the compost were detected 3 months after incorporation into the soil. However, the addition of compost had less influence on the resulting soil microbial biomass and community composition than the addition of ferment or digestate. Specific native soil microbes, members from Chloroflexi, Acidobacteria, and Mortierellomycota, were absent after ferment and digestate application. The addition of OAs increased the soil pH, particularly in the compost-amended soil, whereas the addition of digestate enhanced the concentrations of dissolved organic carbon (DOC) and available nutrients (such as ammonium and potassium). These physicochemical variables were key factors that influenced soil microbial communities. This study furthers our understanding of the effective recycling of organic resources for the development of sustainable soils.


Direct G protein gating of ion channels.
Guanine nucleotide binding (G) proteins couple a variety of receptors to ionic channels. Until recently the pathway was thought to be indirect via cytoplasmic second messengers; now the heterotrimeric G proteins are known to act directly on K+ and Ca2+ channels. Here we summarize recent developments concerning this widespread mechanism which we call G protein gating of ion channels. A specific pertussis toxin-sensitive G protein called Gk, purified from human red blood cells, activates a unique K+ channel and Gk, or a similar G protein, couples this channel to muscarinic atrial receptors. The alpha-subunit (alpha k) at less than 10 pM mediates the effects, and alpha k also activates K+ channels directly in neurosecretory cells. The G protein stimulatory to adenylyl cyclase, Gs, gates directly through its alpha-subunit, specific Ca2+ channels in heart and skeletal muscle T tubules. Hence, one G protein can have two distinct effectors.


Intradiscal thermal therapy using interstitial ultrasound: an in vivo investigation in ovine cervical spine.
In vivo investigation of intradiscal ultrasound thermal therapy in ovine cervical spine model. To evaluate the potential of interstitial ultrasound for selective heating of intradiscal tissue in vivo. Application of heat in the spine using resistive wire and radiofrequency current heating devices is currently being used clinically for minimally invasive treatment of discogenic low back pain. Treatment temperatures are representative of those required for thermal necrosis of ingrowing nociceptor nerve fibers and disc cellularity alone, or with coagulation and restructuring of anular collagen in the high temperature case. Two interstitial ultrasound applicator design configurations with directional heating patterns were evaluated in vivo in ovine cervical intervertebral discs (n = 62), with up to 45-day survival periods. Two heating protocols were employed in which the temperature measured 5 mm away from the applicator was controlled to either <54 C (capable of nerve and cellular necrosis) or >70 C (for coagulation of collagen) for a 10-minute treatment period. Transient and steady state temperature maps, calculated thermal doses (t43), and histology were used to assess the thermal treatments. These studies demonstrated the capability to control spatial temperature distributions within selected regions of the in vivo intervertebral disc and anular wall using interstitial ultrasound. Ultrasound energy is capable of penetrating within the highly attenuating disc tissue to produce more extensive radial thermal penetration, lower maximum intradiscal temperature, and shorter treatment times than can be achieved with current clinical intradiscal heating technology. Thus, interstitial ultrasound offers potential as a more precise and faster heating modality for the clinical management of low back pain and studies of thermal effects on disc tissue in animal models.


Assembly and enlargement of the primary cell wall in plants.
Growing plant cells are shaped by an extensible wall that is a complex amalgam of cellulose microfibrils bonded noncovalently to a matrix of hemicelluloses, pectins, and structural proteins. Cellulose is synthesized by complexes in the plasma membrane and is extruded as a self-assembling microfibril, whereas the matrix polymers are secreted by the Golgi apparatus and become integrated into the wall network by poorly understood mechanisms. The growing wall is under high tensile stress from cell turgor and is able to enlarge by a combination of stress relaxation and polymer creep. A pH-dependent mechanism of wall loosening, known as acid growth, is characteristic of growing walls and is mediated by a group of unusual wall proteins called expansins. Expansins appear to disrupt the noncovalent bonding of matrix hemicelluloses to the microfibril, thereby allowing the wall to yield to the mechanical forces generated by cell turgor. Other wall enzymes, such as (1-->4) beta-glucanases and pectinases, may make the wall more responsive to expansin-mediated wall creep whereas pectin methylesterases and peroxidases may alter the wall so as to make it resistant to expansin-mediated creep.


[Net ecosystem CO2 exchange and its environmental regulation mechanisms in a reed wetland in the Yellow River Delta of China during the growth season].
By using eddy covariance technique, this paper measured the net ecosystem CO2 exchange (NEE) in a reed (Phragmites australis) wetland in the Yellow River Delta of China during the growth season of 2011, and investigated the variation patterns of the NEE and related affecting factors. The average diurnal variation of the NEE in different months showed a U-type curve, with the maximum net CO2 uptake rate and release rate being (0.44 +/- 0.03) and (0.16 +/- 0.01) mg CO2 x m(-2) x s(-1), respectively. The NEE, ecosystem respiration (R(eco)), and gross primary productivity (GPP) were all higher in vigorous growth season (from July to September) and lower in early growth season (from May to June) and late growth season (from October to November). Both R(eco) and NEE reached their maximum values in August, while GPP reached its peak value in July. During the growth season, the ecosystem CO2 exchange was mainly dominated by photosynthetic active radiation (PAR), soil temperature (T(s)), and soil water content (SWC). There was a rectangular hyperbolic relationship between the daytime NEE and PAR. The nighttime ecosystem respiration (R(eco,n)) was exponentially correlated with the T(s) at 5 cm depth, and the temperature sensitivity of the ecosystem respiration (Q10) was 2.30. SWC and T(s) were the main factors affecting the R(eco,n). During the entire growth season, the reed wetland ecosystem in the Yellow River delta was an obvious carbon sink, with the total net carbon sequestration being 780.95 g CO2 x m(-2).


Social anxiety disorder and the risk of depression: a prospective community study of adolescents and young adults.
Social anxiety disorder (SAD) (also known as "social phobia") is frequently comorbid with major depression, and in such cases, almost always precedes it. This has led to interest in SAD as a possible modifier of the risk and/or course of mood disorders. Data come from a prospective, longitudinal epidemiologic study of adolescents and young adults (aged 14-24 years) in Munich, Germany. Respondent diagnoses (N = 2548) at baseline and follow-up (34-50 months later) are considered. The influence of SAD at baseline on the risk, course, and characteristics of depressive disorders (ie, major depression or dysthymia) at follow-up is examined. The baseline prevalence of SAD was 7.2% (95% confidence interval [CI], 6.1%-8.4%). Social anxiety disorder in nondepressed persons at baseline was associated with an increased likelihood (odds ratio [OR] = 3.5; 95% CI, 2.0-6.0) of depressive disorder onset during the follow-up period. Furthermore, comorbid SAD and depressive disorder at baseline was associated with a worse prognosis (compared with depressive disorder without comorbid SAD at baseline). This is exemplified by the greater likelihood of depressive disorder persistence or recurrence (OR = 2.3; 95% CI, 1.2-4.6) and attempted suicide (OR = 6.1; 95% CI, 1.2-32.2). Social anxiety disorder during adolescence or young adulthood is an important predictor of subsequent depressive disorders. Moreover, the presence of comorbid SAD in adolescents who are already depressed is associated with a more malignant course and character of subsequent depressive illness. These findings may inform targeted intervention efforts.


A comparison of the performance of samplers for respirable dust in workplaces and laboratory analysis for respirable quartz.
The divergent sampling techniques for respirable dust and the analyses for crystalline silica are an important area of interest and discussion among industrial occupational hygienists in Europe. The variety of equipment for air sampling, methods and instrumentation can cause differences between results for the analysis of respirable crystalline silica (RCS). In this study, a Workplace Atmosphere Multi-sampler (WAM), developed by Adhesia, was used to compare respirable dust samplers in the workplace. This rotating device enables the comparison of 12 samplers in a workplace in each run. Seven laboratories participated in the comparison, using six different respirable dust samplers [British Cast Iron Research Association (BCIRA) to the Higgins Dewell (HD) design, Dorr Oliver, Casella SIMPEDS, SKC HD with a polycarbonate filter and polyvinylchloride filter, and the CIP10-R). Each laboratory analysed samples supplied by the samplers and reported the total respirable dust concentration and the RCS concentration. The techniques used were X-ray diffraction direct-on-filter, X-ray diffraction with deposition, infrared direct-on-filter, and infrared with potassium bromide (KBr) discs. The experiments were carried out in four different industries (enamel, sand extraction, foundry and brickworks). Generally, the SKC conductive black plastic sampler is oversampled (y = 1.52x + 0.008) and the CIP10 is undersampled (y = 0.74x + 0.068) when compared with the median air concentration. A pair-wise comparison of the different industries using t-tests indicated significant differences (P < 0.05) between the SKC conductive plastic samplers and the other samplers. The same series of statistical calculations were performed for the results obtained for RCS (quartz) and showed significant differences for the CIP10 techniques and the SKC conductive plastic cyclone analyses when using a polyvinylchloride filter.


Cell-cell signalling promotes ferric iron uptake in Xanthomonas oryzae pv. oryzicola that contribute to its virulence and growth inside rice.
Cell-cell communication mediated by diffusible signal factor (DSF) plays an important role in virulence of several Xanthomonas group of plant pathogens. In the bacterial pathogen of rice, Xanthomonas oryzae pv. oryzicola, DSF is required for virulence and in planta growth. In order to understand the role of DSF in promoting in planta growth and virulence, we have characterized the DSF deficient mutant of X. oryzae pv. oryzicola. Mutant analysis by expression analysis, radiolabelled iron uptake studies and growth under low-iron conditions indicated that DSF positively regulates ferric iron uptake. Further, the DSF deficient mutant of X. oryzae pv. oryzicola exhibited a reduced capacity to use ferric form of iron for growth under low-iron conditions. Exogenous iron supplementation in the rice leaves rescued the in planta growth deficiency of the DSF deficient mutant. These data suggest that DSF promotes in planta growth of X. oryzae pv. oryzicola by positively regulating functions involved in ferric iron uptake which is important for its virulence. Our results also indicate that requirement of iron uptake strategies to utilize either Fe(3+) or Fe(2+) form of iron for colonization may vary substantially among closely related members of the Xanthomonas group of plant pathogens.


A domain evolution model for hysteresis in piezoceramic materials.
In this paper, we use a circular distribution to quantify certain domain properties and model the hysteresis behavior of piezoceramic materials. The model is constructed by bridging the characteristics of microscopic domain distribution into the macroscopic (or bulk) behavior. Contributions, other than those associated with the polarization of domains, to bulk quantities are also counted. A domain orientation distribution function is first selected and the corresponding distribution function parameters are chosen as the internal state variables. For the two-dimensional model, a von Mises-Fisher circular distribution is used. Instead of micromechanical analysis of domain motions that would involve large computation efforts, the delineation of domain evolution is simplified by considering the evolution of the domain orientation distribution, which is determined by the dynamic variations of the internal state variables. We also develop a procedure to identify the material constants introduced in the constitutive equations. The models are used to quantitatively characterize various hysteresis loops observed in piezoceramic materials.


Phase conversion from graphite toward a simple monoclinic sp3-carbon allotrope.
We identify by ab initio calculations a simple monoclinic carbon in P2/m (C(2h)(1)) symmetry with an alternating zigzag and armchair buckling of the carbon sheets in AA stacking, which is formed via a distinct one-layer by one-layer conversion mechanism along the [210] direction assisted by a large lattice distortion. It is dynamically stable and energetically favorable as well as recently identified orthorhombic W- and monoclinic M-carbon. Moreover, this new phase has a wider band gap than diamond's, and is compatible with the experimental x-ray diffraction data. These results broaden our understanding of the direct graphite-to-diamond phase transition.


Interference Management with Reflective In-Band Full-Duplex NOMA for Secure 6G Wireless Communication Systems.
The electromagnetic spectrum is used as a medium for modern wireless communication. Most of the spectrum is being utilized by the existing communication system. For technological breakthroughs and fulfilling the demands of better utilization of such natural resources, a novel Reflective In-Band Full-Duplex (R-IBFD) cooperative communication scheme is proposed in this article that involves Full-Duplex (FD) and Non-Orthogonal Multiple Access (NOMA) technologies. The proposed R-IBFD provides efficient use of spectrum with better system parameters including Secrecy Outage Probability (SOP), throughput, data rate and secrecy capacity to fulfil the requirements of a smart city for 6th Generation (6thG or 6G). The proposed system targets the requirement of new algorithms that contribute towards better change and bring the technological revolution in the requirements of 6G. In this article, the proposed R-IBFD mainly contributes towards co-channel interference and security problem. The In-Band Full-Duplex mode devices face higher co-channel interference in between their own transmission and receiving antenna. R-IBFD minimizes the effect of such interference and assists in the security of a required wireless communication system. For a better understanding of the system contribution, the improvement of secrecy capacity and interference with R-IBFD is discussed with the help of SOP derivation, equations and simulation results. A machine learning genetic algorithm is one of the optimization tools which is being used to maximize the secrecy capacity.


DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury.
Injury to retinal ganglion cell (RGC) axons triggers rapid activation of Jun N-terminal kinase (JNK) signaling, a major prodeath pathway in injured RGCs. Of the multiple kinases that can activate JNK, dual leucine kinase (Dlk) is known to regulate both apoptosis and Wallerian degeneration triggered by axonal insult. Here we tested the importance of Dlk in regulating somal and axonal degeneration of RGCs following axonal injury. Removal of DLK from the developing optic cup did not grossly affect developmental RGC death or inner plexiform layer organization. In the adult, Dlk deficiency significantly delayed axonal-injury induced RGC death. The activation of JUN was also attenuated in Dlk deficient retinas. Dlk deficiency attenuated the activation of the somal pool of JNK but did not prevent activation of the axonal pool of JNK after axonal injury, indicating that JNK activation in different cellular compartments of an RGC following axonal injury is regulated by distinct upstream kinases. In contrast to its robust influence on somal degeneration, Dlk deficiency did not alter RGC axonal degeneration after axonal injury as assessed using physiological readouts of optic nerve function.


Human herpesvirus-6 viral load and antibody titer in serum samples of patients with multiple sclerosis.
Despite the number of cases with definite diagnosis of multiple sclerosis (MS) being on increase, the role of human herpesvirus-6 (HHV-6) infection as a trigger for MS disease still is deliberated. Based on antibody detection and quantitative HHV-6 polymerase chain reaction assay, this study was achieved to find out the possible association between infection with HHV-6 and clinical progression of MS disease. A total of 108 serum samples were obtained from 30 MS patients followed prospectively for a 6-month period. These samples were analyzed for the presence of HHV-6 DNA by nested polymerase chain reaction enzyme-linked immunosorbent assay and for anti-HHV-6 IgG titer. Activation of the disease was determined by either magnetic resonance imaging or by clinical status of the patients. Control groups were also included. The average antibody index for the MS patients in the first sample collection was higher than both control groups (p = 0.001). HHV-6 DNA was detected in the serum samples of 10 of 30 MS patients. The mean HHV-6 viral load in patients with relapsing-remitting multiple sclerosis (RRMS) with and without relapse was 973 and 714, respectively. Seven patients showed an exacerbation during the study period. Of those, four patients had HHV-6 DNA in their collected samples. The prevalence of HHV-6 DNA was significantly higher in patients with MS as compared with control groups (p = 0.001). The results indicate that HHV-6 is implicated somehow in MS disease. Over time, rising HHV-6 IgG antibody titers together with an exacerbation and detection of HHV-6 DNA in serum samples of some MS patients suggests possible association between the reactivation of the virus and disease progression.


Hypocretin/orexin disturbances in neurological disorders.
The hypothalamic hypocretin (orexin) system plays a crucial role in the regulation of sleep and wakefulness. The strongest evidence for this is the fact that the primary sleep disorder narcolepsy is caused by disrupted hypocretin signaling in humans as well as various animal models. There is a growing interest in the role of hypocretin defects not only in the pathophysiology of other sleep disorders, but also in neurological diseases with associated sleep symptomatology. In this paper we first review the current methods to measure the integrity of the hypocretin system in human patients. The most widely used technique entails the measurement of hypocretin-1 in lumbar cerebrospinal fluid. In addition, hypocretin levels can be measured in ventricular cerebrospinal fluid and brain tissue extract. Finally, in post-mortem hypothalamic material, the number of hypocretin neurons can be precisely quantified. In the second part of this paper we describe the various neurological disorders in which hypocretin defects have been reported. These include neurodegenerative, neuromuscular and immune-mediated diseases, as well as traumatic brain injury. We conclude with a discussion of the functional relevance of partial hypocretin defects, and the various pathophysiological mechanisms that can lead to such defects.


Pannexin 3 regulates intracellular ATP/cAMP levels and promotes chondrocyte differentiation.
Pannexin 3 (Panx3) is a new member of the gap junction pannexin family, but its expression profiles and physiological function are not yet clear. We demonstrate in this study that Panx3 is expressed in cartilage and regulates chondrocyte proliferation and differentiation. Panx3 mRNA was expressed in the prehypertrophic zone in the developing growth plate and was induced during the differentiation of chondrogenic ATDC5 and N1511 cells. Panx3-transfected ATDC5 and N1511 cells promoted chondrogenic differentiation, but the suppression of endogenous Panx3 inhibited differentiation of ATDC5 cells and primary chondrocytes. Panx3-transfected ATDC5 cells reduced parathyroid hormone-induced cell proliferation and promoted the release of ATP into the extracellular space, possibly by action of Panx3 as a hemichannel. Panx3 expression in ATDC5 cells reduced intracellular cAMP levels and the activation of cAMP-response element-binding, a protein kinase A downstream effector. These Panx3 activities were blocked by anti-Panx3 antibody. Our results suggest that Panx3 functions to switch the chondrocyte cell fate from proliferation to differentiation by regulating the intracellular ATP/cAMP levels.


Genes required for replication of the 15.5-kilobase RNA genome of a plant closterovirus.
A full-length cDNA clone of beet yellows closterovirus (BYV) was engineered and used to map functions involved in the replication of the viral RNA genome and subgenomic RNA formation. Among 10 open reading frames (ORFs) present in BYV, ORFs 1a and 1b suffice for RNA replication and transcription. The proteins encoded in these ORFs harbor putative methyltransferase, RNA helicase, and RNA polymerase domains common to Sindbis virus-like viruses and a large interdomain region that is unique to closteroviruses. The papain-like leader proteinase (L-Pro) encoded in the 5'-proximal region of ORF 1a was found to have a dual function in genome amplification. First, the autocatalytic cleavage between L-Pro and the remainder of the ORF 1a product was essential for replication of RNA. Second, an additional L-Pro function that was separable from proteolytic activity was required for efficient RNA accumulation. The deletion of a large, approximately 5.6-kb, 3'-terminal region coding for a 6-kDa hydrophobic protein, an HSP70 homolog, a 64-kDa protein, minor and major capsid proteins, a 20-kDa protein, and a 21-kDa protein (p21) resulted in replication-competent RNA. However, examination of mutants with replacements of start codons in each of these seven 3'-terminal ORFs revealed that p21 functions as an enhancer of genome amplification. The intriguing analogies between the genome organization and replicational requirements of plant closteroviruses and animal coronavirus-like viruses are discussed.


Studying enzyme binding specificity in acetylcholinesterase using a combined molecular dynamics and multiple docking approach.
A combined molecular dynamics simulation and multiple ligand docking approach is applied to study the binding specificity of acetylcholinesterase (AChE) with its natural substrate acetylcholine (ACh), a family of substrate analogues, and choline. Calculated docking energies are well correlated to experimental k(cat)/K(M) values, as well as to experimental binding affinities of a related series of TMTFA inhibitors. The "esteratic" and "anionic" subsites are found to act together to achieve substrate binding specificity. We find that the presence of ACh in the active site of AChE not only stabilizes the setup of the catalytic triad but also tightens both subsites to achieve better binding. The docking energy gained from this induced fit is 0.7 kcal/mol for ACh. For the binding of the substrate tailgroup to the anionic subsite, both the size and the positive charge of the tailgroup are important. The removal of the positive charge leads to a weaker binding of 1 kcal/mol loss in docking energy. Substituting each tail methyl group with hydrogen results in both an incremental loss in docking energy and also a decrease in the percentage of structures docked in the active site correctly set up for catalysis.


The effects of cAMP on differentiation of cultured Schwann cells: progression from an early phenotype (04+) to a myelin phenotype (P0+, GFAP-, N-CAM-, NGF-receptor-) depends on growth inhibition.
The present experiments were designed to clarify the relationship between cAMP elevation, proliferation and differentiation in Schwann cells. They were carried out on short-term cultures of cells obtained from neonatal rat sciatic nerves. It was found that the myelin-related phenotype was expressed in response to agents that elevate or mimic intracellular cAMP (forskolin, cholera toxin, cAMP analogues), provided cell division was absent. This phenotype included upregulation of the major myelin protein P0 and downregulation of GFAP, N-CAM, A5E3, and NGF receptor. In contrast, when cells were cultured in conditions where cell division occurred, elevation of intracellular cAMP produced an alternative response, characterized by DNA synthesis and absence of myelin-related differentiation. The cAMP mediated induction of an early Schwann cell antigen, 04, followed a different pattern since it was induced equally in dividing and nondividing cells. These observations are consistent with the proposal that during development of the rat sciatic nerve: (a) cAMP elevation, possibly induced by axon-associated factors, is a primary signal responsible for the induction of 04 expression in proliferating Schwann cells during the premyelination period; (b) subsequent withdrawal of cells associated with the larger axons from the cell cycle acts as a permissive secondary signal for induction of myelination, since in quiescent cells the ongoing cAMP elevation will trigger myelination.


Viral and host factors that contribute to pathogenicity of enterovirus 71.
The single-stranded RNA virus enterovirus 71 (EV71), which belongs to the Picornaviridae family, has caused epidemics worldwide, particularly in the Asia-Pacific region. Most EV71 infections result in mild clinical symptoms, including herpangina and hand, foot and mouth disease. However, serious pathological complications have also been reported, especially for young children. The mechanisms of EV71 disease progression remain unclear. The pathogenesis of adverse clinical outcomes may relate to many factors, including cell tropism, cell death and host immune responses. This article reviews the recent advances in the identification of factors determining EV71 cell tropism, the associated mechanisms of viral infection-induced cell death and the interplay between EV71 and immunity.


Targeted overexpression of vav3 oncogene in prostatic epithelium induces nonbacterial prostatitis and prostate cancer.
Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor (AR), and stimulates growth in prostate cancer cells. The purpose of this study is to further determine the potential role of Vav3 in prostate cancer development in genetically engineered mouse model. We generated Vav3 transgenic mice by targeted overexpression of a constitutive active Vav3 in the prostatic epithelium. We found that overexpression of Vav3 led to development of mouse prostatic intraepithelial neoplasia and prostate cancer at the age of as early as 3 months. The AR signaling axis and phosphatidylinositol 3-kinase-Akt signaling were elevated in the prostate glands of Vav3 transgenic mice. In addition to prostate cancer, Vav3 transgenic mice developed significant nonbacterial chronic prostatitis in the prostate gland with notable infiltration of lymphomononuclear cells (monocytes, lymphocytes, and plasma cells), which was associated with elevated incidence of prostate cancer. DNA microarray and signaling pathway analysis revealed that the top diseases and disorders were inflammatory diseases and cancer of the prostate gland in Vav3 transgenic mice. In vitro analysis showed that overexpression of Vav3 in prostate cancer cells enhanced nuclear factor-kappaB (NF-kappaB) activity, implicating an underlying mechanism of innate inflammatory response induced by elevated Vav3 activity. These data showed that Vav3 overexpression in the prostate epithelium enhanced both the AR signaling axis and NF-kappaB-mediated pathway, which potentially contributed to the development of nonbacterial prostatitis and prostate cancer.


Estimating the effectiveness of national health insurance in covering catastrophic health expenditure: Evidence from South Korea.
The catastrophic health expenditure (CHE) indicator has been used to measure the medical cost burden of households. Many countries have institutionalized their health insurance systems to reduce out-of-pocket payments, the main contributor to the financial burden. However, there is no method to estimate how the insurance coverage reduces the CHE. This study proposes an approach to evaluate the effectiveness of insurance in reducing the CHE impacts in terms of incidence and gap, which are based on a modified calculation method of CHE. Additionally, we apply these methods to data from the Korea Health Panel Survey (2011-2016). The results are as follows. First, under the setting of a threshold of 10%, the CHE incidence rate was 19.26% when the Korean national health insurance benefits reduced the CHE's incidence for 15.17% of the population in 2017. Second, the results of the concentration index of CHE showed that the intensity approach of CHE is better than the incidence approach. Third, the new approach we applied revealed that health insurance reduces the burden of CHE to some degree, although it was not an efficient way to reduce CHE. In conclusion, this study provides new policy approaches to save the finances of national health insurance and reduce the intensity of CHE at the same time by raising the low-cost burden of medical services and lowering that of high cost. Moreover, we suggest that policymakers should focus on income level of the households rather than specific diseases.


Dynamics of inherently bounded histone modification domains.
A central goal of chromatin biology is to reveal how posttranslational histone marks modulate gene expression; however, relatively little is known about the spatial or temporal dynamics of these marks. We previously showed that a dynamic model of histone mark nucleation, propagation, and turnover fits the mean enrichment profiles from 99% of noncentromeric histone H3 lysine 9 trimethylation (H3K9me3) domains in mouse embryonic stem cells without the need for boundary or insulator elements. Here we report the full details of this "inherently bounded" model of histone modification dynamics and describe several dynamic features of the model using H3K9me3 as a paradigm. By analyzing the kinetic and structural constraints that drive formation of inherently bounded domains, we find that such domains are optimized when the rates of marking and turnover are comparable. Additionally, we find that to establish such domains, propagation of the histone marks must occur primarily through local contacts.


Beyond critical care: appearance-related afflictions.
There is no reason to believe that humans will not continue in their never-ending quest for self-fulfillment, for in it mankind carries forward the purpose of life itself. Through the art and science of aesthetics, specialists throughout the various health professions are cooperating to help individuals from all socio-economic backgrounds overcome appearance-related afflictions and improve the quality of life. (Figure 10).


Effect of different head-neck positions on physical and psychological stress parameters in the ridden horse.
Different head-neck positions (HNPs) are used in equestrian sports and are regarded as desirable for training and competition by riders, judges and trainers. Even though some studies have been indicative of hyperflexion having negative effects on horses, this unnatural position is frequently used. In the present study, the influence of different HNPs on physical and psychological stress parameters in the ridden horse was investigated. Heart rate (HR), heart rate variability (HRV) and blood cortisol levels were measured in 18 horses. Low frequency (LF) and high frequency (HF) are power components in the frequency domain measurement of HRV which show the activity of the sympathetic and parasympathetic nervous system. Values were recorded at rest, while riding with a working HNP and while riding with hyperflexion of the horse's head, neck and poll. In addition, rideability and behaviour during the different investigation stages were evaluated by the rider and by an observer. Neither the HR nor the HRV showed a significant difference between working HNP (HR = 105 ± 22/min; LF/HF = 3.89 ± 5.68; LF = 37.28 ± 10.77%) and hyperflexion (HR = 110 ± 18; LF/HF = 1.94 ± 2.21; LF = 38.39 ± 13.01%). Blood cortisol levels revealed a significant increase comparing working HNP (158 ± 60 nm) and hyperflexion (176 ± 64 nm, p = 0.01). The evaluation of rider and observer resulted in clear changes of rideability and behavioural changes for the worse in all parameters collected between a working HNP and hyperflexion. In conclusion, changes of the cortisol blood level as a physical parameter led to the assumption that hyperflexion of head, neck and poll effects a stress reaction in the horse, and observation of the behaviour illustrates adverse effects on the well-being of horses during hyperflexion.


Sex and the single transplanted kidney.
Substantial ischemia-reperfusion injury (IRI) to the transplanted kidney occurs in 30% to 50% of transplantation patients who receive the organ from a deceased donor. IRI usually manifests as delayed graft function (DGF) and, in severe cases, results in primary nonfunction. Previous studies, primarily experimental, have demonstrated sex-specific susceptibility to IRI in kidney and other organs. In this issue of the JCI, Aufhauser Jr., Wang, and colleagues further demonstrate the importance of donor and recipient sex in IRI and elucidate the role of estrogen receptors in a murine model. Furthermore, analysis of data from 46,691 renal transplant patients in the United Network for Organ Sharing (UNOS) database revealed that sex affects DGF outcomes in humans. Manipulation of sex-driven molecular pathways offers a fertile opportunity to increase the number of organs available for transplantation and to reduce IRI in kidney and, likely, other organs.


Could the Recent Zika Epidemic Have Been Predicted?
Given knowledge at the time, the recent 2015-2016 zika virus (ZIKV) epidemic probably could not have been predicted. Without the prior knowledge of ZIKV being already present in South America, and given the lack of understanding of key epidemiologic processes and long-term records of ZIKV cases in the continent, the best related prediction could be carried out for the potential risk of a generic Aedes-borne disease epidemic. Here we use a recently published two-vector basic reproduction number model to assess the predictability of the conditions conducive to epidemics of diseases like zika, chikungunya, or dengue, transmitted by the independent or concurrent presence of Aedes aegypti and Aedes albopictus. We compare the potential risk of transmission forcing the model with the observed climate and with state-of-the-art operational forecasts from the North American Multi Model Ensemble (NMME), finding that the predictive skill of this new seasonal forecast system is highest for multiple countries in Latin America and the Caribbean during the December-February and March-May seasons, and slightly lower-but still of potential use to decision-makers-for the rest of the year. In particular, we find that above-normal suitable conditions for the occurrence of the zika epidemic at the beginning of 2015 could have been successfully predicted at least 1 month in advance for several zika hotspots, and in particular for Northeast Brazil: the heart of the epidemic. Nonetheless, the initiation and spread of an epidemic depends on the effect of multiple factors beyond climate conditions, and thus this type of approach must be considered as a guide and not as a formal predictive tool of vector-borne epidemics.


alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetylcholine receptors.
We have isolated and characterized alpha-conotoxin EpI, a novel sulfated peptide from the venom of the molluscivorous snail, Conus episcopatus. The peptide was classified as an alpha-conotoxin based on sequence, disulfide connectivity, and pharmacological target. EpI has homology to sequences of previously described alpha-conotoxins, particularly PnIA, PnIB, and ImI. However, EpI differs from previously reported conotoxins in that it has a sulfotyrosine residue, identified by amino acid analysis and mass spectrometry. Native EpI was shown to coelute with synthetic EpI. The peptide sequence is consistent with most, but not all, recognized criteria for predicting tyrosine sulfation sites in proteins and peptides. The activities of synthetic EpI and its unsulfated analogue [Tyr15]EpI were similar. Both peptides caused competitive inhibition of nicotine action on bovine adrenal chromaffin cells (neuronal nicotinic ACh receptors) but had no effect on the rat phrenic nerve-diaphragm (muscle nicotinic ACh receptors). Both EpI and [Tyr15]EpI partly inhibited acetylcholine-evoked currents in isolated parasympathetic neurons of rat intracardiac ganglia. These results indicate that EpI and [Tyr15]EpI selectively inhibit alpha3beta2 and alpha3 beta4 nicotinic acetylcholine receptors.


Efficient and selective catalysis for hydrogenation and hydrosilation of alkenes and alkynes with PNP complexes of scandium and yttrium.
Scandium and yttrium congeneric complexes, supported by a monoanionic PNP ligand, were studied as catalysts for alkene hydrogenation and hydrosilation, and alkyne semihydrogenation and semihydrosilation. The yttrium congener was found to be much more active in all cases, but this greater activity is accompanied by more rapid catalyst decomposition and therefore higher total yields for some of the reactions with the scandium catalyst. Calculations indicate that the reactions may proceed via σ-bond metathesis of the alkyl complexes to form metal hydride intermediates into which alkenes/alkynes insert.


Availability of Emergency Department Wait Times Information: A Patient-Centered Needs Assessment.
Many Emergency Departments (ED) publish wait times; however, the patient perspective in what information is requested and the quantity of information to post is limited. We conducted a mixed-methods study at a tertiary care academic center. First, we conducted focus groups of 7 patients. We then generated themes following content analysis to create a patient survey. We administered in-person surveys to patients in ED waiting rooms at sites randomized for survey administration. We used preassigned shifts utilized for even patient perspective representation of the 24 hours-a-day/7 days-a-week service. We included waiting room patients over 18 years of age and excluded patients directly referred to a specialty service or who did not speak French or English. We analyzed survey data using descriptive statistics. We identified nine dominant focus group themes: wait time definition, wait time notification, communication, education, patient expectations, utilization of the ED, patient behaviour, physical comfort, and patient empowerment. Of the 240 patient questionnaires administered, 81.3% of respondents wanted to know ED wait times before hospital arrival hospital and 90.8% wanted ED wait times posted in the waiting room. Website (46.7%) was the most popular choice for publishing wait times outside the ED. Within the ED, patients had no preference regarding display modality, if times were displayed (39.6%). Overall, 76.7% stated that their satisfaction with the ED would be improved if wait times were posted. ED patients strongly supported having access to wait time information. Patients believed having wait time information will have a positive impact on their overall ED satisfaction.


Clinical outcome in testicular sex cord stromal tumors: testis sparing vs. radical orchiectomy and management of advanced disease.
To assess the clinical outcome of testicular sex cord stromal tumors (TSCST) according to management and stage. Clinical and pathologic features, stage, and treatment of patients with TSCST were retrieved from our database. The Kaplan-Meier method estimated the relapse-free survival and cancer-specific survival. We identified 67 patients between December 1982 and January 2013: 55 patients (82.1%) had a Leydig cell tumor and 11 patients (16.4%) had a Sertoli cell tumor. Four patients (5.9%) presented with gynecomastia. Forty-eight patients (71.6%) had no pathologic risk factor, and patients 3 had ≥3 risk factors. Testis-sparing surgery was performed in 31 patients (46.3%) and orchiectomy in 36 patients (53.7%). The median tumor diameter was 0.7 cm (interquartile range, 0.6-1.3) and 1.5 cm (interquartile range, 0.9-2.6) in the 2 groups, respectively (P, .007 at Mann-Whitney rank-sum test). The 5-year relapse-free survival was 89.4% (95% confidence interval, 75.9%-95.5%) and cancer-specific survival was 90.3% (95% confidence interval, 72.7%-96.7%), respectively. Metastases were documented in 8 patients (11.9%), 5 relapsing after a median follow-up of 37.4 months. All 3 patients with ≥3 risk factors had metastatic disease. Four of 5 patients with retroperitoneal metastases only were cured by retroperitoneal lymph node dissection (3 patients at presentation and 1 during follow-up); 4 patients undergoing chemotherapy progressed and ultimately died of disease. Most of the patients with TSCST had a favorable prognosis. Testis-sparing surgery may be feasible and effective in case of small tumors. Few patients had metastatic spread, but only those with nodal metastases may benefit from an early retroperitoneal lymph node dissection. Risk factors associate with disease behavior, but indications to prophylactic intervention remain controversial.


Effects of taekwondo intervention on cognitive function and academic self-efficacy in children.
[Purpose] The purpose of this study was to investigate the effects of taekwondo training on cognitive function and academic self-efficacy in children. [Subjects and Methods] Thirty-five children participated in the study. Seventeen children were randomly selected to undergo taekwondo training for 16 weeks (5 times per week). As controls, 18 children received no training. Cognitive function and academic self-efficacy were measured using the Stroop Color and Word Test (Word, Color, and Color-Word) and academic self-efficacy scale (Self-confidence, Self-regulatory Efficacy, and Task Difficulty Preference), respectively. [Results] In the taekwondo group, the Color-Word and Self-confidence scores increased significantly after intervention as compared to those before intervention. [Conclusion] It is suggested that regular taekwondo training may be effective for enhancing cognitive function and academic self-efficacy in growing children.


Galleria mellonella larvae exhibit a weight-dependent lethal median dose when infected with methicillin-resistant Staphylococcus aureus.
Galleria mellonella is a recognised model to study antimicrobial efficacy; however, standardisation across the scientific field and investigations of methodological components are needed. Here, we investigate the impact of weight on mortality following infection with Methicillin-resistant Staphylococcus aureus (MRSA). Larvae were separated into six weight groups (180-300 mg at 20 mg intervals) and infected with a range of doses of MRSA to determine the 50% lethal dose (LD50), and the 'lipid weight' of larvae post-infection was quantified. A model of LD50 values correlated with weight was developed. The LD50 values, as estimated by our model, were further tested in vivo to prove our model. We establish a weight-dependent LD50 in larvae against MRSA and demonstrate that G. mellonella is a stable model within 180-260 mg. We present multiple linear models correlating weight with: LD50, lipid weight, and larval length. We demonstrate that the lipid weight is reduced as a result of MRSA infection, identifying a potentially new measure in which to understand the immune response. Finally, we demonstrate that larval length can be a reasonable proxy for weight. Refining the methodologies in which to handle and design experiments involving G. mellonella, we can improve the reliability of this powerful model.


Translational research in pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011.
The high mortality rate of pancreatic cancer places this uncommon malignancy quite high as a cause of cancer related deaths. Compared to other solid tumors, there is a lag in the development of new effective drugs and the actual clinical benefit remains poor over the last decade or so. The lack of therapeutic options necessitates the invention of the important molecules playing role in pancreatic carcinogenesis and the development of specific targeted therapies. Treatment advances have to be proven first in the bench before applying them at the bedside, thus why translational research is so needed. At the 2011 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, preclinical evidence was presented regarding the efficacy of C4 compound against focal adhesion kinase (FAK) (Abstract #214), the role of the cyclooxygenase-2 (COX-2) inhibitor apricoxib in enhancing the efficacy of gemcitabine and erlotinib (Abstract #227) and the role of curcumin and ABT-888 (a poly-ADP ribose polymerase (PARP) inhibitor) as potent radiosensitizers (Abstracts #222 and #203). Interestingly, the invention of a novel monoclonal antibody (ensituximab) against the mucin epitope NPC-1C in pancreatic and colon cancer cell lines exhibited notable antibody-dependent cellular cytotoxicity (Abstract #235). Finally, enhanced selective targeting of pancreatic tumors was achieved by combining antibody-drug conjugates (ADC) with radioimmunotherapy (Abstract #206).


Use of nasometry as a diagnostic tool for identifying patients with velopharyngeal impairment.
A series of 117 patients were studied in an attempt to determine the extent to which acoustic assessments of speech made with a Kay Elemetrics Nasometer corresponded with aerodynamic estimates of velopharyngeal area and clinical judgments of hypernasality. Nasometer data were obtained while patients read or repeated a standardized passage with no nasal consonants. Pressure-flow data were obtained from 96 of these patients during repeated productions of the word "papa." Listener judgments were made in a clinical setting by the senior author using a 6-point equal-appearing interval scale. Nasometer and pressure-flow results were not known to the senior author when making listener assessments. With a cutoff nasalance score of 32, the sensitivity of Nasometer ratings in correctly identifying the presence or absence of velopharyngeal areas in excess of 0.10 cm2 was 0.78 and 0.79, respectively. The sensitivity and specificity of nasometry in correctly identifying subjects with more than mild hypernasality in their speech was 0.89 while the specificity was 0.95. The results suggest that the Nasometer is an appropriate instrument that can be of value in assessing patients suspected of having velopharyngeal impairment.


Does writing handedness affect neural representation of symbolic number? An fMRI adaptation study.
A key question in the field of numerical cognition is how the human brain represents numerical symbols (e.g., Arabic digits). A large body of research has implicated left parietal regions in symbolic number processing. One possible explanation for this lateralization of neural activity is the handedness of participants. Specifically, participants in neuroimaging research are almost exclusively right-handed. The current study sought to probe whether number representation in the brain is associated with hand preference for handwriting. To address this question, we used functional Magnetic Resonance Imaging (fMRI) to compare brain activation of a group of right-handed participants with a group of left-handed participants during the passive viewing of symbolic numbers. At the whole-brain level, the right-handers demonstrated a previously obtained left-lateralized effect within the intraparietal sulcus (IPS). The left-handers showed some evidence of reverse lateralization of this effect in the IPS. However, when the groups were statistically compared, we found no regions that demonstrated group-level differences. In a follow-up region of interest (ROI) analysis within the left and right parietal lobes, we calculated laterality indices for each participant. Results did not provide support for group differences in laterality within the right or left IPS ROI. These findings do not support the hypothesis that handwriting plays a role in the lateralization of symbolic number processing in the brain. Further research is needed to better understand the factors that lead to left-lateralization for symbolic number processing.


Melatonin and tryptophan affect the activity-rest rhythm, core and peripheral temperatures, and interleukin levels in the ringdove: changes with age.
Aging is known to alter the circadian rhythms of melatonin, serotonin, thermoregulatory responses, cytokine production, and sleep/wakefulness which affect sleep quality. We tested the possible palliative effects of a 3-day administration of melatonin (0.25 or 2.5 mg/kg of body weight [b.w.] to young and old ringdoves, respectively) or tryptophan (300 mg/kg of b.w. to old ringdoves) on these rhythms. Doves are a monophasic, diurnal species; these characteristics are similar in humans. Old animals presented lower melatonin and serotonin levels; higher interleukin (IL)-1beta, IL-6, and tumor necrosis factor alpha values; and reductions in the Midline-Estimating Statistic of Rhythm and amplitude of activity-rest rhythm and in the amplitude of the core temperature rhythm. Melatonin raised serum melatonin levels; tryptophan increased both melatonin and serotonin levels. Melatonin and tryptophan lowered nocturnal activity, core temperature, and cytokine levels and increased peripheral temperature in both groups. Melatonin or tryptophan may limit or reverse some of the changes that occur in sleep-wake rhythms and temperature due to age.


[Point system in diagnostics of the gallbladder cholesterosis].
Development of scoring systems of diagnostics of gallbladder cholesterolosis (GBC) on the grounds of clinical and laboratory-instrumental parameters determined in the general clinical practice. For development of the scoring systems, the methods of the logistic regression (LR) and artificial neuron networks (ANN) were used. The results of specially carried clinical observations of 124 patients, who had cholelithiasis with morphological confirmation of presence of GBC or chronic cholecystitis after planned cholecystectomy, were analysed. The scoring systems of diagnostics of GBC have been created: the detailed scring system, subjected to 24 parameters (12 quantitative ones; 12 qualitative ones) and the diminished scring system subjected to 6 the most informative parameters (3 clinical ones, 3 ultrasonic signs). Using the detailed scoring system of diagnostics of GBC allowed to set a correct diagnosis in 83,8% cases, specificity of the method was 91.80%, sensitiveness--92.11%. Diminished scoring system provides the correct diagnostics of GBC in 68% cases, the model specificity--63.41%, sensitiveness--63.77%. Using LR and ANN allowed to evaluate the influence of individual clinical and laboratory-instrumental parameters on probability of the GBC diagnosis. Developed scoring systems open new possibilities of the early diagnosing of this disease that enables to conduct the identical medication treatment in proper time, cut off clinical presentations and prevent the development of cholelithiasis.