Environmental suitability for lymphatic filariasis in Nigeria.
Lymphatic filariasis (LF) is a mosquito-borne parasitic disease and a major cause of disability worldwide. It is one of the neglected tropical diseases identified by the World Health Organization for elimination as a public health problem by 2020. Maps displaying disease distribution are helpful tools to identify high-risk areas and target scarce control resources. We used pre-intervention site-level occurrence data from 1192 survey sites collected during extensive mapping surveys by the Nigeria Ministry of Health. Using an ensemble of machine learning modelling algorithms (generalised boosted models and random forest), we mapped the ecological niche of LF at a spatial resolution of 1 km2. By overlaying gridded estimates of population density, we estimated the human population living in LF risk areas on a 100 × 100 m scale. Our maps demonstrate that there is a heterogeneous distribution of LF risk areas across Nigeria, with large portions of northern Nigeria having more environmentally suitable conditions for the occurrence of LF. Here we estimated that approximately 110 million individuals live in areas at risk of LF transmission. Machine learning and ensemble modelling are powerful tools to map disease risk and are known to yield more accurate predictive models with less uncertainty than single models. The resulting map provides a geographical framework to target control efforts and assess its potential impacts.


Curcumin reduces Streptococcus mutans biofilm formation by inhibiting sortase A activity.
Sortase A is an enzyme responsible for the covalent attachment of Pac proteins to the cell wall in Streptococcus mutans. It has been shown to play a role in modulating the surface properties and the biofilm formation and influence the cariogenicity of S. mutans. Curcumin, an active ingredient of turmeric, was reported to be an inhibitor for Staphylococcus aureus sortase A. The aim of this study was to investigate the inhibitory ability of curcumin against S. mutans sortase A and the effect of curcumin for biofilm formation. The antimicrobial activity of the curcumin to the S. mutans and inhibitory ability of the curcumin against the purified sortase A in vitro were detected. Western-blot and real-time PCR were used to analysis the sortase A mediated Pac protein changes when the S. mutans was cultured with curcumin. The curcumin on the S. mutans biofilm formation was determined by biofilm formation analysis. Curcumin can inhibit purified S. mutans sortase A with a half-maximal inhibitory concentration (IC50) of (10.2±0.7)μmol/l, which is lower than minimum inhibitory concentration (MIC) of 175μmol/l. Curcumin (15μmol/l) was found to release the Pac protein to the supernatant and reduce S. mutans biofilm formation. These results indicated that curcumin is an S. mutans sortase A inhibitor and has promising anti-caries characteristics through an anti-adhesion-mediated mechanism.


Dermatological and Genital Manifestations of Lyme Disease Including Morgellons Disease.
Although the erythema migrans (EM) skin rash is traditionally considered a hallmark of Lyme disease, other dermatological manifestations of the tickborne disease are less well known. We describe a 49-year-old woman with erosive genital ulcerations, secondary EM rashes and jagged skin lesions associated with Lyme disease. The skin rashes exhibited fibers characteristic of Morgellons disease. Molecular testing confirmed the presence of Borrelia DNA in both vaginal culture and serum specimens. In further studies on a secondary EM lesion containing filaments, Gömöri trichrome staining revealed the presence of collagen in the filaments, while Dieterle and anti-Borrelia immunostaining revealed intracellular and extracellular Borrelia organisms. Intracellular staining for Borrelia was also observed in lymphocytic infiltrates. Lyme disease may present with a variety of genital lesions and dermatological manifestations including Morgellons disease. Careful evaluation is required to determine the presence of Borrelia organisms associated with these dermopathies.


Mesenteric venous thrombosis--1911 to 1984.
The objective of this study was to identify those patients in whom mesenteric venous thrombosis (MVT) is likely to develop and to review the pathophysiology, clinical presentation, diagnostic modalities, and patient outcome. We present a review of the literature from 1911 to 1984 with respect to 372 patients with MVT, including five of our own patients. Data on 99 of these patients were obtained from autopsy reports and were not included in the study. This disease is common in the sixth and seventh decades of life, with 81% of these older patients having associated illnesses. MVT involves segments of the small bowel, but rarely of the colon, with hemorrhagic infarcts rather than gangrene. This disease does not conform to a pattern, although a prodromal period of days or weeks of abdominal pain (which is usually out of proportion to physical findings), marked leukocytosis, and dehydration are all highly suggestive of MVT. Serosanguineous fluid obtained by means of peritoneal tap is a useful diagnostic tool. A high index of suspicion, early diagnosis, and prompt surgical intervention with the addition of anticoagulants seems to improve survival and reduce recurrence.


Overview of players and information in the cancer epidemiology and control world in Asia.
Cancer and related lifestyle diseases are on the increase across Asia and already account for over half the disease-associated mortality in the vast majority of the included countries. An understanding of the epidemiology is therefore of paramount importance. In addition, given the immensity of the problem, cooperation among all the interested parties is of the essence. The present series of reviews were complied with the aim of promoting better comprehension and interaction, focusing on cancer prevalence and the underlying risk and preventive factors in Asia. Data from Cancer Incidence in Five Continents and Globocan 2002, published by the International Agency for Research on Cancer, as well as various other cancer registry sources, were thus married with research information in the public domain, accessible through PubMed. It is hoped that the comprehensive approach adopted for the different regions will help bring together all of the Asian community of individuals involved in cancer epidemiology and control and contribute to establishment of Asian networks for collaborative research. The major players and the overall picture for cancer control are covered in the present overview. Further details are then provided in seven separate regional reviews: for North-Western and Central Asia; South-West Asia; South Asia; Mainland South-East Asia; Peninsular and Island South-East Asia, the Pacific; and North-East Asia. The final section covers possible organ-based strategies for cancer control and, lastly, an Appendix has been included listing research institutes and staff in Asia to facilitate contacts between interested individuals.


Multiple Myeloma: Challenges Encountered and Future Options for Better Treatment.
Multiple myeloma (MM) is a malignant hematological disease. The disease is characterized by the clonal proliferation of malignant plasma cells in the bone marrow. MM accounts for 1.3% of all malignancies and has been increasing in incidence all over the world. Various genetic abnormalities, mutations, and translocation, including epigenetic modifications, are known to contribute to the disease's pathophysiology. The prognosis is good if detected early, or else the outcome is very bad if distant metastasis has already occurred. Conventional treatment with drugs poses a challenge when there is drug resistance. In the present review, we discuss multiple myeloma and its treatment, drug resistance, the molecular basis of epigenetic regulation, the role of natural products in epigenetic regulators, diet, physical activity, addiction, and environmental pollutants, which may be beneficial for clinicians and researchers.


Risk of Fractures With Concomitant Use of Calcium Channel Blockers and Selective Serotonin Reuptake Inhibitors.
Despite their frequent concurrent use, little is known about the concomitant use of calcium channel blockers (CCBs) and selective serotonin reuptake inhibitors (SSRIs) on fracture risk. We compared risk of fractures in patients concomitantly treated with CCBs and SSRIs versus CCB-only users. We compared risk of fractures among concomitant CCB-SSRI users initiating cytochrome P450 3A4 (CYP3A4)-inhibiting SSRIs versus non-CYP3A4 inhibiting SSRIs. This retrospective cohort study used IBM MarketScan commercial claims and Medicare Supplemental database (2007-2019). We included adults diagnosed with hypertension and depression, newly initiating SSRIs while being treated with CCBs (ie, concomitant CCB-SSRI users) and those who did not (ie, CCB-only users). Primary outcome was the first occurrence of any fracture. We used stabilized inverse probability of treatment weighting (sIPTW) based on propensity scores to balance baseline risk between groups. Cox proportional hazard regression modeling was used to compare fracture risk. We identified 191 352 concomitant CCB-SSRI and 956 760 CCB-only users (mean age = 56 years, 50.1% males). After sIPTW, compared with CCB-only users, CCBs-SSRIs users had a higher risk of fractures (hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.22-1.66). No difference in the risk of fractures between concomitant users of CCB-CYP3A4-inhibiting SSRIs and those of CCB-non-CYP3A4 inhibiting SSRIs (HR: 1.10, 95% CI: 0.87-1.40) was observed. Short-term concomitant CCB-SSRI use was associated with increased fracture risk. Concomitant CCBs and CYP3A4-inhibiting SSRIs compared with CCBs and non-CYP3A4 inhibiting SSRIs use was not associated with increased risk.


Control programmes for streptococcal disease among rural school children.
Rheumatic fever remains important in New Zealand, and rheumatic heart disease is common. In a high risk area, a study of primary preventive strategies was undertaken among primary school children. The principal aim was to reduce beta-haemolytic streptococcal throat carriage. Subordinate aims were to reduce sickness-related absenteeism and the clinical incidence of streptococcal disease. The strategies compared included (1) identification and treatment of asymptomatic carriers at three-monthly surveys; (2) between-survey home visits of a nurse to identify infections and encourage prompt referral to the family doctor; (3) an exercise programme intended to increase general and respiratory fitness. Some benefit resulted from each strategy but the exercise programme was the least costly. The benefits of treatment of carriers and home visiting are probably insufficient to make them worthwhile.


Conflict and mental health: a cross-sectional epidemiological study in Nepal.
The aim of this epidemiological study was to identify prevalence rates of mental health problems, factors associated with poor mental health and protective and risk factors in a post-conflict situation in Nepal. This cross-sectional study was conducted among 720 adults in 2008. A three-stage sampling procedure was used following a proportionate stratified random sampling strategy. The outcome measures used in the study were locally validated with Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Post-Traumatic Stress Disorder (PTSD)-Civilian Version (PCL-C) and locally constructed function impairment scale, resources and coping. Of the sample, 27.5% met threshold for depression, 22.9% for anxiety, and 9.6% for PTSD. Prevalence rates were higher among women (depression, OR 2.14 [1.52-3.47]; anxiety, OR 2.30 [1.45-3.17] and PTSD, OR 3.32 [1.87-5.89]) and older age categories (depression, OR 1.02 [1.01-1.04]; anxiety, OR 1.04 [1.03-1.05] and PTSD, OR 1.02 [1.0-1.03]). Respondents who perceived more negative impact of the conflict (e.g., hampered the business/industry; hindered in getting medical treatment, etc.) in their communities were more at risk for depression (OR 1.1 [1.06-1.14]), anxiety (OR 1.05 [1.01-1.09]) and PTSD (OR 1.09 [1.04-1.14]). Other risk factors identified in the study were ethnicity, district of residence and poverty (lack of clothing, medicine and information via radio at home). Overall, the prevalence rates of depression and anxiety in the sample are comparable to, or lower than, other studies conducted with populations affected by conflict and with refugees. However, the findings underscore the need to address the current lack of mental health care resources in post-conflict rural Nepal, especially for marginalized populations.


Extreme 13C,15N and 17O isotopic enrichment in the young planetary nebula K4-47.
Carbon, nitrogen and oxygen are the three most abundant elements in the Galaxy after hydrogen and helium. Whereas hydrogen and helium were created in the Big Bang, carbon, nitrogen and oxygen arise from nucleosynthesis in stars. Of particular interest1,2 are the isotopic ratios 12C/13C, 14N/15N and 16O/17O because they are effective tracers of nucleosynthesis and help to benchmark the chemical processes that occurred in primitive interstellar material as it evolved into our Solar System3. However, the origins of the rare isotopes 15N and 17O remain uncertain, although novae and very massive stars that explode as supernovae are postulated4-6 to be the main sources of 15N. Here we report millimetre-wavelength observations of the young bipolar planetary nebula K4-47 that indicate another possible source for these isotopes. We identify various carbon-bearing molecules in K4-47 that show that this object is carbon-rich, and find unusually high enrichment in rare carbon (13C), oxygen (17O) and nitrogen (15N) isotopes: 12C/13C = 2.2 ± 0.8, 16O/17O = 21.4 ± 10.3 and 14N/15N = 13.6 ± 6.5 (uncertainties are three standard deviations); for comparison, the corresponding solar ratios7 are 89.4 ± 0.2, 2,632 ± 7 and 435 ± 57. One possible interpretation of these results is that K4-47 arose from a J-type asymptotic giant branch star that underwent a helium-shell flash (an explosive nucleosynthetic event that converts large quantities of helium to carbon and other elements), enriching the resulting planetary nebula in 15N and 17O and creating its bipolar geometry. Other possible explanations are that K4-47 is a binary system or that it resulted from a white dwarf merger, as has been suggested for object CK Vul8. These results suggest that nucleosynthesis of carbon, nitrogen and oxygen is not well understood and that the classification of certain stardust grains must be reconsidered.


A short term high-fat high-sucrose diet in mice impairs optic nerve recovery after injury and this is not reversed by exercise.
The aim of the current work was to test whether increased intake of dietary fat and sucrose in mice modifies the response of retinal ganglion cells (RGCs) of the optic nerve to injury, and whether any effects of diet are influenced by physical activity levels. C57BL/6J mice were given a high-fat high-sucrose (HFS) diet for 7 weeks, with or without exposure to regular exercise by swimming (60 min/day, 5 days/week). Injury to RGCs was subsequently induced by acute elevation of intraocular pressure (IOP) and retinas were assessed for function and structure. We report that mice on a HFS diet had similar body mass and blood glucose levels compared to mice on a control diet but suffered a 30% greater loss of RGC function following injury, as measured in vivo with the electroretinogram. RGC dysfunction in retinas from mice on the HFS diet was accompanied by activation of retinal macroglia but was not associated with neuronal cell loss. Exercising mice by swimming did not prevent HFS-induced RGC dysfunction in response to injury. This study shows for the first time that a short term increase in dietary fat and sucrose enhances the vulnerability of RGCs to dysfunction and cell stress after an acute injury, and that this is independent of obesity or hyperglycemia. Furthermore, our results suggest that detrimental effects of diet predominate over protective effects of exercise.


[Psychobiological aspects of posttraumatic stress disorder].
The exposure to a traumatic event may result in posttraumatic stress disorder (PTSD), which is characterized by a complex symptomatology, clustered into three groups of symptoms, i.e. intrusive memories, avoidance behavior, and hyperarousal. Since PTSD is a stress reaction, alterations of stress-responses of neurobiological systems have been examined in patients suffering from PTSD. The investigation of biological parameters refers to the hypothalamic-pituitary-adrenal axis (HPA), studies of the noradrenergic and the endogenous opiate system as well as psychophysiological and neuroimaging studies. Besides others, the observed biological dysregulations refer to hypocortisolism with an enhanced negative feedback of the HPA axis, enhanced noradrenergic activity, and neuroanatomical changes. To elucidate the specificity of this findings for PTSD, the dysregulations will be discussed with reference to findings in major depression and somatoform disorders.


The dependence of photocatalytic activity and photoinduced self-stability of photosensitive AgI nanoparticles.
AgI is instable under light irradiation owing to its photosensitive properties, while a supported Ag-AgI composite has been demonstrated to be a stable photocatalyst. However, seldom investigations have been focused on the photocatalytic activity (including deactivation) and photoinduced stability of the photosensitive AgI materials. In this study, the AgI nanoparticles were immobilized on the surface of Ag(8)W(4)O(16) nanorods by an anion-exchange route and their photocatalytic activities were evaluated by photocatalytic decomposition of methyl orange and phenol solutions under visible-light irradiation. A photoinduced self-stabilizing mechanism of the AgI nanoparticles was proposed to account for the formation of a stable Ag-AgI photocatalyst, namely, instable AgI can transform into a stable Ag-AgI photocatalyst after in situ formation of partial Ag on the surface of AgI nanoparticles. The photocatalytic performance of the immobilized AgI photocatalyst was greatly influenced by the formation of metallic Ag. With increasing repetitions of photocatalytic experiments, the initial deactivation was accompanied by the rapid increase of metallic Ag owing to the reduction of lattice Ag(+), while the subsequently stable activity corresponds to the formation of a stable Ag-AgI composite photocatalyst. Compared with the un-immobilized AgI photocatalyst, the immobilized AgI nanoparticles exhibited a higher and more stable photocatalytic performance.


Ambient particulate matter and health effects: publication bias in studies of short-term associations.
Time-series studies have shown short-term temporal associations between low levels of ambient particulate air pollution and adverse health effects. It is not known whether or to what extent this literature is affected by publication bias. We obtained effect estimates from time-series studies published up to January 2002. These were summarized and examined for funnel plot asymmetry. We compared summary estimates between single-city and prospective multicity studies. Using 1 multicity study, we examined the sensitivity of summary estimates to alternative lag selection policies. We found evidence for publication bias among single-city studies of daily mortality, hospital admissions for chronic obstructive lung disease (COPD), and incidence of cough symptom, but not for studies of lung function. Statistical correction for this bias reduced summary relative risk estimates for a 10 microg/m increment of particulate matter less than 10 microm aerodynamic diameter (PM10) as follows: daily mortality from 1.006 to 1.005 and admissions for COPD from 1.013 to 1.011; and odds ratio for cough from 1.025 to 1.015. Analysis of results from a large multicity study suggested that selection of positive estimates from a range of lags could increase summary estimates for PM10 and daily mortality by up to 130% above those based on nondirectional approaches. We conclude that publication bias is present in single-city time-series studies of ambient particles. However, after correcting for publication bias statistically, associations between particles and adverse health effects remained positive and precisely estimated. Differential selection of positive lags may also inflate estimates.


Segmental biomechanics of the normal and glaucomatous human aqueous outflow pathway.
The conventional aqueous outflow pathway, encompassing the trabecular meshwork (TM), juxtacanalicular connective tissue (JCT), and inner wall endothelium of Schlemm's canal (SC), governs intraocular pressure (IOP) regulation. This study targets the biomechanics of low-flow (LF) and high-flow (HF) regions within the aqueous humor outflow pathway in normal and glaucomatous human donor eyes, using a combined experimental and computational approach. LF and HF TM/JCT/SC complex tissues from normal and glaucomatous eyes underwent uniaxial tensile testing. Dynamic motion of the TM/JCT/SC complex was recorded using customized green-light optical coherence tomography during SC pressurization in cannulated anterior segment wedges. A hyperviscoelastic model quantified TM/JCT/SC complex properties. A fluid-structure interaction model simulated tissue-aqueous humor interaction. FluoSpheres were introduced into the pathway via negative pressure in the SC, with their motion tracked using two-photon excitation microscopy. Tensile test results revealed that the elastic moduli of the LF and HF regions in glaucomatous eyes are 3.5- and 1.5-fold stiffer than the normal eyes, respectively. The FE results also showed significantly larger shear moduli in the TM, JCT, and SC of the glaucomatous eyes compared to the normal subjects. The LF regions in normal eyes demonstrated larger elastic moduli compared to the HF regions in glaucomatous eyes. The resultant strain in the outflow tissues and velocity of the aqueous humor in the FSI models were in good agreement with the digital volume correlation and 3D particle image velocimetry data, respectively. This study uncovers stiffer biomechanical responses in glaucomatous eyes, with LF regions stiffer than HF regions in both normal and glaucomatous eyes. STATEMENT OF SIGNIFICANCE: This study delves into the biomechanics of the conventional aqueous outflow pathway, a crucial regulator of intraocular pressure and ocular health. By analyzing mechanical differences in low-flow and high-flow regions of normal and glaucomatous eyes, this research unveils the stiffer response in glaucomatous eyes. The distinction between regions' properties offers insights into aqueous humor outflow regulation, while the integration of experimental and computational methods enhances credibility. These findings have potential implications for disease management and present a vital step toward innovative ophthalmic interventions. This study advances our understanding of glaucoma's biomechanical basis and its broader impact on ocular health.


Are neuropsychiatric symptoms associated with evidence of right brain injury in referrals to a neuropsychiatric brain injury unit?
Studies suggest that neuropsychiatric symptoms are more common in patients with injury to the right side of the brain. However, most studies have examined patients with penetrating injuries because these allow more accurate localization of brain damage. This study investigates whether a similar association would be found in patients with non-penetrating brain injuries presenting to a neuropsychiatric unit. Over a 2 year period, 98 referrals were examined. Damage was localized using routine operation notes, EEG and neuroimaging. In total, 34 patients (35%) had a predominately right-sided injury, 33 (34%) had a left-sided injury and 31 (32%) had a diffuse or bilateral injury. Right-sided injuries were associated with hallucinations (p = 0.05), and left-sided injuries were associated with confabulation (p = 0.05) and lack of insight (p = 0.07). These results are consistent with findings from patients with penetrating head injuries. They suggest that evidence of the laterality of injury may be useful for planning the rehabilitation of patients seen in neuropsychiatric brain injury units.


An efficient post-processing adaptive filtering technique to rectifying the flickering effects.
Compression at a very low bit rate(≤0.5bpp) causes degradation in video frames with standard decoding algorithms like H.261, H.262, H.264, and MPEG-1 and MPEG-4, which itself produces lots of artifacts. This paper focuses on an efficient pre-and post-processing technique (PP-AFT) to address and rectify the problems of quantization error, ringing, blocking artifact, and flickering effect, which significantly degrade the visual quality of video frames. The PP-AFT method differentiates the blocked images or frames using activity function into different regions and developed adaptive filters as per the classified region. The designed process also introduces an adaptive flicker extraction and removal method and a 2-D filter to remove ringing effects in edge regions. The PP-AFT technique is implemented on various videos, and results are compared with different existing techniques using performance metrics like PSNR-B, MSSIM, and GBIM. Simulation results show significant improvement in the subjective quality of different video frames. The proposed method outperforms state-of-the-art de-blocking methods in terms of PSNR-B with average value lying between (0.7-1.9db) while (35.83-47.7%) reduced average GBIM keeping MSSIM values very close to the original sequence statistically 0.978.


Change of serotype pattern of Group D non-typhoidal Salmonella isolated from pediatric patients in southern Taiwan.
Group D non-typhoidal Salmonella infection is increasing in Taiwan. This study aimed to investigate the changing serotypes and antibiotic resistance of childhood group D Salmonella infection. From 1998 through 2004, children (<16 years) infected with group D Salmonella were retrospectively reviewed. Demographic data, clinical and laboratory features, and risk factors of bacteremia were analyzed. Enrolled patients were classified as acute gastroenteritis with bacteremia (Group I) and acute gastroenteritis without bacteremia (Group II). The minimal inhibitory concentrations were determined by agar dilution method. Genotyping was performed by use of pulsed-field gel electrophoresis (PFGE). Eighty one children (Group I, n = 15; Group II, n = 66) were enrolled with a mean (+/- standard deviation) age of 3.1 +/- 2.6 years. Group I patients were younger and had a longer duration of fever prior to admission (> or =5 days, 40% vs 9.2%; p=0.003) and total fever duration (8.3 vs 4.1 days, p<0.001) than Group II. Salmonella enterica serotype Enteritidis (80%) was the most common serotype, followed by Salmonella Panama (7%). The antibiotic resistance rates of S. Enteritidis were: tetracycline (36.5%), trimethoprim-sulfamethoxazole (25.4%), ampicillin (14.3%), and chloramphenicol (12.7%). S. Panama was associated with a higher rate of bacteremia. All strains were susceptible to quinolone and third-generation cephalosporins. PFGE study showed a single genotype of S. Enteritidis and diverse genotypes of S. Panama circulating in the area. S. Enteritidis was the predominant serotype of group D Salmonella that caused pediatric infection in southern Taiwan during the study period from 1998 to 2004. S. Panama is associated with higher rates of bacteremia and antimicrobial resistance.


Spatiotemporal Observation of Quasi-Ballistic Transport of Electrons in Graphene.
We report spatiotemporal observations of room-temperature quasi-ballistic electron transport in graphene, which is achieved by utilizing a four-layer van der Waals heterostructure to generate free charge carriers. The heterostructure is formed by sandwiching a MoS2 and MoSe2 heterobilayer between two graphene monolayers. Transient absorption measurements reveal that the electrons and holes separated by the type-II interface between MoS2 and MoSe2 can transfer to the two graphene layers, respectively. Transient absorption microscopy measurements, with high spatial and temporal resolution, reveal that while the holes in one graphene layer undergo a classical diffusion process with a large diffusion coefficient of 65 cm2 s-1 and a charge mobility of 5000 cm2 V-1 s-1, the electrons in the other graphene layer exhibit a quasi-ballistic transport feature, with a ballistic transport time of 20 ps and a speed of 22 km s-1, respectively. The different in-plane transport properties confirm that electrons and holes move independently of each other as charge carriers. The optical generation of ballistic charge carriers suggests potential applications for such van der Waals heterostructures as optoelectronic materials.


One billion years of Myb.
The v-myb oncogene of the avian myeloblastosis virus has led to the discovery of a large and growing family of myb-related genes in a wide variety of eukaryotes including animals, plants, fungi and slime molds. The Myb-related proteins contain a highly conserved sequence, often present in multiple tandem repeats which constitute a DNA-binding domain. These proteins generally function in the regulation of cell growth and differentiation, often by coregulating gene expression along with DNA-binding proteins of other classes. This review focuses on the evolution of the myb gene family and the role of these genes in development.


Graphene-based frequency tripler.
Graphene has captured the imagination of researchers worldwide as an ideal two-dimensional material with exceptional electrical transport properties. The high electron and hole mobility quickly inspired scientists to search for electronic applications that require high-performance channel materials. However, the absence of a bandgap in graphene immediately revealed itself in terms of ambipolar device characteristics and the nonexistence of a device off-state. The question is: How can the superior electronic properties of graphene be harvested while dealing appropriately with its unique characteristics rather than enforcing conventional device concepts? Here, we report a novel device idea, a graphene-based frequency tripler, an application that employs an innovative electrostatic doping approach and exploits the unique ambipolar behavior of graphene.


Common carotid artery peak systolic velocity ratio predicts high-grade common carotid stenosis.
Screening for common carotid artery (CCA) stenosis with duplex ultrasound (DUS) velocity criteria alone can be limited by within-patient and between-patients hemodynamic variability. This study aimed to evaluate inter-CCA velocity ratio criteria to predict high-grade CCA stenosis. This was a retrospective review of consecutive patients who underwent computed tomography angiography and DUS peak systolic velocity (PSV) measurements of bilateral CCAs, independently recorded, between 2008 and 2014. Patients with dampened CCA waveforms on DUS composed group B. The remainder without dampened waveforms constituted group A. Inter-CCA PSV ratios were calculated by dividing the higher CCA PSV by the lower one of the other side, so the ratios would always be ≥1. Ratios were subsequently paired with each respective unilateral CCA diameter stenosis and differential bilateral CCA diameter stenosis. A quadratic regression model was fitted to predict unilateral and differential stenosis. Receiver operating characteristic curve was used to determine optimal ratios for ≥50% and ≥80% CCA stenosis. The study excluded patients with carotid artery occlusion. From a total of 201 patients, 193 patients were included in group A and 8 in group B. Within group A, 31 patients had ≥50% unilateral stenosis and 17 had ≥50% differential stenosis. All stenoses ≥50% were identified on the same side with the higher PSV. Inter-CCA PSV ratio predicted ≥50% unilateral (r(2) = 0.536; P < .001) and differential stenosis (r(2) = 0.581; P < .001). In group B, all patients had ≥60% stenosis that was near or involved the vessel origin. An increasing inter-CCA PSV ratio showed a trend toward contralateral high-grade stenosis (r(2) = 0.596; P = .1). Receiver operating characteristic curves showed an optimal threshold CCA ratio ≥2.16 for ≥50% unilateral stenosis with 92% accuracy, 62% sensitivity, and 98% specificity (area under curve = 0.854; 95% confidence interval, 0.759-0.948) and a ratio ≥2.62 for ≥50% differential stenosis with 97% accuracy, 83% sensitivity, and 98% specificity (area under curve = 0.94; 95% confidence interval, 0.835-1). DUS-based CCA PSV ratio can accurately predict unilateral and differential high-grade CCA stenosis. Also, in patients with unilateral dampened waveforms, it implied contralateral severe proximal stenosis. This parameter should be further validated in prospective studies and may serve as an adjunct screening tool to detect high-grade CCA stenosis.


Ankyrin-based subcellular gradient of neurofascin, an immunoglobulin family protein, directs GABAergic innervation at purkinje axon initial segment.
Distinct classes of GABAergic synapses are segregated into subcellular domains (i.e., dendrite, soma, and axon initial segment-AIS), thereby differentially regulating the input, integration, and output of principal neurons. In cerebellum, for example, basket interneurons make exquisitely precise "pinceau synapses" on AIS of Purkinje neurons, but the underlying mechanism is unknown. Using BAC transgenic reporter mice, we found that basket axons always contacted Purkinje soma before innervating AIS. This synapse targeting process followed the establishment of a subcellular gradient of neurofascin186 (NF186), an L1 family immunoglobulin cell adhesion molecule (L1CAM), along the Purkinje AIS-soma axis. This gradient was dependent on ankyrinG, an AIS-restricted membrane adaptor protein that recruits NF186. In the absence of neurofascin gradient, basket axons lost directional growth along Purkinje neurons and precisely followed NF186 to ectopic locations. Disruption of NF186-ankyrinG interactions at AIS reduced pinceau synapse formation. These results implicate ankyrin-based localization of L1CAMs in subcellular organization of GABAergic synapses.


The Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5): Background and rationale.
This article presents the Child Sport Concussion Assessment Tool 5th Edition (Child SCAT5). The Sport Concussion Assessment Tool was introduced in 2004, following the 2nd International Conference on Concussion in Sport in Prague, Czech Republic. Following the 4th International Consensus Conference, held in Zurich, Switzerland, in 2012, the SCAT 3rd edition (Child SCAT3) was developed for children aged between 5 and12 years. Research to date was reviewed and synthesised for the 5th International Consensus Conference on Concussion in Sport in Berlin, Germany, leading to the current revision of the test, the Child SCAT5. This article describes the development of the Child SCAT5.


Genome-wide analysis of binding sites and direct target genes of the orphan nuclear receptor NR2F1/COUP-TFI.
Identification of bona fide direct nuclear receptor gene targets has been challenging but essential for understanding regulation of organismal physiological processes. We describe a methodology to identify transcription factor binding sites and target genes in vivo by intersecting microarray data, computational binding site queries, and evolutionary conservation. We provide detailed experimental validation of each step and, as a proof of principle, utilize the methodology to identify novel direct targets of the orphan nuclear receptor NR2F1 (COUP-TFI). The first step involved validation of microarray gene expression profiles obtained from wild-type and COUP-TFI(-/-) inner ear tissues. Secondly, we developed a bioinformatic tool to search for COUP-TFI DNA binding sites in genomes, using a classification-type Hidden Markov Model trained with 49 published COUP-TF response elements. We next obtained a ranked list of candidate in vivo direct COUP-TFI targets by integrating the microarray and bioinformatics analyses according to the degree of binding site evolutionary conservation and microarray statistical significance. Lastly, as proof-of-concept, 5 specific genes were validated for direct regulation. For example, the fatty acid binding protein 7 (Fabp7) gene is a direct COUP-TFI target in vivo because: i) we identified 2 conserved COUP-TFI binding sites in the Fabp7 promoter; ii) Fapb7 transcript and protein levels are significantly reduced in COUP-TFI(-/-) tissues and in MEFs; iii) chromatin immunoprecipitation demonstrates that COUP-TFI is recruited to the Fabp7 promoter in vitro and in vivo and iv) it is associated with active chromatin having increased H3K9 acetylation and enrichment for CBP and SRC-1 binding in the newborn brain. We have developed and validated a methodology to identify in vivo direct nuclear receptor target genes. This bioinformatics tool can be modified to scan for response elements of transcription factors, cis-regulatory modules, or any flexible DNA pattern.


Understanding the health and wellbeing challenges of the food banking system: A qualitative study of food bank users, providers and referrers in London.
In the UK, food poverty has been associated with conditions such as obesity, malnutrition, hypertension, iron deficiency, and impaired liver function. Food banks, the primary response to food poverty on the ground, typically rely on community referral and distribution systems that involve health and social care professionals and local authority public health teams. The perspectives of these key stakeholders remain underexplored. This paper reports on a qualitative study of the health and wellbeing challenges of food poverty and food banking in London. An ethnographic investigation of food bank staff and users was carried out alongside a series of healthcare stakeholder interviews. A total of 42 participants were interviewed. A Critical Grounded Theory (CGT) analysis revealed that contemporary lived experiences of food poverty are embedded within and symptomatic of extreme marginalisation, which in turn impacts upon health. Specifically, food poverty was conceptualised by participants to: firstly, be a barrier to providing adequate care and nutrition for young children; secondly, be exacerbated by lack of access to adequate fresh food, food storage and cooking facilities; and thirdly, amplify existing health and social problems. Further investigation of the local government structures and professional roles that both rely upon and serve to further embed the food banking system is necessary in order to understand the politics of changing welfare landscapes.


Rapid, microtubule-dependent fluctuations of the cell margin.
Using data automatically acquired by microinterferometry from large numbers of chick fibroblasts, we have detected rapid microfluctuations in the rates of protrusion and retraction of the cell margin which were strongly suppressed by colcemid, nocodazole and taxol. Fluctuations in the rate of retraction of the margin were about twice as powerful as fluctuations in the rate of protrusion. High-frequency fluctuations were also apparent in the cell track and in measures of cell spreading, shape and speed. These rapid fluctuations were also all suppressed by colcemid and nocodazole, sometimes by doses insufficient to disrupt the majority of microtubules. Taxol on the other hand did not suppress fluctuations in direction of the cell track nor fluctuations in the spreading of the cells but it was very effective at suppressing variations in protrusion and retraction and in cell speed and shape. We discovered that much slower, larger-scale variations in protrusion, retraction, spreading, shape and speed resulted from the accumulation of these rapid, microtubule-dependent fluctuations of the cell margin. These large-scale variations in cell behaviour were also suppressed by the same drug treatments that were effective in suppressing the corresponding high-frequency fluctuations. We speculate that a function of microtubules is to enhance the fibroblast's responses to its environment by causing microfluctuations of the cell's margin which give rise to large-scale variations in cell behaviour.


DFNA5 (ICERE-1) contributes to acquired etoposide resistance in melanoma cells.
Resistance to drug treatment is a common observation in malignant melanoma. In order to analyze alterations in mRNA expression profiles associated with drug resistance in melanoma cells we previously established a panel of various drug-resistant cell variants derived from the human melanoma line MeWo and compared the mRNA expression profiles by a differential display technique. By that approach it could be demonstrated that the expression level of a mRNA encoded by a gene found to be mutated in non-syndromic hearing impairment, DFNA5 (ICERE-1), was distinctly decreased in the 33-fold etoposide-resistant melanoma cell line MeWo ETO 1. To evaluate the hypothesis that a decrease in DFNA5 mRNA expression level contributes to the acquired etoposide resistance phenotype exhibited by MeWo ETO 1 cells, this drug-resistant line was stably transfected with the DFNA5-encoding cDNA. Transfected clones showed a 30-35% reduced etoposide susceptibility by comparing the IC(25), IC(50) and IC(75) values of these clones with those displayed by the non-transfected, etoposide-resistant melanoma cell line MeWo ETO 1 and controls. Furthermore, etoposide exposure of stable DFNA5 transfectants resulted in an increase of caspase-3-mediated apoptotic events in DFNA5-transfected clones in comparison to MeWo ETO 1 cells and controls. The data therefore demonstrate that a decrease in DNFA5 mRNA expression level is associated with an increased etoposide resistance in melanoma cells due to an elevated cellular susceptibility to trigger a caspase-3-depending signal pathway leading to programmed cell death.


Ca2+ release and InsP3 production in avian uterine cells: effects of PGF2 alpha and AVT.
Primary cultures of smooth muscle cells isolated from the shell gland ("uterus") of the domestic hen were permeabilized with digitonin and loaded with 45Ca2+ in the presence of ATP. When these cells were stimulated with prostaglandin F2 alpha (PGF2 alpha), arginine vasotocin (AVT), or D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], there was a rapid, biphasic, and dose-related release of 45Ca2+ from nonmitochondrial pools. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate, an inhibitor of phospholipase C, had no effect on PGF2 alpha - and Ins(1,4,5)P3-promoted 45Ca2+ efflux, whereas it significantly inhibited AVT-stimulated and a stable analogue of GTP-stimulated 45Ca2+ release. In fura-2-loaded intact cells, both PGF2 alpha and AVT increased intracellular Ca2+ levels [( Ca2+]i) in a dose-related manner in the presence of extracellular Ca2+. However, omission of extracellular Ca2+ prevented a PGF2 alpha, but not AVT-induced, rise in [Ca2+]i In D-myo-[3H]inositol-labeled cells, 10 nM AVT caused a rapid, two- to threefold increase in [3H]-Insp3, whereas PGF2 alpha up to 1 microM was infective. Raising PGF2 alpha to 10 microM increased total inositol phosphates by 22% over controls (P less than 0.05). These results point to marked differences in the mechanisms by which AVT and PGF2 alpha regulate [Ca2+]i in uterine smooth muscle cells. It is suggested that the two agonists act in concert to initiate oviposition.


Training future physicians in the era of genomic medicine: trends in undergraduate medical genetics education.
Advances in genomic technologies are transforming medical practice, necessitating the expertise of genomically-literate physicians. This study examined 2013-2014 trends in genetics curricula in US and Canadian medical schools to ascertain whether and how curricula are keeping pace with this rapid evolution. Medical genetics course directors received a 60-item electronic questionnaire covering curriculum design, assessment, remediation of failing grades, and inclusion of specific topics. The response rate was 74%. Most schools teach the majority of genetics during the first 2 years, with an increase in the number of integrated curricula. Only 26% reported formal genetics teaching during years 3 and 4, and most respondents felt the amount of time spent on genetics was insufficient preparation for clinical practice. Most participants are using the Association of Professors of Human and Medical Genetics Core Curriculum(1) as a guide. Topics recently added include personalized medicine (21%) and direct-to-consumer testing (18%), whereas eugenics (17%), linkage analysis (16%), and evolutionary genetics (15%) have been recently eliminated. Remediation strategies were heterogeneous across institutions. These findings provide an important update on how genetics and genomics is taught at US and Canadian medical schools. Continuous improvement of educational initiatives will aid in producing genomically-literate physicians.


Calcaneocuboid Joint Arthritis of the Midfoot Precedes Tibiotalar Joint Arthritis.
Surgical models have best shown the relationship between ankle and mid-foot osteoarthritis, although findings regarding the calcaneocuboid joint have varied. To the authors' knowledge, no studies have evaluated the relationship between degenerative changes across the tibiotalar and calcaneocuboid joints. The goal of this study was to determine whether such a relationship exists and which joint degenerates first. A single examiner evaluated 694 tibiotalar and calcaneocuboid joints to determine the presence of osteoarthritis. Multiple linear regression analysis was conducted with a standard P value cutoff (P<.05) and 95% confidence interval. The average incidence of tibiotalar and calcaneocuboid osteoarthritis in specimens older than 40 years was compared with the incidence in those 40 years and younger. A positive correlation between tibiotalar and calcaneocuboid osteoarthritis was noted. African-American subjects were less likely than white subjects to have tibiotalar osteoarthritis. The finding of right and left tibiotalar and calcaneocuboid osteoarthritis in subjects 40 years and younger showed that midfoot arthritis was significantly more common than arthritis of the ankle. The prevalence of calcaneocuboid osteoarthritis remains stable after 40 years of age, and the prevalence of tibiotalar osteoarthritis approaches that of calcaneocuboid osteoarthritis. Calcaneocuboid osteoarthritis precedes tibiotalar osteoarthritis. Altered biomechanics involved in calcaneocuboid osteoarthritis are transferred to the tibiotalar joint, leading to tibiotalar osteoarthritis as the subject ages. Early education, surveillance, physical therapy, shoe adjustment, and orthotics may help to reduce the forces across the midfoot and prevent ankle arthritis in the long term. [Orthopedics. 2016; 39(6):e1112-e1116.].


Characteristics, outcomes, prognostic factors and treatment of patients with T-cell prolymphocytic leukemia (T-PLL).
T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive disease. In this study, we report our experience from 119 patients with T-PLL. We reviewed the clinico-pathologic records of 119 consecutive patients with T-PLL, who presented to our institution between 1990 and 2016. One hundred and nineteen patients with T-PLL were analysed. Complex karyotype and aberrations in chromosome 14 were seen in 65% and 52% patients, respectively. Seventy-five patients (63%) were previously untreated and 43 (37%) were initially treated outside our institution. Sixty-three previously untreated patients (84%) received frontline therapies. Overall, 95 patients (80%) have died. Median overall survival (OS) from diagnosis was 19 months [95% confidence interval (CI) 16-26 months]. Using recursive partitioning (RP), we found that patients with hemoglobin < 9.3 g/dl, lactate dehydrogenase (LDH) ≥ 1668 IU/l, white blood cell ≥ 208 K/l and β2M ≥ 8 mg/l had significantly inferior OS and patients with hemoglobin < 9.3 g/dl had inferior progression-free survival (PFS). In multivariate analysis, we identified that presence of pleural effusion [hazard ratio (HR) 2.08 (95% CI 1.11-3.9); P = 0.02], high LDH (≥ 1668 IU/l) [HR 2.5 (95% CI 1.20-4.24); P < 0.001)], and low hemoglobin (< 9.3 g/dl) [HR 0.33 (95% CI 0.14-0.75); P = 0.008] were associated with shorter OS. Fifty-five previously untreated patients received treatment with an alemtuzumab-based regimen (42 monotherapy and 13 combination with pentostatin). Overall response rate, complete remission rate (CR) for single-agent alemtuzumab and alemtuzumab combined with pentostatin were 83%, 66% and 82%, 73% respectively. In patients who achieved initial CR, stem cell transplantation was not associated with longer PFS and OS. Outcomes in T-PLL remain poor. Multicenter collaborative effort is required to conduct prospective studies.


Urbanization alters plastic responses in the common dandelion Taraxacum officinale.
Urban environments expose species to contrasting selection pressures relative to rural areas due to altered microclimatic conditions, habitat fragmentation, and changes in species interactions. To improve our understanding on how urbanization impacts selection through biotic interactions, we assessed differences in plant defense and tolerance, dispersal, and flowering phenology of a common plant species (Taraxacum officinale) along an urbanization gradient and their reaction norms in response to a biotic stressor (i.e., herbivory). We raised plants from 45 lines collected along an urbanization gradient under common garden conditions and assessed the impact of herbivory on plant growth (i.e., aboveground biomass), dispersal capacity (i.e., seed morphology), and plant phenology (i.e., early seed production) by exposing half of our plants to two events of herbivory (i.e., grazing by locusts). Independent from their genetic background, all plants consistently increased their resistance to herbivores by which the second exposure to locusts resulted in lower levels of damage suffered. Herbivory had consistent effects on seed pappus length, with seeds showing a longer pappus (and, hence, increased dispersal capacities) regardless of urbanization level. Aboveground plant biomass was neither affected by urbanization nor herbivore presence. In contrast to consistent responses in plant defenses and pappus length, plant fitness did vary between lines. Urban lines had a reduced early seed production following herbivory while rural and suburban lines did not show any plastic response. Our results show that herbivory affects plant phenotypes but more importantly that differences in herbivory reaction norms exist between urban and rural populations.


Laparoscopic donor nephrectomy in unusual venous anatomy - donor and recepient implications.
Laparoscopic donor nephrectomy is now a commonly performed procedure in most of renal transplantation centers. However, the suitability of laparoscopy for donors with abnormal venous anatomy is still a subject of debate. Between August 2007 and August 2014, 243 laparoscopic donor nephrectomies were performed in our institution. All donors were evaluated with preoperative three-dimensional spiral computed tomography (CT) angiography Thirteen (5.35%) donors had a left renal vein anomaly. A retrospective analysis was performed to collect donor and recipient demographics and perioperative data. Four donors had a type I retroaortic vein, seven had type II retroaortic vein and a circumaortic vein was seen in three donors. The mean operative time was 114±11 minutes and mean warm ischemia time was 202±12 seconds. The mean blood loss was 52.7±18.4mL and no donor required blood transfusion. Mean recipient creatinine at the time of discharge was 1.15±0.18mg/dL, and creatinine at six months and one year follow-up was 1.12±0.13mg/dL and 1.2±0.14mg/dL, respectively. There were no significant differences in operative time, blood loss, warm ischemia time, donor hospital stay or recipient creatinine at 6 months follow-up, following laparoscopic donor nephrectomy in patients with or without left renal vein anomalies. Preoperative delineation of venous anatomy using CT angiography is as important as arterial anatomy. Laparoscopic donor nephrectomy is safe and feasible in patients with retroaortic or circumaortic renal vein with good recipient outcome.


[Chiral safety of the biosphere as a biophysical problem].
The biosphere with its inherent chiral asymmetry fixed in the process of biological evolution at the level of L-amino acids and D-hydrocarbons and some other biologically active compounds of biogenic origin is under strong pressure of chiral substances produced by chemical, pharmaceutical, and other branches of industry and agriculture. Effective use of enantiomers is accompanied by toxic and even mutagenic effects of their mirror-image enantiomorphs. Only small amounts of products are tested for chiral purity; there is no system of global biosphere monitoring as well as no common standards of permissible concenrations. The investigation of the molecular basis of chiral stereospecificity of enzymes and cell receptors is of great interest from the point of view of fundamental biophysics. On the other hand, the development of chiral-selective sensors for environmental monitoring is important from the viewpoint of applied biophysics.


A Qualitative Assessment of Mothers' Experience With Pediatric Anemia Care in Arequipa, Peru.
Background: Despite national efforts to control pediatric anemia in Peru, each year, 67.4% of all newborns are diagnosed with anemia during their first year of life. The literature on Peruvian mothers' understanding and beliefs of pediatric anemia is limited. In the present study, we aimed to understand mother's perspective of pediatric anemia and explore their perceptions on how to prevent and treat anemia in Peru. Methods: During May-June 2018, we administered a short demographic questionnaire and conducted language-sensitive interviews with mothers of children clinically diagnosed with anemia in three different governmental health centers in Arequipa, Peru. Interviews were audio-recorded and transcribed verbatim. We used the Framework Analysis approach to analyze qualitative data. Results: A total of 14 Peruvian mothers were interviewed. Across interviews, three main themes emerged: (I) Mothers' Understanding of Pediatric Anemia; (II) Attitudes about Provider Recommendations for Pediatric Anemia Control; and (III) Barriers to Effective Pediatric Anemia Control. Peruvian mothers expressed skepticism toward national pediatric anemia guidelines as they believe recommendations received at health clinics jeopardized their children's overall health. Participants identified several barriers to effective anemia control: limited and confusing health information received during pediatric healthcare appointments, lack of systematic protocols in health clinics, and inconsistent referral processes. Conclusion: We identified factors that limit the acceptance of current pediatric anemia control guidelines followed at governmental health centers in Arequipa, Peru. Understanding maternal beliefs concerning pediatric anemia can guide future anemia control guidelines at the primary care level for pediatric patients in Peru.


The GRAPPA-OMERACT Working Group: 4 Prioritized Domains for Completing the Core Outcome Measurement Set for Psoriatic Arthritis 2019 Updates.
The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group provided updates at the 2019 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. The working group prioritized 4 domains, including musculoskeletal disease activity (enthesitis and dactylitis), fatigue, physical function, and structural damage. In this report, the working group summarizes its progress in standardizing the core outcome set for these 4 domains.


Inconsistencies with screening for traumatic brain injury in spinal cord injury across the continuum of care.
Explore how traumatic brain injury (TBI) is screened among spinal cord injury (SCI) patients across the continuum of care. Retrospective chart review Setting: Emergency department, trauma, inpatient rehabilitation Participants: 325 patients with SCI from inpatient rehabilitation facility (IRF) between March 1, 2011 and December 31, 2014 were screened. 49 eligible subjects had traumatic SCI and received care in adjoining acute care (AC) hospital. Demographic characteristics and variables that capture diagnosis of TBI/SCI included documentation from ambulance, emergency department, AC, and IRF including ICD-9 codes, altered mental status, loss of consciousness (LOC), Glasgow Coma Score, Post Traumatic Amnesia (PTA), neuroimaging, and cognitive assessments. Participants were male (81%), white (55%), privately insured (49%), and aged 39.3±18.0 years with 51% paraplegic and 49% tetraplegic. Mechanisms of injury were gunshot wound (31%), fall (29%), and motor vehicle accident (20%). TBI occurred in 65% of SCI individuals, however documentation of identification of TBI, LOC, and CT imaging results varied in H&P, discharge notes, and ICD-9 codes across the continuum. Cognitive assessments were performed on 16% of subjects. Documentation showed variability between AC and IRF and among disciplines. Imaging and GCS were more consistently documented than LOC and PTA. It is necessary to standardize screening processes between AC and IRF to identify dual diagnosis.


The association between air pollution and type 2 diabetes in a large cross-sectional study in Leicester: The CHAMPIONS Study.
Observational evidence suggests there is an association between air pollution and type 2 diabetes; however, there is high risk of bias. To investigate the association between air pollution and type 2 diabetes, while reducing bias due to exposure assessment, outcome assessment, and confounder assessment. Data were collected from 10,443 participants in three diabetes screening studies in Leicestershire, UK. Exposure assessment included standard, prevailing estimates of outdoor nitrogen dioxide and particulate matter concentrations in a 1×1km area at the participant's home postcode. Three-year exposure was investigated in the primary analysis and one-year exposure in a sensitivity analysis. Outcome assessment included the oral glucose tolerance test for type 2 diabetes. Confounder assessment included demographic factors (age, sex, ethnicity, smoking, area social deprivation, urban or rural location), lifestyle factors (body mass index and physical activity), and neighbourhood green space. Nitrogen dioxide and particulate matter concentrations were associated with type 2 diabetes in unadjusted models. There was no statistically significant association between nitrogen dioxide concentration and type 2 diabetes after adjustment for demographic factors (odds: 1.08; 95% CI: 0.91, 1.29). The odds of type 2 diabetes was 1.10 (95% CI: 0.92, 1.32) after further adjustment for lifestyle factors and 0.91 (95% CI: 0.72, 1.16) after yet further adjustment for neighbourhood green space. The associations between particulate matter concentrations and type 2 diabetes were also explained away by demographic factors. There was no evidence of exposure definition bias. Demographic factors seemed to explain the association between air pollution and type 2 diabetes in this cross-sectional study. High-quality longitudinal studies are needed to improve our understanding of the association.


A di-boron pair doped MoS2 (B2@MoS2) single-layer shows superior catalytic performance for electrochemical nitrogen activation and reduction.
Developing efficient electrocatalysts to convert nitrogen into ammonia represents a major chemistry challenge and is of great significance for sustaining life. A lot of recent studies have been focusing on the single-atom electrocatalysts for the N2 reduction reaction (NRR), yet the double-atom or few-atom catalysts, based on the non-metal catalytic center, in particular, have been rarely investigated. Herein from DFT simulations, we report diatomic boron doped single-layer MoS2, B2@MoS2, as the potential electrocatalyst for the nitrogen reduction reaction, and compare it with single boron atom doped MoS2, B@MoS2, based on thermodynamics, selectivity, and kinetics analysis. The results reveal that this novel diatomic modified catalyst exhibits excellent structural and thermodynamic stability, and shows significant improvement in the conductivity of MoS2 which is essential for the electrocatalytic NRR. Furthermore, the B2@MoS2 catalyst can effectively activate the inert N2 and promote N2 reduction to NH3via the enzymatic mechanism, and shows much better electrocatalytic activity than B@MoS2, as reflected by the significantly reduced overpotential (0.02 V vs. 0.30 V) and the much lower activation barrier (1.24 eV vs. 2.84 eV). Particularly, the close-to-zero overpotential predicted for B2@MoS2 is lower than those of most ever-reported single-atom electrocatalysts. The extraordinary activity of B2@MoS2 is closely related to the efficient electron transport as well as the synergism effect of diatomic boron. Our predictions hence suggest B2@MoS2 as a superior promising catalyst for efficient dinitrogen fixation and reduction.


Helicoverpa armigera ATP-binding cassette transporter ABCA2 is a functional receptor of Bacillus thuringiensis Cry2Ab toxin.
Crystalline (Cry) proteins from the bacterium Bacillus thuringiensis (Bt) are widely used in transgenic crops to control important insect pests. Bt crops have many benefits compared with traditional broad-spectrum insecticides, including improved pest control with reduced negative impacts on off-target organisms and fewer environmental consequences. Transgenic corn and cotton producing Cry2Ab Bt toxin are used globally to control several major lepidopteran pests, including the cotton bollworm, Helicoverpa armigera. Resistance to the Cry2Ab toxin and to Bt crops producing Cry2Ab is associated with mutations in the midgut ATP-binding cassette transporter ABCA2 gene in several lepidopterans. Gene-editing knockout has further shown that ABCA2 plays an important functional role in Cry2Ab intoxication. However, the precise role of ABCA2 in the mode of action of Cry2Ab has yet to be reported. Here, we used two in vitro expression systems to study the roles of the H. armigera ABCA2 (HaABCA2) protein in Cry2Ab intoxication. Cry2Ab bound to cultured Sf9 insect cells producing HaABCA2, resulting in specific and dose-dependent susceptibility to Cry2Ab. In contrast, Sf9 cells expressing recombinant mutant proteins missing at least one of the extracellular loop regions 1, 3, 4, and 6 or the intracellular loop containing nucleotide-binding domain 1 lost susceptibility to Cry2Ab, indicating these regions are important for receptor function. Consistent with these results, Xenopus laevis oocytes expressing recombinant HaABCA2 showed strong ion membrane flux in the presence of Cry2Ab, suggesting that HaABCA2 is involved in promoting pore formation during Cry2Ab intoxication. Together with previously published data, our results support HaABCA2 being an important receptor of Cry2Ab where it functions to promote intoxication in H. armigera.


ATR induces hepatic lipid metabolism disorder in rats by activating IRE1α/XBP1 signaling pathway.
Atrazine (ATR) is a widely used herbicide and due to its persistence in environment and bioaccumulation, it can cause harmful impacts on human health. ATR exposure can lead to disorders of lipid metabolism in the liver, but its underlying mechanism is still unclear. 40 eight-week-old rats were given different doses of ATR (0, 0.5, 5 and 50 mg/kg/d) for 90 days. The liver tissue and serum were collected for histological observation and biochemical analysis. The levels of lipid and oxidative stress were assessed using colorimetry. Changes in MMP and ROS of liver cells were observed through flow cytometry. The expression of mRNA and protein was detected using Real-Time PCR and western blot. The results showed that TC and HDL-C levels in both the liver and serum were increased in the ATR-treated groups. The levels of MDA were accumulated, while the levels of SOD and GSH were depleted in the liver with ATR exposure. The expression of liver lipid metabolism related genes (SCD1, DGAT2, ACC1, PPARγ) was elevated. The liver ERS was activated and the gene expression of IRE1α/XBP1 signal pathway and GRP78, GRP94 in the liver was increased. There was a correlation between the levels of ERS and the levels of lipid metabolism. These results suggested that ATR can activate ERS and promote the expression of IRE1α/XBP1 signaling pathway, and further lead to lipid metabolism disorders in rat liver. This study can provide valuable insights as a reference for the prevention and control of hazards associated with agricultural residues.


Mycobacterium grossiae sp. nov., a rapidly growing, scotochromogenic species isolated from human clinical respiratory and blood culture specimens.
A previously undescribed, rapidly growing, scotochromogenic species of the genus Mycobacterium (represented by strains PB739T and GK) was isolated from two clinical sources - the sputum of a 76-year-old patient with severe chronic obstructive pulmonary disease, history of tuberculosis exposure and Mycobacterium avium complex isolated years prior; and the blood of a 15-year-old male with B-cell acute lymphoblastic leukaemia status post bone marrow transplant. The isolates grew as dark orange colonies at 25-37 °C after 5 days, sharing features in common with other closely related species. Analysis of the complete 16S rRNA gene sequence (1492 bp) of strain PB739T demonstrated that the isolate shared 98.8 % relatedness with Mycobacterium wolinskyi. Partial 429 bp hsp65 and 744 bp rpoB region V sequence analyses revealed that the sequences of the novel isolate shared 94.8 and 92.1 % similarity with those of Mycobacterium neoaurum and Mycobacterium aurum, respectively. Biochemical profiling, antimicrobial susceptibility testing, HPLC/gas-liquid chromatography analyses and multilocus sequence typing support the taxonomic status of these isolates (PB739T and GK) as representatives of a novel species. Both isolates were susceptible to the Clinical and Laboratory Standards Institute recommended antimicrobials for susceptibility testing of rapidly growing mycobacteria including amikacin, ciprofloxacin, moxifloxacin, doxycycline/minocycline, imipenem, linezolid, clarithromycin and trimethropin/sulfamethoxazole. Both isolates PB739T and GK showed intermediate susceptibility to cefoxitin. We propose the name Mycobacterium grossiae sp. nov. for this novel species and have deposited the type strain in the DSMZ and CIP culture collections. The type strain is PB739T (=DSM 104744T=CIP 111318T).


The synthesis, properties, and reactivity of Lewis acidic aminoboranes.
The evolution of frustrated Lewis pair chemistry has led to significant research into the development of new Lewis acidic boranes. Much of this has focused on modifying aryl substituents rather than introducing heteroatoms bound to boron. We recently reported that bis(pentafluorophenyl)phenothiazylborane (1) could be used as a Lewis acid catalyst for the heterolytic dehydrocoupling of stannanes. In this work, we synthesize and characterize a family of Lewis acidic aminoboranes and explored their reactivity with various Lewis bases as well as their efficacy as catalysts for stannane dehydrocoupling and hydrosilylation. Quantum chemical calculations were undertaken to understand the origins of the Lewis acidity and the most Lewis acidic aminoborane (5) was found to be an effective catalyst even in coordinating solvents such as water or acetonitrile, suggesting the amino substituent provides a level of protection against competing donors.


Effect of the Titanium Nanoparticle on the Quantum Chemical Characterization of the Liquid Sodium Nanofluid.
Suspension state of a titanium nanoparticle in the liquid sodium was quantum chemically characterized by comparing physical characteristics, viz., electronic state, viscosity, and surface tension, with those of liquid sodium. The exterior titanium atoms on the topmost facet of the nanoparticle were found to constitute a stable Na-Ti layer, and the Brownian motion of a titanium nanoparticle could be seen in tandem with the surrounding sodium atoms. An electrochemical gradient due to the differences in electronegativity of both titanium and sodium causes electron flow from liquid sodium atoms to a titanium nanoparticle, Ti + Na → Ti(δ-) + Na(δ+), making the exothermic reaction possible. In other words, the titanium nanoparticle takes a role as electron-reservoir by withdrawing free electrons from sodium atoms and makes liquid sodium electropositive. The remaining electrons in the liquid sodium still make Na-Na bonds and become more stabilized. With increasing size of the titanium nanoparticle, the deeper electrostatic potential, the steeper electric field, and the larger Debye atmosphere are created in the electric double layer shell. Owing to electropositive sodium-to-sodium electrostatic repulsion between the external shells, naked titanium nanoparticles cannot approach each other, thus preventing the agglomeration.


Combining epidemiology and biomechanics in sports injury prevention research: a new approach for selecting suitable controls.
Several important methodological issues need to be considered when designing sports injury case-control studies. Major design goals for case-control studies include the accounting for prior injury risk exposure, and optimal definitions of both cases and suitable controls are needed to ensure this. This article reviews methodological aspects of published sports injury case-control studies, particularly with regard to the selection of controls. It argues for a new approach towards selecting controls for case-control studies that draws on an interface between epidemiological and biomechanical concepts. A review was conducted to identify sport injury case-control studies published in the peer-review literature during 1985-2008. Overall, 32 articles were identified, of which the majority related to upper or lower extremity injuries. Matching considerations were used for control selection in 16 studies. Specific mention of application of biomechanical principles in the selection of appropriate controls was absent from all studies, including those purporting to evaluate the benefits of personal protective equipment to protect against impact injury. This is a problem because it could lead to biased conclusions, as cases and controls are not fully comparable in terms of similar biomechanical impact profiles relating to the injury incident, such as site of the impact on the body. The strength of the conclusions drawn from case-control studies, and the extent to which results can be generalized, is directly influenced by the definition and recruitment of cases and appropriate controls. Future studies should consider the interface between epidemiological and biomechanical concepts when choosing appropriate controls to ensure that proper adjustment of prior exposure to injury risk is made. To provide necessary guidance for the optimal selection of controls in case-control studies of interventions to prevent sports-related impact injury, this review outlines a new case-control selection strategy that reflects the importance of biomechanical considerations, which ensures that controls are selected based on the presence of the same global injury mechanism as the cases. To summarize, the general biomechanical principles that should apply to the selection of controls in future case-control studies are as follows: (i) each control must have been exposed to the same global injury mechanism as the case, (e.g. head impact, fall onto outstretched arm); and (ii) intrinsic (individual) factors (e.g. age, sex, skill level) that might modify the person's response to the relevant biomechanical loads are adjusted when either selecting the controls or are in the analysis phase. The same considerations for control selection apply to other study designs such as matched cohort studies or case-crossover studies.


[Treatment of Crohn's disease with anti TNF alpha antibodies--the experience in the Tel Aviv Medical Center].
TNF alpha is a pro-inflammatory cytokine in Crohn's disease and it's neutralization is beneficial in patients with active disease. Remicade is a chimeric monoclonal anti-TNF antibody. Remicade is used in our center since December 1998 in 13 patients who were treated for active disease or fistula. We followed the patients and treatment results in order to estimate the efficacy and safety of this preparation. Response to treatment was measured by the Crohn's Disease Activity Index (CDAI) in patients treated due to active disease, or by the presence of discharge from external fistulae. Five out of seven patients with fistulae had less or no discharge after completing a course of 3 infusions. Four out of 6 patients treated due to active disease improved significantly after a single infusion. Five out of the six needed additional injections due to symptom recurrence. Intervals between infusions were 2 weeks--for fistulae patients to 32 weeks for patients with active disease. Adverse events for the 13 patients were usually mild except for 4 patients that suffered from anaphylactic shock, disseminated eruption (2) and eosinophilic pneumonitis. In summary, treatment of patients with active Crohn's disease or fistulae with monoclonal anti-TNF antibodies is an effective and relatively safe option after established treatment has failed. Analyzing the results of on going clinical trials and of the patients treated off-protocol will enable to establish new treatment strategies for patients with active Crohn's disease and fistulae.


[Phosphorylation and dephosphorylation of rna polymerase III holoenzyme are modifications regulating the level of transcription in vitro].
Two subforms of RNA polymerase III-IIIa and IIIb--were identified in human placenta nuclei. These subforms differed in molecular weight of one subunit, and in buoyant density in glycerol concentration gradient. Protein kinase activity, which phosphorylates at least four subunits of RNA polymerase IIIa and three subunits of RNA polymerase IIIb in vitro, was copurified with both the subforms. Protein kinase activity was inhibited by wortmannin, a specific PI3-kinase inhibitor. RNA polymerase III dephosphorylation by alkaline phosphatase in vitro decrease the transcription level on specific Alu-template. The associated protein kinase was not able to phosphorylate dephosphorylated RNA polymerase IIIa and to restore the transcription level up to the control one.


The Rural Physician as Preceptor: How rural physicians can supervise residents in a rural practice.
Rural family practice offers a wealth of potential clinical teaching material for family practice residents. In order to exploit this potential, the Department of Family Practice at the University of British Columbia has developed a community-based program in which second-year residents in family practice spend the year in rural communities under the supervision of a family physician preceptor. This paper describes some of the problems and satisfactions facing the rural physician who is interested in becoming a preceptor and offers practical guidelines on how a resident can be incorporated into the practice.


[Malignant melanoma of the nasal cavity and paranasal sinuses].
Malignant melanomas represent about 3% of all nasosinusal neoplasms. They usually are located in the nasal septum and their maximum incidence is in the sixth and seventh decades. In the early stages they are asymptomatic, which delays diagnosis and reduces the possibilities of cure to 15-30%. Eight cases of nasosinusal melanoma are reported and their characteristics are reviewed with special attention to prognostic factors.


Biofilm formation of mucosa-associated methanoarchaeal strains.
Although in nature most microorganisms are known to occur predominantly in consortia or biofilms, data on archaeal biofilm formation are in general scarce. Here, the ability of three methanoarchaeal strains, Methanobrevibacter smithii and Methanosphaera stadtmanae, which form part of the human gut microbiota, and the Methanosarcina mazei strain Gö1 to grow on different surfaces and form biofilms was investigated. All three strains adhered to the substrate mica and grew predominantly as bilayers on its surface as demonstrated by confocal laser scanning microscopy analyses, though the formation of multi-layered biofilms of Methanosphaera stadtmanae and Methanobrevibacter smithii was observed as well. Stable biofilm formation was further confirmed by scanning electron microscopy analysis. Methanosarcina mazei and Methanobrevibacter smithii also formed multi-layered biofilms in uncoated plastic μ-dishes(TM), which were very similar in morphology and reached a height of up to 40 μm. In contrast, biofilms formed by Methanosphaera stadtmanae reached only a height of 2 μm. Staining with the two lectins ConA and IB4 indicated that all three strains produced relatively low amounts of extracellular polysaccharides most likely containing glucose, mannose, and galactose. Taken together, this study provides the first evidence that methanoarchaea can develop and form biofilms on different substrates and thus, will contribute to our knowledge on the appearance and physiological role of Methanobrevibacter smithii and Methanosphaera stadtmanae in the human intestine.


Stress, social support, and depressive symptomatology in children with congenital/acquired limb deficiencies.
Ongoing chronic strain of living with limb deficiencies and normal daily hassles may interact to produce a negative impact on adjustment. Degree of limb loss, daily hassles/microstressors, and classmate, parent, teacher, and friend social support were investigated as predictors of depressive symptomatology in 27 children with congenital/acquired limb deficiencies. Hierarchical multiple regression analyses were utilized to test the main effects and buffering interactions effects models of the stress-social support-depressive symptomatology relationship. Degree of limb loss was not a significant predictor. Microstressors and classmate, parent, and teacher social support were all significant predictors of depressive symptomatology. None of the Stress X Social Support interaction terms were statistically significant. The overall model of stress and social support predicted 73% of the variance in depressive symptomatology.


Gene variants of TCF7L2 are histopathologically important in colorectal cancers but do not have direct association with MYC expression.
Rapidly accumulating preclinical and clinical studies have helped us to unveil underlying mechanisms of colorectal cancer development and progression. Deregulated signaling pathways play instrumental role in carcinogenesis, drug resistance and metastasis. Wnt signaling cascade has attracted considerable attention in colorectal cancer as many ground-breaking researches have highlighted central role of Wnt pathway in pathogenesis of colorectal cancer. T-Cell Transcription Factors (TCFs) have been shown to work synchronously with β-catenin to fuel colorectal cancer development and progression. Chromatin immuno-precipitation coupled with high-throughput sequencing (ChIP-Seq) data sets has deepened our knowledge about critical role of risk-associated SNPs. Increasingly it is being reported that many risk-associated SNPs are located within binding sites for transcription factors and consequently risk status of these SNPs may modify binding pattern of transcriptional factors and thus rewire the transcriptional regulation. DNA was extracted from peripheral blood samples of 117 colorectal cancer patients and 127 healthy subjects. TCF7L2 variants (rs6983267, rs7903146) were examined by the PCR-RFLP method. Tumor and the surrounding tissues were dissected from 37 CRC patients and RNA isolation was performed. The gene expression of c-myc was determined by RT-PCR. T allele carriage of rs6983267 variant was found to be associated with CRC (p=0.042). TT genotype of rs7903146 was associated with late tumor stage (T3+T4) (p=0.037) and presence of mucinous component (p=0.031). TTCT haplotype was found to be statistically higher in CRC compared to the control group (p=0.007). There was no statistically significant difference in c-myc gene expression. TCF7L2 gene variants may play an important role in histopathologic aspects associated with CRC and it is independent of c-myc gene expression.


Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response.
Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.


Recent Outbreaks of Diphtheria in Dibrugarh District, Assam, India.
Diphtheria is still a significant child health problem in countries with low immunization coverage. Reports of diphtheria in adult population are also increasing. Here we describe three recent outbreaks of diphtheria in Dibrugarh district, Assam in two consecutive years. The study was undertaken in Assam Medical College & Hospital, Dibrugarh after the diagnosis of two Diphtheria cases in the month of September and October 2015 and another in January 2016. Outbreak investigation was done after defining operational definition and throat swabs were collected from thirty three (33) individuals including three (3) index cases and thirty (30) close contacts. Diagnosis was done by clinical findings, direct microscopy, bacteriological culture and in-house designed multiplex Polymerase Chain Reaction (PCR) of the isolates for the expression of Corynebacterium diphtheriae specific rpoB gene and tox gene. Out of the 10 confirmed cases, 2 and 7 were in the first two outbreaks while only one in the third outbreak respectively. All the cases were of age > 10 years, unimmunized or partially immunized. The overall mortality was 20%. PCR results revealed all the culture positive isolates to be tox gene positive. Diphtheria is a resurgent problem in our region with a significant age shift towards adult.


Relation of abdominal height to cardiovascular risk factors in young adults: the Bogalusa heart study.
Obesity and fat patterns are important predictors of coronary heart disease risk. The relations of abdominal height (sagittal diameter) and various obesity measures to coronary heart disease risk factors were examined in a community-based sample of 409 Blacks and 1,011 Whites aged 20-38 years in Bogalusa, Louisiana (1995-1996). Obesity measures used included weight, waist circumference, waist:hip ratio, waist:height ratio, abdominal height, triceps and subscapular skinfold thicknesses, body mass index, and conicity index. Abdominal height was highly correlated with other obesity measures, especially waist circumference (0.937-0.944, p < 0.001), and was least correlated with height. In multivariate analysis, abdominal height was an independent predictor of levels of total cholesterol, triglycerides, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, glucose, and insulin and of systolic and diastolic blood pressures (p < 0.05 to p < 0.001), with total R2 values ranging from 0.13 to 0.52. Abdominal height contributed more to the prediction of blood pressure than did other measures of central obesity. In canonical analysis, abdominal height was correlated more strongly with the coronary disease risk factor variables as a group than were other obesity measures. These results suggest that abdominal height adds another dimension to measures of obesity in that it may help to assess a component of visceral fat that other measures miss.


Centre-specific or average unit costs in multi-centre studies? Some theory and simulation.
Costing issues are increasingly being addressed in multi-centre studies. In this paper, two methods for collecting costing information are compared within a simulated clinical trial setting. One method estimates average treatment costs by applying unit costs averaged across treatment centres to centre-specific volumes of resource use. The second uses centre-specific information for both the unit costs and the resource volumes, and then averages across centres. Using a pre-specified production relation between the different volumes of resource use, and simulating changes in unit costs, it is shown that these two methods result in statistically different estimates of average treatment costs. This finding holds, regardless of the degree of substitutability between the resource volumes, except when considerable uncertainty surrounds treatment centre responses to relative changes in unit costs. The findings suggest that a more cautious approach should be adopted in the collection, calculation and interpretation of treatment costs in multi-centre studies.


[Changed health problems in a changing pig-farming concern in The Netherlands until 1980].
In 1905 Poels published 'Disease of swine in the Netherlands'. This book dealt predominantly with swine fever, erysipelas, tuberculosis and 'pneumonia'. Between 1920 and 1940 others reported on streptococci, lobular haemmorrhagic pneumonia, bordetellosis, Aujeszky's disease and postweaning diarrhoea. After the second world war, particularly after 1960, the Dutch pig-farming industry developed at a tremendous rate. As a consequence, the health problems changed. Certain diseases became less important: tuberculosis, erysipelas, Leptospira tarrasovi, enteroviruses. Yet other diseases including postweaning diarrhoea, atrophic rhinitis and Aujeszky's disease became problems of increasing importance. At the end of the seventies the knowledge of E. coli toxin types was substantial. On the other hand, information concerning the pathogenesis and pathophysiology was very limited. Bordetella bronchiseptica was still considered to be the most important agent in AR, zootechnical factors being predisposing. However, one was aware of missing links. Aujeszky's disease was obscure until the late fifties. Until 1972 only occasional reports were made. In that year, an epidemic occurred in the Gelderse Vallei. Another epidemic occurred in 1974 in the provinces of Brabant and Limburg. By 1980 proper vaccines were available and Aujeszky's disease was not yet a political problem.


Self-monitoring diabetes with multiple mobile health devices.
The purpose of this study was to examine the use of multiple mobile health technologies to generate and transmit data from diverse patients with type 2 diabetes mellitus (T2DM) in between clinic visits. We examined the data to identify patterns that describe characteristics of patients for clinical insights. We enrolled 60 adults with T2DM from a US healthcare system to participate in a 6-month longitudinal feasibility trial. Patient weight, physical activity, and blood glucose were self-monitored via devices provided at baseline. Patients also responded to biweekly medication adherence text message surveys. Data were aggregated in near real-time. Measures of feasibility assessing total engagement in device submissions and survey completion over the 6 months of observation were calculated. It was feasible for participants from different socioeconomic, educational, and racial backgrounds to use and track relevant diabetes-related data from multiple mobile health devices for at least 6 months. Both the transmission and engagement of the data revealed notable patterns and varied by patient characteristics. Using multiple mobile health tools allowed us to derive clinical insights from diverse patients with diabetes. The ubiquitous adoption of smartphones across racial, educational, and socioeconomic populations and the integration of data from mobile health devices into electronic health records present an opportunity to develop new models of care delivery for patients with T2DM that may promote equity as well.


Effect of prefabricated bar design with implant-stabilized prostheses on ridge resorption: a clinical report.
This investigation was concerned with the resorption of the posterior mandibular residual ridge in patients wearing mandibular overdentures supported by either parallel-sided bars (rigid joint) or oval straight bars (resilient joint) on two activated implants. Rotational tomographs were taken shortly after implant placement and up to 8 years later. Using proportional measurement, the area of residual ridge was measured in bilateral posterior areas. Patients rehabilitated with implant-stabilized mandibular overdentures demonstrated posterior mandibular residual ridge resorption at low rates, which were not significantly influenced by the design of the prefabricated bar.


Effects of community-level bed net coverage on malaria morbidity in Lilongwe, Malawi.
The protective effect of insecticide-treated bed nets against individual-level malaria transmission is well known, however community-level effects are less understood. Protective effects from community-level bed net use against malaria transmission have been observed in clinical trials, however, the relationship is less clear outside of a controlled research setting. The objective of this research was to investigate the effect of community-level bed net use against malaria transmission outside of a bed net clinical trial setting in Lilongwe, Malawi following national efforts to scale-up ownership of long-lasting, insecticide-treated bed nets. An annual, cross-sectional, household-randomized, malaria transmission intensity survey was conducted in Lilongwe, Malawi (2011-2013). Health, demographic, and geographic-location data were collected. Participant blood samples were tested for Plasmodium falciparum presence. The percentage of people sleeping under a bed net within 400-m and 1-km radii of all participants was measured. Mixed effects logistic regression models were used to measure the relationship between malaria prevalence and surrounding bed net coverage. Each year, 800 people were enrolled (400 <5 years; 200 5-19 years; 200 ≥20 years; total n = 2400). From 2011 to 2013, malaria prevalence declined from 12.9 to 5.6%, while bed net use increased from 53.8 to 78.6%. For every 1% increase in community bed net coverage, malaria prevalence decreased among children under 5 years old [adjusted odds ratio: 0.98 (0.96, 1.00)]. Similar effects were observed in participants 5-19 years [unadjusted odds ratio: 0.98 (0.97, 1.00)]; the effect was attenuated after adjusting for individual-level bed net use. Community coverage was not associated with malaria prevalence among adults ≥20 years. Supplemental analyses identified more pronounced indirect protective effects from community-level bed net use against malaria transmission among children under 5 years who were sleeping under a bed net [adjusted odds ratio: 0.97 (0.94, 0.99)], compared to children who were not sleeping under a bed net [adjusted odds ratio: 0.99 (0.97, 1.01)]. Malawi's efforts to scale up ownership of long-lasting, insecticide-treated bed nets are effective in increasing reported use. Increased community-level bed net coverage appears to provide additional protection against malaria transmission beyond individual use in a real-world context.


Observation of Quantum-Size Effects at Room Temperature on Metal Surfaces With STM.
Surface steps act as confining barriers for electrons in metal-surface states. Thus, narrow terraces and small single-atom-high metal islands act as low-dimensional, electron-confining structures. In sufficiently small structures, quantum-size effects are observable even at room temperature. Scanning tunneling spectroscopy is used to image the probability amplitude distributions and discrete spectra of the confined states. Examination of the electronic structure of the steps provides evidence for electron-density smoothing and the formation of step-edge states. Estimates of the electron-confining barriers are obtained.


Evolution in impedance at the electrode-skin interface of two types of surface EMG electrodes during long-term recordings.
The evolution in impedance at the electrode-skin interface of Beckman and Red Dot electrodes was assessed during long-term recordings. Impedance was measured between each pair of electrodes, arranged in a bipolar configuration on tibialis anterior (n=13). A waveform constructed of sinusoids of known frequencies, evenly distributed on a log scale from 1-16,384 Hz, was applied through the electrodes, and the result recorded by a DAQ system. SEMG signals were recorded at 1000 Hz during isometric dorsiflexion contractions of 30 s, performed every 15 min for 2 h. Impedance data were acquired at 65,536 Hz immediately before and after SEMG recordings. Large individual differences in impedance levels were observed at low frequencies. At high frequencies, impedance values depended only on the electrode type. Impedance decreased steadily with time for Beckman electrodes (p < 0.05), but did not decrease significantly for Red Dot electrodes. The magnitude of the reduction over time varied widely between individuals, and was related to the initial impedance values. The impedance-bandwidth product remained constant for each electrode type (95% confidence intervals 146.2-148.2 and 126.1-127.8 for Beckman and Red Dot electrodes respectively). When skin impedance is electrically modelled with a simple network containing a resistor and a capacitor, the capacitance varies with the properties of the electrode used, whereas resistance is dependent on the subject. Furthermore, the EMG spectrum is unaffected by impedance provided skin preparation is sufficient to reduce the impedance below 55 komega.


Melt Extrusion of High-Dose Co-Amorphous Drug-Drug Combinations : Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li.
Many future drug products will be based on innovative manufacturing solutions, which will increase the need for a thorough understanding of the interplay between drug material properties and processability. In this study, hot melt extrusion of a drug-drug mixture with minimal amount of polymeric excipient was investigated. Using indomethacin-cimetidine as a model drug-drug system, processability of physical mixtures with and without 5% (w/w) of polyethylene oxide (PEO) were studied using Differential Scanning Calorimetry (DSC) and Small Amplitude Oscillatory Shear (SAOS) rheometry. Extrudates containing a co-amorphous glass solution were produced and the solid-state composition of these was studied with DSC. Rheological analysis indicated that the studied systems display viscosities higher than expected for small molecule melts and addition of PEO decreased the viscosity of the melt. Extrudates of indomethacin-cimetidine alone displayed amorphous-amorphous phase separation after 4 weeks of storage, whereas no phase separation was observed during the 16 week storage of the indomethacin-cimetidine extrudates containing 5% (w/w) PEO. Melt extrusion of co-amorphous extrudates with low amounts of polymer was found to be a feasible manufacturing technique. Addition of 5% (w/w) polymer reduced melt viscosity and prevented phase separation.


Extrachromosomal inheritance of carbon dioxide sensitivity in the mosquito Culex quinquefasciatus.
Mosquitoes from a laboratory colony of Culex quinquefasciatus from Matsu Island, China, develop irreversible paralytic symptoms after exposure to carbon dioxide at 1 degree. This CO2 sensitivity is caused by an inherited infectious agent, probably a virus. Crossing studies between CO2-sensitive and -resistant mosquitoes showed that the sensitivity trait is inherited extrachromosomally in a fashion strictly analogous to the hereditary transmission of sigma virus in Drosophila melanogaster. Sensitivity could be maintained through maternal transmission alone, despite nine generations of backcrossing of "stabilized" CO2-sensitive females to males from a resistant strain. CO2-sensitive males crossed to resistant females transmitted sensitivity to a portion of their F1 progeny, and only the female F1 sensitives were capable of further hereditary transmission.--Matsu, or a very similar hereditary infectious agent, is common in natural populations of Cx. quinquefasciatus on Oahu, Hawaii. Fifty-nine percent of the families reared from field-collected egg rafts contained CO2-sensitive mosquitoes, and some families contained only sensitive mosquitoes.


Rapid Divergence of Nesting Depth and Digging Appendages among Tunneling Dung Beetle Populations and Species.
Many dung beetle communities are characterized by species that share very similar morphological, ecological, and behavioral traits and requirements yet appear to be stably maintained. Here, we document that the morphologically nearly indistinguishable, sympatric, and syntopic tunneling sister species Onthophagus taurus and Onthophagus illyricus may be avoiding competitive exclusion by nesting at remarkably different soil depths. Intriguingly, we also find rapid divergence in preferred nesting depth across native and recently established O. taurus populations. Furthermore, geometric morphometric analyses reveal that both inter- and intraspecific divergences in nesting depth are paralleled by similar changes in the shape of the primary digging appendages, the fore tibiae. Collectively, our results identify preferred nesting depth and tibial shape as surprisingly evolutionarily labile and with the potential to ease interspecific competition and/or to facilitate adaptation to local climatic conditions.