Antigenicity of a recombinant Ro (SS-A) fusion protein.
The antigenicity of the 60-kd human Ro (SS-A) synthesized in vitro from its complementary DNA as a beta-galactosidase fusion protein (beta-gal-Ro) was evaluated by Western blotting. In this analysis, almost all the anti-Ro (SS-A)-positive sera that bound beta-gal-Ro also bound affinity-purified 60-kd human Ro (SS-A) (P less than 0.005). Three of the 27 anti-Ro (SS-A) precipitin-positive sera, however, did not show reactivity on Western blot analysis, which suggests that in some sera, antigenicity to Ro (SS-A) is destroyed by denaturation. Of the 22 sera that were reactive with beta-gal-Ro, 2 were not reactive with affinity-purified human Ro (SS-A). Two serum samples that did not react with beta-gal-Ro were also reactive with affinity-purified human Ro (SS-A). Nevertheless, except for a small percentage of Ro (SS-A) precipitin-positive sera, the frequency of antibody binding to the fusion protein was similar to the frequency of binding to the purified antigen in Western blots. Recombinant Ro (SS-A) antigen may therefore be valuable in the serologic evaluation of anti-Ro (SS-A) autoantibodies.


Visco-Elastic and Thermal Properties of Microbiologically Synthesized Polyhydroxyalkanoate Plasticized with Triethyl Citrate.
The current research is devoted to the investigation of the plasticization of polyhydroxybutyrate (PHB) and polyhydroxybutyrate-co-hydroxyvalerate (PHBV) with triethyl citrate (TEC). Three different PHB or PHBV-based systems with 10, 20, and 30 wt.% of TEC were prepared by two-roll milling. The effect of TEC on the rheological, thermal, mechanical, and calorimetric properties of the developed compression-molded PHB and PHBV-based systems was determined. It was revealed that the addition of TEC significantly influenced the melting behavior of both polyhydroxyalkanoates (PHA), reducing their melting temperatures and decreasing viscosities. It was also revealed that all the investigated systems demonstrated less than 2% weight loss until 200 °C and rapid degradation did not occur until 240-260 °C in an oxidative environment. Apart from this, a remarkable increase (ca 2.5 times) in ultimate tensile deformation εB was observed by increasing the amount of TEC in either PHB or PHBV. A concomitant, considerable drop in ultimate strength σB and modulus of elasticity E was observed. Comparatively, the plasticization efficiency of TEC was greater in the case of PHBV.


Charge Number Dependence of the Dephasing Rates of a Graphene Double Quantum Dot in a Circuit QED Architecture.
We use an on-chip superconducting resonator as a sensitive meter to probe the properties of graphene double quantum dots at microwave frequencies. Specifically, we investigate the charge dephasing rates in a circuit quantum electrodynamics architecture. The dephasing rates strongly depend on the number of charges in the dots, and the variation has a period of four charges, over an extended range of charge numbers. Although the exact mechanism of this fourfold periodicity in dephasing rates is an open problem, our observations hint at the fourfold degeneracy expected in graphene from its spin and valley degrees of freedom.


[Autoantibodies against the exocrine pancreas and against intestinal goblet cells in the diagnosis of Crohn's disease and ulcerative colitis].
It was demonstrated by indirect immunofluorescence that Crohn's disease and ulcerative colitis are serologically distinct. In 59 patients with Crohn's disease, confirmed by endoscopy and histology, 23 (39%) had serum autoantibodies against exocrine pancreas; in 17 (29%) the titre was 1 : 100 or higher. In 46 patients with confirmed ulcerative colitis pancreas antibodies were demonstrated only twice, in 100 healthy control subjects only 3 times, with titres less than 1 : 100. Pancreas antibodies do not occur in high concentrations in pancreatitis; titres higher than 1 : 100 therefore suggest Crohn's disease. The pancreas antibodies of patients with Crohn's disease were predominantly immunoglobulins IgA and IgG, twice they were IgD and once IgM, never IgE. In 6 patients the pancreas antibodies fixed complement. Autoantibodies against intestinal goblet cells were found only in patients with ulcerative colitis (13 of 46 = 28%). The titres range was from 1 : 10 to 1 : 1000. The goblet-cell antibodies consisted only of IgA and IgG, never reacting with complement. These results indicate that determining pancreas and goblet-cell antibodies alone will make it possible to diagnose either Crohn's disease or ulcerative colitis in more than a quarter of patients with chronic inflammatory intestinal disease.


Building capacity for librarian support and addressing collaboration challenges by formalizing library systematic review services.
Many health sciences librarians are noticing an increase in demand for systematic review support. Developing a strategic approach to supporting systematic review activities can address commonly reported barriers and challenges including time factors, methodological issues, and supporting student-led projects. This case report describes how a health sciences library at a mid-sized university developed and implemented a structured and defined systematic review service in order to build capacity for increased librarian support and to maximize librarians' time and expertise. The process also revealed underlying collaboration challenges related to student-led systematic reviews and research quality concerns that needed to be addressed. The steps for developing a formal service included defining the librarian's role and a library service model, building librarian expertise, developing documentation to guide librarians and patrons, piloting and revising the service model, marketing and promoting the service, and evaluating service usage. The two-tiered service model developed for advisory consultation and collaboration provides a framework for supporting systematic review activities that other libraries can adapt to meet their own needs. Librarian autonomy in deciding whether to collaborate on reviews based on defined and explicit considerations was crucial for maximizing librarians' time and expertise and for promoting higher quality research. Monitoring service usage will be imperative for managing existing and future librarian workload. These data and tracking of research outputs from librarian collaborations may also be used to advocate for new librarian positions.


Inter-species comparative antioxidant assay and HPTLC analysis of sakuranetin in the chloroform and ethanol extracts of aerial parts of Rhus retinorrhoea and Rhus tripartita.
Extensive research on Rhus (Anacardiaceae) shows their antioxidant potential, which warrants further evaluation of its other species. To perform a comparative antioxidant assay on extracts of R. retinorrhoea and R. tripartita, including sakuranetin quantification by a validated HPTLC method. In vitro antioxidant assay was performed on chloroform and ethanol extracts of R. retinorrhoea Steud. ex Oliv. (RRCE and RREE) and R. tripartita (Ucria) Grande (RTCE and RTEE) by DPPH radical scavenging (at 31.25, 62.5, 125, 250 and 500 μg/mL concentrations) and β-carotene-linoleic acid bleaching methods at 500 μg/mL concentration. Densitometric HPTLC method was developed and validated using toluene: ethyl acetate: methanol (8:2:0.2; v/v/v) as mobile phase, executed on glass-backed silica gel F254 plate and scanned at 292 nm. Antioxidant activity of Rhus extracts tested by the two methods (DPPH/BCB) was found in order of RTEE > RREE > RTCE > RRCE with IC50 118.67/256.26, 315.75/82.35, 827.92/380.0 and 443.69/292.75, respectively. Scanning of the HPTLC plate provided an intense peak of sakuranetin at Rf = 0.59. The estimated sakuranetin content in the dry weight of the extracts was highest in RREE (27.95 μg/mg) followed by RRCE (25.22 μg/mg), RTEE (0.487 μg/mg) and RTCE (0.0 μg/mg). Presence of sakuranetin in RREE, RRCE and RTEE supported the highest antioxidant property of the two Rhus species. Nonetheless, low sakuratenin in R. tripartita indicated the presence of other bioactive constituents responsible for synergistic antioxidant activity. The developed HPTLC method therefore guarantees its application in quality control of commercialized herbal drugs and formulations containing sakuranetin.


A multistate platform model for time-to-event endpoints in oncology clinical trials.
A multistate platform model was developed to describe time-to-event (TTE) endpoints in an oncology trial through the following states: initial, tumor response (TR), progressive disease (PD), overall survival (OS) event (death), censor to the last evaluable tumor assessment (progression-free survival [PFS] censor), and censor to study end (OS censor), using an ordinary differential equation framework. Two types of piecewise functions were used to describe the hazards for different events. Piecewise surge functions were used for events that require tumor assessments at the scheduled study visit times (TR, PD, and PFS censor). Piecewise constant functions were used to describe hazards for events that occur evenly throughout the study (OS event and OS censor). The multistate TTE model was applied to describe TTE endpoints from a published phase III study. The piecewise surge functions well-described the observed surges of hazards/events for TR, PD, PFS, and OS occurring near scheduled tumor assessments and showed good agreement with all Kaplan-Meier curves. With the flexibility of piecewise hazard functions, the model was able to evaluate covariate effects in a time-variant fashion to better understand the temporal patterns of disease prognosis through different disease states. This model can be applied to advance the field of oncology trial design and optimization by: (1) enabling robust estimations of baseline hazards and covariate effects for multiple TTE endpoints, (2) providing a platform model for understanding the composition and correlations between different TTE endpoints, and (3) facilitating oncology trial design optimization through clinical trial simulations.


Intravenous gamma globulin as first line therapy in polymyositis and dermatomyositis: an open study in 11 adult patients.
Polymyositis (PM) and dermatomyositis (DM) are inflammatory muscle diseases of presumed autoimmune origin. Many possible interventions are available to treat these patients: corticosteroids, immunosuppressive drugs, plasmapheresis, and total body irradiation. But these therapies are not always effective and may be responsible for certain serious side effects. Polyvalent intravenous immunoglobulin (IVIG) has been tried with success in inflammatory myopathies after failure of traditional treatment. An attempt was made to evaluate the efficacy of IVIG as first line therapy in patients with PM or DM. Eleven Caucasian patients [6 women, 5 men, mean age 55.6 (SD 10.1) years], with active recent inflammatory myopathy, were treated by high doses of IVIG as first choice. The average duration of inflammatory myopathy before IVIG was 9.6 months (SD 10.2 months, with a range of 1 month to 3 years). Five patients had PM and 6 had DM. None had myositis associated with connective tissue disease. Two patients had a history of malignant disease: 1 lymphoma and 1 breast tumor with relapse of the malignancy during the study. One patient had a probable lung carcinoma and in another patient, ovarian carcinoma was diagnosed a few months after the onset of IVIG. We used preparations of polyvalent human i.v. gamma globulins with intact IgG. All patients received 1 g/kg daily for 2 days each month. The mean course of treatment was 4 months. Clinical assessment, evaluated by proximal muscle power and biochemical tests, was carried out before each treatment period. Significant clinical improvement was noted in only 3 of the 11 patients (one with acute coxsackie virus B infection, and one with possible drug induced myopathy). Mean muscle power estimated for the 11 patients before and after IVIG therapy was not significantly improved. Eight patients showed significant biochemical improvement (more than 50%). Mean CK levels for the 11 patients showed a statistically significant decrease during IVIG therapy (p < 0.01). Minor IVIG side effects were noted in one patient. IVIG therapy seems effective rarely as first therapy in patients with inflammatory myopathy but may be considered especially in viral or drug induced myopathy. IVIG therapy as the first treatment may also be tried in patients with contraindication for steroids, and in mild myopathy, especially in the elderly, to avoid steroid induced side effects.


S100 protein-positive sustentacular cells in malignant and locally aggressive adrenal pheochromocytomas.
The absence or presence of S100-positive sustentacular cells has been previously shown to be correlated with benign and malignant pheochromocytomas and paragangliomas. We evaluated a total of 17 malignant and recurrent or locally aggressive adrenal pheochromocytomas for their quantity of sustentacular cells. An absence of sustentacular cells was demonstrated in the majority of malignant cases, while the locally aggressive or recurrent group usually contained an abundance of these cells. However, in one malignant case a constant moderate number of sustentacular cells in the primary site and in two sequential metastases was found. We conclude that the absence of sustentacular cells in pheochromocytomas may indicate a lesion with a greater potential for metastasis and that sustentacular cells, when they are present in a malignant pheochromocytoma, are an integral part of the tumor.


Quantitative evaluation of a clinical intervention aimed at changing prescriber behaviour in response to new guidelines.
The objective of the study was to assess prescribers' compliance with guidelines for acute community-acquired pneumonia management in a paediatric university hospital centre before and after its dissemination. This quasi-experimental study without a control group was conducted before and after new community-acquired pneumonia management guidelines were disseminated in a tertiary care paediatric hospital. The pre-intervention (baseline) period was from October 2004 to March 2005. The intervention period was divided into two phases: (1) October 2005 to January 14, 2006 (consultation by peer leaders and networking) and (2) January 15, 2006, to March 2006 (dissemination of official guidelines and of a pre-printed prescription sheet, an educational session led by a peer leader for residents and further networking). We used a compliance score to assess prescriptions written by prescribers who practised in the units where the guidelines had to be followed. The study included a total of 1151 prescriptions. The prescription compliance with the guidelines increased from 131/652 (20.1%) in the pre-intervention period to 264/499 (52.9%) in the post-intervention intervention period: a difference of 32.8% (CI 95% 27.4-38.0). Similar results were found if analysed according to affiliation (emergency department or wards). An inappropriate choice of antibiotic agent represented 347/521 (66.6%) of the causes of non-compliance in the pre-intervention period and 99/235 (42.1) in the intervention period: a difference of -24.5% (95% CI -31.8, -16.8). Guideline dissemination for the management of acute community-acquired pneumonia significantly increased prescriber compliance in the emergency department and on wards.


Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants.
Docosahexaenoic acid is present in high concentration in retina and does not influence visual development in preterm infants. It is still under discussion whether docosahexaenoic acid is important for visual development in term infants. Thirty-seven infants fed formula for a median of 14 days were randomized at median age of 25 days to three formulas: a) DHAGF: 0.3 wt% docosahexaenoic acid and 0.5 wt% gamma-linolenic acid; b) DHAF 0.3 wt% docosahexaenoic acid; or c) STF: standard formula without long-chain polyunsaturated fatty acids and 17 breast-fed infants were observed, using blood samples and anthropometric measurements from 1 to 4 months of age. At 4 months, visual acuity was measured by swept steady-state visual evoked potential. A cross-sectional study on 25 breast-fed infants was carried out as a reference group for the analyses. Infants fed the two docosahexaenoic acid-supplemented formula had relative docosahexaenoic acid concentrations in red blood cell phospholipids almost as high as those in breast-fed infants, whereas infants in the standard formula group had significantly lower levels. The addition of gamma-linolenic acid to the formula had a positive effect on red blood cell arachidonic acid levels, compared with levels obtained using fish oil only. Visual acuity was significantly different among all feeding groups (analysis of variance; p = 0.05, means +/- standard deviation: breast-fed, 0.37+/-0.06 logMAR; DHAF and DHAGF combined, 0.40+/-0.07 logMAR; and standard formula 0.44+/-0.07 logMAR. However, there was no statistical difference among the formula groups. In a multiple regression analysis including all formula-fed infants, weight at delivery (p = 0.002), but not type of formula, was significantly associated with visual acuity at 4 months of age. The addition of docosahexaenoic acid resulted in concentrations in red blood cells at similar levels as those in breast-fed infants, whereas the increase in visual acuity did not reach significance. The addition of gamma-linolenic acid resulted in higher arachidonic acid concentrations in red blood cells.


Flagellate dermatitis after bleomycin. A histological and immunohistochemical study.
A case of flagellate dermatitis after administration of bleomycin is reported in a patient with Hodgkin's disease. Histopathological and immunohistochemical analysis revealed a drug-induced skin toxic reaction rather than a lymphomatous infiltrate. Pigmentary changes observed after the early erythematous eruption were due to a postinflammatory effect.


Clinical impact of variability in HbA1c as assessed by simultaneously measuring fructosamine and use of error grid analysis.
Haemoglobin A1c (HbA1c) is the only measure of glycaemic control used for many patients with diabetes, but it has limitations and might sometimes be misleading. HbA(1c) concentrations are influenced by conditions that alter red-cell life and there is evidence that biochemical variation in intracellular glycation rates also influence HbA1c concentrations. This paper is the first to propose a method of using simultaneously measured HbA1c and fructosamine, and error grid analysis, in the clinical setting, to gain a better understanding of glycaemic control. Cross-sectional analytical study using HbA1c and fructosamine measures on the same blood sample from 1744 patients having blood taken for hospital diabetes clinic appointments. No other selection or exclusion criteria were applied. The fructosamine results were converted to a HbA1c equivalent which was then compared with the HbA1c. In an Altman-Bland plot, the paired result differences ranged between -6.9% and +5.5% HbA1c with 1139 (65%), 438 (25%), 130 (8%) and 37 (2%) being < or =1%, 1-2%, 2-3% or >3% of HbA1c difference, respectively. In clinical error grid analysis, 864 (50%) results had tight concordance for clinical interpretation, 761 (43%) had one block disunity of probably little clinical significance, but 105 (6%) were two blocks and 14 (1%) were three blocks discordant. HbA1c may not accurately reflect glucose control. Our method, utilizing co-assessment with serum fructosamine, evaluates the possible clinical impact of this. We suggest the analysis used in this paper should be used routinely in diabetes practice.


Recurrent Mixed Cryoglobulinemia (MCS): A Case Report and Literature Review.
We report a case of recurrent mixed type II cryoglobulinemia with difficult diagnosis and treatment dilemma and uncertain prognosis in view of limited studies. A 60-year-old male with history of essential mixed cryoglobulinemia 12 years ago treated successfully with six months of cyclophosphamide and prednisone presented with bilateral lower extremity pupuric rash and swelling. He was found to have proteinuria, hematuria, RBC casts, low serum complement levels, and acute kidney injury (AKI). Initial therapy with methylprednisone and oral cyclophosphamide was ineffective (patient developed respiratory failure due to alveolar hemorrhage). Additional labs revealed positive type II cryoglobulins, high free Kappa/Lambda, UPEP with minimal urine protein, SPEP with marked hypogammaglobulinemia, and negative tests for HIV, HCV, ANA, and ANCA. More aggressive therapy with daily plasmapheresis and rituximab was instituted with very good clinical response. He achieved clinical remission but developed another flare 8 months later. Kidney biopsy showed membranoproliferatve glomerulonephritis with cryoglobulin deposits. Flow cytometry and biopsy of bone marrow was consistent with lymphoplasmacytic lymphoma. His diagnosis was eventually confirmed and responded clinically to another course of rituximab and plasmapheresis, but prognosis is yet to be seen.


[Surgical treatment of bilateral pulmonary tuberculosis].
Two hundred and eighty two patients with different types of bilateral tuberculous lesion of the lung were operated on. Most (n = 124) patients underwent consecutive operations, 106 one-stage resections of the lung through transsternal access on the one side and video thoracoscopic resections on the other. One-stage bilateral video thoracoscopic operations were made in 52 cases. The greatest number of postoperative complications was noted with multistage operations, which is accounted for a critically ill patient group, advanced processes, concurrent pyoseptic infection. The patients undergone-transsternal resections showed minimum mortality rates with a rather low incidence of postoperative complications.


Percutaneous treatment of dysfunctional Brescia-Cimino fistulae through a radial arterial approach.
Dysfunctional Brescia-Cimino fistulae contribute to significant morbidity in hemodialysis patients. These fistulae normally are treated through a retrograde venous approach. There are no data regarding a transradial approach. Furthermore, measurement of pressure reduction in the radial artery appears to be useful. We retrospectively examined 50 interventions to treat 49 patients (17 men, 32 women; mean age, 61.8 +/- 10.6 years) with Brescia-Cimino fistulae. Inclusion criteria were patients with palpable radial arteries and dysfunctional end-to-side Brescia-Cimino fistulae. Patients with infected fistulae, contrast allergy, upper-arm/synthetic graft/central-vein stenosis, and end-to-end Brescia-Cimino fistulae were excluded from the study. Radial arterial pressures before and after angioplasty were compared as a surrogate of stenosis relief. Anatomic and clinical success rates were calculated. Sixty-five stenoses and 4 total occlusions were treated through radial access. All radial punctures were successful, except in 1 patient. Most lesions were located in the cephalic vein (87%). Mean length of treated lesions was 4.1 +/- 2.8 cm. Mean pretreatment diameter of lesion stenoses was 76.7% +/- 12.1%. Mean posttreatment diameter stenosis was 22.6% +/- 8.2% (P < 0.001). Systolic, diastolic, and mean blood pressures recorded from the radial artery decreased from 130 +/- 40, 60 +/- 18, and 87 +/- 27 to 88 +/- 40, 43 +/- 18, and 60 +/- 26 mm Hg (P < 0.001, P < 0.001, and P < 0.001), respectively. The anatomic success rate of the transradial approach was 91.3%. The clinical success rate of the transradial approach was 96%. The transradial approach is a feasible and highly effective approach to treat dysfunctional Brescia-Cimino fistulae. Measuring blood pressure reduction through the radial artery appears promising as a hemodynamic evaluation method.


MUSCULOSKELETAL IMPAIRMENT IN PRYMARY HYPOTHYROIDISM.
This article contains bibliographical data concerning the rheumatic clinical manifestations in hypothyroidism: polyarthralgias, lack of recent skill of fine movements of the hands, carpal tunnel syndrome or tarsal, degenerative arthropathy or acute type (gout, chondrocalcinosis), adhesive capsulitis (frozen shoulder syndrome), generalized muscular stiffness, hypothyroid myopathy, secondary osteoarthritis, Dupuytren's contracture, "trigger finger" (also called as stenosing tenosynovitis or trigger thumb) etc. and data on the short history, epidemiology, of these disorders. Review include 60 bibliographical sources.


Lung cancer mortality among workers making lead chromate and zinc chromate pigments at three English factories.
Lung cancer mortality among 1152 men working at three English chromate pigment factories was studied from the 1930s or 1940s until 1981. Workers at factory C were exposed only to lead chromate and experienced normal mortality (Obs/Exp deaths 7/6.45). Workers at factories A and B were exposed to both lead and zinc chromate; mortality was normal among those who had only low exposure (O/E 7/6.95). For workers with high or medium exposure lung cancer mortality was significantly raised among men remaining at least a year after entering service at factory A during 1932-54 (O/E 21/9.45) and at factory B during 1948-67 (O/E 11/2.50). At factory A, 1933-46 entrants staying only 3-11 months were not affected (O/E 6/5.04) and 1955-63 entrants also appeared unaffected (O/E 2/2.00); working conditions there improved in 1955. The hazard at factories A and B affected workers who left after one year as well as those with longer service, and latent intervals were unusually short. The results indicate that moderate or heavy exposure to zinc chromate may give rise to a severe risk of developing lung cancer, but that exposure which is relatively mild or lasts less than a year may not constitute an effective risk. The results provide no indication that lead chromate induces lung cancer in man, even under conditions conducive to lead poisoning.


Genome editing abrogates angiogenesis in vivo.
Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases.Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.


Obstructive sleep apnea in pregnancy.
A 25-year-old woman, gravida 4 para 2, at 37 weeks gestation was evaluated and treated for preeclampsia. Overnight, the patient had a witnessed apneic episode with maternal oxygen desaturation and concurrent fetal heart rate deceleration. She subsequently delivered an infant that was small for gestational age. This is the first case described with confirmed obstructive sleep apnea by formal polysomnography and witnessed maternal desaturation with fetal heart rate decelerations. Recognizing obstructive sleep apnea (OSA) early in gestation will help dictate treatment options and may prevent adverse maternal fetal outcomes. Continuous positive airway pressure (CPAP) seems to be a safe treatment with minimal adverse effects. Questioning of patients at the first prenatal visit and monitoring for increased snoring during gestation may help detect early signs and symptoms of OSA. Treatment of OSA with CPAP might improve perinatal outcomes.


Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers.
SNARE proteins are the core machinery to drive fusion of a vesicle with its target membrane. Inspired by the tethering proteins that bridge the membranes and thus prepare SNAREs for docking and fusion, we developed a lipid-conjugated ssDNA mimic that is capable of regulating SNARE function, in situ. The DNA-lipid tethers consist of a 21 base pairs binding segment at the membrane distal end that can bridge two liposomes via specific base-pair hybridization. A linker at the membrane proximal end is used to control the separation distance between the liposomes. In the presence of these artificial tethers, SNARE-mediated lipid mixing is significantly accelerated, and the maximum fusion rate is obtained with the linker shorter than 40 nucleotides. As a programmable tool orthogonal to any native proteins, the DNA-lipid tethers can be further applied to regulate other biological processes where capturing and bridging of two membranes are the prerequisites for the subsequent protein function.


Tissue-specific androgen-inhibited gene expression of a submaxillary gland protein, a rodent homolog of the human prolactin-inducible protein/GCDFP-15 gene.
The human PRL-inducible protein (PIP)/gross cystic disease fluid protein-15 is expressed in pathological conditions of the mammary gland and in several exocrine tissues, such as the lacrimal, salivary, and sweat glands. In human breast cancer cells, the expression of PIP/gross cystic disease fluid protein-15 is stimulated by androgen and PRL, and inhibited by estrogen. However, it is not known whether the expression of PIP in other tissues is under similar hormonal regulation. In the present study we employed reverse transcriptase-polymerase chain reaction followed by rapid amplification of complementary DNA (cDNA) ends to amplify the PIP cDNA homolog, the submaxillary gland protein (SMGP) in the mouse. The mouse PIP/SMGP cDNA encodes a putative secreted peptide of 144 amino acids with a 51% identity with human PIP. Using the mouse PIP/SMGP cDNA as a probe, we examined the tissue- and cell-specific expression of PIP/SMGP messenger RNA by in situ hybridization and Northern blot analysis of mouse and rat tissues. Hormonal regulation was also studied in the rat. PIP/SMGP messenger RNA expression was only detected in the lacrimal and submaxillary glands of the rodents. In the rat submaxillary gland, PIP/SMGP gene expression was confined to the acinar cells. In the male rat lacrimal gland, castration resulted in an increase in expression, and in both male and female rats, androgen replacement abolished PIP/SMGP gene expression. This pattern of regulation was not observed in the submaxillary gland and was actually reversed in human breast cancer cells. PRL had no effect on the regulation of PIP/SMGP in either salivary or lacrimal glands. Our study indicates that tissue-specific factors are important in determining the hormone responsiveness of the PIP/SMGP gene. Regulation of the PIP/SMGP gene in vivo may provide a useful model system to study the mechanism of down-regulation of expression by androgen in a tissue-specific manner.


[Actions of neuroactive steroids in neurons].
The term "neuroactive steroids" applies to those steroids that have biological activities in nervous system. These neuroactive steroids can be divided into three categories according to the mechanism of their effects: (1) Effects mediated by membrane receptors including GABAA receptor and NMDA receptor that are ion channels; (2) Effects mediated by membrane receptors that are coupled with second messenger systems; (3) Effects mediated by intracellular receptors which in turn modulate gene expression. These neuronal effects of steroids, especially modulation of the ion-channel receptor and G protein--coupled receptor, have drawn more attention of the researchers.


Effect of health disparities on overall survival of patients with glioblastoma.
Examine the potential effects of health disparities in survival of glioblastoma (GB) patients. We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS). We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance. GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.


Physical Mechanism Behind Enhanced Photoelectrochemical and Photocatalytic Properties of Superhydrophilic Assemblies of 3D-TiO2 Microspheres with Arrays of Oriented, Single-Crystalline TiO2 Nanowires as Building Blocks Deposited on Fluorine-Doped Tin Oxide.
In comparison to the one-dimensional (1D) semiconductor nanostructures, the hierarchical, three-dimensional (3D) microstructures, composed of the arrays of 1D nanostructures as building blocks, show quite unique physicochemical properties due to efficient photon capture and enhanced surface to volume ratio, which aid in advancing the performance of various optoelectronic devices. In this contribution, we report the fabrication of surfactant-free, radially assembled, 3D titania (rutile-phase) microsphere arrays (3D-TMSAs) composed of bundles of single-crystalline titania nanowires (NWs) directly on fluorine-doped conducting oxide (FTO) substrates with tunable architecture. The effects of growth parameters on the morphology of the 3D-TMSAs have been studied thoroughly. The 3D-TMSAs grown on the FTO-substrate showed superior photon-harvesting owing to the increase in light-scattering. The photocatalytic and photon to electron conversion efficiency of dye-sensitized solar cells (DSSC), where the optimized 3D-TMSAs were used as an anode, showed around 44% increase in the photoconversion efficiency compared to that of Degussa P-25 as a result of the synergistic effect of higher surface area and enhanced photon scattering probability. The TMSA film showed superhydrophilicity without any prior UV irradiation. In addition, the presence of bundles of almost parallel NWs led to the formation of arrays of microcapacitors, which showed stable dielectric performance. The fabrication of single-crystalline, oriented, self-assembled TMSAs with bundles of titania nanowires as their building blocks deposited on transparent conducting oxide (TCO) substrates has vast potential in the area of photoelectrochemical research.


Controllable synthesis of few-layer ammoniated 1T'-phase WS2 as an anode material for lithium-ion batteries.
Two-dimensional transition metal dichalcogenide (TMDC) nanosheets have received significant attention as anode materials for lithium-ion batteries, especially in their metallic 1T/1T' phase. However, controllable synthesis of few-layer 1T/1T' phase is still a challenge. In the present study, we report a facile two-step hydrothermal method to controllably synthesize few-layer 1T'-phase WS2. By tuning the redox-temperature of (NH4)2WS4 from 160 to 200 °C, the thickness of 1T'-phase WS2 can be adjusted from 4-6 to 20 layers. A higher reversible capacity is achieved in 1T'-phase WS2 with a smaller thickness, but the cycling stability decreases due to the lower crystallinity. The 1T'-phase WS2 synthesized by reduction of (NH4)2WS4 at 180 °C shows a moderate thickness of 10 layers and crystallinity, exhibiting the optimal Li-ion storage properties, i.e. a reversible capacity of 855.9 mA h g-1 at 100 mA g-1 and a good rate performance of 354.4 mA h g-1 at 5000 mA g-1. These results provide new insights into understanding the impacts of layer number on the Li-ion storage properties of 1T'-phase WS2.


Multistage dynamics of Hg2+-DNA interactions: a single-molecule study.
The metal ion-DNA interaction is key to biochemical processes and has applications in areas such as metal ion sensors and DNA nanomachines. For example, the formation of the T-Hg2+-T structure has been used in technologies such as DNA-based mercuric ion sensors. Though the interaction is widely used for practical purposes, the underlying mechanism has not been fully understood. In the present study, we used magnetic tweezers to explore the interactions between λ-DNA and two metal ions, Hg2+ and Cd2+, at the single-molecule level. Both metal ions caused considerable DNA conformational changes. The resulting DNA compaction dynamics were related to the ion concentration and the exerted force. The increase in the ion concentration promoted DNA compaction, whereas exerting greater forces inhibited this process. Application of a high force generated two-stage dynamics of the Hg2+-DNA interaction. However, at a sufficiently high Hg2+ concentration, a lower force led to a three-stage process. In contrast, the curves of the binding of Cd2+ ions to DNA had a stepwise pattern. Both the AFM scanning results and the single-molecule measurements confirmed that Hg2+ influences the DNA conformation in a more pronounced manner than Cd2+. The multistage Hg2+-DNA interaction was considered to be a result of the different binding mechanisms, including the mismatched base-pair formation. A model was then proposed to explain the peculiar dynamics.


Survivin expression in early hepatocellular carcinoma and post-treatment with anti-cancer drug under hypoxic culture condition.
To investigate the expression of survivin during the early stages of hepatocellular carcinoma (HCC). Immunohistochemical expression of survivin in liver tumor and non-tumor tissue specimens taken from 17 patients was compared. In addition, to determine the survivin expression in response to anti-cancer drugs in early stage HCC, the survivin expression was determined after the treatment of the HCC cells with anti-cancer drugs under hypoxic culture conditions. Survivin proteins were expressed in 64.7% of cells in early HCC specimens. A correlation between the survivin expression rate in the peritumoral hepatocytes and the rate of expression in the HCC specimens (low-rate group vs high-rate group) was observed. The survivin protein concentration in HCC cells was increased by the combination of hypoxia and anti-cancer drugs. This study suggests that survivin could be used as a therapeutic target in early HCC.


Dissemination of extended-spectrum beta-lactamase-producing Enterobacteriaceae in intensive care units of a medical center in Taiwan.
The prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in a tertiary hospital in Taiwan was assessed over a 16-month period. A total of 125 nonrepetitive ESBL-producing isolates of Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae were available for investigation using molecular methods. Four predominant intensive care units (ICUs) were identified, and SHV-12 (59%), CTX-M- 3 (36%), and CTX-M-14 (14%) were the three most frequent ESBLs. SHV-12 was predominant among E. cloacae in the burn unit and K. pneumoniae in the other three chest medicine-related ICUs. CTX-M-3 was predominant among E. coli and K. pneumoniae in three other ICUs. The dissemination of ESBL-producing Enterobacteriaceae in four ICUs of a medical center in Taiwan is a consequence of the clonal dissemination of a few epidemic strains along with the horizontal transmission of resistance genes-carrying plasmids among bacterial organisms.


Effects of denosumab as compared with parathyroidectomy regarding calcium, renal, and bone involvement in osteoporotic patients with primary hyperparathyroidism.
To evaluate the effects of denosumab (Dmb) on calcium, renal, and bone involvement in osteoporotic patients with primary hyperparathyroidism (PHPT) and compare with those who underwent a parathyroidectomy (PTX) procedure. This retrospective, longitudinal study included patients treated with Dmb (60 mg) once every 6 months (n = 19) and those who successfully underwent a PTX procedure (n = 19) corrected calcium (cCa), eGFR, bone mineral density (BMD) in the lumbar spine (LS), total hip (TH), and femoral neck (FN) and LS-trabecular bone score (TBS) changes at 1 year after beginning Dmb or undergoing PTX were measured. Dmb group had older age, and showed milder disease activity and lower eGFR as compared with PTX group. In PTX group, cCa and eGFR were significantly decreased following surgery, while those were stable in Dmb group. There were significant increases in LS, TH, and FN-BMD in both Dmb (LS: 6.0 ± 0.8%, TH: 3.7 ± 1.0%, FN: 4.3 ± 1.5%) and PTX (LS: 11.2 ± 1.5%, TH: 7.5 ± 1.5%, FN: 7.9 ± 2.1%) groups. In Dmb group, LS-TBS was significantly improved by 3.0 ± 1.0%, while TBS change in PTX group approached significance (2.8 ± 1.5%). Percent change in TH-BMD was significantly correlated with baseline tartrate-resistant acid phosphatase-5b (TRACP-5b) in both groups. Dmb treatment not only increased BMD, dependent on bone turnover status, the same as PTX, but also improved LS-TBS. In addition, it did not decrease the level of eGFR, whereas PTX did. These results suggest that Dmb treatment help in the clinical management of osteoporotic patients with PHPT who do not undergo surgery as alternative to PTX.


Uptake and utilization of amino acids by resting cells of Nitrosomonas europaea.
Incorporation of selected amino acids by resting cells was studied with regard to effects of concentration, rate and extent of incorporation, cellular distribution, effect of ammonium ion on uptake, and competitive effects. l-Aspartic acid, l-alanine, l-serine, and glycine presented at trace levels were incorporated at rates ranging from 0.11 to 8.2 mumumoles per mg (dry weight) per minute, and maximal incorporation was 11 to 333 mumumoles per mg (dry weight). When glycine and aspartic acid were supplied at substrate level, the rate of incorporation increased 14- and 109-fold, respectively. The presence of ammonium ion further increased both the rate and extent of uptake of glycine and aspartic acid. The distribution of cellular radioactivity arising from (14)C amino acids indicated that cell pool radioactivity was concentrated from 1.2- to 24.5-fold over the external medium. Aspartic acid pool radioactivity accounted for 50% or more of the total cellular radioactivity, whereas radioactivity in glycine and serine pools dropped from initially high levels to 20 to 25% during incubation. The decrease in pool radioactivity with both glycine and serine was accompanied by an increase in other fractions, especially in the cell residue. The growth-inhibiting amino acid l-valine, supplied at substrate level, contributed more carbon per milligram (dry weight) than any other amino acid studied. l-Leucine, in the presence of l-valine, was observed to decrease valine incorporation.


Hydrogen Atom Transfer (HAT) Processes Promoted by the Quinolinimide-N-oxyl Radical. A Kinetic and Theoretical Study.
A kinetic study of the hydrogen atom transfer (HAT) reactions from a series of organic compounds to the quinolinimide-N-oxyl radical (QINO) was performed in CH3CN. The HAT rate constants are significantly higher than those observed with the phthalimide-N-oxyl radical (PINO) as a result of enthalpic and polar effects due to the presence of the N-heteroaromatic ring in QINO. The relevance of polar effects is supported by theoretical calculations conducted for the reactions of the two N-oxyl radicals with toluene, which indicate that the HAT process is characterized by a significant degree of charge transfer permitted by the π-stacking that occurs between the toluene and the N-oxyl aromatic rings in the transition state structures. An increase in the HAT reactivity of QINO was observed in the presence of 0.15 M HClO4 and 0.15 M Mg(ClO4)2 due to the protonation or complexation with the Lewis acid of the pyridine nitrogen that leads to a further decrease in the electron density in the N-oxyl radical. These results fully support the use of N-hydroxyquinolinimide as a convenient substitute for N-hydroxyphthalimide in the catalytic aerobic oxidations of aliphatic hydrocarbons characterized by relatively high C-H bond dissociation energies.


Are some of the stigmas of addictions culturally sanctioned?
We provide three examples of how addiction stigma is sanctioned: (a) discrimination against people with addictions is often legal; (b) public health communications frequently use stigma to promote prevention; (c) some programmes, such as '12 steps' promote self-stigma. The implications of sanctioned stigma for stigma-change programmes are then discussed.


Inflammasome-Dependent Induction of Adaptive NK Cell Memory.
Monobenzone is a pro-hapten that is exclusively metabolized by melanocytes, thereby haptenizing melanocyte-specific antigens, which results in cytotoxic autoimmunity specifically against pigmented cells. Studying monobenzone in a setting of contact hypersensitivity (CHS), we observed that monobenzone induced a long-lasting, melanocyte-specific immune response that was dependent on NK cells, yet fully intact in the absence of T- and B cells. Consistent with the concept of "memory NK cells," monobenzone-induced NK cells resided in the liver and transfer of these cells conferred melanocyte-specific immunity to naive animals. Monobenzone-exposed skin displayed macrophage infiltration and cutaneous lymph nodes showed an inflammasome-dependent influx of macrophages with a tissue-resident phenotype, coinciding with local NK cell activation. Indeed, macrophage depletion or the absence of the NLRP3 inflammasome, the adaptor protein ASC or interleukin-18 (IL-18) abolished monobenzone CHS, thereby establishing a non-redundant role for the NLRP3 inflammasome as a critical proinflammatory checkpoint in the induction of hapten-dependent memory NK cells.


Quantum dots-based multiplexed immunohistochemistry of protein expression in human prostate cancer cells.
Semiconductor quantum dots (QDs) are bright fluorescent nanoparticles that have been successfully used for the detection of biomarker expression in cells. The objective of the present study is to use this technology in a multiplexing manner to determine at a single cell level the expression of a cell-specific bio-marker, prostate-specific antigen (PSA) expressed by human prostate cancer LNCaP and ARCaP cell lines. Here we compared the sensitivity of immunohistochemistry (IHC) and QD-based detection of AR and PSA expression in these cell lines. Further, we conducted multiplexing QD-based detection of PSA and androgen receptor (AR) expression in LNCaP cells subjecting to androgen (R1881) stimulation. The involvement of AR in PSA regulation in LNCaP cells, at a single cell level, was confirmed by the co-incubation of LNCaP cells in the presence of both R1881 and its receptor antagonist, bicalutamide (Casodex). We showed here the superior quality of QDs, in comparison to IHC, for the detection of AR and PSA in cultured LNCaP and ARCaP cells. Multiplexing QDs technique can be used to detect simultaneously AR and PSA expression induced by R1881 which promoted AR translocation from its cytosolic to the nuclear compartment. We observed AR antagonist, bicalutamide, inhibited AR nuclear translocation and PSA, but not AR expression in LNCaP cells.


Metal-Corrole-Based Porous Organic Polymers for Electrocatalytic Oxygen Reduction and Evolution Reactions.
Integrating molecular catalysts into designed frameworks often enables improved catalysis. Compared with porphyrin-based frameworks, metal-corrole-based frameworks have been rarely developed, although monomeric metal corroles are usually more efficient than porphyrin counterparts for the electrocatalytic oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). We herein report on metal-corrole-based porous organic polymers (POPs) as ORR and OER electrocatalysts. M-POPs (M=Mn, Fe, Co, Cu) were synthesized by coupling metal 10-phenyl-5,15-(4-iodophenyl)corrole with tetrakis(4-ethynylphenyl)methane. Compared with metal corrole monomers, M-POPs displayed significantly enhanced catalytic activity and stability. Co-POP outperformed other M-POPs by achieving four-electron ORR with a half-wave potential of 0.87 V vs. RHE and reaching 10 mA cm-2 OER current density at 340 mV overpotential. This work is unparalleled to develop and explore metal-corrole-based POPs as electrocatalysts.


Reduced graphene oxide-silicon interface involving direct Si-O bonding as a conductive and mechanical stable ohmic contact.
Metal-semiconductor junctions are essential contacts for semiconductor devices, but high contact junction resistance is a limiting operational factor. Here, we establish an ohmic contact of low resistance of <4 × 10-6 Ω cm2 between platinum and n-type Si (111)-H surfaces. This involved Si-O covalent bonding a monolayer of graphene oxide (GO) to the Si surface followed by electrochemical reduction to form reduced graphene oxide (rGO). Current-voltage plots demonstrate that the GO/rGO transformation is associated with a change from a rectifying to an ohmic contact. The process is a viable method for constructing semiconductor-rGO interfaces and demonstrates that GO/rGO monolayers can be used as active components in tuning the contact resistance of metal-semiconductor junctions.


Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium.
Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium.


Stress and coping in a week-long disabled submarine exercise.
Emotional stress could impair cognitive performance and decision-making in the initial period within a disabled submarine (SUBSUNK). The aim of the present study was to explore stress reactions over time in submarine crewmembers exposed to a simulated SUBSUNK trial. There were 18 Norwegian sailors who were confined within the front section of a conventional diesel-electric submarine for 6 d 18 h complying with emergency SUBSUNK procedures. Self-reported measures of habitual coping and personality hardiness were completed before the simulation, and measures of emotional stress symptoms and quality of life were assessed daily during the exercise and at 2 wk after the exercise. A repeated measures analysis of variance showed that emotional stress symptoms declined [F (6,14) = 2.76, p < 0.05], while quality of life improved over time [F (6,14) = 4.00, p < 0.01] from the first day compared with subsequent days of the experiment. Personality hardiness was negatively associated with emotional stress (r = -0.52) and lower quality of life (r = -0.47), while avoidant coping was positively associated with lower quality of life (r = 0.53) in the first 24 h of the SUBSUNK situation (all p < 0.05). These findings suggest that the level of emotional stress was highest in the first 24-h period, and that the level of distress was related to scores on personality hardiness and personality traits. These data have possible implications for selection and healthcare of personnel, and also suggest that crews will benefit from external help especially in the first 24 h of emergency response techniques.


Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function.
During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4-28 hours after admission; <70 mmHg, 70-80 mmHg, >80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival (P=0.35) or neuron-specific enolase levels (P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase (Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function (n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher (Pgroup=0.03). In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.


Comparison of spike sorting and thresholding of voltage waveforms for intracortical brain-machine interface performance.
For intracortical brain-machine interfaces (BMIs), action potential voltage waveforms are often sorted to separate out individual neurons. If these neurons contain independent tuning information, this process could increase BMI performance. However, the sorting of action potentials ('spikes') requires high sampling rates and is computationally expensive. To explicitly define the difference between spike sorting and alternative methods, we quantified BMI decoder performance when using threshold-crossing events versus sorted action potentials. We used data sets from 58 experimental sessions from two rhesus macaques implanted with Utah arrays. Data were recorded while the animals performed a center-out reaching task with seven different angles. For spike sorting, neural signals were sorted into individual units by using a mixture of Gaussians to cluster the first four principal components of the waveforms. For thresholding events, spikes that simply crossed a set threshold were retained. We decoded the data offline using both a Naïve Bayes classifier for reaching direction and a linear regression to evaluate hand position. We found the highest performance for thresholding when placing a threshold between -3 and -4.5 × Vrms. Spike sorted data outperformed thresholded data for one animal but not the other. The mean Naïve Bayes classification accuracy for sorted data was 88.5% and changed by 5% on average when data were thresholded. The mean correlation coefficient for sorted data was 0.92, and changed by 0.015 on average when thresholded. For prosthetics applications, these results imply that when thresholding is used instead of spike sorting, only a small amount of performance may be lost. The utilization of threshold-crossing events may significantly extend the lifetime of a device because these events are often still detectable once single neurons are no longer isolated.


Critical Review: When the Party is Over: A Systematic Review of Behavioral Interventions for Substance-Using Men Who Have Sex with Men.
Because problematic patterns of alcohol and other substance use are prevalent drivers of the HIV/AIDS epidemic, comprehensive interventions are needed for substance-using men who have sex with men (SUMSM). We conducted a systematic review of 12 randomized controlled trials (RCTs) of behavioral interventions for reducing condomless anal intercourse (CAI) in SUMSM. Three RCTs observed that cognitive behavioral or motivational interviewing interventions achieved a 24% to 40% decrease in CAI. Interventions also tended to demonstrate greater efficacy for reducing CAI and substance use among those who had lower severity of substance use disorder symptoms. Although behavioral interventions for SUMSM are one potentially important component of biobehavioral HIV/AIDS prevention, further research is needed to examine whether integrative approaches that cultivate resilience and target co-occurring syndemic conditions demonstrate greater efficacy. Multilevel intervention approaches are also needed to optimize the effectiveness of pre-exposure prophylaxis and HIV treatment as prevention with SUMSM.


Myxomas in the fingertips.
The myxoma, a benign connective-tissue neoplasm consisting of stellate cells and a loose mucoid stroma, rarely involves the hand. Only three previous cases of myxoma in the finger have been reported in the literature. Two cases of myxoma in the fingers are presented here, one occurring in the finger pulp and the other in the subungual region. Cases described in the literature and the authors' experience indicate that the tumor is cured by a meticulous, marginal resection, though slight nail deformity can be a sequela.


Knowledge, attitudes and practices of general practitioners and paediatricians towards Group A beta-haemolytic streptococcal tonsillopharyngitis: A cross-sectional study from Türkiye.
General practitioners (GPs) and paediatricians are very important in the management of sore throat in terms of providing correct diagnosis and treatment. The aim of this study was to evaluate the knowledge, attitudes and practices of GPs and paediatricians towards Group A beta-haemolytic streptococcal (GABHS) tonsillopharyngitis. Three vignettes/case studies, in which the causative agents were GABHS, Epstein-Barr virus (EBV) and non-EBV viral infection, were presented as part of a questionnaire sent to paediatricians and GPs to elicit information regarding their diagnosis and treatment of tonsillopharyngitis. In all, 236 physicians responded to the questionnaire (126 paediatricians, 106 GPs). GPs registered more accurate diagnoses of GABHS tonsillopharyngitis and tended to administer more symptomatic treatment in the case of non-EBV tonsillopharyngitis than paediatricians. Paediatricians requested more tests in the diagnosis of GABHS tonsillopharyngitis than GPs. Most GPs and paediatricians possess adequate knowledge regarding GABHS diagnosis and the differential diagnosis of patients. Differences between the hospital and general practice settings may have affected the approach to symptomatic treatment and requesting tests.


Deciphering amphibian diversity through DNA barcoding: chances and challenges.
Amphibians globally are in decline, yet there is still a tremendous amount of unrecognized diversity, calling for an acceleration of taxonomic exploration. This process will be greatly facilitated by a DNA barcoding system; however, the mitochondrial population structure of many amphibian species presents numerous challenges to such a standardized, single locus, approach. Here we analyse intra- and interspecific patterns of mitochondrial variation in two distantly related groups of amphibians, mantellid frogs and salamanders, to determine the promise of DNA barcoding with cytochrome oxidase subunit I (cox1) sequences in this taxon. High intraspecific cox1 divergences of 7-14% were observed (18% in one case) within the whole set of amphibian sequences analysed. These high values are not caused by particularly high substitution rates of this gene but by generally deep mitochondrial divergences within and among amphibian species. Despite these high divergences, cox1 sequences were able to correctly identify species including disparate geographic variants. The main problems with cox1 barcoding of amphibians are (i) the high variability of priming sites that hinder the application of universal primers to all species and (ii) the observed distinct overlap of intraspecific and interspecific divergence values, which implies difficulties in the definition of threshold values to identify candidate species. Common discordances between geographical signatures of mitochondrial and nuclear markers in amphibians indicate that a single-locus approach can be problematic when high accuracy of DNA barcoding is required. We suggest that a number of mitochondrial and nuclear genes may be used as DNA barcoding markers to complement cox1.


Endoscopic endonasal anatomical study of the cavernous sinus segment of the ophthalmic nerve.
This cadaveric study analyzes the endoscopic endonasal anatomy of the ophthalmic division of the trigeminal nerve (V1 ), from the middle fossa to its orbital entry via the superior orbital fissure. Anatomical relationships with the surrounding cranial nerves and blood vessels are described, with emphasis on their clinical correlation during surgery in this region. Our objective was to describe the anatomical relationships of the ophthalmic division of the trigeminal nerve. Cadaveric study. Thirty middle cranial fossae, in adult human cadaveric specimens, were dissected endonasally under direct endoscopic visualization. During the dissection, we noted the relationships of the V1 nerve with the other trigeminal branches, as well as with the oculomotor and trochlear nerves, the paraclival and cavernous portions of the internal carotid artery, and the superior orbital fissure (SOF). The V1 nerve is the most superior trigeminal branch and runs upward and obliquely, along the middle portion of the lateral wall of the cavernous sinus. The V1 nerve joins the oculomotor and trochlear nerves to exit the cavernous sinus and enter the orbit through the SOF. Ten percent of the specimens displayed the trochlear nerve running along as a mate of the V1 nerve. The V1 nerve borders two key triangles in the lateral wall of the cavernous sinus, and the Parkinson's and anteromedial triangles. In this study, the V1 nerve was a constant and reliable landmark, thus allowing the identification of the anteromedial triangle. This potential space can serve as an adequate window to access the temporal lobe. Knowledge of this anatomy is essential when planning and executing endonasal surgery in this region. NA.


Sequencing of avian influenza virus genomes following random amplification.
Increasing surveillance for the avian influenza virus (AIV) has underscored the need for quickly and precisely characterizing isolates of this highly variable target. Random amplification, sequencing, and assembly of total RNA from nonpurified virus overcomes the need for specific primers for DNA microarray or PCR protocols.


Caries reduction in belgian 12-year-old children related to socioeconomic status.
This study compares dental caries reduction in Belgian 12-year-old children of different socioeconomic status in 1983 and 1998. Moreover, the relative effect of dental health factors on caries reduction is estimated. In the region of Brussels, children in the 7th grade at the same schools participated in cohort 1983 (n = 533) and in cohort 1998 (n = 496). DMFT, DMFS, and dental fluorosis were clinically recorded. The socioeconomic status of the children was established on the basis of their parents' education and profession. Data on children's home-based and professional dental health care habits were registered. Caries reduction was observed in both privileged and non-privileged children. However, non-privileged children, in cohort 1983 and cohort 1998, had significantly higher DMF scores than privileged children (P < 0.01). Dental fluorosis was more often identified in privileged children than in non-privileged ones. Most of the dental factors relating to children's home based and professional care were associated with caries reduction. Caries reduction was strongly related to socioeconomic status; non-privileged children registered lower than their counterparts.


One-stage reconstruction of full-thickness lower eyelid using a Tripier flap lining by a septal mucochondral graft.
Basal cell carcinoma (BCC) is the most frequent cutaneous neoplasm of the periorbital region. After tumor excision, the function of the eyelid has to be preserved, keeping the protection of the eyeball with preservation of damp, avoiding epiphora and ectropion. The authors describe the reconstruction, in a single surgical procedure, of a full-thickness defect of the outer half of the free edge of the lower eyelid through free chondromucosal graft of the septum and Tripier flap. There are very few cases that describe the septal chondromucosal flap in eyelid reconstruction. This case also corroborates the fact that the chondromucosal graft is a valuable surgical option for reconstruction of full-thickness lower eyelid defects.


Genomic Analysis Reveals Heterogeneity Between Lesions in Synchronous Primary Right-Sided and Left-Sided Colon Cancer.
Background: The synchronous primary right-sided and left-sided colon cancer (sRL-CC) is a peculiar subtype of colorectal cancer. However, the genomic landscape of sRL-CC remains elusive. Methods: Twenty-eight paired tumor samples and their corresponding normal mucosa samples from 14 patients were collected from the Second Affiliated Hospital of Harbin Medical University from 2011 to 2018. The clinical-pathological data were obtained, and whole-exome sequencing was performed based on formalin-fixed and paraffin-embedded samples of these patients, and then, comprehensive bioinformatic analyses were conducted. Results: Both the lesions of sRL-CC presented dissimilar histological grade and differentiation. Based on sequencing data, few overlapping SNV signatures, onco-driver gene mutations, and SMGs were identified. Moreover, the paired lesions harbored a different distribution of copy number variants (CNVs) and loss of heterozygosity. The clonal architecture analysis demonstrated the polyclonal origin of sRL-CC and inter-cancerous heterogeneity between two lesions. Conclusion: Our work provides evidence that lesions of sRL-CC share few overlapping mutational signatures and CNVs, and may originate from different clones.


Mechanism of arsenite toxicity in embryonic stem cells.
Environmental arsenite exposure has been linked to cancer as well as other diseases, presenting an important and serious public health problem. Toxicity of inorganic arsenite (iAs) has been investigated using animal models and cell culture, yet its developmental effects are poorly understood. This study investigated the molecular mechanism of iAs toxicity to ascertain insight into development and differentiation processes using mouse embryonic stem cells (ESCs). The results showed that iAs exposure affected morphology and integrity of ESC colonies as well as inhibited cell growth in a concentration-dependent manner, excluding concentrations <1 μM iAs which stimulated ESC growth. ESCs self-renewal and pluripotency was also affected as evident from the downregulation of transcription circuitry, Oct4, Nanog, Sox2 and Klf4 resulting in non-specific differentiation. ESCs exposed to iAs randomly differentiated into three germ layers, mesoderm, endoderm and ectoderm, as judged by transcriptional expression of Brachyury, Gata4 and FGF2, as well as translational expression of BRACHYURY, GATA4 and TUJ1 respectively. The differentiated cells represented osteogenic, chondrogenic, myogenic and neurogenic lineages as evident from upregulation of Col1, Sox9, Col2, Myog, Notch, Nes and Nef. Although iAs caused slight apoptosis with a concomitant increase in ROS levels, the exposed ESCs had significant Bcl2 expression, which could be involved in the protection against apoptosis. Further analysis revealed upregulation of Jun and P38 in ESCs with an increase in iAs concentration. These observations indicated that iAs stress caused random differentiation of ESCs via JNK/P38 pathways. These findings suggest that iAs exposure may cause teratogenicity during early fetal development. Copyright © 2017 John Wiley & Sons, Ltd.


Trichotomy of awareness, outlook and practice of food handlers towards food and water safety in food establishments in Addis Ababa, Ethiopia.
Food and waterborne diseases are the commonest global public health problems. Specifically, in Ethiopia, public health problems associated with deterioration of food and water safety situations are much more complicated due to poverty, economic and environment related risks. Awareness, outlook and practice of food handlers are the three important factors that play major roles in the occurrence and outbreak of food borne diseases. Therefore, this study aimed to evaluate awareness, outlook and practice of food handlers towards food and water safety. Institution based cross sectional study was conducted among food handlers of Addis Ababa city administration. In this study, 416 participants were selected using a stratified, simple random sampling technique; and were interviewed using structured questionnaire. Linear Regression Model and analysis of variance were used for data analysis. In this study, 55.5%, 66.1% and 60.6% of the food handlers had good awareness, outlook and proper hygiene practices respectively. This study revealed that, 17.5% and 23.1% of the respondents did not know about food and water borne disease respectively. Only 39.4% of the participants had proper practice of covering mouth with tidy cloth when they cough. Moreover, 75.7% of the food handlers reported that they did not wear personal protective devices during the working time. Predictor variables like educational status and length of work experience were correlated positively and significantly with awareness. However, being married was correlated negatively with awareness. Assessing awareness, outlook and practice of food handlers regarding food and water safety is a vital activity to reduce public health problems. Significant number of food handlers had poor awareness, outlook and practice towards food and water safety. There is a call for enhancing the awareness, outlook and practice of food and water safety to achieve an excellent practice. Better food and water safety policy and firm regulatory actions are needed.


Treatment of complex intracranial aneurysms using flow-diverting silk® stents. An analysis of 32 consecutive patients.
This study describes the peri-procedural and late complications and angiographic follow-up results of 32 patients with 34 complex aneurysms treated with flow diverter Silk stents in a single centre. In this retrospective study, 40 Silk stents (SS) were implanted in 34 complex intracranial aneurysms in 32 patients. In our series, 20 (58.8%) carotid-ophthalmic internal carotid artery (ICA), six (17.6%) cavernous ICA, two (5.9%) supraclinoid ICA, two (5.9%) petrosal ICA (the same patient- bilateral) and four (11.8%) posterior circulation aneurysms were treated. One of the posterior circulation lesions was a fenestrated-type aneurysm. Twenty wide-necked, saccular; eight neck remnant; four fusiform and two blister-like aneurysms were included in our series. SS were successfully implanted in all patients (100%). Misdeployment occurred in 17.6% of patients. In two of these patients adequate stent openness was achieved via Hyperglide balloon dilatation. Coil embolization in addition to SS placement was utilized in four aneurysms. One patient (3%) experienced transient morbidity due to a thromboembolic event and there was one mortality (3%) due to remote intraparenchymal haemorrhage. Complete occlusion of 27/33 (81.8 %) and 29/33 (87.9 %) aneurysms was achieved six and 12 months after the procedure, respectively. In-stent intimal hyperplasia was detected in 6.1 % patients. Flow-diverter Silk stent implantation is an effective method of treating complex aneurysms with acceptable mortality and morbidity rates. Complete occlusion is achieved in most of the complex aneurysms.


A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer.
To investigate the effect on participation in colorectal cancer screening of testing for blood products in faeces using technologies that remove dietary restrictions (i.e. immunochemical tests) and simplify faecal sampling (i.e. tests that use brush sampling). Urban residents (n=1818) of Adelaide, Australia, aged between 50 and 69 years, randomly selected from the electoral roll. Three randomised cohorts of 606 invitees were offered a screening test by mail in 2001. The Hemoccult SENSA and FlexSure OBT cohorts were instructed to sample three stools using a spatula while the InSureTM cohort sampled two stools using a brush. The Hemoccult SENSA cohort was asked to restrict certain (high-peroxidase) foods and drugs. Participation (i.e. return of completed sample kits within 12 weeks) and generalised linear modelling (GLM) of relationships between participation, test technologies and demographic variables. Participation was 23.4%, 30.5% and 39.6% for the Hemoccult, FlexSure and InSure cohorts, respectively (chi(2)=37.1, p<0.00001). GLM demonstrated that participation was increased by 28% by removal of restrictions (p=0.01) and by 30% by simplification of sampling (p=0.001); both together increased participation by 66% (p<0.001). The differences in participation between tests occurred in the first three weeks. Socio-economic status, gender or age did not significantly influence technology-based improvements in participation. The brush-sampling faecal immunochemical test for haemoglobin (InSure) achieves the best participation rates by simplifying sampling and removing the need for restrictions of diet and drugs. Because participation in screening is vital to detection, this new technology should contribute to better detection of neoplasia at the population level.


Unusual but completely avoidable complication during central venous catheterization.
Central venous catheterization is generally a safe procedure, but several complications such as pneumothorax, arrhythmias, arterial puncture, infection, and thrombosis are known to occur even in the experienced hands. Complications related to guide wire are very rare and mostly relate to the expertise of operating person. We hereby report a rare but completely avoidable complication, that is, complete loss of the guide wire into the subclavian vein which was successfully retrieved by surgery.


Expression of HIF-1α and VEGF in feline mammary gland carcinomas: association with pathological characteristics and clinical outcomes.
The microenvironment within solid malignant tumors, including feline mammary gland carcinomas (FMGCs), is commonly hypoxic, possibly due to the lack of functional blood vessels in rapidly proliferating neoplastic tissue. Malignant cells can undergo genetic and adaptive changes that prevent them from dying due to oxygen deprivation through expressions of hypoxia-inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). Therefore, HIF-1α and VEGF are ideal biomarkers for cancer therapy and prognostic evaluation. The aims of this study were to evaluate the expression of HIF-1α and VEGF in feline mammary carcinomas and analyze their correlations with clinical and pathological factors, such as clinical stage, histologic grading, regional metastasis, and overall survival rate. Paraffin-embedded tissue samples collected from 72 cats with FMGCs were retrospectively studied. Histologic pattern and histologic grading (Elston and Ellis grading system) of these FMGCs were determined. Our data indicated that grade II tubulopapillary carcinomas (43/72, 59.7%) prevailed in this study, and most FMCGs showed apparent necrosis, squamous metaplasia, and intratumoral stromal response. According to the results of immunohistochemical (IHC) stainings performed in tissue microarrays (TMAs), HIF-1α and VEGF overexpressions were respectively noted in 69.4% (50/72) and 77.8% (56/72) of FMGC cases. Chi-square test showed no correlation of HIF-1α overexpression with clinical and pathological factors. VEGF overexpression was significantly correlated with histologic pattern (p = 0.021), stromal response (p = 0.048), squamous metaplasia (p = 0.001), and lymphovascular invasion (p = 0.007). However, neither HIF-1α nor VEGF overexpression was correlated with histologic grading and metastasis. Of 38 cats with 1-year follow-up, IHC stainings of HIF-1α and VEGF were performed on whole tissue sections. The results showed that overexpression of HIF-1α was significantly correlated with the overall survival rate (p < 0.05) (log-rank test), whereas there was no significant correlation between VEGF overexpression and overall survival rate. This study suggests that the overexpression of HIF-1α may indicate poor prognosis/overall survival rate in cats with FMGCs. Developing compounds that inhibit HIF-1α may be a potential approach to FMGC treatment.


Maternal Smoking: A Life Course Blood Pressure Determinant?
Exposure to maternal smoking early in life may affect blood pressure (BP) control mechanisms. We examined the association between maternal smoking (before conception, during pregnancy, and 4 years after delivery) and BP in preschool children. We evaluated 4295 of Generation XXI children, recruited at birth in 2005-2006 and reevaluated at the age of 4. At birth, information was collected by face-to-face interview and additionally abstracted from clinical records. At 4-year follow-up, interviews were performed and children's BP measured. Linear regression models were fitted to estimate the association between maternal smoking and children's BP. Children of smoking mothers presented significantly higher BP levels. After adjustment for maternal education, gestational hypertensive disorders, and child's body mass index, children exposed during pregnancy to maternal smoking presented a higher systolic BP (SBP) z-score (β = 0.08, 95% confidence interval [CI] 0.04 to 0.14). In crude models, maternal smoking was associated with higher SBP z-score at every assessed period. However, after adjustment, an attenuation of the association estimates occurred (β = 0.08, 95% CI 0.03 to 0.13 before conception; β = 0.07, 95%CI 0.02 to 0.12; β = 0.04, 95%CI -0.02 to 0.10; and β = 0.06, 95%CI 0.00 to 0.13 for the first, second, and third pregnancy trimesters, respectively; and β = 0.07, 95%CI 0.02 to 0.12 for current maternal smoking). No significant association was observed for diastolic BP z-score levels. Maternal smoking before, during, and after pregnancy was independently associated with systolic BP z-score in preschool children. This study provides additional evidence to the public health relevance of maternal smoking cessation programs if early cardiovascular health of children is envisaged. Using observational longitudinal data from the birth cohort Generation XXI, this study showed that exposure to maternal smoking-before pregnancy, during pregnancy, and 4 years after delivery-was associated with a systolic BP-raising effect in children at the age of 4. The findings of this study add an important insight into the need to support maternal smoke-free environments in order to provide long-term cardiovascular benefit, starting as early as possible in life.


The use and reporting of cluster analysis in health psychology: a review.
Cluster analysis is a collection of relatively simple descriptive statistical techniques with potential value in health psychology, addressing both theoretical and practical problems. There are many methods of cluster analysis from which to choose, with no clear guidelines to aid researchers. In the absence of guidelines it is likely that methods already reported by published researchers will be adopted, and so clear reporting of statistical methodology, while always important, is particularly crucial with cluster analysis. The aim of this review is to describe and evaluate the reporting of cluster analysis in health psychology publications. Electronic searches of 18 health psychology journals identified 59 articles using cluster analysis published between 1984 and 2002. Articles were submitted to systematic evaluation against published criteria for the reporting of cluster analysis. Just 27% of the papers reviewed met all five criteria, although 61% met at least four. Details of the similarity measure and the computer program used were most frequently omitted. Furthermore, while researchers usually reported the procedures employed to determine the number of clusters and to validate the clusters, these procedures were often lacking in rigour, and were reported in insufficient detail for replication. The reporting of cluster analysis was found to be generally unsatisfactory, with many studies failing to provide enough information to allow replication or the evaluation of the quality of the research. Clear guidelines for conducting and reporting cluster analyses in health psychology are needed.


On the automaticity of reactive item-specific control as evidenced by its efficiency under load.
Traditionally cognitive control is described as slow-acting, effortful, and strategic. Against this backdrop, the notion of "automatic control" is an oxymoron. However, recent findings indicate control also operates quickly with adjustments occurring outside awareness, leaving open the possibility that control could be automatic under certain conditions. Harnessing one such finding, the item-specific proportion congruent (ISPC) effect (i.e., reduction in congruency effect for mostly incongruent compared with mostly congruent items), we systematically investigated the automaticity of reactive item-specific control by examining its efficiency under a concurrent load. In four experiments using a picture-word Stroop task, participants first performed a block of trials in which an ISPC manipulation was embedded to acquire the item-control associations. In later blocks, we manipulated working memory load within-subjects (verbal in Experiment 1, visuospatial in Experiment 2, and n-back updating in Experiments 3 and 4) and compared the ISPC effect between low- and high-load conditions. The results of all four experiments showed that the ISPC effect was robust regardless of working memory load. In Experiment 4, we additionally included diagnostic items to assess whether transfer of item-specific control settings was also automatic. The ISPC transfer effect was abolished under high working memory load. Collectively, the findings suggest that reactive item-specific control is triggered and executed in an automatic manner (regardless of the available attentional resources), but only for items that directly support learning of the item-control associations that underlie item-specific control. We propose several hypotheses to account for these findings and discuss theoretical implications for control. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Dynamic obstructions of the equine upper respiratory tract. Part 2: comparison of endoscopic findings at rest and during high-speed treadmill exercise of 600 Thoroughbred racehorses.
The reliability of diagnoses of obstructive conditions of the upper respiratory tract (URT) based on examinations performed at rest vs. at exercise is controversial. To compare diagnosis of URT by endoscopy at rest with that achieved during high-speed treadmill exercise (HSTE). Endoscopy of URT at rest, when performed in isolation from other simpler techniques is unreliable in the prediction of dynamic respiratory obstructions. Endoscopic findings of 600 Thoroughbred racehorses during quiet breathing were compared with findings during high-speed treadmill exercise. Other parameters were also assessed for their specificity in diagnosis. Endoscopy of the resting horse showed low sensitivity (0.15) in the diagnosis of dorsal displacement of the soft palate (DDSP) and palatal instability (PI). When endoscopy and reported noises were taken together there was still a 35% misdiagnosis rate. Although there was significant association between resting laryngeal function score (LFS) and dynamic vocal cord and/or arytenoid cartilage collapse at exercise, 19% of horses with a grade 4/5 LFS were able to attain and maintain full abduction during exercise and 7% of those with 'normal' grades 1 or 2 LFS at rest showed dynamic laryngeal collapse when exerted. Sensitivity of the diagnostic model was greatly increased (80%) when a history of inspiratory noise and palpable intrinsic muscle atrophy were included. Endoscopy of the upper respiratory tract of static horses is unreliable in the diagnosis of dynamic obstructions of the URT and should not be used in isolation in surgical decision-making or in the assessment of horses at the time of sale.


Promotion to change lifestyle: securing participation and success.
Corporate wellness programs designed to promote employee health are becoming increasingly popular due to their improved productivity, lower health care costs, and reduced absenteeism. The success of the lifestyle intervention measures they promote depends on employees' participation, which is a key challenge. The study uses partial least squares (PLS) path modeling and logistic regression to (a) identify, based on the health belief model, the factors likely to influence employee participation in personal coaching and health challenges, and (b) study their impact on lifestyle and overall health among participants. Results show that participation is influenced by initial lifestyle, attendance in educational events, peer influence, and communication through different channels.


Interferon immunoregulation of antibody response in normal and autoimmune mice is mediated by suppressor T cell subsets.
The mechanism through which interferon exerts immunoregulatory influence on antibody production in autoimmune NZB mice and normal Balb/C mice was studied. Interferon suppressed T cell-dependent anti-SRBC response in normal mice indirectly by activating suppressor T cells. The suppressor cell activity by interferon is mediated by Ly123+ cells presumably acting as feedback regulators for the suppression.


Structural and functional integration between dorsal and ventral language streams as revealed by blunt dissection and direct electrical stimulation.
The most accepted framework of language processing includes a dorsal phonological and a ventral semantic pathway, connecting a wide network of distributed cortical hubs. However, the cortico-subcortical connectivity and the reciprocal anatomical relationships of this dual-stream system are not completely clarified. We performed an original blunt microdissection of 10 hemispheres with the exposition of locoregional short fibers and six long-range fascicles involved in language elaboration. Special attention was addressed to the analysis of termination sites and anatomical relationships between long- and short-range fascicles. We correlated these anatomical findings with a topographical analysis of 93 functional responses located at the terminal sites of the language bundles, collected by direct electrical stimulation in 108 right-handers. The locations of phonological and semantic paraphasias, verbal apraxia, speech arrest, pure anomia, and alexia were statistically analyzed, and the respective barycenters were computed in the MNI space. We found that terminations of main language bundles and functional responses have a wider distribution in respect to the classical definition of language territories. Our analysis showed that dorsal and ventral streams have a similar anatomical layer organization. These pathways are parallel and relatively segregated over their subcortical course while their terminal fibers are strictly overlapped at the cortical level. Finally, the anatomical features of the U-fibers suggested a role of locoregional integration between the phonological, semantic, and executive subnetworks of language, in particular within the inferoventral frontal lobe and the temporoparietal junction, which revealed to be the main criss-cross regions between the dorsal and ventral pathways. Hum Brain Mapp 37:3858-3872, 2016. © 2016 Wiley Periodicals, Inc.


Media coverage of youth suicides and its impact on paediatric mental health emergency department presentations.
To examine mental health (MH) presentations to the emergency department (ED) of a paediatric hospital following two highly publicized local teen suicides. Youths aged 12-18 years with a MH chief complaint and/or diagnosis were included. Differences in frequencies were analyzed using chi-square tests, and relative risks were evaluated using generalized linear modelling. Significant increases in the number of ED presentations were found within the months of the publicized suicides compared to the same months of previous years. No differences were found in symptom acuity, suicidal status and psychiatric hospitalization rates. Significant increases were found in relative risk of presenting to the ED 28 and 90 days post both publicized suicides. RESULTS suggest there was an association between highly publicized suicides and an increase in the number of MH presentations to the local paediatric ED. Considerations of media's potentially positive role in MH awareness are needed.


Validating audiovisual reviews as a strategy for teaching behavioral medicine to primary care residents.
A study examining the usefulness of audiovisual reviews (AVR's) as a method of teaching behavioral medicine was done with family medicine residents and faculty at the UNC School of Medicine. A set of educational goals for family medicine residency training was established. In a survey faculty and residents were asked to rate the importance of teaching each goal during residency and the appropriateness of AVR's for teaching it. Observers recorded the content of discussion in 18 regularly scheduled AVR's. In survey results both faculty and residents agreed that AVR's are best suited for teaching behavioral medicine skills. However, there were different goals, depending on level of training. Content analysis of the observed AVR's showed that the four most valued teaching goals comprised 50% of the topics discussed in actual AVR's. Results of this study validate the use of AVR's as a teaching strategy for behavioral medicine skills.


Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling.
Nuclear import of proteins containing classical nuclear localization signals (NLS) is mediated by the importin-alpha:beta complex that binds cargo in the cytoplasm and facilitates its passage through nuclear pores, after which nuclear RanGTP dissociates the import complex and the importins are recycled. In vertebrates, import is stimulated by nucleoporin Nup50, which has been proposed to accompany the import complex through nuclear pores. However, we show here that the Nup50 N-terminal domain actively displaces NLSs from importin-alpha, which would be more consistent with Nup50 functioning to coordinate import complex disassembly and importin recycling. The crystal structure of the importin-alpha:Nup50 complex shows that Nup50 binds at two sites on importin-alpha. One site overlaps the secondary NLS-binding site, whereas the second extends along the importin-alpha C-terminus. Mutagenesis indicates that interaction at both sites is required for Nup50 to displace NLSs. The Cse1p:Kap60p:RanGTP complex structure suggests how Nup50 is then displaced on formation of the importin-alpha export complex. These results provide a rationale for understanding the series of interactions that orchestrate the terminal steps of nuclear protein import.


Effect of solvent polarization on the reorganization energy of electron transfer from molecular dynamics simulations.
The solvent contribution lambda(s) to the reorganization energy of electron transfer can be estimated from averages of the potential energy gaps between neutral-pair and ion-pair states over an ensemble of structures generated from molecular dynamics simulations. Invoking a Marcus-type two-sphere model for charge separation and recombination in an aqueous environment, we explored the effect of a polarizable force field and noted a strong reduction of lambda(s) (by approximately 45%) compared to the corresponding value obtained with a standard nonpolarizable force field. Both types of force fields yield lambda(s) values that in agreement with the Marcus theory, vary strictly linearly with the inverse of the donor-acceptor distance; the corresponding slopes translate into appropriate effective optical dielectric constants, epsilon(infinity) approximately 1.0+/-0.2 for a nonpolarizable and epsilon(infinity) approximately 1.7+/-0.4 for a polarizable force field. The reduction in the solvent reorganization energy due to a polarizable force field translates into a scaling factor that is essentially independent of the donor-acceptor distance. The corresponding effective optical dielectric constant, epsilon(infinity) approximately 1.80, is in excellent agreement with experiment for water.


The electronic structure of a strongly bound sandwich MoS2-WS2 heterobilayer.
First of all, we show that two kinds of sandwich bilayers (BLs) are dynamically, thermally, and mechanically stable, which are degenerate p-type materials with intercalated Ca atoms, i.e., Nb-doped MoS2 homobilayers (HoBLs) and Nb-doped WS2-MoS2 heterobilayers (HtBLs) with 25% Nb content. Specifically, their interlayer bindings are five times stronger than van der Waals interactions in their pristine counterparts. Both of them are semiconductors with indirect band gaps in the visible region within the HSE06 exchange-correlation functional. Depending upon the presence and absence of centrosymmetry, they display interesting spin-valley coupling effects in such a way that opposite hidden spin polarization or opposite spin splitting is observed at opposite k-points. They can be easily engineered into direct gap materials under compressive (>2%) strain along the zigzag direction even with an explicit consideration of giant spin splitting. Under strain, they satisfy thermodynamic conditions for bifunctional catalysis in photocatalytic water splitting. In addition, the photoholes of the BLs can be subjected to lower overpotentials than those of pristine BLs for the oxygen evolution reaction. Electrons and holes in the sandwich HtBL can be separated into different layers under photon irradiation, allowing it to be more efficient than the corresponding HoBL in solar energy harvesting.


Role of statins in Alzheimer's disease: a retrospective meta-analysis for commonly investigated clinical parameters in RCTs.
This review was conducted to assess the role of statins in the treatment of Alzheimer's disease (AD). We conducted meta-analysis using the randomised controlled trials (RCTs) conducted in patients who suffered from Alzheimer's disease, by conducting searches for RCTs in MEDLINE, EMBASE and Cochrane (up to 2012). An overall of five studies were included and analysed. The evaluation was done for some commonly evaluated clinical parameters like Clinical Global Impression of Change (CGIC), Mini Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale (ADAS-CoG). Statistical evaluation was done as per method described by Neyeloff et al. and forest plots were plotted for each evaluated parameter. MMSE score showed a significant difference in favour of statins. ADAS-CoG and CGIC did not show a significant advantage for statins in comparison to placebo. Highly heterogeneous distribution was seen for MMSE score. Further trials need to be conducted to arrive at more robust results.