Cloning, expression and characterization of theta-class glutathione S-transferase from the silkworm, Bombyx mori.
This study focused on glutathione S-transferase (GST), one of the detoxification enzymes, from the silkworm, Bombyx mori (GSTT1). A cDNA encoding a putative GST was amplified by reverse transcriptase-polymerase chain reaction and sequenced. The deduced amino acid sequence revealed 59%, 57% and 56% identities to theta-class GSTs of Musca domestica, Anopheles gambiae and Drosophila melanogaster, respectively. GSTT1 was also estimated to be close to those GSTs in a phylogenetic tree. Recombinant GST (rGSTT1) was functionally overexpressed in Escherichia coli in a soluble form, purified to homogeneity, and characterized. The pH-optimum of rGSTT1 was broad from pH 4 to 9 and rGSTT1 retained more than 75% of its original activity after incubation at pH 5-11. Incubation for 30 min at temperatures below 50 degrees C also affected the activity insignificantly. The Michaelis constant for 1-chloro-2,4-dinitrobenzene was 0.48 mM.


Predicting Attentional Impairment in Women With Posttraumatic Stress Disorder Using Self-Reported and Objective Measures of Sleep.
There is growing evidence to support sleep impairment as a core feature of posttraumatic stress disorder (PTSD). Sleep impairment in PTSD is associated with severe distress and poorer treatment outcomes. Therefore, specific attention to this symptom of PTSD is warranted and accurate assessment of sleep impairment is critical. The current study investigated the association between self-reported and objective assessment of sleep and sustained attention in women with PTSD. Study participants include 50 treatment-seeking, female, interpersonal violence survivors who have PTSD. Nocturnal sleep duration was measured with self-report sleep diaries and objective actigraphy assessment over the course of 7 nights. Sustained attention during daytime was measured by the Psychomotor Vigilance Task (PVT). Results indicated that self-reported nocturnal sleep duration, but not objective or global sleep quality measures, best predicted attentional deficits as indicated by lapses and inverse reaction time on the PVT. Daily sleep diaries predicted 19% and 14% of the variance in attentional lapses and inverse reaction time, respectively. In a sample of women with PTSD, self-reported nocturnal sleep duration predicted deficits in sustained attention. Conversely, sleep duration as measured by actigraphy and global sleep quality, did not predict sustained attention. Findings suggest that assessing sleep impairment on a daily basis may provide clinically relevant information in evaluating daytime symptoms and provide guidance in targeting this particularly troublesome symptom in the treatment of PTSD. Werner KB, Arditte Hall KA, Griffin MG, Galovski TE. Predicting attentional impairment in women with posttraumatic stress disorder using self-reported and objective measures of sleep. J Clin Sleep Med. 2019;15(9):1329-1336.


Value of multiplanar reformations (MPR) in multidetector CT (MDCT) of acute vertebral fractures: do we still have to read the transverse images?
To determine the value of multiplanar reformations (MPRs) in multidetector computed tomography (MDCT) diagnosis of acute vertebral fractures and to assess the necessity to read the whole set of transverse images. Retrospectively, 56 MDCT of 55 patients with acute vertebral fractures were included. The images were analyzed by two radiologists in a consensus procedure. First, the diagnosis was made exclusively from sagittal and coronal MPRs; secondly, the transverse images were analyzed with knowledge of the MPRs. Diagnostic accuracy is given as percentage. Image amounts were compared using the Wilcoxon test. In 244 vertebral bodies, all 70 fractured vertebrae were diagnosed on reviewing MPRs only. There were no false positive cases. In 2/70 fractures, the anatomically exact diagnosis was complemented by reading the transverse images. Forty-two of 43 unstable fractures were diagnosed correctly on MPRs only. With preference of MPR reading, the total number of images to be analyzed could be reduced significantly (P < 0.01). Reading of MPRs alone is a feasible approach for correct assessment of vertebral fractures and classifying them into stable/unstable, if MPRs are done properly. Transverse images must be analyzed in complex fractures or uncertain findings.


The modulating effects of endogenous substances on drug metabolising enzymes and implications for inter-individual variability and quantitative prediction.
The cytochrome P450 family of enzymes play an important role in the metabolism of drugs and other xenobiotics. While genotypic variation can contribute to the inter-individual variability in drug metabolism, individuals sharing the same genotype for an enzyme can still show considerable variability in drug metabolising capacity by that enzyme. It is well recognised that in some disease states (e.g. inflammation, infection, diabetes) or other physiological conditions (e.g. pregnancy), the clearance of drugs may significantly alter, possibly via modulation of drug metabolising enzymes by varying levels of endogenous substances. This review investigates the current knowledge on the modulating effects of various endogenous substances on DMEs in vitro and possible utility of available in vitro data for quantitative prediction of clinical outcome. It is postulated that understanding and estimating the inter-individual variability in DMEs within each population might be possible by application of in vitro in vivo extrapolation linked physiologically-based pharmacokinetic modelling. However, in vitro information for building such quantitative relationships is currently not abundant.


In vitro heterogeneous degradation of poly(n-alkyl alpha-cyanoacrylates).
Methods by which in vitro heterogeneous phase degradation rates of the poly(n-alkyl alpha-cyanoacrylates) have been directly obtained are described. The data indicate that the rates of degradation in aqueous buffer solutions depend not only upon pH of the medium and length of the monomer alkyl side chain, but also critically upon polymer particle specific surface, particle size, polymer molecular weight, and molecular weight distribution. A modification of the currently held theory of degradation of these polymers is required, and postulated.


[The role of bivalent cations in the binding of hexokinase II isoenzyme to mitochondrial membranes].
A comparative study of Mg2+ and Ca2+ effects on the ability of rat skeletal muscle hexokinase isozyme II to bind mitochondrial membranes isolated from the same source was carried out. It was found that the binding ability of the enzyme increases in a similar way in the presence of equimolar amounts of both cations. The dependence of binding ability on cation concentration is hyperbolic, which points to the existence of specific and equivalent metal binding sites during hexokinase attachment to the membranes. Substitution of Ca2+ for Mg2+ does not influence the tightness of the enzyme binding to membranes, which can be evidenced from the type of dependence of the bound hexokinase solubilization degree on KCl concentration in the eluting buffer. The enzyme absorption mediated by various cations is accompanied by corresponding changes in its kinetic properties (V, Km for glucose, Ki for ADP). The role of bivalent cations in the formation of the specific hexokinase-membrane binding is discussed.


Uterine prolapse in a non-pregnant bitch.
A ten-year-old mixed breed bitch was presented for a tissue prolapse protruding from her vulva. Following detailed examination and stabilization, the ovaries and uterine horns were removed by laparotomy, whereas the prolapsed tissue identified as uterus including cervix was removed vaginally. Histology confirmed uterine prolapse, a rare condition in bitches usually found shortly after birth especially due to dystocia. In contrast, the present case was found in a nulliparous non-pregnant bitch. Diagnostic and therapeutic approaches, including microbiological and histological findings, are described and discussed critically.


Effect of isoliquiritigenin for the treatment of atopic dermatitis-like skin lesions in mice.
Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized with high heterogeneity. Recent studies have suggested that it is driven by both terminal keratinocyte differentiation defects and type 2 immune responses. The mainstay steroid topical therapy has severe side effect and new treatment is in demand. Isoliquiritigenin (ISLG) is a small phenolic bioactive molecule from licorice that has shown multiple pharmacological effects against cancer, inflammatory disorder, and cardiovascular diseases. ISLG was evaluated in AD-like lesion model induced by the repetitive application of 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. Overall symptom score, serological and molecular changes of the skin lesions were evaluated. ISLG could ameliorate the overall manifestation of AD-like symptoms including scratching behavior incidence and skin lesion severity. At blood level, ISLG significantly suppressed the DNCB-induced IgE and Th2 cytokines up-regulation. At skin lesion site, ISLG also inhibited DNCB-induced pro-inflammatory cytokines like TNF-α, IL-6 as well as IL-4 expressions. In a human monocyte model THP-1, ISLG suppressed the up-regulation of CD86 and CD54 and abolished the DNCB-induced p38-α and ERK activation, suggesting a molecular mechanism for ISLG therapy. This study indicated that ISLG could be a potential therapeutic agent for the treatment of AD.


Risk factors and high-risk subgroups of severe acute maternal morbidity in twin pregnancy: A population-based study.
To determine risk factors of severe acute maternal morbidity in women with twin pregnancies and identify subgroups at high risk. In a prospective, population-based study of twin deliveries, the JUMODA cohort, all women with twin pregnancies at or after 22 weeks of gestation were recruited in 176 French hospitals. Severe acute maternal morbidity was a composite criterion. We determined its risk factors by multilevel multivariate Poisson regression modeling and identified high-risk subgroups by classification and regression tree (CART) analysis, in two steps: first considering only characteristics known at the beginning of pregnancy and then adding factors arising during its course. Among the 8,823 women with twin pregnancies, 542 (6.1%, 95% confidence interval (CI) 5.6-6.6) developed severe acute maternal morbidity. Risk factors for severe maternal morbidity identified at the beginning of pregnancy were maternal birth in sub-Saharan Africa (adjusted relative risk (aRR) 1.6, 95% CI 1.1-2.3), preexisting insulin-treated diabetes (aRR 2.2, 95% CI 1.1-4.4), nulliparity (aRR 1.6, 95% CI 1.3-2.0), IVF with autologous oocytes (aRR, 1.3, 95% CI, 1.0-1.6), and oocyte donation (aRR 2.0, 95% CI 1.4-2.8); CART analysis identified nulliparous women with oocyte donation as the subgroup at highest risk (SAMM rate: 14.7%, 95% CI, 10.3-19.1). At the end of pregnancy, additional risk factors identified were placenta praevia (aRR 3.5, 95% CI 2.3-5.3), non-severe preeclampsia (aRR 2.5, 95% CI 1.9-3.2), and macrosomia for either twin (aRR 1.7, 95% CI 1.3-2.1); CART analysis identified women with both oocyte donation and non-severe preeclampsia (SAMM rate: 28.9%, 95% CI, 19.9-37.9) and sub-Saharan nulliparous women with non-severe preeclampsia (SAMM rate: 26.9%, 95% CI, 9.9-43.9) as the two subgroups at highest risk. In woman with twin pregnancy, rates of severe acute maternal morbidity vary between subgroups from 4.6% to 14.7% and from 3.8% to 28.9% at the beginning and at the end of pregnancy respectively, depending on the combined presence of risk factors.


Lymphatic vessel density as a prognostic marker in clinical stage I endocervical adenocarcinoma.
There are limited data evaluating the significance of lymphatic vessel density (LVD) as a prognostic marker in cervical adenocarcinoma. In this study, we investigated intratumoral and peritumoral LVD, using the lymphatic marker D2-40, as a prognostic marker in endocervical adenocarcinoma. Surgical specimens from 50 consecutive patients with endocervical adenocarcinoma treated with complete staging surgical procedures were reviewed. Selected tumor blocks were immunostained for D2-40 and CD31. Positively stained microvessels (MVs) were counted in densely vascular/lymphatic foci (hot spots) at 400x field in each specimen (0.17 mm). Results were expressed as the highest MV count identified within any single field. Both intratumoral CD31 MV and peritumoral D2-40 LVD showed significant correlation with depth of invasion (r=0.39, 0.37, respectively), percentage of circumferential involvement (r=0.36, 0.48, respectively), and lymphovascular invasion detected by D2-40 (r=0.45, 0.51, respectively; P<0.01). Only peritumoral D2-40 LVD showed a significant correlation with lymph node metastases (r=0.40; P<0.01), disease-free and overall survivals. Using univariate analysis, peritumoral D2-40 LVD showed significant correlation with lymphovascular invasion detected by D20-40 and lymph node metastases (P<0.05), which was maintained on multivariate analysis. D2-40 detected lymphovascular invasion in 16 of 50 (32%) cases, and showed a significant correlation with depth of invasion, lymph node metastases, involvement of parametrium (r=0.41, 0.38, 0.32, respectively; P<0.01), and disease-free survival. Our study showed that both angiogenesis and lymphangiogenesis play an important role in the progression of endocervical adenocarcinoma, and that peritumoral D2-40 LVD is an independent predictor of lymph node metastasis.


JASPAC: Japan Spastic Paraplegia Research Consortium.
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by weakness and spasticity of the lower extremities. HSPs are heterogeneous disorders that involve over 80 causative genes. The frequency of HSPs is estimated to be 10⁻100/1,000,000. With this background, the Japanese research group "Japan Spastic Paraplegia Research Consortium: JASPAC" was organized in 2006 to elucidate the molecular epidemiologies of HSPs in Japan and the molecular pathologies of HSPs. To date, the JASPAC has collected 714 HSP families and analyzed 488 index patients. We found 279 pathogenic variants or probable pathogenic variants of causative genes in the 488 HSP patients. According to our results, we found 178 families with autosomal dominant patients (65%), and 101 with autosomal recessive and sporadic patients (48%). We found 119 patients with SPG4, 17 with SPG3A, 15 with SPG31, 13 with SPG11, and 11 with SPG10. Other HSP genes were the cause in less than five patients. On the other hand, we could not find causative genes in 35% of the autosomal dominant patients, or 52% of the autosomal recessive and sporadic patients. We are now trying to find new causative genes and elucidate the molecular mechanisms underlying HSPs.


[Action of levorin on glucose transport in the rat small intestine].
The technique of accumulating preparation of the mucosa and "turned out sac" was used to show that levorin, a polyenic antibiotic in a concentration of 10(-6) M, lowered the transport rate and accumulation of glucose by the epithelial cells of the rat thin intestine under conditions of oxygenation. Suppression of the glucose transport in the first stages resulted in partial inhibition of the transmembrane transfer. It is suggested that levorin suppression of the glucose transport through the erythrocyte apical membrane in the thin intestine is associated with a decrease in the electrochemical gradient of Na+.


Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy.
Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced renal complications and mechanisms to facilitate readministration of ERT in these patients remain unexplored. This work identifies a new antigen responsible for secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB [rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB titer and dramatically improved clinical manifestations. However, 16 months later, the patient suddenly developed nephrotic syndrome resistant to steroid therapy 1 week after orthopedic surgery. Examination of the kidney biopsy specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN. Double immunofluorescence staining showed that subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted from the patient's biopsy specimen reacted specifically with rhASB. On discontinuation of ERT, proteinuria progressively decreased, but the patient's clinical condition markedly deteriorated. Induction of tolerance to rhASB was initiated by coadministration of low-dose corticosteroids, rituximab, intravenous Igs, and oral methotrexate. ERT was resumed 8 weeks after starting immunosuppressive therapy without inducing a rebound of antibody titer or an increase in proteinuria. We conclude that the allo-immune response to the recombinant rhASB caused the nephropathy. Considering the critical requirement for ERT in patients with such enzyme deficiencies, immune tolerance induction should be advocated in the patients with allo-immune MN.


A reliable subtyping of de novo Parkinson disease: biomarkers, medication effects and longitudinal progression.
Divergent clinical symptoms and pathological progression suggest multiple subtypes of Parkinson disease (PD). Here, we proposed a reliable PD subtyping approach that quantifies the disturbance of an individual patient to the reference structural covariance networks derived from healthy controls. We revealed two subtypes of de novo PD patients by using longitudinal data from the PPMI dataset. Compared to the conventional clinical TD/PIGD phenotypes, our subtyping was highly stable in 5 years' visits. The two subtypes of PD showed significant differences in motor symptoms, medication effects, CSF biomarkers, and longitudinal progression. Moreover, patients of subtype 2 showed widespread lower cortical-to-dorsal raphe nucleus (DRN) connections and higher medication effects on motor symptoms which was regulated by 5-HT neurons in DRN. Our results suggest distinct neuropathological pathways underlying the two subtypes, such that, in contrast to the typical PD subtype, patients of subtype 2 may be affected by serotonergic modulation on dopaminergic neurons in striatum. Our study opens new avenue to precision medicine and personalized treatments in PD and may be applicable to other neurodegenerative diseases.


Mandibular fractures: an appraisal of the weak regions.
There is no uniformity in the role of different aetiologic factors in mandibular fractures in different cities of the world. Cultural and socioeconomic factors appear to have important contribution to the aetiologies. The condyle and the angle-body regions are most commonly fractured. There is no obvious relationship between aetiology and the site of fracture. Structural considerations suggest that differences between dentate (open section structure) and non dentate (closed section structure) regions are important determinants of fracture sites. Some modifications of standard teaching materials are recommended.


Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise.
Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex interaction between environmental and genetic factors. In recent years, the role of the gut microbiota in brain health has received particular attention, and compelling evidence has shown that patients suffering from depression have gut dysbiosis. Several studies have reported that gut dysbiosis-induced inflammation may cause and/or contribute to the development of depression through dysregulation of the gut-brain axis. Indeed, as a consequence of gut dysbiosis, neuroinflammatory alterations caused by microglial activation together with impairments in neuroplasticity may contribute to the development of depressive symptoms. The modulation of the gut microbiota has been recognized as a potential therapeutic strategy for the management of MMD. In this regard, physical exercise has been shown to positively change microbiota composition and diversity, and this can underlie, at least in part, its antidepressant effects. Given this, the present review will explore the relationship between physical exercise, gut microbiota and depression, with an emphasis on the potential of physical exercise as a non-invasive strategy for modulating the gut microbiota and, through this, regulating the gut-brain axis and alleviating MDD-related symptoms.


Pan-mTOR inhibitor MLN0128 is effective against intrahepatic cholangiocarcinoma in mice.
Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy without effective treatment options. MLN0128, a second generation pan-mTOR inhibitor, shows efficacy for multiple tumor types. We evaluated the therapeutic potential of MLN0128 vs. gemcitabine/oxaliplatin in a novel ICC mouse model. We established a novel ICC mouse model via hydrodynamic transfection of activated forms of AKT (myr-AKT) and Yap (YapS127A) protooncogenes (that will be referred to as AKT/YapS127A). Genetic approaches were applied to study the requirement of mTORC1 and mTORC2 in mediating AKT/YapS127A driven tumorigenesis. Gemcitabine/oxaliplatin and MLN0128 were administered in AKT/YapS127A tumor-bearing mice to study their anti-tumor efficacy in vivo. Multiple human ICC cell lines were used for in vitro experiments. Hematoxylin and eosin staining, immunohistochemistry and immunoblotting were applied for the characterization and mechanistic study. Co-expression of myr-AKT and YapS127A promoted ICC development in mice. Both mTORC1 and mTORC2 complexes were required for AKT/YapS127A ICC development. Gemcitabine/oxaliplatin had limited efficacy in treating late stage AKT/YapS127A ICC. In contrast, partial tumor regression was achieved when MLN0128 was applied in the late stage of AKT/YapS127A cholangiocarcinogenesis. Furthermore, when MLN0128 was administered in the early stage of AKT/YapS127A carcinogenesis, it led to disease stabilization. Mechanistically, MLN0128 efficiently inhibited AKT/mTOR signaling both in vivo and in vitro, inducing strong ICC cell apoptosis and only marginally affecting proliferation. This study suggests that mTOR kinase inhibitors may be beneficial for the treatment of ICC, even in tumors that are resistant to standard of care chemotherapeutics, such as gemcitabine/oxaliplatin-based regimens, especially in the subset of tumors exhibiting activated AKT/mTOR cascade. Lay summary: We established a novel mouse model of intrahepatic cholangiocarcinoma (ICC). Using this new preclinical model, we evaluated the therapeutic potential of mTOR inhibitor MLN0128 vs. gemcitabine/oxaliplatin (the standard chemotherapy for ICC treatment). Our study shows the anti-neoplastic potential of MLN0128, suggesting that it may be superior to gemcitabine/oxaliplatin-based chemotherapy for the treatment of ICC, especially in the tumors exhibiting activated AKT/mTOR cascade.


Assessing physical activity in older adults: required days of trunk accelerometer measurements for reliable estimation.
We investigated the reliability of physical activity monitoring based on trunk accelerometry in older adults and assessed the number of measured days required to reliably assess physical activity. Seventy-nine older adults (mean age 79.1 ± 7.9) wore an accelerometer at the lower back during two nonconsecutive weeks. The duration of locomotion, lying, sitting, standing and shuffling, movement intensity, the number of locomotion bouts and transitions to standing, and the median and maximum duration of locomotion were determined per day. Using data of week 2 as reference, intraclass correlations and smallest detectable differences were calculated over an increasing number of consecutive days from week 1. Reliability was good to excellent when whole weeks were assessed. Our results indicate that a minimum of two days of observation are required to obtain an ICC ≥ 0.7 for most activities, except for lying and median duration of locomotion bouts, which required up to five days.


Evaluation of various biomarkers as potential mediators of the association between coffee consumption and incident type 2 diabetes in the EPIC-Potsdam Study.
The inverse association between coffee consumption and the risk of type 2 diabetes (T2D) is well established; however, little is known about potential mediators of this association. We aimed to investigate the association between coffee consumption and diabetes-related biomarkers and their potential role as mediators of the association between coffee consumption and T2D. We analyzed a case-cohort study (subcohort: n = 1610; verified incident T2D cases: n = 417) nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam study involving 27,548 middle-aged participants. Habitual coffee consumption was assessed with a validated, semiquantitative food-frequency questionnaire. We evaluated the association between coffee consumption and several T2D-related biomarkers, such as liver markers (reflected by γ-glutamyltransferase, fetuin-A, and sex hormone-binding globulin), markers of dyslipidemia (high-density lipoprotein cholesterol and triglycerides), inflammation [C-reactive protein (CRP)], an adipokine (adiponectin), and metabolites, stratified by sex. Coffee consumption was inversely associated with diacyl-phosphatidylcholine C32:1 in both sexes and with phenylalanine in men, as well as positively associated with acyl-alkyl-phosphatidylcholines C34:3, C40:6, and C42:5 in women. Furthermore, coffee consumption was inversely associated with fetuin-A (P-trend = 0.06) and CRP in women and γ-glutamyltransferase and triglycerides in men. Coffee consumption tended to be inversely associated with T2D risk in both sexes, reaching significance only in men [HR (95% CI): women: ≥4 compared with >0 to <2 cups coffee/d: 0.78 (0.46, 1.33); men: ≥5 compared with >0 to <2 cups coffee/d: 0.40 (0.19, 0.81)]. The association between coffee consumption and T2D risk in men was slightly reduced after adjustment for phenylalanine or lipid markers. Coffee consumption was inversely associated with a diacyl-phosphatidylcholine and liver markers in both sexes and positively associated with certain acyl-alkyl-phosphatidylcholines in women. Furthermore, coffee consumption showed an inverse trend with CRP in women and with triglycerides and phenylalanine in men. However, these markers explained only to a small extent the inverse association between long-term coffee consumption and T2D risk.


Recognition and Management of Emergent Spinal Pathology Among First-Line Providers.
Spinal emergencies require prompt identification, management, and surgical referral (if needed) from first-line providers. Diagnostic delays from a failure to recognize emergency conditions can lead to adverse patient outcomes. The objective of this study was to understand the proficiency with which first-line providers can recognize and manage spinal conditions, particularly spinal emergencies. This was a cross-sectional analysis of 143 internal medicine, family medicine, emergency care, and neurology questionnaires collected at a single-site academic center. Participants were predominantly physicians (88.1%, n=126), with a smaller percentage of midlevel providers (11.9%, n=17). Only 35.0% (n=50) of respondents felt "very prepared" to handle spinal emergencies. Bivariate analyses revealed interdepartmental differences in clinical knowledge pertaining to the management of lumbar radiculopathy (P<.0001), epidural abscess (P=.0002), and cervical myelopathy (P<.0001). Following pairwise comparisons of interdepartmental differences, emergency medicine statistically outperformed internal medicine (P=.0007) and neurology (P<.0001) on initial management of lumbar radiculopathy, while also having markedly higher success in identifying and managing epidural abscess with respect to family medicine (P<.0001). The likelihood of appropriate initial treatment of cervical myelopathy was significantly higher for neurology than for emergency medicine (P<.0001). A minority of first-line providers reported being very prepared to handle spinal emergencies. Disparities exist between first-line provider specialties regarding clinical knowledge in managing and proficiently identifying emergent and nonemergent spinal conditions. Because appropriate handling of emergent spinal pathologies is essential to patient outcomes and optimal resource use, measures should be taken to further educate first-line providers regarding the spinal conditions they will be treating. [Orthopedics. 2020;43(4):e244-e250.].


[Regeneration of the parathyroid glands following mechanical trauma].
During the interval of 3h-42 days regeneration of the parathyroid glands traumatized by means of forceps has been studied in 66 rats. The model presented reproduces the postoperative state of hypoparathyreosis occurring in the clinic. Ten intact and 30 pseudooperated animals serve as controls. The material is treated by means of histological, histochemical and morphometric methods (the stereological one including). The function of the gland is estimated according to total calcium content in blood serum. After 3-17th the parathyroid gland trauma produces some foci of parenchymal destruction. On the second day connective tissue begins developing in them. Epithelial regeneration occurs at the expense of an increased mitotic activity of the chief cells in the noninjured parts of the gland up to 0.9-1.5%, after 3-4 days hypertrophy of epitheliocytes, their nuclei and nucleoli, increasing number of nucleoli in the nucleus. After 5-10 days a limited outgrowth of the glandular parenchyma within large foci of the lesion is observed in some animals. Because of a rapid development of the connective tissue scars, however, at the place of the destroyed glandular parenchyma areas, there is no normalization of the organ's structure and function by the 42d day. A relative volume of stroma increases as much as 3-4 times as compared to the noninjured gland. The quantitative data dynamics analised demonstrate certain phasing in the regenerative processes: period of an alteration and an active macrophagal reaction (first 48 h after trauma), period of an active regeneration (the 2d - the 6th day), period of a temporary compensation (the 8th - the 13th day), period of a stable hyperfunction of the organ (the 16th - the 42d day).


Declines in motor transfer following upper extremity task-specific training in older adults.
Age-related declines in function can limit older adults' independence with activities of daily living (ADLs). While task-specific training maybe a viable approach to improve function, limited clinical resources prevent extensive training on wide ranges of skills and contexts. Thus, training on one task for the benefit of another (i.e., transfer) is important in geriatric physical rehabilitation. The purpose of this study was to test whether motor transfer would occur between two functionally different upper extremity tasks that simulate ADLs in a sample of older adults following task-specific training. Ninety community dwelling adults ages 43 to 94 years old performed two trials of a functional dexterity and functional reaching task at baseline, and were then assigned to one of two groups. The training group completed 3 days of task-specific training (150 trials) on the functional reaching task, whereas the no-training group received no training on either task. Both groups were re-tested on both tasks at the end of Day 3. No significant interactions were observed between group (training vs. no-training) and time (baseline vs. re-test) on the functional dexterity task (i.e. transfer task), indicating no difference in the average amount of change from baseline to re-test between the groups. However, post hoc bivariate linear regression revealed an effect of age on motor transfer within the training group. For those who trained on the functional reaching task, the amount of transfer to the dexterity task was inversely related to age. There was no significant relationship between age and motor transfer for the no-training group. Results of our a priori group analysis suggest that functional reaching training did not, on average, transfer to the dexterity task. However, post hoc regression analysis showed that motor transfer was both experience- and age-dependent, such that motor transfer may decline with advanced age. Future research will consider how functional and cognitive aging influences transfer of motor skills across different activities of daily living.


The relation between staging fluorine-18 fluorodeoxyglucose positron emission tomog- raphy/computed tomography metabolic parameters and tumor necrosis rate in pediatric osteosarcoma patients
The aim of this study was to investigate the contribution of fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in staging of pediatric osteosarcoma patients and also to evaluate the ability of metabolic parameters from the primary tumor to predict tumor necrosis rate (TNR). F-18 FDG-PET/CT imaging was performed in staging 37 pediatric osteosarcoma patients. The metabolic pa- rameters SUVmax (maximum standardised uptake value), MTV (metabolic tumour volume), and TLG (total lesion glycolysis) were measured from the primary tumor. TNR level of the primary tumor was histopathologically measured after standard neoadjuvant chemotherapy treatment. The contribution of F-18 FDG-PET/CT to staging of pediatric osteosarcoma patients and the accuracy of metabolic parameters of the primary tumor to predict TNR were analized by regression analysis. MTV and TLG of the primary tumor were found to efficiently predict histopathologic TNR, whereas SUVmax was not (P = 0.012, P = 0.027, P = 0.25, respectively). Also 5 of 12 patients (41.6%) who were initially defined as localised osteosarcoma were upstaged in consequence of staging F-18 FDG-PET/CT findings. F-18 FDG-PET/CT staging in pediatric osteosarcoma patients can effectively distinguish metastatic-localised disease. MTV and TLG values are important parameters, which can efficiently be used to predict TNR.


Sensitivity to Neutralizing Antibodies and Resistance to Type I Interferons in SARS-CoV-2 R.1 Lineage Variants, Canada.
Isolating and characterizing emerging SARS-CoV-2 variants is key to understanding virus pathogenesis. In this study, we isolated samples of the SARS-CoV-2 R.1 lineage, categorized as a variant under monitoring by the World Health Organization, and evaluated their sensitivity to neutralizing antibodies and type I interferons. We used convalescent serum samples from persons in Canada infected either with ancestral virus (wave 1) or the B.1.1.7 (Alpha) variant of concern (wave 3) for testing neutralization sensitivity. The R.1 isolates were potently neutralized by both the wave 1 and wave 3 convalescent serum samples, unlike the B.1.351 (Beta) variant of concern. Of note, the R.1 variant was significantly more resistant to type I interferons (IFN-α/β) than was the ancestral isolate. Our study demonstrates that the R.1 variant retained sensitivity to neutralizing antibodies but evolved resistance to type I interferons. This critical driving force will influence the trajectory of the pandemic.


Engineering the gain-bandwidth product of phototransistor diodes.
In recent years, phototransistors have considerably expanded their field of application, including for instance heterodyne detection and optical interconnects. Unlike in low-light imaging, some of these applications require fast photodetectors that can operate in relatively high light levels. Since the gain and bandwidth of phototransistors are not constant across different optical powers, the devices that have been optimized for operation in low light level cannot effectively be employed in different technological applications. We present an extensive study of the gain and bandwidth of short-wavelength infrared phototransistors as a function of optical power level for three device architectures that we designed and fabricated. The gain of the photodetectors is found to increase with increasing carrier injection. Based on a Shockley-Read-Hall recombination model, we show that this is due to the saturation of recombination centers in the phototransistor base layer. Eventually, at a higher light level, the gain drops, due to the Kirk effect. As a result of these opposing mechanisms, the gain-bandwidth product is peaked at a given power level, which depends on the device design and material parameters, such as doping and defect density. Guided by this physical understanding, we design and demonstrate a phototransistor which is capable of reaching a high gain-bandwidth product for high-speed applications. The proposed design criteria can be employed in conjunction with the engineering of the device size to achieve a wide tunability of the gain and bandwidth, hence paving the way toward fast photodetectors for applications with different light levels.


Hyperactivated FRS2α-mediated signaling in prostate cancer cells promotes tumor angiogenesis and predicts poor clinical outcome of patients.
Metastasis of tumors requires angiogenesis, which is comprised of multiple biological processes that are regulated by angiogenic factors. The fibroblast growth factor (FGF) is a potent angiogenic factor and aberrant FGF signaling is a common property of tumors. Yet, how the aberration in cancer cells contributes to angiogenesis in the tumor is not well understood. Most studies of its angiogenic signaling mechanisms have been in endothelial cells. FGF receptor substrate 2α (FRS2α) is an FGF receptor-associated protein required for activation of downstream signaling molecules that include those in the mitogen-activated protein and AKT kinase pathways. Herein, we demonstrated that overactivation and hyperactivity of FRS2α, as well as overexpression of cJUN and HIF1α, were positively correlated with vessel density and progression of human prostate cancer (PCa) toward malignancy. We also demonstrate that FGF upregulated the production of vascular endothelial growth factor A mainly by increasing expression of cJUN and HIF1α. This then promoted recruitment of endothelial cells and vessel formation for the tumor. Tumor angiogenesis in mouse PCa tissues was compromised by tissue-specific ablation of Frs2α in prostate epithelial cells. Depletion of Frs2α expression in human PCa cells and in a preclinical xenograft model, MDA PCa 118b, also significantly suppressed tumor angiogenesis accompanied with decreased tumor growth in the bone. The results underscore the angiogenic role of FRS2α-mediated signaling in tumor epithelial cells in angiogenesis. They provide a rationale for treating PCa with inhibitors of FGF signaling. They also demonstrate the potential of overexpressed FRS2α as a biomarker for PCa diagnosis, prognosis and response to therapies.


Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets.
Human blood contains 2 populations of dendritic cells (DCs): plasmacytoid and myeloid (mDC). mDCs are subdivided into 3 subsets using the surface markers CD16, CD1c, and BDCA-3. Their role as pathogen sentinels and adjuvant targets was tested by phenotypic and functional analysis. We show that mDC subsets are immature and express mRNA for most toll-like receptors (TLRs), except for TLR3 in CD16-mDCs. The most represented subsets, CD16- and CD1c-mDCs, are similarly responsive to all TLR agonists. Among 31 cytokines tested, both subsets produce CXCL8 (IL-8)/tumor necrosis factor-alpha (TNF-alpha)/IL-6/CCL3 (MIP-1 alpha)/CCL4 (MIP-1beta)/IL-1 beta. CXCL8 (IL-8) is the predominant cytokine produced by CD1c-mDCs on TLR engagement, whereas all other cytokines, particularly TNF-alpha, are secreted in 10-fold to 100-fold higher amounts by CD16-mDCs. CD16-mDCs cocultured with human umbilical vein endothelial cells induce a significantly higher production of CXCL10 (IP-10), granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor than CD1c-mDCs. In addition, interleukin-3 and type I interferons are stimuli specifically for DC maturation rather than cytokine secretion, whereas TNF-alpha is almost ineffective in inducing either function, suggesting a mechanism of T-cell-DC crosstalk and of rapid induction of antigen-presenting cell function during viral infection rather than inflammation. In conclusion, CD16-mDCs show strong proinflammatory activity, whereas CD1c-mDCs appear to be mainly inducers of chemotaxis.


New obesity body mass index threshold for self-reported data.
Since subjects included in population studies tend to underreport their weight and overestimate their height, obesity prevalence based on these data is often inaccurate. A reduced obesity threshold for self-reported height and weight was proposed and evaluated for its accuracy. Self-reported heights and weights were compared with measured heights and weights in a Swiss city adult population representative sample. Participants were asked their height and weight and were invited to undergo a health examination, during which these data were measured. An optimal body mass index (BMI) value was assessed using receiver operating characteristic (ROC) curve analysis and its ability to correctly estimate obesity prevalence was tested on an external French population sample. The Swiss population sample consisted of 13 162 subjects (mean age 51.4). The comparison between self-reported and measured data showed that obesity prevalence calculated from declarations was underestimated: among obese subjects (according to measured BMI), 33.6% of men and 27.5% of women were considered to be non-obese according to their self-report. Considering measures as a reference, a lower BMI cut-off of 29.2 kg/m(2) was identified for both genders for the definition of obesity based on self-report. Respective misclassification was reduced to 17.9% in men and 16.9% in women. The validation procedure on a French population sample (n = 1858) yielded similar results. The reduced threshold based on self-report allowed a better estimation of obesity prevalence. Its use should be limited to population studies only.


Experiences of Changes in Cognitive Function for Women treated with Chemotherapy for Breast Cancer.
The purpose of this study was to describe the experiences of the process of the change in cognitive function for women treated with chemotherapy for breast cancer. There were ten participants in total in this study. Data were gathered utilizing in-depth interviews over 3 times from September 2010 to January 2011. Data were analyzed by employing Strauss and Corbin's (1998) grounded theory methodology. Findings indicate that causal conditions of these results were 'side effects of chemotherapy' and 'menopausal state', including contextual conditions as, 'mental fatigue' and 'anxiety about recurrence'. The core category was identified as 'confronting with unexpected chaos'. Intervening conditions were 'support from other people', 'lack of information on cognitive impairment'. Interaction strategies were 'changing the habit of life', 'making efforts for living life' and 'seeking for medical information'. Consequences of the process were 'physical restriction', 'difficulty in social life', 'disturbed working ability' and 'psychological distress'. The results of this study show that nurses should recognize there is a notable difference between individual patient's contextual conditions and interactive strategies. Furthermore educational information and individualized intervention should be provided to improve cognitive function for women with breast cancer.


Rising trend of reported primary genital syphilis and genital ulcer disease in Burkina Faso.
Recent trends in reported primary genital syphilis and genital ulcer disease (GUD) were assessed in Burkina Faso using incidence data reported to the Ministry of Health. From 1978 to 1983 the yearly reports of genital syphilis and GUD rose by 42%. A single period moving average was calculated for each consecutive 13-week period from 1978 to 1983, documenting an average 7% rise per year. Severe limitations in the Ministry of Health of personnel and other resources for surveillance were noted and no improvements in surveillance methods were evident during this study. The rising trend suggests a growing problem of ulcerative sexually transmitted diseases, which may, in turn, facilitate infection with sexually acquired human immunodeficiency virus, coincident with the expansion of this epidemic in Africa. Syphilis complications are also almost certain to include adverse pregnancy outcome due to maternal syphilis. The rising trend in genital syphilis and GUD, and the probable increase in associated adverse sequellae, require that prevention and control of sexually transmitted diseases should be made a high priority.


Effect of change in passive stiffness following low-intensity eccentric hamstring exercise on peak torque angle.
[Purpose] The purpose of this study was to investigate the acute effect of low-intensity eccentric hamstring exercise on peak torque angle, range of motion, and passive stiffness. [Participants and Methods] Fourteen healthy young adults exercised as follows: 1) Under low-intensity eccentric hamstring exercise condition, participants performed a stiff-leg deadlift using a 20-kg barbell, 2) Under control condition with participants seated. The peak torque angle during eccentric knee flexion, hip flexion and knee extension range of motion, passive torque, and passive stiffness were measured before and after two conditions in the dominant leg. [Results] The low-intensity stiff-leg deadlift significantly increased hip flexion and knee extension range of motion and significantly decreased passive stiffness. Although the low-intensity stiff-leg deadlift did not change the peak torque angle, the changes in passive torque and passive stiffness were negatively correlated with the change in peak torque angle. [Conclusion] These results suggest that low-intensity eccentric hamstring exercise enhances flexibility, and a decrease in passive torque and passive stiffness are negatively associated with producing the eccentric peak knee flexion torque at a shorter muscle length.


Factors Associated with Patient Satisfaction of Community Mental Health Services: A Multilevel Approach.
Community care is increasingly the mainstay of mental healthcare provision in many countries and patient satisfaction is an important barometer of quality of patient care. This paper explores the key factors associated with patient satisfaction with community mental health services in England and then compares providers' performance on patient satisfaction. Our analysis is based on patient-level responses from the community mental health survey, which is run annually by the Care Quality Commission (CQC) for the years 2010 to 2013. We perform a repeated cross-section analysis, identifying factors associated with patient satisfaction via a multi-level ordered probit model, including both patient- and provider-level variables. We identify hospital-specific effects via empirical Bayes estimation. Our analysis identifies a number of novel results. First, patient characteristics such as older age, being employed, and being able to work, are associated with higher satisfaction, while being female is associated with lower satisfaction. Service contact length, time since last visit, condition severity and admission to a mental health institution, are all associated with lower satisfaction. Second, treatment type affects satisfaction, with patients receiving talking therapies or being prescribed medications being more satisfied. Third, care continuity and involvement, as proxied by having a care plan, is associated with higher satisfaction. Fourth, seeing a health professional closer to the community improves satisfaction, with patients seeing a community-psychiatric nurse, a social worker or a mental-health support worker being more satisfied. Finally, our study identifies the need for service integration, with patients experiencing financial, accommodation, or physical health needs being less satisfied. At a provider level, we find a negative association between the percentage of occupied beds and satisfaction. We further identify significant provider-specific effects after accounting for observable differences in patient and provider characteristics which suggests significant differences in provider quality of care.


Enhancement of alkaline water splitting activity by Co-P coating on a copper oxide nanowire.
Hydrogen is the most attractive source of energy in the 21st century. However, high-efficiency mass production of hydrogen still faces many challenges. Although electrochemical water splitting is an ideal way to produce hydrogen, it requires low-cost and efficient electrocatalysts. In this work, a hybrid shell/core Co-P/CuO nanowire array was fabricated by Co-P film electrodeposition on a CuO nanowire array. Because of the synergy between Co-P and CuO nanowire arrays, Co-P/CuO shows remarkable activity toward the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER). This bifunctional electrocatalyst achieving 20 mA cm-2 requires a cell voltage of only 1.645 V, and has superb long-term electrochemical stability and high faradaic efficiency.


Atypical Vascular Involvement in a Case of Behçet's Disease.
Introduction. Behçet's disease (BD) is a form of vasculitis of unknown etiology which is rare in our environment. It is characterized by a variety of clinical manifestations and usually affects young adults. Recurrent oral and genital ulcers are a characteristic and extremely frequent symptom, but mortality is linked with more significant symptoms such as aortic pseudoaneurysm, pulmonary pseudoaneurysm, and cerebral venous thrombosis. Patient and Method. We present a case of a young male with atypical BD and severe polyvascular involvement (previous cerebral venous thrombosis and current peripheral venous thrombosis, acute ischemia, and peripheral arterial pseudoaneurysm) who required urgent surgical intervention due to a symptomatic external iliac pseudoaneurysm. Result. The pseudoaneurysm was successfully treated, we performed an iliofemoral bypass, and we treated it with steroids and immunosuppressive therapy. Conclusions. These rare clinical manifestations highlight the importance of considering BD in young patients, even in usual cases of vascular intervention, whether arterial or venous in nature.


A bioassay system for two types of colony stimulating factor in human serum.
The biological assay of factors with granulocyte-macrophage colony stimulating activity in human serum poses special problems. Assays based on colony counts suggest, often erroneously, that serum lacks colony stimulating factors (CSF) but interacts with other materials to potentiate or produce factors. Although the scoring of total clone numbers reveals the presence of CSF in serum, this is still no sufficient for the interpretation of the effects of mixing materials containing CSF, because increments in clone numbers are not directly proportional to increments in CSF. This is particularly important in serum assays because two types of activity are present, one which stimulates progenitor cells directly, and another which results from the interation of serum and bone marrow adherent CSF-producing) cells or peripheral blood leucocytes, indicating the presence of both direct acting and "adherent cell dependent" CSF. A biological assay is described which uses analysis of dose-response curves of clone formation in agar culture, and allows simultaneous assay of both types of activity. The criteria for the selection of suitable target progenitor cell populations are discussed.


Long-term outcome for infants and children with sacrococcygeal teratoma: a report from the Childrens Cancer Group.
Sacrococcygeal teratomas (SCT) are a relatively uncommon tumor affecting neonates, infants, and children. This study was designed to determine the effect of therapy on the long-term outcome of neonates and children with sacrococcygeal teratomas (SCT). The authors conducted a retrospective review of children with SCT treated at 15 Childrens Cancer Group institutions from 1972 to 1994. One hundred twenty-six children presented with SCT diagnosed prenatally (n = 32), at birth (n = 79), or later in infancy (n = 15). For neonates, complete resection was performed except in two babies with lethal associated defects. All others (n = 15) underwent resection at the age of diagnosis. Six had a sacral mass identified at birth but had delayed surgery (1.5 to 11 months) and of these, two were malignant. Resection was via sacral (n = 96) or abdominosacral (n = 28) approach. Histology showed mature teratoma (MT, 69%), immature teratoma (IT, 20%), or endodermal sinus tumor (EST, 11%) at presentation. Seven neonates (5.6%) died of perioperative complications, whereas the remaining 117 were available for long-term follow-up. Between 6 and 34 months postresection, recurrent disease developed in 9 of 80 MT patients (11%) followed-up for a mean of 5 years. Recurrent disease was MT (n = 2) and EST (n = 7). The recurrent EST patients were treated with adjuvant chemotherapy. Six are alive with mean follow-up of 114 months, whereas one with metastatic disease was lost to follow-up. Recurrence (MT) developed in only 1 of 24 IT patients, and all are alive and well at mean follow-up of 39 months. Patients presenting with EST (n = 13) underwent excision, with two dying from non-EST causes. Six EST patients received no chemotherapy, with two of the six (33%) experiencing recurrence within 11 months and both disease free after salvage chemotherapy. The remaining five EST patients received adjuvant chemotherapy; four are alive and one died of metastatic disease. Of the 18 EST patients followed-up after resection (presentation, 11, recurrent teratoma, 7), 16 (89%) are free of disease with a mean follow-up of 91 months. (1) Benign teratomas have a significant recurrence rate mandating close follow-up for more than 3 years. (2) Surgical resection alone is adequate therapy for nonmetastatic malignant tumors. (3) Survival for malignant lesions with metastases is excellent with modern chemotherapy.


Total body fat percentage and body mass index and the association with lower extremity injuries in children: a 2.5-year longitudinal study.
Overweight youths are generally recognised as being at increased risk of sustaining lower extremity injuries in sports. However, previous studies are inconclusive and choices for measuring overweight are manifold. To examine two different measures of overweight, body mass index (BMI) and total body fat percentage (TBF%), as risk factors for lower limb injuries in a school-based cohort. A longitudinal cohort study. A total of 632 school children, baseline age 7.7-12.0 years, were investigated. Whole body dual energy x-ray absorptiometry scans provided measures of TBF%. Measures of BMI were obtained by standard anthropometric methods. Musculoskeletal complaints were reported by parents answering weekly mobile phone text messages during 2.5 years. Injuries were diagnosed by clinicians. Leisure time sports participation was reported weekly using text messaging. During 2.5 years of follow-up, 673 lower extremity injuries were diagnosed. Children being overweight by both BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)). Children who were overweight using BMI and TBF% showed the highest risk of sustaining lower extremity injuries (IRR 1.38 (95% CI 1.05 to 1.81)). The risk of lower extremity injuries appeared to be increased for overweight children. When comparing two different measures of overweight, overweight by TBF% is a higher risk factor than overweight by BMI. This suggests that a high proportion of adiposity is more predictive of lower extremity injuries, possibly due to a lower proportion of lean muscle mass.


Cdk1-dependent destruction of Eco1 prevents cohesion establishment after S phase.
Accurate genome segregation depends on cohesion mechanisms that link duplicated sister chromatids, thereby allowing their tension-dependent biorientation in metaphase. In Saccharomyces cerevisiae, cohesion is established during DNA replication when Eco1 acetylates the cohesin subunit Smc3. Cohesion establishment is restricted to S phase of the cell cycle, but the molecular basis of this regulation is unknown. Here, we show that Eco1 is negatively regulated by the protein kinase Cdk1. Phosphorylation of Eco1 after S phase targets it to SCF(Cdc4) for ubiquitination and subsequent degradation. A nonphosphorylatable mutant of Eco1 establishes cohesion after DNA replication, suggesting that Cdk1-dependent phosphorylation of Eco1 is a key factor limiting establishment to S phase. We also show that deregulation of Eco1 results in chromosome separation defects in anaphase. We conclude that this regulatory mechanism helps optimize the level of sister chromatid cohesion, ensuring a robust and efficient anaphase.


A variable precision attribute reduction approach in multilabel decision tables.
Owing to the high dimensionality of multilabel data, feature selection in multilabel learning will be necessary in order to reduce the redundant features and improve the performance of multilabel classification. Rough set theory, as a valid mathematical tool for data analysis, has been widely applied to feature selection (also called attribute reduction). In this study, we propose a variable precision attribute reduct for multilabel data based on rough set theory, called δ-confidence reduct, which can correctly capture the uncertainty implied among labels. Furthermore, judgement theory and discernibility matrix associated with δ-confidence reduct are also introduced, from which we can obtain the approach to knowledge reduction in multilabel decision tables.


Zygomatic salivary mucocoele as a postoperative complication following caudal hemimaxillectomy in a dog.
Zygomatic mucocoele is reported as a postoperative complication occurring secondary to a caudal hemimaxillectomy in a two-year-old Labrador retriever. The dog was presented with a history of a rapidly growing oral mass, identified as a soft tissue sarcoma. A caudal hemimaxillectomy via an intraoral approach was performed as treatment for local control of the oral mass. Fifteen days postoperatively, periorbital swelling and exophthalmos developed on the ipsilateral side. The degree of swelling progressed and was identified by computed tomography, ultrasound and cytology as a salivary mucocoele. Zygomatic sialoadenectomy was performed via a modified lateral approach with zygomatic osteotomy. A small amount of discharge persisted from the surgical site but gradually resolved. Recurrence of the periorbital swelling and exophthalmos was noted 25 days later and further surgery was performed to excise residual salivary tissue. Adjuvant radiotherapy was performed, however local recurrence of the oral mass was identified 5 months postoperatively and the patient subsequently euthanased. Salivary mucocoele has been cited as a possible postoperative complication following maxillectomy and mandibulectomy procedures; however to the authors' knowledge, only one previous case report exists in the literature. The current case documents a zygomatic salivary mucocoele occurring subsequent to caudal hemimaxillectomy.


Occupational Plasmodium falciparum malaria following accidental blood exposure: a case, published reports and considerations for post-exposure prophylaxis.
A French nurse presented Plasmodium falciparum malaria 10 d after a needlestick while sampling blood in a source patient with malaria. As did the source patient, the nurse recovered fully although diagnosis was delayed and her malaria severe. We proceeded to a thorough description of the transmission profile of P. falciparum following occupational needlestick. A review of the literature found 21 published reports of occupational malaria including our own, documenting 22 P. falciparum infections. One of these was lethal. The mean incubation time to fever onset was documented in 21 reports including our own and is 11.60 +/- 3.38 d (median 12.0, range 4-17 d). The incubation period was compatible to that found in experimental anopheline bites or transfusion malaria. The transmission profile cites a pathogen which may be more easily transmissible by occupational exposure to blood than human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Undiagnosed malaria in non-immune health care workers can be lethal. Presumptive treatment of malaria is widely available and well tolerated. Clinicians should consider P. falciparum malaria when faced with a febrile patient who has or may have been exposed to biological fluids. Further research is needed in the field of P. falciparum prophylaxis following accidental exposure to a malaria patient's blood.


MACC: a visual interactive knowledgebase of metabolite-associated cell communications.
Metabolite-associated cell communications play critical roles in maintaining the normal biological function of human through coordinating cells, organs and physiological systems. Though substantial information of MACCs has been continuously reported, no relevant database has become available so far. To address this gap, we here developed the first knowledgebase (MACC), to comprehensively describe human metabolite-associated cell communications through curation of experimental literatures. MACC currently contains: (a) 4206 carefully curated metabolite-associated cell communications pairs involving 244 human endogenous metabolites and reported biological effects in vivo and in vitro; (b) 226 comprehensive cell subtypes and 296 disease states, such as cancers, autoimmune diseases, and pathogenic infections; (c) 4508 metabolite-related enzymes and transporters, involving 542 pathways; (d) an interactive tool with user-friendly interface to visualize networks of multiple metabolite-cell interactions. (e) overall expression landscape of metabolite-associated gene sets derived from over 1500 single-cell expression profiles to infer metabolites variations across different cells in the sample. Also, MACC enables cross-links to well-known databases, such as HMDB, DrugBank, TTD and PubMed etc. In complement to ligand-receptor databases, MACC may give new perspectives of alternative communication between cells via metabolite secretion and adsorption, together with the resulting biological functions. MACC is publicly accessible at: http://macc.badd-cao.net/.


Working for food shifts nocturnal mouse activity into the day.
Nocturnal rodents show diurnal food anticipatory activity when food access is restricted to a few hours in daytime. Timed food access also results in reduced food intake, but the role of food intake in circadian organization per se has not been described. By simulating natural food shortage in mice that work for food we show that reduced food intake alone shifts the activity phase from the night into the day and eventually causes nocturnal torpor (natural hypothermia). Release into continuous darkness with ad libitum food, elicits immediate reversal of activity to the previous nocturnal phase, indicating that the classical circadian pacemaker maintained its phase to the light-dark cycle. This flexibility in behavioral timing would allow mice to exploit the diurnal temporal niche while minimizing energy expenditure under poor feeding conditions in nature. This study reveals an intimate link between metabolism and mammalian circadian organization.


Effectiveness of a multisite personal protective equipment (PPE)-free zone intervention in acute care.
Determine the effectiveness of a personal protective equipment (PPE)-free zone intervention on healthcare personnel (HCP) entry hand hygiene (HH) and PPE donning compliance in rooms of patients in contact precautions. Quasi-experimental, multicenter intervention, before-and-after study with concurrent controls. All patient rooms on contact precautions on 16 units (5 medical-surgical, 6 intensive care, 5 specialty care units) at 3 acute-care facilities (2 academic medical centers, 1 Veterans Affairs hospital). Observations of PPE donning and entry HH compliance by HCP were conducted during both study phases. Surveys of HCP perceptions of the PPE-free zone were distributed in both study phases. A PPE-free zone, where a low-risk area inside door thresholds of contact precautions rooms was demarcated by red tape on the floor. Inside this area, HCP were not required to wear PPE. We observed 3,970 room entries. HH compliance did not change between study phases among intervention units (relative risk [RR], 0.92; P = .29) and declined in control units (RR, 0.70; P = .005); however, the PPE-free zone did not significantly affect compliance (P = .07). The PPE-free zone effect on HH was significant only for rooms on enteric precautions (P = .008). PPE use was not significantly different before versus after the intervention (P = .15). HCP perceived the zone positively; 65% agreed that it facilitated communication and 66.8% agreed that it permitted checking on patients more frequently. HCP viewed the PPE-free zone favorably and it did not adversely affect PPE or HH compliance. Future infection prevention interventions should consider the complex sociotechnical system factors influencing behavior change.


Host chemokines bind to Staphylococcus aureus and stimulate protein A release.
There are few examples of host signals that are beneficial to bacteria during infection. Here we found that 31 out of 42 host immunoregulatory chemokines were able to induce release of the virulence factor protein A (SPA) from a strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Detailed study of chemokine CXCL9 revealed that SPA release occurred through a post-translational mechanism and was inversely proportional to bacterial density. CXCL9 bound specifically to the cell membrane of CA-MRSA, and the related SPA-releasing chemokine CXCL10 bound to both cell wall and cell membrane. Clinical samples from patients infected with S. aureus and samples from a mouse model of CA-MRSA skin abscess all contained extracellular SPA. Further, SPA-releasing chemokines were present in mouse skin lesions infected with CA-MRSA. Our data identify a potential new mode of immune evasion, in which the pathogen exploits a host defense factor to release a virulence factor; moreover, chemokine binding may serve a scavenging function in immune evasion by S. aureus.


Motivation of fitness center participants toward resistance training.
There is a need to better understand the behavior and sense of motivation of fitness center participants. The purpose of this study was to assess whether or not demographic characteristics and health self-determinism (intrinsic or extrinsic motivation) of fitness center participants were predictive of their levels of resistance training. A cross-sectional design was used; participants were recruited via the Internet to complete an online survey. There were 185 participants (age = 39.1 +/- 11.3 years) in the study. The majority of respondents reported having carried out levels of resistance training that met national health organization recommendations. Regression analysis of the data revealed that health self-determinism predicted quantity of resistance training reported (p = 0.014), whereas demographics did not. Being intrinsically motivated to health self-determinism predicted meeting national resistance training recommendations compared to participants extrinsically motivated (p = 0.007). For those who work with fitness center participants, our findings are useful by identifying participants as a predominantly intrinsically motivated group of people that performs adequate quantities of resistance training; the methodology employed in this study can be used to identify participants in need of increased levels of resistance training and heightened sense of motivation to do so.


Myeloid-related protein complex 8/14 increases in hypertensive patients with excessive renal damage .
Hypertension is a complex condition, and it is difficult to know whether inflammation is a cause or an effect. Information on the association between MRP-8/14 (myeloid-related protein) and hypertension is limited. In this study, we aimed to examine the relationship of MRP-8/14 with carotid intima-media thickness (CIMT) and albuminuria in hypertensive patients and to investigate whether early assay of MRP-8/14 levels could be helpful in assessment of renal damage and carotid atherosclerosis among hypertensive patients. 61 hypertensive patients and 40 age-, gender-, and body mass index-matched controls were included into the study. Blood samples including fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, albumin, urea creatinine, uric acid, sedimentation, C-reactive protein (CRP), and MRP-8/14 were collected. 24-hour urine albumin excretion and CIMT measurements were also obtained. All inflammatory variables including uric acid, CRP, sedimentation, MRP-8/14, and CIMT were statistically higher in patients with hypertension than in controls. MRP-8/14 was significantly higher in hypertensive patients with macroalbuminuria than in controls (339.3 (IQR (215.2 - 661.7)) ng/mL vs. 204.9 (IQR (140.1 - 339.3)) -ng/mL, p = 0.005, respectively). The levels of CIMT were the highest in macroalbuminuric hypertensive patients (controls vs. normoalbuminuria, microalbuminuria, macroalbuminuria groups, 0.57 (0.53 - 0.67) mm vs. 0.84 (0.76 - 0.89) mm, p = 0.000; 0.57 (0.53 - 0.67) mm vs. 0.87 (0.67 - 0.93) mm, p = 0.000; 0.57 (0.53 - 0.67) mm vs. 0.92 (0.85 - 0.97) mm, p = 0.000, respectively). Plasma MRP-8/14 levels were elevated in hypertensive patients with macroalbuminuria, however, it could not serve as an early marker to determine renal damage and carotid atherosclerosis in patients with hypertension. .


Veterans' distress related to participation in a study about detainee abuse.
Unintended consequences of participating in research studies are not well characterized, particularly in veterans who are frequent study participants. Our objective, then, was to assess the rate of and variables associated with distress resulting from veterans' participation in a study on a sensitive subject. Veterans Administration (VA) hospital outpatients were administered questionnaires with three increasingly severe scenarios of a U.S. soldier abusing a detainee. Distress--upset requiring clinical intervention--was assessed, as were sociodemographic characteristics, post-traumatic stress disorder (PTSD), depression, and locus of control (LOC). Three hundred fifty-one veterans participated. Forty-three (12%) became distressed. Modeling indicated distress was associated with minority status (odds ratio [OR] = 5.72, 95% confidence interval [CI] = 1.59, 20.58), PTSD (OR = 2.66, 95% CI = 1.12, 6.29), and external LOC (OR = 6.27, 95% CI = 2.82, 13.90). Distress related to study participation was high in this veteran sample. Higher rates in some subgroups suggested that some individuals may not be able to accurately anticipate risk for harm in sensitive studies.


Effect of biotin and niacin on lipid content of livers in the laying hen.
Single Comb White Leghorn layers maintained in cages were fed a corn-soy diet with a simplified vitamin premix for a 12-week experimental period to determine the effect on liver lipid accumulation. Lipid content was only 29.6% of the liver dry matter and, therefore, was in the normal range and less than that seen in hens with fatty liver syndrome. Adding niacin (44 mg./kg.) or biotin (110 mug./kg.) either alone or in combination failed to significantly alter liver weight or liver lipid content. Liver lipid content of hens fed another diet with a more complex vitamin premix also was not significantly different from that of hens fed the diet with the simplified vitamin premix. None of the diets significantly affected egg production, egg weight, feed consumption or body weight changes observed over the 12-week period.


Inherited DNA lesions determine G1 duration in the next cell cycle.
Replication stress is a major source of DNA damage and an important driver of cancer development. Replication intermediates that occur upon mild forms of replication stress frequently escape cell cycle checkpoints and can be transmitted through mitosis into the next cell cycle. The consequences of such inherited DNA lesions for cell fate and survival are poorly understood. By using time-lapse microscopy and quantitative image-based cytometry to simultaneously monitor inherited DNA lesions marked by the genome caretaker protein 53BP1 and cell cycle progression, we show that inheritance of 53BP1-marked lesions from the previous S-phase is associated with a prolonged G1 duration in the next cell cycle. These results suggest that cell-to-cell variation in S-phase commitment is determined, at least partially, by the amount of replication-born inherited DNA damage in individual cells. We further show that loss of the tumor suppressor protein p53 overrides replication stress-induced G1 prolongation and allows S-phase entry with excessive amounts of inherited DNA lesions. Thus, replication stress and p53 loss may synergize during cancer development by promoting cell cycle re-entry with unrepaired mutagenic DNA lesions originating from the previous cell cycle.


A dosimetric comparison between the supine and prone positions for three-field intact breast radiotherapy.
Supine tangential radiotherapy for the intact breast is a standard component of breast conservation management; a supraclavicular (SCV) field can be added for patients at high risk for nodal failure. Treatment in the prone position has demonstrated improvements in lung sparing, but has been limited to early-stage patients in whom radiation to only the breast was indicated. We sought to investigate the dosimetric feasibility of treating women in the prone position, using a 3-field monoisocentric technique. A total of 10 patients previously simulated supine and prone were selected for replanning. The heart, ipsilateral breast, contralateral breast, and axillary/SCV lymph node regions were contoured in accordance with Radiation Therapy Oncology Group guidelines. The 3-field monoisocentric plans were created for both the supine and prone scans. Target coverage, homogeneity, and organ at risk sparing were examined. Both plans achieved acceptable coverage of the breast. The mean percentage of the breast receiving at least 95% of the prescription dose (V95%) were similar in the prone and supine positions, 89.3% versus 90.7% (P = 0.29). Mean V95% of the level 3 axilla and SCV were 93.8% versus 97.0% prone versus supine (P = 0.16). The percentage of ipsilateral lung receiving >20 Gy was substantially reduced from 21.2% supine to 9.3% prone (P = 0.001). Three-field radiotherapy in the prone position appears to be dosimetrically equivalent to supine treatment with respect to target coverage, but the prone position decreases lung dose.


A prospective study of conventional transbronchial needle aspiration: performance and cost utility.
Conventional transbronchial needle aspiration (TBNA) is a cheap, minimally invasive tool for lung cancer staging and diagnosis. Endobronchial ultrasound-guided TBNA (EBUS-TBNA) is more sensitive but is more expensive and less widely available. We describe a prospective analysis of TBNA diagnostic, staging and cost utility in a centre in the UK. To illustrate the potential diagnostic, staging and cost utility of a low cost conventional TBNA service. A prospective analysis of 79 TBNA procedures over a 2-year period was performed looking at performance and cost utility in a 'mixed' cohort with variable pre-test probability of malignancy (year 1) followed by a high probability cohort (year 2). TBNA avoided mediastinoscopy in 25% of the cases overall (37% in high probability vs. 13% in the 'mixed' cohort, p = 0.03). The overall prevalence of malignancy was 84%, sensitivity 79%, negative predictive value 58% and accuracy 85%. Diagnostic utility varied with pre-test probability and nodal station. TBNA down-staged 8% of lung cancer patients to receive surgery and confirmed the pre-treatment stage (inoperability) in 74%. TBNA led to theoretical cost savings of GBP 560 per patient. TBNA can achieve a high diagnostic sensitivity for cancer in high probability patients and stage the majority appropriately, thereby avoiding unnecessary mediastinoscopies and reducing costs. It may also down-stage a minority to have surgery. TBNA is cheap, routinely available and learnable. As EBUS-TBNA will take time to develop due to its costs, all respiratory centres should perform TBNA at flexible bronchoscopy in suspected lung cancer with accessible mediastinal adenopathy.


[An modified culture method of primary human gingival epithelial cells].
To establish a stable primary culture method of human gingival epithelial cells, with a higher successful rate and shorter culture time. Nine patients who received "crown-lengthening surgery" with relatively healthy periodontal conditions were selected (n=9). Gingival samples were collected from the 9 donors during gingivectomy. Gingival epithelial cells were isolated and cultured by both an advanced enzyme digestion method and a tissue explant method. In the advanced enzyme digestion culture process, 2.5 g/L DispaseIIwas used to separate the epithelial tissue part from the connective tissue part, which lasted for one night. Then the epithelial tissues were digested by 0.025% trypsin without EDTA for 10 minutes, and centrifuged by keeping the digested epithelial tissues that remained. This advanced method not only decreased the concentration and digesting time of the two above-mentioned enzymes, but also simplified the centrifugel process. The tissue explant method was not changed too much compared with the original method. Growing processes of the primary cells cultured by the two methods were observed and recorded respectively, and indirect immunocytochemical staining was used to identify the type of cultured cells. At the same time, successful rates and cell culture time were also compared between the two methods. Human gingival epithelial cells with typical morphology could be cultured within a shorter period by the advanced enzyme digestion method with a successful rate of 88.9%, and proliferated rapidly as sheets. After 10-14 d cells could be passaged, gradually turned to be like fibroblasts when passaged to the third generation, and eventually went to apoptosis. The primary culture time was longer by using the tissue explant method, and approximately after 17-22 d cells could be passaged, although the successful rate was the same as the enzyme digestion method. Cytokeratin staining was both positive by indirect immunocytochemical staining of cells. Primary human gingival epithelial cells cultured by the advanced enzyme digestion method could grow faster and be passaged to the second generation successfully, which could supply a stable origin for cellular experiments.


A platform for nitric oxide delivery.
Nitric oxide (NO) is one of the structurally smallest pharmaceutical molecules, which shows great potential as an anti-restenosis, wound healing, anticancer, and antibacterial agent. To date, while most of the studies have focused mainly on demonstrating the versatility of the NO-releasing materials, little effort has been made on developing successful NO-delivery strategies for advancing NO-mediated therapy. Thus, the quest for a rationally designed NO-delivery system is becoming one of the important issues in the biomedical applications of NO. This feature article discusses the overall research trends in the NO-delivery, focusing mainly on the various particle-type and coating platforms. The objective of this article is not only to highlight the fundamental principle and challenges associated with NO-delivery, but also to provide insight for the further development of novel NO-delivery platforms for clinical applications in the near future.


Temporal trends and metric variation in the mandibles and dentition of Australopithecus afarensis.
The Pliocene hominin samples from Hadar and Laetoli are thought to represent one species, Australopithecus afarensis, that exhibits stasis throughout its temporal range and has high levels of skeletal sexual dimorphism. In this paper, we test the hypothesis of stasis in dental and mandibular dimensions using nonparametric rank correlation methods to detect temporal trends and randomization tests to evaluate their statistical significance. We then use two methods (CV resampling; Fligner-Killeen test) to compare overall levels of variation in the fossil sample to those of extant hominoid species. Together, these analyses allow us to gauge the effects of changes through time on variation in mandibles and teeth of A. afarensis.P(3)mesiodistal length, M(3)size, and canine shape change through time but do not appear unusually variable in the sample as a whole. These temporal trends possibly reflect differences between the Laetoli and Hadar site-samples. For mandibles, a pronounced trend towards greater corpus size occurs late in the temporal sequence and contributes to high levels of variation compared to African apes. These results show that significant directional changes do occur in the A. afarensis mandibles and teeth, and in these elements, at least, the species is not static. Temporal variation is clearly an important component of overall variation in the A. afarensis lineage, even though other factors, such as sexual dimorphism, may also play a part.


Osteochondroma with compression of the spinal cord. A report of two cases.
We report two cases of vertebral osteochondroma. In one patient a solitary cervical lesion presented as entrapment neuropathy of the ulnar nerve and in the other as a thoracic tumour associated with hereditary multiple exostoses producing paraplegia. We highlight the importance of an adequate preoperative evaluation in such patients.


[Longidase in the treatment of chronic prostatitis].
Twenty eight patients with documented chronic prostatitis (CP) received standard therapy (a control group) while a study group of 28 patients received standard therapy plus a 10 longidase injections in a dose of 3000 IU. Treatment results showed that longidase is highly effective in bacterial and abacterial CP. Longidase addition to standard therapeutic methods significantly reduced the disease symptoms and regression of inflammatory-proliferative alterations in the prostate. Thus, a domestic drug longidase is effective and safe in CP. It can be widely used in combined therapy of CP.


Association between polymorphisms in the vesicular monoamine transporter 1 gene (VMAT1/SLC18A1) on chromosome 8p and schizophrenia.
Linkage studies have suggested a susceptibility locus for schizophrenia (SZ) exists on chromosome 8p21-22. The vesicular monoamine transporter 1 gene (VMAT1), also known as SLC18A1, maps to this SZ susceptibility locus. Vesicular monoamine transporters are involved in the presynaptic vesicular packaging of monoamine neurotransmitters, which have been postulated to play a role in the etiology of SZ. Variations in the VMAT1 gene might affect transporter function and/or expression, and might be involved in the etiology of SZ. Genotypes of 62 patients with SZ and 188 control subjects were obtained for 4 missense single nucleotide polymorphisms (Thr4Pro, Thr98Ser, Thr136Ile, Val392Leu) and 2 noncoding single nucleotide polymorphisms (rs988713, rs2279709). All cases and controls were of European descent. The frequency of the minor allele of the Thr4Pro polymorphism was significantly increased in SZ patients when compared to controls (p = 0.0140; d.f. = 1; OR = 1.69; 95% CI = 1.11-2.57). Assuming a recessive mode of inheritance, the frequency of homozygote 4Pro carriers was significantly increased in the SZ patients when compared to controls (24 vs. 8%, respectively; p = 0.0006; d.f. = 1; OR = 3.74; 95% CI = 1.703-8.21). Haplotype analysis showed nominal significance for an individual risk haplotype (p = 0.013); however, after permutation correction, the global p value did not attain a statistically significant level (p = 0.07). Results suggest that variations in the VMAT1 gene may confer susceptibility to SZ in patients of European descent. Further studies are necessary to confirm this effect, and to elucidate the role of VMAT1 in central nervous system physiology and possible involvement in the genetic origins of SZ.


[Pneumoperitoneum solely diagnosed with CT scanning].
The authors report 3 cases of pneumoperitoneum due to visceral perforation and whose diagnosis was not performed on plain abdominal radiographs. In the 3 cases, pneumoperitoneum diagnosis and laparotomy decision were based on the results of an emergency abdominal CT Scan. Each time, the origin of the pneumoperitoneum was also clearly evidenced. When visceral perforation is suspected, we advice to perform CT Scan of the abdomen if pneumoperitoneum diagnosis has not been made by plain abdominal radiographs. CT Scan is an accurate exam for pneumoperitoneum diagnosis that permits undelayed surgical treatment.


Interactions between tricarboxylic acid cycle intermediates and phosphate uptake by proximal renal cells and renal brush border membranes.
Glucose and other hexoses as well as amino acids have been shown to inhibit the renal transport of phosphate (Pi). Although studies with renal brush border membrane vesicles showed that such an inhibitory effect on Pi transport is due to the dissipation of the Na electrochemical gradient, the mechanism(s) responsible for such an action in the intact cell is not clear. The present study examined the effects of tricarboxylic acid (TCA) cycle intermediates (succinate and fumarate) and acetate on the uptake of Pi and alpha-methylglucoside (AMG) at 37 degrees C by intact rabbit renal cells. These TCA cycle compounds significantly (p less than 0.05) inhibited the uptake of both Pi and AMG. In the presence of 5-10 mM succinate the ATP content of the renal cells increased by 40% (p less than 0.02). Inhibition of succinate-induced gluconeogenesis by 3-mercaptopicolinic acid did not modify the inhibition of Pi uptake. Studies with renal brush border membrane vesicles showed that succinate inhibited Pi uptake at 15 and 60 s but not at 1 s and only under conditions of Na gradient (outside greater than inside). Succinate did not inhibit Pi uptake during Na equilibrium conditions. The data demonstrate that the succinate-induced inhibition of the Pi uptake by intact proximal renal cells is not due to competition for metabolic energy, is not related to stimulation of gluconeogenesis nor due to allosteric interaction between Pi carrier and succinate transporter. The results support the notion that the inhibition of Pi uptake by succinate in the intact renal cell is due to dissipation of the Na chemical gradient.


Integrating evidence-based practice into RN-to-BSN clinical nursing education.
This study examines the effects of integrating evidence-based practice (EBP) into clinical practicum on EBP efficacy and barriers to research utilization among Korean RN-to-BSN students. A one-group pretest-posttest design was used. Eighty-one students were recruited from a school of nursing in Korea. Evidence-based practice clinical practicum was composed of two consecutive programs during one semester. Lectures, individual mentoring on EBP practicum, small group, and wrap-up conferences were provided. Outcomes of EBP efficacy and barriers to research utilization were analyzed using paired t tests for 74 final participants. Evidence-based practice efficacy scores increased significantly (p < 0.05), and the barriers to research utilization scores decreased significantly after the EBP clinical practicum. The results highlight the effectiveness of EBP education among RN-to-BSN students. These results may help health educators develop effective educational strategies to integrate EBP concepts into a clinical practicum.


RGS1 mediates renal interstitial fibrosis through activation of the inflammatory response.
Renal interstitial fibrosis (RIF) is considered as a common pathway for all patients with chronic kidney disease (CKD) to progress to end-stage kidney disease (ESRD). The basic pathological manifestation is the increase of matrix component in the tubular interstitium, while the injury of tubular epithelial cells in the renal interstitium and the excessive accumulation of matrix will eventually lead to tubular atrophy and obstruction, loss of effective renal units, and finally impaired renal filtration function. The relevant mechanism of RIF remains unclear. The present study will investigate the function and relevant mechanism of RGS1 in RIF. The RIF-related microarrays GSE22459 and GSE76882 were downloaded and analyzed. Renal parenchymal atrophic calyx tissues were collected from clinical RIF patients. Cellular inflammation, fibrosis and animal RIF models were constructed using Lipopolysaccharide (LPS), TGF-β1 and unilateral ureteral occlusion (UUO). HE and Masson staining were performed to detect morphological alterations of renal tissue samples. qRT-PCR, Western blot and ELISA were carried out to detect the expression of relevant genes/proteins. RGS1 is a gene co-differentially expressed by GSE22459 and GSE76882. RGS1 expression was elevated in renal tissues of RIF patients, cells and animal RIF models. Knockdown of RGS1 inhibited renal cell inflammatory response, fibrosis and renal fibrosis in RIF mice. Overexpression of RGS1 plays the opposite role. Knockdown of RGS1 inhibited the inflammatory response in the RIF cell and mouse model. Targeting RGS1 might be a potential therapeutic strategy for RIF treatment.


Androgen receptor inhibition suppresses anti-tumor neutrophil response against bone metastatic prostate cancer via regulation of TβRI expression.
Bone metastatic disease of prostate cancer (PCa) is incurable and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone neutrophils initially inhibit bone metastatic PCa growth yet metastatic PCa becomes resistant to neutrophil response. Further, neutrophils isolated from tumor-bone lost their ability to suppress tumor growth through unknown mechanisms. With this study, our goal was to define the impact of metastatic PCa on neutrophil function throughout tumor progression and to determine the potential of neutrophils as predictive biomarkers of metastatic disease. Using patient peripheral blood polymorphonuclear neutrophils (PMNs), we identified that PCa progression dictates PMN cell surface markers and gene expression, but not cytotoxicity against PCa. Importantly, we also identified a novel phenomenon in which second generation androgen deprivation therapy (ADT) suppresses PMN cytotoxicity via increased transforming growth factor beta receptor I (TβRI). High dose testosterone and genetic or pharmacologic TβRI inhibition rescued androgen receptor-mediated neutrophil suppression and restored neutrophil anti-tumor immune response. These studies highlight the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa.


Comparison of short-term and long-term protocols for stabilization and preservation of RNA and DNA of Leishmania, Trypanosoma, and Plasmodium.
Molecular tools continue to be important in the prevention and control of parasitic diseases. However, using these techniques directly in the field remains a major challenge. Therefore, the preservation of clinical samples collected from endemic field areas for later analysis remains an important preanalytical process. This study aimed at identifying a suitable protocol for stabilization and preservation of RNA and DNA in bioclinical specimens for Trypanosoma, Leishmania, and Plasmodium research. Both spiked and unspiked blood samples were preserved in 7 protocols (different media; storage temperatures). Samples were evaluated for possible degradation of DNA and RNA along the storage duration up to the 10th week. Nucleic acid targets were assessed as follows: (i) Trypanosoma and Plasmodium RNA analysis was done using real-time nucleic acid sequence-based amplification (RT-NASBA) for 18S rRNA and for stage-specific Pfs25 mRNA, respectively; (ii) Trypanosoma DNA assessment analysis was conducted by using a conventional PCR for 18S rDNA; (iii) Leishmania RNA analysis was performed with a quantitative NASBA for 18S rRNA and Leishmania DNA assessment with an RT-PCR for 18S rDNA. Findings suggested that a newly developed L3™ buffer proved to be reliable and suitable for both short- and long-term preservation of parasite nucleic acid material. This buffer is envisaged to be suitable for utilization in field situations where resources are limited.


Validating a conceptual model for an inter-professional approach to shared decision making: a mixed methods study.
Following increased interest in having inter-professional (IP) health care teams engage patients in decision making, we developed a conceptual model for an IP approach to shared decision making (SDM) in primary care. We assessed the validity of the model with stakeholders in Canada. In 15 individual interviews and 7 group interviews with 79 stakeholders, we asked them to: (1) propose changes to the IP-SDM model; (2) identify barriers and facilitators to the model's implementation in clinical practice; and (3) assess the model using a theory appraisal questionnaire. We performed a thematic analysis of the transcripts and a descriptive analysis of the questionnaires. Stakeholders suggested placing the patient at its centre; extending the concept of family to include significant others; clarifying outcomes; highlighting the concept of time; merging the micro, meso and macro levels in one figure; and recognizing the influence of the environment and emotions. The most common barriers identified were time constraints, insufficient resources and an imbalance of power among health professionals. The most common facilitators were education and training in inter-professionalism and SDM, motivation to achieve an IP approach to SDM, and mutual knowledge and understanding of disciplinary roles. Most stakeholders considered that the concepts and relationships between the concepts were clear and rated the model as logical, testable, having clear schematic representation, and being relevant to inter-professional collaboration, SDM and primary care. Stakeholders validated the new IP-SDM model for primary care settings and proposed few modifications. Future research should assess if the model helps implement SDM in IP clinical practice.


Is there a role for podiatric surgeons in public hospitals? An audit of surgery to the great toe joint in Victoria, 1999-2003.
This project aimed to describe and compare the frequencies of procedures performed by podiatric surgeons and orthopaedic surgeons for elective surgery to the great toe joint, an area of identified clinical need. The objective was to determine whether podiatric surgeons in the Australian context possess a surgical skill set which can be utilised in the public health sector. The Medicare Benefits Schedule (Medicare Australia) was reviewed to identify all codes relating to great toe joint surgery and frequency data were obtained for the period July 1999 to June 2003. A separate audit of the activity of Victorian podiatric surgeons was conducted. During the 4 years in Victoria, the number of procedures performed on this joint by 152 orthopaedic surgeons was 5882. Two podiatric surgeons in Victoria performed 1260 operations on this joint over this period (17.6% of great toe joint surgery on average each year in the private sector). Utilising orthopaedic workforce figures and on a per-surgeon basis, during this period the podiatric surgeons performed this type of surgery between 2 and 16 times more often than the orthopaedic surgeons, and consideration should be given to using these skills in the public sector to address the growing demand.


Surface plasmon resonance sensing properties of a 3D nanostructure consisting of aligned nanohole and nanocone arrays.
Molecular surface plasmon resonance (SPR) sensing is one of the most common applications of an array of periodic nanoholes in a metal film. However, metallic nanohole arrays (NHAs) with low-hole count have lower resolution and SPR sensing performance compared to NHAs with high-hole count. In this paper, we present a compact three-dimensional (3D) plasmonic nanostructure with extraordinary optical transmission properties benefiting from surface plasmon matching and enhanced localized surface plasmon coupling. The 3D nanostructure consisted of a gold film containing a NHA with an underlying cavity and a gold nanocone array (NCA) at the bottom of the cavity. Each nanocone was aligned with the nanohole above and the truncated apex of each nanocone was in close proximity (100 nm) to the gold film. The NHA-NCA structures outperformed conventional NHA structures in terms of bulk sensitivity and Figure of Merit (FOM). Furthermore, the NHA-NCA structure with 525 nm periodicity was capable of sensing streptavidin down to 2 nM exhibiting a 10-fold increase in streptavidin sensitivity compared to conventional NHA structures. The sensitivity and performance of the 3D nanostructure can be further improved by exploiting multiplexing methods in combination with stable light sources and detection systems.