Attitudes of students of a health sciences university towards the extension of smoke-free policies at the university campuses of Barcelona (Spain).
To assess attitudes towards the extension of outdoor smoke-free areas on university campuses. Cross-sectional study (n=384) conducted using a questionnaire administered to medical and nursing students in Barcelona in 2014. Information was obtained pertaining to support for indoor and outdoor smoking bans on university campuses, and the importance of acting as role models. Logistic regression analyses were performed to examine agreement. Most of the students agreed on the importance of health professionals and students as role models (74.9% and 64.1%, respectively) although there were statistically significant differences by smoking status and age. 90% of students reported exposure to smoke on campus. Students expressed strong support for indoor smoke-free policies (97.9%). However, only 39.3% of participants supported regulation of outdoor smoking for university campuses. Non-smokers (OR=12.315; 95% CI: 5.377-28.204) and students ≥22 years old (OR=3.001; 95% CI: 1.439-6.257) were the strongest supporters. The students supported indoor smoke-free policies for universities. However, support for extending smoke-free regulations to outdoor areas of university campuses was limited. It is necessary to educate students about tobacco control and emphasise their importance as role models before extending outdoor smoke-free legislation at university campuses.


Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF-induced thyrotropin release by the amphibian pituitary gland.
Corticotropin-releasing factor (CRF) is considered to be a main adrenocorticotropin-releasing factor in vertebrates. In non-mammalian species, CRF and related peptides cause the release of thyroid-stimulating hormone (TSH) from the anterior pituitary. The actions of CRF peptides are mediated by two G protein coupled receptors (CRF1 and CRF2) that have different ligand specificities. Using ligands that bind preferentially or selectively to the CRF2 we tested the hypothesis that TSH release by the amphibian pituitary gland is mediated by the CRF2. Injection of frog CRF, urocortin 1 or the CRF2-specific ligand urocortin 3 all produced significant, acute increases (by 2 h) in plasma thyroxine concentration in prometamorphic tadpoles. Chronic injections of CRF peptides accelerated tadpole metamorphosis, and the peptides with the highest affinity for the CRF2 (urocortin 1 and sauvagine) had the greatest potency. Ligands selective for the CRF2 (frog urocortin 3, mouse urocortins 2 and 3) all accelerated tadpole metamorphosis. We then tested frog urocortins 1 and 3, mouse urocortin 2 and sauvagine for their TSH-releasing activity using dispersed frog anterior pituitary cells in culture. All of the peptides tested markedly enhanced the release of TSH. Secretagogue-induced TSH release was completely blocked by the general CRF receptor antagonist astressin or the CRF2-specific antagonist antisauvagine-30. Conversely, the type 1 CRF receptor-specific antagonist antalarmin had no effect on TSH secretion. Our results support the hypothesis that CRF-induced TSH release by the amphibian pituitary gland is mediated by the CRF2.


Validation of self-reported diabetes in a representative sample of São Paulo city.
OBJECTIVE To validate the self-reported diabetes mellitus in adults and older adults living in the city of São Paulo, Brazil. METHODS We have used data of 569 subjects (284 adults and 285 older adults), participants of the population-based cross-sectional study Inquérito de Saúde do Município de São Paulo (Health Survey of São Paulo). Fasting glucose ≥ 7.0 mmol/L (126 mg/dL) and/or use of drugs (oral hypoglycemic and/or insulin) defined the diagnosis of diabetes mellitus. We have validated the self-reported diabetes mellitus by calculating the sensitivity, specificity, positive predictive values, and negative predictive values. We have used Poisson regression with robust variance to verify the factors associated with the sensitivity of the self-reported datum. For all analyses, we have considered the sample design of the study. RESULTS The sensitivity of self-reported diabetes mellitus was 63.8% (95%CI 49.2-76.3), specificity was 99.7% (95%CI 99.1-99.9), positive predictive value was 95.5% (95%CI 84.4-98.8), and negative predictive value was 96.9% (95%CI 94.9-98.2). The correct reporting of diabetes mellitus was more prevalent among older adults (PR = 2.0; 95%CI 1.2-3.5) than among adults. CONCLUSIONS The use of the datum of self-reported diabetes mellitus is valid, especially among older adults living in the city of São Paulo. The results highlight the need to track diabetes mellitus in asymptomatic subjects who have one or more risk factors for it, mainly in the adult population of this city.


Knockdown of HIF-1α and IL-8 induced apoptosis of hepatocellular carcinoma triggers apoptosis of vascular endothelial cells.
A local hypoxic microenvironment is one of the most important characteristics of solid tumors. Hypoxia inducible factor-1α (HIF-1α) and Interleukin-8 (IL-8) activate tumor survival from hypoxic-induced apoptosis in each pathway. This study aimed to evaluate whether knockdown of HIF-1α and IL-8 induced apoptosis of the hepatocellular carcinoma (HCC) and endothelial cell lines. HCC cell lines were infected with adenovirus-expressing shRNA for HIF-1α and IL-8 and maintained under hypoxic conditions (1% O2, 24 h). The expression levels of HIF-1α and both apoptotic and growth factors were examined by real-time quantitative PCR and western blot. We also investigated apoptosis by TUNEL assay (FACS and Immunofluorescence) and measured the concentration of cytochrome C. Inhibition of HIF-1α and IL-8 up-regulated the expression of apoptotic factors while downregulating anti-apoptotic factors simultaneously. Knockdown of HIF-1α and IL-8 increased the concentration of cytochrome C and enhanced DNA fragmentation in HCC cell lines. Moreover, culture supernatant collected from the knockdown of HIF-1α and IL-8 in HCC cell lines induced apoptosis in human umbilical vein endothelial cells under hypoxia, and the expression of variable apoptotic ligand increased from HCC cell lines, time-dependently. These data suggest that adenovirus-mediated knockdown of HIF-1α and IL-8 induced apoptosis in HCC cells and triggered apoptosis of vascular endothelial cells.


Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis.
Notch is the receptor in a signalling pathway that operates in a diverse spectrum of developmental processes. Its ligands (e.g. Serrate) are transmembrane proteins whose signalling competence is regulated by the endocytosis-promoting E3 ubiquitin ligases, Mindbomb1 and Neuralized. The ligands also inhibit Notch present in the same cell (cis-inhibition). Here, we identify two conserved motifs in the intracellular domain of Serrate that are required for efficient endocytosis. The first, a dileucine motif, is dispensable for trans-activation and cis-inhibition despite the endocytic defect, demonstrating that signalling can be separated from bulk endocytosis. The second, a novel motif, is necessary for interactions with Mindbomb1/Neuralized and is strictly required for Serrate to trans-activate and internalise efficiently but not for it to inhibit Notch signalling. Cis-inhibition is compromised when an ER retention signal is added to Serrate, or when the levels of Neuralized are increased, and together these data indicate that cis-inhibitory interactions occur at the cell surface. The balance of ubiquitinated/unubiquitinated ligand will thus affect the signalling capacity of the cell at several levels.


Optical-flow analysis toolbox for characterization of spatiotemporal dynamics in mesoscale optical imaging of brain activity.
Wide-field optical imaging techniques constitute powerful tools to investigate mesoscale neuronal activity. The sampled data constitutes a sequence of image frames in which one can investigate the flow of brain activity starting and terminating at source and sink locations respectively. Approaches to the analyses of information flow include qualitative assessment to identify sources and sinks of activity as well as their trajectories, and quantitative measurements based on computing the temporal variation of the intensity of pixels. Furthermore, in a few studies estimates of wave motion have been reported using optical-flow techniques from computer vision. However, a comprehensive toolbox for the quantitative analyses of mesoscale brain activity data is still lacking. We present a graphical-user-interface toolbox based in Matlab® for investigating the spatiotemporal dynamics of mesoscale brain activity using optical-flow analyses. The toolbox includes the implementation of three optical-flow methods namely Horn-Schunck, Combined Local-Global, and Temporospatial algorithms for estimating velocity vector fields of flow of mesoscale brain activity. From the velocity vector fields we determined the locations of sources and sinks as well as the trajectories and temporal velocities of flow of activity. Using simulated data as well as experimentally derived sensory-evoked voltage and calcium imaging data from mice, we compared the efficacy of the three optical-flow methods for determining spatiotemporal dynamics. Our results indicate that the combined local-global method we employed, yields the best results for estimating wave motion. The automated approach permits rapid and effective quantification of mesoscale brain dynamics and may facilitate the study of brain function in response to new experiences or pathology.


Cultivating the Therapeutic Alliance in a Telemental Health Setting.
Telemental health services have broadened during the last decade (Choi et al. 2019; Pierce et al. 2020). More recently, Severe Acute Respiratory Syndrome Coronavirus 2019 (COVID-19) restrictions have led to an escalation in clinical services through telemental health settings. The purpose of this phenomenological study was to consider perspectives of Marriage and Family Therapists (MFT)s who are working in telemental health settings prior to and/or as a result of COVID-19 restrictions and consider the role that telemental health has in building therapeutic connections with clients. Researchers presented an online survey that explored participants' perceptions of providing telemental health. Participants included 23 MFTs who were currently licensed or working under an MFT supervisor. Data analysis uncovered the following thematic responses: (a) doing telemental health is similar, but different, than in-person therapy, (b) adapting to telemental health is worthwhile, and (c) validating clients' voices and experiences is fundamental to building an alliance in telemental health therapy. Findings supported the importance of further training in telemental health, specifically related to cultural humility and alliance building within telemental health settings.


[Diminution of the rate of growth of HeLa cells caused by thioproline (Tp) and 2-aminothiazoline HCl (2-AT). Effect of L-proline].
Some aspects of the effect of thioproline and 2-amino-thiazoline-HCl on HeLa cell cultures are studied. Both drugs, at 1 mM concentrations, produce morphological changes that become stabilized after four days. The morphology changes depend on the microtubules, microfilaments, and de novo protein synthesis. Both drugs diminish the growth rate of HeLa cells, the effect being partially reverted by high concentrations (2 mM) of L-proline.


Infrared photodissociation spectra of mass selected homoleptic nickel carbonyl cluster cations in the gas phase.
Infrared spectra of mass-selected homoleptic nickel carbonyl cluster cations including dinuclear Ni2(CO)7(+) and Ni2(CO)8(+), trinuclear Ni3(CO)9(+) and tetranuclear Ni4(CO)11(+) are measured via infrared photodissociation spectroscopy in the carbonyl stretching frequency region. The structures are established by comparison of the experimental spectra with simulated spectra derived from density functional calculations. The Ni2(CO)7(+) cation is characterized to have an unbridged asymmetric (OC)4Ni-Ni(CO)3(+) structure with a Ni-Ni single bond. The Ni2(CO)8(+) cation has a Ni-Ni half-bonded D3d structure with both nickel centers exhibiting an 18-electron configuration. The trinuclear Ni3(CO)9(+) cluster cation is determined to have an open chain like (OC)4Ni-NiCO-Ni(CO)4 structure. The tetranuclear Ni4(CO)11(+) cluster cation is determined to have a tetrahedral structure with two-center and three-center bridge-bonded carbonyl units. These nickel carbonyl cluster cations all involve trigonal pyramid like Ni(CO)4 building blocks that satisfy the 18-electron configuration of the nickel centers.


Separate proteolipid protein/DM20 enhancers serve different lineages and stages of development.
The gene encoding DM20 emerged in cartilaginous fish, descending from a bilaterian ancestor of the M6 proteolipid gene family. Its proteolipid protein (PLP) isoform appeared in amphibians, contains an additional 35 amino acids, and, in the mammalian CNS, is the dominant myelin protein in which it confers an essential neuroprotective function. During development, the DM20 isoform is prominent in a number of tissues, and plp/DM20 transcripts are detected in multiple progenitor populations, including those that continue to express plp/DM20 as they differentiate into myelinating oligodendrocytes. The locus also encodes isoforms with extended leader sequences that accumulate in the cell bodies of several types of neurons. Here, to locate and characterize regulatory sequences controlling the complex plp/DM20 transcription program, putative regulatory sequences, suggested by interspecies conservation, were ligated individually to a minimally promoted eGFPlacZ reporter gene. These constructs were inserted in single copy at a common site adjacent to the hypoxanthine-guanine phosphoribosyltransferase locus in embryonic stem cells and their in vivo expression programs were compared in transgenic mice. Most expressed developmental and cell-specific subprograms accommodated within the known expression phenotype of the endogenous plp/DM20 locus, thus defining multiple components of the combinatorial mechanism controlling its normal temporal and cell-specific program. Along with previously characterized nervous system enhancers, those described here should help expose the content and configuration of elements that are operational in multiple glial and neuronal lineages. The transgenic lines derived here also provide effective markers for multiple stages of glial and neuronal lineage progression.


Acute aortic dissection associated with sleep apnea syndrome.
Sleep apnea syndrome (SAS) is an independent risk factor for hypertension which is a major risk factor for acute aortic dissection. The purposes of this study were to assess the prevalence of SAS in patients with acute aortic dissection, delineate the characteristics of patients who have acute aortic dissection with SAS. Of 95 consecutive patients with acute aortic dissection, 13 had episodes of sleep apnea and nocturnal hypoxemia. A portable sleep monitoring system was used to assess sleep status in the 13 patients. The SAS-positive group consisted of 12 patients (12.6%), 8 with type A dissection and 4 with type B dissection. Age was significantly lower in the SAS-positive group (47.2 ± 8.5 years) than in the SAS-negative group (64.9 ± 10.3 years)(p <0.001). The male:female ratio was significantly higher in the SAS-positive group than in the SAS-negative group (p <0.001). The body mass index was significantly greater in the SAS-positive group than in the SAS-negative group (p <0.001). All 12 patients in the SAS-positive group had hypertension. Patients who have acute aortic dissection with SAS are characterized by being tall, fat, and relatively young men with hypertension. Sleep apnea syndrome may be a risk factor for acute aortic dissection in middle-aged men.


Effects of methylprednisolone on sputum biochemical components in asthmatic bronchitis.
Nineteen patients with chronic mucus hypersecretion and reversible airway obstruction were studied during an acute exacerbation. One group of patients was treated with antibiotics and aminophylline, the other, additionally, with gradually decreasing doses of methylprednisolone, starting with 80 mg/day. The sputum specimens were collected on the day of admission and 2 weeks later. In whole sputum, we examined macromolecular components both transudated from serum and locally secreted: albumin, fucose, N-acetylneuraminic acid, total protein, IgA, IgM, IgG. At the end of the second week albumin (marker of serum transudate), and fucose (marker of mucus glycoproteins), were significantly lower in the group treated with corticosteroids. IgG and albumin behaved in the same way suggesting a marked IgG serum exudation. IgM was partially reduced by corticosteroids while IgA remained unchanged.


First-principles, structure-based transdermal transport model to evaluate lipid partition and diffusion coefficients of hydrophobic permeants solely from stratum corneum permeation experiments.
To account for the effect of branched, parallel transport pathways in the intercellular domain of the stratum corneum (SC) on the passive transdermal transport of hydrophobic permeants, we have developed, from first-principles, a new theoretical model-the Two-Tortuosity Model. This new model requires two tortuosity factors to account for: (1) the effective diffusion path length, and (2) the total volume of the branched, parallel transport pathways present in the SC intercellular domain, both of which may be evaluated from known values of the SC structure. After validating the Two-Tortuosity model with simulated SC diffusion experiments in FEMLAB (a finite element software package), the vehicle-bilayer partition coefficient, K(b), and the lipid bilayer diffusion coefficient, D(b), in untreated human SC were evaluated using this new model for two hydrophobic permeants, naphthol (K(b) = 225 +/- 42, D(b) = 1.7 x 10(-7) +/- 0.3 x 10(-7) cm(2)/s) and testosterone (K(b) = 92 +/- 29, D(b) = 1.9 x 10(-8) +/- 0.5 x 10(-8) cm(2)/s). The results presented in this paper demonstrate that this new method to evaluate K(b) and D(b) is comparable to, and simpler than, previous methods, in which SC permeation experiments were combined with octanol-water partition experiments, or with SC solute release experiments, to evaluate K(b) and D(b).


METLIN: A Technology Platform for Identifying Knowns and Unknowns.
METLIN originated as a database to characterize known metabolites and has since expanded into a technology platform for the identification of known and unknown metabolites and other chemical entities. Through this effort it has become a comprehensive resource containing over 1 million molecules including lipids, amino acids, carbohydrates, toxins, small peptides, and natural products, among other classes. METLIN's high-resolution tandem mass spectrometry (MS/MS) database, which plays a key role in the identification process, has data generated from both reference standards and their labeled stable isotope analogues, facilitated by METLIN-guided analysis of isotope-labeled microorganisms. The MS/MS data, coupled with the fragment similarity search function, expand the tool's capabilities into the identification of unknowns. Fragment similarity search is performed independent of the precursor mass, relying solely on the fragment ions to identify similar structures within the database. Stable isotope data also facilitate characterization by coupling the similarity search output with the isotopic m/ z shifts. Examples of both are demonstrated here with the characterization of four previously unknown metabolites. METLIN also now features in silico MS/MS data, which has been made possible through the creation of algorithms trained on METLIN's MS/MS data from both standards and their isotope analogues. With these informatic and experimental data features, METLIN is being designed to address the characterization of known and unknown molecules.


Metal and selenium concentrations in blood and feathers of petrels of the genus Procellaria.
Concentrations of copper (Cu), zinc (Zn), cadmium (Cd), lead (Pb), mercury (Hg), and selenium (Se) were determined in blood and feathers of spectacled (Procellaria conspicillata) and white-chinned (Procellaria aequinoctialis) petrels, species that are phylogenetically related, but with distinct ecological niches. In winter, they feed on similar foods, indicated by an overlapping range of whole-blood stable isotopes values (δ(15) N; δ(13) C). No relation was found between blood metal concentration and stable isotope values. In spectacled petrels, metal concentrations appeared lower in blood (Cu = 0.79-20.77 µg/g; Zn = 10.95-28.02 µg/g; Cd = 1.73-10.11 µg/g; Pb = 5.02-26.03 µg/g; Hg = 0.84-9.86 µg/g) than in feathers (Cu = 1.05-21.57 µg/g; Zn = 45.30-81.49 µg/g; Cd = 3.76-10.44 µg/g; Pb = 16.53-59.00 µg/g; Hg = 4.24-24.03 µg/g). In white-chinned petrels, metal concentrations also appeared lower in blood (Cu = 0.62-10.4 µg/g; Zn = 10.73-24.69 µg/g; Cd = 2.00-6.31 µg/g; Pb = 5.72-24.03 µg/g) than in feathers (Cu = 2.68-23.92 µg/g; Zn = 48.96-93.54 µg/g; Cd = 5.72-24.03 µg/g; Pb = 18.62-55.51 µg/g), except for Hg (blood = 0.20-15.82 µg/g; feathers = 0.19-8.91 µg/g). Selenium (0.24-14.18 µg/g) and Hg (0.22-1.44 µg/g) concentrations showed a positive correlation in growing feathers of spectacled petrels. Blood and feather Hg levels were higher in spectacled petrels while feathers Cu and Zn concentrations were greater in white-chinned petrels. Juvenile white-chinned petrels exhibited greater blood Hg concentrations than adults. In the south Atlantic Ocean, discards from commercial fishing operations consumed by spectacled petrels year-round and by white-chinned petrels during the wintering period have elevated Hg concentrations. Because Hg toxicity is associated with behavioral and reproductive changes in birds, it could potentially have impacts on breeding of these seabirds, as both species are listed as threatened by extinction.


Steroid 5alpha-reductase 1 promotes 5alpha-androstane-3alpha,17beta-diol synthesis in immature mouse testes by two pathways.
5alpha-Androstane-3alpha,17beta-diol (androstanediol) is the predominant androgen in immature mouse testes, and studies were designed to investigate its pathway of synthesis, the steroid 5alpha-reductase isoenzyme involved in its formation, and whether testicular androstanediol is formed in embryonic mouse testes at the time of male phenotypic development. In 24-26-day-old immature testes, androstanediol is formed by two pathways; the predominant one involves testosterone --> dihydrotestosterone --> androstanediol, and a second utilizes the pathway progesterone --> 5alpha-dihydroprogesterone --> 5alpha-pregnane-3alpha-ol-20-one --> 5alpha-pregnane-3alpha,17alpha-diol-20-one --> androsterone --> androstanediol. Formation of androstanediol was normal in testes from mice deficient in steroid 5alpha-reductase 2 but absent in testes from mice deficient in steroid 5alpha-reductase 1, indicating that isoenzyme 2 is not expressed in day 24-26 testes. The fact that androstenedione and testosterone were the only androgens identified after incubation of day 16 and 17 embryonic testes with [3H]progesterone implies that androstanediol formation in the testis plays no role in male phenotypic differentiation in the mouse.


Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis.
Scleroderma is a systemic autoimmune disease characterized mainly by skin manifestations and involvement of various visceral organs, especially the lungs. Lung involvement is the leading cause of mortality in patients with scleroderma. There are data to suggest that cyclophosphamide (CYC) and mycophenolate mofetil (MMF) are effective in the management of scleroderma interstitial lung disease (SSc-ILD) but no head to head comparative data are available to date. For the last 3 years, patients with SSc-ILD have been treated at our centre by protocol-based administration of intravenous CYC and MMF. Results of lung function tests (spirometry) were recorded at baseline, 3 months and 6 months in every patient. The clinical records of patients with systemic sclerosis and significant ILD, who were not previously exposed to any immunosuppressant and were treated with MMF OR CYC, were reviewed. The efficacy of treatment was assessed by the change in forced vital capacity on spirometry. Of the total 57 patients included in the analysis, 34 were treated with MMF and 23 were treated with CYC. Mean duration of illness was 4.19 ± 2.82 years in the MMF and 6.04 ± 5.96 years in the CYC group. After 6 months of therapy, FVC increased by 10.84 ± 13.81 % in the CYC group and by 6.07 ± 11.92 % in the MMF group. This improvement from baseline was statistically significant in both groups (P < 0.01). The improvement was comparable with no statistically significant differences between groups (P = 0.373). There were no major adverse events reported in either arm. Both MMF and CYC were equally effective in stabilizing lung function in patients with scleroderma and ILD.


The role of Arabidopsis MYB2 in miR399f-mediated phosphate-starvation response.
In plants, microRNA399 (miR399) is a major regulator of phosphate (Pi) homeostasis by way of post-transcriptional mechanisms including transcript cleavage and transcriptional repression. Although miRNA genomic organization, biogenesis, and mode of action in plants are known, the regulatory mechanisms affecting miRNAs are poorly understood. We have shown that AtMYB2 functions as a transcriptional activator for miR399f expression in the context of phosphate homeostasis. AtMYB2 directly binds to a MYB-binding site in the promoter of the miR399f precursor and regulates miR399f expression. In addition, AtMYB2 transcripts are induced under Pi deficiency. The overexpression of AtMYB2 affects root system architecture (RSA), indicated by suppression of primary root growth and enhanced development of root hairs. AtMYB2 and miR399f are expressed and localized in the same tissues under Pi limitation. This study establishes that AtMYB2 regulates Pi-starvation responses (PSR) by activating of miR399f transcript, suggesting that an analysis of this miRNA promoter could reveal the existence and extent of crosstalk with other signaling mechanisms.


Development and Validation of a Nomograph Model for Post-Operative Central Nervous System Infection after Craniocerebral Surgery.
A nomograph model of predicting the risk of post-operative central nervous system infection (PCNSI) after craniocerebral surgery was established and validated. The clinical medical records of patients after cranial surgery in Renmin Hospital of Wuhan University from January 2020 to September 2022 were collected, of whom 998 patients admitted to Shouyi Hospital District were used as the training set and 866 patients admitted to Guanggu Hospital District were used as the validation set. Lasso regression was applied to screen the independent variables in the training set, and the model was externally validated in the validation set. A total of 1864 patients after craniocerebral surgery were included in this study, of whom 219 (11.75%) had PCNSI. Multivariate logistic regression analysis showed that age > 70 years, a previous history of diabetes, emergency operation, an operation time ≥ 4 h, insertion of a lumbar cistern drainage tube ≥ 72 h, insertion of an intracranial drainage tube ≥ 72 h, intraoperative blood loss ≥ 400 mL, complicated with shock, postoperative albumin ≤ 30 g/L, and an ICU length of stay ≥ 3 days were independent risk factors for PCNSI. The area under the curve (AUC) of the training set was 0.816 (95% confidence interval (95%CI), 0.773-0.859, and the AUC of the validation set was 0.760 (95%CI, 0.715-0.805). The calibration curves of the training set and the validation set showed p-values of 0.439 and 0.561, respectively, with the Hosmer-Lemeshow test. The analysis of the clinical decision curve showed that the nomograph model had high clinical application value. The nomograph model constructed in this study to predict the risk of PCNSI after craniocerebral surgery has a good predictive ability.


Osteogenesis imperfecta. Review of the literature with presentation of 29 cases.
Twelve families with 29 patients showing various patterns of osteogenesis imperfecta are described, along with the genetic, pathological, and clinical features. No abnormal blochemical features were found. It has been shown that the best treatment is prophylactic (such as intramedullary nailingy or supportive. There was no remarkable improvement from any form of medical treatment. These data are compared to those of other authors.


Brief Report: "I Didn't Really Have a Primary Care Provider Until I Got PrEP": Patients' Perspectives on HIV Preexposure Prophylaxis as a Gateway to Health Care.
HIV prevention is the primary goal of preexposure prophylaxis (PrEP); however, ancillary benefits may exist, including PrEP as an entry point to primary care. To explore PrEP users' perspectives on how PrEP use relates to broader engagement in health care. In-depth qualitative interviews. We recruited PrEP users aged 18 years or older from a social media group for people interested in PrEP information and a Boston community health center specializing in health care for sexual and gender minorities. Inductive content analysis to identify emergent themes. All 25 participants were men who have sex with men, whose mean age was 34 years, and 84% were White. Three major themes emerged: (1) accessing PrEP was a strong motivator for initial and continued engagement in health care, which for some evolved over time into accessing comprehensive primary care; (2) provider awareness and attitudes about PrEP influenced participants' ongoing engagement in health care; and (3) PrEP engendered a positive sense of control over users' personal health, giving them agency in reducing their risk of HIV and engaging in other aspects of their health. Quarterly PrEP visits helped participants establish and maintain a relationship with a primary care provider, access non-HIV-related care services, and feel empowered to keep themselves healthy. The benefits of PrEP extend beyond HIV prevention to broader engagement in health care, including new relationships with primary care providers and use of other preventive health care services. To maximize those benefits, efforts are needed to ensure that providers are aware, nonjudgmental, and supportive of PrEP use.


Biological studies with continuous-wave radiofrequency (28 MHz) radiation.
Effects of high-frequency (28 MHz) continuous-wave radiation have been studied in the rat and monkey. No histopathological (rat-125 mW cm-2 for 28 days) or hematological (monkey-25 mW cm-2 for 24 days) changes could be attributed to the radiation. In the monkey (125 mW cm-2 for 11 days) there was an increase in urinary calcium concentration which was most likely due to restricted movement. In the rat (220 mW cm-2 for 13 days) there was reduced uptake of iodine by the thyroid, lower levels of plasma thyroid-stimulating hormone, and reduced ratio of protein bound to nonprotein bound iodine. Food consumption was also decreased. The changes are likely to have arisen as a compensatory response to an induced heat load. A nonthermal effect of continuous-wave high-frequency radiation has not been shown in this study. The effects were likely to be associated with either physiological compensation for induced heating or restriction of movement.


The impact of mammography quality improvement legislation in Michigan: implications for the National Mammography Quality Standards Act.
This study examined the impact of state legislation on mammography quality and access in Michigan. The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery.


Comparison of Marginal Fit of Metal Copings in Two Different States with and without Using Ring Liners: An In Vitro Study.
To compare the marginal fit of Ni-Cr copings made by casting in two different states (dry and wet) with either cellulose ring liners or no ring liners. An in vitro study was conducted on 40 patterns which were invested, and a burnout casting procedure was used, using a Ni-Cr alloy to obtain the cast copings. The cast copings were divested, cleaned, and run through a finishing procedure. The copings were seated on the stainless steel die and microscopically evaluated for marginal discrepancies at two predetermined reference points using an optical microscope (Rieichert, Austria). Statistical analysis was done using Pearson's correlation coefficient and Chi-square test, keeping 95% confidence intervals and having a p value of less than 0.05 statistically significant. Our results identified marginal discrepancies in all the Ni-Cr cast copings, which significantly differed from each other. The copings obtained from casting with a cellulose ring liner in a wet state showed a significantly higher value followed by casting using a cellulose ring liner in a dry state. The mean marginal discrepancy values were within the clinically acceptable range for all the Ni-Cr cast copings included in two groups. Our study concludes that the copings cast with a cellulose ring liner in dry states had the least amount of vertical marginal discrepancies as compared to those that were cast with a ring liner in two different forms or those cast without a ring liner, suggesting that the use of cellulose ring liner in a dry state is favorable for all casting procedures. Measuring gaps or discrepancies at margins is the commonly used method to determine the fit of Ni-Cr copings. In order to minimize marginal inaccuracies, various authors have suggested different methods to improve the marginal adaptation of cast restorations. There are compensation methods like setting expansion, hygroscopic expansion, and thermal expansion of the investment, which are used to assess metal shrinkage during cooling.


Biophysical and ion channel functional characterization of the Torpedo californica nicotinic acetylcholine receptor in varying detergent-lipid environments.
The nicotinic acetylcholine receptor (nAChR) of Torpedo electric rays has been extensively characterized over the last three decades. However, high-resolution structural studies have been hampered by the lack of mechanistic molecular models that describe how detergents influence membrane protein stability and function. Furthermore, elucidation of the dynamic detergent-lipid-protein interactions of solubilized membrane proteins is a largely unexplored research field. This study examines the effects of nine detergents on: (1) nAChR-lipid composition (gas chromatography with flame ionization; GC-FID and/or mass selective detectors; GC-MSD), (2) stability and aggregation state (analytical size exclusion chromatography; A-SEC and electron microscopy; EM) and (3) ion channel function (planar lipid bilayers). Detergent solubilization of nAChR-enriched membranes did not result in significant native lipid depletion or destabilization. Upon purification, native lipid depletion occurred in all detergents, with lipid-analogue detergents CHAPS {(3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate}, FC-12 (n-dodecylphosphocholine) and sodium cholate (3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic acid) maintaining stability and supporting ion channel function, and non-lipid-analogue detergents Cymal-6 (6-cyclohexyl-1-hexyl-beta-D-maltoside), DDM (n-dodecyl-beta-D-maltopyranoside), LDAO (lauryldimethylamine-N-oxide) and OG (n-octyl-beta-d-glucopyranoside) decreasing stability and significantly reducing or completely suppressing ion channel function. Anapoe-C(12)E(9 )(polyoxyethylene-[9]-dodecyl ether) and BigCHAP (N,N'-bis-[3-d-gluconamidopropyl] cholamide) retained residual amounts of native lipid, maintaining moderate stability and ion channel function compared to lipid-analogue detergents. Therefore, the nAChR can be stable and functional in lipid-analogue detergents or in detergents that retain moderate amounts of residual native lipids, but not in non-lipid-analogue detergents.


Low energy induced homolytic fragmentation of flavonol 3-O-glycosides by negative electrospray ionization tandem mass spectrometry.
Negative ESI-QIT-MS of several subtypes of flavonoid O-glycosides is known to produce deprotonated molecular ions which undergo homolytic fragmentation at the glycosidic bond upon collision-induced dissociation (CID). However, these subtypes have never been simultaneously compared under unified MS conditions. The (-)-ESI-MS(n) fragmentations of 69 flavonoid O-glycosides, involving eight subtypes, were analyzed using a quadrupole ion-trap mass spectrometer with collision energies varying from 18-44%. Factors influencing the homolytic glycosidic bond fragmentation, such as collision energy, hydroxylation of aglycone, and glycosylation pattern, were comprehensively studied. Under the unified CID-QIT-MS(2) conditions, the precursor deprotonated molecular ions [M-H](-) for 3-O-glycosyl, 3,7-di-O-glycosyl and 3,6,7-tri-O-glycosyl flavonols experienced homolytic fragmentation at the glycosidic bond and generated the radical aglycone ion [Y0-H](-•). This gas-phase CID fragmentation behavior was not observed for the other subtypes. A general trend was found that hydroxyl substitution at C-6, glycosylation at C-6/C-7, and acetylation of the saccharide moiety remarkably suppressed this fragmentation. In addition, flavonol 3-O-diglycosides (disaccharides) possessing a 1 → 2 glycosidic bond generated more abundant [Y0-H](-•) product ions than those with a 1 → 3 or 1 → 6 bond. The terminal sugar triggered the homolytic fragmentation in the order Rha > Xyl > Glc. Moreover, new counterexamples were found for previously reported fragmentation rules. The low-energy CID homolytic fragmentation was diagnostic for structural identification of flavonol 3-O-glycosides. We have summarized key factors affecting this fragmentation. The results could be useful for rapid characterization of flavonoid O-glycosides in complicated herbal extracts.


Clinical management. Remains of the day.
The Healthcare Commission has found 45 per cent of theatre time allocated for day surgery is going to waste. Not having dedicated facilities is no excuse not to increase day surgery. Process change is more important, with political leadership from the top. Trusts need an 'opt-out' culture in day surgery, where all surgical patients are considered eligible unless proven otherwise.


[Endothelial cells in tumors of the rectum and large intestine].
In 40 controls and 102 patients with tumours of the rectum and large intestine the number of circulating anuclear cell residues of endothelial cells was investigated. The number of these endothelia in the blood of patients was significantly higher (p < 0.001) than in healthy subjects. After successful surgery of the tumour and subsequent chemotherapy the number of endothelia in venous blood reached normal levels with in 1-2 months. Conversely in patients where despite surgery secondaries were detected in other organs, the number of endothelia remained elevated.


The importance of polyreactive antibodies in protection against pneumococcal infection.
Antibodies are a key element of the immune response. They can bind their molecular targets with exquisite sensitivity and specificity, providing protection against a multitude of pathogens. They have long been understood to be markers of a successful response to vaccination, and are now widely manufactured as highly specific and robust immunotherapeutic agents. Less well understood are the polyreactive antibodies, found in serum, which are able to bind more than one target molecule. Here, we highlight new research into these naturally occurring polyreactive antibodies, which demonstrates their importance for protection against Streptococcus pneumoniae, a common cause of airway infection.


Caudal regression syndrome and sirenomelia in only one twin in two diabetic pregnancies.
Many authors consider sirenomelia to be an extreme form of caudal regression syndrome (CRS), while others argue that they are two distinct entities. Maternal diabetes mellitus is considered to be an important predisposing factor for both CRS and sirenomelia. Two rare cases of diabetic, dizygotic twin pregnancies, each with one normal and one affected fetus are presented. In case 1 the affected fetus had CRS. In case 2 the affected fetus had sirenomelia. The present cases suggest that the pathogenesis of CRS and sirenomelia is more complex than previously thought, that maternal diabetes is not the only underlying pathogenetic mechanism and that genetic or epigenetic factors probably contribute to the formation of these conditions.


Building the biomedical data science workforce.
This article describes efforts at the National Institutes of Health (NIH) from 2013 to 2016 to train a national workforce in biomedical data science. We provide an analysis of the Big Data to Knowledge (BD2K) training program strengths and weaknesses with an eye toward future directions aimed at any funder and potential funding recipient worldwide. The focus is on extramurally funded programs that have a national or international impact rather than the training of NIH staff, which was addressed by the NIH's internal Data Science Workforce Development Center. From its inception, the major goal of BD2K was to narrow the gap between needed and existing biomedical data science skills. As biomedical research increasingly relies on computational, mathematical, and statistical thinking, supporting the training and education of the workforce of tomorrow requires new emphases on analytical skills. From 2013 to 2016, BD2K jump-started training in this area for all levels, from graduate students to senior researchers.


Accurate tissue area measurements with considerably reduced radiation dose achieved by patient-specific CT scan parameters.
A low-dose technique was compared with a standard diagnostic technique for measuring areas of adipose and muscle tissue and CT numbers for muscles in a body composition application. The low-dose technique was intended to keep the expected deviation in the measured area of adipose and muscle tissue to <1% of the total tissue area. The largest diameter of the patient determined the parameters for the low-dose technique. 17 patients - chosen to cover a wide range of diameters (31-47 cm) for both abdomen and thighs - were examined using both techniques. Tissue areas were compared, as were CT numbers for muscle tissue. Image noise was quantified by standard deviation measurements. The area deviation was <1%, except in the smallest subjects, in whom it was <2%. The integral radiation dose of the low-dose technique was reduced to 2-3% for diameters of 31-35 cm and to 7.5-50% for diameters of 36-47 cm as compared with the integral dose by the standard diagnostic technique. The CT numbers of muscle tissue remained unchanged with reduced radiation dose. Image noise was on average 20.9 HU (Hounsfield units) for subjects with diameters of 31-35 cm and 11.2 HU for subjects with diameters in the range of 36-47 cm. In conclusion, for body composition studies with CT, scan protocols can be adjusted so that the integral dose is lowered to 2-60% of the standard diagnostic technique at our centre without adversely altering area measurements of adipose and muscle tissue and without altering CT numbers of muscle tissue.


Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice.
Parkinson's disease is characterized by loss of nigral dopaminergic neurons and presence of Lewy bodies, whose major component is alpha-synuclein. In the present study, we generated transgenic mice termed Syn130m that express truncated human alpha-synuclein (amino acid residue number: 1-130) in dopaminergic neurons. Notably, dopaminergic neurons were selectively diminished in the substantia nigra pars compacta of Syn130m, while transgenic mice that expressed comparable amount of full-length human alpha-synuclein did not develop such pathology. Therefore, the truncation of human alpha-synuclein seems to be primarily responsible for the loss of nigral dopaminergic neurons. The nigral pathology resulted in impairment of axon terminals in the striatum and concomitant decrease in striatal dopamine content. Behaviorally, spontaneous locomotor activities of Syn130m were reduced, but the abnormality was ameliorated by treatment with L-DOPA. The loss of nigral dopaminergic neurons was not progressive and seemed to occur during embryogenesis along with the onset of expression of the transgene. Our results indicate that truncated human alpha-synuclein is deleterious to the development and/or survival of nigral dopaminergic neurons.


Killing, letting die and moral perception: a reply to Grant Gillett.
A number of philosophers in recent times have employed arguments to show that there is no morally relevant difference between killing a patient and allowing that patient to die in those circumstances where the outcome is virtually identical and where death is preventable, at least for a significant time. From his perspective as both a philosopher and a clinician, Grant Gillett has rejected such general and abstract arguments in the light of the intuitions and moral perceptions available to clinicians and those who care for the terminally ill. I argue that his strategy fails, is massively question-begging, and that his appeal to the notion of 'moral particularism', far from being an alternative to cogent philosophical argument, actually supports the very position he has attempted to discredit.


Fulminant presentation of oral mucosal leishmaniasis as severe stomatitis and periodontitis.
This case report shows an atypical presentation of mucosal leishmaniasis infantum in the oral cavity resulting in severe stomatitis and periodontitis. The patient was immunocompromised because of rheumatoid arthritis for which he used prednisone and methotrexate. He was treated with intravenous liposomal amphotericin B and recovered within four weeks.


Intramucosal ganglion cells are common in diverticular disease.
Ganglion cells were thought not to occur within the mucosa of the normal colon and found only in the setting of inflammatory bowel disease and neuronal intestinal dysplasia. The aim of this study was to firmly establish the incidence of intramucosal ganglion cells in diverticular disease, normal mucosa and in a spectrum of gastrointestinal diseases. We retrospectively reviewed 50 resection specimens from cases of symptomatic diverticular disease and biopsies and/or resection specimens for several neoplastic and non-neoplastic gastrointestinal diseases (50 normal and 120 cases for a variety of gastrointestinal diseases). Normal cases were constituted by biopsies with no clinical history of large bowel disease and no pathology detected microscopically. All 50 cases of diverticular disease contained intramucosal ganglion cells, located within the muscularis mucosae (49/50 cases) as well as within the lamina propria in nine cases. Intramucosal ganglion cells occurred throughout the colorectum within the muscularis mucosae or lamina propria in normal mucosa in 11 cases and in a further 26 colorectal specimens with Crohn's disease (11/20), ulcerative colitis (11/20), adenocarcinoma (1/20), tubular adenoma (2/20), and mucosal prolapse (1/20). None of the 20 hyperplastic polyps contained intramucosal ganglion cells. We have firmly established the existence of the intramucosal ganglion cells in normal and diseased colorectum, especially in the mucosa of cases of diverticular disease (100% of cases), Crohn's disease and ulcerative colitis. These three conditions are linked by motility abnormalities which may underlie the reason for the presence of intramucosal ganglion cells.


Level of consciousness in dying patients. The role of palliative sedation: a longitudinal prospective study.
Patients suffering from a terminal illness often are confronted with severe symptoms during the last phase of their lives. Palliative sedation, although one of the options of last resort, remains a much debated and controversial issue and is often referred to as a form of slow euthanasia or euthanasia in disguise. A prospective longitudinal and descriptive design was used. Each patient admitted in one of the 8 participating units was included if they met the inclusion criteria and gave written informed consent. 266 patients were included. The incidence of palliative sedation was 7;5%. For the group of sedated patients results show that 90% entered the palliative care unit being fully conscious. Two patients were comatose upon arrival. 90% of the patients remained fully conscious up to the day palliative sedation was started. When looking at the effect of palliative sedation on the level of consciousness the analysis strongly suggest that the palliative sedation - as expected- has an impact on the GCS score. Irrespective of the dichotomization of the score the probability of having a lower GCS increases substantially once sedation is initiated. Additionally, results show that once palliative sedation is administered, the level of consciousness gradually goes down up until the day of death. Palliative sedation is nor slow euthanasia nor an ambivalent practice. It is an intentional medical treatment which is administered in a proportional way when refractory suffering occurs. It occurs in extraordinary situations and at the very end of the dying process.


An NS5A single optimized method to determine genotype, subtype and resistance profiles of Hepatitis C strains.
The objective was to develop a method of HCV genome sequencing that allowed simultaneous genotyping and NS5A inhibitor resistance profiling. In order to validate the use of a unique RT-PCR for genotypes 1-5, 142 plasma samples from patients infected with HCV were analysed. The NS4B-NS5A partial region was successfully amplified and sequenced in all samples. In parallel, partial NS3 sequences were analyzed obtained for genotyping. Phylogenetic analysis showed concordance of genotypes and subtypes with a bootstrap >95% for each type cluster. NS5A resistance mutations were analyzed using the Geno2pheno [hcv] v0.92 tool and compared to the list of known Resistant Associated Substitutions recently published. In conclusion, this tool allows determination of HCV genotypes, subtypes and identification of NS5A resistance mutations. This single method can be used to detect pre-existing resistance mutations in NS5A before treatment and to check the emergence of resistant viruses while undergoing treatment in major HCV genotypes (G1-5) in the EU and the US.


Prepartum fatty acid supplementation in sheep I. Eicosapentaenoic and docosahexaenoic acid supplementation do not modify ewe and lamb metabolic status and performance through weaning.
Fatty acids are involved in the regulation of many physiological pathways, including those involved in gene expression and energy metabolism. Through effects on these pathways, fatty acids may have lifelong impacts on offspring development and metabolism via maternal supplementation. Therefore, our objective was to investigate the impact of supplementing a source of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during late gestation on productive and metabolic responses of ewes and their offspring. Eighty-four gestating ewes (28 pens) were blocked and randomly assigned to a diet with 0.39% added fat during the last 50 d of gestation (d -0). The fat sources were Ca salts of a palmitic fatty acid distillate (PFAD) or EPA + DHA. After lambing (d 1), all ewes and lambs were placed on the same pasture. The ewes were weighed and BCS was measured on d -50, -20, 30, and 60 (weaning) of the experiment. Blood samples were taken from the ewes on d -50, -20, 1 (lambing), 30, and 60. Milk yield and composition were measured at 30 d postpartum. Lambs were weighed and bled at d 1, 30, and 60, and ADG was calculated. All plasma samples were analyzed for glucose and NEFA. Ghrelin, prostaglandin E metabolites (PGEM), and the prostaglandin D2 metabolite 11β-PGF2α were measured in d -20 ewe samples. Insulin and adropin were measured in lamb samples at d 60. There was no difference on ewe BW (P = 0.48) or BCS (P = 0.55), or plasma concentrations of glucose (P = 0.57), NEFA (P = 0.44), ghrelin (P = 0.36), PGEM (P = 0.32), and 11β-PGF2α (P = 0.86) between ewes supplemented with PFAD or EPA + DHA. Neither milk yield nor its composition was different (P > 0.10) among treatments. Lambs born from ewes supplemented with PFAD or EPA + DHA did not have different BW (P = 0.22), ADG (P = 0.21) or plasma NEFA (P = 0.52), glucose (P = 0.50), insulin (P = 0.59), and adropin (P = 0.72) concentrations. These results suggest that supplementation of EPA and DHA during late gestation did not affect ewe metabolic profile or milk production. Lamb performance and metabolism through weaning were not affected by maternal supplementation with an enriched source of EPA and DHA.


Effect of tumor necrosis factor alpha on electrically induced calcium transients elicited in C2C12 skeletal myotubes.
Diseases involving chronic inflammation can lead to prolonged exposure of skeletal muscle to inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), which may contribute to the skeletal muscle weakness seen in these conditions. In this study we examined the effect of a prolonged exposure to TNFalpha on intracellular Ca(2+) transients elicited in skeletal C(2)C(12) myotubes. A 48-h exposure to TNFalpha (10 ng/mL) significantly reduced the peaks, time to peak, and rate of Ca(2+) decay of electrically induced Ca(2+) transients elicited in C(2)C(12) skeletal myotubes. TNFalpha exposure had no significant effect on the resting Ca(2+) levels. The results of this study indicate that prolonged exposure to TNFalpha decreases sarcoplasmic reticulum Ca(2+) release in cultured skeletal muscle cells. This altered Ca(2+) release could contribute to the muscle weakness found in conditions involving chronic inflammation.


Bis[benzidinium(1-)] pentamolybdate.
The title compound, [(C12H13N2)2[Mo5O16]]n, was synthesized under hydrothermal conditions. The structure contains a two-dimensional layer, constructed from [(Mo4O14)n]4n- chains linked through MoO6 octahedra, which lie across twofold axes. The [(Mo4O14)n]4n- chain consists of [Mo4O14]4- clusters connected to one another by sharing their MoO5 square-pyramidal and MoO6 octahedral vertices in an anti disposition. The layers are linked by the cation, to which they are connected via N-H...O hydrogen bonds.


Systematic evaluation of the toxicity and biodistribution of virus mimicking mucus-penetrating DLPC-NPs as oral drug delivery system.
Development of nanoparticle (NP) to simultaneously overcome the diffusion and absorption barrier has drawn much attention. Our group recently demonstrated that the virus mimicking dilauroylphosphatidylcholine functionalized NP (DLPC-NP) could rapidly penetrate across mucus layer and subsequently enter epithelia effectively, and exhibited high potential for oral drug delivery. However, the safety of the NP has provoked some scientific concerns, which debates from their properties that circuiting the protections of mucus and exhibiting strong interaction with cell membrane. To be further developed for oral drug delivery, the possible toxicity of DLPC-NPs was systematically evaluated in current study. For in vitro studies, the exposure of NPs to Caco-2 cells had no effect on cell viability and membrane integrity. Then the oxidative stress, cytokine production and genotoxicity assay indicated that the NPs did not induce any cell responses. The hemolysis test also demonstrated the good hemocompatibility of NPs. For in vivo studies, the biodistribution results showed that a large proportion of DLPC-NPs were detected in liver (0.51 O.D%/g), and followed by kidney (0.39 O.D%/g). Then the hematology test, blood biochemical assay and pathological assay were performed after a long oral administration periods of 28days. All the results indicated that the NPs could not induce any toxic response or histopathological lesions. Thus, based on these results, it can be concluded that the zwitterion-functionalized NPs might be a biocompatible potential candidate for oral drug delivery. More importantly, we aimed to emphasis the safety of the nanocarriers and also provide a reference for toxicity studies.


Enalapril improves impairment of SERCA-derived relaxation and enhancement of tyrosine nitration in diabetic rat aorta.
We investigated the involvement of angiotensin II and vascular smooth muscle sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) function in the impaired NO-induced relaxation seen in established streptozotocin-induced diabetes. Plasma angiotensin II levels, which were elevated in untreated diabetic rats (vs age-matched controls), were improved by treatment with the angiotensin-converting enzyme inhibitor enalapril. Systolic blood pressure was significantly decreased in chronic enalapril-treated diabetics (vs the other two groups). Intact aortae from diabetic rats and chronic angiotensin II-infused control rats, but not those from diabetic rats treated with enalapril, showed impaired endothelium-dependent relaxations to acetylcholine (vs controls). The relaxation induced by Angeli's Salt (a NO donor) was significantly impaired in endothelium-denuded aortae from diabetic rats (vs controls) but it was normalised by enalapril treatment. After preincubation with the irreversible SERCA inhibitor, thapsigargin, the relaxation induced by Angeli's Salt was significantly impaired in endothelium-denuded aortae from the controls, but not from the diabetics, and there was no significant difference between the thapsigargin-treated groups. Nitrotyrosine, an indirect marker of peroxynitrite, was markedly increased in aortic smooth muscle from diabetic rats, while chronic enalapril administration reduced this increase. These results suggest that in streptozotocin-induced diabetic rats, excessive angiotensin II production may lead to the generation of peroxynitrite and that this may in turn trigger a dysfunction of vascular smooth muscle SERCA. Enalapril improved the diabetes-related impairments.


[Late results after extensive resection of the small intestine].
In eight patients (two women and six men) aged from 31 to 80 years, extensive resection of the small intestine had been performed before many years. The most frequent causes of the operation were thrombosis and embolism of the superior mesenteric artery (three cases each). In all patients the small intestine was resected, at least partially, and in two patients also hemicolectomy with resection of Bauhin valve was performed. The most frequent complaint reported by the patients is periodical diarrhoea which becomes more intense particularly after fat consumption. Laboratory investigations and absorption tests were carried out in the patients at least one year after the operation. In all patients impaired absorption and hypoalbuminaemia were found. No significant correlation was found between the extent and time after the resection and the degree of intensity of the observed abnormalities.


Rapid administration of Kcentra® during cardiopulmonary arrest.
We present a case of cardiopulmonary arrest secondary to rivaroxaban related oropharyngeal hemorrhage, which required rapid intravenous (IV) push administration of 4-factor prothrombin complex concentrate (4F-PCC). Manufacturers recommend administering 4F-PCC IV at a rate of 0.12 mL/kg/min (approximately 3 units/kg/min) up to a maximum rate of 8.4 mL/min (approximately 210 units/min) [1]. The concern with rapid administration is increased potential for thromboembolic complications. There have been small studies assessing infusion rates greater than the manufacturer's recommendation with few reported thromboembolic events [2-5]. Our patient was an 81-year-old female presenting to the emergency department (ED) with sudden onset oropharyngeal hemorrhage. The patient had a pertinent history of oral and esophageal cancer and was prescribed rivaroxaban 20 mg once daily for treatment of deep vein thrombosis. Within moments of the patient arriving, she produced a large volume of blood from her nose and mouth. The source of the bleeding could not be determined, and as suctioning was attempted to clear her airway, the patient became unresponsive and pulseless. Advanced Cardiac Life Support (ACLS) procedures were initiated and 1000 mg of tranexamic acid were administered. Once the patient's active medication list was discovered, 2000 units of 4F-PCC was given as an IV push over roughly 20 s. Bleeding was controlled enough to secure the patient's airway within 5 min after 4F-PCC administration and subsequently return of spontaneous circulation was achieved. Unfortunately, the patient suffered a poor neurologic outcome and the family withdrew care after discussion with the treatment team and the patient's oncologist. This case report demonstrates rapid administration of 4F-PCC may be an effective intervention to treat immediately life threatening rivaroxaban related bleeding.


Candida colonisation within a silicone tissue expander.
The fungal contamination of tissue expanders is rarely reported. There are, however, occasional reports of fungi in association with inflatable mammary implants. We describe the colonisation of a tissue expander with Candida albicans, resulting in the fluid becoming a turbid brown colour. The possible modes of inoculation and survival of the microorganism within the expander shell were investigated by means of biochemical and microbiological analyses of the fluid. The colonisation of silicone implants by opportunistic fungi is probably more common than has been reported, and precautions that can be taken to avoid this complication are emphasised.


Intrinsic roles in the crosshair - strategic analysis of multi-site role implementation with an adapted matrix map approach.
The implementation of competency-based intrinsic roles in undergraduate medical education remains a challenge. Faculties in transition need to be provided with generalizable curricular data in order to facilitate orientation on curricular roles' representation and to decide on steps of curriculum development. Explicit and implicit representation of objectives and multi-site agreement can be viewed as status indicators for the adoption of roles. Our aim was to develop a pragmatic cross-locational approach to capture roles' developmental status in an overview and prioritize strategic recommendations. Based on the mapping data from six German medical faculties, the relationship between explicit and implicit curricular representation of role' objectives (weighting) and extent of programs' consent (agreement) was calculated. Data was visualized in a role-specific Matrix Map to analyse roles' implicit-explicit relation and risk-value potential. The matrix was combined with Roger's stages of innovation diffusion for differentiated interpretation of the developmental role status. Entangling multi-site agreement and curricular weighting, the 4-Field-Matrix allows to assess objectives based on their current localization in a quadrant: "Disregard" (lower left) and "Progress" quadrant (upper left) reveal the diffusion period; "Potential" (lower right) and "Emphasis" quadrant (upper right) indicate the adoption period. The role patterns differ in curricular representation, progression and clarity: (1) Scholar: explicit/implicit - scattered across the matrix; most explicit objectives in "Progress". (2) Health Advocate: explicit - primarily in "Emphasis"; only role in which the explicit representation significantly exceeds the implicit. (3) Collaborator: explicit - mainly "Potential"; implicit - "Progress" or "Emphasis". (4) Professional: explicit - primarily "Potential" but also "Emphasis"; implicit - "Progress" and "Emphasis"; appears better adopted but scattered in weighting; high hidden curricula. (5) Manager: explicit and implicit - exclusively in "Potential", without signs of development. Role patterns correspond to evidences from literature. Exemplified with roles, quadrant-specific strategies and measures are suggested. Framework reviewers may gain information for discussion of critical content. The Matrix Map enables to catch intuitively the status of intrinsic roles' profiles regarding role pattern, implicit-explicit relation and programs agreement. Thus, interpretation and informed discussions are fostered. Further target-oriented analyses and strategic developments can be conducted to enhance transparency and resource-efficiency.


Comparison of four phenotypic methods for detection of metallo-β-lactamase-producing Gram-negative bacteria in rural teaching hospital.
Metallo-β-lactamase (MBL)-producing bacteria lead to resistance to carbapenem an antibiotic that used as the last resort for treatment of multidrug-resistant bacteria, extended spectrum beta-lactamases, and AmpC β-lactamase-producing Gram-negative bacteria (GNB). The emergence of MBL-producing GNB is challenge to microbiology laboratories because there are no standardized guidelines available to detect them. The aim of this study was to compare four phenotypic methods to detect MBL production in GNB and to determine antibiotic sensitivity of MBL-producing isolates. A total of 107 clinical isolates of GNB were tested for MBL production. Imipenem (IPM)-resistant GNB were taken as positive for MBL screening. MBL detection was done using ethylene diamine tetra acetic acid (EDTA) as MBL inhibitor. Four phenotypic methods were evaluated: (1) Combined disk synergy test (CDST) with 0.5M EDTA (CDST-0.5 M EDTA), (2) CDST with 0.1 M EDTA (CDST-0.1 M EDTA), (3) double-disk synergy test (DDST) with 0.5M EDTA (DDST-0.5 M EDTA), and (4) DDST with 0.1 M EDTA (DDST-0.1 M EDTA). Out of 107 GNB, 30 were resistant to IPM considered as screening positive. Out of 30, 21 (70%) isolates were MBL positive by CDST-0.1 M EDTA, 19 (63.33%) by CDST-0.5M EDTA, 17 (56.67%) by DDST-0.1 M EDTA, and 16 (53.33%) by DDST-0.5M EDTA. All MBL-producing Gram-negative Bacilli were resistant to ampicillin/sulbactam. Polymyxin B was found to be the most sensitive drug. CDST-0.1 M EDTA is the most sensitive method MBL detection. The detection of MBL-producing GNB is very important to control spread of the resistance.


[Medical students and psychiatry. A survey of students' opinion].
In the last years research on the didactics of Psychiatry and opinions of medical students on Psychiatry has gained great interest. The authors think that this research could be useful for the improvement of didactics, for better understanding the meanings of professional choice, the identity of psychiatrist and their relationship with colleagues in other medical field. The goal of this research work was a preliminary survey of Genoese University Medical Student's opinions about psychiatry didactics, and choice of specialization. A questionnaire was submitted to all the students who passed Clinical Psychiatry examination in the period from November 1987 to December 1988. The students were divided in two randomized groups: the first group of students (224) was submitted to the questionnaire immediately after Clinical Psychiatry examination; while to the second group of students (66) the questionnaire was mailed. The aim of the questions was to assess the student's opinions on psychiatry, psychoanalysis, psychotherapy, the career they wanted to take up, and the difficulties of studying psychiatry: 69% of the students of the first group and 42% of the students of the second group answered the questionnaire. Female students answered that they preferred psychiatric specialization more than their male colleagues did, but the difference has no statistical importance. In most cases, the students who answered that they have taken into account psychiatry as a choice of specialisation, are more interested in medical specialties (primary care, etc.) than in surgical specialties. Most of the medical students declare some emotional troubles (anxiety, sleeplessness, problem in social relations).(ABSTRACT TRUNCATED AT 250 WORDS)


Estradiol-Treated Female Mice as Surrogate Hosts for Neisseria gonorrhoeae Genital Tract Infections.
Historically, animal modeling of gonorrhea has been hampered by the exclusive adaptation of Neisseria gonorrhoeae to humans. Genital tract infection can be established in female mice that are treated with 17β-estradiol, however, and many features of experimental murine infection mimic human infection. Here we review the colonization kinetics and host response to experimental murine gonococcal infection, including mouse strain differences and evidence that IL-17 responses, toll-like receptor 4, and T regulatory cells play a role in infection. We also discuss the strengths and limitations of the mouse system and the potential of transgenic mice to circumvent host restrictions. Additionally, we review studies with genetically defined mutants that demonstrated a role for sialyltransferase and the MtrC-MtrD-MtrE active efflux pump in evading innate defenses in vivo, but not for factors hypothesized to protect against the phagocytic respiratory burst and H(2)O(2)-producing lactobacilli. Studies using estradiol-treated mice have also revealed the existence of non-host-restricted iron sources in the female genital tract and the influence of hormonal factors on colonization kinetics and selection for opacity (Opa) protein expression. Recent work by others with estradiol-treated mice that are transgenic for human carcinoembryonic adhesion molecules (CEACAMs) supports a role for Opa proteins in enhancing cellular attachment and thus reduced shedding of N. gonorrhoeae. Finally we discuss the use of the mouse model in product testing and a recently developed gonorrhea chlamydia coinfection model.


Conscious and unconscious uses of memory in multiple sclerosis.
Conscious and unconscious uses of memory and priming were studied in 30 patients with multiple sclerosis (MS) and 15 normal control (NC) subjects. MS patients were classified into two subgroups according to their cognitive status; 15 of them were cognitively deteriorated (the MS-D group) and 15 cognitively preserved (the MS-P group). A process dissociation procedure [J. Mem. Lang. 30 (1991) 513] was used to separate conscious and unconscious memory performance in a word stem completion task. The results showed that the MS-D group had deficient conscious memory performance, but had intact unconscious memory as well as priming. The MS-P group showed normal conscious and unconscious uses of memory and priming. Thus, in MS-related cognitive decline, conscious memory seems to be vulnerable, whereas unconscious memory remains intact. The results provide neuropsychological support for the distinction between conscious and unconscious memory processes. Moreover, the results show the importance of studying cognitively homogenous MS groups as opposed to heterogenous ones, in order to find the underlying mechanisms of memory deficits in MS. Interestingly, the neural systems needed for the unconscious use of memory do not seem to deteriorate even in MS patients with deficient overall cognitive capacity. This finding encourages the development of future rehabilitation programs, suggesting that unconscious remembering might help MS patients with deficient conscious memory to cope with their daily activities.


Evaluation of Improved Glycogen Synthase Kinase-3α Inhibitors in Models of Acute Myeloid Leukemia.
The challenge for glycogen synthase kinase-3 (GSK-3) inhibitor design lies in achieving high selectivity for one isoform over the other. The therapy of certain diseases, such as acute myeloid leukemia (AML), may require α-isoform specific targeting. The scorpion shaped GSK-3 inhibitors developed by our group achieved the highest GSK-3α selectivity reported so far but suffered from insufficient aqueous solubility. This work presents the solubility-driven optimization of our isoform-selective inhibitors using a scorpion shaped lead. Among 15 novel compounds, compound 27 showed high activity against GSK-3α/β with the highest GSK-3α selectivity reported to date. Compound 27 was profiled for bioavailability and toxicity in a zebrafish embryo phenotype assay. Selective GSK-3α targeting in AML cell lines was achieved with compound 27, resulting in a strong differentiation phenotype and colony formation impairment, confirming the potential of GSK-3α inhibition in AML therapy.


Lumbar laminotomy and replantation for the treatment of lumbar spinal epidural lipomatosis: A case report.
Lumbar spinal epidural lipomatosis (SEL) is a rare condition characterized by excessive overgrowth of extradural fat within the lumbar spinal canal. Surgical decompression is commonly performed to treat symptomatic SELs. Fenestration or laminectomy with epidural fat debulking was a routine surgical procedure according to the literature, that may be causing postoperative lumbar instability. In the present study, we presented a brief report of lumbar SEL and introduced another surgical approach. A 55-year-old man complained of severe low back pain and right leg radicular pain for a year, accompanied by neurogenic intermittent claudication. He received a variety of conservative treatments, including non-steroidal anti-inflammatory drugs, acupuncture, and physical therapy. However, his pain did not diminish. Finally, a posterior epidural mass in the dorsal spine extending from the L3 to L5 level, which caused dural sac compression was found on lumbar magnetic resonance imaging. This mass was homogeneously hyperintense in both T1W1 and T2W1 images, suggestive of epidural fat accumulation. Lumbar SEL. The patient underwent lumbar laminectomy, epidural fat debulking, and spinous process-vertebral plate in situ replantations. The patient presented with complete recovery of radiculopathy and low back pain after surgery. Postoperative magnetic resonance imaging showed that the increased adipose tissue disappeared, and the dural sac compression was relieved. A computed tomography scan revealed the lumbar lamina in situ. He was able to walk normally and remained relatively asymptomatic for 12 months after the operation at the last follow-up visit. Lumbar laminotomy and replantation provide an ideal option to treat lumbar SEL because it can achieve sufficient and effective decompression, simultaneously reconstruct the anatomy of the spinal canal, and reduce the risk of iatrogenic lumbar instability.


Is the Preoperative Administration of Amiodarone or Metoprolol More Effective in Reducing Atrial Fibrillation: After Coronary Bypass Surgery?
This study examined the influence of preoperative administration of amiodarone and metoprolol in preventing postoperative atrial fibrillation (AF) after coronary artery bypass grafting (CABG) surgery.The study comprised 251 patients who underwent CABG surgery at our hospital between January 2012 and May 2014. The patients were randomly divided into 2 groups: amiodarone therapy group (n = 122 patients) and metoprolol therapy group (n = 129 patients).In the amiodarone group, the patients received amiodarone tablet orally 1 week before coronary bypass surgery and during the postoperative period. In the metoprolol group, the patients received metoprolol tablet orally 1 week before surgery and during the postoperative period. The AF development rate was retrospectively evaluated between the first 3 days and 4 weeks after surgery.AF developed in 14 patients in the amiodarone group and 16 patients in the metoprolol group 4 weeks after the operation (P = 0.612).No significant difference was observed between the groups in terms of intensive care unit and hospital stay. Furthermore, hospital charges were similar in both groups (P = 0.741).The results of the logistic regression analysis showed age, left ventricular ejection fraction, left atrial diameter, and aortic cross-clamping time to be predictors for postoperative AF.This study demonstrates that amiodarone and metoprolol have similar effects in prevention of AF after cardiac surgery. However, larger-scale studies need to be conducted to substantiate these findings.


Reduced catabolic protein expression in Clostridium butyricum DSM 10702 correlate with reduced 1,3-propanediol synthesis at high glycerol loading.
Higher initial glycerol loadings (620 mM) have a negative effect on growth and 1,3-propanediol (1,3-PDO) synthesis in Clostridium butyricum DSM 10702 relative to lower initial glycerol concentrations (170 mM). To help understand metabolic shifts associated with elevated glycerol, protein expression levels were quantified by LC/MS/MS analyses. Thirty one (31) proteins involved in conversion of glycerol to 1,3-PDO and other by-products were analyzed by multiple reaction monitoring (MRM). The analyses revealed that high glycerol concentrations reduced cell growth. The expression levels of most proteins in glycerol catabolism pathways were down-regulated, consistent with the slower growth rates observed. However, at high initial glycerol concentrations, some of the proteins involved in the butyrate synthesis pathways such as a putative ethanol dehydrogenase (CBY_3753) and a 3-hydroxybutyryl-CoA dehydrogenase (CBY_3045) were up-regulated in both exponential and stationary growth phases. Expression levels of proteins (CBY_0500, CBY_0501 and CBY_0502) involved in the reductive pathway of glycerol to 1,3-PDO were consistent with glycerol consumption and product concentrations observed during fermentation at both glycerol concentrations, and the molar yields of 1,3-PDO were similar in both cultures. This is the first report that correlates expression levels of glycerol catabolism enzymes with synthesis of 1,3-PDO in C. butyricum. The results revealed that significant differences in the expression of a small subset of proteins were observed between exponential and stationary growth phases at both low and high glycerol concentrations.


Tourniquet use in out-of-hospital emergency care: a systematic review.
Uncontrolled bleeding from serious injuries continues to be one of the main causes of preventable deaths outside hospitals. Tourniquets could be useful for quickly stemming blood flow and prevent exsanguination, although evidence supporting their use and effectiveness in civilian accidents is limited. To analyze the effectiveness of tourniquets for stopping bleeding in out-of-hospital emergencies and to explore factors associated with effectiveness. We undertook a systematic review of the literature in Spanish and English. Search protocols to identify studies that evaluated the use of various devices and their effectiveness in stemming arterial blood flow. We included studies published between 2011 and 2016 in which tourniquets were used to prevent massive blood loss. We included 17 articles. Tourniquets were effective in stopping massive bleeding in all studies. Pain, the most frequently described adverse effect, was observed in 420 patients (35.7%). Delayed application of a tourniquet was associated with more negative outcomes. Tourniquets are effective for stopping massive blood loss. There are few complications, most of which are attributable to the critical state of patients rather than to application of the tourniquet. A tourniquet should be applied in major trauma cases in civilian settings if massive, life-threatening bleeding cannot be stopped with direct pressure.


Comparative trophic ecology of two sympatric guitarfishes Pseudobatos (Chondrichthyes, Rhinobatidae) from Southeast Brazil, southwestern Atlantic.
The present study compares the trophic ecology of two guitarfishes (Pseudobatos percellens and Pseudobatos horkelii) from the continental shelf of the São Paulo State, Brazil, caught by the bottom pair trawls between 2007 and 2009. These two sympatric species are under different threat categories, "Vulnerable" and "Critically Endangered," respectively, according to Brazilian agencies. Thus, any study considering trophic ecology parameters is pivotal in understanding the trophic ecology role of such species in the ecosystem. The authors analysed 500 stomachs of P. percellens and 108 of P. horkelii, quantifying with dietary indexes: numerical (%N), gravimetric (%W), frequency of occurrence (%FO) and the prey-specific index of relative importance (%PSIRI). For P. percellens and P. horkelii, 26 and 14 different prey items were found, respectively. Crustacea and Teleostei were the most important prey items for both species, indicating a specialist feeding behaviour due to their low niche amplitude. The results provide evidence related to ontogenetic dietary shift in P. percellens and individual-level diet specialization in both species. These two benthic-demersal elasmobranchs are important mesopredators (3,7 for P. percellens, and 3,5 for P. horkelii) in the study area, with high trophic-level values.


Evaluation of a New Thermal Fog Machine for Control of Adult Aedes albopictus in a Large Enclosed Space.
Testing of the PSO BASDKA-AC1200 multifunction ultrafine particle atomization machine, a thermal fog machine, with Aqualuer 20-20(®) (permethrin 20.6%, piperonyl butoxide 20.6%) was conducted against Aedes albopictus. The machine was set at a 40 sec maximum burst interval dispersing 36 ml of chemical with an average droplet volume of 50%. Female adult Ae. albopictus were placed into cylindrical paper cages and adhered to poles at 5, 8, 10, 15, and 25 m from the center point of the machine. Control cages consisted of 1 cage placed at 5, 10, and 25 m. Control and treatment groups were left in the experiment area for 15 min. Initial knockdown after 15 min and 24 h mortality were documented. At 15 min post-treatment, Ae. albopictus displayed less than 50% knockdown. After 24 h, all treatment cages displayed greater than 90% mortality. Further bottle bioassays were conducted to determine the lowest chemical dose possible to achieve a lethal dose of 90%. A 1% dilution (10 ml Aqualuer 20-20 to 1,000 ml of polyether) of Aqualuer showed high mortality in the laboratory. However, after running 3 repetitions of a 1% dilution, there was no significant difference between the mortality of the mosquitoes at any of the distances 24 h post-treatment. This study indicates that the test machine would be an applicable and suitable machine for control of Ae. albopictus in enclosed spaces.


Growth and Consequences.
In response to the growth of JOSPT, Editor-in-Chief J. Haxby Abbott introduces 3 new Associate Editors to the JOSPT Editorial Board, and announces the promotion of 1 outstanding Editorial Board member to an Editor role. J Orthop Sports Phys Ther 2016;46(8):610-612. doi:10.2519/jospt.2016.0111.


An ultrastructural study on the endocrine pancreas of Caiman latirostris, with special reference to pancreatic motilin cells.
Pancreatic endocrine cells of Caiman latirostris were investigated by electron microscopy using conventional and immunocytochemical methods. Ultrastructurally, four types of endocrine cells were classified according to the morphology of their secretory granules. Three types of endocrine cells were identified as either glucagon, insulin or somatostatin cells by the presence of such characteristic granules well established in mammals. The remaining endocrine cell type could not be classified by its ultrastructural features alone. Immunocytochemical observations confirmed the ultrastructural classification of glucagon, insulin and somatostatin cells. In addition, endocrine cells immunoreactive for either pancreatic polypeptide (PP) or motilin were identified. Morphometric analysis of PP- and motilin-immunoreactive granules demonstrated that they were the most polymorphous and smallest granules among the pancreatic endocrine cell granules. Although both PP and motilin granules closely resemble each other, motilin granules were smaller in size and more spherical in shape than PP granules.


Psychosocial influences in onset and progression of late life disability.
Disability in older age has been related to several psychosocial characteristics, including social networks, social engagement, and depression. However, the exact role of these characteristics in the disablement process remains uncertain. Data come from a population-based study of black and white adults aged ≥65 years (N = 5,306), with up to 9 yearly data on the primary outcome measure, activities of daily living (ADL) disability. We use a two-part regression model to simultaneously test the association between each psychosocial characteristic and both onset and progression of ADL disability, while controlling for demographic variables, education, and mode of interview in the first model and health status variables in the second model. Social networks were negatively associated with onset of ADL disability but not associated with progression. The association became non-significant after adjustment for health status. Social engagement was negatively associated with both onset and progression of disability, even after adjustment for health status. Depression was significantly associated with onset of disability after adjustment for health status but not with progression of disability. The results suggest a differential role for psychosocial characteristics in the disablement process, with generally stronger associations for transitions to onset of ADL disability than progression of ADL disability.


Abdominal manifestations of pulmonary embolism.
The cardiopulmonary manifestations of acute pulmonary embolism are well known. However, abdominal manifestations of thromboembolic disease are less well appreciated. We recently encountered three patients with pulmonary emboli who also had complications of abdominal signs and symptoms. Two patients initially had abdominal complaints that obscured the diagnosis. In the other patient, symptoms and signs developed that were indistinguishable from an acute surgical condition of the abdomen after the diagnosis of massive pulmonary embolism was established. Abdominal manifestations alone may be the presenting features of pulmonary embolism or may complicate the clinical course.


Role of NuMA in vertebrate cells: review of an intriguing multifunctional protein.
The 236 kDa large coiled-coil protein NuMA plays diverse important roles in vertebrate cells. It is an important component of the nuclear matrix in interphase cells, and is possibly involved in nuclear re-assembly after mitosis. In dividing cells, upon phosphorylation, NuMA disperses into the cytoplasm, associates with cytoplasmic dynein/dynactin to form a complex, and translocates along microtubules to the spindle poles where it organizes and tethers microtubules to spindle poles. It is thought that the stable complex of NuMA/dynein/dynactin is needed to focus microtubule minus ends to the spindle poles. But, it has also been reported that NuMA can organize microtubules in the absence of centrosomes and dynein. Another hypothesis suggests that once localized to the spindle poles, spindle-associated NuMA's exchange with cytoplasmic soluble pools and its stable crosslinking with the microtubule fibers are independent of dynein/dyactin. NuMA's function in spindle microtubule organization is regulated by RanGTP and Pins-related protein LGN. NuMA becomes dephosphorylated, loses its association with dynein/dynactin, and releases from spindle poles after anaphase onset to allow spindle disassembly and reformation of interphase daughter nuclei. The cell-cycle-dependent phosphorylation of NuMA is regulated by the balanced activities of protein kinases and phosphatases. It has been shown that phosphorylation of NuMA by cyclin B/cdc2 kinase allows NuMA to release from the nucleus and to associate with centrosomes and/or microtubules at the spindle poles, while NuMA's dephosphorylation due to the cyclin B degradation allows NuMA to dissociate from the spindle poles after anaphase onset. Overexpression of NuMA interferes with spindle-associated dynein localization and promotes multipolar spindle formation and cancer. On the other hand, NuMA is absent in many kinds of non-proliferating cells and highly differentiated cells. NuMA also functions during meiotic spindle organization in male and female germ cells. Degradation of NuMA results in the breakdown of normal nuclear structure, and has been used as a marker of cell apoptosis. The implications of NuMA protein in somatic cell animal cloning by nuclear transfer are discussed.


Feeding frequency for lactating cows: diurnal patterns of hormones and metabolites in peripheral blood in relation to milk-fat concentration.
1. The present paper reports the effects of dietary modifications on the diurnal pattern of concentrations of certain metabolites and hormones in the peripheral blood of lactating dairy cows. The cows were given fixed rations of hay and high-cereal concentrates in the proportions of 30:70 or 10:90 (w/w). The concentrates were given in either two or six equal meals daily; the hay was given twice daily. 2. Previous reports of the same experiment had shown that milk-fat yield and concentration were reduced by increasing the proportion of concentrates in the diet and increased by more frequent feeding of the concentrates. These changes could be explained in part by changes in rumen volatile fatty acid (VFA) proportions and mean daily concentrations of VFA, particularly propionic acid, and insulin in the peripheral blood, but these factors failed to explain all the increase in milk-fat concentration caused by more frequent feeding. 3. Analysis of blood samples taken at hourly intervals for 24 h at two stages of lactation showed that, in the cows fed six times daily, the concentrations of metabolites and hormones remained relatively constant over the day. In the cows fed twice daily, the concentrations of VFA, 3-hydroxybutyric acid and insulin all increased after both meals whereas the concentrations of glucose and growth hormone tended to fall. The concentration of non-esterified fatty acids tended to increase overnight and fall rapidly after the morning feed. The concentrations of glucagon, thyroxine and prolactin showed no clear pattern in relation to meals. The postprandial responses of propionate, insulin and growth hormone were greater with the higher concentrate diet. 4. The maximum concentration and the diurnal range of concentrations were reduced by more frequent feeding of both diets in the case of propionic acid and of the higher concentrate diet in the case of insulin, but the effects on insulin concentrations of more frequent feeding of the lower concentrate diet were smaller and not significant. The maximum concentration and the diurnal range of concentrations of growth hormone were unaffected by meal frequency. 5. It is concluded that the severity of milk-fat depression in cows fed twice daily is increased by the rapid rise in propionic acid concentration in the peripheral blood after a meal, which in turn increases insulin secretion and may be accompanied by a suppression of growth hormone release. This causes lipogenesis to be diverted towards adipose tissue at the expense of the mammary gland.(ABSTRACT TRUNCATED AT 400 WORDS)


Omega-3 Fatty Acids-Enriched Fish Oil Activates AMPK/PGC-1α Signaling and Prevents Obesity-Related Skeletal Muscle Wasting.
Obesity is known to cause skeletal muscle wasting. This study investigated the effect and the possible mechanism of fish oil on skeletal muscle wasting in an obese rat model. High-fat (HF) diets were applied to induce the defects of lipid metabolism in male Sprague-Dawley rats with or without substitution of omega-3 fatty acids-enriched fish oil (FO, 5%) for eight weeks. Diets supplemented with 5% FO showed a significant decrease in the final body weight compared to HF diet-fed rats. The decreased soleus muscle weights in HF diet-fed rats could be improved by FO substitution. The decreased myosin heavy chain (a muscle thick filament protein) and increased FOXO3A and Atrogin-1 (muscle atrophy-related proteins) protein expressions in soleus muscles of HF diet-fed rats could also be reversed by FO substitution. FO substitution could also significantly activate adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation, peroxisome-proliferator-activated receptor-γ (PPARγ) coactivator 1α (PGC-1α), and PPARγ protein expression and lipoprotein lipase (LPL) mRNA expression in soleus muscles of HF diet-fed rats. These results suggest that substitution of FO exerts a beneficial improvement in the imbalance of lipid and muscle metabolisms in obesity. AMPK/PGC-1α signaling may play an important role in FO-prevented obesity-induced muscle wasting.


The hemostatic effects of desmopressin on patients who had total joint arthroplasty. A double-blind randomized trial.
The effects of desmopressin on postoperative bleeding and postoperative transfusion requirements were studied in ninety-two hemostatically normal patients who had had an elective primary total hip or total knee arthroplasty. The patients were randomized into either a placebo or a desmopressin group in a double-blind prospective clinical trial. During closure of the wound, desmopressin (0.03 microgram per kilogram of body mass) or the placebo was infused into a peripheral vein over a twenty-minute period. Compared with the placebo, desmopressin did not significantly decrease blood loss or transfusion requirements, and it did not affect the postoperative platelet or fibrinogen levels or the bleeding time. The results were no different even when the treatment and control groups were matched according to surgeon, use of cement for the femoral and knee components, preoperative use of non-steroidal anti-inflammatory agents, or performance of a lateral release for total knee arthroplasty. We concluded that desmopressin does not reduce blood loss or transfusion requirements after total joint arthroplasty.


Epidemiology of Clostridium difficile infection and risk factors for unfavorable clinical outcomes: results of a hospital-based study in Barcelona, Spain.
Prospective hospital-based surveillance for Clostridium difficile-associated disease (CDAD) was conducted in Barcelona (Spain) to describe the epidemiology of this condition and investigate the risk factors for an unfavorable outcome. All patients diagnosed with CDAD during 2009 were included. Using logistic regression modeling, we analyzed the potential risk factors associated with recurrent and complicated CDAD, defined as a need for colectomy or death within 30 days. There were 365 episodes of CDAD, yielding an incidence of 22.5 cases/10(5) person-years, 1.22 cases/10(3) hospital discharges, and 1.93 cases/10(4) patient-days. The main PCR ribotypes identified were 241 (26%), 126 (18%), 078 (7%), and 020 (5%). PCR ribotype 027 was not detected. Among the 348 cases analyzed, 232 (67%) patients were cured, 63 (18%) had a recurrence of CDAD, and 53 (15%) developed complicated CDAD. Predictors of complicated CDAD were continued use of antibiotics following CDAD diagnosis (odds ratio [OR], 2.009; 95% confidence interval [CI], 1.012 to 3.988; P = 0.046), Charlson comorbidity index score (OR, 1.265; 95% CI, 1.105 to 1.449; P = 0.001), and age (OR, 1.028; 95% CI, 1.005 to 1.053; P = 0.019). A leukocyte count of >15 × 10(3) cells/ml (OR, 2.277; 95% CI, 1.189 to 4.362; P = 0.013), continuation of proton pump inhibitor (PPI) use after CDAD diagnosis (OR, 2.168; 95% CI, 1.081 to 4.347; P = 0.029), and age (OR, 1.021; 95% CI, 1.001 to 1.041; P = 0.036) were independently associated with higher odds of recurrence. The incidence of CDAD in Barcelona during 2009 was on the lower end of the previously described range for all of Europe. Our analysis suggests that the continuation of non-C. difficile antibiotics and use of PPIs in patients diagnosed with CDAD are associated with unfavorable clinical outcomes.


[Protein S deficiency and thrombophilia: presentation of a clinical case and review of the literature].
We report the case of a 22-year-old obese woman with severe protein S deficiency, probably genetic in nature, associated with recurrent venous thrombosis. Protein S deficiency is a rather rare disease: it may be an inherited, either homozygous (purpura fulminans at neonatal age), heterozygous, or acquired disorder. The thrombophilic state may be manifested as deep vein thrombosis or thrombophlebitis of the superficial veins with a high risk of pulmonary embolism in the young, and it is often exacerbated by pregnancy. In our case, the presenting event, bilateral deep venous (iliac-femoral) thrombosis complicated by disseminated intravascular coagulation, had occurred when the patient was 13 years old. We started long-term therapy with oral coagulants, i.e. warfarin even if the latter may cause skin necrosis ("warfarin dermatitis") in some patients with protein S deficiency. The clinician must consider protein S deficiency in cases of recurrent thrombosis, particularly in young patients: the importance of early implementation of long-term preventive therapy should not be underestimated.