The relationship of stress, competitive anxiety, mood state, and social support to athletic injury.
We examined the role of stress, competitive anxiety, mood state, and social support in athletic injury. Specifically, we hypothesized that athletes reporting high levels of stress, high competitive trait anxiety, negative mood state, and low social support would exhibit greater incidence of injury and injury severity. Correlational analysis. Major Canadian university. Voluntary sample, 55 male varsity athletes (42 football, 81% of the football team, and 13 rugby, 74% of the rugby team), ages 19-28 yr (x = 22). The inventories Sport Competition Anxiety Test (SCAT), Social Support Scale, Social Athletic Readjustment Rating Scale (SARRS), and Profile of Mood States (POMS) were administered. Internal consistency of the self- report measures was tested using Cronbach's alpha coefficient. Injury rate and severity were recorded by the head student therapist throughout the season. Correlational analyses performed using Pearson correlational coefficient revealed that competitive anxiety (r = .29, p = .03) and tension/anxiety mood states (r = .43, p = .001) were related to injury frequency, and that tension/anxiety (r = .44, p = .008), anger/hostility (r = .30, p = .02), and total negative mood state (r = .28, p = .038) were related to injury severity. Individually, the two sports yielded somewhat different results: for football, injury frequency and injury severity were related to tension/ anxiety (r = .43, p = .004 and r = .47, p = .002, respectively). Vigor/activity was found to be significantly related to injury rate (p = .02), but since the internal consistency of vigor/activity was less than .70 on the Cronbach alpha scale, this significant finding was disregarded. In rugby, injury frequency was related to tension/anxiety (r = .58, p = .04) and depression/ dejection (r = .57, p = .04). These findings are useful for athletic trainers in identifying athletes who may possess psychological factors predisposing them to athletic injury. Subsequently, athletic trainers can instruct these athletes or refer them for assistance in psychological preventive interventions.


Total hip arthroplasty for adult patients with hip arthritis in Jordan: clinical profiles and patient characteristics.
Total Hip Arthroplasty (THA) is one of the most commonly performed orthopaedic surgeries, with hip arthritis being the main indication. This procedure is usually performed when other non-surgical methods fail to relieve patients' hip pain and improve their quality of life. However, limited information exists to identify and compare the demographics and clinical characteristics of patients undergoing this procedure in Jordan. This study aims to identify these demographic and clinical characteristics and compare the findings in terms of gender differences. This is a retrospective study that analysed the hospital records of 650 patients undergoing THA in tertiary referral hospital in Jordan over a four-year period from January 2019 to December 2022. The collected data were classified into three categories: demographic characteristics, perioperative variables, and patients' related health profiles. IBM's Statistical Package for the Social Sciences (SPSS) version 23 software (IBM, USA) and descriptive analysis were used for data analysis. Two-thirds of the sample studied were female (63.4%). In terms of bleeding profiles, the mean intraoperative blood loss was 542 millilitres. The major indication for THA was degenerative hip arthritis (50.5%), followed by hip dysplasia (40.3%).. Comparing the findings of the two gender groups, females were more likely to have degenerative and dysplastic hip arthritis (221 and 157, p = 0.04 and p = 0.1, respectively) when compared to males. Although males were more likely to lose more blood during the surgery (557 ml vs. 533 ml, p = 0.33, females needed more blood transfusions both during (21 vs. 6 patients, p = 0.12) and after the surgery (57 vs. 16 patients, p = 0.006). Furthermore, females were more likely to have comorbidities such hypertension (293 vs. 179 patients, p = 0.20), and hypothyroidism (313 vs 187, p = 0.36), and diabetes (85 vs. 38 patients, p = 0.15), among many other health conditions. However, in the study sample, male smokers outnumbered female smokers (132 vs. 63). Gender highly impacted the immediate surgical outcomes of patients who underwent THA. Females were more likely to need blood transfusions both during and after the surgery and had lower post-operative haemoglobin readings. In addition, females had more comorbidities and degenerative hip osteoarthritis. We believe that raising awareness about comorbidity management, preoperative smoking cessation, and perioperative blood transfusion management can improve medical and surgical outcomes.


The relationship between fetal hemoglobin and disease severity in children with sickle cell anemia.
A study was conducted in a sample of 140 children with sickle cell anemia to evaluate the relationship between hematological variables (%HbF, %HbA2, %Hb, and mean cell volume) and disease severity. A patient's severity status was determined by whether he/she was hospitalized, had a transfusion, and/or had a pain crisis at 2 evaluation periods; the first was based on a patient's history taken at the initial assessment visit to the Wayne State Comprehensive Sickle Cell Center, and the second was based on a 1-3 year follow-up at the center. Fetal hemoglobin was a strong predictor of a patient's hospitalization and transfusion status. A decrease in %HbF of 4.76% (one SD of %HbF) was associated with a 3.58 fold (95% confidence interval, 1.18-7.28) greater odds of being hospitalized both prior to initial assessment and on follow-up, compared to not being hospitalized at either evaluation. Similarly, a decrease in %HbF of 4.76% was associated with a 5.56 fold (95% confidence interval, 1.67-18.96) greater odds of having a transfusion both prior to initial assessment and on follow-up compared to not having a transfusion at either evaluation. Patients who were both hospitalized and transfused at initial assessment and on follow-up (n = 12) had a mean %HbF of 7.59%, while patients who were not hospitalized or transfused at either evaluation (n = 19) had a mean %HbF of 13.61%. Fetal hemoglobin was not a significant predictor of pain crises in this sample of patients. None of the other hematological variables were significant predictors of disease severity in this study. The strong relationship between %HbF and disease severity identified in this study suggests that a single %HbF measurement may be useful in predicting important aspects of the clinical course of children with sickle cell anemia.


Alfalfa mosaic virus: coat protein-dependent initiation of infection.
SUMMARY Taxonomy: Alfalfa mosaic virus (AMV) is the type species of the genus Alfamovirus and belongs to the family Bromoviridae. In this family, the tripartite RNA genomes of bromo-, cucumo- and probably oleaviruses are infectious as such, whereas infection with the three genomic RNAs of alfamo- and ilarviruses requires addition to the inoculum of a few molecules of coat protein (CP) per RNA molecule. RNAs 1 and 2 encode the replicase proteins P1 and P2, RNA 3 encodes the movement protein and CP. CP is translated from the subgenomic RNA 4. Physical properties: RNAs 1 (3.65 kb), 2 (2.6 kb) and 3 (2.2 kb) are separately encapsidated into bacilliform particles which are 19 nm wide and 35-56 nm long. In addition, the virus preparations contain spheroidal particles each containing two copies of RNA 4 (0.88 kb). Virus particles contain 16-17% RNA and are mainly stabilized by protein-RNA interactions. The 3'-termini of the viral RNAs contain a homologous sequence of 145 nucleotides that can adopt two alternative conformations: one represents a high-affinity binding site for CP, the other resembles a tRNA-like structure and is required for minus-strand promoter activity. Hosts: AMV mostly infects herbaceous plants, but several woody species are included in the natural host range. The experimental and natural host ranges include over 600 species in 70 families. At least 15 aphid species are known to transmit the virus in the stylet-borne or non-persistent manner. Economic importance: AMV is a significant pathogen in alfalfa and sweet clover and can spread from these forages to neighbouring crops like pepper, tobacco or soybean. The recent introduction of the soybean aphid (Aphis glycines) in the mid-west states of the USA has increased the incidence of AMV in soybean. AMV occurs world-wide in potato and is referred to as 'calico mosaic' because of its characteristic symptoms on the foliage. However, the economic importance of AMV in potato is limited. <http://www.socgenmicrobiol.org.uk/JGV/080/1089/0801089A.PDF> review paper; <http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/10010001.htm> host range and physical properties; <http://mmtsb.scripps.edu/viper/1amv.html> structural information.


Reconstitution of plant nitrate reductase by Escherichia coli extracts and the molecular cloning of the chlA gene of Escherichia coli K12.
Extracts from Escherichia coli, wild type and chlB, chlC, chlD, chlE, and chlG, but not chlA mutants, were able to reconstitute the nitrate reductase activity in Nicotiana tabacum cnx68 and Hyoscyamus muticus MA-2 mutant extracts. Because cnx68 and MA-2 lack the molybdenum cofactor required for nitrate reductase activity, these results indicate that the functional chlA gene is essential to produce the molybdenum cofactor in E. coli. A clone containing a gene capable of complementing the chlA mutation SA493 was obtained on a large cosmid pJT1. A 1.9 kb BclI fragment subcloned from pJT1 in the vector plasmid pBR322 was shown to complement the chlA SA493 mutant when inserted in either of the two possible orientations. This suggested that the chlA gene was contained intact, including its own promoter, on the 1.9 kb BclI fragment.


MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices.
Previous work has shown that endothelial cell (EC)-derived matrix metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a plasmin- and MMP-1 dependent manner. Here we report that a number of serine proteases can activate MMP-1 and cause capillary tube regression; namely plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase. Plasma prekallikrein failed to induce regression without coactivators such as high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G) and the mast cell serine proteases (tryptase and chymase) each caused MMP-1 activation and collagen type I proteolysis, capillary tubular network collapse, regression and EC apoptosis. Capillary tube collapse is accompanied by collagen gel contraction, which is strongly related to the wound contraction that occurs during regression of granulation tissue in vivo. We also report that proMMP-10 protein expression is markedly induced in ECs undergoing capillary tube morphogenesis. Addition of each of the serine proteases described above led to activation of proMMP-10, which also correlated with MMP-1 activation and capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in ECs using recombinant adenoviral delivery markedly accelerated serine protease-induced capillary tube regression. ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs. Thus, MMP-10-induced activation of MMP-1 correlated with tube regression and gel contraction. In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices.


Cutting edge: novel RNA ligands able to bind CD4 antigen and inhibit CD4+ T lymphocyte function.
The value of high affinity-specific reagents in immunology is exemplified by the use of mAbs. Recent in vitro selection methods suggested that oligonucleotides may provide a useful alternative, especially where Abs have been insufficient thus far. We used a systematic evolution of ligands by exponential enrichment (SELEX) procedure to derive high affinity oligonucleotide ligands (aptamers) recognizing CD4. These RNase-resistant aptamers bound with high affinity and specificity as demonstrated using BIAcore (Stevenage, U.K.) technology. They also bound native CD4 on rat lymphocytes and specifically interfered with labeling by high affinity mAbs. All aptamers recognized the same binding site in the CDR2-like region in domain 1 of CD4. The applicability of these aptamers for immunologic studies was clearly demonstrated by their ability to block a fully allogeneic MLR in a CD4-specific manner. The high affinity and stability of aptamers point to their value in the analysis and functional manipulation of the immune system.


Reconstruction of the chest wall after excision of a giant malignant peripheral nerve sheath tumor.
Primary chest wall tumors are uncommon and constitute 0.2-2% of all tumors. Metastatic tumors and tumors of local extension are more common. Malignant peripheral nerve sheath tumor (MPNST) of the chest wall is even rarer and its incidence on the chest wall not stated in the literature. The incidence in the general population is 0.0001% while the risk is approximately 4600 times higher in patients with type I neurofibromatosis and 3-13% of them will finally develop into MPNST, usually after latent periods of 10-20 years. Clinically, these tumors are aggressive, locally invasive, and highly metastatic. Excision of giant chest wall tumor leaves a defect that is reconstructed using musculocutaneous flaps with or without a mesh. We report the case of a 24-year-old man who presented at the surgical outpatient clinic with 7 months history of persistent left sided chest pain minimally relieved by analgesics, 5 months of cough and worsening dyspnoea, and 3 months history of anterior chest swelling on the left side of the manubrium. Following evaluation and investigations, the tumor was excised and the residual defect closed with methylmetacrylate sandwiched between two prolene meshes and overlaid with both pectoralis major muscles. The histology of the excised mass revealed MPNST He made an uneventful postoperative recovery, but died barely 3 months later from widespread pulmonary metastases. A review of the literature revealed that such tumors hardly ever reach such large-size as in our case.


Techniques for Formulation of Nanoemulsion Drug Delivery System: A Review.
Nanoemulsion drug delivery systems are advanced modes for delivering and improving the bioavailability of hydrophobic drugs and the drug which have high first pass metabolism. The nanoemulsion can be prepared by both high energy and low energy methods. High energy method includes high-pressure homogenization, microfluidization, and ultrasonication whereas low energy methods include the phase inversion emulsification method and the self-nanoemulsification method. Low energy methods should be preferred over high energy methods as these methods require less energy, so are more efficient and do not require any sophisticated instruments. However high energy methods are more favorable for food grade emulsion as they require lower quantities of surfactant than low energy methods. Techniques for formulation of nanoemulsion drug delivery system are overlapping in nature, especially in the case of low energy methods. In this review, we have classified different methods for formulation of nanoemulsion systems based on energy requirements, nature of phase inversion, and self-emulsification.


From ISET to InDRE. IV. Institute of Epidemiological Diagnosis and Reference: new orientation, 1990-2012.
From 1990 to 2012, the Sanitary and Tropical Diseases Institute experienced the most important changes. In 1989, its name and orientation were modified to become the National Institute of Epidemiological Diagnosis and Reference. Shortly before, it had been formalized as the apex of the National Network of Public Health Laboratories and had incorporated laboratories for preventive programs such as exfoliative cytology and rabies, malaria and tuberculosis diagnosis; subsequently, it would incorporate other networks that emerged as part of the response to major epidemic outbreaks and to the new epidemiological outlook. In this period, 27 priority diagnostic algorithms were defined, organized in 18 networks, some of which began to collaborate with global networks. In 2001, the Institute started working with pathogens related to bioterrorism. By then, space restrictions of the headquarter's building were evident; in 2008, starting the construction of new facilities was decided. The Institute and its diagnostic networks constitute a milestone in Latin American public health of the 21st century.


Advances in crosslinking strategies of biomedical hydrogels.
Biomedical hydrogels as sole repair matrices or combined with pre-seeded cells and bioactive growth factors are extensively applied in tissue engineering and regenerative medicine. Hydrogels normally provide three dimensional structures for cell adhesion and proliferation or the controlled release of the loading of drugs or proteins. Various physiochemical properties of hydrogels endow them with distinct applications. In this review, we present the commonly used crosslinking method for hydrogel synthesis involving physical and chemical crosslinks and summarize their current progress and future perspectives.


Self-report and longitudinal predictors of violence in Iraq and Afghanistan war era veterans.
This study, using a longitudinal design, attempted to identify whether self-reported problems with violence were empirically associated with future violent behavior among Iraq and Afghanistan war veterans and whether and how collateral informant interviews enhanced the risk assessment process. Data were gathered from N = 300 participants (n = 150 dyads of Iraq and Afghanistan war veterans and family/friends). The veterans completed baseline and follow-up interviews 3 years later on average, and family/friends provided collateral data on dependent measures at follow-up. Analyses showed that aggression toward others at follow-up was associated with younger age, posttraumatic stress disorder, combat exposure, and a history of having witnessed parental violence growing up. Self-reported problems controlling violence at baseline had robust statistical power in predicting aggression toward others at follow-up. Collateral report enhanced detection of dependent variables: 20% of cases positive for violence toward others would have been missed relying only on self-report. The results identify a subset of Iraq and Afghanistan war veterans at higher risk for problematic postdeployment adjustment and indicate that the veterans' self-report of violence was useful in predicting future aggression. Underreporting of violence was not evidenced by most veterans but could be improved upon by obtaining collateral information.


Cl- and K+ conductances activated by cell swelling in primary cultures of rabbit distal bright convoluted tubules.
Ionic currents induced by cell swelling were characterized in primary cultures of rabbit distal bright convoluted tubule (DCTb) by the whole cell patch-clamp technique. Cl- currents were produced spontaneously by whole cell recording with an isotonic pipette solution or by exposure to a hypotonic stress. Initial Cl- currents exhibited outwardly rectifying current-voltage relationship, whereas steady-state currents showed strong decay with depolarizing pulses. The ion selectivity sequence was I- = Br- > Cl- >> glutamate. Currents were inhibited by 0.1 mM 5-nitro-2-(3-phenylpropylamino) benzoic acid and 1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and strongly blocked by 1 mM diphenylamine-2-carboxylate. Currents were insensitive to intracellular Ca2+ but required the presence of extracellular Ca2+. They were not activated in cells pretreated with 200 nM staurosporine, 50 microM LaCl3, 10 microM nifedipine, 100 microM verapamil, 5 microM tamoxifen, and 50 microM dideoxyforskolin. Staurosporine, tamoxifen, verapamil, or the absence of external Ca2+ was without effect on the fully developed Cl- currents. Osmotic shock also activated K+ currents in Cl- free conditions. These currents were time independent, activated at depolarized potentials, and inhibited by 5 mM BaCl2. The activation of Cl- and K+ currents by an osmotic shock may be implicated in regulatory volume decrease in DCTb cells.


[A closer look at the Mozambique reality: nursing and health].
Identity and memory of Nursing are built through studies on historical, political and social aspects of the profession and its collective organizations searching to strengthening its values. In this view, goals of this study are: to share with nursing professionals and students an experience of visiting Mozambique and collecting some information on social, political, health and living conditions of people within this country; and, to disseminate this experience among nurses and colleagues in order to stimulate similar very enriching learning opportunities.


A new phospholipase A2 isolated from the sea anemone Urticina crassicornis - its primary structure and phylogenetic classification.
Disulfide pairings and active site residues are highly conserved in secretory phospholipases A(2) (PLA(2)s). However, secretory PLA(2)s of marine invertebrates display some distinctive structural features. In this study, we report the isolation and characterization of a PLA(2) from the northern Pacific sea anemone, Urticina crassicornis (UcPLA(2)), containing a C27N substitution and a truncated C-terminal sequence. This novel cnidarian PLA(2) shares about 60% identity and almost 70% homology with two putative PLA(2)s identified in the starlet sea anemone (Nematostella vectensis) genome project. UcPLA(2) lacks hemolytic and neurotoxic activities. A search of available sequences revealed that Asn27-'type' PLA(2)s are present in a few other marine animal species, including some vertebrates. The possibility that the C27N replacement represents a structural adaptation for PLA(2) digestion/activity in the marine environment was not supported by experiments testing the influence of ionic strength on UcPLA(2) enzymatic activity. Because of the highly divergent sequences among invertebrate group I PLA(2)s, it is currently not possible to identify orthologous relationships. As the Asn27-containing PLA(2)s are scattered among the other invertebrate group I PLA(2)s, they do not constitute a new, monophyletic PLA(2) clade.


Medical alternatives to oocyte donation in women with premature ovarian failure: a systematic review.
Oocyte donation can satisfy the desire to have children in women with premature ovarian failure (POF) but little progress has been made to improve reproduction using the patients' own gametes. The aim of this study was to assess the effectiveness of alternative treatments to oocyte donation in patients with POF. A systematic search of MEDLINE, EMBASE and Cochrane databases from January 1988 to January 2012 using descriptors related to POF, ovulation induction, and pregnancy was made. Randomized clinical trials of women with POF undergoing various treatments to achieve ovulation induction, often compared with alternative treatment and placebo groups, were only selected. Outcomes of interest were those related to pregnancy (biochemical and live birth). Twelve trials were included and analysed for methodology, inclusion and exclusion criteria, number of patients included, characteristics and type of intervention, and results in terms of ovulation rate, pregnancy rate and ongoing pregnancy rate. The large methodological variability among studies prevented to combined data for a meta-analysis. None of the studies showed statistically significant differences between the study groups. The lack of case-control studies with a placebo group makes it impossible to establish differences between a treatment and no treatment.


The Practice of Midwifery in Rural US Hospitals.
Workforce shortages limit access to care for pregnant women in rural and remote areas. The goal of this analysis was to describe the role of certified nurse-midwives (CNMs) in providing maternity care in rural US hospitals and to examine state-level variation in rural CNM practice. We identified 306 rural hospitals with at least 10 births in 2010 using discharge data from the Statewide Inpatient Databases for 9 US states. We conducted a telephone survey of hospital maternity unit managers (N = 244) from November 2013 to March 2014 to understand their maternity care workforce and practice models. We describe the presence of CNMs attending births by hospital and state characteristics. Using logistic multivariate regression, we examined whether CNMs attend births, adjusting for hospital characteristics, practice regulations, and state. We also analyzed the content of open-ended responses about staffing plans, challenges, and opportunities that unit managers identified, with a focus on midwifery practice. CNMs attend births at one-third of rural maternity hospitals in 9 US states. Significant variability across states appears to be partially related to autonomous practice regulations: states allowing autonomous midwifery practice have a greater proportion of rural hospitals with midwives attending births (34% vs 28% without autonomous midwifery practice). In rural maternity hospitals, CNMs practice alongside obstetricians in 86%, and with family physicians in 44%, of hospitals. Fourteen percent of all respondents planned recruitment to increase the number of midwives at their hospital, although many, especially in smaller hospitals, noted challenges in doing so. CNMs play a crucial role in the maternity care workforce in rural US hospitals. The participation of CNMs in birth attendance varies by hospital birth volume and across state settings. Interprofessional practice is common for CNMs attending births in rural hospitals, and administrators hope to increase the number of midwives in rural maternity practice.


Isolation, taxonomy and phylogeny of hyperthermophilic microorganisms.
Hyperthermophilic Archaea and Bacteria with optimal growth temperatures between 80 and 110°C have been isolated from geo- and hydro-thermally heated terrestrial and submarine environments. 16S rRNA sequence comparisons indicate great phylogenetic diversity among the 23 different genera represented. Hyperthermophiles consist of anaerobic and aerobic chemolithoautotrophs and heterotrophs growing at neutral or acidic pH. Their outstanding heat resistance makes them as interesting objects for basic research as for biotechnology in the future.


Immediate early gene expression to examine neuronal activity following acute and chronic stressors in rat pups: examination of neurophysiological alterations underlying behavioral consequences of prenatal cocaine exposure.
Altered behavioral responses to stressors have been observed in animals exposed to cocaine prenatally. In the present study, both behavioral and physiological responses to repeated and single stressor exposure were measured in animals prenatally exposed to cocaine. Offspring were derived from 3 prenatal treatment groups: dams that were administered 40 mg/kg cocaine from gestational day 8-20 (C40); dams that were pair-fed and -watered to weight-matched C40 dams (PF); and untreated dams (LCC). Starting on postnatal day 16-17 (P16-17), offspring from the 3 prenatal treatment groups were exposed to either footshock or isolation daily for 5 days. Two days after the last day of stressor exposure (P21-22), subjects were given 1 final exposure to the stressor to which they were previously exposed. In addition, at P21-22, littermates of animals given repeated exposure to stressors were exposed to either footshock or isolation for the first and only time. During all footshock sessions, the duration of freezing behavior was recorded. Plasma adrenocorticotrophin (ACTH) and corticosterone levels were determined from blood samples taken immediately following the final stressor session and brains were processed for C-FOS immunoreactivity (FOS-IR). Plasma corticosterone was increased following either single or repeated exposure to either stressor compared to homecage control animals. Plasma ACTH was increased by exposure to both repeated and single footshock exposure, but the increase was not as great following repeated footshock exposure, suggesting adaptation to repeated exposure to this stressor. Following both single and repeated footshock exposure, FOS-IR was increased relative to baseline levels in the paraventricular nucleus of the hypothalamus (PVN) and in the supraoptic nucleus (SON), but not the locus coeruleus (LC). Repeatedly footshocked animals exhibited more time freezing than animals given a single footshock session. Prenatal exposure to cocaine resulted in more time spent freezing in C40 than LCC animals during the chronic footshock exposure period; however, no differences were seen in any of the physiological measures taken from these 2 groups on the final test day. The implications of these findings are discussed in the context of other research examining the effects of prenatal cocaine exposure on stress responses.


Myosin subfragment-1 is sufficient to move actin filaments in vitro.
The rotating crossbridge model for muscle contraction proposes that force is produced by a change in angle of the crossbridge between the overlapping thick and thin filaments. Myosin, the major component of the thick filament, is comprised of two heavy chains and two pairs of light chains. Together they form two globular heads, which give rise to the crossbridge in muscle, and a coiled-coil rod, which forms the shaft of the thick filament. The isolated head fragment, subfragment-1 (S1), contains the ATPase and actin-binding activities of myosin (Fig. 1). Although S1 seems to have the requisite enzymatic activity, direct evidence that S1 is sufficient to drive actin movement has been lacking. It has long been recognized that in vitro movement assays are an important approach for identifying the elements in muscle responsible for force generation. Hynes et al. showed that beads coated with heavy meromyosin (HMM), a soluble proteolytic fragment of myosin consisting of a part of the rod and the two heads, can move on Nitella actin filaments. Using the myosin-coated surface assay of Kron and Spudich, Harada et al. showed that single-headed myosin filaments bound to glass support movement of actin at nearly the same speed as intact myosin filaments. These studies show that the terminal portion of the rod and the two-headed nature of myosin are not required for movement. To restrict the region responsible for movement further, we have modified the myosin-coated surface assay by replacing the glass surface with a nitrocellulose film. Here we report that myosin filaments, soluble myosin, HMM or S1, when bound to a nitrocellulose film, support actin sliding movement (Fig. 2). That S1 is sufficient to cause sliding movement of actin filaments in vitro gives strong support to models of contraction that place the site of active movement in muscle within the myosin head.


Sexual orientation and mental health: results from a community survey of young and middle-aged adults.
Community surveys have reported a higher rate of mental health problems in combined groups of homosexual and bisexual participants, but have not separated these two groups. To assess separately the mental health of homosexual and bisexual groups compared with heterosexuals. A community survey of 4824 adults was carried out in Canberra, Australia. Measures covered anxiety, depression, suicidality, alcohol misuse, positive and negative affect and a range of risk factors for poorer mental health. The bisexual group was highest on measures of anxiety, depression and negative affect, with the homosexual group falling between the other two groups. Both the bisexual and homosexual groups were high on suicidality. Bisexuals also had more current adverse life events, greater childhood adversity, less positive support from family, more negative support from friends and a higher frequency of financial problems. Homosexuals reported greater childhood adversity and less positive support from family. The bisexual group had the worst mental health, although homosexual participants also tended to report more distress.


Brain-Gut-Microbiota Axis in Alzheimer's Disease.
Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The Aβ seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.


Immediate Dental Implants Enriched with L-PRF in the Esthetic Zone.
The aim of this article is to present the clinical application of immediate implant placement with L-PRF and immediate prosthetic loading in anterior esthetic region. A 24-year-old healthy female patient reported with a chief complaint of poor esthetics in the upper front tooth region with retained deciduous teeth. On oral examination, there were retained deciduous teeth (52, 53, and 63) with congenitally missing permanent successors. The retained deciduous teeth were extracted, and immediate implant placement was done in the extraction sockets along with L-PRF membranes in one surgical session under local anesthesia. Immediate temporization was performed with composite crowns on immediately placed dental implants. After 3 months of the healing period, the final implant-level impressions were made and the temporary composite crowns were replaced with the final zirconia porcelain crowns. A 12-month follow-up was made, and satisfactory esthetic and functional results were obtained.


Intracellular generation and accumulation of amyloid beta-peptide terminating at amino acid 42.
Amyloid beta-peptide (Abeta) is known to accumulate in senile plaques of Alzheimer's disease (AD) patients and is now widely believed to play a major role in the disease. Two populations of peptides occur terminating either at amino acid 40 or at amino acid 42 (Abeta1-40 and Abeta1-42). Alternative N-terminal cleavages produce additional heterogeneity (Abetax-40 and Abetax-42). Peptides terminating at amino acid 42 are believed to be the major player in sporadic AD as well as familial AD (FAD). Whereas the cellular mechanism for the generation of Abeta terminating at amino acid 40 is well understood, very little is known about the cleavage of Abeta after amino acid 42. By using two independent methods we demonstrate intracellular Abeta1-42 as well as Abetax-42 but less Abetax-40 and Abeta1-40 in kidney 293 cells stably transfected with wild type beta-amyloid precursor protein (betaAPP) or the FAD-associated Val/Gly mutation. Moreover, retention of betaAPP within the endoplasmic reticulum (ER) by treatment with brefeldin A does not block the cleavage at amino acid 42 but results in an increased production of all species of Abeta terminating at amino acid 42. This indicates that the cleavage after amino acid 42 can occur within the ER. Treatment of cells with monensin, which blocks transport of (betaAPP) within the Golgi causes a marked accumulation of intracellular Abetax-42 and Abetax-40. Therefore these experiments indicate that the gamma-secretase cleavage of Abeta after amino acid 42 can occur within the ER and later within the secretory pathway within the Golgi. Moreover inhibition of reinternalization by cytoplasmic deletions of betaAPP as well as inhibition of intracellular acidification by NH4Cl does not block intracellular Abeta1-42 or Abetax-42 production.


A third broad lineage of major histocompatibility complex (MHC) class I in teleost fish; MHC class II linkage and processed genes.
Most of the previously studied teleost MHC class I molecules can be classified into two broad lineages: "U" and "Z/ZE." However, database reports on genes in cyprinid and salmonid fishes show that there is a third major lineage, which lacks detailed analysis so far. We designated this lineage "L" because of an intriguing linkage characteristic. Namely, one zebrafish L locus is closely linked with MHC class II loci, despite the extensively documented nonlinkage of teleost class I with class II. The L lineage consists of highly variable, nonclassical MHC class I genes, and has no apparent orthologues outside teleost fishes. Characteristics that distinguish the L lineage from most other MHC class I are (1) absence of two otherwise highly conserved tryptophan residues W51 and W60 in the alpha1 domain, (2) a low GC content of the alpha1 and alpha2 exons, and (3) an HINLTL motif including a possible glycosylation site in the alpha3 domain. In rainbow trout (Oncorhynchus mykiss) we analyzed several intact L genes in detail, including their genomic organization and transcription pattern. The gene Onmy-LAA is quite different from the genes Onmy-LBA, Onmy-LCA, Onmy-LDA, and Onmy-LEA, while the latter four are similar and categorized as "Onmy-LBA-like." Whereas the Onmy-LAA gene is organized like a canonical MHC class I gene, the Onmy-LBA-like genes are processed and lack all introns except intron 1. Onmy-LAA is predominantly expressed in the intestine, while the Onmy-LBA-like transcripts display a rather homogeneous tissue distribution. To our knowledge, this is the first description of an MHC class I lineage with multiple copies of processed genes, which are intact and transcribed. The present study significantly improves the knowledge of MHC class I variation in teleosts.


Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors.
We report here the development of the transgenic green fluorescent protein (GFP) nude mouse with ubiquitous GFP expression. The GFP nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives GFP expression in essentially all tissues. In crosses between nu/nu GFP male mice and nu/+ GFP female mice, the embryos fluoresced green. Approximately 50% of the offspring of these mice were GFP nude mice. Newborn mice and adult mice fluoresced very bright green and could be detected with a simple blue-light-emitting diode flashlight with a central peak of 470 nm and a bypass emission filter. In the adult mice, the organs all brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, and duodenum. The following systems were dissected out and shown to have brilliant GFP fluorescence: the entire digestive system from tongue to anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The skinned skeleton highly expressed GFP. Pancreatic islets showed GFP fluorescence. The spleen cells were also GFP positive. Red fluorescent protein (RFP)-expressing human cancer cell lines, including PC-3-RFP prostate cancer, HCT-116-RFP colon cancer, MDA-MB-435-RFP breast cancer, and HT1080-RFP fibrosarcoma were transplanted to the transgenic GFP nude mice. All of these human tumors grew extensively in the transgenic GFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor-host interaction by whole-body imaging and at the cellular level in fresh and frozen tissues. The GFP mouse model should greatly expand our knowledge of human tumor-host interaction.


Pharmacological strategies used to manage symptoms of patients dying of COVID-19: A rapid systematic review.
COVID-19 has tragically resulted in over 2.5 million deaths globally. Despite this, there is a lack of research on how to care for patients dying of COVID-19, specifically pharmacological management of symptoms. The aim was to determine the dose ranges of pharmacological interventions commonly used to manage symptoms in adult patients dying of COVID-19, establish how effectiveness of these interventions was measured, and whether the pharmacological interventions were effective. This was a rapid systematic review with narrative synthesis of evidence, prospectively registered on PROSPERO (ID: CRD42020210892). We searched MEDLINE, EMBASE, CINAHL via the NICE Evidence Health Databases Advanced Search interface; medRxiv; the Cochrane COVID-19 Study Register; and Google Scholar with no date limits. We included primary studies which documented care of patients dying of COVID-19 under the care of a specialist palliative care team. Seven studies, documenting the care of 493 patients met the inclusion criteria. Approximately two thirds of patients required a continuous subcutaneous infusion with median doses of 15 mg morphine and 10 mg midazolam in the last 24 h of life. Four studies described effectiveness by retrospective review of documentation. One study detailed the effectiveness of individual medications. A higher proportion of patients required continuous subcutaneous infusion than is typically encountered in palliative care. Doses of medications required to manage symptoms were generally modest. There was no evidence of a standardised yet holistic approach to measure effectiveness of these medications and this needs to be urgently addressed.


Polymeric controlled release systems.
There are wide applications of great importance for the improved and efficient administration of many materials--particularly in the pharmaceutical area. The introduction of novel polymeric materials and related formulation technologies now provide a versatile means for the precisely controlled delivery of many physiologically active substances. A further advantage is a decrease in patient discomfort and compliance, and decreased side-effects.


Nonaspirin Nonsteroidal Antiinflammatory Drug Use in the Nordic Countries from a Cardiovascular Risk Perspective, 2000-2016: A Drug Utilization Study.
Evidence on the cardiotoxicity of nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), particularly diclofenac and the newer selective cyclooxygenase (COX)-2 inhibitors, has accumulated over the last decade. Our objective was to examine whether the use of NSAIDs in the Nordic countries changed with the emerging evidence, regulatory statements, and clinical guidelines advocating caution for the use of specific NSAIDs. Drug utilization study. Nationwide wholesale statistics and prescription registries in Denmark, Finland, Iceland, Norway, and Sweden (2000-2016). Our main outcome measures were yearly total sales, expressed as number of sold defined daily doses (DDDs)/1000 inhabitants/day, and yearly prevalence of prescription use, expressed as number of prescription users per 1000 inhabitants. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. Total sales of NSAIDs increased in all countries and were highest in Iceland, with 74.3 DDDs/1000 inhabitants/day sold in 2016, followed by Finland (73.9), Sweden (54.4), Norway (43.8), and Denmark (31.8). Diclofenac use declined after 2008 in all countries but remained the most widely prescribed NSAID in Norway, with 63 prescription users/1000 inhabitants in 2016. Diclofenac sales also remained high in Iceland (12.7 DDD/1000 inhabitants/day), Norway (8.1), and Sweden (7.8). Since its introduction in 2003, the use of etoricoxib, a newer selective COX-2 inhibitor, increased in all countries except Denmark, with highest sales in Finland (6.7 DDD/1000 inhabitants/day in 2016). Sales and prescription patterns of NSAIDs in the Nordic countries has changed along with the accumulating evidence for the cardiovascular risks of specific NSAIDs. However, given existing evidence on the cardiovascular risks associated with the use of diclofenac and etoricoxib, the persistent high use of diclofenac in Iceland, Norway, and Sweden, the persistent over-the-counter availability of diclofenac in Norway and Sweden, and the increasing use of etoricoxib in most of the Nordic countries pose a cardiovascular health concern.


Comparison of chosen physical fitness characteristics of Turkish professional basketball players by division and playing position.
The purpose of the present study was to compare chosen physical fitness characteristics of Turkish professional basketball players in different divisions (first and second division) and playing positions. Forty-five professional male basketball players (14 guards, 15 forwards, 16 centers) participated in this study voluntarily. For each player, anthropometric measurements were performed, as well as a multi-stage 20 m shuttle run, isokinetic leg strength, squat jump (SJ), countermovement jump (CMJ), 10-30 meter single-sprint and T-drill agility tests. The differences in terms of division were evaluated by independent t-test and the differences by playing position were evaluated by one-way ANOVA with Post Hoc Tukey test. First division players' CMJ measurements were significantly higher than those of second division players' (p≤0.05), whereas second division players' 10 m sprint times were significantly better than those of first division players' (p≤0.05). In addition, forwards and centers were significantly taller than guards. Centers were significantly heavier and their T-drill test performances were inferior to those of forwards and guards (p≤0.05). Moreover, guards had a significantly higher maximal oxygen uptake (VO2 max) than centers. Guards and forwards showed significantly better performance in the 10 and 30 m sprint tests than centers (p≤0.05). Forwards and centers had significantly better left leg flexor strength at 180°.s(-1)(p≤0.05). In conclusion, the findings of the present study indicated that physical performance of professional basketball players differed among guards, forwards and centers, whereas there were not significant differences between first and second division players. According to the present study, court positions have different demands and physical attributes which are specific to each playing position in professional basketball players. Therefore, these results suggest that coaches should tailor fitness programs according to specific positions on the court.


Autologous bone marrow transplantation for progressive non-Hodgkin's lymphoma: clinical impact of immunophenotype and in vitro purging.
From 1983 to 1989 we performed a prospective trial of 70 consecutive, in vitro purged autologous bone marrow transplants (BMT) for patients with progressive non-Hodgkin's lymphoma. Forty-nine patients had responsive disease at the time of transplantation while 21 others had refractory high risk lymphoma. Forty-two patients with B-lineage lymphoma received autologous marrow purged in vitro with monoclonal antibody (anti CD9, CD10, CD24) plus complement, 12 with T-lineage lymphoma received monoclonal antibody immunotoxins (anti CD5, CD7-ricin conjugates) along with 4-hydroperoxycyclophosphamide purging and 16 received unpurged marrow. All received cyclophosphamide, 57 with fractionated total body irradiation, and 13 with BCNU and cytarabine. Hematologic engraftment was prompt and unaffected by phenotype (B vs. T) or by in vitro purging used (B vs. T vs. none) although nine of 16 non-relapse deaths were related to poor graft function. Fifty-one patients (73%) were alive in complete remission (CR) 1 month following transplantation while 15 patients (12 with initially refractory disease) had persistent disease. Subsequently, 41 +/- 18% (by Kaplan-Meier estimate; +/- 95% confidence limits) of those who achieved CR remained relapse free 1-6.4 (median 3) years post-BMT. Neither risk group, purging, nor immunophenotype predicted subsequent post-transplant relapse. Among those 51 who achieved CR, 13 of 43 (27 +/- 14%) with responsive disease survive disease free while three of eight (38 +/- 34%) refractory patients survive disease free (p = 0.96). Overall, 24 patients survive, 16 in continuous complete remission 1-6.5 years following transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)


[The quality of platelet concentrates in dependence on storage time before pathogen inactivation].
Pathogen inactivation procedure performed just before distribution of platelet concentrates (PCs) may decrease costs caused by loss of these components due to relatively short expiry date. To evaluate the quality of PCs pathogen inactivated on the first or the fifth day of storage. PCs preparated from buffy-coats were suspended in platelet additive solution (Intersol, Baxter Healthcare Corporation, Belgium). The photochemical pathogen inactivation was performed on the 1st or the 5th day of storage using amotosalen and UVA (Cerus, Europe BV). PCs were stored for 7 days. There were observed increased expression of CD62 and CD63, elevated activity of LDH and lower concentration of glucose in PCs pathogen inactivated on day 1 compare to the control group. PCs pathogen inactivated on day 5 showed decreased expression of CD62 and CD63 compare to the control group. There were no significant differences in platelet number, pH, lactate concentration, hypotonic shock response and release of platelet derived microparticles in both groups of pathogen inactivated PCs. Time of storage of PCs before pathogen inactivation has no significant impact on PCs quality. Pathogen inactivation procedure performed just after having received request for PCs is more cost effective than the routine pathogen inactivation in all PCs before storage.


Laboratory diagnosis of Clostridium difficile infections: there is light at the end of the colon.
Single molecular or multistep assays (glutamate dehydrogenase, toxin A/B, ± molecular) are recommended for the diagnosis of CDI in patients with clinically significant diarrhea. Rapid and accurate tests can improve resource allocations and improve patient care. Enzyme immunoassay (EIA) for toxins A/B is too insensitive for use as a stand-alone assay. This guideline will examine the use of molecular tests and multitest algorithms for the diagnosis of Clostridium difficile infection (CDI). These new tests, alone or in a multistep algorithm consisting of >1 assay, are more expensive than the older EIA assays; however, rapid and accurate testing can save money overall by initiating appropriate treatment and infection control protocols sooner and by possibly reducing length of hospital stay. We recommend testing only unformed stool in patients with clinically significant diarrhea by a molecular method or by a 2- to 3-step algorithm.


Dissociation of Centrally and Peripherally Induced Transcranial Magnetic Stimulation Effects in Nonhuman Primates.
Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent centrally induced neural mechanisms and peripherally induced sensory costimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging because of the limited spatiotemporal resolution of available noninvasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in a male and a female nonhuman primate (rhesus macaque) to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response curve with stimulation intensity. We further show that stimulation responses are spatially specific. We use several control conditions to dissociate centrally induced neural responses from auditory and somatosensory coactivation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.SIGNIFICANCE STATEMENT Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method to stimulate the human brain. To advance its utility for clinical applications, a clear understanding of its underlying physiological mechanisms is crucial. Here, we perform invasive electrophysiological recordings in the nonhuman primate brain during TMS, achieving a spatiotemporal precision not available in human EEG experiments. We find that evoked potentials are dose dependent and spatially specific, and can be separated from peripheral stimulation effects. This means that TMS-evoked responses can indicate a direct physiological stimulation response. Our work has important implications for the interpretation of human TMS-EEG recordings and biomarker development.


Central Versus Peripheral Pulmonary Embolism: Analysis of the Impact on the Physiological Parameters and Long-term Survival.
Studies aimed at assessing whether the emboli lodged in the central pulmonary arteries carry a worse prognosis than more peripheral emboli have yielded controversial results. To explore the impact on survival and long-term prognosis of central pulmonary embolism. Consecutive patients diagnosed with acute symptomatic pulmonary embolism by means of computed tomography (CT) angiography were evaluated at episode index and traced through the computed system of clinical recording and following-up. Central pulmonary embolism was diagnosed when thrombi were seen in the trunk or in the main pulmonary arteries and peripheral pulmonary embolism when segmental or subsegmental arteries were affected. A total of 530 consecutive patients diagnosed with pulmonary embolism were evaluated; 255 patients had central pulmonary embolism and 275 patients had segmental or subsegmental pulmonary embolism. Patients with central pulmonary embolism were older, had higher plasma levels of N-terminal of the prohormone brain natriuretic peptide (NT-ProBNP), troponin I, D-dimer, alveolar-arterial gradient, and shock index (P < .001 for each one). Patients with central pulmonary embolism had an all-cause mortality of 40% while patients with segmental or subsegmental pulmonary embolism (PE) had an overall mortality of 27% and odds ratio of 1.81 [confidence interval (CI) 95% 1.16-1.9]. Survival was lower in patients with central PE than in patients with segmental or subsegmental pulmonary embolism, even after avoiding confounders (P = .018). Apart from a greater impact on hemodynamics, gas exchange, and right ventricular dysfunction, central pulmonary embolism associates a shorter survival and an increased long-term mortality.


A clustered randomised trial examining the effect of social marketing and community mobilisation on the age of uptake and levels of alcohol consumption by Australian adolescents.
Throughout the world, alcohol consumption is common among adolescents. Adolescent alcohol use and misuse have prognostic significance for several adverse long-term outcomes, including alcohol problems, alcohol dependence, school disengagement and illicit drug use. The aim of this study was to evaluate whether randomisation to a community mobilisation and social marketing intervention reduces the proportion of adolescents who initiate alcohol use before the Australian legal age of 18, and the frequency and amount of underage adolescent alcohol consumption. The study comprises 14 communities matched with 14 non-contiguous communities on socioeconomic status (SES), location and size. One of each pair was randomly allocated to the intervention. Baseline levels of adolescent alcohol use were estimated through school surveys initiated in 2006 (N=8500). Community mobilisation and social marketing interventions were initiated in 2011 to reduce underage alcohol supply and demand. The setting is communities in three Australian states (Victoria, Queensland and Western Australia). Students (N=2576) will complete school surveys in year 8 in 2013 (average age 12). (1) lifetime initiation and (2) monthly frequency of alcohol use. Reports of social marketing and family and community alcohol supply sources will also be assessed. Point estimates with 95% CIs will be compared for student alcohol use in intervention and control communities. Changes from 2006 to 2013 will be examined; multilevel modelling will assess whether random assignment of communities to the intervention reduced 2013 alcohol use, after accounting for community level differences. Analyses will also assess whether exposure to social marketing activities increased the intervention target of reducing alcohol supply by parents and community members. ACTRN12612000384853.


Neuromuscular transmission at newly formed neuromuscular junctions in the regenerating soleus muscle of the rat.
1. A study of neuromuscular function in regenerating skeletal muscle fibres in the rat soleus muscle has been made. The muscle fibres were damaged in vivo by the injection of the myotoxic venom component notexin, and then allowed to regenerate spontaneously. 2. Regenerating muscle fibres generated action potentials and contracted following direct intracellular stimulation as early as 4 days after the injection of notexin. 3. Miniature endplate potentials (MEPPs) were recorded at a minority of synapses at 3 days, and from all synapses by 5 days. The mean amplitude of MEPPs in a given fibre was directly proportional to muscle fibre input resistance. 4. Spontaneous transmitter release in the regenerating fibres was relatively insensitive to changes in [K+]0 but the effect of Ruthenium Red on spontaneous release was similar in the regenerating and control muscle fibres. 5. Functional innervation, defined as the ability to generate an indirect action potential, was restored in 97% of fibres by 10 days. The generation of an action potential was always associated with a twitch of the muscle fibre. Those fibres that were unable to generate an action potential usually exhibited a low membrane potential (ca -50 mV). These fibres could generate action potentials if they were hyperpolarized using an intracellular current-passing microelectrode. 6. The quantal content of endplate potentials (EPPs) was estimated from the mean EPP and mean MEPP amplitudes in cut muscle fibre preparations. These estimates suggested that quantal content was low at the earliest stages of regeneration, but increased as the muscle fibres matured and became normal at 10-21 days. 7. During repetitive stimulation at 30 Hz there was a fall in the amplitude of EPPs of 40-45%. The fall was similar in regenerating and control fibres. Conducting synapses never exhibited failure to generate an EPP during the period of high-frequency stimulation.


[Early commissural ileus after appendectomy in children].
The results of treatment of early commissural ileus (ECI) after appendectomy in children for the period of from 1971 to 1988 are presented. Before 1980, the active tactics of treatment was predominantly used. Of the 4412 patients who underwent appendectomy, ECI developed in 28 (0.68%), 18 were operated on, including the 7--repeatedly. Since 1980, the complex of conservative measures permitting to avoid the operative intervention more than in 60% of the patients has been introduced. Of the 4281 patient operated on for acute appendicitis, ECI developed in 12 (0.28%). The conservative measures has proved to be effective in 2/3 patients. Recurrency of commissural ileus was noted in 1 patient. There were no lethal outcomes.


DNA adducts of the tobacco carcinogens 2-amino-9H-pyrido[2,3-b]indole and 4-aminobiphenyl are formed at environmental exposure levels and persist in human hepatocytes.
Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25-100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM-10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers.


The neocortex of cetaceans: cytoarchitecture and comparison with other aquatic and terrestrial species.
The evolutionary process of readaptation to the aquatic environment was accompanied by extreme anatomical and physiological changes in the brain. This review discusses cortical specializations in the three major lineages of marine mammals in comparison to related terrestrial and semiaquatic species. Different groups of marine mammals adopted a wide range of strategies to cope with the challenges of aquatic living. Cetaceans and hippopotamids possess a completely agranular neocortex in contrast to phocids and sirenians; vertical modules are observed in deep layers V and VI in manatees, cetaceans, phocids, and hippopotamids, but in different cortical areas; and clustering in layer II appears in the insular cortex of hippopotamids, phocids, and cetaceans. Finally, von Economo neurons are present in cetaceans, hippopotamids, sirenians, and some phocids, with specific, yet different, cortical distributions. The interpretation of the evolutionary and functional significance of such specializations, and their relationships with the degrees of adaptation to the aquatic environment and phylogeny, remain difficult to trace, at least until comprehensive data, including representative species from all of the major mammalian families, become available.


Quantal analysis of a decremental response at hair cell-afferent fibre synapses in the goldfish sacculus.
1. On application of a step decrement in the sound intensity, the amplitude of excitatory post-synaptic potentials (e.p.s.p.s) recorded intracellularly from large afferent auditory fibres in goldfish's sacculus showed a decremental response in which the amplitude of the e.p.s.p.s was temporarily reduced to a very low level, but soon returned to a new steady level appropriate to the decreased sound intensity. This response seems to underlie the temporary reduction in the rate of afferent discharge observed in the mammalian cochlea upon cessation of sound or upon reduction of its intensity 2. A statistical analysis revealed that reduction in the size of the mean quantal content (m) during the decremental response was associated with reduction in the size of binomial population (n), but not that of the probability (p) of any one of the available quanta actually being used. 3. The temporary reduction in the size of n during the decremental responses can be explained if it is assumed that replenishment to vacant release sites was channelled to high threshold sites and that the low threshold sites were bypassed. The mechanism underlying this special type of replenishment is discussed in relation to the ultrastructural features of presynaptic sites in the hair cell.


Screening of urine cultures by three automated systems.
A study was conducted to compare three automated systems and the Gram stain for their ability to detect significant bacteriuria. A total of 1,000 urine specimens were evaluated by Autobac MTS (General Diagnostics), Auto Microbic system (AMS; Vitek Systems, Inc.), and MS-2 (Abbott Laboratories) and compared with a semiquantitative culture plate method. Two hundred thirty-nine (23.9%) specimens had colony counts of >10(5) colony-forming units (CFU)/ml by the culture plate method (group I). Of these, 204 (85.3%) were positive by Autobac, 198 (82.8%) were positive by AMS, and 179 (74.9%) were positive by MS-2. When pure cultures of diphtheroids, lactobacilli, and viridans streptococci not group D were considered contaminants and therefore excluded, there were 118 specimens containing pure cultures of probable pathogens. The percentage of significant isolates detected was 97.4% (115 of 118) by the Gram stain, 96.6% (114 of 118) by Autobac, and 95.8% (113 of 118) by AMS and MS-2. The average detection time for all organisms was 2.2 h by Autobac, 6.1 h by AMS, and 1.8 h by MS-2; therefore, all three methods were more rapid than the 18- to 24-h standard plate culture method. One hundred sixty-one (16.1%) specimens had colony counts of 10(4) to 10(5) CFU/ml (group II). The probable pathogens not detected in this group were two (1.2%) by Autobac and MS-2 and three by AMS (1.9%). The average detection time for group II was 4.2 h by Autobac, 8.9 h by AMS, and 3.8 h by MS-2. Six hundred specimens had colony counts of <10(4) CFU/ml. Of these, 188 had colony counts equal to 10(3) and <10(4) CFU/ml (group III), and 412 cultures were below detectable limits by the standard plate method (group IV). Less than 37 and 15% of groups III and IV, respectively, were detected by instrumentation. Average detection times for groups III and IV were 4.6 and 4.8 h by Autobac, 10 and 11 h by AMS, and 4.2 and 4.4 h by MS-2. The cost of supplies and technical time with Gram stain, Autobac, and MS-2, when used as screening methods, were comparable and considerably less expensive than for the reference method. The AMS was the least expensive system when the cost for identifying probable pathogens was included.


The protective value of the colour and shape of the mountain katydid's antipredator defence.
Deimatic behaviour is performed by prey when attacked by predators as part of an antipredator strategy. The behaviour is part of a sequence that consists of several defences, for example they can be preceded by camouflage and followed by a hidden putatively aposematic signal that is only revealed when the deimatic behaviour is performed. When displaying their hidden signal, mountain katydids (Acripeza reticulata) hold their wings vertically, exposing striking red and black stripes with blue spots and oozing an alkaloid-rich chemical defence derived from its Senecio diet. Understanding differences and interactions between deimatism and aposematism has proven problematic, so in this study we isolated the putative aposematic signal of the mountain katydid's antipredator strategy to measure its survival value in the absence of their deimatic behaviour. We manipulated two aspects of the mountain katydid's signal, colour pattern and whole body shape during display. We deployed five kinds of clay models, one negative control and four katydid-like treatments, in 15 grids across part of the mountain katydid's distribution to test the hypothesis that their hidden signal is aposematic. If this hypothesis holds true, we expected that the models, which most closely resembled real katydids would be attacked the least. Instead, we found that models that most closely resembled real katydids were the most likely to be attacked. We suggest several ideas to explain these results, including that the deimatic phase of the katydid's display, the change from a camouflaged state to exposing its hidden signal, may have important protective value.


Combined hormonal contraceptives and the risk of venous and arterial thromboembolism and cardiovascular death: misuse of automated databases.
In December 2011, the US Food and Drug Administration (FDA) convened a public Advisory Committee meeting to review evidence from a study commissioned by the agency. An analysis of findings derived from four databases was published on the FDA website, and presented at the meeting. Among users of combined hormonal contraceptives containing ethinylestradiol (EE) plus drospirenone (DRSP) the risks of venous (VTE) and arterial thromboembolism (ATE) were higher than among users of older reference contraceptives containing other progestogens. The findings have now been published in a peer-reviewed journal. To evaluate the published evidence. Generally accepted epidemiological principles of causality are applied. The findings did not satisfy the criteria of time order, bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency, or biological plausibility. The best evidence continues to suggest that the increased risk of VTE in combined hormonal contraceptive users is dependent on the dose of estrogen, and independent of the progestogen used. The best evidence also suggests that DRSP does not increase the risk of ATE, and may reduce it.


Protein Phosphatase 1α enhances renal aldosterone signaling via mineralocorticoid receptor stabilization.
Stimulation of the mineralocorticoid receptor (MR) by aldosterone controls several physiological parameters including blood pressure, inflammation or metabolism. We previously showed that MR turnover constitutes a crucial regulatory step in the responses of renal epithelial cells to aldosterone. Here, we identified Protein Phosphatase 1 alpha (PP1α), as a novel cytoplasmic binding partner of MR that promotes the receptor activity. The RT-PCR expression mapping of PP1α reveals a high expression in the kidney, particularly in the distal part of the nephron. At the molecular level, we demonstrate that PP1α inhibits the ubiquitin ligase Mdm2 by dephosphorylation, preventing its interaction with MR. This results in the accumulation of the receptor due to reduction of its proteasomal degradation and consequently a greater aldosterone-induced Na+ uptake by renal cells. Thus, our findings describe an original mechanism involving a phosphatase in the regulation of aldosterone signaling and provide new and important insights into the molecular mechanism underlying the MR turnover.


Isolation and characterization of Mycoplasma sphenisci sp. nov. from the choana of an aquarium-reared jackass penguin (Spheniscus demersus).
Strain UCMJ was isolated from the choana of a jackass penguin (Spheniscus demersus) with recurrent mucocaseous choanal discharge. Isolation of this mycoplasma expands the known range of species hosting mycoplasmas. The name Mycoplasma sphenisci sp. nov. is proposed for this new species, for which strain UCMJ is the type strain.


Performance comparison between crystalline and co-amorphous salts of indomethacin-lysine.
The introduction of a highly water soluble amino acid as co-amorphous co-former has previously been shown to significantly improve the dissolution rate of poorly water soluble drugs. In this work, dry ball milling (DBM) and liquid assisted grinding (LAG) were used to prepare different physical forms of salts of indomethacin (IND) with the amino acid lysine (LYS), allowing the direct comparison of their solid-state properties to their in vitro performance. X-ray powder diffraction and Fourier-transformed infrared spectroscopy showed that DBM experiments led to the formation of a fully co-amorphous salt, while LAG resulted in a crystalline salt. Differential scanning calorimetry showed that the samples prepared by DBM had a single glass transition temperature (Tg) of approx. 100°C for the co-amorphous salt, while a new melting point (223°C) was obtained for the crystalline salt prepared by LAG. Intrinsic dissolution and powder dissolution studies demonstrated an increased dissolution rate of the drug in the co-amorphous salt compared to pure amorphous IND and also the crystalline drug-LYS salt. Furthermore, the co-amorphous IND-LYS salt presented long term physical stability in dry conditions at 25°C and 40°C. Overall, it has been shown that the co-amorphous form of a salt has a superior performance in comparison to a crystalline salt.


Ellagitannin consumption improves strength recovery 2-3 d after eccentric exercise.
Dietary supplementation with polyphenols,particularly ellagitannins, may attenuate the muscular damage experienced after eccentric exercise, producing delayed-onset muscle soreness. The purpose of this study was to determine whether ellagitannin supplementation from Wonderful variety pomegranate extract (POMx) improved recovery of skeletal muscle strength after eccentric exercise. Recreationally active males were randomized into a crossover design with either pomegranate extract (POMx) or placebo (PLA), each given during a period of 9 d.To produce delayed-onset muscle soreness, subjects performed two sets of 20 maximal eccentric elbow flexion exercises with one arm.Maximal isometric elbow flexion strength and muscle soreness as well as serum measures of creatine kinase, myoglobin, interleukin 6, and C-reactive protein were made at baseline and 2, 24, 48, 72, and 96 h after exercise. With both treatments, strength was similarly reduced 2 h after exercise (i.e., 72% of baseline), and recovery of strength was incomplete after 96 h (i.e., 91% of baseline).However, strength was significantly higher in POMx compared with that in PLA at 48 h (85.4% +/- 2.5% and 78.3% +/- 2.6%, P = 0.01) and 72 h (88.9% +/- 2.0% and 84.0% +/- 2.0%, P = 0.009) after exercise. Serum markers of inflammation and muscle damage did not provide insight regarding possible mechanisms. Supplementation with ellagitannins from pomegranate extract significantly improves recovery of isometric strength 2-3 d after a damaging eccentric exercise.


Racial/Ethnic Disparities in the Prevalence of Diabetes and Prediabetes by BMI: Patient Outcomes Research To Advance Learning (PORTAL) Multisite Cohort of Adults in the U.S.
To examine racial/ethnic disparities in the prevalence of diabetes and prediabetes by BMI category. In a consortium of three U.S. integrated health care systems, 4,906,238 individuals aged ≥20 years during 2012-2013 were included. Diabetes and prediabetes were ascertained by diagnosis and laboratory results; antihyperglycemic medications were also included for diabetes ascertainment. The age-standardized diabetes and prediabetes prevalence estimates were 15.9% and 33.4%, respectively. Diabetes but not prediabetes prevalence increased across BMI categories among all racial/ethnic groups (P for trend < 0.001). Racial/ethnic minorities reached a given diabetes prevalence at lower BMIs than whites; Hawaiians/Pacific Islanders and Asians had a diabetes prevalence of 24.6% (95% CI 24.1-25.2%) in overweight and 26.5% (26.3-26.8%) in obese class 1, whereas whites had a prevalence of 23.7% (23.5-23.8%) in obese class 2. The age-standardized prediabetes prevalence estimates in overweight among Hispanics (35.6% [35.4-35.7%]), Asians (38.1% [38.0-38.3%]), and Hawaiians/Pacific Islanders (37.5% [36.9-38.2%]) were similar to those in obese class 4 among whites (35.3% [34.5-36.0%]), blacks (36.8% [35.5-38.2%]), and American Indians/Alaskan Natives (34.2% [29.6-38.8%]). In adjusted models, the strength of association between BMI and diabetes was highest among whites (relative risk comparing obese class 4 with normal weight 7.64 [95% CI 7.50-7.79]) and lowest among blacks (3.16 [3.05-3.27]). The association between BMI and prediabetes was less pronounced. Racial/ethnic minorities had a higher burden of diabetes and prediabetes at lower BMIs than whites, suggesting the role of factors other than obesity in racial/ethnic disparities in diabetes and prediabetes risk and highlighting the need for tailored screening and prevention strategies.


Use of a non-medicated plaster in shoulder tendinopathies.
We assessed 20 shoulders with rotator cuff tendinopathy and partial tendon tears treated with FIT® plasters (far infrared technology). The criteria for inclusion were pain at night and during active shoulder movement. Patients with restricted passive movement (adhesive capsulitis) and complete tendon tears were excluded. Two different types of FIT® plasters were used according to the different power of action. Plasters were replaced after 7 days and dismissed after 15 days. The patients were assessed using the VAS pain scale and the Constant Murley score for function. The use of FIT® plasters have shown a certain effectiveness in activation of the endogenous analgesic action, with a role in alleviate painful symptoms and improve function in rotator cuff tendinopathies, without adverse events. On the base of the safety of this technology and promising results of our study, further studies should be encouraged to confirm its effectiveness, increasing the sample number and follow up so as to demonstrate definitely that the use of technologies, on which FIT® plasters is based, may be a valid alternative as "non-medicated pain relief".


Chronic Voluntary Morphine Intake Is Associated with Changes in Brain Structures Involved in Drug Dependence in a Rat Model of Polydrug Use.
Chronic opioid intake leads to several brain changes involved in the development of dependence, whereby an early hedonistic effect (liking) extends to the need to self-administer the drug (wanting), the latter being mostly a prefrontal-striatal function. The development of animal models for voluntary oral opioid intake represents an important tool for identifying the cellular and molecular alterations induced by chronic opioid use. Studies mainly in humans have shown that polydrug use and drug dependence are shared across various substances. We hypothesize that an animal bred for its alcohol preference would develop opioid dependence and further that this would be associated with the overt cortical abnormalities clinically described for opioid addicts. We show that Wistar-derived outbred UChB rats selected for their high alcohol preference additionally develop: (i) a preference for oral ingestion of morphine over water, resulting in morphine intake of 15 mg/kg/day; (ii) marked opioid dependence, as evidenced by the generation of strong withdrawal signs upon naloxone administration; (iii) prefrontal cortex alterations known to be associated with the loss of control over drug intake, namely, demyelination, axonal degeneration, and a reduction in glutamate transporter GLT-1 levels; and (iv) glial striatal neuroinflammation and brain oxidative stress, as previously reported for chronic alcohol and chronic nicotine use. These findings underline the relevance of polydrug animal models and their potential in the study of the wide spectrum of brain alterations induced by chronic morphine intake. This study should be valuable for future evaluations of therapeutic approaches for this devastating condition.


Rater methodology for stroboscopy: a systematic review.
Laryngeal endoscopy with stroboscopy (LES) remains the clinical gold standard for assessing vocal fold function. LES is used to evaluate the efficacy of voice treatments in research studies and clinical practice. LES as a voice treatment outcome tool is only as good as the clinician interpreting the recordings. Research using LES as a treatment outcome measure should be evaluated based on rater methodology and reliability. The purpose of this literature review was to evaluate the rater-related methodology from studies that use stroboscopic findings as voice treatment outcome measures. Systematic literature review. Computerized journal databases were searched for relevant articles using terms: stroboscopy and treatment. Eligible articles were categorized and evaluated for the use of rater-related methodology, reporting of number of raters, types of raters, blinding, and rater reliability. Of the 738 articles reviewed, 80 articles met inclusion criteria. More than one-third of the studies included in the review did not report the number of raters who participated in the study. Eleven studies reported results of rater reliability analysis with only two studies reporting good inter- and intrarater reliability. The comparability and use of results from treatment studies that use LES are limited by a lack of rigor in rater methodology and variable, mostly poor, inter- and intrarater reliability. To improve our ability to evaluate and use the findings from voice treatment studies that use LES features as outcome measures, greater consistency of reporting rater methodology characteristics across studies and improved rater reliability is needed.


Prevention of Infections in Cardiac Surgery study (PICS): study protocol for a pragmatic cluster-randomized factorial crossover pilot trial.
A wide range of prophylactic antibiotic regimens are used for patients undergoing open-heart cardiac surgery. This reflects clinical equipoise in choice and duration of antibiotic agents. Although individual-level randomized control trials (RCT) are considered the gold standard when evaluating the efficacy of an intervention, this approach is highly resource intensive and a cluster RCT can be more appropriate for testing clinical effectiveness in a real-world setting. We are conducting a factorial cluster-randomized crossover pilot trial in cardiac surgery patients to evaluate the feasibility of this design for a definite trial to evaluate the optimal duration and choice of perioperative antibiotic prophylaxis. Specifically, we will evaluate: (a) the non-inferiority of a single preoperative dose compared to prolonged prophylaxis and (b) the potential superiority of adding vancomycin to routine cefazolin in terms of preventing deep and organ/space sternal surgical site infections (s-SSIs). There are four strategies: (i) short-term cefazolin, (ii) long-term cefazolin, (iii) short-term cefazolin + vancomycin, and (iv) long-term cefazolin + vancomycin. These strategies are delivered in a different order in each health-care center participating in the trial. The centers are randomized to an order, and the current strategy becomes the standard operating procedure in that center during the study. The three feasibility outcomes include: (1) the proportion of patients receiving preoperative, intra-operative, and postoperative antibiotics according to the study protocol, (2) the proportion of completed follow-up assessments, and (3) a full and final assessment of the incidence of s-SSIs by the outcome adjudication committee. We believe that a cluster-randomized factorial crossover trial is an effective and feasible design for these research questions, allowing an evaluation of the clinical effectiveness in a real-world setting. A waiver of individual informed consent was considered appropriate by the research ethics boards in each participating site in Canada as long as an information letter with an opt-out option was provided. However, a waiver of consent was not approved at two sites in Germany and Switzerland, respectively. Clinicaltrials.gov, NCT02285140 . Registered on 15 October 2015.


Breast cancer stem cells: a new target for therapy.
Normal adult tissue stem cells awake from a dormant state to grow, differentiate, and regenerate damaged tissue. They also travel in the circulation and colonize distant organs at sites undergoing tissue repair. These same traits are utilized or co-opted by metastatic cancer cells. The cancer stem cell theory proposes that tumors emerge from a subpopulation of cancer cells that possess stem cell properties. This theory has profound implications for therapy. A small number of cancer stem cells may lie dormant following conventional therapy and tumor remission, only to re-emerge and regenerate the entire recurrent cancer. Consequently, it has been proposed that targeting cancer stem cells is the only way to obtain durable cancer treatment responses. Several strategies for targeting cancer stem cells have been proposed. Nevertheless, a number of issues must be investigated and resolved before effective treatments targeting cancer stem cells can enter clinical testing.


Identifying Wild Versus Cultivated Gene-Alleles Conferring Seed Coat Color and Days to Flowering in Soybean.
Annual wild soybean (G. soja) is the ancestor of the cultivated soybean (G. max). To reveal the genetic changes from soja to max, an improved wild soybean chromosome segment substitution line (CSSL) population, SojaCSSLP5, composed of 177 CSSLs with 182 SSR markers (SSR-map), was developed based on SojaCSSLP1 generated from NN1138-2(max)×N24852(soja). The SojaCSSLP5 was genotyped further through whole-genome resequencing, resulting in a physical map with 1366 SNPLDBs (SNP linkage-disequilibrium blocks), which are composed of more markers/segments, shorter marker length and more recombination breakpoints than the SSR-map and caused 721 new wild substituted segments. Using the SNPLDB-map, two loci co-segregating with seed-coat color (SCC) and six loci for days to flowering (DTF) with 88.02% phenotypic contribution were identified. Integrated with parental RNA-seq and DNA-resequencing, two SCC and six DTF candidate genes, including three previously cloned (G, E2 and GmPRR3B) and five newly detected ones, were predicted and verified at nucleotide mutant level, and then demonstrated with the consistency between gene-alleles and their phenotypes in SojaCSSLP5. In total, six of the eight genes were identified with the parental allele-pairs coincided to those in 303 germplasm accessions, then were further demonstrated by the consistency between gene-alleles and germplasm phenotypes. Accordingly, the CSSL population integrated with parental DNA and RNA sequencing data was demonstrated to be an efficient platform in identifying candidate wild vs. cultivated gene-alleles.


An effective biomedical document classification scheme in support of biocuration: addressing class imbalance.
Published literature is an important source of knowledge supporting biomedical research. Given the large and increasing number of publications, automated document classification plays an important role in biomedical research. Effective biomedical document classifiers are especially needed for bio-databases, in which the information stems from many thousands of biomedical publications that curators must read in detail and annotate. In addition, biomedical document classification often amounts to identifying a small subset of relevant publications within a much larger collection of available documents. As such, addressing class imbalance is essential to a practical classifier. We present here an effective classification scheme for automatically identifying papers among a large pool of biomedical publications that contain information relevant to a specific topic, which the curators are interested in annotating. The proposed scheme is based on a meta-classification framework using cluster-based under-sampling combined with named-entity recognition and statistical feature selection strategies. We examined the performance of our method over a large imbalanced data set that was originally manually curated by the Jackson Laboratory's Gene Expression Database (GXD). The set consists of more than 90 000 PubMed abstracts, of which about 13 000 documents are labeled as relevant to GXD while the others are not relevant. Our results, 0.72 precision, 0.80 recall and 0.75 f-measure, demonstrate that our proposed classification scheme effectively categorizes such a large data set in the face of data imbalance.


Macrophage NADPH oxidase flavocytochrome B localizes to the plasma membrane and Rab11-positive recycling endosomes.
Flavocytochrome b(558), the catalytic core of the phagocytic NADPH oxidase, mediates the transfer of electrons from NADPH to molecular oxygen to generate superoxide for host defense. Flavocytochrome b is a membrane heterodimer consisting of a large subunit gp91(phox) (NOX2) and a smaller subunit, p22(phox). Although in neutrophils flavocytochrome b has been shown to localize to the plasma membrane and specific granules, little is known about its distribution in macrophages. Using immunofluorescent staining and live cell imaging of fluorescently tagged gp91(phox) and p22(phox), we demonstrate in a Chinese hamster ovary cell model system and in RAW 264.7 and primary murine bone marrow-derived macrophages that flavocytochrome b is found in the Rab11-positive recycling endocytic compartment, as well as in Rab5-positive early endosomes and plasma membrane. Additionally, we show that unassembled p22(phox) and gp91(phox) subunits localize to the endoplasmic reticulum, which redistribute to the cell surface and endosomal compartments following heterodimer formation. These studies show for the first time that flavocytochrome b localizes to intracellular compartments in macrophages that recycle to the plasma membrane, which may act as a reservoir to deliver flavocytochrome b to the cell surface and phagosome membranes.


Paraoxonase 192 Gln/Arg gene polymorphism, coronary artery disease, and myocardial infarction in type 2 diabetes.
Paraoxonase is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. Its biallelic gene polymorphism at codon 192 (glutamine/arginine) has been associated with coronary artery disease (CAD). To further evaluate the role of this paraoxonase gene polymorphism for CAD in type 2 diabetes, we determined the paraoxonase genotype in 288 type 2 diabetic patients (170 with and 118 without angiographically documented CAD). The paraoxonase 192 Gln/Arg genotype was assessed using polymerase chain reaction followed by AlwI digestion. The frequency of the Gln allele was 0.656 in the CAD patients and 0.746 in the controls (chi2 = 5.36, P = 0.02). Compared with the Gln/Gln genotypes, the age-adjusted odds ratio for CAD was 1.78 (95% CI 1.08-2.96, P = 0.02) in subjects carrying at least one Arg allele. In the multivariate analysis, this association was even stronger after correction for the possible confounders age, sex, smoking history, and hypertension. Among current and former smokers, the odds ratio (OR) for having CAD among patients with at least one Arg allele was 3.58 (1.45-9.53, P < 0.01). The paraoxonase Arg allele was not associated with the history of myocardial infarction (OR 1.20 [0.73-1.99, NS]), but was with the extent of CAD (OR for three-vessel disease 1.92 [1.15-3.27, P = 0.01]). Our data indicate that the 192 Arg allele of the human paraoxonase gene is a risk factor for CAD but not myocardial infarction in type 2 diabetic patients, a risk factor further modified by cigarette smoking. This risk could possibly be explained by a reduced ability of the paraoxonase Arg isoform to protect lipoproteins against peroxidation.


Quality of life and its related factors in infertile couples.
Health related quality of life (QoL) has now been considered as a main tool for outcome measurement in infertility. The present study aimed to determine the association between general and specified QoL with different psychological aspects of self-esteem, social support, sexual satisfaction, and marital satisfaction in a sample of Iranian infertile couples. This cross-sectional study was conducted on 385 infertile couples referred to the Fatemieh Hospital in Hamadan City, western Iran in 2012.To measure the self-esteem, the Iseng test was used. The social support scaling developed by Cassidy and Long was used for assessment of social support. The sexual satisfaction was also assessed by the Lindaberg questionnaire. For assessing the general QoL state, the WHO-QoL-BREF and FertiQoL tools were employed. Self-esteem scores were lower in the couples with longer infertility duration. The social support mean score was lower in low income couples. Those with higher educational level, shorter infertility duration, and higher income were more satisfied from their marital relationships. Besides, we revealed that the previous failed efforts for treatment of infertility were adversely associated with the lower social support and sexual satisfaction. The higher educational level, higher monthly income, living in urban area, shorter duration of marriage and infertility, and male gender were associated with better. QoL status in the most components.Associations between QoL and self-esteem, social support, sexual satisfaction, and marital satisfaction were significant (P<0.05). The QoL status in infertile couples is directly associated with their self-esteem, social support, sexual satisfaction, and marital satisfaction.


Recent Advances in Biosorption of Copper and Cobalt by Filamentous Fungi.
Copper (Cu) and Cobalt (Co) are among the most toxic heavy metals from mining and other industrial activities. Both are known to pose serious environmental concerns, particularly to water resources, if not properly treated. In recent years several filamentous fungal strains have been isolated, identified and assessed for their heavy metal biosorption capacity for potential application in bioremediation of Cu and Co wastes. Despite the growing interest in heavy metal removal by filamentous fungi, their exploitation faces numerous challenges such as finding suitable candidates for biosorption. Based on current findings, various strains of filamentous fungi have high metal uptake capacity, particularly for Cu and Co. Several works indicate that Trichoderma, Penicillium, and Aspergillus species have higher Cu and Co biosorption capacity compared to other fungal species such as Geotrichum, Monilia, and Fusarium. It is believed that far more fungal species with even higher biosorption capability are yet to be isolated. Furthermore, the application of filamentous fungi for bioremediation is considered environmentally friendly, highly effective, reliable, and affordable, due to their low technology pre-requisites. In this review, we highlight the capacity of various identified filamentous fungal isolates for biosorption of copper and cobalt from various environments, as well as their future prospects.


A Simplified Approach for Restoration of Worn Dentition Using the Full Mock-up Concept: Clinical Case Reports.
Treatment of tooth wear has increased over the last two decades. However, the treatments involved have not been satisfactory to most patients, nor have they achieved the expected goal on some worn teeth. New approaches have emerged to reconstruct full arches in a minimally invasive way that take advantage of developments in the field of adhesive dentistry. These new concepts constitute a revolution in dentistry and their application requires adapted techniques and training. The purpose of this article is to suggest a precise and reproducible method that simplifies the treatment of worn dentition. A wax-up and a mock-up are primarily used to design the esthetic outcome and then used as a guide for the preparation of anterior teeth or the occlusal surfaces of posterior teeth. This not only provides the exact new vertical dimension of occlusion but serves as a guide for precisely controlling occlusal preparation simultaneously with buccal preparation. The classical cavity design for a partial bonded restoration on posterior worn dentition is also reviewed. The authors believe that during the preparation of the occlusal surfaces of the posterior teeth surfaces, the marginal ridges must be preserved to reduce the biologic cost and mechanical stress leading to fracture. A new type of thin and reduced restoration called tabletop is presented.


A selective glial barrier at motor axon exit points prevents oligodendrocyte migration from the spinal cord.
Nerve roots have specialized transition zones that permit axon extension but limit cell movement between the CNS and PNS. Boundary cap cells prevent motor neuron soma from following their axons into the periphery, thereby contributing to a selective barrier. Transition zones also restrict movement of glial cells. Consequently, axons that cross the CNS-PNS interface are insulated by central and peripheral myelin. The mechanisms that prevent the migratory progenitors of oligodendrocytes and Schwann cells, the myelinating cells of the CNS and PNS, respectively, from crossing transition zones are not known. Here, we show that interactions between myelinating glial cells prevent their movements across the interface. Using in vivo time-lapse imaging in zebrafish we found that, in the absence of Schwann cells, oligodendrocyte progenitors cross ventral root transition zones and myelinate motor axons. These studies reveal that distinct mechanisms regulate the movement of axons, neurons, and glial cells across the CNS-PNS interface.