Group B streptococcal bacteriuria during pregnancy as a risk factor for maternal intrapartum colonization: a prospective cohort study.
Current evidence is inconclusive regarding the intrapartum administration of chemoprophylaxis, merely based on the presence of group B streptococcal (GBS) bacteriuria of any colony count, in the prevention of early-onset neonatal GBS infection. The aim of this study was to assess whether GBS bacteriuria is a risk factor for intrapartum colonization (IPC) regardless of urinary concentration or the results of late third-trimester rectovaginal screening cultures (RVSCs). Six hundred and eight pregnant women, with urine specimens cultured between May 2011 and May 2013, were enrolled in this prospective cohort study. RVSCs were available for 582 women and intrapartum rectovaginal cultures for 246. The prevalence of GBS bacteriuria and positive RVSCs was 10.8 and 16.5 %, respectively. The frequency of IPC was 15.9 % (39/246). Sensitivity, specificity, positive and negative predictive values of urine culture and of RVSC in predicting GBS IPC were 41, 94.7, 59.3 and 89.5 %, and 76.9, 95.4, 76.9 and 95.4 %, respectively. GBS bacteriuria was significantly associated with IPC, overall [relative risk (RR) 5.6] and in women with negative RVSC (RR 8.5), with bacteriuria <104 c.f.u. ml-1 (RR 5.9) or when both circumstances coexisted (RR 8.9). The urinary colony count was <104 c.f.u. ml-1 in 13 of the 16 women with GBS bacteriuria and IPC. GBS bacteriuria is a risk factor for IPC, irrespective of urinary GBS concentration or of colonization status at late gestation. Therefore, microbiology laboratories should search, and report, GBS of any colony count in urine from pregnant women, and not only in the presence of ≥104 c.f.u. ml-1 as the 2010 CDC guidelines recommend.


Distribution of nitric oxide synthase activity in arterioles and venules of rat and human intestine.
NO is produced within peripheral blood vessels through the action of the differentially distributed constitutive and inducible NO synthase isoforms in the vessel wall. As in other sites in the periphery, NO exerts local vasodilatory actions in the gastrointestinal microvasculature and is proposed to play a role in enteric vasomotor regulation. Using NO synthase histochemistry and endothelial cell immunohistochemistry, we provide the first anatomic evidence of NO synthesis in both endothelial and smooth muscle cells of submucosal blood vessels in the rat and human intestine. The findings of this study indicate that 1) as in the periphery, both the endothelial and vascular smooth muscle cells of the microvessels irrigating the rat and human intestinal wall possess NO synthesis potential, 2) NO synthase activity is predominantly localized to discrete subcellular patches, and 3) the source of NO within the vascular wall, either intimal or medial, should be a consideration in future studies in terms of the relative contribution of these sources of vasomotor tone in the rat and human gut wall.


Epstein-Barr virus infection in chronically inflamed periapical granulomas.
Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.


What is the role of quality circles in strategies to optimise antibiotic prescribing? A pragmatic cluster-randomised controlled trial in primary care.
To evaluate the effect on antibiotic prescribing of an intervention in existing local quality circles promoting an evidence-based guideline for acute rhinosinusitis. A pragmatic cluster-randomised controlled trial comparing standard dissemination of the guideline by mail with an additional strategy using quality circles. General practice in Flanders, Belgium. General practitioners (GPs) in 18 local quality circles were randomly allocated to two study arms. All GPs received the guideline by mail. GPs in the nine quality circles allocated to the intervention arm received an additional group intervention, which consisted of one self-led meeting using material introduced to the group moderator by a member of the research team. Adherence to the guideline was measured as differences in the proportion of antibiotic prescriptions, including the choice of antibiotic, between the two study arms after the intervention period. GPs registered their encounters with patients presenting with signs and symptoms of acute rhinosinusitis in a booklet designed for the study. A total of 75 doctors (29% of GPs in the participating quality circles) registered 408 consultations. In the intervention group, 56.9% of patients received an antibiotic compared with 58.3% in the control group. First-choice antibiotics were issued in 34.5% of antibiotic prescriptions in the intervention group compared with 29.4% in the control group. After adjusting for patient and GP characteristics, the ORadj for antibiotics prescribed in the intervention arm compared with the control arm was 0.63 (95% CI 0.29 to 1.37). There was no effect on the choice of antibiotic (ORadj 1.07, 95% CI 0.34 to 3.37). A single intervention in quality circles of GPs integrated in the group's normal working procedure did not have a significant effect on the quality of antibiotic prescribing. More attention to the context and structure of primary care practice, and insight into the process of self-reflective learning may provide clues to optimise the effectiveness of quality circles.


Endothelial progenitor cell therapy for atherosclerosis: the philosopher's stone for an aging population?
Much of the increased risk for atherosclerosis progression with age may be a result of age-related declines in the capacity of precursor cells to repair damage in the arterial endothelium. To estimate the impact of progenitor cell therapy for atherosclerosis on cardiovascular disease (CVD) mortality, life expectancy, and survival, as compared with the lifetime control of conventional risk factors, we modeled the health effects of bone marrow-derived endothelial progenitor cell therapy using data from the 1950 to 1996 follow-up of the Framingham Heart Study. To model cardiovascular disease mortality, we assumed that progenitor cell therapy was applied at age 30, with the effect assumed to be a 10-year delay in atherosclerosis progression. Age projections were constructed analytically using the stochastic process model for risk factor dynamics and mortality and microsimulation techniques. We considered three types of interventions: (i) keeping risk factors within selected limits to model current clinical recommendations; (ii) an age shift of 10 years to model the effects of progenitor cell therapy; and (iii) elimination of a competing risk (such as cancer). Our study suggests that progenitor cell therapy might increase life expectancy in the population as much as the complete elimination of cancer (in females, an additional 3.67 versus 3.37 years; in males, an additional 5.94 versus 2.86 years, respectively).


Exploring the relevance of autonomy and relatedness for mental health in healthy and depressed women from two different cultures: when does culture matter?
It is well known that the absence of both autonomy and social support (relatedness) are two important etiologic pathways to major depressive disorder (MDD). However, cross-cultural researchers state that the implications of autonomy and relatedness for mental health vary across cultures. To test these assumptions, the current study investigated the relevance of autonomy and relatedness for mental health in healthy and depressed women from two different cultures (Germans and Turkish immigrants in Germany). One hundred and eight (108) women were evaluated for their levels of autonomy/relatedness satisfaction, for overall psychopathological complaints including depression, for affectivity and for perceived loneliness through self-report measures. Among healthy groups, relatedness satisfaction predicted better mental health in Turkish women, whereas in German women, autonomy satisfaction was the better mental health predictor. Within depressed groups however, cultural differences in mental health outcomes regarding autonomy were no longer evident. Autonomy was associated with higher levels of mental health in Turkish as well as in German patients. Our findings indicate that the relationship between autonomy and mental health is culture-specific in healthy women, but disappears in depressed women. These findings are discussed with consideration of clinical implications and an outlook regarding further research.


Social and psychological burden of dysphagia: its impact on diagnosis and treatment.
The social and psychological impact of dysphagia has not been routinely reported in large studies. We sought to determine the effects of dysphagia on broad measures of the quality of life of patients and to explore the relationship between the psychological handicaps of the condition and the frequency of diagnosis and treatment. A total of 360 patients selected on the basis of known subjective dysphagia complaints, regardless of origin, in nursing homes and clinics in Germany, France, Spain, and the United Kingdom were interviewed using an established questionnaire. Qualitative interviews with a total of 28 health professionals were conducted to improve understanding of the patient data in the context of each country. Over 50% of patients claimed that they were "eating less" with 44% reporting weight loss during the preceding 12 months. Thirty-six percent of patients acknowledged receiving a confirmed diagnosis of dysphagia; only 32% acknowledged receiving professional treatment for it. Most people with dysphagia believe their condition to be untreatable; only 39% of the sufferers believed that their swallowing difficulties could be treated. Eighty-four percent of patients felt that eating should be an enjoyable experience but only 45% actually found it so. Moreover, 41% of patients stated that they experienced anxiety or panic during mealtimes. Over one-third (36%) of patients reported that they avoided eating with others because of their dysphagia. In a largely elderly population that might accept dysphagia as an untreatable part of the aging process, clinicians need to be aware of the adverse effects of dysphagia on self-esteem, socialization, and enjoyment of life. Careful questioning should assess the impact of the condition on each patient's life, and patients should be educated on their choices for treatment in the context of any coexisting illness. Awareness of the condition, diagnostic procedures, and treatment options must be increased in society and among the medical profession.


GaAs-based multiple-quantum-well spatial light modulators fabricated by a wafer-scale process.
The design, fabrication, and characterization of large, two-dimensional multiple-quantum-well modulator arrays are presented. Such arrays present a speed advantage compared with competing technologies such as liquid crystals and micromirrors, which are intrinsically limited to the kilohertz range. We discuss the design compromises to reach high-contrast, low-voltage swing optical structures compatible with complementary metal-oxide semiconductor-based integrated circuits and present experimental results. Contrast ratio of 5:1 (limited by the fill factor), variations in uniformity below 1nm, and frame rates in excess of 10kHz are demonstrated. Technology maturity for volume production is also discussed.


TRPV4 as a therapeutic target for joint diseases.
Biomechanical factors play a critical role in regulating the physiology as well as the pathology of multiple joint tissues and have been implicated in the pathogenesis of osteoarthritis. Therefore, the mechanisms by which cells sense and respond to mechanical signals may provide novel targets for the development of disease-modifying osteoarthritis drugs (DMOADs). Transient receptor potential vanilloid 4 (TRPV4) is a Ca(2+)-permeable cation channel that serves as a sensor of mechanical or osmotic signals in several musculoskeletal tissues, including cartilage, bone, and synovium. The importance of TRPV4 in joint homeostasis is apparent in patients harboring TRPV4 mutations, which result in the development of a spectrum of skeletal dysplasias and arthropathies. In addition, the genetic knockout of Trpv4 results in the development of osteoarthritis and decreased osteoclast function. In engineered cartilage replacements, chemical activation of TRPV4 can reproduce many of the anabolic effects of mechanical loading to accelerate tissue growth and regeneration. Overall, TRPV4 plays a key role in transducing mechanical, pain, and inflammatory signals within joint tissues and thus is an attractive therapeutic target to modulate the effects of joint diseases. In pathological conditions in the joint, when the delicate balance of TRPV4 activity is altered, a variety of different tools could be utilized to directly or indirectly target TRPV4 activity.


Anti-cancer gallotannin penta-O-galloyl-beta-D-glucose is a nanomolar inhibitor of select mammalian DNA polymerases.
Penta-1,2,3,4,6-O-galloyl-beta-D-glucose (PGG) has been shown by us and others to inhibit the in vivo growth of human prostate cancer (PCa) xenografts in athymic nude mice and mouse lung cancer allograft in syngenic mice without evident adverse effect on their body weight. We observed a rapid inhibition of DNA synthesis in S-phase cells in PGG-exposed cancer cells and in PGG-treated isolated nuclei. The purpose of the present study was to test the hypothesis that PGG inhibits DNA replicative synthesis through a direct inhibition of one or more DNA polymerases (pols). Using purified pols, we show that PGG exhibited a selective inhibition against the activities of B-family replicative pols (alpha, delta and epsilon) and Y-family (eta, iota and kappa) of bypass synthesis pols, and the inhibitory effect of PGG on pol alpha was the strongest with IC(50) value of 13 nM. PGG also inhibited pol beta, but the potency was an order of magnitude less than against pol alpha. PGG inhibition of pol alpha and kappa activity was non-competitive with respect to the DNA template-primer and the dNTP substrate; whereas it inhibited pol beta competitively. Docking simulation on pol beta, which is the only mammalian pol with solved crystal structure, suggests several favorable interactions with the catalytic pocket/binding site for the incoming dNTP. These results support PGG as a novel inhibitor of select families of mammalian pols by distinct mechanisms, and suggest that the potent pol inhibition may contribute to its anti-cancer efficacy.


Platelet Indices in the Diagnosis of Ventriculoperitoneal Shunt Infection in Children.
Ventriculoperitoneal shunt infection (VPSI) is one of the main causes of mortality and morbidity in hydrocephalus. Platelet indices, mean platelet volume (MPV) and platelet distribution width (PDW) have been evaluated for some infectious diseases. In this study we aimed to investigate whether MPV and PDW values are decisive for the diagnosis of VPSI in children. Charts of VPSI from 2012 to 2015 were reviewed retrospectively. Twenty-five ventriculoperitoneal shunt infected patients and 25 healthy children as the control group were included in the study. Platelet indices were recorded. A total of 25 VPSI patients and 25 healthy children were enrolled in the study. Significant differences were detected between the MPV and PDW values in the two groups (p < 0.001). ROC curve analysis suggested a cut off point for MPV as below 9.2 fl (smaller values indicate patients) for the diagnosis of VPSI, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 80%, 92%, 91% and 82%, respectively. For PDW, the cut-off point was 12.25 (larger values indicate pathology) for diagnosis of VPSI, with sensitivity, specificity, PPV and NPV of 68%, 80%, 77% and 71%, respectively. Our results suggest that MPV and PDW can be used for the diagnosis of VPSI in children with an accuracy of at least 75%. Moreover, MPV"s specificity is higher than the other platelet parameters and leucocyte count.


Evaluation of the Bio-Rad BioPlex Measles, Mumps, Rubella, and Varicella-Zoster Virus IgG multiplex bead immunoassay.
The goal of this study was to compare the BioPlex 2200 measles, mumps, rubella, and varicella-zoster virus (MMRV) IgG multiplex assays (Bio-Rad Laboratories, Hercules, CA) to routine testing by enzyme immunoassay (EIA). Serum specimens (n = 500) submitted to our reference laboratory for routine MMRV IgG testing by EIA were also tested by the BioPlex assays. Following testing, the BioPlex measles, mumps, rubella, and varicella-zoster virus assays demonstrated agreements of 91.6% (95% confidence interval [CI], 88.8% to 93.7%), 94.2% (95% CI, 91.7% to 95.7%), 94.4% (95% CI, 92.0% to 96.1%), and 91.8% (95% CI, 89.0% to 93.9%), respectively, compared to the results of EIA. Timing studies showed that the BioPlex MMRV assay could provide complete analysis of 100 serum specimens in 1.7 h, compared to 5.5 h by EIA. These data indicate that the BioPlex MMRV IgG assays exhibit comparable performance (93% overall agreement [1,860/2,000 results]; κ = 0.67) to routine testing by EIA. The BioPlex assays allow for the simultaneous detection of all four analytes, thereby eliminating potential aliquot errors and reducing turnaround time.


Global variations of large megathrust earthquake rupture characteristics.
Despite the surge of great earthquakes along subduction zones over the last decade and advances in observations and analysis techniques, it remains unclear whether earthquake complexity is primarily controlled by persistent fault properties or by dynamics of the failure process. We introduce the radiated energy enhancement factor (REEF), given by the ratio of an event's directly measured radiated energy to the calculated minimum radiated energy for a source with the same seismic moment and duration, to quantify the rupture complexity. The REEF measurements for 119 large [moment magnitude (Mw) 7.0 to 9.2] megathrust earthquakes distributed globally show marked systematic regional patterns, suggesting that the rupture complexity is strongly influenced by persistent geological factors. We characterize this as the existence of smooth and rough rupture patches with varying interpatch separation, along with failure dynamics producing triggering interactions that augment the regional influences on large events. We present an improved asperity scenario incorporating both effects and categorize global subduction zones and great earthquakes based on their REEF values and slip patterns. Giant earthquakes rupturing over several hundred kilometers can occur in regions with low-REEF patches and small interpatch spacing, such as for the 1960 Chile, 1964 Alaska, and 2011 Tohoku earthquakes, or in regions with high-REEF patches and large interpatch spacing as in the case for the 2004 Sumatra and 1906 Ecuador-Colombia earthquakes. Thus, combining seismic magnitude Mw and REEF, we provide a quantitative framework to better represent the span of rupture characteristics of great earthquakes and to understand global seismicity.


Fully enzymatic method for determining 1,5-anhydro-D-glucitol in serum.
We have developed a fully enzymatic method to measure 1,5 anhydro-D-glucitol (1,5-AG) in serum through use of pyranose oxidase (PROD: EC 188.8.131.52), glucokinase (EC 184.108.40.206), and an ATP-regenerating system. In a previous report (Clin Chem 1989;35:2039-43) the glucose interfering with the measurement of 1,5-AG was removed with a minicolumn. In the method used here, glucokinase and an ATP-regenerating system efficiently convert glucose to the unreactive compound, glucose 6-phosphate, making the method selective for 1,5-AG. The hydrogen peroxide produced in the oxidation of 1,5-AG by PROD is detected with a standard enzymatic color-developing system. The within-run and day-to-day precision (CV) of this method was 0.52-1.29% and 1.17-4.48%, respectively. The correlation (r) between the results obtained with our proposed method (y) and those obtained with the mini-column method (x) was 0.998 (y = 1.007x + 0.493 mg/L; n = 100; Sy/x = 0.641 mg/L). This newly developed method allows quicker and easier measurement of serum 1,5-AG than previously described methods.


[Influence of a high fat diet on the rabbit's heart muscle].
Changes having been caused during the application of high fat diet were estimated in the rabbit's heart muscle. The animals were divided into three groups. The control group was given the basic diet. The second group received high fat diet, while the third group got high fat diet and one of the 5 hypolipemic drugs (ME3, ME4, clofibrate, diprophylline, cernitin). The specimens from the left ventricle of the heart muscle were evaluated under light microscope for carrying out a number of histological and histochemical examinations, use was also made of electron microscopy. On the basis of the performed studies it has been ascertained that: 1) atherogenic diet in rabbits causes injury involving all the layers of the heart; 2) mechanism originating changes depends on vascular bed diminution, and on primary lesion of the mitochondrial system in cardiomyocytes; 3) the used drugs with hypolipemic action fail to exert favourable influence upon the image of the damaged heart muscle.


Zebrafish models of skeletal dysplasia induced by cholesterol biosynthesis deficiency.
Human disorders of the post-squalene cholesterol biosynthesis pathway frequently result in skeletal abnormalities, yet our understanding of the mechanisms involved is limited. In a forward-genetic approach, we have found that a late-onset skeletal mutant, named kolibernu7 , is the result of a cis-acting regulatory mutation leading to loss of methylsterol monooxygenase 1 (msmo1) expression within pre-hypertrophic chondrocytes. Generated msmo1nu81 knockdown mutation resulted in lethality at larval stage. We demonstrated that this is a result of both cholesterol deprivation and sterol intermediate accumulation by creating a mutation eliminating activity of Lanosterol synthase (Lss). Our results indicate that double lssnu60;msmo1nu81 and single lssnu60 mutants survive significantly longer than msmo1nu81 homozygotes. Liver-specific restoration of either Msmo1 or Lss in corresponding mutant backgrounds suppresses larval lethality. Rescued mutants develop dramatic skeletal abnormalities, with a loss of Msmo1 activity resulting in a more-severe patterning defect of a near-complete loss of hypertrophic chondrocytes marked by col10a1a expression. Our analysis suggests that hypertrophic chondrocytes depend on endogenous cholesterol synthesis, and blocking C4 demethylation exacerbates the cholesterol deficiency phenotype. Our findings offer new insight into the genetic control of bone development and provide new zebrafish models for human disorders of the cholesterol biosynthesis pathway.


The role of replication bypass pathways in dicentric chromosome formation in budding yeast.
Gross chromosomal rearrangements (GCRs) are large scale changes to chromosome structure and can lead to human disease. We previously showed in Saccharomyces cerevisiae that nearby inverted repeat sequences (∼20-200 bp of homology, separated by ∼1-5 kb) frequently fuse to form unstable dicentric and acentric chromosomes. Here we analyzed inverted repeat fusion in mutants of three sets of genes. First, we show that genes in the error-free postreplication repair (PRR) pathway prevent fusion of inverted repeats, while genes in the translesion branch have no detectable role. Second, we found that siz1 mutants, which are defective for Srs2 recruitment to replication forks, and srs2 mutants had opposite effects on instability. This may reflect separate roles for Srs2 in different phases of the cell cycle. Third, we provide evidence for a faulty template switch model by studying mutants of DNA polymerases; defects in DNA pol delta (lagging strand polymerase) and Mgs1 (a pol delta interacting protein) lead to a defect in fusion events as well as allelic recombination. Pol delta and Mgs1 may collaborate either in strand annealing and/or DNA replication involved in fusion and allelic recombination events. Fourth, by studying genes implicated in suppression of GCRs in other studies, we found that inverted repeat fusion has a profile of genetic regulation distinct from these other major forms of GCR formation.


Effect of aspiration of the preovulatory follicle on luteinization, corpus luteum function, and peripheral plasma gonadotropin concentrations in the mare.
Follicular fluid from small- to medium-sized follicles has been shown to have an inhibiting effect on luteinization of granulosa cells in vitro. This study was conducted to investigate the effect of in vivo removal of follicular fluid on luteinization, peripheral gonadotropin concentrations, and ovulation of secondary follicles in the mare. Follicular fluid was aspirated from the preovulatory follicles of mares when the diameter of the follicle was 30-34 mm (Group A), 35-39 mm (Group B), or 40-44 mm (Group C). Mares in Group D served as controls and the preovulatory follicle was not aspirated. Mares in Group A had a significantly earlier rise in peripheral progesterone concentrations than did controls. There was no difference in duration of progesterone secretion or peak progesterone production between groups. LH and FSH values were significantly higher for mares in Groups A and B than for control mares. Mares in Group A tended to have a higher incidence of secondary ovulations than did mares in other groups. These data support the in vitro findings that follicular fluid from small- to medium-sized follicles may contain a luteinization inhibitor, and indicate that presence of follicular fluid during the final days of follicular maturation is not essential for development of a normal CL.


Netcombin: An algorithm for constructing optimal phylogenetic network from rooted triplets.
Phylogenetic networks construction is one the most important challenge in phylogenetics. These networks can present complex non-treelike events such as gene flow, horizontal gene transfers, recombination or hybridizations. Among phylogenetic networks, rooted structures are commonly used to represent the evolutionary history of a species set, explicitly. Triplets are well known input for constructing the rooted networks. Obtaining an optimal rooted network that contains all given triplets is main problem in network construction. The optimality criteria include minimizing the level or the number of reticulation nodes. The complexity of this problem is known to be NP-hard. In this research, a new algorithm called Netcombin is introduced to construct approximately an optimal network which is consistent with input triplets. The innovation of this algorithm is based on binarization and expanding processes. The binarization process innovatively uses a measure to construct a binary rooted tree T consistent with the approximately maximum number of input triplets. Then T is expanded using a heuristic function by adding minimum number of edges to obtain final network with the approximately minimum number of reticulation nodes. In order to evaluate the proposed algorithm, Netcombin is compared with four state of the art algorithms, RPNCH, NCHB, TripNet, and SIMPLISTIC. The experimental results on simulated data obtained from biologically generated sequences data indicate that by considering the trade-off between speed and precision, the Netcombin outperforms the others.


Sleep disorders in preschoolers: prevalence and comorbidity with psychiatric symptoms.
This study provides data on the prevalence of diagnosable sleep disorders in preschoolers and examined the relationship between specific sleep disorders and a range of DSM-4-defined psychiatric symptoms. All children born in 2003 or 2004 in Trondheim, Norway, who attended regular community health checkups for 4 year olds were asked to participate (97.2% attendance; 82.0% consent rate, N = 2475). A screen-stratified subsample of 1250 children was recruited to participate in an additional comprehensive study that included a structured diagnostic interview (the Preschool-Age Psychiatric Assessment). Nine hundred ninety-five parents (79.6%) completed the interview. The estimated sleep disorder rate was 19.2%. Rates of specific disorders were as follows: primary insomnia (16.6%), primary hypersomnia (0.8%), nightmare disorder (2.2%), and sleepwalking disorder (0.7%). When adjusted for a range of common psychiatric symptoms, primary insomnia was specifically related to symptoms of depression, generalized anxiety disorder, separation anxiety, and specific phobia. When sleep problems were excluded as a symptom of depression, the association between depression and primary insomnia was no longer significant. Nightmare disorder was significantly related to generalized anxiety disorder. This first study of the prevalence and comorbidity of diagnosable sleep disorders in preschoolers indicates that primary insomnia is common in young children, whereas other sleep disorders are rare. Sleep disorders are related to psychiatric symptoms, particularly symptoms of anxiety disorders.


Experimental and credentialing capital: an adaptable framework for facilitating science outreach for underrepresented youth.
Increasing the numbers of black, latino and native youth in STEM careers is both an important way to reduce poverty in low income communities, and a contribution to the diversity of thought and experience that drives STEM research. But underrepresented youth are often alienated from STEM. Two new forms of social capital have been identified that can be combined to create a learning environment in which students and researchers can meet and explore an area of shared interest. Experimental capital refers to the intrinsic motivation that students can develop when they learn inquiry techniques for exploring topics that they feel ownership over. Credentialing capital denotes a shared interest and ability between all parties engaged in the experimental endeavor. These two forms of social capital form an adaptable framework for researchers to use to create effective outreach programs. In this case study sports biomechanics was utilized as the area of shared interest and understanding the slam dunk was used as experimental capital.


The glorious years leading Doppler flow to the heart, the odyssey of the pioneers!
This review pays tribute to those pioneers in Doppler flow during an early and exciting period ranging from the end of the 1960s to the 1990s. Three major 'approaches' contributed to what is nowadays built into every patient's investigation. The source was Daniel Kalmanson, who developed flow directionality, assigning a physiological meaning to the recordings. This was the first time Doppler flow was used on the heart, providing new insights in cardiac pathophysiology. The second approach relied on the Norwegian group who applied the laws of physics to fluid dynamics. Simplification of the formula provided a new non-invasive approach enabling quantification of valvular lesions and haemodynamic measurements. This new tool pushed back previous routine catheterisation. To crown it all, the introduction of colour Doppler flow, mainly relying on the Japanese groups, overcame the long-lasting scepticism of the scientific community: cardiologists started to "believe" in the Doppler technique. Other innovative pioneers around the world joined the three groups to develop this new field of cardiology. At the turning of the new millennium, the Doppler technique is mature, through a strong methodology. Convergence of the three original approaches for mutual benefit, constant update of examination modalities according to improved technology, and new insights into cardiac dynamics, are the three cornerstones supporting this methodology. They should contribute to keep it alive and efficient, independently of the imaging modality of the future.


Prevalence and correlates of intimate partner violence victimization among men and women entering substance use disorder treatment.
Intimate partner violence victimization was examined in men (N = 4,459) and women (N = 1,774) entering substance use disorder treatment. Nearly 1 in 2 women and 1 in 10 men reported lifetime victimization by an intimate partner. Entering treatment for alcohol, as compared to drug abuse and history of childhood abuse, were each associated with intimate partner violence victimization. Victimization by an intimate partner was also associated with mental health problems, including depression, anxiety, and attempted suicide. Although victimization was linked to physical health problems, the nature of these problems varied by gender. Women and men with a history of intimate partner victimization present to substance use disorder treatment with a complex array of mental and physical health problems.


[Response to antibiotics of Proteus strains isolated from different types of clinical material].
The data on the study of the antibiotic response to 42 Proteus strains isolated from different sources in the hospitals of Kharkov are presented. The isolates belonged to P. mirabilis and P. vulgaris. Many strains were resistant to gentamicin, ampicillin and carbenicillin irrespective of the isolation source. 58.0 and 90.3 per cent of the strains isolated from patients with intestinal infections, 66.6 and 100 per cent of the strains isolated from patients with otitis, 33.3 and 66.6 per cent of the strains isolated from patients with bronchopulmonary affections and 100 and 100 per cent of the strains isolated from patients with urological diseases were resistant to gentamicin and carbenicillin, respectively. As for ampicillin, the respective figures were 74.2, 66.6, 66.6 and 100 per cent. All the strains of P. vulgaris isolated from patients with otitis, urological diseases and bronchopulmonary affections were resistant to ampicillin. The MIC of carbenicillin for all the strains except 4 indole-positive strains of P. vulgaris isolated from the faeces and bronchial excreta was much higher than the borderline values.


Mapping climate change vulnerabilities to infectious diseases in Europe.
The incidence, outbreak frequency, and distribution of many infectious diseases are generally expected to change as a consequence of climate change, yet there is limited regional information available to guide decision making. We surveyed government officials designated as Competent Bodies for Scientific Advice concerning infectious diseases to examine the degree to which they are concerned about potential effects of climate change on infectious diseases, as well as their perceptions of institutional capacities in their respective countries. In 2007 and 2009/2010, national infectious disease experts from 30 European Economic Area countries were surveyed about recent and projected infectious disease patterns in relation to climate change in their countries and the national capacity to cope with them. A large majority of respondents agreed that climate change would affect vector-borne (86% of country representatives), food-borne (70%), water-borne (68%), and rodent-borne (68%) diseases in their countries. In addition, most indicated that institutional improvements are needed for ongoing surveillance programs (83%), collaboration with the veterinary sector (69%), management of animal disease outbreaks (66%), national monitoring and control of climate-sensitive infectious diseases (64%), health services during an infectious disease outbreak (61%), and diagnostic support during an epidemic (54%). Expert responses were generally consistent with the peer-reviewed literature regarding the relationship between climate change and vector- and water-borne diseases, but were less so for food-borne diseases. Shortcomings in institutional capacity to manage climate change vulnerability, identified in this assessment, should be addressed in impact, vulnerability, and adaptation assessments.


The environment of the successful clinician-scientist.
The number of clinician-scientists has declined over the past several decades and evidence suggests this trend also applies to orthopaedic surgery. A previous study identified only 64 principle investigator orthopaedic surgeons with over 100,000 dollars of NIH funding from 1992 to 2001, during which funding declined for orthopaedic surgeons. We surveyed 58 of these 64 surgeons (six were retired) to ascertain aspects of their environment that might lead to success and what obstacles they encountered. The common definition of a clinician-scientist was an individual who obtained external funding for research. With a response rate of 79%, 26 of 40 (65%) began their research careers before residency. Nearly half had additional specialized training in research and most thought at least 6 months training was important. Thirty four of 46 respondents (74%) percent spent less than 20% of their time in research but 43 of 45 (95%) thought at least 30% ideal. Twenty five of 43 (58%) had unshared laboratory space and those without typically share with three or more scientists. Twenty eight of 43 (65%) believed their level of external funding adequate. Twenty of 46 (43%) believed their colleagues resented the time they spent in research. Demands on clinical time continue to be a major impediment to orthopaedic clinician-scientists. The orthopaedic community must develop supportive environments for clinician-scientists.


The Association of Diet and Exercise With Body Composition in Pediatric Crohn's Disease.
In pediatric Crohn's disease, fat mass improves over time with treatment, but lean mass deficits persist. This observational study of the associations of physical activity and dietary intake with lean mass and muscle strength in children with Crohn's disease was ancillary to a previously reported randomized clinical trial of an intervention to improve bone health. In this study, 138 participants were followed at baseline and at 6, 12, and 24 months with evaluation of lean and fat mass using DXA, muscle strength (peak torque), Crohn's characteristics, dietary intake, time in moderate to vigorous physical activity (MVPA), and serum insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-alpha (TNF-α). Race- and sex-specific Z-scores for leg lean mass and whole body fat mass were generated. Quasi least square regression evaluated determinants of changes in body composition and muscle strength. Leg lean mass and muscle strength were positively associated with time in MVPA (P < 0.05) and negatively associated with increasing clinical disease activity (P < 0.05). Both leg lean mass and strength were positively associated with IGF-1 Z-score (P ≤ 0.03) but negatively associated with serum TNF-α (P ≤ 0.04). Neither lean mass nor muscle strength was associated with caloric or protein intake. Persistence of lean mass deficits was related to ongoing Crohn's disease activity but improved with greater time spent in moderate to vigorous physical activity. Future trials are needed to evaluate the efficacy of physical activity in improving lean mass in pediatric Crohn's disease.


Dialysis in nursing homes.
The number of geriatric end-stage renal disease (ESRD) patients in the United States is increasing disproportionately to other age groups on dialysis. Thus there will be more dialysis patients that will require the assistance of nursing homes or extended care facilities. Nursing homes may be beneficial for the geriatric patient in terms of social and physical rehabilitation. Many of these facilities, however, may not take care of or may not have the capacity to adequately care for dialysis patients. Such patients have a higher rate of peritonitis when on peritoneal dialysis (PD) and have higher mortality rates on hemodialysis (HD) or PD compared to similar dialysis patients in the community. Cooperation and communication between the dialysis center and the nursing home, given the complex management issues involved in the care of these patients, are essential. One promising approach to the care of elderly dialysis patients is an integration of nursing home and dialysis unit. Although another approach could be to more fully utilize the services of adult day care centers, this has proven logistically difficult and has not been reported to be successful since it was first suggested more than a decade ago.


Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy.
Sympathetic nerve activity is increased in awake and regularly breathing patients with obstructive sleep apnea (OSA). Over time, repetitive hypoxic stress could alter sympathetic chemoreflex function in OSA. We determined the responses to acute hypoxia (fraction of inspired oxygen of 0.1, for 5 min), static handgrip exercise, and the cold pressor test (CPT) in 24 patients with OSA (age, 50 +/- 3 years [mean +/- SEM]; apnea-hypopnea index, 47 +/- 6 events per hour) and in 14 age- and weight-matched nonapneic control subjects. Muscle sympathetic nerve activity (MSNA) [peroneal microneurography], BP, and ventilation were monitored. Basal MSNA was higher in OSA patients compared to control subjects (45 +/- 4 bursts per minute vs 33 +/- 4 bursts per minute, respectively; p < 0.05). Furthermore, compared to control subjects, the MSNA responses to hypoxia were markedly enhanced in OSA (p < 0.001). Whereas the ventilatory responses to hypoxia tended to be increased in OSA (p = 0.06), the BP responses did not differ between the groups (p = 0.45). The neurocirculatory reflex responses to handgrip exercise and to the CPT were similar in the two groups (p = not significant). In OSA patients who were retested after 1 to 24 months of continuous positive airway pressure (CPAP) therapy (n = 11), basal MSNA (p < 0.01) and the responses of MSNA to hypoxia (p < 0.01) decreased significantly, whereas the ventilatory responses remained unchanged (p = 0.82). These data suggest that the sympathetic responses to hypoxic chemoreflex stimulation are enhanced in OSA and may normalize in part following CPAP therapy.


Comprehensive Evaluation and Implementation of Improvement Actions in Butcher Shops.
Foodborne pathogens can cause acute and chronic diseases and produce a wide range of symptoms. Since the consumption of ground beef is a risk factor for infections with some bacterial pathogens, we performed a comprehensive evaluation of butcher shops, implemented improvement actions for both butcher shops and consumers, and verified the impact of those actions implemented. A comprehensive evaluation was made and risk was quantified on a 1-100 scale as high-risk (1-40), moderate-risk (41-70) or low-risk (71-100). A total of 172 raw ground beef and 672 environmental samples were collected from 86 butcher shops during the evaluation (2010-2011) and verification (2013) stages of the study. Ground beef samples were analyzed for mesophilic aerobic organisms, Escherichia coli and coagulase-positive Staphylococcus aureus enumeration. Salmonella spp., E. coli O157:H7, non-O157 Shiga toxin-producing E. coli (STEC), and Listeria monocytogenes were detected and isolated from all samples. Risk quantification resulted in 43 (50.0%) high-risk, 34 (39.5%) moderate-risk, and nine (10.5%) low-risk butcher shops. Training sessions for 498 handlers and 4,506 consumers were held. Re-evaluation by risk quantification and microbiological analyses resulted in 19 (22.1%) high-risk, 42 (48.8%) moderate-risk and 25 (29.1%) low-risk butcher shops. The count of indicator microorganisms decreased with respect to the 2010-2011 period. After the implementation of improvement actions, the presence of L. monocytogenes, E. coli O157:H7 and stx genes in ground beef decreased. Salmonella spp. was isolated from 10 (11.6%) ground beef samples, without detecting statistically significant differences between both study periods (evaluation and verification). The percentage of pathogens in environmental samples was reduced in the verification period (Salmonella spp., 1.5%; L. monocytogenes, 10.7%; E. coli O157:H7, 0.6%; non-O157 STEC, 6.8%). Risk quantification was useful to identify those relevant facts in butcher shops. The reduction of contamination in ground beef and the environment was possible after training handlers based on the problems identified in their own butcher shops. Our results confirm the feasibility of implementing a comprehensive risk management program in butcher shops, and the importance of information campaigns targeting consumers. Further collaborative efforts would be necessary to improve foodstuffs safety at retail level and at home.


Compartmentalized calcium transients trigger dendrite pruning in Drosophila sensory neurons.
Dendrite pruning is critical for sculpting the final connectivity of neural circuits as it removes inappropriate projections, yet how neurons can selectively eliminate unnecessary dendritic branches remains elusive. Here, we show that calcium transients that are compartmentalized in specific dendritic branches act as temporal and spatial cues to trigger pruning in Drosophila sensory neurons. Calcium transients occurred in local dendrites at ~3 hours before branch elimination. In dendritic branches, intrinsic excitability increased locally to activate calcium influx via the voltage-gated calcium channels (VGCCs), and blockade of the VGCC activities impaired pruning. Further genetic analyses suggest that the calcium-activated protease calpain functions downstream of the calcium transients. Our findings reveal the importance of the compartmentalized subdendritic calcium signaling in spatiotemporally selective elimination of dendritic branches.


Scrape-loaded p21ras down-regulates agonist-stimulated inositol phosphate production by a mechanism involving protein kinase C.
The effect of scrape-loaded [Val-12]p21ras on agonist-stimulated phosphatidylinositol 4,5-bisphosphate (PIP2) turnover in Swiss-3T3 cells was studied. Previously [Morris, Price, Lloyd, Marshall & Hall (1989) Oncogene 4, 27-31] we demonstrated that [Val-12]p21ras activates protein kinase C within 10 min of scrape loading. Here, we show that [Val-12]p21ras inhibits bombesin and platelet-derived growth factor-stimulated PIP2 breakdown 1.5-4 h after scrape loading. This effect persisted for at least 18 h and could be mimicked in control cells by activation of protein kinase C with 12-O-tetradecanoyl 13-acetate (TPA) 15 min prior to ligand stimulation. When protein kinase C was down-regulated by chronic TPA treatment, [Val-12]p21ras was no longer able to inhibit agonist-stimulated inositol phosphate production. These results indicate that changes in inositol phosphate levels caused by ras protein are probably due to activation of protein kinase C and not to an interaction of ras with phospholipase C.


A genome-wide association study of suicide attempts in the million veterans program identifies evidence of pan-ancestry and ancestry-specific risk loci.
To identify pan-ancestry and ancestry-specific loci associated with attempting suicide among veterans, we conducted a genome-wide association study (GWAS) of suicide attempts within a large, multi-ancestry cohort of U.S. veterans enrolled in the Million Veterans Program (MVP). Cases were defined as veterans with a documented history of suicide attempts in the electronic health record (EHR; N = 14,089) and controls were defined as veterans with no documented history of suicidal thoughts or behaviors in the EHR (N = 395,064). GWAS was performed separately in each ancestry group, controlling for sex, age and genetic substructure. Pan-ancestry risk loci were identified through meta-analysis and included two genome-wide significant loci on chromosomes 20 (p = 3.64 × 10-9) and 1 (p = 3.69 × 10-8). A strong pan-ancestry signal at the Dopamine Receptor D2 locus (p = 1.77 × 10-7) was also identified and subsequently replicated in a large, independent international civilian cohort (p = 7.97 × 10-4). Additionally, ancestry-specific genome-wide significant loci were also detected in African-Americans, European-Americans, Asian-Americans, and Hispanic-Americans. Pathway analyses suggested over-representation of many biological pathways with high clinical significance, including oxytocin signaling, glutamatergic synapse, cortisol synthesis and secretion, dopaminergic synapse, and circadian rhythm. These findings confirm that the genetic architecture underlying suicide attempt risk is complex and includes both pan-ancestry and ancestry-specific risk loci. Moreover, pathway analyses suggested many commonly impacted biological pathways that could inform development of improved therapeutics for suicide prevention.


Pre- and postshunting magnetization transfer ratios are in accordance with neurological and behavioral changes in hydrocephalic immature rats.
Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.


Beyond JAK-STAT: novel therapeutic targets in Ph-negative MPN.
The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share a common pathobiology of constitutive activation of the JAK and STAT pathway, despite having the 3 distinct phenotypes of essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Targeting the JAK-STAT pathway has led to remarkable clinical benefit, including reduction in splenomegaly, amelioration of cytokine-driven symptoms, improvement in quality of life, and even some improvement in survival. However, targeting this pathway has not resulted in consistent disease modification by current metrics, including a reduction in mutant allele burden or reversal of fibrosis. Moreover, targeting JAK-STAT can lead to limiting treatment-emergent side effects, such as anemia and thrombocytopenia. Continued discovery points to a complex system of pathogenesis beyond JAK-STAT driving the formation and evolution of MPNs. This article reviews the successes and limitations of JAK-STAT inhibition, surveys the strategies behind emerging therapies, and discusses the challenges that are present in moving beyond JAK-STAT.


Acute Effect of a Saffron Extract (Safr'InsideTM) and Its Main Volatile Compound on the Stress Response in Healthy Young Men: A Randomized, Double Blind, Placebo-Controlled, Crossover Study.
According to animal studies, saffron and its main volatile compound safranal may reduce biological and behavioral signs of acute stress. However, little is known about its impact in humans. This study investigated the acute effect of a saffron extract and safranal on the biological and psychological stress responses in healthy men experiencing a laboratory stress procedure. In this double-blind, placebo-controlled, randomized, cross-over study, 19 volunteers aged 18-25 received a single dose of 30 mg saffron extract (Safr'InsideTM), 0.06 mg synthetic safranal, or a placebo on three visits separated by a 28-day washout. Thirteen minutes after administration, participants were exposed to the Maastricht acute stress test (MAST). Salivary cortisol and cortisone were collected from 15 min before the MAST (and pre-dose), 3 min before the MAST, and then 15, 30, 45, 60, and 75 min after the MAST, and stress and anxiety were measured using visual analogic scales. Compared to the placebo, stress and anxiety were significantly toned down after Safranal and Safr'InsideTM administration and coupled with a delay in the times to peak salivary cortisol and cortisone concentrations (p < 0.05). Safr'InsideTM and its volatile compound seem to improve psychological stress response in healthy men after exposure to a lab-based stressor and may modulate the biological stress response.


How to die chemically? Whole body apoptosis.
What would you do if your body decided to die when you were not ready? It appears that some biological program can shut down all bodily functions, in much the same way as apoptosis does so at the cellular level. Pacific salmon and annual cicada die after reproduction. How do they die chemically? Their programmed death after reproduction should have chemical signals. Similarly, pro-inflammatory cytokines, particularly tumor necrosis factor-α and interleukin-1β, could induce death in mammals. Acute massive production of them in sepsis and chronic tiny production in aging could lead to death. Thus, the mechanism of the whole body suicide program could be determined and some people could be rescued from this type of death by elucidating the death program. I propose that the concept of whole body apoptosis, defined as programmed whole body death, be adopted by scientific community.


Regenerating optic axons restore topography after incomplete optic nerve injury.
Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons intact, restores normal topography. Strict RGC axon topography allowed us to preserve RGC axons on one side of the nerve (projecting to medial tectum) while lesioning those on the other side (projecting to lateral tectum). Topography and response properties for both RGC axon populations were assessed electrophysiologically. The majority of intact RGC axons retained appropriate topography in medial tectum and had normal, consistently brisk, reliable responses. Regenerate RGC axons fell into two classes: those that projected topographically to lateral tectum with responses that tended to habituate and those that lacked topography, responded weakly, and habituated rapidly. Axon tracing by localized retinal application of carbocyanine dyes supported the electrophysiological data. RGC soma counts were normal in both intact and axotomized RGC populations, contrasting with the 30% RGC loss after complete injury. Unlike incomplete optic nerve injury in mammals, where RGC axon regeneration fails and secondary cell death removes many intact RGC somata, lizards experience a "win-win" situation: intact RGC axons favorably influence the functional outcome for regenerating ones and RGCs do not succumb to either primary or secondary cell death.


Inhibition of Autophagy Does Not Re-Sensitize Acute Myeloid Leukemia Cells Resistant to Cytarabine.
Elevated activation of the autophagy pathway is currently thought to be one of the survival mechanisms allowing therapy-resistant cancer cells to escape elimination, including for cytarabine (AraC)-resistant acute myeloid leukemia (AML) patients. Consequently, the use of autophagy inhibitors such as chloroquine (CQ) is being explored for the re-sensitization of AraC-resistant cells. In our study, no difference in the activity of the autophagy pathway was detected when comparing AraC-Res AML cell lines to parental AraC-sensitive AML cell lines. Furthermore, treatment with autophagy inhibitors CQ, 3-Methyladenine (3-MA), and bafilomycin A1 (BafA1) did not re-sensitize AraC-Res AML cell lines to AraC treatment. However, in parental AraC-sensitive AML cells, treatment with AraC did activate autophagy and, correspondingly, combination of AraC with autophagy inhibitors strongly reduced cell viability. Notably, the combination of these drugs also yielded the highest level of cell death in a panel of patient-derived AML samples even though not being additive. Furthermore, there was no difference in the cytotoxic effect of autophagy inhibition during AraC treatment in matched de novo and relapse samples with differential sensitivity to AraC. Thus, inhibition of autophagy may improve AraC efficacy in AML patients, but does not seem warranted for the treatment of AML patients that have relapsed with AraC-resistant disease.


[Method of sphincter-preserving operation for low localization of rectal cancer].
The authors have developed a method and defined indications for sphincter-preserving operation--proctectomy for low localization of rectal cancer. The method of operation suggests ablation of the rectum together with its internal sphincter and preservation of all components of the external sphincter of the rectum that provides realization of voluntary (volitional) component of the anal holding. The operation used in 37 patients gave better functional results of treatment and better quality of their life.


Genetics and epigenetics of liver cancer.
Hepatocellular carcinoma (HCC) represents a major form of primary liver cancer in adults. Chronic infections with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse are the major factors leading to HCC. This deadly cancer affects more than 500,000 people worldwide and it is quite resistant to conventional chemo- and radiotherapy. Genetic and epigenetic studies on HCC may help to understand better its mechanisms and provide new tools for early diagnosis and therapy. Recent literature on whole genome analysis of HCC indicated a high number of mutated genes in addition to well-known genes such as TP53, CTNNB1, AXIN1 and CDKN2A, but their frequencies are much lower. Apart from CTNNB1 mutations, most of the other mutations appear to result in loss-of-function. Thus, HCC-associated mutations cannot be easily targeted for therapy. Epigenetic aberrations that appear to occur quite frequently may serve as new targets. Global DNA hypomethylation, promoter methylation, aberrant expression of non-coding RNAs and dysregulated expression of other epigenetic regulatory genes such as EZH2 are the best-known epigenetic abnormalities. Future research in this direction may help to identify novel biomarkers and therapeutic targets for HCC.


The Clermont Escherichia coli phylo-typing method revisited: improvement of specificity and detection of new phylo-groups.
There is extensive genetic substructure within the species Escherichia coli. In 2000 a simple triplex PCR method was described by Clermont and colleagues that enables an E. coli isolate to be assigned to one of the phylo-groups A, B1, B2 or D. The growing body of multi-locus sequence data and genome data for E. coli has refined our understanding of E. coli's phylo-group structure and eight phylo-groups are now recognized: seven (A, B1, B2, C, D, E, F) belong to E. coli sensu stricto, whereas the eighth is the Escherichia cryptic clade I. Here a new PCR-based method is developed that enables an E. coli isolate to be assigned to one of the eight phylo-groups and which allows isolates that are members of the other cryptic clades (II to V) of Escherichia to be identified. The development of the method is described and the method is validated. Over 95% of E. coli isolates can be correctly assigned to a phylo-group. Two collections of human faecal isolates were screened using the new phylo-group assignment method demonstrating that about 13% of E. coli isolates belong to the newly described phylo-groups C, E, F and clade I.


miR-10b promotes cell invasion through RhoC-AKT signaling pathway by targeting HOXD10 in gastric cancer.
MicroRNAs play critical roles in tumorigenesis as either oncogenes or tumor suppressors. As a microRNA induced by Twist, miR-10b function as a metastasis driver in different types of cancer, in which the downstream target gene HOXD10 is the main mediator. In gastric tumor species, miR-10b levels were dramatically elevated in lymphoma node metastasis-positive tumor tissues compared with lymphoma node metastasis-free tumor tissues, and were correlated to dowregulation of HOXD10 expression. In gastric cell lines with distinct degrees of differentiation, miR-10b was highly expressed in the cell line with strong metastatic ability. In MNK45 cells, inhibition of miR-10b led to abrogation of cell invasion. While in GES-1 cells, miR-10 overexpression resulted in enhancement of invasiveness through translational inhibition of HOXD10, and constitutive expression of HOXD10 reversed the effects of miR-10b on cell invasion. Furthermore, either knockdown of RhoC or inhibition of AKT activation interfered miR-10-induced invasiveness in GES-1 cells. In summary, these observations suggest that miR-10b can stimulate the upregulation of RhoC and AKT phosphorylation through targeting HOXD10, thus promoting cell invasion in gastric tumors.


Nonreactive spreading at high-temperature revisited for metal systems via molecular dynamics.
The spreading for Cu and Ag droplets on top of a rigid solid surface modeling Mo is herewith considered via molecular dynamics. The dynamics of the base radius and the contact angle are recorded and fitted using the molecular-kinetic theory. A method is described to determine for liquid metals at the microscopic level the parameters appearing in this theory. These microscopic parameters are calculated directly in the simulations and compared to the fitted values. The agreement between the fitted values and the calculated ones shows that the dissipation of energy within the drop is caused primarily by the friction of liquid atoms over the substrate. This validation supports the understanding of the mechanisms controlling the spreading of liquid metals which, up to now, were based on experimental data and fitting procedures.


Induction of IgG antibodies directed to a M(r) 31,000 melanoma antigen in patients immunized with vaccinia virus melanoma oncolysates.
Pre- and postimmunization sera from eight tumor-free melanoma patients undergoing vaccinia melanoma oncolysate (VMO) therapy were used to investigate the humoral response to antigens from infected and uninfected melanoma cells and from vaccinia virus. Immunodetection on Western blots showed that all patients, in addition to reacting to several other proteins, developed IgG antibodies to a M(r) 31,000 protein antigen within 1 month of immunization. This M(r) 31,000 antigen is expressed both on VMO and on melanoma metastases in situ, disappears in primary cultures of these metastases, and is absent in extracts from vaccinia virus, from human melanoma cell lines, and from normal melanocytes, suggesting that this M(r) 31,000 protein is reexpressed following vaccinia virus infection of human melanoma cells. Periodate treatment of the blotted antigens abolished reactivity of patients' postimmunization sera with the M(r) 31,000 antigen, thus showing that this antigen is a glycoprotein and that the relevant epitope is likely to reside on its carbohydrate moiety. These anti-M(r) 31,000 IgG antibodies were absent in the sera of VMO-treated patients before immunization, absent in the serum of a normal donor hyperimmunized with vaccinia virus, and absent in normal human sera. In addition, these anti-M(r) 31,000 antibodies appeared 1 week after the first VMO injection, remained stable during the treatment, and decreased when the treatment was stopped. Such antibodies can also be demonstrated in sera of melanoma patients bearing metastases but disappeared following resection of their metastases. Thus, in melanoma patients, immunization with VMO induces an antibody response directed against a M(r) 31,000 glycoprotein likely to represent a new melanoma antigen. Further identification of this antigen could be of utmost interest for the further development of melanoma vaccines.


[Patterns in the cellular organization of ovule growth in the pine, Pinus silvestris L. I. Growth processes in endosperm].
The dynamics of growth processes was studied in the endosperm of Pinus silvestris during the year of fertilization. The growth of endosperm is described by an diauxic curve where the period of delay corresponds, by time, to fertilization. The growth of tissue proceeds, mainly, at the expense of cell proliferation. The mitotic activity is preserved in the endosperm till the beginning of formation of reserve substances in the cells; cell division and elongation occur simultaneously. The unfavourable environmental conditions influence the mitotic activity of cells only. The size of fully grown cells is relatively constant and somewhat decreases later, during maturation. One can distinguish rather early those regions in the endosperm where the cell size is 2-3 times less than in the rest tissue; the size of cells and nuclei in these regions suffers only insignificant changes during the growth. The large nuclei are observed in the beginning of the cell endosperm formation and, then, their size decreases 1.5-2 times; the second increase in nuclear size in the endosperm is observed during the period prior to the formation of reserve substances.


[Patient advisors and coercion in psychiatry. The situation 3 months after the introduction of the Act on restriction of liberty and other coercive measures in psychiatry].
In a retrospective investigation, we attempted to estimate the effect of introduction of a new law about coercive measures and loss of liberty in psychiatric wards during the first three months after enforcement of the law. By examination of case reports we found that 69 patients, i.e. 14%, were exposed to one or several types of coercive measures. Restraint was the most frequent form of coercive measures. Eight patients lodged complaints about the coercive measures. The decisions of the psychiatrists were all sanctioned. Replies to complaints about treatment with coersion were available within five to 14 days. In an investigation by questionnaire, we found that there was satisfaction with the patient advisors introduced in the wards by the new law. Collaboration with the patient advisors took considerable time for the staff members. Both staff members, doctors and patient advisors suggest that the patient advisors should receive more education in psychiatry. We suggest changes in the law when this is revised.


[Psoriasis and haemodialysis: changes in plasma hormone concentration as a possible therapeutic mechanism (author's transl)].
Free dehydroepiandrosterone (DHEA), DHEA sulphate, testosterone, LH and FSH were measured in plasma from 67 patients with renal disease before and after haemodialysis or haemofiltration. Plasma concentration of the steroid hormones was lower in patients with renal failure than in normal controls, while that of the gonadotrophic hormones was elevated. After haemodialysis or haemofiltration DHEA sulphate level in plasma decreased, free DHEA increased significantly reaching almost the initial value of the control group. There was no change in concentration of the other steroid and gonadotrophic hormones. The likely mechanism is that haemodialysis removes DHEA deficiency in patients with psoriasis which is assumed to be an aetiopathogenetic factor in the disease.


Inhibition of wound healing in mice by local interferon alpha/beta injection.
Tumour vascular endothelium has been observed previously to be damaged by local injection of interferon alpha/beta, apparently before the onset of necrosis and regression of experimental tumours. In order to distinguish the effect of interferon alpha/beta on the vasculature from direct effects on tumour, the angiogenesis of wound healing was chosen for study. Injection of interferon alpha/beta subcutaneously adjacent to each wound at days 0 to 4 resulted in a markedly reduced rate of healing with poor edge reunion by day 3. Histologically, there was delay in the initiation of proliferation of not only capillary buds, but also fibroblasts and, to a lesser extent, epithelium across the incision. Nevertheless, no endothelial injury was seen at light or electron microscopic level. Healing subsequently resumed the normal pattern, though delayed, day 9 wounds resembling normal day 5 wounds. We conclude that interferon alpha/beta inhibits wound healing in mice by inhibition of proliferation of many cell types in addition to endothelium.


Effect of Tumor Complexity and Technique on Efficacy and Complications after Percutaneous Microwave Ablation of Stage T1a Renal Cell Carcinoma: A Single-Center, Retrospective Study.
Purpose To evaluate the effects of tumor complexity and technique on early and midterm oncologic efficacy and rate of complications for 100 consecutive biopsy-proved stage T1a renal cell carcinomas (RCCs) treated with percutaneous microwave ablation. Materials and Methods This HIPAA-compliant, single-center retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety-six consecutive patients (68 men, 28 women; mean age, 66 years ± 9.4) with 100 stage T1a N0M0 biopsy-proved RCCs (median diameter, 2.6 cm ± 0.8) underwent percutaneous microwave ablation between March 2011 and June 2015. Patient and procedural data were collected, including body mass index, comorbidities, tumor histologic characteristics and grade, RENAL nephrometry score, number of antennas, generator power, and duration of ablation. Technical success, local tumor progression, and presence of complications were assessed at immediate and follow-up imaging. The Kaplan-Meier method was used for survival analyses. Results Technical success was achieved for all 100 tumors (100%), including 47 moderately and five highly complex RCCs. Median clinical and imaging follow-up was 17 months (range, 0-48 months) and 15 months (range, 0-44 months), respectively. No change in estimated glomerular filtration rate was noted after the procedure (P = .49). There were three (3%) procedure-related complications and six (6%) delayed complications, all urinomas. One case of local tumor progression (1%) was identified 25 months after the procedure. Three-year local progression-free survival, cancer-specific survival, and overall survival were 88% (95% confidence interval: 0.52%, 0.97%), 100% (95% confidence interval: 1.0%, 1.0%), and 91% (95% confidence interval: 0.51%, 0.99%), respectively. Conclusion Percutaneous microwave ablation is an effective and safe treatment option for stage T1a RCC, regardless of tumor complexity. Long-term follow-up is needed to establish durable oncologic efficacy and survival relative to competing ablation modalities and surgery. © RSNA, 2017.


Late relapsing Wilms tumor with rhabdomyomatous differentiation.
The authors report a patient with abdominally relapsed Wilms tumor with rhabdomyomatous differentiation leading to renal failure and death 9 years after the initial diagnosis. The patient was treated with intensive chemotherapy because of inoperable tumor but no response was obtained. The prognosis of children with Wilms tumor relapsed in abdomen and in previously irradiated fields is poor and intensive chemotherapy protocols for differentiated tumors after chemotherapy will increase the risk of complications without obvious benefit.


Long-Term Outcome of Monochorionic Twins after Fetoscopic Laser Therapy Compared to Matched Dichorionic Twins.
The only causal therapy is fetoscopic laser surgery (FLS). The aims of this study were to analyze the long-term outcome of monochorionic twins treated by FLS, including their school career, need for therapy and special aid equipment, and free-time activities, and compare their outcome to matched dichorionic twins. Among the 57 women treated at a single fetal treatment center between 2008 and 2017 with FLS because of twin-to-twin transfusion syndrome, 25 women with 42 children were included in the FLS group. The control group consisted of 16 dichorionic twin pairs matched for birth year, gestational age (GA), birth weight, and sex. The long-term outcome was assessed by a parental questionnaire and a standardized neurodevelopmental examination for children born before 32 gestational weeks or with a birth weight lower than 1500 g. They were also registered into the Swiss Neonatal Network database. The primary outcome was event-free survival, defined as normal neurology, behavior, vision, and hearing. The secondary outcomes were school career, need for therapy and special aid equipment, and free-time activities. An event-free survival was found in 32 children (76%) in the laser and in 24 children (75%) in the control group (p = 0.91). Neurological anomalies were found in 5 children (12%) in the laser group and 3 children (9%) in the control group (p = 1.00). Multiple logistic regression analysis showed that GA at delivery was the only predictive factor for event-free survival. There were no significant differences regarding school career, therapies, or special aid equipment between the 2 groups. We found that children without FLS were involved in more free-time activities and needed fewer breaks during physical activity than children with FLS during pregnancy. The outcome of monochorionic twins treated with FLS is comparable to the outcome of dichorionic twins. Long-term neurodevelopment in the cohort was mainly dependent on GA at birth.


Higher frequency of T-cell response to M. tuberculosis latency antigen Rv2628 at the site of active tuberculosis disease than in peripheral blood.
Due to the invasive nature of the procedures involved, most studies of Mycobacterium tuberculosis (Mtb)-specific immunity in humans have focused on the periphery rather than the site of active infection, the lung. Recently, antigens associated with Mtb-latency and -dormancy have been described using peripheral blood (PB) cells; however their response in the lung is unknown. The objective of this report was to evaluate, in patients prospectively enrolled with suspected active tuberculosis (TB), whether the latency antigen Rv2628 induces local-specific immune response in bronchoalveolar lavage (BAL) cells compared to PB cells. Among the 41 subjects enrolled, 20 resulted with active TB. Among the 21 without active disease, 9 were defined as subjects with latent TB-infection (LTBI) [Quantiferon TB Gold In-tube positive]. Cytokine responses to Rv2628 were evaluated by enzyme linked immunospot (ELISPOT) assay and flow cytometric (FACS) analysis. RD1-secreted antigen stimulation was used as control. There was a significantly higher frequency of Rv2628- and RD1-specific CD4+ T-cells in the BAL of active TB patients than in PB. However the trend of the response to Rv2628 in subjects with LTBI was higher than in active TB in both PB and BAL, although this difference was not significant. In active TB, Rv2628 and RD1 induced a cytokine-response profile mainly consisting of interferon (IFN)-γ-single-positive over double-IFN-γ/interleukin (IL)-2 T-cells in both PB and BAL. Finally, BAL-specific CD4+ T-cells were mostly effector memory (EM), while peripheral T-cell phenotypes were distributed among naïve, central memory and terminally differentiated effector memory T-cells. In this observational study, we show that there is a high frequency of specific T-cells for Mtb-latency and RD1-secreted antigens (mostly IFN-γ-single-positive specific T-cells with an EM phenotype) in the BAL of active TB patients. These data may be important for better understanding the pathogenesis of TB in the lung.


Clinical stage B prostate carcinoma: staging with MR imaging.
Magnetic resonance (MR) imaging studies were performed in 29 patients with clinical findings of stage B prostatic carcinoma with use of both T1 and T2-weighted spin echo sequences. MR imaging findings were correlated with surgical/pathologic results in 18 patients who underwent an operation. Periprostatic fat, periprostatic venous plexus, seminal vesicles, and lymph nodes were assessed from MR imaging studies. When each was assessed independently, the periprostatic fat signal had a sensitivity of 29%, specificity of 100%, and accuracy of 85% in detecting extracapsular tumor extension, whereas the periprostatic venous plexus had a sensitivity of 57%, specificity of 86%, and accuracy of 80%. MR imaging had a sensitivity of 50%, specificity of 97%, and accuracy of 89% for detecting seminal vesicular involvement. When all four anatomic features were taken into consideration, MR imaging had an accuracy of 89% (16 of 18 patients) in differentiating stage B from stage C or D disease (sensitivity 87%, specificity 90%). Our data indicate that MR imaging is a promising method for staging prostatic carcinoma.


Pacing in World-Class Age Group Swimmers in 200 and 400 m Individual Medley.
The present research investigated pacing for world-class age group swimmers competing in individual medley in 200 m and 400 m. Data on 3,242 unique finishers (1,475 women and 1,767 men) competing in four Master World Championships [XV FINA WMC held in Montreal (Canada) in 2014, the XVI FINA WMC held in Kazan (RUS) in 2015, the FINA WMC held in Budapest (HUN) in 2017, and the XVIII FINA WMC held in Gwangju (KOR] in 2019) were analyzed. Men were faster than women among all age groups in both 200 and 400 m. Additionally, differences were found between almost all adjacent age groups, with the exception (p > 0.05) of age groups 25-29 to 30-34, 35-39 to 40-44 years in 200 m races and 25-29 to 30-34, 30-34 to 35-39, 35-39 to 40-44, and 45-49 to 50-54 years in 400 m races. Men showed a higher pacing variation in 200 m among all male age groups and all female age groups up to 69 years. Pace-variation pairwise comparisons between men and women showed no consistencies throughout age groups, with the exception of a higher variation in men in age groups ≥55-year-old. Men were faster for all splits and strokes in both 200 and 400 m, and significant changes were identified for each split and stroke for both men and women in both 200 and 400 m. Front crawl (freestyle, 4th split) was the fastest butterfly (1st split), backstroke (2nd split), and breaststroke (3rd split). In summary, men were faster than women for all age groups in both 200 and 400 m. Men showed a higher pacing variation in 200 m in all age groups, where women had a higher variation in age groups up to 69 years. The fastest stroke for the final spurt was front crawl, followed by butterfly, backstroke, and breaststroke. Based on these findings, coaches should advise their master athletes to focus on the final spurt in both 200 and 400 m individual medley for a fast final race time.


Effects of Teriparatide, Denosumab, or Both on Spine Trabecular Microarchitecture in DATA-Switch: a Randomized Controlled Trial.
In postmenopausal women, 2 yr of combined teriparatide and denosumab increases bone mineral density more than either drug alone, and switching from either combination or teriparatide to denosumab for an additional 2 yr further increases bone mineral density. Conversely, switching from denosumab to teriparatide results in transient bone loss. The effects of these interventions on spine microarchitecture are unknown. In the DATA and DATA-Switch studies, 94 postmenopausal osteoporotic women were randomized to receive 24 mo of teriparatide (20 µg daily), denosumab (60 mg every 6 mo), or both. Then, women originally assigned to 24 mo of teriparatide received 24 mo of denosumab, whereas subjects originally randomized to 24 mo of denosumab received 24 mo of teriparatide. Subjects who received both drugs received an additional 24 mo of denosumab alone. Spine trabecular bone score (TBS, a gray-level textural assessment of bone microarchitecture) was measured blinded from treatment groups using images from 2-dimensional dual-energy X-ray absorptiometry spine scans at 0, 12, 24, 30, 36, and 48 mo in 65 women who had posterior-anterior spine dual-energy X-ray absorptiometry images suitable for TBS analysis. After 24 mo, TBS increased by 2.7 ± 4.7% in the teriparatide group (p = 0.009 vs baseline), by 1.8 ± 5.0% in the denosumab group (p = 0.118 vs baseline), and by 4.5 ± 6.7% in the combination group (p = 0.017 vs baseline), with no significant between-group differences. In the 6 mo after the treatments were switched (months 24-30), TBS continued to increase in the combination-to-denosumab and teriparatide-to-denosumab groups but decreased by -1.1 ± 4.0% in the denosumab-to-teriparatide group (p < 0.05 vs other groups). After 48 mo, compared to month 0, TBS increased by 5.1 ± 5.8% in the teriparatide-to-denosumab group, by 3.6 ± 4.2% in the denosumab-to-teriparatide group, and by 6.1 ± 4.7% in the combination-to-denosumab group (p < 0.001 vs baseline for all groups, p = not significant for between-group differences). Switching from teriparatide to denosumab also increased spine TBS. Conversely, switching from denosumab to teriparatide transiently degraded spine trabecular microarchitecture, the clinical consequences of which require further study.


Multifunctional 3D electrode platform for real-time in situ monitoring and stimulation of cardiac tissues.
Cardiovascular diseases are a major cause of death around the world underlining the importance of efficient treatments including novel medication. In vitro models of cardiac tissues are highly desired for monitoring electrophysiological response to screen pharmaceutical compounds at an early stage. Here, we report a platinum based 3D pillar electrode platform with cell growth guiding channel, which allows integrated, continuous electrical stimulation and recording of the cardiac tissues. This platform was successfully used to culture beating cardiomyocytes over weeks. The Pt-PDMS pillar electrode showed an impedance of 2.5 ± 0.3 kΩ at 10 Hz that is stable for using in cell cultures at 37 °C. Electrically pacing the cells improved maturation of the cardiac tissues. Contraction activities of 3D cardiac tissues were monitored in real-time through the pillar electrodes to evaluate physiological parameters. Adding 100 nM Isoproterenol clearly increased the spontaneous beating rate and decreased the extracellular field potential duration of the microtissues observed with electrical recording through the pillar electrodes. Overall, this platform has a potential to be applied in drug screening for in situ monitoring the biophysical parameters of the heart tissue in real-time.


Chronic meningitis and Lyme disease in Sweden.
We studied 35 patients with chronic meningitis. The neurological abnormalities included aseptic meningitis, cranial neuropathy (mostly facial palsy), motor and sensory peripheral radiculoneuropathy, and myelitis. Neurological symptoms were sometimes preceded by erythema chronicum migrans or an insect bite and were often accompanied by fever, malaise, profound fatigue, and weight loss. The cerebrospinal fluid (CSF) abnormalities consisted of a predominantly mononuclear pleocytosis, an elevated CSF protein (mean 2.3 g/l), intrathecal synthesis of oligoclonal immunoglobulin G, and, in half of the patients, a fall in the CSF/blood glucose ratio. High antibody titers to the Lyme spirochete and the Swedish Ixodes ricinus spirochete were demonstrated by immunofluorescence in 26 of the 35 patients. By imprint immunofixation of electrofocused samples of serum and CSF, intrathecal production of oligoclonal Lyme-spirochete-specific IgG was demonstrated in one patient with chronic meningitis. Four sequential paired samples of serum and CSF from this patient showed local synthesis of spirochete-specific antibodies in CSF. The 35 patients improved or recovered, sometimes dramatically, during a two-week course of intravenous penicillin G.


Trends in socioeconomic disparities in the utilization of dental care in Brazil and Sweden.
To describe trends in socioeconomic disparities in utilization of dental care. We obtained cross-sectional data from Sweden in the period 1968-2000 and from Brazil in 1986 and 2002 for 16 state capitals. The outcome was the percentage of people who reported that they had visited the dentist in the last 12 months, calculated for a higher and a lower income group and stratified by sex, age (two groups: young and adults) and dental status. Adjusted prevalence differences and prevalence ratios were produced using Poisson regression. In Brazil, there was a decline in use of dental care among the 15-19 year olds in the period 1986-2002, but not among the 35-44 year olds. In Sweden, there was a decline among the young and adults between 1991 and 2000. Overall, socioeconomic disparities in use of dental services between the higher and the lower economic groups showed a decline in both countries. The reduction in disparities among young Brazilians was 1.1 percentage points per year (p < 0.01), but among the other age groups the decline was not significant (p>0.01). In the last surveys, the gap remained in both countries and age groups (p < 0.01). The recent decline in utilization of dental care and in the socioeconomic gap may mirror improvements in oral health. However, there are still relevant and persistent disparities in utilization of dental care in both countries, with a higher proportion of people of higher socioeconomic status visiting the dentist.


Heterogeneous antibody responses in tuberculosis.
Antibody responses during tuberculosis were analyzed by an enzyme-linked immunosorbent assay with a panel of 10 protein antigens of Mycobacterium tuberculosis. It was shown that serum immunoglobulin G antibodies were produced against a variety of M. tuberculosis antigens and that the vast majority of sera from tuberculosis patients contained antibodies against one or more M. tuberculosis antigens. The number and the species of serologically reactive antigens varied greatly from individual to individual. In a given serum, the level of specific antibodies also varied with the antigen irrespective of the total number of antigens recognized by that particular serum. These findings indicate that person-to-person heterogeneity of antigen recognition, rather than recognition of particular antigens, is a key attribute of the antibody response in tuberculosis.


Career aspirations of dental students in a dental college in Calcutta, India.
Career aspirations of dental students at Dr. R. Ahmed Dental College & Hospital, Calcutta have been studied through a survey by questionnaire among 215 undergraduate dental students. The response rate was 78.6%. Private practice and clinical jobs were the commonest choices. Academic research jobs formed a very low priority area for career persual. Trends in junior through senior classes show low research interests in the senior as compared to the junior classes. More females preferred clinical jobs with private practice the second most common choice.


Cell therapy in joint disorders.
Articular cartilage possesses poor natural healing mechanisms, and a variety of non-cell-based and cell-based treatments aim to promote regeneration of hyaline cartilage. A review of the literature to December 2013 using PubMed with search criteria including the keywords stem cell, cell therapy, cell transplantation, cartilage, chondral, and chondrogenic. Forty-five articles were identified that employed local mesenchymal stem cell (MSC) therapy for joint disorders in humans. Nine comparative studies were identified, consisting of 3 randomized trials, 5 cohort studies, and 1 case-control study. Clinical review. Level 4. Studies were assessed for stem cell source, method of implantation, comparison groups, and concurrent surgical techniques. Two studies comparing MSC treatment to autologous chondrocyte implantation found similar efficacy. Three studies reported clinical benefits with intra-articular MSC injection over non-MSC controls for cases undergoing debridement with or without marrow stimulation, although a randomized study found no significant clinical difference at 2-year follow-up but reported better 18-month magnetic resonance imaging and histologic scores in the MSC group. No human studies have compared intra-articular MSC therapy to non-MSC techniques for osteoarthritis in the absence of surgery. Mesenchymal stem cell-based therapies appear safe and effective for joint disorders in large animal preclinical models. Evidence for use in humans, particularly, comparison with more established treatments such as autologous chondrocyte implantation and microfracture, is limited.


Cerebral Artery Gas Embolism Following Navigational Bronchoscopy.
Cerebral artery gas embolism (CAGE) is a rare but serious adverse event with potentially devastating neurologic sequelae. Bronchoscopy is a frequently performed procedure but with only a few reported cases of CAGE. We report the first documented case of CAGE associated with electromagnetic navigational bronchoscopy. A 61-year-old man with a left lower lobe nodule underwent electromagnetic navigational bronchoscopy. The target lesion underwent transbronchial biopsy, brushing and an end-procedure lavage. Following the procedure, he developed seizures, evidence of hypoxic injury and cerebral edema, and air emboli were seen on computed tomography imaging. He then underwent treatment with hyperbaric oxygen with a full and complete neurologic recovery. Review of other cases reported in the literature suggests improved neurologic outcomes with hyperbaric oxygen treatment. Biopsy techniques performed during bronchoscopy and electromagnetic navigational bronchoscopy can result in CAGE. Comparison with other reported cases suggests improved neurologic outcomes in those treated with hyperbaric oxygen. Prompt recognition of this complication and timely treatment with hyperbaric oxygen are the cornerstones to recovery.


Conservative surgical treatment of renal cell carcinoma. The University of Miami experience.
Thirty-four patients with renal cell carcinoma underwent renal parenchymal-sparing surgery; 10 enucleation (Group A), 15 partial nephrectomy (Group B), and nine a combination of procedures (Group C). Conservative surgery was performed in the presence of normal contralateral unit in four patients (11.7%). Local recurrence (group A = 1, group B = 2, group C = 2) developed in five patients. Metastases appeared in six patients (17.6%) from 12 to 58 months postoperatively. Adequate renal function was obtained in 32 of the 34 patients. Mean follow-up for all patients was 64.6 months overall, 75.6 months from group A, 64.1 months for group B and 53.4 months for group C. The three and five year probabilities of survival for all patients were 77.8% and 69.5% respectively, 80% for group A, 80% for group B and 85% and 57.1% for group C. Enucleation and partial nephrectomy are both viable options in the management of solitary or bilateral renal cell carcinoma. There is no decline ineffective tumor control and prognosis.


Extraction and Characterization of Gelatin from Skin By-Products of Seabream, Seabass and Rainbow Trout Reared in Aquaculture.
The expansion of fish filleting, driven by the increasing demand for convenience food, concomitantly generates a rising amount of skinning by-products. Current trends point to a growing share of aquaculture in fish production, so we have chosen three established aquaculture species to study the properties of gelatin extracted from their skin: rainbow trout, commonly filleted; and seabass and seabream, marketed whole until very recently. In the first case, trout skin yields only 1.6% gelatin accompanied by the lowest gel strength (96 g bloom), while yield for the other two species exceeds 6%, and gel strength reaches 181 and 229 g bloom for seabass and seabream, respectively. These results are in line with the proportion of total imino acids analyzed in the gelatin samples. Molecular weight profiling shows similarities among gelatins, but seabass and seabream gelatins appear more structured, with higher proportion of β-chains and high molecular weight aggregates, which may influence the rheological properties observed. These results present skin by-products of seabream, and to a minor extent seabass, as suitable raw materials to produce gelatin through valorization processes.


Perceptions of oral cholera vaccine and reasons for full, partial and non-acceptance during a humanitarian crisis in South Sudan.
Oral cholera vaccination (OCV) campaigns were conducted from February to April 2014 among internally displaced persons (IDPs) in the midst of a humanitarian crisis in Juba, South Sudan. IDPs were predominantly members of the Nuer ethnic group who had taken refuge in United Nations bases following the eruption of violence in December 2013. The OCV campaigns, which were conducted by United Nations and non-governmental organizations (NGOs) at the request of the Ministry of Health, reached an estimated 85-96% of the target population. As no previous studies on OCV acceptance have been conducted in the context of an on-going humanitarian crisis, semi-structured interviews were completed with 49 IDPs in the months after the campaigns to better understand perceptions of cholera and reasons for full, partial or non-acceptance of the OCV. Heightened fears of disease and political danger contributed to camp residents' perception of cholera as a serious illness and increased trust in United Nations and NGOs providing the vaccine to IDPs. Reasons for partial and non-acceptance of the vaccination included lack of time and fear of side effects, similar to reasons found in OCV campaigns in non-crisis settings. In addition, distrust in national institutions in a context of fears of ethnic persecution was an important reason for hesitancy and refusal. Other reasons included fear of taking the vaccine alongside other medication or with alcohol. The findings highlight the importance of considering the target populations' perceptions of institutions in the delivery of OCV interventions in humanitarian contexts. They also suggest a need for better communication about the vaccine, its side effects and interactions with other substances.


Exploring the stability of the NHC-metal bond using thiones as probes.
The metal-carbon bond in N-heterocyclic carbene (NHC) metal complexes, which are ubiquitous in modern homogeneous catalysis, is often conjectured to be robust. Here, carbene dissociation was evaluated from a series of complexes with metals of relevance in catalysis containing either an Arduengo-type 2-imidazolylidene or a mesoionic 1,2,3-triazolylidene ligand through thione formation, revealing remarkable kinetic lability of the NHC-metal bond for, e.g. IrIII, RhIII, and NiII complexes.


A Novel Missense Variant in the Gene PPP2R5D Causes a Rare Neurodevelopmental Disorder with Increased Phenotype.
PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the PPP2R5D gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the PPP2R5D gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of PPP2R5D associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.