Virtual Reality Applications in Medicine During the COVID-19 Pandemic: Systematic Review.
Virtual reality can play an important role during the COVID-19 pandemic in the health care sector. This technology has the potential to supplement the traditional in-hospital medical training and treatment, and may increase access to training and therapies in various health care settings. This systematic review aimed to describe the literature on health care-targeted virtual reality applications during the COVID-19 crisis. We conducted a systematic search of the literature on the PsycINFO, Web of Science, and MEDLINE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search string was as follows: "[(virtual reality)] AND [(COVID-19) OR (coronavirus) OR (SARS-CoV-2) OR (healthcare)]." Papers published in English after December 2019 in peer-reviewed journals were selected and subjected to the inclusion and exclusion criteria. We used the Mixed Methods Appraisal Tool to assess the quality of studies and the risk of bias. Thirty-nine studies met the inclusion criteria. Seventeen studies showed the usefulness of virtual reality during the COVID-19 crisis for reducing stress, anxiety, depression, and pain, and promoting physical activity. Twenty-two studies revealed that virtual reality was a helpful learning and training tool during the COVID-19 crisis in several areas, including emergency medicine, nursing, and pediatrics. This technology was also used as an educational tool for increasing public understanding of the COVID-19 pandemic. Different levels of immersion (ie, immersive and desktop virtual reality), types of head-mounted displays (ie, PC-based, mobile, and standalone), and content (ie, 360° videos and photos, virtual environments, virtual reality video games, and embodied virtual agents) have been successfully used. Virtual reality was helpful in both face-to-face and remote trials. Virtual reality has been applied frequently in medicine during the COVID-19 pandemic, with positive effects for treating several health conditions and for medical education and training. Some barriers need to be overcome for the broader adoption of virtual reality in the health care panorama. International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) INPLASY202190108; https://inplasy.com/inplasy-2021-9-0108/.


Sustained-Release Buprenorphine Improves Postsurgical Clinical Condition but Does Not Alter Survival or Cytokine Levels in a Murine Model of Polymicrobial Sepsis.
Cecal ligation and perforation (CLP) is a common technique for studying sepsis in mice. Because of the invasiveness of the procedure and its effects on clinical condition, many animal care and use committees require the use of analgesics with CLP. However, some analgesics have immunomodulatory effects and thus can hinder the overall research outcomes of a project. Here we sought to determine the effects of buprenorphine hydrochloride (Bup HCl) compared with sustained-release buprenorphine (Bup SR) on clinical condition, plasma concentrations of monocyte chemoattractant protein (MCP) 1 and IL6, and overall mortality in a murine CLP model of sepsis. Male C57/BL6 mice underwent CLP surgery and received Bup HCl or Bup SR as a component of an IACUCapproved analgesic dosing regimen. Mice were observed twice daily for clinical condition scoring by the same blinded investigator for the duration of the study. MCP1 and IL6 levels and mortality did not differ significantly between the 2 groups. Scoring of clinical condition revealed a significant decrease in behaviors associated with perceived pain at 12 and 24 h postoperatively in mice in the Bup SR group compared with the Bup HCl group. Because of the lack of significant effect on MCP1 and IL6 levels and mortality and the superior analgesic effects of Bup SR, we recommend the use of Bup SR for analgesia during the murine CLP model of sepsis.


Distribution of bovine fetuin and albumin in plasma, allantoic and amniotic fluids during development.
A radioimmunoassay for bovine fetuin was developed and its specificity and validity established. Albumin was measured by radial-immunodiffusion assay. Fetuin levels in fetal plasma increased from 10 to 15 mg/ml between 4 and 8 months of gestation; albumin levels remained higher than fetuin. Neonatal plasma fetuin levels rapidly declined during the first 14 days post partum, coincident with a marked reciprocal increase in albumin levels. In allantoic fluid fetuin and albumin concentrations reached a peak at 7 months but fetuin values were always higher. In amniotic fluid both proteins peaked at 8 months; albumin levels were similar to those in allantoic fluid but fetuin values remained consistently lower than those in allantoic fluid throughout gestation. Fetuin levels in maternal plasma declined from 0.7 to 0.4 mg/ml between 1 month and term. We conclude that (1) at term there is an abrupt change from fetuin synthesis to increased albumin synthesis by the neonatal liver; (2) fetuin appears to be preferentially accumulated in the allantois whereas albumin is equally concentrated in the allantois and amnion.


Duplication and diversification of the spermidine/spermine N1-acetyltransferase 1 genes in zebrafish.
Spermidine/spermine N(1)-acetyltransferase 1 (Ssat1) is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis. In addition, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis. Using cross-genomic bioinformatic analysis in 10 deuterostomes, we found that ssat1 only exists in vertebrates. Comparing with mammalian, zebrafish, an evolutionarily distant vertebrate, contains 3 homologous ssat1 genes, named ssat1a, ssat1b, and ssat1c. All zebrafish homologues could be transcribed and produce active enzymes. Despite the long history since their evolutionary diversification, some features of human SSAT1 are conserved and subfunctionalized in the zebrafish family of Ssat1 proteins. The polyamine-dependent protein synthesis was only found in Ssat1b and Ssat1c, not in Ssat1a. Further study indicated that both 5' and 3' sequences of ssat1b mediate such kind of translational regulation inside the open reading frame (ORF). The polyamine-dependent protein stabilization was only observed in Ssat1b. The last 70 residues of Ssat1b were crucial for its rapid degradation and polyamine-induced stabilization. It is worth noting that only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, were able to interact with integrin α9 and Hif-1α. Thus, Ssat1b and Ssat1c might not only be a polyamine metabolic enzyme but also simultaneously respond to polyamine levels and engage in cross-talk with other signaling pathways. Our data revealed some correlations between the sequences and functions of the zebrafish family of Ssat1 proteins, which may provide valuable information for studies of their translational regulatory mechanism, protein stability, and physiological functions.


"Whether I like it or not, it's important": Implicit importance of means predicts self-regulatory persistence and success.
To effectively self-regulate, people must persevere on tasks that they deem important, regardless of whether those tasks are enjoyable. Building on past work that has noted the fundamental role of implicit cognition in guiding effective self-regulation, the present paper tests whether an implicit association between goal means and importance predicts self-regulatory persistence and success. Implicit importance predicted markers of effective self-regulation-better grades, more studying and exercise, and stronger standardized testing performance-over and above, and often better than, explicit beliefs about the importance of that self-regulation, as well as implicit evaluations of those means. In particular, those for whom tasks were fairly taxing to complete (i.e., those for whom this self-regulation required effortful self-control) were those who most benefitted from the implicit association between means and importance. Moreover, when participants were reminded of recent self-regulatory failure that they believed could be overcome through hard work, implicit importance toward the means increased as if to prepare them to achieve self-regulatory persistence. A final study sought to reconcile the present findings with previous work showing the key role that implicit evaluations play in effective self-regulation. We reasoned that means are important precisely because they are associated with valued end-states. Consistent with this account, implicit evaluations of end-states predicted the implicit importance of means, which in turn predicted effective self-regulation. (PsycINFO Database Record


Diagnostic Leukapheresis Enables Reliable Transcriptomic Profiling of Single Circulating Tumor Cells to Characterize Inter-Cellular Heterogeneity in Terms of Endocrine Resistance.
Circulating tumor cells (CTCs) hold great promise with regard to prognosis, treatment optimization, and monitoring of breast cancer patients. Single CTC transcriptome profiling might help reveal valuable information concerning intra-patient heterogeneity relevant to therapeutic interventions. In this study, we combined Diagnostic Leukapheresis (DLA), which is a microfluidic enrichment using the ParsortixTM system, micromanipulation with CellCelectorTM and subsequent single cell multi-marker transcriptome profiling. First, a PCR panel consisting of 30 different endocrine resistance and phenotypic marker genes was validated for single cell profiling by using different breast cancer cell lines. Second, this panel was applied to characterize uncultured and cultured CTCs, which were enriched from a cryopreserved DLA product obtained from a patient suffering from metastatic breast cancer resistant to endocrine therapy. Gene expression profiles of both CTC populations uncovered inter CTC heterogeneity for transcripts, which are associated with response or resistance to endocrine therapy (e.g., ESR1, HER2, FGFR1). Hierarchical clustering revealed CTC subpopulations with different expressions of transcripts regarding the CTCs' differential phenotypes (EpCAM, CD44, CD24, MYC, MUC1) and of transcripts involved in endocrine signaling pathways (FOXO, PTEN). Moreover, ER-positive CTCs exhibited significant higher expression of Cyclin D1, which might be relevant for CDK4/6 inhibitor therapies. Overall, gene expression profiles of uncultured and cultured CTCs resulted in a partly combined grouping. Our findings demonstrate that multi-marker RNA profiling of enriched single uncultured CTCs and cultured CTCs form cryopreserved DLA samples may provide important insights into intra-patient heterogeneity relevant for targeted therapies and therapy resistance.


Tissue distribution and metabolism of radioiodinated DTPA0, D-Tyr1 and Tyr3 derivatives of octreotide in rats.
Lesions containing somatostatin receptors (SSR) in rats and in man can be visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With the latter the residence time of radioactivity (111In) in SSR-positive targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs. [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized, and all 4 showed high and specific binding to the SSR in vitro, with IC50 values in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50 values. The metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood ratios were calculated. High uptake of all OCT analogs was found in the somatostatin receptor-positive tissues at 4 hours, but only remained high at 24 and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I-D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D-Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours respectively). The position of the Tyr residues and the addition of the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT analogs.


Labelling and cross-linking of Escherichia coli penicillin-binding proteins with bis-beta-lactam antibiotics.
We have synthesized a number of radioactively labelled bis-beta-lactams, which are nearly symmetrical dimers of well-known beta-lactam antibiotics and act as bifunctional specific cross-linking reagents for the penicillin-binding proteins of Escherichia coli envelopes. We have observed that some of our bis-beta-lactam antibiotics cross-link two molecules of penicillin-binding protein 1b or 1c or 3. Furthermore our bis-beta-lactam antibiotics bind to E. coli proteins with higher affinities than the beta-lactams from which they were derived. Therefore, a number of monomeric protein bands are consistently labelled with our bis-beta-lactam antibiotics (190, 170, 145 and 124 kDa) as well as the previously described penicillin-binding proteins 1a, 1b, 1c, 2, 3, 4, 5, 6, 7 and 8. We do not know yet the possible enzymic activities of the penicillin-binding proteins of 190 kDa, 170 kDa, 145 kDa and 125 kDa that were not described previously. We have also detected some protein bands moving very slowly, which appear to be dimers or cross-linking species of these new high-molecular-mass penicillin-binding proteins described above.


[Detection of HTLV-III-specific sequences in T-lymphocyte lines by molecular hybridization].
The methods of molecular hybridization are described using 32P-labeled plasmid pBHIO carrying the cloned HTLV-III provirus employed for the detection of HTLV-III-specific sequences in lines of T-lymphocytes from patients with acquired immune deficiency syndrome. The presence of virus-specific sequences was demonstrated in 13 out of 20 lines examined by the dot-blot hybridization method. The blot-hybridization method revealed differences in sites of Hind III restriction in 2 out of 6 lines studied. The possibility of combined infection of line No. 17 with two different variants of HTLV-III is discussed.


A Statistical Consideration Regarding the Threshold of the Psychopathy Checklist-Revised.
The Psychopathy Checklist-Revised (PCL-R; Hare, 2003 ) is one of the most commonly used measures of psychopathy. Scores range from 0 to 40, and legal and mental health professionals sometimes rely on a cut score or threshold to classify individuals as psychopaths. This practice, among other things, assumes that all items contribute equally to the overall raw score. Results from an item response theory analysis (Bolt, Hare, Vitale, & Newman, 2004 ), however, indicate that PCL-R items differ in the amount of information they can provide about psychopathy. We examined the consequences of these item differences for using a cut score, detailing the consequences for a previously applied cut score of 30 as an example. Results indicated that there were more than 8.5 million different response combinations that equaled 30 and more than 14.2 million that equaled 30 or more. This raw score, like others, corresponded to a broad range of PCL-R-defined psychopathy, indicating that applying cut scores on this measure results in imprecise quantifications of psychopathy. We show that by using the item parameters along with an individual's particular scores on the PCL-R items, it is possible to arrive at a more precise understanding of an individual's level of psychopathy on this instrument.


Optimizing Genomic Prediction of Host Resistance to Koi Herpesvirus Disease in Carp.
Genomic selection (GS) is increasingly applied in breeding programs of major aquaculture species, enabling improved prediction accuracy and genetic gain compared to pedigree-based approaches. Koi Herpesvirus disease (KHVD) is notifiable by the World Organization for Animal Health and the European Union, causing major economic losses to carp production. GS has potential to breed carp with improved resistance to KHVD, thereby contributing to disease control. In the current study, Restriction-site Associated DNA sequencing (RAD-seq) was applied on a population of 1,425 common carp juveniles which had been challenged with Koi herpes virus, followed by sampling of survivors and mortalities. GS was tested on a wide range of scenarios by varying both SNP densities and the genetic relationships between training and validation sets. The accuracy of correctly identifying KHVD resistant animals using GS was between 8 and 18% higher than pedigree best linear unbiased predictor (pBLUP) depending on the tested scenario. Furthermore, minor decreases in prediction accuracy were observed with decreased SNP density. However, the genetic relationship between the training and validation sets was a key factor in the efficacy of genomic prediction of KHVD resistance in carp, with substantially lower prediction accuracy when the relationships between the training and validation sets did not contain close relatives.


Application of the passive haemolysis test for the determination of rubella virus antibodies.
A passive haemolysis test for the determination of antibodies against rubella virus haemagglutinin is presented. According to this method, the principle of radial immunodiffusion techinque is applied. Rubella haemagglutinin-coated chick erythrocytes in the agarose gel were lysed by the diffusing positive sera of complement at 37 degrees C. The passive haemolysis test was compared with the conventional haemagglutination inhibition method, and the diameter of the haemolysis zones was shown to be a direct measure of the quantity of antibody added to the well. A plot of the log (HI titre) against the zone diameter gives a straight line. There is no need to remove nonspecific haemagglutination inhibitors. However, all serum samples must be inactivated at 56 degrees C for 30 minutes before testing. Tests of 200 serum samples from healthy women showed a good correlation between the haemagglutination inhibition titre and the antibody titre determined by the passive haemolysis technique. Twenty-one samples with a haemagglutination inhibition titre less than 10 were also negative in the passive haemolysis test. With the exception of one, all sera with a positive haemagglutination inhibition titre showed a positive haemolysis reaction. The method was found to be as specific and as sensitive as the haemagglutination inhibition test. In addition, the technique is rapid and simple for quantitative studies of antibodies against rubella virus.


Multiple endocrine neoplasia type 2A (MEN 2A) syndrome in a South African family. Biochemistry and molecular genetics.
Multiple endocrine neoplasia type 2A (MEN 2A), an uncommon heritable disease, was investigated in an Afrikaner kindred. Serum calcitonin levels after combined pentagastrin and calcium chloride stimulation were measured to determine thyroid involvement, as were urinary metadrenalin levels to determine adrenal gland involvement. MEN 2A genotype status was determined using the DNA probe MCK2 (D10S15). The index patient, who showed both thyroid and adrenal gland involvement, died of phaeochromocytoma complications. Thirty-four of his 114 family members, in 4 generations, were investigated. Nine had positive histological and calcitonin tests and were predicted to be MEN 2A genotypes by DNA analysis. One asymptomatic individual had a positive calcitonin test after being predicted to be a MEN 2A genotype with the probe MCK2. In 3 DNA-positive cases calcitonin stimulation tests were negative. Preclinical detection of the heritable form of MEN 2A will be facilitated by utilising the DNA probe MCK2 to determine carrier status in this large South African family. It is also the first South African family in which biochemical and molecular genetic techniques were used to facilitate diagnosis.


Coping, stress, and social resources among adults with unipolar depression.
We used a stress and coping paradigm to guide the development of indices of coping responses and to explore the roles of stress, social resources, and coping among 424 men and women entering treatment for depression. We also used an expanded concept of multiple domains of life stress to develop several indices of ongoing life strains. Although most prior studies have focused on acute life events, we found that chronic strains were somewhat more strongly and consistently related to the severity of dysfunction. The coping indices generally showed acceptable conceptual and psychometric characteristics and only moderate relationships to respondents' sociodemographic characteristics or to the severity of the stressful event for which coping was sampled. Coping responses directed toward problem solving and affective regulation were associated with less severe dysfunction, whereas emotional-discharge responses, more frequently used by women, were linked to greater dysfunction. Stressors, social resources, and coping were additively predictive of patient's functioning, but coping and social resources did not have stress-attenuation or buffering effects.


Expression of laccase gene lcc1 in Coprinopsis cinerea under control of various basidiomycetous promoters.
Coprinopsis cinerea laccase gene lcc1 was expressed in this basidiomycete under naturally non-inductive conditions using various homologous and heterologous promoters. Laccase expression was achieved in solid and liquid media with promoter sequences from the C. cinerea tub1 gene, the Agaricus bisporus gpdII gene, the Lentinus edodes priA gene and the Schizophyllum commune Sc3 gene. As measured by enzyme activity in liquid cultures, a 277-bp gpdII promoter fragment, followed by a 423-bp priA fragment, was most efficient. A shorter priA sequence of 372 bp was inactive. tub1 promoter fragments were reasonably active, whereas the S. commune Sc3 promoter sequence was less active, in comparison. Irrespective of the promoter used, addition of copper to the medium increased enzymatic activities for highly active transformants by 10- to 50-fold and for less active transformants for 2- to 7-fold. The highest enzymatic activities (3 U/ml) were reached with the gpdII promoter in the presence of 0.1 mM CuSO(4).


An exploration of teaching presence in online interprofessional education facilitation.
Although the prevalence of online asynchronous interprofessional education (IPE) has increased in the last decade, little is known about the processes of facilitation in this environment. The teaching presence element of the Community of Inquiry Framework offers an approach to analyze the contributions of online facilitators, however, to date it has only been used on a limited basis in health professions education literature. Using an exploratory case study design, we explored the types of contributions made by IPE facilitators to asynchronous interprofessional team discussions by applying the notion of teaching presence. Using a purposeful sampling approach, we analyzed 14 facilitators' contributions to asynchronous team discussion boards in an online IPE course. We analyzed data using directed content analysis based on the key indicators of teaching presence. The online IPE facilitators undertook the three critical pedagogical functions identified in teaching presence: facilitating discourse, direct instruction, and instructional design and organization. While our data fitted well with a number of key activities embedded in these three functions, further modification of the teaching presence concept was needed to describe our facilitators' teaching presence. This study provides an initial insight into the key elements of online asynchronous IPE facilitation. Further research is required to continue to illuminate the complexity of online asynchronous IPE facilitation.


Lack of Impact of Body Mass Index at Young Age on Otitis Media Occurrence During Preschool Years: Wheezing Illnesses Study Leidsche Rijn Cohort Study.
Using data on weight and height at 6 and 11 months of age and primary care electronic health records data from 1960 children participating in the Wheezing Illnesses Study Leidsche Rijn birth cohort study, we found that body mass index at 6 and 11 months of age was not associated with otitis media occurrence during the first 4 years of life.


Effect of late pregnancy on salicylate, diazepam, warfarin, and propranolol binding: use of fluorescent probes.
Serum protein binding was measured in six women 38 wk pregnant and in five control subjects. Three distinct binding sites for drugs on human serum albumin have been identified. To determine whether changes in binding during pregnancy occur for common drugs or only for drugs that bind to a specific binding site, serum protein binding of three drugs--diazepam (site I), warfarin (site III), and salicylate--and four fluorescent probes--dansylsarcosine (site I), 1-anilino-8-naphthalenesulfonate (site I), 7-anilinocoumarin-4-acetic acid (site II), and 5-dimethylaminonaphthalene-1-sulfonamide (DNSA) (site III)--were determined in control and pregnant sera. Unbound fractions of diazepam and salicylate in pregnant women increased but the unbound fraction of warfarin did not change. Dissociation constants (Kd1) of all fluorescent probes but DNSA were almost the same in control and pregnant sera, while the Kd1 of DNSA in pregnant serum was approximately 50% of control. Binding capacities of all probes decreased, which was attributed to decreased serum albumin concentration. We concluded that serum protein binding of drugs that bind to site I or site II on albumin decreased largely because of the reduced serum albumin concentration during pregnancy and that the binding of drugs that bind to site III changed little because of compensating effects of the decrease in serum albumin concentration and the increase in binding affinity to serum albumin. Serum concentration of alpha 1-acid glycoprotein and serum binding of propranolol did not change in pregnant women.


Reduction in nosocomial infection with improved hand hygiene in intensive care units of a tertiary care hospital in Argentina.
Hand hygiene is a fundamental measure for the control of nosocomial infection. However, sustained compliance with hand hygiene in health care workers is poor. We attempted to enhance compliance with hand hygiene by implementing education, training, and performance feedback. We measured nosocomial infections in parallel. We monitored the overall compliance with hand hygiene during routine patient care in intensive care units (ICUs); 1 medical surgical ICU and 1 coronary ICU, of 1 hospital in Buenos Aires, Argentina, before and during implementation of a hand hygiene education, training, and performance feedback program. Observational surveys were done twice a week from September 2000 to May 2002. Nosocomial infections in the ICUs were identified using the National Nosocomial Infections Surveillance (NNIS) criteria, with prospective surveillance. We observed 4347 opportunities for hand hygiene in both ICUs. Compliance improved progressively (handwashing adherence, 23.1% (268/1160) to 64.5% (2056/3187) (RR, 2.79; 95% CI: 2.46-3.17; P < .0001). During the same period, overall nosocomial infection in both ICUs decreased from 47.55 per 1000 patient-days (104/2187) to 27.93 per 1000 patient days (207/7409) RR, 0.59; 95% CI: 0.46-0.74, P < .0001). A program consisting of focused education and frequent performance feedback produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction in nosocomial infection rates in the ICUs.


A Pilot Randomized Controlled Trial on the Effects of a Progressive Exercise Program on the Range of Motion and Upper Extremity Grip Strength in Young Adults With Breast Cancer.
The diagnosis of breast cancer in young women (aged 18-45 years) has been increasing. Women are commonly left coping with treatment-related disabilities of the upper limb that can persist for > 2 years postoperatively. A total of 59 young breast cancer patients (29 in the intervention group and 30 in the control group) participated in a pilot prospective randomized controlled trial to determine whether a 12-week postradiation exercise program would improve long-term arm mobility, pain, and handgrip strength. During an 18-month period, range of motion, handgrip strength, and pain with shoulder movements were evaluated at 6 points. Although the differences were not statistically significant, external rotation and horizontal abduction of the shoulder improved in the intervention group immediately after the exercise intervention (3 months) and showed a trend toward less pain on movement. However, at 18 months after radiation the control and intervention groups both retained a residual loss of range and persistent pain with movement. Radiation to the axilla and/or chest wall yielded long-term (18 months) limitations in flexion and horizontal abduction compared with hypofractionation, which resulted in greater flexion and external rotation at 18 months. The median grip strength of the study participants corresponded to the 10th percentile of healthy aged-matched white women. The exercise intervention timed shortly after radiation improved short-term shoulder mobility and pain; however, these gains were not sustained at 18 months after radiation.


Understanding the Full Spectrum of Organ Injury Following Intrapartum Asphyxia.
Birth asphyxia is a significant global health problem, responsible for ~1.2 million neonatal deaths each year worldwide. Those who survive often suffer from a range of health issues including brain damage-manifesting as cerebral palsy (CP)-respiratory insufficiency, cardiovascular collapse, and renal dysfunction, to name a few. Although the majority of research is directed toward reducing the brain injury that results from intrapartum birth asphyxia, the multi-organ injury observed in surviving neonates is of equal importance. Despite the advent of hypothermia therapy for the treatment of hypoxic-ischemic encephalopathy (HIE), treatment options following asphyxia at birth remain limited, particularly in low-resource settings where the incidence of birth asphyxia is highest. Furthermore, although cooling of the neonate results in improved neurological outcomes for a small proportion of treated infants, it does not provide any benefit to the other organ systems affected by asphyxia at birth. The aim of this review is to summarize the current knowledge of the multi-organ effects of intrapartum asphyxia, with particular reference to the findings from our laboratory using the precocial spiny mouse to model birth asphyxia. Furthermore, we reviewed the current treatments available for neonates who have undergone intrapartum asphyxia, and highlight the emergence of maternal dietary creatine supplementation as a preventative therapy, which has been shown to provide multi-organ protection from birth asphyxia-induced injury in our preclinical studies. This cheap and effective nutritional supplement may be the key to reducing birth asphyxia-induced death and disability, particularly in low-resource settings where current treatments are unavailable.


Effects of terpenoid precursor feeding on Catharanthus roseus hairy roots over-expressing the alpha or the alpha and beta subunits of anthranilate synthase.
Among the pharmacologically important terpenoid indole alkaloids produced by Catharanthus roseus are the anti-cancer drugs vinblastine and vincristine. These two drugs are produced in small yields within the plant, which makes them expensive to produce commercially. Metabolic engineering has focused on increasing flux through this pathway by various means such as elicitation, precursor feeding, and introduction of genes encoding specific metabolic enzymes into the plant. Recently in our lab, a feedback-resistant anthranilate synthase alpha subunit was over-expressed in C. roseus hairy roots under the control of a glucocorticoid inducible promoter system. Upon induction we observed a large increase in the indole precursors, tryptophan, and tryptamine. The current work explores the effects of over-expressing the anthranilate synthase alpha or alpha and beta subunits in combination with feeding with the terpenoid precursors 1-deoxy-D-xylulose, loganin, and secologanin. In feeding 1-deoxy-D-xylulose to the hairy root line expressing the anthranilate synthase alpha subunit, we observed an increase of 125% in hörhammericine levels in the induced samples, while loganin feeding increased catharanthine by 45% in the induced samples. Loganin feeding to the hairy root line expressing anthranilate synthase alpha and beta subunits increases catharanthine by 26%, ajmalicine by 84%, lochnericine by 119%, and tabersonine by 225% in the induced samples. These results suggest that the terpenoid precursors to the terpenoid indole alkaloids are important factors in terpenoid indole alkaloid production.


The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study.
Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population. In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants. The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache. Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.


Beta-functionalised polythiophenes as microelectrode modifiers in low conductive media.
A study on polythiophene coated microelectrodes is reported, the goal being that of checking the capability of these electrochemical systems to work in low conductive media. The possibility of electrochemically p-doping the polymer in the presence of very low concentrations or even in the absence of supporting electrolyte in the solution is ascertained, opening the way to the use of similar systems in pure solvent media. This result is obtained in such conditions that the presence of residual charges--and corresponding counterions--trapped inside the film coating can be reasonably hypothesised.


The fragile self: narcissistic disturbance and the protective function of depression.
The role of self-esteem in the aetiology of depressive disorders is not limited to negative self-evaluations. A broader concept, embracing the experience of the self, is necessary. A developmental model of self-esteem regulation is proposed, derived in part from Mahler's work on separation-individuation in infants and Kohut's work on narcissism. A concept of a 'fragile self' is formulated and developed; the depressive state is seen as protecting this fragile self. The model provides a coherent account of individual differences in proneness to depression (in interaction with environmental factors) which is useful to psychotherapists, yet open to empirical test and research use. The model is discussed in relation to psychological research on depression and implications for clinical practice are outlined.


Evaluation of altered expression of miR-9 and miR-106a as an early diagnostic approach in gastric cancer.
The role of microRNAs (miRNAs) in cellular processes such as growth, apoptosis, differentiation and proliferation verifies the importance of miRNAs in carcinogenesis. Moreover, levels of miRNAs are dysregulated in cancer cells, so they could be used as novel classes of biomarkers for diagnosing cancer. The oncogenic role of miR-106a and its increased expression have been demonstrated in some cancers. In contrast, there is no consensus for miR-9 expression rate in different cancers. Therefore, this study was done to investigate the role of miR-106a and miR-9 in gastric cancer (GC). The current study was performed on 31 GC tissues as case, and 31 healthy adjacent tissues as a control group. Quantitative reverse transcriptase (q-RT) PCR was used for studying the expression rate of both miR-106a and miR-9. The expression rate of both miRNAs in cancerous tissues was significantly higher than healthy adjacent tissues (≈10 folds) (P<0.05). The results showed that the expression rate of both markers was significantly increased in cancerous tissues. Therefore, they can be suggested as potential biomarkers for cancer diagnosis and prognosis as well as targets for therapy.


Rehabilitation in nursing homes.
Rehabilitation is a key concept in the government's plans to modernize the NHS. Its aim is to restore a person's autonomy, although there are sometimes barriers to making effective rehabilitation a reality, some of which are explored here, along with ways of helping teams in nursing homes to undertake more effective rehabilitation.


Roles of lncRNAs Mediating Wnt/β-Catenin Signaling in HCC.
Hepatocellular carcinoma (HCC) is considered the second most deadly cancer worldwide. Due to the absence of early diagnostic markers and effective therapeutic approaches, distant metastasis and increasing recurrence rates are major difficulties in the clinical treatment of HCC. Further understanding of its pathogenesis has become an urgent goal in HCC research. Recently, abnormal expression of long noncoding RNAs (lncRNAs) was identified as a vital regulator involved in the initiation and development of HCC. Activation of the Wnt/β-catenin pathway has been reported to obviously impact cell proliferation, invasion, and migration of HCC. This article reviews specific interactions, significant mechanisms and molecules related to HCC initiation and progression to provide promising strategies for treatment.


High CTC-TRPC5 Expression Significantly Associated With Poor Prognosis in Radical Resected Colorectal Cancer Patients.
Recurrence is the main reason of treatment failure of redical resected colorectal cancer (CRC). Although some factors including staging and differentiation have been proven to useful for recurrence evaluation, prognosis of certain patients does not conform to this evaluation approach. Circulating tumor cells (CTC) have been found to have prognostic value in CRC, and previous studies on CTC have primarily focused on their numbers. CTC are functionally heterogeneous cell populations, and different CTC subgroups may have different functions and clinical values. In our previous study, we discovered that elevated expression of the transient receptor potential channel TRPC5 was associated with a significantly poor prognosis in CRC. In this study, we collected peripheral blood from CTC-positive CRC patients, identified the TRPC5 protein expression on CTC (CTC-TRPC5), and analyzed the relationship between CTC-TRPC5 expression levels and the prognosis. The results showed that CTC-TRPC5 level is significantly related to the T stage and differentiation of tumors. High level of CTC-TRPC5 is more common in a high T stage as well as poorly differentiated tumors and is significantly associated with shorter disease free survival (DFS). The median DFS of CRC patients with high and low CTC-TRPC5 level was 17.1 and 22.0 months, respectively (p < 0.05). This study revealed a clinically significant CTC subgroup of CRC, providing a new indicator for clinical evaluation of CRC prognosis.


Robust Virtual Sensing of the Vehicle Sideslip Angle through the Cross-Combination of Multiple Filters Using a Decision Tree Algorithm.
This paper presents a state-of-the-art estimation technique by cross-combining a number n of filters for high-precision, reliable and robust vehicle sideslip angle state estimation, over a full range of vehicle operations irrespective of the driving mission and disruptions that may occur in the system. A machine-learning algorithm based on decision trees connects several filters together to switch between them according to the driving context, ensuring the best possible state estimate for relatively small and large sideslip angle values. In conjunction with the above-mentioned aspects, a seamless transition between different vehicle models is attained by observing the key parameters characterizing the lateral motion of the vehicle. The tests conducted using a prototype vehicle on a snow-covered track confirm the effectiveness and reliability of the proposed approach.


Studies on reticulin. I: Serological and immunohistological investigations of the occurrence of collagen type III, fibronectin and the non-collagenous glycoprotein of Pras and Glynn in reticulin.
Collagen Type III, fibronectin and a non-collagenous reticulin component (NCRC) are all secretory products of fibroblasts and other mesenchymal cells. Antisera to human collagen III (isolated from the placenta) human plasma fibronectin, and NCRC (from spleen) have been used to examine possible antigenic relationships between these proteins both by serological studies and by comparison of the distribution of the proteins in various tissues using immunofluorescence. For other comparative purposes, the distribution of collagen and of reticulin in the same tissues was also sought using conventional histological methods. Serologically, the 3 antisera showed distinct specificities. However, when used on sections all 3 antisera gave closely similar staining patterns broadly resembling that of histological "reticulin", although minor differences were noted to be characteristic of the distribution of the respective antigens in certain tissues and in cell monolayers. The results support previous suggestions that histological "reticulin" is not a single entity but is a compound fibrous structure containing collagen Type III, fibronectin and at least 1 additional non-collagenous glycoprotein (NCRC).


Aqueous Nyctanthes arbortristis and doxorubicin conjugated gold nanoparticles synergistically induced mTOR-dependent autophagy-mediated ferritinophagy in paclitaxel-resistant breast cancer stem cells.
Aim: Nyctanthes arbortristis Linn is a potential anti-diabetic drug that reduces glucose levels by delaying carbohydrate digestion. The tumor microenvironment is characterized by elevated glucose levels that activate various genes, such as mTOR. mTOR plays a critical role in maintaining the hypoxic environment and inhibiting autophagy. Although natural compounds pose fewer side effects, their hydrophobic nature makes these compounds not suitable as therapeutics. Hence, we conjugated aqueous NAT into gold nanoparticles (AuNP) in the current study and evaluated the ability of the chosen drugs to induce cell death in breast cancer cells resistant to Paclitaxel. Materials and methods: Particle size analyzer, UV-Vis spectrophotometer, FTIR, and XRD were used in the present study to characterize NAT and Doxorubicin encapsulated AuNPs. To check the cytotoxic effect of AuNP-NAT and AuNP-doxorubicin on PacR/MCF-7 stem cells MTT assay was performed. RT-PCR was performed to check the altered expression of ferritinophagy-related genes. The proliferation and migration potential of the cells before and after treatment with the desired drug combinations was evaluated by clonogenic and scratch assays, respectively. Flow cytometry analysis was done to quantify apoptotic bodies and cell cycle arrest. Cellular ROS was determined using DCD-FA staining. Results and conclusion: NAT and doxorubicin loaded into AuNP showed enhanced stability and induced ferritinophagy in PacR/MCF-7 stem cells. The obtained results suggest that AuNP-NAT, combined with a low AuNP-Doxorubicin nanoconjugate dose, might be an effective anti-neoplastic drug targeting the necroptosis-autophagy axis, thereby reducing the adverse side-effects induced by the conventional chemotherapeutic drugs.


Control mechanisms operating for lipid biosynthesis differ in oil-palm (Elaeis guineensis Jacq.) and olive (Olea europaea L.) callus cultures.
As a prelude to detailed flux control analysis of lipid synthesis in plants, we have examined the latter in tissue cultures from two important oil crops, olive (Olea europaea L.) and oil palm (Elaeis guineensis Jacq.). Temperature was used to manipulate the overall rate of lipid formation in order to characterize and validate the system to be used for analysis. With [1-14C]acetate as a precursor, an increase in temperature from 20 to 30 degrees C produced nearly a doubling of total lipid labelling. This increase in total lipids did not change the radioactivity in the intermediate acyl-(acyl carrier protein) or acyl-CoA pools, indicating that metabolism of these pools did not exert any significant constraint for overall synthesis. In contrast, there were some differences in the proportional labelling of fatty acids and of lipid classes at the two temperatures. The higher temperature caused a decrease in polyunsaturated fatty acid labelling and an increase in the proportion of triacylglycerol labelling in both calli. The intermediate diacylglycerol was increased in olive, but not in oil palm. Overall the data indicate the suitability of olive and oil-palm cultures for the study of lipid synthesis and indicate that de novo fatty acid synthesis may exert more flux control than complex lipid assembly. In olive, diacylglycerol acyltransferase may exert significant flux control when lipid synthesis is rapid.


[Osteonecrosis of the femoral head].
The femoral head is the main location of avascular osteonecrosis. The lesion remains asymptomatic for several months or years before causing non specific hip pain. Risk factors have been identified, mainly femoral neck fractures, corticosteroid therapy and related conditions (lupus erythematosus, organ transplantations), alcohol abuse, dyslipidemia, sickle cell disease, HIV infection, caisson workers, Gaucher's disease, male sex. When typical radiological signs are lacking, MRI is the best investigation. Progression toward hip joint damage highly depends on the necrotic volume assessed at MRI. The combination of plain radiographs which help staging the severity of osteonecrosis, and MRI which indicates the prognosis of the lesion, determines the therapeutic options: symptomatic pain relief therapies or surgical treatment (core decompression, osteotomy or total hip replacement).


A fine structural study of the development of the chick flexor digital tendon: a model for synovial sheathed tendon healing.
The development of the synovial sheathed flexor digital tendon in the chick was studied by light and electron microscopy in 12-day embryos to 22-day post-hatched chickens. Areas of specialized connective tissue differentiation were identified in this complex structure consisting of a lubricated synovial sheath, elastic vincula and fibrocartilaginous adaptations on the surface of the tendon. The presence of some of these specialized adaptations may be related to the specific types of mechanical forces and stresses applied to the developing connective tissue system. This model system appears to be appropriate for the experimental study of tendon injuries related to the human hand.


Search for a low-mass standard model Higgs boson in the ττ decay channel in pp collisions at sqrt[s]=1.96 TeV.
We report on a search for the standard model Higgs boson decaying into pairs of τ leptons in pp collisions produced by the Tevatron at sqrt[s]=1.96 TeV. The analyzed data sample was recorded by the CDFII detector and corresponds to an integrated luminosity of 6.0 fb(-1). The search is performed in the final state with one τ decaying leptonically and the second one identified through its semihadronic decay. Since no significant excess is observed, a 95% credibility level upper limit on the production cross section times branching ratio to the ττ final state is set for hypothetical Higgs boson masses between 100 and 150 GeV/c2. For a Higgs boson of 120 GeV/c2 the observed (expected) limit is 14.6 (15.3) the predicted value.


Steps to Ensure a Successful Implementation of Occupational Health and Safety Interventions at an Organizational Level.
There is increasing meta-analytic evidence that addresses the positive impact of evidence-based occupational health and safety interventions on employee health and well-being. However, such evidence is less clear when interventions are approached at an organizational level and are aimed at changing organizational policies and processes. Given that occupational health and safety interventions are usually tailored to specific organizational contexts, generalizing and transferring such interventions to other organizations is a complex endeavor. In response, several authors have argued that an evaluation of the implementation process is crucial for assessing the intervention's effectiveness and for understanding how and why the intervention has been (un)successful. Thus, this paper focuses on the implementation process and attempts to move this field forward by identifying the main factors that contribute toward ensuring a greater success of occupational health and safety interventions conducted at the organizational level. In doing so, we propose some steps that can guide a successful implementation. These implementation steps are illustrated using examples of evidence-based best practices reported in the literature that have described and systematically evaluated the implementation process behind their interventions during the last decade.


Prognostic power of ventilatory responses during submaximal exercise in patients with chronic heart disease.
Although parameters obtained during submaximal exercise are known to be useful for predicting mortality in cardiac patients, it has been a matter of debate whether the submaximal parameters are superior to peak oxygen uptake (VO(2)). For this purpose, we aimed to determine the best index among exercise variables in predicting long-term mortality in patients with chronic heart disease. The study population consisted of 385 consecutive patients with chronic heart disease who performed a symptom-limited incremental exercise test on a cycle ergometer. Breath-by-breath respiratory gas analysis was used to estimate the peak VO(2), the ratio of the increase in VO(2) to the increase in work rate (WR) [VO(2)/Delta WR], and the ratio of the increase in minute ventilation E to the increase in carbon dioxide output (VCO(2)) [Delta VE/Delta VCO(2)]. After 1,899 +/- 495 days of follow-up (mean +/- SD), 33 cardiovascular-related deaths occurred. Nonsurvivors achieved lower peak VO(2), lower VO(2)/Delta VWR, and higher Delta VE/Delta VCO(2) compared to the survivors. In the univariate Cox proportional hazards analysis, peak VO(2), VO(2)/Delta VWR, and Delta VE/Delta VCO(2) were found to be significant prognostic indexes of survival. However, multivariate analysis revealed O(2)/Delta VWR as an independent predictor of mortality and Delta VE/delta VCO(2) as a slightly weaker predictor. In this analysis, the prognostic power of peak O(2) was insignificant. Submaximal respiratory gas indexes are very likely to be more sensitive than peak VO(2) for predicting poor survival in ambulatory patients with chronic heart disease.


Seasonal influence on biochemical profile and serum protein electrophoresis for Boa constrictor amarali in captivity.
Similarly to other reptiles, snakes are ectothermic animals and depend exclusively on the environment for the maintenance of their physiological, biochemical and immunological processes. Thus, changes in biochemical values can be expected due to seasonal influence. Twenty-two adult specimens of Boa constrictor amarali kept in captivity were used. Blood collections were done in two different seasons: winter (July 2004) and summer (January 2005) for the following assays: uric acid, aspartate aminotransferase (AST), glucose, cholesterol, total protein, and serum protein electrophoresis. The mean biochemical results found in summer and winter, respectively, were: 6.3 ± 3.4 and 11.3 ± 6.2 mg/dL for uric acid; 28.7 ± 12.4 and 20.7 ± 16.2 UI/L for AST; 26.3 ± 17 and 17.4 ± 6.8 mg/dL for glucose; 67.3 ± 30.2 and 69.7 ± 38.5 mg/dL for cholesterol; and 5.9 ± 1.6 and 5.9 ± 1.4 g/dL for total protein. Results regarding electrophoresis in summer and winter, respectively, were: 1.9 ± 0.7 and 2.4 ± 0.6 g/dL for albumin; 0.7 ± 0.2 and 0.5 ± 0.2 g/dL for α-globulin; 1.5 ± 0.5 and 1.7 ± 0.6 g/dL for β-globulin; and 1.8 ± 0.5 and 1.5 ± 0.5 g/dL for γ-globulin. In the summer, there was a significant increase in AST and a decrease in uric acid (p < 0.05). Serum protein electrophoresis showed a significant increase in α-globulin fraction (p < 0.05) in the same season. There were not significant differences between seasons for the remaining variables. Based on these results, the period of the year must be considered in the interpretation of some biochemical values for these animals.


Mutant p53: it's not all one and the same.
Mutation of the TP53 tumor suppressor gene is the most common genetic alteration in cancer, and almost 1000 alleles have been identified in human tumors. While virtually all TP53 mutations are thought to compromise wild type p53 activity, the prevalence and recurrence of missense TP53 alleles has motivated countless research studies aimed at understanding the function of the resulting mutant p53 protein. The data from these studies support three distinct, but perhaps not necessarily mutually exclusive, mechanisms for how different p53 mutants impact cancer: first, they lose the ability to execute wild type p53 functions to varying degrees; second, they act as a dominant negative (DN) inhibitor of wild type p53 tumor-suppressive programs; and third, they may gain oncogenic functions that go beyond mere p53 inactivation. Of these possibilities, the gain of function (GOF) hypothesis is the most controversial, in part due to the dizzying array of biological functions that have been attributed to different mutant p53 proteins. Herein we discuss the current state of understanding of TP53 allele variation in cancer and recent reports that both support and challenge the p53 GOF model. In these studies and others, researchers are turning to more systematic approaches to profile TP53 mutations, which may ultimately determine once and for all how different TP53 mutations act as cancer drivers and whether tumors harboring distinct mutations are phenotypically unique. From a clinical perspective, such information could lead to new therapeutic approaches targeting the effects of different TP53 alleles and/or better sub-stratification of patients harboring TP53 mutant cancers.


Does the presence of coexisting diseases modulate the effectiveness of a low-dose estrogen/progestin, ethinylestradiol/drospirenone combination tablet in dysmenorrhea? Reanalysis of two randomized studies in Japanese women.
The purpose of this study was to investigate the effectiveness of a combination of ethinylestradiol (EE) and 0.02 mg/drospirenone (DRSP) 3 mg in Japanese women with dysmenorrhea and in particular to determine whether or not the presence of specific coexisting organic diseases (eg, endometriosis, uterine fibroids, uterine adenomyosis) has an impact on treatment. Four hundred and ten patients with dysmenorrhea aged 20 years or older (315 without coexisting organic disease, 28 with endometriosis, 37 with uterine fibroids, and 46 with uterine adenomyosis [some patients had multiple coexisting organic diseases]) were enrolled and treated with EE/DRSP in either a 16-week comparator study or a 52-week long-term safety study. Evaluations included changes in total dysmenorrhea score, visual analog scale for dysmenorrhea, severity of symptoms, hormone levels, endometrial thickness, and safety outcomes. In both studies, the total dysmenorrhea score was significantly (P<0.001) decreased from baseline during treatment with EE/DRSP. Time-dependent changes in visual analog score for dysmenorrhea and alleviation of symptoms, such as lower abdominal pain, low back pain (lumbago), headache, and nausea/vomiting, were similar in all patient groups with and without any specific coexisting organic diseases. These improvements with EE/DRSP were observed for both short-term (16 weeks) and long-term (52 weeks) use. These effects were associated with suppressed increases in serum estradiol and progesterone levels and decreased endometrial thickness. The safety profile of EE/DRSP was similar in all patients, irrespective of the presence of coexisting organic diseases. EE/DRSP may be prescribed for patients with dysmenorrhea irrespective of the presence of any specific coexisting organic diseases.


The Mammalian Ribo-interactome Reveals Ribosome Functional Diversity and Heterogeneity.
During eukaryotic evolution, ribosomes have considerably increased in size, forming a surface-exposed ribosomal RNA (rRNA) shell of unknown function, which may create an interface for yet uncharacterized interacting proteins. To investigate such protein interactions, we establish a ribosome affinity purification method that unexpectedly identifies hundreds of ribosome-associated proteins (RAPs) from categories including metabolism and cell cycle, as well as RNA- and protein-modifying enzymes that functionally diversify mammalian ribosomes. By further characterizing RAPs, we discover the presence of ufmylation, a metazoan-specific post-translational modification (PTM), on ribosomes and define its direct substrates. Moreover, we show that the metabolic enzyme, pyruvate kinase muscle (PKM), interacts with sub-pools of endoplasmic reticulum (ER)-associated ribosomes, exerting a non-canonical function as an RNA-binding protein in the translation of ER-destined mRNAs. Therefore, RAPs interconnect one of life's most ancient molecular machines with diverse cellular processes, providing an additional layer of regulatory potential to protein expression.


Opposing views on animal experimentation: do animals have rights?
Animals have moral standing; that is, they have properties (including the ability to feel pain) that qualify them for the protections of morality. It follows from this that humans have moral obligations toward animals, and because rights are logically correlative to obligations, animals have rights.


Fast and sensitive protein alignment using DIAMOND.
The alignment of sequencing reads against a protein reference database is a major computational bottleneck in metagenomics and data-intensive evolutionary projects. Although recent tools offer improved performance over the gold standard BLASTX, they exhibit only a modest speedup or low sensitivity. We introduce DIAMOND, an open-source algorithm based on double indexing that is 20,000 times faster than BLASTX on short reads and has a similar degree of sensitivity.


Nocturnal resveratrol administration inhibits chemically induced breast cancer formation in rats.
Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female Sprague-Dawley rats after the nocturnal administration of RES. Application of a high dose of RES (100 mg/kg body weight), starting 2 weeks before the first N-methyl-N-nitrosourea dose (NMU) (50 mg/kg body weight), reduced tumor incidence and markedly prolonged latency period (P < 0.01) in the NMU + RES group in comparison to NMU tumor bearing animals. In addition, the tumor volume decreased significantly (P < 0.05) together with tumor frequency (P < 0.05). We also observed that food but not water intake was significantly reduced by 17% between weeks 4 and 12 in the NMU + RES group leading to a pronounced reduction in the body mass of about 25% as compared to untreated controls. In addition to direct effects of RES in tumor tissues, this polyphenol did also improve metabolic functions in RES-treated animals since it normalizes hypoproteinemia and urea levels and increases the number of lymphocytes when compared with NMU. Higher level of reactive oxygen species (ROS) in leukocytes and the elevation of proinflammatory plasma cytokines IL-1 and IL-2 may contribute to the observed reduction in tumor development. These results indicate for the first time that nocturnal administration of a high dose of RES significantly affects tumor development in vivo. Therefore, we conclude that RES is a promising candidate for cancer chemoprevention. However, it should be noted that the mode of application might significantly affect RES ability to fight cancer.


Electrospun Sandwich-like Structure of PVDF-HFP/Cellulose/PVDF-HFP Membrane for Lithium-Ion Batteries.
Cellulose membranes have eco-friendly, renewable, and cost-effective features, but they lack satisfactory cycle stability as a sustainable separator for batteries. In this study, a two-step method was employed to prepare a sandwich-like composite membrane of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)/cellulose/ PVDF-HFP (PCP). The method involved first dissolving and regenerating a cellulose membrane and then electrospinning PVDF-HFP on its surface. The resulting PCP composite membrane exhibits excellent properties such as high porosity (60.71%), good tensile strength (4.8 MPa), and thermal stability up to 160 °C. It also has exceptional electrolyte uptake properties (710.81 wt.%), low interfacial resistance (241.39 Ω), and high ionic conductivity (0.73 mS/cm) compared to commercial polypropylene (PP) separators (1121.4 Ω and 0.26 mS/cm). Additionally, the rate capability (163.2 mAh/g) and cycling performance (98.11% after 100 cycles at 0.5 C) of the PCP composite membrane are superior to those of PP separators. These results demonstrate that the PCP composite membrane has potential as a promising separator for high-powered, secure lithium-ion batteries.


Movement of entomophagous arthropods in agricultural landscapes: links to pest suppression.
Entomophagous arthropods can provide valuable biological control services, but they need to fulfill their life cycle in agricultural landscapes often dominated by ephemeral and disturbed habitats. In this environment, movement is critical to escape from disturbances and to find resources scattered in space and time. Despite considerable research effort in documenting species movement and spatial distribution patterns, the quantification of arthropod movement has been hampered by their small size and the variety of modes of movement that can result in redistribution at different spatial scales. In addition, insight into how movement influences in-field population processes and the associated biocontrol services is limited because emigration and immigration are often confounded with local-scale population processes. More detailed measurements of the habitat functionality and movement processes are needed to better understand the interactions between species movement traits, disturbances, the landscape context, and the potential for entomophagous arthropods to suppress economically important pests.


Characteristics of EMG responses to imposed limb displacement in patients with vascular hemiplegia.
The segmented EMG activity in flexor carpi radialis to imposed wrist movements was studied in 18 hemiplegic subjects with vascular lesions of the sensorimotor cortex or internal capsule and compared to that in age-matched normal subjects. The segmented EMG activity in the stretched muscle was normalized against the maximum M response elicited by electrical stimulation of its peripheral nerve in hemiplegic and normal subjects. This M response was used to estimate the maximal activity of the motoneuron pool. Twelve of the hemiplegic patients showed a stereotyped abnormal segmentation pattern of the EMG activity characterized by: an increased M1 segment of prolonged duration with both an increased sensitivity to low initial velocities of displacement and an increased slope of the input-output relationship for the range of velocities tested; absent or diminished activity during the interval of the normal M2-3 segment; and a late component not evident in normal subjects. The increased magnitude of the EMG activity during the M1 interval, markedly exceeded the normal range of control values. A method to demonstrate the response distribution of the interrelationship of the magnitude of the M1 segment using two variables (background EMG activity and initial velocity) for individual responses rather than average responses is presented. The results of the study indicate that: the increased excitability, reflected in the enhanced EMG over the M1 segment does not result from increased levels of resting alpha motoneuron activity and may result from disruption of polysynaptic internuncial influences on alpha motoneurons; the absent or diminished activity over the interval of the normal M2-3 segment may partially result from the interruption of a transcortical reflex by the vascular lesions.


Four-way-branched DNA-porphyrin conjugates for construction of four double-helix-DNA assembled structures.
[reaction: see text] DNA-porphyrin conjugates having four DNA strands were designed and synthesized. Four double helices were assembled using two DNA-porphyrin conjugates and their complementary strands, and the formation of the four double-helix assembled structures with the two DNA-porphyrin units was examined by gel electrophoresis and spectroscopic analysis. The interaction between two porphyrin chromophores in the complex was investigated by measurement of fluorescence lifetimes, and the singlet energy transfer between the two different phorphyrin units (Zn-porphyrin and H2-porphyrin) was observed. These results indicate that multiple and different porphyrin chromophores can be integrated into the DNA structures by programming the sequences of the DNA strands.


epsABCJ genes are involved in the biosynthesis of the exopolysaccharide mauran produced by Halomonas maura.
The moderately halophilic strain Halomonas maura S-30 produces a high-molecular-mass acidic polymer (4.7 x 10(6) Da) composed of repeating units of mannose, galactose, glucose and glucuronic acid. This exopolysaccharide (EPS), known as mauran, has interesting functional properties that make it suitable for use in many industrial fields. Analysis of the flanking regions of a mini-Tn5 insertion site in an EPS-deficient mutant of H. maura, strain TK71, led to the identification of five ORFs (epsABCDJ), which form part of a gene cluster (eps) with the same structural organization as others involved in the biosynthesis of group 1 capsules and some EPSs. Conserved genetic features were found such as JUMPstart and ops elements, which are characteristically located preceding the gene clusters for bacterial polysaccharides. On the basis of their amino-acid-sequence homologies, their putative hydropathy profiles and the effect of their mutations, it is predicted that EpsA (an exporter-protein homologue belonging to the OMA family) and EpsC (a chain-length-regulator homologue belonging to the PCP family) play a role in the assembly, polymerization and translocation of mauran. The possibility that mauran might be synthesized via a Wzy-like biosynthesis system, just as it is for many other polysaccharides, is also discussed. This hypothesis is supported by the fact that EpsJ is homologous with some members of the PST-exporter-protein family, which seems to function together with each OMA-PCP pair in polysaccharide transport in Gram-negative bacteria, transferring the assembled lipid-linked repeating units from the cytoplasmic membrane to the periplasmic space. Maximum induction of the eps genes is reached during stationary phase in the presence of 5 % (w/v) marine salts.


A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals.
Gene losses provide an insightful route for studying the morphological and physiological adaptations of species, but their discovery is challenging. Existing genome annotation tools focus on annotating intact genes and do not attempt to distinguish nonfunctional genes from genes missing annotation due to sequencing and assembly artifacts. Previous attempts to annotate gene losses have required significant manual curation, which hampers their scalability for the ever-increasing deluge of newly sequenced genomes. Using extreme sequence erosion (amino acid deletions and substitutions) and sister species support as an unambiguous signature of loss, we developed an automated approach for detecting high-confidence gene loss events across a species tree. Our approach relies solely on gene annotation in a single reference genome, raw assemblies for the remaining species to analyze, and the associated phylogenetic tree for all organisms involved. Using human as reference, we discovered over 400 unique human ortholog erosion events across 58 mammals. This includes dozens of clade-specific losses of genes that result in early mouse lethality or are associated with severe human congenital diseases. Our discoveries yield intriguing potential for translational medical genetics and evolutionary biology, and our approach is readily applicable to large-scale genome sequencing efforts across the tree of life.


Combined venomics, antivenomics and venom gland transcriptome analysis of the monocoled cobra (Naja kaouthia) from China.
We conducted an omics-analysis of the venom of Naja kaouthia from China. Proteomics analysis revealed six protein families [three-finger toxins (3-FTx), phospholipase A2 (PLA2), nerve growth factor, snake venom metalloproteinase (SVMP), cysteine-rich secretory protein and ohanin], and venom-gland transcriptomics analysis revealed 28 protein families from 79 unigenes. 3-FTx (56.5% in proteome/82.0% in transcriptome) and PLA2 (26.9%/13.6%) were identified as the most abundant families in venom proteome and venom-gland transcriptome. Furthermore, N. kaouthia venom expressed strong lethality (i.p. LD50: 0.79μg/g) and myotoxicity (CK: 5939U/l) in mice, and showed notable activity in PLA2 but weak activity in SVMP, l-amino acid oxidase or 5' nucleotidase. Antivenomic assessment revealed that several venom components (nearly 17.5% of total venom) from N. kaouthia could not be thoroughly immunocaptured by commercial Naja atra antivenom. ELISA analysis revealed that there was no difference in the cross-reaction between N. kaouthia and N. atra venoms against the N. atra antivenom. The use of commercial N. atra antivenom in treatment of snakebites caused by N. kaouthia is reasonable, but design of novel antivenom with the attention on enhancing the immune response of non-immunocaptured components should be encouraged. The venomics, antivenomics and venom-gland transcriptome of the monocoled cobra (Naja kaouthia) from China have been elucidated. Quantitative and qualitative differences are evident when venom proteomic and venom-gland transcriptomic profiles are compared. Two protein families (3-FTx and PLA2) are found to be the predominated components in N. kaouthia venom, and considered as the major players in functional role of venom. Other protein families with relatively low abundance appear to be minor in the functional significance. Antivenomics and ELISA evaluation reveal that the N. kaouthia venom can be effectively immunorecognized by commercial N. atra antivenom, but still a small number of venom components could not be thoroughly immunocaptured. The findings indicate that exploring the precise composition of snake venom should be executed by an integrated omics-approach, and elucidating the venom composition is helpful in understanding composition-function relationships and will facilitate the clinical application of antivenoms.


Cut-off values of anthropometric indices to determine insulin resistance in Pakistani adults.
To determine the cut-off values of anthropometric indices to indicate insulin resistance and correlation of these indices with insulin resistance in Pakistani adults. The cross-sectional study was conducted at the Military Hospital and Army Medical College, Rawalpindi, Pakistan, from June 2010 to November 2011. The study measured 209 adults for body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio and conicity index. Receiver operating characteristics curve analyses were done to determine the predictive values of these anthropometric measures and their cut-off values for insulin resistance by triglyceride/high density lipoprotein ratio. Overall mean age was 51.5 +/- 1.16 years (range: 28-73) and there were 136 (65%) males and 73 (35%) females. Body mass index had the maximum predictive value for insulin resistance followed by waist circumference and waist-to-height ratio in males (p < 0.0001), sensitivity and specificity being 68% and 62% respectively with cut-off value of 25.04 kg/m2. ROC curve analyses showed the maximum predictive value of conicity index for insulin resistance followed by waist circumference and waist-to-height ratio in females (p < 0.08), sensitivity and specificity being 65% and 50% respectively with cut-off value of 1.39. In Pakistani male adults, BMI is the best indicator of insulin resistance, while in female adults, conicity index is the best indicator.This is the first study in Pakistan reporting predictive values of anthropometric indices as a non-invasive method in determining insulin resistance.


Determining adolescents' suitability for inpatient psychotherapy: utility of the clinician-rated Readiness for Inpatient Psychotherapy Scale with an adolescent inpatient sample.
Growing economic pressure on inpatient services for adolescents has resulted in fewer clinicians to provide individual psychotherapy. As a result, inpatient treatment trends have favored group psychotherapy modalities and psychopharmacological interventions. Currently, no clinician-rated measures exist to assist clinicians in determining who would be able to better utilize individual psychotherapy on inpatient units. The current study sought to demonstrate the utility of the Readiness for Inpatient Psychotherapy Scale with an adolescent inpatient sample. This study also used the RIPS as it is intended to be used in everyday practice. Results from the authors' analyses reveal that the RIPS demonstrates good psychometrics and interrater reliability, as well as construct validity.


Alterations in the central vasopressin and oxytocin axis after lesion of a brain osmotic sensory region.
The anteroventral region of the third ventricle (AV3V) is critical in mediating osmotic sensitivity. AV3V lesions increase plasma osmolality and block osmotic-induced vasopressin (VP) and oxytocin (OT) secretion. The aim was to evaluate the effects of AV3V lesions on neurosecretion under control/water replete conditions and after 48 h dehydration. The focus was on central peptidergic changes with measurement of OT and VP content in the hypothalamic paraventricular (PVN) and supraoptic (OT) regions and the posterior pituitary. AV3V-lesioned rats exhibited an elevated plasma osmolality and higher OT content in SON and PVN. There was an increase in VP content in PVN, but no change in SON. As predicted, the plasma peptide response to dehydration was absent in lesioned animals. However, dehydration produced depletion in posterior pituitary VP in lesioned animals with no change in OT. No changes in nuclear VP and OT levels were seen after dehydration. These results demonstrate that AV3V lesions alter the VP and OT neurosecretory system, seen as a blockade of osmotic-induced release and an increase in basal nuclear peptide content. The data indicate that interruption of the osmotic sensory system affects the central neurosecretory axis, resulting in a backup in content and likely changes in synthesis and processing.


Testicular choriocarcinoma: diagnosed on cervical lymph node biopsy.
Choriocarcinoma is a very rare germinal testicular tumour and in literature its incidence has been reported to be 0.3% of all germinal testicular tumours. An important tumour marker is serum beta-hCG which not only helps in establishing diagnosis but also in assessing response to chemotherapy. In this study we present a case of testicular choriocarcinoma, who presented with abdominal pain, cough, generalized weakness and left sided cervical mass. Incisional biopsy of cervical mass was performed. Histopathology revealed metastatic choriocarcinoma. Serum beta-hCG levels were 1227 ng/mL. Patient received intravenous cycles of PEB (cisPlatin, Etoposide, Bleomycin) chemotherapy but he had progressive disease both radiologically and on tumour marker monitoring. He was planned for salvage chemotherapy but was lost to follow up there after. It is concluded that in males, choriocarcinoma carries a very dismal prognosis and a very poor response to chemotherapy and radiotherapy; surgery has no role in the management.


Minimally Invasive Off-Pump Anaortic Complete Arterial Coronary Artery Bypass: How to Do It?
Minimally invasive direct coronary artery bypass has empowered coronary artery bypass grafting to compete with the appeal of percutaneous coronary procedures. Successful results of off-pump coronary artery bypass surgery and without touching the aorta have facilitated the development and use of minimally invasive methods. Multivessel coronary bypass surgery performed using a minimally invasive method through a small thoracotomy in the left chest with off-pump, anaortic, and all-arterial grafts is described step by step. Technical considerations, description of operation stages, and tips and pitfalls will be examined. A 64-year-old male patient with no known comorbidities except smoking revealed 3 vessels and a side vessel disease, and the heart team decided on surgical revascularization with a low-risk procedure. Experienced surgeons may perform this operation successfully, and the development of efficient simulation systems will increase its use.


Myeloid cells and lymphangiogenesis.
The lymphatic vascular system and the hematopoietic system are intimately connected in ontogeny and in physiology. During embryonic development, mammalian species derive a first lymphatic vascular plexus from the previously formed anterior cardinal vein, whereas birds and amphibians have a lymphatic vascular system of dual origin, composed of lymphatic endothelial cells (LECs) of venous origin combined with LECs derived from mesenchymal lymphangioblasts. The contribution of hematopoietic cells as building blocks of nascent lymphatic structures in mammals is still under debate. In contrast, the importance of myeloid cells to direct lymphatic vessel growth and function postnatally has been experimentally shown. For example, myeloid cells communicate with LECs via paracrine factors or cell-cell contacts, and they also can acquire lymphatic endothelial morphology and marker gene expression, a process reminiscent of developmental vasculogenesis. Here, we present an overview of the current understanding of how lymphatic vessels and the hematopoietic system, in particular myeloid cells, interact during embryonic development, in normal organ physiology, and in disease.


Integrin linked kinase regulates the transcription of AQP2 by NFATC3.
Two processes are associated with progressive loss of renal function: 1) decreased aquaporin-2 (AQP2) expression and urinary concentrating capacity (Nephrogenic Diabetes Insipidus, NDI); and 2) changes in extracellular matrix (ECM) composition, e.g. increased collagen I (Col I) deposition, characteristic of tubule-interstitial fibrosis. AQP2 expression is regulated by both the ECM-to-intracellular scaffold protein integrin-linked kinase (ILK) by NFATc/AP1 and other transcription factors. In the present work, we used in vivo and in vitro approaches to examine ILK participation in NFATc3/AP-1-mediated increases in AQP2 gene expression. Both NFATc3 knock-out mice and ILK conditional-knockdown mice (cKD-ILK) display symptoms of NDI (polyuria and reduced AQP2 expression). NFATc3 is upregulated in the renal medulla tubular cells of cKD-ILK mice but with reduced nuclear localization. Inner medullary collecting duct mIMCD3 cells were subjected to ILK depletion and transfected with reporter plasmids. Pharmacological activators or inhibitors determined the effect of ILK activity on NFATc/AP-1-dependent increases in transcription of AQP2. Finally, mIMCD3 cultured on Col I showed reduced activity of the ILK/GSK3β/NFATc/AQP2 axis, suggesting this pathway is a potential target for therapeutic treatment of NDI.


Prospective study of a systemic sclerosis/dermatomyositis overlap patient presenting with anti-Ku and anti-Ki antibodies.
Abstract A 60-year-old woman visited the Keigu Clinic in January 1998 complaining of morning stiffness and flexion contracture of the distal interphalangeal joint. Blood tests showed the presence of antinuclear antibody at a 1 : 40 dilution with speckled staining. She was suspected of having Heberden's node. Nine months later, she developed Raynaud's phenomenon, sclerodactyly, and Gottron's sign, and was diagnosed with systemic sclerosis/dermatomyositis (SSc/DM) overlap. Blood tests revealed the presence of antinuclear antibody at a 1 : 5120 dilution, along with high titer of anti-Ku and anti-Ki antibodies. Subsequently, the patient developed interstitial pneumonia in January 2000. It is thought that the appearance of antinuclear antibody and development of other immunological events played an important role in determining this patient's limited SSc/DM overlap.


ABO blood type A is associated with increased risk of ARDS in whites following both major trauma and severe sepsis.
ABO glycosyltransferases catalyze antigen modifications on various glycans and glycoproteins and determine the ABO blood types. Blood type A has been associated with increased risk of vascular diseases and differential circulating levels of proteins related to inflammation and endothelial function. The objective of this study was to determine the association of ABO blood types with ARDS risk in patients with major trauma and severe sepsis. We conducted prospective cohort studies in two populations at an urban tertiary referral, level I trauma center. Critically ill patients (n 5 732) presenting after major trauma were followed for 5 days for ARDS development. Additionally, 976 medical patients with severe sepsis were followed for 5 days for ARDS. Multivariable logistic regression was used to adjust for confounders. ARDS developed in 197 of the 732 trauma patients (27%). Blood type A was associated with increased ARDS risk among whites (37% vs 24%; adjusted OR, 1.88; 95% CI, 1.14-3.12; P 5 .014), but not blacks (adjusted OR, 0.61; 95% CI, 0.33-1.13; P=.114). ARDS developed in 222 of the 976 patients with severe sepsis (23%). Blood type A was also associated with an increased ARDS risk among whites (31% vs 21%; adjusted OR, 1.67; 95% CI, 1.08-2.59; P=.021) but, again, not among blacks (adjusted OR, 1.17; 95% CI, 0.59-2.33; P=.652). Blood type A is associated with an increased risk of ARDS in white patients with major trauma and severe sepsis. These results suggest a role for ABO glycans and glycosyltransferases in ARDS susceptibility.


[Cerebrospinal fluid leak due to inner ear malformations].
A case of inner ear anomalies associated with recurrent meningitis found in a 66-year-old female is reported. The patient had had 2 episodes of meningitis in the previous one year period. Multidetector-row CT of the temporal bone and three-demensional fast imaging employing steady-state acquisition MRI revealed dysplasia of the bony labyrinth and enlarged fundus of the internal auditory canal (IAC). During surgical treatment, we confirmed the cerebrospinal fluid (CSF) leakage through a bony defect in the stapedial footplate. The inner ear was obliterated and contained small pieces of temporal fascia. A meningitis or CSF leakage due to inner ear malformation is extreamly rear condition for neurosurgeon. Though we always have to take it into condideration as a cause of CSF leakage.


Preoperative simulation and intraoperative navigation with three-dimensional functional images.
Recent advances in computer graphics have facilitated three-dimensional image reconstruction from magnetic resonance (MR) imagea, contributing to better understanding of the morphological structure of the brain and to preoperative neurosurgical planning. Functional brain mapping used in conjunction with this three-dimensional imaging technique provides preoperative information regarding the three-dimensional relationship between the eloquent cortex and the location of lesions, and allows accurate preoperative planning. In this article, we present a preoperative simulation and intraoperative navigational system for use with three-dimensional functional images.


Natural killer cells: from bench to cancer therapy.
Natural killer (NK) cells are effectors of the innate immune system that play an important role in host response against viruses and tumour cells through the production of cytokines and direct cytolytic activity. There has been limited success reported from clinical trials in cancer patients treated with activated NK cells. Over the last decade, a better understanding of the biology of NK cells, NK cell receptors and the role of interleukin-15 has led to the development of new strategies using NK cells as immunotherapy for cancer treatment in the transplant and non-transplant settings.


Electronic Cigarette Use Among Working Adults - United States, 2014.
Electronic cigarettes (e-cigarettes) are battery-powered devices that deliver a heated aerosol, which typically contains nicotine, flavorings, and other additives, to the user. The e-cigarette marketplace is rapidly evolving, but the long-term health effects of these products are not known. Carcinogens and toxins such as diacetyl, acetaldehyde, and other harmful chemicals have been documented in the aerosol from some e-cigarettes (1-3). On May 5, 2016, the Food and Drug Administration (FDA) finalized a rule extending its authority to all tobacco products, including e-cigarettes.* The prevalence of e-cigarette use among U.S. adults has increased in recent years, particularly among current and former conventional cigarette smokers (4); in 2014, 3.7% of all U.S. adults, including 15.9% of current cigarette smokers, and 22.0% of former cigarette smokers, used e-cigarettes every day or some days (5). The extent of current e-cigarette use among U.S. working adults has not been assessed. Therefore, CDC analyzed 2014 National Health Interview Survey (NHIS) data for adults aged ≥18 years who were working during the week before the interview, to provide national estimates of current e-cigarette use among U.S. working adults by industry and occupation. Among the estimated 146 million working adults, 3.8% (5.5 million) were current (every day or some days) e-cigarette users; the highest prevalences were among males, non-Hispanic whites, persons aged 18-24 years, persons with annual household income <$35,000, persons with no health insurance, cigarette smokers, other combustible tobacco users, and smokeless tobacco users. By industry and occupation, workers in the accommodation and food services industry and in the food preparation and serving-related occupations had the highest prevalence of current e-cigarette use. Higher prevalences of e-cigarette use among specific groups and the effect of e-cigarette use on patterns of conventional tobacco use underscore the importance of continued surveillance of e-cigarette use among U.S. working adults to inform public health policy, planning, and practice.


Microbial communities and activities in alpine and subalpine soils.
Soil samples were collected along two slopes (south and north) at subalpine (1500-1900 m, under closed vegetation, up to the forest line) and alpine altitudes (2300-2530, under scattered vegetation, above the forest line) in the Grossglockner mountain area (Austrian central Alps). Soils were analyzed for a number of properties, including physical and chemical soil properties, microbial activity and microbial communities that were investigated using culture-dependent (viable heterotrophic bacteria) and culture-independent methods (phospholipid fatty acid analysis, FISH). Alpine soils were characterized by significantly (P<0.01) colder climate conditions, i.e. lower mean annual air and soil temperatures, more frost and ice days and higher precipitation, compared with subalpine soils. Microbial activity (soil dehydrogenase activity) decreased with altitude; however, dehydrogenase activity was better adapted to cold in alpine soils compared with subalpine soils, as shown by the lower apparent optimum temperature for activity (30 vs. 37 degrees C) and the significantly (P<0.01-0.001) higher relative activity in the low-temperature range. With increasing altitude, i.e. in alpine soils, a significant (P<0.05-0.01) increase in the relative amount of culturable psychrophilic heterotrophic bacteria, in the relative amount of the fungal population and in the relative amount of Gram-negative bacteria was found, which indicates shifts in microbial community composition with altitude.


Long-term rates of mitochondrial protein synthesis are increased in mouse skeletal muscle with high-fat feeding regardless of insulin-sensitizing treatment.
Skeletal muscle mitochondrial protein synthesis is regulated in part by insulin. The development of insulin resistance with diet-induced obesity may therefore contribute to impairments to protein synthesis and decreased mitochondrial respiration. Yet the impact of diet-induced obesity and insulin resistance on mitochondrial energetics is controversial, with reports varying from decreases to increases in mitochondrial respiration. We investigated the impact of changes in insulin sensitivity on long-term rates of mitochondrial protein synthesis as a mechanism for changes to mitochondrial respiration in skeletal muscle. Insulin resistance was induced in C57BL/6J mice using 4 wk of a high-fat compared with a low-fat diet. For 8 additional weeks, diets were enriched with pioglitazone to restore insulin sensitivity compared with nonenriched control low-fat or high-fat diets. Skeletal muscle mitochondrial protein synthesis was measured using deuterium oxide labeling during weeks 10-12 High-resolution respirometry was performed using palmitoyl-l-carnitine, glutamate+malate, and glutamate+malate+succinate as substrates for mitochondria isolated from quadriceps. Mitochondrial protein synthesis and palmitoyl- l-carnitine oxidation were increased in mice consuming a high-fat diet, regardless of differences in insulin sensitivity with pioglitazone treatment. There was no effect of diet or pioglitazone treatment on ADP-stimulated respiration or H2O2 emission using glutamate+malate or glutamate+malate+succinate. The results demonstrate no impairments to mitochondrial protein synthesis or respiration following induction of insulin resistance. Instead, mitochondrial protein synthesis was increased with a high-fat diet and may contribute to remodeling of the mitochondria to increase lipid oxidation capacity. Mitochondrial adaptations with a high-fat diet appear driven by nutrient availability, not intrinsic defects that contribute to insulin resistance.


Enantioselective formal total synthesis of the antitumor macrolide bryostatin 7.
A new enantioselective synthesis of Masamune's AB fragment (1) for bryostatin 7 is described. Key steps in the new route include a Meerwein-Ponndorf-Verley reduction to set the O(7) stereocenter and an alkylative union between the dithiane 6 and iodide 5 to construct the C(9)-C(10) bond. Because we have previously published a synthesis of Masamune's C-ring phenyl sulfone 2, our new route to 1 constitutes a formal total synthesis of bryostatin 7; it also corrects the previously reported spectral data for 1 in CDCl3.


[Eyebrow reconstruction with a scalp island flap based on the superficial temporal artery].
The Authors describe the reconstruction of an eyebrow, in a case of complete traumatic avulsion, using a scalp island flap based on the superficial temporal artery, in a young person aged 32 years. The lesion represented a serious aesthetic disablement capable of causing disturbed psychic equilibrium and individual relationships, in view of the fact that the eyebrows play a decisive role in the characterisation of the face and expressive gestures. The strategy of using a scalp island flap with a limited amplitude only slightly larger than that of the site in which it was inserted enabled optimal projection of the newly constructed eyebrow to be achieved during suturing.


Epidemic spread of Pandoraea apista, a new pathogen causing severe lung disease in cystic fibrosis patients.
We show that Pandoraea apista must be added to the increasing list of pathogens capable of causing chronic lung infection in cystic fibrosis (CF) patients. It is most likely that this strain of P. apista was transmissible among patients with CF, leading to spread of infection from the index patient to 5 other patients exposed during participation in winter camps and/or hospitalization. All patients developed chronic infection with high levels of antibodies, and 4 patients had a downhill course of lung disease. P. apista must therefore be considered a new and sometimes important pathogen for CF patients. Cohort isolation prevented further spread of P. apista in our CF center.


The role of executive function and social-emotional skills in the development of literacy and numeracy during preschool: a cross-lagged longitudinal study.
The majority of evidence on the interplay between academic and non-academic skills comes from high-income countries. The aim of this study was to examine the bidirectional associations between Ghanaian children's executive function, social-emotional, literacy, and numeracy skills longitudinally. Children (N = 3,862; M age = 5.2 years at time 1) were assessed using direct assessment at three time points over the course of two school years. Controlling for earlier levels of the same skill, early executive function predicted higher subsequent literacy and numeracy skills, and early literacy and numeracy skills predicted higher subsequent executive function, indicating that the development of executive function and academic skills is inter-related and complementary over time. Early literacy and numeracy predicted subsequent social-emotional skills, but early social-emotional skills did not predict subsequent literacy and numeracy skills. The findings provide longitudinal evidence on children's learning and development in West Africa and contribute to a global understanding of the relations between various developmental skills over time.


[Changes in abdominal muscle strength with respect to aging].
It has been generally agreed that muscle strength decreases with advance of age in adulthood. In order to study the effect of aging in abdominal muscle strength, abdominal muscle strength, height, body weight and grip strength were measured in 144 healthy subjects aged from 20 to 88 years old. The abdominal muscle strength was measured using a grip dynamometer. Curve between aging and strength revealed that the abdominal muscle strength gradually decreased with aging during many decades, but rapidly decreased in the fifth decade and over in males and seventh decade and over in females. Among these data, significant correlations were observed between abdominal muscle strength and age (only in males; r = -0.64), abdominal muscle strength and grip strength (in males; r = 0.75, in females; r = 0.47), age and grip strength (in males; -0.72, in females; r = -0.60), and, age and height (in males; r = -0.55, in females; r = -0.46). The results suggest that decrease of abdominal muscle strength is due to aging, although the degree of the decrease is affected by the generation studied. The method to measure abdominal muscle strength originally developed by us is easy and useful to understand changes of age-related muscular strength.


Composition-dependent ordering transformations in Pt-Fe nanoalloys.
SignificanceDynamically understanding the microscopic processes governing ordering transformations has rarely been attained. The situation becomes even more challenging for nanoscale alloys, where the significantly increased surface-area-to-volume ratio not only opens up a variety of additional freedoms to initiate an ordering transformation but also allows for kinetic interplay between the surface and bulk due to their close proximity. We provide direct evidence of the microscopic processes controlling the ordering transformation through the surface-bulk interplay in Pt-Fe nanoalloys and new features rendered by variations in alloy composition and chemical stimuli. These results provide a mechanistic detail of ordering transformation phenomena which are widely relevant to nanoalloys as chemical ordering occurs in most multicomponent materials under suitable environmental bias.