Mealtime behavior among siblings and body mass index of 4-8 year olds: a videotaped observational study.
Being a last-born child and having a sister have been associated with higher body mass index (BMI). Encouragement to eat that overrides children's self-regulation has been reported to increase the risk of obesogenic eating behaviors. This study sought to test the hypothesis that encouragement to eat during mealtime from older siblings and sisters mediates associations of being last-born or having a sister with higher BMI. Children aged 4-8 years (n = 75) were videotaped while eating a routine evening meal at home with one sibling present. Encouragement to eat (defined as direct prompts to eat or general positive statements about food) delivered to the index child (IC) from the sibling was coded from the videotape. Path analysis was used to examine associations between IC's birth order, sibling's sex, encouragement counts, and IC's measured BMI z-score (BMIz). Being the younger sibling in the sibling dyad was associated with the IC receiving more encouragements to eat from the sibling (β: 0.93, 95 % confidence interval (CI): 0.59, 1.26, p < 0.0001). The IC having a sister compared with a brother was not associated with the IC receiving more encouragements to eat from the sibling (β: 0.18, 95 % CI: -0.09, 0.47, p = 0.20). The IC receiving more encouragements to eat from the sibling was associated with lower IC BMIz (β: -0.06, 95 % CI: -0.12, 0.00, p = 0.05). Children were more likely to receive encouragements to eat from older siblings than younger siblings. Being the recipient of encouragements to eat from a sibling was associated with lower, not higher, child BMIz, which may reflect sibling modeling of maternal behavior. Future longitudinal studies are needed to examine whether encouragements to eat from siblings lead to increase in BMI over time. Encouragements from siblings may be a novel intervention target for obesity prevention.


Packing-induced conformational and functional changes in the subunits of alpha -crystallin.
The heteroaggregate alpha-crystallin and homoaggregates of its subunits, alphaA- and alphaB-crystallins, function like molecular chaperones and prevent the aggregation of several proteins. Although modulation of the chaperone-like activity of alpha-crystallin by both temperature and chaotropic agents has been demonstrated in vitro, the mechanism(s) of its regulation in vivo have not been elucidated. The subunits of alpha-crystallin exchange freely, resulting in its dynamic and variable quaternary structure. Mixed aggregates of the alpha-crystallins and other mammalian small heat shock proteins (sHSPs) have also been observed in vivo. We have investigated the time-dependent structural and functional changes during the course of heteroaggregate formation by the exchange of subunits between homoaggregates of alphaA- and alphaB-crystallins. Native isoelectric focusing was used to follow the time course of subunit exchange. Circular dichroism revealed large tertiary structural alterations in the subunits upon subunit exchange and packing into heteroaggregates, indicating specific homologous and heterologous interactions between the subunits. Subunit exchange also resulted in quaternary structural changes as demonstrated by gel filtration chromatography. Interestingly, we found time-dependent changes in chaperone-like activity against the dithiothreitol-induced aggregation of insulin, which correlated with subunit exchange and the resulting tertiary and quaternary structural changes. Heteroaggregates of varying subunit composition, as observed during eye lens epithelial cell differentiation, generated by subunit exchange displayed differential chaperone-like activity. It was possible to alter chaperone-like activity of preexisting oligomeric sHSPs by alteration of subunit composition by subunit exchange. Our results demonstrate that subunit exchange and the resulting structural and functional changes observed could constitute a mechanism of regulation of chaperone-like activity of alpha-crystallin (and possibly other mammalian sHSPs) in vivo.


[Locoregional radiotherapy after mastectomy and chemotherapy for breast cancer: prolonged survival and better local tumor control].
In two recent randomized clinical trials from Denmark and Canada the usefulness of radiotherapy was evaluated in premenopausal patients with breast cancer who had been operated and in whom the findings indicated a poor prognosis. Over 2000 patients participated. After follow-up periods of 10 and 15 years, respectively, addition of locoregional therapy to mastectomy and chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF) was found to result in better locoregional control and a better disease-free survival. These studies also demonstrated, for the first time, that the overall survival was increased after postoperative radiotherapy. In view of these findings, the indication for postoperative locoregional radiotherapy in breast cancer in the Netherlands should be reconsidered.


From Synthesis to Microstructure: Engineering the High-entropy Ceramic Materials of the Future.
Sintering and microstructural development in ceramics has long been studied in a two-dimensional grain size-density space, with only texture (i.e. deviation of grain orientation from random) used to gain first insights into additional parametric spaces. Following an increased interest for grain boundary engineering and a deeper understanding of dopant effects on sintering and grain boundaries, the theory of complexion transitions for ceramics has been introduced over the last decade, providing a new base for advanced microstructure engineering in ceramics. With emergence of high entropy ceramics over the last 5 years, the combination of both yields new grounds for exploration and engineering of functional ceramic materials of the future.


Residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese men and women.
To determine the residual lifetime and 10 year absolute risks of osteoporotic fractures in Chinese men and women. A validated state-transition microsimulation model was used. Microsimulation and probabilistic sensitivity analyses were performed to address the uncertainties in the model. All parameters including fracture incidence rates and mortality rates were retrieved from published literature. Simulated subjects were run through the model until they died to estimate the residual lifetime fracture risks. A 10 year time horizon was used to determine the 10 year fracture risks. We estimated the risk of only the first osteoporotic fracture during the simulation time horizon. The residual lifetime and 10 year risks of having the first osteoporotic (hip, clinical vertebral or wrist) fracture for Chinese women aged 50 years were 40.9% (95% CI: 38.3-44.0%) and 8.2% (95% CI: 6.8-9.3%) respectively. For men, the residual lifetime and 10 year fracture risks were 8.7% (95% CI: 7.5-9.8%) and 1.2% (95% CI: 0.8-1.7%) respectively. The residual lifetime fracture risks declined with age, whilst the 10 year fracture risks increased with age until the short-term mortality risks outstripped the fracture risks. Residual lifetime and 10 year clinical vertebral fracture risks were higher than those of hip and wrist fractures in both sexes. More than one third of the Chinese women and approximately one tenth of the Chinese men aged 50 years are expected to sustain a major osteoporotic fracture in their remaining lifetimes. Due to increased fracture risks and a rapidly ageing population, osteoporosis will present a great challenge to the Chinese healthcare system. While national data was used wherever possible, regional Chinese hip and clinical vertebral fracture incidence rates were used, wrist fracture rates were taken from a Norwegian study and calibrated to the Chinese population. Other fracture sites like tibia, humerus, ribs and pelvis were not included in the analysis, thus these risks are likely to be underestimates. Fracture risk factors other than age and sex were not included in the model. Point estimates were used for fracture incidence rates, osteoporosis prevalence and mortality rates for the general population.


Effects of Aeriscardovia aeriphila on growth performance, antioxidant functions, immune responses, and gut microbiota in broiler chickens.
Aeriscardovia aeriphila, also known as Bifidobacterium aerophilum, was first isolated from the caecal contents of pigs and the faeces of cotton-top tamarin. Bifidobacterium species play important roles in preventing intestinal infections, decreasing cholesterol levels, and stimulating the immune system. In this study, we isolated a strain of bacteria from the duodenal contents of broiler chickens, which was identified as A. aeriphila, and then evaluated the effects of A. aeriphila on growth performance, antioxidant functions, immune functions, and gut microbiota in commercial broiler chickens. Chickens were orally gavaged with A. aeriphila (1×109 CFU/mL) for 21 d. The results showed that A. aeriphila treatment significantly increased the average daily gain and reduced the feed conversion ratio (P<0.001). The levels of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) were significantly increased following A. aeriphila treatment (P<0.05). Blood urea nitrogen and aspartate aminotransferase levels were decreased, whereas glucose and creatinine levels increased as a result of A. aeriphila treatment. Furthermore, the levels of serum antioxidant enzymes, including catalase (P<0.01), superoxide dismutase (P<0.001), and glutathione peroxidase (P<0.05), and total antioxidant capacity (P<0.05) were enhanced following A. aeriphila treatment. A. aeriphila treatment significantly increased the levels of serum immunoglobulin A (IgA) (P<0.05), IgG (P<0.01), IgM (P<0.05), interleukin-1 (IL-1) (P<0.05), IL-4 (P<0.05), and IL-10 (P<0.05). The broiler chickens in the A. aeriphila group had higher secretory IgA (SIgA) levels in the duodenum (P<0.01), jejunum (P<0.001), and cecum (P<0.001) than those in the control group. The messenger RNA (mRNA) relative expression levels of IL-10 (P<0.05) and IL-4 (P<0.001) in the intestinal mucosa of chickens were increased, while nuclear factor-κB (NF-κB) (P<0.001) expression was decreased in the A. aeriphila group compared to the control group. Phylum-level analysis revealed Firmicutes as the main phylum, followed by Bacteroidetes, in both groups. The data also found that Phascolarctobacterium and Barnesiella were increased in A. aeriphila-treated group. In conclusion, oral administration of A. aeriphila could improve the growth performance, serum antioxidant capacity, immune modulation, and gut health of broilers. Our findings may provide important information for the application of A. aeriphila in poultry production.


Transition radiation at the boundary of a chiral isotropic medium.
This study analyzes the radiation produced by a point charge intersecting the interface between a vacuum and a chiral isotropic medium. We deduce analytical expressions for the Fourier components of an electromagnetic field in both vacuum and medium for arbitrary charge velocity. The main focus is on investigating the far field in a vacuum. The distinguishing feature of the interface with a chiral isotropic medium is that the field in the vacuum area contains both copolarization (coinciding with the polarization of the self-field of a charge) and cross-polarization (orthogonal to the polarization of the self-field). Using a saddle-point approach, we obtain asymptotic representations for the field components in the far-field zone for typical frequency ranges of the Condon model of the chiral medium. We note that a so-called lateral wave is generated in a vacuum for certain parameters. The main contribution to the radiation at large distances is presented by two (co- and cross-) spherical waves of transition radiation. These waves are coherent and result in a total spherical wave with elliptical polarization, with the polarization coefficient being determined by the chirality of the medium. We present typical radiation patterns and ellipses of polarization.


Tai chi as a balance improvement exercise for older adults: a systematic review.
The purpose of this systematic review was to identify exercise parameters and the most common outcome measures used in tai chi (TC) research. Ovid Medline and PubMed were used to identify longitudinal studies published from January 2000 to July 2007 written in English with the key words tai chi, tai ji, tai chi quan, tai ji quan, balance, falls, and falling. Qualifying studies had subjects aged 60 years or older. In all 19 qualified prospective studies, older vigorous and likely transitional frail individuals seemed to benefit more from TC than did older frail individuals. The most commonly used TC parameters were Yang's style, with 12 or fewer forms, durations of 12 weeks or longer, frequencies of twice a week or more, and session lengths of at least 45 minutes. The most common outcome measures observed were a combination of 2 to 5 of the following 10 measures (from most to least common): fear of falling, single-leg stance, posturography, rate of falling, flexibility, walking velocity, Berg Balance Scale, Timed up and Go, Functional Reach, and ankle and knee joint strength and range of motion. Improvements were reported in almost all of these measures. This review indicates that TC may be an economic and effective exercise program for improving balance and balance confidence in older adults.


Identification of a novel one-carbon metabolism regulon in Saccharomyces cerevisiae.
Glycine specifically induces genes encoding subunits of the glycine decarboxylase complex (GCV1, GCV2, and GCV3), and this is mediated by a fall in cytoplasmic levels of 5,10-methylenetetrahydrofolate caused by inhibition of cytoplasmic serine hydroxymethyltransferase. Here it is shown that this control system extends to genes for other enzymes of one-carbon metabolism and de novo purine biosynthesis. Northern analysis of the response to glycine demonstrated that the induction of the GCV genes and the induction of other amino acid metabolism genes are temporally distinct. The genome-wide response to glycine revealed that several other genes are rapidly co-induced with the GCV genes, including SHM2, which encodes cytoplasmic serine hydroxymethyltransferase. These results were refined by examining transcript levels in an shm2Delta strain (in which cytoplasmic 5,10-methylenetetrahydrofolate levels are reduced) and a met13Delta strain, which lacks the main methylenetetrahydrofolate reductase activity of yeast and is effectively blocked at consumption of 5,10-methylene tetrahydrofolate for methionine synthesis. Glycine addition also caused a substantial transient disturbance to metabolism, including a sequence of changes in induction of amino acid biosynthesis and respiratory chain genes. Analysis of the glycine response in the shm2Delta strain demonstrated that apart from the one-carbon regulon, most of these transient responses were not contingent on a disturbance to one-carbon metabolism. The one-carbon response is distinct from the Bas1p purine biosynthesis regulon and thus represents the first example of transcriptional regulation in response to activated one-carbon status.


High-sensitivity compact ultrasonic detector based on a pi-phase-shifted fiber Bragg grating.
A highly sensitive compact hydrophone, based on a pi-phase-shifted fiber Bragg grating, has been developed for the measurement of wideband ultrasonic fields. The grating exhibits a sharp resonance, whose centroid wavelength is pressure sensitive. The resonance is monitored by a continuous-wave (CW) laser to measure ultrasound-induced pressure variations within the grating. In contrast to standard fiber sensors, the high finesse of the resonance--which is the reason for the sensor's high sensitivity--is not associated with a long propagation length. Light localization around the phase shift reduces the effective size of the sensor below that of the grating and is scaled inversely with the resonance spectral width. In our system, an effective sensor length of 270 μm, pressure sensitivity of 440 Pa, and effective bandwidth of 10 MHz were achieved. This performance makes our design attractive for medical imaging applications, such as optoacoustic tomography, in which compact, sensitive, and wideband acoustic detectors are required.


Borrelia burgdorferi sensu lato in an endemic environment: wild sika deer (Cervus nippon yesoensis) with infected ticks and antibodies.
Ticks and blood samples were collected from wild sika deer (Cervus nippon yesoensis) during a hunting season (August to October) of 1991 at a selected location in Hokkaido, Japan. Ixodes persulcatus (adult and nymph) and I. ovatus (adult) were the common ticks on sika deer. Spirochetes were detected in the midgut of the ticks by the indirect peroxidase-conjugated antibody staining method and by dark-field microscopy after cultivation. By the reactive pattern of monoclonal antibodies, isolates were considered to belong to Borrelia garinii or B. japonica. In an antibody test, the percentage of seropositive deer was 69.0%. Most of the adult sika deer were positive for antibodies to the spirochetes. There are significant age-dependency in antibody level and seropositive rate. The surveillance of deer should be valuable in monitoring the transmission risk of B. burgdorferi sensu lato in nature.


Can VEGFR-3 be a better tumor marker for breast cancer than CA 15-3?
Vascular Endothelial Growth Factor Receptor 3 (VEGFR-3) is a very important factor which promotes lymphangiogenesis not only in physiological but also in pathological processes in which we can include neoplasia. The aim of this study was to analyze the plasma concentrations and diagnostic utility of this parameter in comparison and in combination with CA 15-3 in breast cancer (BC) patients and in relation to the control groups. The study included 120 breast cancer and 60 control patients (28 with benign breast tumors and 32 healthy women). Plasma levels of VEGFR-3 were determined by an Enzyme-Linked Immunosorbent Assay (ELISA), and those of CA 15-3 by a Chemiluminescent Microparticle Immuno Assay (CMIA). Differences in concentrations of both of the tested parameters were statistically significant when breast cancer patients were compared to the control groups. VEGFR-3 had higher values of sensitivity (SE), specificity (SP), predictive value of a positive (PPV) and negative test result (NPV) in the whole BC group (90%; 98.33%; 99.08%; 83.10%, respectively) and, more importantly, in the early stages of BC, than CA 15-3. VEGFR-3 was also a better parameter in terms of statistically significant Area Under Curve (0.9656) in the whole group and at all BC stages (I-IV), but a maximum range was obtained for the combination of VEGFR-3 and CA 15-3 (0.9710). The combined analysis of VEGFR-3 and CA 15-3 provides hope that a new BC diagnostic panel may be developed in the future.


The prevalence of selected non-communicable disease risk factors among HIV patients on anti-retroviral therapy in Bushbuckridge sub-district, Mpumalanga province.
The rates of non-communicable diseases (NCD's) appear to be increasing in human immunodeficiency virus (HIV) infected people as compared to non-HIV infected people and this will have major implications for clinical care. The aim of the current study was to profile selected cardiovascular disease risk factors among HIV patients on anti-retroviral therapy (ART) in Bushbuckridge sub-district. The current study followed a quantitative cross-sectional study design using a questionnaire which was adapted from World Health Organization STEPwise approach to Surveillance (WHO STEPS). Participants were HIV infected people on ART and data was entered into a computer software Microsoft excel, then imported to Stata 12 for analysis. The overall prevalence of overweight at the initiation of ART amongst the participants was 18.1% and obesity was 11.5% as compared to the time of the study which was 21.4% overweight and 19.6% obese. The average time of ART initiation to study period was 3.6 years. The study findings revealed a significant difference (p-value 0.006) between the baseline and current body mass index at time of study for females. Hypertension was found to be having a significant difference (p-value 0.026 and 0.038) between the baseline and current body mass index at time of study for males and females respectively. The overall prevalence of hypertension was found to be 34.6%, overweight was 21.4% obesity was 19.6%. The overall prevalence of abnormal waist circumference was 31.9% and females had a higher prevalence of 42.5% as compared to 4.4% of males. The overall prevalence of smoking 10.8% and alcohol consumption was 21.7%. Males were 22.5 times more likely to be smokers than females (p < 0.001) and older people were found to be 0.3 times less likely to consume alcohol as compared to young people. The high levels of selected risk factors for NCDs among adults on ART in the current study area suggest an urgent need for health interventions to control risk factors in an era of HIV with an aim of reducing multiple morbidity of chronic diseases. Occurrence of NCDs and their risk factors with an aim to achieve positive effects of the long-term ART.


[On the history of teaching to Russian physicians the communicative skills].
The views of G.A. Zkhariin and S.P. Botkin, the founders of national therapeutic scientific schools, concerning the skills of communication with patients drastically differed. The detailed systematic questioning, the priority of examining the anamnesis data prior to the results of instrumental examination are the characteristic traits of the technique developed by G.A. Zkhariin. S.P. Botkin proposed to apply the communicative technology targeted on the questioning and gathering the anamnesis data in a free manner and having minor importance in comparison with the instrumental examination.


Organic acid production and plant growth promotion as a function of phosphate solubilization by Acinetobacter rhizosphaerae strain BIHB 723 isolated from the cold deserts of the trans-Himalayas.
An efficient phosphate-solubilizing plant growth-promoting Acinetobacter rhizosphaerae strain BIHB 723 exhibited significantly higher solubilization of tricalcium phosphate (TCP) than Udaipur rock phosphate (URP), Mussoorie rock phosphate (MRP) and North Carolina rock phosphate (NCRP). Qualitative and quantitative differences were discerned in the gluconic, oxalic, 2-keto gluconic, lactic, malic and formic acids during the solubilization of various inorganic phosphates by the strain. Gluconic acid was the main organic acid produced during phosphate solubilization. Formic acid production was restricted to TCP solubilization and oxalic acid production to the solubilization of MRP, URP and NCRP. A significant increase in plant height, shoot fresh weight, shoot dry weight, root length, root dry weight, and root, shoot and soil phosphorus (P) contents was recorded with the inoculated treatments over the uninoculated NP(0)K or NP(TCP)K treatments. Plant growth promotion as a function of phosphate solubilization suggested that the use of bacterial strain would be a beneficial addition to the agriculture practices in TCP-rich soils in reducing the application of phosphatic fertilizers.


Effects of glucosamine on lysis, glycerol formation, and sporulation in Myxococcus xanthus.
Glucosamine (GlcN), which has previously been shown to rescue fruiting body formation, lysis, and sporulation in a developmental mutant (G. Janssen and M. Dworkin, Dev. Biol. 112:194-202, 1985), induced lysis in vegetative and developing wild-type cells and inhibited fruiting body formation. It also resulted in a transient, intracellular increase in the concentration of glycerol, a known sporulation inducer, and sporulation of the surviving cells. Phospholipase activity, which was shown to be normally developmentally regulated, increased 7.6-fold after treatment of vegetative cells with 50 mM GlcN. Likewise, autocidal activity, which normally increased 18 to 24 h after the initiation of development, increased 20% when vegetative or developing cells were exposed to GlcN. Two mutants resistant to GlcN-induced lysis (MD1021 and MD1022) were isolated and showed neither an increase in autocide production nor an increase in phospholipase activity in response to added GlcN. MD1021 was developmentally deficient, and GlcN rescued fruiting body formation as well as phospholipase activity and autocide production. We propose that GlcN exerts its lytic effect by regulating the activity of phospholipase enzymes that release autocides, compounds that are believed to be responsible for developmental autolysis. GlcN-induced sporulation was found to depend on several factors: the initial cell density, the amount of lysis induced by GlcN, and the presence of tan-phase variants. An initial cell density of greater than 2 x 10(5) cells per ml was required to support GlcN-induced sporulation, and sporulation did not occur unless 50 to 75% of these cells had lysed. Mutants that were resistant to GlcN-induced lysis also did not sporulate in the presence of GlcN. The effects of GlcN on developing cells depended on the concentration of GlcN added; the addition of low concentrations of GlcN resulted in enhancement of sporulation, while higher concentrations resulted in the inhibition of sporulation. The ultrastructure of GlcN-induced spores resembled that of spores induced by the exogenous addition of glycerol, in contrast to spores isolated from mature fruiting bodies. A model by which GlcN may regulate both lysis and sporulation is presented.


Immunohistochemical comparative analysis of transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor in normal, hyperplastic and neoplastic human prostates.
Immunoreaction to TGF-alpha was limited to the basal epithelial cells of focal areas in the normal prostates. In benign prostatic hyperplasia (BPH) the immunostained areas were more widespread and immunolabelling was observed in both basal and columnar (secretory) cells of the epithelium. Some cells in the connective tissue stroma were also stained. In prostatic adenocarcinoma, epithelial immunostaining was even more extensive and intense than in BPH, and some stromal cells were also stained. Epidermal growth factor (EGF) immunostaining was only present in some basal cells in normal prostates. In BPH, this immunoreaction was strong in the basal cells and even stronger in the secretory cells. In prostatic cancer, the intensity of epithelial cell immunoreactivity was intermediate between that of normal prostates and that of BPH specimens. EGF-receptor immunostaining was focal and located in the basal cells in normal prostates. In BPH, labelling was also localized in basal cells but extended to wider areas. Some stromal cells appeared weakly labelled. In the prostatic carcinoma, both basal and columnar cells appeared stained and the number of immunolabelled stromal cells was higher than in BPH. The results presented suggest that, in normal conditions, EGF and TGF-alpha act as autocrine growth factors for the basal cells of the prostatic epithelium. In BPH this action is maintained and, in addition, the columnar cells start to secrete both factors which are bound by the basal cell receptors, giving rise to a paracrine regulation which probably overstimulates basal cell proliferation. In prostatic carcinoma, besides these regulatory mechanisms, the acquisition of EGF-receptors by the secretory cells develops an autocrine regulation which might induce their proliferation.


Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice.
Intestinal epithelial cells secrete exosome-like vesicles. The aim of this study was to characterise murine intestinal epithelial exosomes and to analyse their capacity to inform the immune system in vivo in mice. Epithelial exosomes were obtained from the murine epithelial cell line MODE K incubated in the presence or absence of interferon gamma (IFN-gamma) together with pepsin/trypsin ovalbumin hydrolysate (hOVA) to mimic luminal digestion. Exosomes isolated from MODE K conditioned media (EXO-hOVA and EXO-hOVA-IFN) were characterised by western blot, peptide mapping, and mass spectrometry. They were injected intraperitoneally to C3H/HeN mice to test their immunocompetence. MODE K epithelial exosomes displayed major histocompatibility complex (MHC) class I and class II (upregulated by IFN-gamma) molecules and tetraspan proteins (CD9, CD81, CD82) potentially involved in the binding to target cells. A33 antigen, an Ig-like molecule highly specific for intestinal epithelial cells, was enriched in exosomes and was also found in mice mesenteric lymph nodes, suggesting exosome migration towards the gut associated lymphoid tissues. Intraperitoneal injection of EXO-hOVA or EXO-hOVA-IFN did not induce humoral or cellular tolerance to OVA in mice. In contrast, exosomes obtained after incubation with IFN-gamma (EXO-hOVA-IFN), bearing abundant MHC class II/OVA complexes, induced a specific humoral immune response. Epithelial exosomes are antigen presenting vesicles bearing MHC class II/peptide complexes that prime for an immunogenic rather than tolerogenic response in the context of a systemic challenge. In the intestine, both the mucosal microenvironment and local effector cells are probably key players in determining the outcome of the immune response to exosome derived epitopes.


Effects of resonant absorption and inhomogeneous broadening on reflection and absorption spectra of optical lattices diamond NV centers.
Using the transfer-matrix method, the effects of absorption and inhomogeneous broadening, in one-dimensional optical lattice constructed from inhomogeneously broadened spin transitions of nitrogen-vacancy color centers in single crystal diamond (NV diamond), on the reflection and absorption spectrum are presented. Further analysis show that, in realistic periodic stacks of the NV diamond, modulating the geometrical configuration of the external optical potential, the absorption lineshape scale, and the inhomogeneous broadening, one could easily access the diverse gap structures and a high band-gap reflectivity. These pretty useful calculations hold more potential for effective control of the light-matter interaction and realization in practice.


[Timing of radiotherapy in the treatment of breast carcinoma. Review of the literature].
Combined modality treatments are indicated for most patients with breast cancer. The definition of a proper treatment schedule and of the timing of each modality is a relevant issue that affects the feasibility and the clinical outcome of the treatment. A review of the literature was done on the timing of radiation therapy (RT) in the post-operative treatment of breast cancer. Retrospective studies and randomized clinical trials addressing the issue were considered and grouped according to the combined modality treatments performed. With regard to breast conserving surgery and adjuvant RT, it was verified that a delay up to 8 weeks between breast surgery and start of RT is not associated with an increased risk of local failure if compared with RT started within 4 weeks. Concerning breast conserving surgery followed by adjuvant RT and chemotherapy, the choice of the best schedule is still a complex unresolved issue. More results on sequential schedule of adjuvant RT and chemotherapy from recently published randomized studies are available. The reconstruction of the breast after conservative surgery is rarely necessary and is usually performed immediately after surgical treatment. With regard to mastectomy followed by adjuvant RT and breast reconstruction, it appears from some retrospective studies that autologous tissue transfer offers better results over implants. Concerning the transverse rectus abdominis muscle (TRAM) procedure, either immediate reconstruction before RT or delayed reconstruction after RT was feasible without significative differences in complication rates. Further randomized clinical studies are required to address the unresolved issues linked to the timing of RT. At present the treatment plan should be based on the patient's individual circumstances with regard to risk of metastasis and local failure.


Six-month-olds' categorization of natural infant-directed utterances.
In this study, the authors demonstrated that 6-month-old infants are able to categorize natural, 650 Hz low-pass filtered infant-directed utterances. In Experiment 1, 24 male and 24 female infants heard 7 different tokens from 1 class of utterance (comforting or approving). Then, some infants heard a novel test stimulus from the familiar class of tokens; others heard a test stimulus from the unfamiliar class. Infants categorized these tokens as evidenced by response recovery to tokens from the unfamiliar class but not to novel tokens from the familiar class. Experiment 2 confirmed that the infants were able to discriminate between closely matched tokens from within each category, supporting the conclusion that the results of Experiment 1 indicated categorization. The authors discuss both a mechanism that might explain the development of this ability and the mutual adaptation seen in parent-infant communication.


Breast cancer risk associated with congeners of polychlorinated biphenyls.
Experimental studies show that hormonal and nonhormonal activities of polychlorinated biphenyls (PCBs) are structure dependent, suggesting that the breast cancer risk associated with PCBs may vary according to specific PCB congeners. In 1994-1997, the authors conducted a case-control study of Connecticut women to investigate whether breast cancer risk is associated with body burden of PCBs and varies by PCB congeners. A total of 304 breast cancer cases and 186 controls aged 40-79 years were recruited into the study. Fresh breast adipose tissue was analyzed for PCBs. The age- and lipid-adjusted geometric mean tissue levels of total PCBs were not significantly different (p = 0.46) for the cases (478.6 parts per billion) and controls (494.1 parts per billion). The covariate-adjusted odds ratio was 0.7 (95% confidence interval: 0.4, 1.1) for all study participants when the third tertile was compared with the lowest tertile. No individual congeners or groups of congeners were associated with a significantly increased risk of breast cancer. Further stratification by type of breast disease; menopausal, parity, and lactation status; and body size also showed no significant association with body levels of PCBs. These results suggest that environmental exposure to PCBs may not substantially affect breast cancer risk.


Two-Step Estimation of the Impact of Contextual Variables on Technical Efficiency of Hospitals: The Case Study of Public Hospitals in Iran.
Background: Measuring the efficiency and productivity of hospitals is a key tool to cost contamination and management that is very important for any healthcare system for having an efficient system. Objective: The purpose of this study is to examine the effects of contextual factors on hospital efficiency in Iranian public hospitals. Methods: This was a quantitative and descriptive-analytical study conducted in two steps. First, we measured the efficiency score of teaching and non-teaching hospitals by using the Data Envelopment Analysis (DEA) method. Second, the relationship between efficiency score and contextual factors was analyzed. We used median statistics (first and third quarters) to describe the concentration and distribution of each variable in teaching and non-teaching hospitals, then the Wilcoxon test was used to compare them. The Spearman test was used to evaluate the correlation between the efficiency of hospitals and contextual variables (province area, province population, population density, and the number of beds per hospital). Results: On average, the efficiency score in non-teaching hospitals in 31 provinces was 0.67 and for teaching hospitals was 0.54. Results showed that there is no significant relationship between the efficiency score and the number of hospitals in the provinces (p = 0.1 and 0.15, respectively). The relationship between the number of hospitals and the population of the province was significant and positive. Also, there was a positive relationship between the number of beds and the area of the province in both types of teaching and non-teaching hospitals. Conclusion: Multilateral factors influence the efficiency of hospitals and to address hospital inefficiency multi-intervention packages focusing on the hospital and its context should be developed. It is necessary to pay attention to contextual factors and organizational architecture to improve efficiency.


The foster care system and health status of foster children.
The foster home care system is the most commonly used alternative for the care of dependent children in the United States. However, it often fails to achieve its objective of returning the child to his home or providing a permanent substitute family. Children entering foster care have frequently suffered social, emotional, and medical neglect, and physical abuse. They have a high rate of chronic medical problems, educational handicaps, and severe emotional impairment. In many cases the health care that foster children receive fails to recognize and/or adequately address their disabilities. In order for the pediatric practitioner to work successfully with a foster child, he must not only provide comprehensive health care, but also must be familiar with the social welfare system within which the child lives.


Low-volume hybrid bowel preparation combining saline laxatives with oral contrast agents versus standard polyethylene glycol lavage for colonoscopy.
The aim of this study was to compare the quality of low-volume hybrid computed tomography colonography bowel preparation, using both laxatives and oral contrast, with standard polyethylene glycol lavage. The study group consisted of 300 consecutive adults (mean age, 58.3 years) who underwent colonoscopy immediately after positive computed tomography colonography. Hybrid bowel preparation for study group was <1 L in total volume, consisting of osmotic cathartic (sodium phosphate or magnesium citrate) in conjunction with oral contrast (2% barium and diatrizoate). A control group of 300 adults (mean age, 58.3 years) underwent primary colonoscopy after standard 4-liter polyethylene glycol lavage without oral contrast. The prospective preparation quality rating by the endoscopist served as the reference standard. A rating of poor/marginal was considered inadequate and adequate/good/excellent was considered diagnostic. The frequency of inadequate bowel preparation was 4.3% (13/300) in the study group vs 12.3% (37/300) for the control group (P < .001). Specifically, preparation was poor or marginal in 10 and 3 cases in the hybrid cohort, respectively, and in 29 and 8 cases in the polyethylene glycol cohort, respectively. Preparation quality was scored as excellent in 32% (96/300) in the hybrid cohort and 23.3% (70/300) in the polyethylene glycol cohort (P < .05). At colonoscopy, low-volume laxative-oral contrast hybrid preparations are effective for bowel cleansing, perhaps even more so than polyethylene glycol lavage. Beyond improvements in quality, the low-volume preparation may improve patient compliance and would allow for immediate computed tomography colonography if colonoscopy is incomplete, without the need for additional oral contrast tagging.


Problematic internet use in emerging adulthood to escape from maternal helicopter parenting: defensive functioning as a mediating mechanism.
The increasing use of the Internet has raised concerns about its problematic use, particularly among emerging adults who grew up in a highly digitalized world. Helicopter parenting, characterized by excessive involvement, overcontrol, and developmentally inappropriate behavior, has been identified as a potential factor contributing to problematic Internet use (PIU). Under these circumstances, considering that emerging adults navigate their adult lives and strive to reduce their sense of being in-between, implicit emotion regulation strategies, such as defense mechanisms, may help comprehend PIU. The present questionnaire-based study investigated the associations between maternal and paternal helicopter parenting and PIU through defensive functioning among a community sample of 401 cisgender emerging adults (71.82% females; 82.04% heterosexuals; Mage=24.85, SD=2.52) living in Italy. About one-fourth (25.19%) reported PIU. Greater maternal, B=0.904, SE=0.235, p<.001, but not paternal, B=0.343, SE=0.188, p=.068, helicopter parenting was significantly associated with PIU through a less mature defensive functioning. Conversely, neither maternal, B=1.158, SE=0.722, p=.109, nor paternal, B=0.355, SE=0.731, p=.628, helicopter parenting had a direct association with PIU. The results suggest the importance for psychotherapists to incorporate individuals' defense mechanisms and parent-child relationship history when designing tailored interventions for effective treatment of PIU. This emphasis is crucial because, in the context of a developmentally appropriate parenting style, relying on more mature defenses after psychotherapeutic intervention can lead to healthier adjustment among emerging adults.


Hip arthroplasty in Norway 1989-2008.
Since information on regional variation in the frequency of primary total hip arthroplasty in Norway is scarce, we studied differences by county and regional health authority throughout the last 20 years. We included 112, 514 primary total hip arthroplasties reported to the Norwegian Arthroplasty Register in the years 1989-2008. Annual gender and age standardized frequencies were calculated, and Poisson regression was used for group comparisons (RR = rate ratio). We observed an increase in hip arthroplasty frequency from 109 operations per 100, 000 inhabitants in the years 1991-1995 to 140 in 2006-2008 (RR = 1.28), and more so for operations performed due to coxarthrosis (RR = 1.46). An increased frequency over time was evident in all five regions and 19 counties. Differences between counties and regions had decreased throughout the study period. In the years 2006-2008, Helse Midt (152 operations) had a statistically significant higher frequency than the other regions except for Helse Sør. The lowest frequencies at county level were found for Finnmark (116 operations) and the highest for Aust-Agder (172). While regional differences have decreased since the early 1990 s, existing differences may in part be due to differing access to surgery, varying indications for surgery, or possibly also genetic or cultural differences.


Cooperative interactions of LPPR family members in membrane localization and alteration of cellular morphology.
The lipid phosphate phosphatase-related proteins (LPPRs), also known as plasticity-related genes (PRGs), are classified as a new brain-enriched subclass of the lipid phosphate phosphatase (LPP) superfamily. They induce membrane protrusions, neurite outgrowth or dendritic spine formation in cell lines and primary neurons. However, the exact roles of LPPRs and the mechanisms underlying their effects are not certain. Here, we present the results of a large-scale proteome analysis to determine LPPR1-interacting proteins using co-immunoprecipitation coupled to mass spectrometry. We identified putative LPPR1-binding proteins involved in various biological processes. Most interestingly, we identified the interaction of LPPR1 with its family member LPPR3, LPPR4 and LPPR5. Their interactions were characterized by co-immunoprecipitation and colocalization analysis using confocal and super-resolution microscopy. Moreover, co-expressing two LPPR members mutually elevated their protein levels, facilitated their plasma membrane localization and resulted in an increased induction of membrane protrusions as well as the phosphorylation of S6 ribosomal protein. Taken together, we revealed a new functional cooperation between LPPR family members and discovered for the first time that LPPRs likely exert their function through forming complex with its family members.


Uniportal video-assisted thoracoscopic thymectomy and resection of a giant thymoma in a patient witness of Jehova.
A rare case of a giant thymoma in a patient witness of Jehova treated by single port thoracoscopic resection is reported. A 78-year-old man with chest pain and mild dyspnea had been previously diagnosed with giant thymoma went to our hospital and asked for second opinion of operation. Computed tomography showed a 12.5 cm × 9.5 cm × 10 cm mass in the anterior mediastinum. Under the request of this patient, he is only willing to receive minimal invasive surgery without blood transfusion. Thirty-six hours after surgical resection, the patient safely discharged from our hospital without complication. Pathological diagnosis indicated a thymoma without capsular invasion, and a diagnosis of Masaoka stage I thymoma was made. Giant mediastinal thymoma is not rare, but how to perform minimal invasive surgery without complication and blood transfusion is a great challenge even for an experienced surgeon.


The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin.
Pertussis toxin treatment of rabbit peritoneal neutrophils causes a concentration-dependent inhibition of granule enzyme secretion induced by formylmethionyl-leucyl-phenylalanine, C5a, and leukotriene B4. It also inhibits chemotaxis induced by formylmethionyl-leucyl-phenylalanine. The same toxin treatment, however, has no effect on granule enzyme secretion induced by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate. Moreover, pertussis toxin treatment does not affect either the number or affinity of the formylpeptide receptors on the neutrophil nor does it have any effect on the unstimulated levels of cyclic AMP (cAMP) or the transient rise in cAMP induced by chemotactic factor stimulation in these cells. We hypothesize that pertussis toxin, as in other cells, interacts with a GTP binding regulatory protein identical with or analogous to either Ni or transducin which mediates the receptor-induced inhibition or activation of a target protein or proteins required in neutrophil activation. The nature of the target protein is unknown, but it is not the catalytic unit of adenylate cyclase. The target protein acts after binding of chemotactic factor to its receptor in the sequence that leads to the receptor-induced rise in intracellular Ca2+. It does not affect the responses elicited by the direct introduction of calcium into the cells or the activity of protein kinase C.


The expression and stage-specific localization of protein kinase C isotypes during mouse preimplantation development.
Signaling events mediate many processes that act during embryogenesis to initiate the program of early development. Within the cell many of these changes are mediated through the activation or inactivation of kinases and phosphatases. Protein kinase C (PKC) is one kinase that has been shown to be involved in at least two developmental transitions during early development, fertilization and embryonic compaction. PKC is a family of kinases whose various isotypes have differing requirements for activation of the kinase that include the availability of calcium, diacylglycerol, and negatively charged phospholipids. The presence of more than one isotype in an egg or blastomere of the embryo would provide the possibility that different isotypes mediate distinct signaling pathways in the cells. To address this possibility the different isotypes of PKC were examined at the mRNA and protein levels during preimplantation development in the mouse. Our results demonstrate that seven isotypes of PKC are present during preimplantation development in mouse, some are of maternal origin and others appear after fertilization. Two isotypes have a stage-dependent nuclear localization. In addition, within each blastomere PKC isotypes occupy different subcellular locations in a stage-dependent fashion.


Triclosan: environmental exposure, toxicity and mechanisms of action.
Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad spectrum antibacterial agent used in personal care, veterinary, industrial and household products. TCS is commonly detected in aquatic ecosystems, as it is only partially removed during the wastewater treatment process. Sorption, biodegradation and photolytic degradation mitigate the availability of TCS to aquatic biota; however the by-products such as methyltriclosan and other chlorinated phenols may be more resistant to degradation and have higher toxicity than the parent compound. The continuous exposure of aquatic organisms to TCS, coupled with its bioaccumulation potential, have led to detectable levels of the antimicrobial in a number of aquatic species. TCS has been also detected in breast milk, urine and plasma, with levels of TCS in the blood correlating with consumer use patterns of the antimicrobial. Mammalian systemic toxicity studies indicate that TCS is neither acutely toxic, mutagenic, carcinogenic, nor a developmental toxicant. Recently, however, concern has been raised over TCS's potential for endocrine disruption, as the antimicrobial has been shown to disrupt thyroid hormone homeostasis and possibly the reproductive axis. Moreover, there is strong evidence that aquatic species such as algae, invertebrates and certain types of fish are much more sensitive to TCS than mammals. TCS is highly toxic to algae and exerts reproductive and developmental effects in some fish. The potential for endocrine disruption and antibiotic cross-resistance highlights the importance of the judicious use of TCS, whereby the use of TCS should be limited to applications where it has been shown to be effective.


How well do general practitioners manage laboratory test results for patients with diabetes mellitus and cardiovascular disease?: A systematic review.
To evaluate how well general practitioners (GPs) manage and respond to laboratory results for patients with diabetes mellitus (DM) and cardiovascular disease (CVD). MEDLINE, CINAHL, Embase, EBM reviews, ProQuest and Scopus. Peer-reviewed journal articles published between 2000 and 2015 that assessed GPs' management of laboratory results for patients with DM or CVD. Study design and demographics, laboratory tests and key findings relating to GP management of laboratory results were extracted from studies. Thirteen articles were included, comprising seven studies which utilized surveys, four observational studies, one cohort study and one randomized controlled trial. Findings indicate that GPs often overestimate the risk of complications associated with DM and CVD based on laboratory results and have unrealistically high expectations regarding the precision of laboratory tests. Considerable variation existed in the use of repeat testing for diagnostic confirmation and in GPs' identification of the difference between two consecutive results required to indicate a change in patient condition. GPs also often failed to initiate appropriate treatment for patients with DM and CVD based on laboratory results. Feedback to GPs about their test ordering patterns and educational messages on laboratory results improved clinical outcomes. Evidence about how well GPs manage results and its impact on patient outcomes remains weak and inconclusive. This review identified a number of areas where interventions could support GPs to improve the interpretation and management of laboratory test results, including feedback to GPs and educational messages on test result reports.


Reasons for attempting suicide among men who use alcohol and other drugs.
Objective To understand the reasons that lead men who use alcohol and other drugs to attempt suicide. Methods Qualitative research at an alcohol and psychosocial drugs support centre (CAPSad) in the state of Rio Grande do Sul, Brazil, in December of 2011, with 11 men who use alcohol and other drugs and who attempted suicide. Data were collected by means of phenomenological interviewing. The phenomenological sociology of Alfred Schütz was used to analyse and interpret the interview statements. Results The results led to three categories: attempted suicide triggered by alcohol and drug use; attempted suicide triggered by the family lifeworld; and attempted suicide triggered by everyday feelings. Conclusion We found that alcohol and drug abuse and the different life circumstances of men in their families and social relationships contributed to the suicide attempt.


Maturation of TonEBP expression in developing rat kidney.
Tonicity-responsive enhancer binding protein (TonEBP) is a transcriptional activator of the Rel family. In the renal medulla, TonEBP stimulates genes encoding proteins involved in cellular accumulation of organic osmolytes, the vasopressin-regulated urea transporters (UT-A), and heat shock protein 70. To understand the role of TonEBP in the development of urinary concentrating ability, TonEBP expression during rat kidney development was investigated. In embryonic kidneys, TonEBP immunoreactivity was detected 16 days postcoitus in the cytoplasm of the endothelial cells surrounding the medullary collecting ducts (MCD). By 20 days, TonEBP was detected in most tubular profiles in the medulla, including the loop of Henle and MCD, and interstitial cells. The intensity of TonEBP immunoreactivity was much higher in the vasa recta than the tubules. In addition, immunoreactivity was localized predominantly to the cytoplasm. On postnatal day 1, two major changes were observed. TonEBP immunoreactivity shifted to the nucleus, and the intensity of TonEBP immunoreactivity of the tubules increased dramatically. These changes were associated with an increase in TonEBP and sodium-myo-inositol cotransporter mRNA abundance. Thereafter, TonEBP expression in tubular profiles increased moderately. The adult pattern of TonEBP expression was established at postnatal day 21 coincident with full maturation of the renal medulla. Thus expression of TonEBP in developing kidneys occurred predominantly in the medulla and preceded expression of its target genes, including UT-A. These data suggest that TonEBP contributes to the development of urine-concentrating ability.


Benefits of preventing a death associated with child maltreatment: evidence from willingness-to-pay survey data.
Although assessing the costs of an intervention to prevent child maltreatment is straightforward, placing a monetary value on benefits is challenging. Respondents participating in a statewide random-digit-dialed survey were asked how much they would be willing to pay to prevent a death caused by child maltreatment. Our results suggested that society may value preventing a death from child maltreatment at $15 million. If a child maltreatment intervention is effective enough to save even 1 life, then in many cases, its benefits will outweigh its costs.


SCTR hypermethylation is a diagnostic biomarker in colorectal cancer.
Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of the secretin receptor (SCTR) gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA) CRC methylation data (N = 440), and verified in a large-scale test set (N = 938) from the Gene Expression Omnibus (GEO). Targeted bisulfite sequencing analysis was developed and applied to detect the methylation status of SCTR in our independent validation set (N = 374). Our findings revealed that the SCTR gene was frequently hypermethylated at its CpG islands in CRC. In the TCGA discovery set, the diagnostic score was constructed using 4 CpG sites (cg01013590, cg20505223, cg07176264, and cg26009192) and achieved high diagnostic performance (area under the ROC curve [AUC] = 0.964). In the GEO test set, the diagnostic score had robust diagnostic ability to distinguish CRC (AUC = 0.948) and its precursor lesions (AUC = 0.954) from normal samples. Moreover, hypermethylation of the SCTR gene was also found in cell-free DNA samples collected from CRC patients, but not in those from healthy controls. In the validation set, consistent results were observed using the targeted bisulfite sequencing array. Our study highlights that hypermethylation at CpG islands of the SCTR gene is a potential diagnostic biomarker in CRCs and its precursor lesions.


[Medical x-ray equipment on the threshold of the 21st century].
The authors, specialists in medical X-ray engineering, have been engaged in it for about 40 years, forecast that this medical engineering field will be under development and regard its development as transition to a qualitative new level prepared by latest technologies in X-ray apparatus making, digital television, and computed technology rather than an ultimate landmark of evolution.


Evaluation of the clinical performances of a large NaI(Tl) crystal 3D PET scanner.
This study was aimed at assessing the clinical performances of a NaI(Tl) crystal 3D PET scanner, C-PET (ADAC-UGM), using a multi-ring 2D BGO PET scanner (multi-ring PET), as a reference. Thirty-seven oncological patients were studied in sequence with multi-ring PET and C-PET, within 30 days of a CT study. In order to assess the behaviour of C-PET in relation to acquisition count rate, patients were divided into 3 groups according to the count rate at the time of the C-PET scan acquisition. Group A (n=21): 3000-5000 kcounts/sec (recommended count rate range); Group B (n=8): <3000 Kcounts/sec and Group C (n=8): >5000 Kcounts/sec. The number of lesions detected by multi-ring PET and C-PET, classified according to size, was compared. For Group A and Group B there was a good agreement between C-PET and multi-ring PET in terms of lesion detectability (relative sensitivity: 99.9% and 96.0%, respectively), while for Group C the relative sensitivity of C-PET was 61.9%. Optimal performances of the C-PET scanner can thus be obtained at a count rate within or below the recommended range. Despite a lower lesion/background contrast resulting from a high scatter and random noise, the sensitivity of C-PET in detecting hypermetabolic lesions is comparable to that of multi-ring PET. These findings are discussed in relation to the physical performance of the two scanners and particularly in relation to the 3D vs 2D acquisition modality.


Does surgery have a role in T4N0 and T4N1 lung cancer?
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed whether [surgery] has a role in [treatment of T4N0 and T4N1 lung cancer]. Altogether more than 151 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that upfront surgery for locally invasive T4 tumours without mediastinal lymph node involvement (T4N0 and T4N1 non-small cell lung cancer) is of benefit in terms of survival rates in carefully selected patients. Overall five-year survival rates following resection of T4N0-N2 tumours vary from 19.1% to 57% (from six studies), within which, involvement of certain structures were found to greatly affect prognosis. Pulmonary artery invasion has a good prognosis (five-year survival; 52.8%) relative to other mediastinal structures [five-year survival: left atrium; N0; 28.94%, N1; 27.92%, N2; 17.95% (three-year survival), aorta; N0; 100%, N1; 37.1%, N2; 0%, superior vena cava (SVC); 11%, -29.4% (from four studies), carina; 28-42.5% (two studies), veterbral bodies; 16%, oesophagus; 12%, pleural dissemination; 0%]. When considering isolated invasion of the pulmonary great vessels there are mixed outcomes, one study reporting reduced mortality (reduced risk -0.483, P=0.004) in contrast to another that found five-year survival of 35.7% with great vessel invasion vs. 58.3% for invasion of all other structures excluding the pulmonary great vessels. The prognostic variables found to be of greatest determinacy were; first, the completeness of resection, wherein five-year survival rates ranged from 37.5 to 46.2% (from three studies) with complete tumour removal, and 15.9-22.4% (from three studies) with incomplete resection, and second, nodal status of the patients, N0/N1 having five-year survival of 43-74% and N2 of 15.1-17.5% (P=0.022 and P=0.007, for two studies). Multiple intralobar lesions represent either multilobar metastasis or NSCLC with multifocal origin and have been found to behave differently to invasive T4 tumours. Reported five-year survival in NSCLC with satellite nodules is 48.2-57% compared with 18-30% from T4 invasive tumours (three studies), respectively (P=0.011) corroborating the change in TNM ipsilobar multifocal T4 disease to be recoded as T3.


Isolation of polyribosomes from yeast during sporulation and vegetative growth.
Exponentially growing and sporulating cells of Saccharomyces cerevisiae have been subjected to a variety of conditions which mechanically disrupt the cell in an effort to establish conditions which permit the recovery of intact polyribosomes. Grinding cells for 10 s with glass beads in a Bronwill cell homogenizer was sufficiently gentle to yield a polyribosome content in exponentially growing cells which was similar to values obtained from yeast spheroplasts. Polyribosome patterns in sporulating yeast were similar to those from exponentially growing cells. This technique is fast, reproducible over a wide range of cell concentrations, and eliminates the need to make spheroplasts to recover intact polyribosomes.


A highly selective and stable ZnO-ZrO2 solid solution catalyst for CO2 hydrogenation to methanol.
Although methanol synthesis via CO hydrogenation has been industrialized, CO2 hydrogenation to methanol still confronts great obstacles of low methanol selectivity and poor stability, particularly for supported metal catalysts under industrial conditions. We report a binary metal oxide, ZnO-ZrO2 solid solution catalyst, which can achieve methanol selectivity of up to 86 to 91% with CO2 single-pass conversion of more than 10% under reaction conditions of 5.0 MPa, 24,000 ml/(g hour), H2/CO2 = 3:1 to 4:1, 320° to 315°C. Experimental and theoretical results indicate that the synergetic effect between Zn and Zr sites results in the excellent performance. The ZnO-ZrO2 solid solution catalyst shows high stability for at least 500 hours on stream and is also resistant to sintering at higher temperatures. Moreover, no deactivation is observed in the presence of 50 ppm SO2 or H2S in the reaction stream.


Is Toxoplasma gondii a potential risk factor for Alzheimer's disease? A systematic review and meta-analysis.
Toxoplasmosis is a major public health concern due to neurotropic nature and role in the development of mental and behavioral disorders. Alzheimer's disease (AD) is an important nervous disease that results in the reduction of the amount of beta-amyloid plaque deposition and irreversible loss of neurons in the brain. Although a few studies evaluated the association between AD and toxoplasmosis, the present study as a systematic review and meta-analysis of published studies investigated the possible association between Toxoplasma gondii (T. gondii) and AD. A systematic literature search was conducted using seven electronic databases from the inception to 25th of November 2018 with no restriction of language that looked at toxoplasmosis (as an exposure) and AD (as a disease). The random effect model was used to determine the total odds ratio (OR) and total p-value. Generally, eight studies containing 3239 subjects (360 patients and 2879 controls) met the eligibility criteria. Then, eight articles were used for meta-analysis with respect to inclusion and exclusion criteria. The results of the meta-analysis (random effect model) showed a common OR of 1.53 (95% CI: 1.07-2.18). Despite the fact that there was no evidence of publication bias (P = 0.079) using formal statistical test, the visual inspection of the funnel graph suggested that the observed effect was fueled mainly by three studies with large effects (and large standard errors). Moreover, the file-drawer effect (i.e. publishing mainly studies with positive results) might play a role in the phenomenon. Results of this meta-analytic study suggested that T. gondii can be considered a risk factor for the development of AD and exacerbation of its symptoms. However, the number of published relevant studies is still relatively low, and the risk of the presence of publication bias is relatively high. Therefore, the investigation of the clinically important question of the possible association between toxoplasmosis and AD definitively deserves further attention.


Spinal muscular atrophy: manifestations and management.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion in the SMN1 gene and is manifested by loss of the anterior horn cells of the spinal cord. Classifications of the disorder are based on age of onset and the patient's level of function. Scoliosis and hip subluxation or dislocation are two musculoskeletal manifestations associated with SMA. Severity of scoliosis correlates with age at presentation. Bracing has been unsuccessful in halting curve progression and may interfere with respiratory effort. Early onset scoliosis associated with SMA has been successfully treated with growing rod constructs, and posterior spinal fusion can be used in older children. Hip subluxations and dislocations are best treated nonsurgically if the patient reports no pain because a high rate of recurrent dislocation has been reported with surgical intervention.


Stress, stress-related symptoms and social support among Taiwanese primary family caregivers in intensive care units.
To explore the associations between stress, sleep disturbances, fatigue severity and social support among primary family caregivers in intensive care units during the early period of ICU hospitalisation. Cross-sectional, descriptive correlational study. Intensive Care Units in a teaching hospital in Taiwan. Perceived stress (Impact of Events Scale-Revised), sleep disturbances (General Sleep Disturbance Scale), fatigue severity (Lee's Fatigue Scale), social support (Norbeck Social Support Questionnaire) and one open-ended question. The primary family caregivers (N = 87) were distressed and experienced poor sleep quality and fatigue during the early period of ICU hospitalisation. Primary family caregivers have various social support needs but being updated on the patients' prognosis was at the top of the list. Perceived ICU hospitalisation stress was the only significant predictor for fatigue while age along with perceived event stress were the significant predictors for sleep disturbances. Stress-coping interventions are needed to reduce stress-related symptoms for the primary family caregivers. Social supports did not buffer stress in this study, which calls for further research to explore the culture variance and quality of social support.


Prediction performance of serum placental growth factor (PLGF) human chorionic gonadotropin β (β-hCG) and PAPP-A levels in early pregnancy for pregnancy outcomes.
To investigate the prediction performance of serum placental growth factor (PLGF), free human chorionic gonadotropin β (β-hCG) and pregnancy-associated plasma protein A (PAPP-A) levels in early pregnancy for pregnancy outcomes. A total of 4256 pregnant women who underwent obstetric examinations in our hospital from June 2018 to June 2020 and completed their full pregnancy were included in the study. The clinical pregnancy outcomes of pregnant women with different PLGF, PAPP-A and β-hCG levels in early pregnancy were recorded, and the prediction performance of the above indicators for adverse pregnancy outcomes was discussed. Pregnant women with increased or decreased PLGF or increased PAPP-A or β-hCG had significantly higher incidence of adverse pregnancy outcomes than normal pregnant women. Pregnant women with abnormal pregnancy had significantly higher β-hCG and PLGF, and lower PAPP-A than those with normal pregnancy. The sensitivity of serum PLGF, β-hCG and PAPP-A in early pregnancy for predicting adverse pregnancy outcomes was 95.13%, 94.19% and 97.75%, and the specificity was 84.31%, 85.80% and 83.22%, respectively. Serum PLGF, PAPP-A and β-hCG in early pregnancy are more effective in predicting adverse pregnancy outcomes. Clinical monitoring of patients with increased PLGF, decreased PAPP-A, and increased β-hCG should be strengthened, especially the monitoring of antepartum examination and B-ultrasound detection of pregnant women with abnormal indicators in middle and late pregnancy, so as to identify adverse pregnancy outcomes as early as possible and give targeted intervention.


The metabolic fate of independently initiated VSV mRNA transcripts.
The kinetics of synthesis and the metabolic stability of uncapped vesicular stomatitis virus (VSV) mRNA transcripts have been studied using techniques which clearly differentiate them from other RNA species. The triphosphate-initiating mRNA transcripts accumulate for at least 5 h during a typical in vitro transcription reaction. The great majority of these transcripts are smaller than a functional message and have been released from the template-transcriptase complex. Label that accumulates in them is stable and is not detectably diminished after a 1 h chase with unlabelled precursor. These kinetic properties are not these expected for active intermediates in mRNA synthesis and suggest that the uncapped transcripts are products of aborted transcription that accumulate during the transcriptive process. However, we cannot rule out that a small subset of these transcripts may be elongated into mature mRNA. Initiation of transcription at internal positions along the VSV genome is both frequent (one-half to one-sixth as frequent as initiations at the leader RNA gene) and site-specific (occurring only at the beginning of cistrons). The relevance of these results to the models for VSV transcription is discussed.


Chemical speciation of dissolved Cu, Ni, and Co in a contaminated estuary in southwest Spain and its influence on plankton communities.
Four surveys of the Huelva Estuary in southwest Spain and its sources, the Tinto and the Odiel Rivers, were carried out between 1996 and 1998. The surveys investigated the impact of metalliferous mining of sulfide-rich ores in the catchment area on metal speciation, metal concentrations in a macrophyte, and phytoplankton diversity and abundance. Chemical speciation measurements in the lower Tinto Estuary showed that metals were predominantly electrochemically labile (> 99% of total dissolved Cu, Co, and Ni at 10 microM Cu, 424 nM Co, and 500 nM Ni, S = 28). Concentrations of Cu complexing ligands and free cupric ions [Cu2+] in the Gulf of Cádiz ranged between 5.3 and 38 nM and 0.2-7.9 pM, respectively, with conditional stability constants of the ligands of log K'(CuL) = 11.7-12.6. At enhanced dissolved Cu concentrations in the lower Huelva Estuary, Cu complexing ligands were saturated with Cu, resulting in nanomolar [Cu2+], which increased upstream. Metal tissue concentrations of the macrophyte Blindingia marginata were high, and a clear relationship between dissolved labile Cu and macrophyte tissue Cu concentrations was observed. A low biodiversity was observed in the Huelva system (Shannon-Wiener indices (H) typically < 0.2). Nevertheless, the maximum biomass was observed in the lower Tinto Estuary, which showed high labile metal and nutrient concentrations and a low biodiversity (H < 0.02), thereby suggesting adaptation through evolutionary processes of the phytoplankton community to the harsh conditions.


Mobilization and mechanism of transcription of integrated self-inactivating lentiviral vectors.
Permanent genetic modification of replicating primitive hematopoietic cells by an integrated vector has many potential therapeutic applications. Both oncoretroviral and lentiviral vectors have a predilection for integration into transcriptionally active genes, creating the potential for promoter activation or gene disruption. The use of self-inactivating (SIN) vectors in which a deletion of the enhancer and promoter sequences from the 3' long terminal repeat (LTR) is copied over into the 5' LTR during vector integration is designed to improve safety by reducing the risk of mobilization of the vector genome and the influence of the LTR on nearby cellular promoters. Our results indicate that SIN vectors are mobilized in cells expressing lentiviral proteins, with the frequency of mobilization influenced by features of the vector design. The mechanism of transcription of integrated vector genomes was evaluated using a promoter trap design with a vector encoding tat but lacking an upstream promoter in a cell line in which drug resistance depended on tat expression. In six clones studied, all transcripts originated from cryptic promoters either upstream or within the vector genome. We estimate that approximately 1 in 3,000 integrated vector genomes is transcribed, leading to the inference that activation of cryptic promoters must depend on local features of chromatin structure and the constellation of nearby regulatory elements as well as the nature of the regulatory elements within the vector.


Polyclonal engraftment after unrelated donor bone marrow and cord blood transplantation.
Data on a small number of allogeneic sibling donor marrow transplants have indicated that reconstituted hematopoiesis can be oligoclonal or even monoclonal, suggesting that hematopoiesis can be reconstituted from a very small number of stem cells. However, other studies have failed to confirm this observation. Animal data indicate that hematopoiesis is likely to be oligoclonal after transplantation using limiting numbers of hematopoietic stem cells, or in cases of poor engraftment. In this study we investigated clonality of engraftment after unrelated donor (URD) bone marrow (BM) and cord blood transplantation, clinical settings in which human leukocyte antigen (HLA) disparities have been known to impair engraftment and in which stem cell numbers have been limiting. Twenty-four URD transplant recipients (20, BM; 4, cord blood) together with 8 sibling donor marrow, 2 sibling donor peripheral blood stem cells (PBSC), and 1 sibling donor cord blood recipients were studied at 28 days, 100 days, 6 months, and 1 year post-bone marrow transplantation (BMT) using the polymerase chain reaction (PCR)-based human androgen receptor assay (HUMARA) as a marker of clonality. URD marrow and cord blood recipients show polyclonal reconstitution in all cases, and results are similar at early and late time points after BMT. Similar results were seen in sibling donor marrow and cord blood recipients. These data indicate that oligoclonal hematopoiesis is not a frequent event after URD stem cell transplantation, even for cases in which limited numbers of stem cells are infused.


Neighborhood perceptions and active commuting to school among adolescent boys and girls.
Active commuting (AC) to school can increase daily minutes of physical activity yet research is lacking on its determinants. This study examined perceptions of the physical environment as a correlate of AC among adolescents. Cross-sectional data were collected from 1143 males and 1016 females (mean age 16.04 +/- 0.66) who lived within 2.5 miles of their school. Participants' self-reported active (walk or cycle) or inactive (car, bus, or train) mode of travel to school and perceptions of their neighborhood environment. Bivariate logistic regression examined perceived environmental features associated with active versus inactive modes, adjusted for sociodemographic factors. Significant variables were examined in multivariate models, adjusted for population density and distance. Positive correlates of AC included well-lit streets, land-use-mix diversity, access to shops/public transport, the presence of public parks/bike lanes, and accessible well-maintained paths. Connectivity was unrelated to mode choice. In multivariate analyses, land-use-mix diversity, and the perceived presence of public parks remained significant among males, whereas excess traffic speed, shops within walking distance, and paths separate from the road remained significant among females. Environmental characteristics were associated with active commuting to school, however research must address methodological issues before making recommendations for intervention.


Screening for potential nuclear substrates for the plant cell death suppressor kinase Adi3 using peptide microarrays.
The tomato AGC protein kinase Adi3 is a Ser/Thr kinase that functions as a negative regulator of programmed cell death through cell death suppression (CDS) activity in the nucleus. In this study, to understand the mechanism of Adi3 CDS, peptide microarrays containing random Ser- and Thr-peptide phosphorylation substrates were used to screen for downstream phosphorylation substrates. In the microarray phosphorylation assay, Adi3 showed promiscuous kinase activity more toward Ser-peptides compared to Thr-peptides, and a preference for aromatic and cyclic amino acids on both Ser- and Thr-peptides was seen. The 63 highest phosphorylated peptide sequences from the Ser-peptide microarray were selected as queries for a BLAST search against the tomato proteome. As a result, 294 candidate nuclear Adi3 substrates were selected and categorized based on their functions. Many of these proteins were classified as DNA/RNA polymerases or regulators involved in transcription and translation events. The list of potential Adi3 substrates was narrowed to eleven and four candidates were tested for phosphorylation by Adi3. Two of these candidates, RNA polymerase II 2nd largest subunit (RPB2) and the pathogen defense related transcription factor Pti5, were confirmed as Adi3 phosphorylation substrates by in vitro kinase assays. Using a mutational approach two residues, Thr675 and Thr676, were identified as Adi3 phosphorylation sites on RPB2. This study provides the foundation for understanding Adi3 CDS mechanisms in the nucleus as well as other cellular functions.


[Acoustic conditions in open plan office - Application of technical measures in a typical room].
Noise in open plan offices should not exceed acceptable levels for the hearing protection. Its major negative effects on employees are nuisance and impediment in execution of work. Specific technical solutions should be introduced to provide proper acoustic conditions for work performance. Acoustic evaluation of a typical open plan office was presented in the article published in "Medycyna Pracy" 5/2016. None of the rooms meets all the criteria, therefore, in this article one of the rooms was chosen to apply different technical solutions to check the possibility of reaching proper acoustic conditions. Acoustic effectiveness of those solutions was verified by means of digital simulation. The model was checked by comparing the results of measurements and calculations before using simulation. The analyzis revealed that open plan offices supplemented with signals for masking speech signals can meet all the required criteria. It is relatively easy to reach proper reverberation time (i.e., sound absorption). It is more difficult to reach proper values of evaluation parameters determined from A-weighted sound pressure level (SPLA) of speech. The most difficult is to provide proper values of evaluation parameters determined from speech transmission index (STI). Finally, it is necessary (besides acoustic treatment) to use devices for speech masking. The study proved that it is technically possible to reach proper acoustic condition. Main causes of employees complaints in open plan office are inadequate acoustic work conditions. Therefore, it is necessary to apply specific technical solutions - not only sound absorbing suspended ceiling and high acoustic barriers, but also devices for speech masking. Med Pr 2018;69(2):153-165.


Feasibility of external rhythmic cueing with the Google Glass for improving gait in people with Parkinson's disease.
New mobile technologies like smartglasses can deliver external cues that may improve gait in people with Parkinson's disease in their natural environment. However, the potential of these devices must first be assessed in controlled experiments. Therefore, we evaluated rhythmic visual and auditory cueing in a laboratory setting with a custom-made application for the Google Glass. Twelve participants (mean age = 66.8; mean disease duration = 13.6 years) were tested at end of dose. We compared several key gait parameters (walking speed, cadence, stride length, and stride length variability) and freezing of gait for three types of external cues (metronome, flashing light, and optic flow) and a control condition (no-cue). For all cueing conditions, the subjects completed several walking tasks of varying complexity. Seven inertial sensors attached to the feet, legs and pelvis captured motion data for gait analysis. Two experienced raters scored the presence and severity of freezing of gait using video recordings. User experience was evaluated through a semi-open interview. During cueing, a more stable gait pattern emerged, particularly on complicated walking courses; however, freezing of gait did not significantly decrease. The metronome was more effective than rhythmic visual cues and most preferred by the participants. Participants were overall positive about the usability of the Google Glass and willing to use it at home. Thus, smartglasses like the Google Glass could be used to provide personalized mobile cueing to support gait; however, in its current form, auditory cues seemed more effective than rhythmic visual cues.


Beta-2 adrenergic control of ornithine decarboxylase activity in brain regions of the developing rat.
Development of brain tissue is thought to be regulated, in part, by biogenic amines. We examined the role of noradrenergic stimulation in regulation of ornithine decarboxylase (ODC), an enzyme whose activity is obligatory for neuronal development and which has been used as a biochemical marker for cellular maturation. Intracisternal administration of adrenergic agonists produced a prompt increase in ODC in neonatal rat cerebellum, an effect mediated through beta-2 receptors: the rank order of activity was isoproterenol greater than epinephrine greater than norepinephrine greater than methoxamine; the effect could be blocked by propranolol but not phenoxybenzamine; and zinterol (a beta-2 selective agonist) was equipotent to isoproterenol whereas prenalterol (a beta-1 agonist) was ineffective. The elevation of ODC caused by adrenergic stimulation was cyclic AMP-dependent, as evidenced by: direct measurement of cyclic AMP levels after isoproterenol administration; comparisons of the dose-response curve for stimulation of cyclic AMP with that of ODC; examination of the time course of effect on the two variables; stimulation of ODC by administration of cyclic AMP analogs; demonstration of identical kinetic mechanisms for ODC stimulation by dibutyryl-cyclic AMP and isoproterenol; and potentiation of the actions of isoproterenol on both cyclic AMP and ODC by RO-201724, a specific inhibitor of phosphodiesterase. Examination of the ontogenetic pattern of phosphodiesterase.(ABSTRACT TRUNCATED AT 250 WORDS)


A ferrocene-based pseudopeptide chiroptical switch.
We present a double-stranded ferrocene pseudopeptide 2b which exhibits stimuli responsive chirality inversion triggered by solvent exchange or acid addition. Compound 2b exists as a mixture of self-assembled fast exchanging oligomers which macroscopically behave as a chiroptical switch with two stable states. The ferrocene group inversion results in a distinct CD signal in the visible part of the spectrum. The inversion is accomplished through a conformational change due to a rearrangement of hydrogen bonding forcing the rotation of ferrocene rings.


Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins.
Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.


Monte Carlo simulation of energy spectra for (123)I imaging.
(123)I is a radionuclide frequently used in nuclear medicine imaging. The image formed by the 159 keV photopeak includes a considerable scatter component due to high energy gamma-ray emission. In order to evaluate the fraction of scattered photons, a Monte Carlo simulation of a scintillation camera used for (123)I imaging was undertaken. The Monte Carlo code consists of two modules, the HEXAGON code modelled the collimator with a complex hexagonal geometry and the NAI code modelled the NaI detector system including the back compartment. The simulation was carried out for various types of collimators under two separate conditions of the source locations in air and in water. Energy spectra of (123)I for every pixel (matrix size = 256 x 256) were obtained by separating the unscattered from the scattered and the penetrated photons. The calculated energy spectra (cps MBq(-1) keV(-1)) agreed with the measured spectra with approximately 20% deviations for three different collimators. The difference of the sensitivities (cps MBq(-1)) for the window of 143-175 keV was less than 10% between the simulation and the experiment. The partial sensitivities for the scattered and the unscattered components were obtained. The simulated fraction of the unscattered photons to the total photons were 0.46 for LEHR, 0.54 for LEGP and 0.90 for MEGP for the 'in air' set-up, and 0.35, 0.40 and 0.68 for the 'in water' set-up, respectively. The Monte Carlo simulation presented in this work enabled us to investigate the design of a new collimator optimum for (123)I scintigraphy.


Bacterial cytochromes c biogenesis.
We report the primary sequence analyses of two loci, hel and ccl, whose gene products are required specifically for the biogenesis of c-type cytochromes in the Gram-negative photosynthetic bacterium Rhodobacter capsulatus. Genetic and molecular analyses show that the hel locus contains at least four genes, helA, helB, helC, and orf52, and the ccl locus contains two genes, ccl1 and ccl2, that are essential for cytochromes c biogenesis. HelA is homologous to a class of proteins called ABC transporters and helA, helB, and helC are proposed to encode an export complex. Cytochrome c2-alkaline phosphatase gene fusions were used to show that apocytochrome c2 synthesis and secretion are not affected by the hel and ccl defects. Ccl1 and Ccl2 possess typical signal sequences to direct them to the periplasm. The periplasmic orientation of Ccl1 was confirmed using a Ccl1-alkaline phosphatase gene fusion. The Ccl1-alkaline phosphatase gene fusion analysis also demonstrated that Ccl1 does not require hel genes for its synthesis and secretion. Ccl1 is homologous to proteins encoded by chloroplast and mitochondrial genes, suggesting analogous functions in these organelles. Taken together, these results support the hypothesis that the hel-encoded proteins are required for the export of heme to the periplasm where it is subsequently ligated to the c-type apocytochromes.


Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives.
Life expectancy in autoimmune rheumatic diseases (ARDs) remains lower compared to the general population, due to various comoborbidities. Cardiovascular disease (CVD) represents the main contributor to premature mortality. Conventional and biologic disease-modifying antirheumatic drugs (DMARDs) have considerably improved long-term outcomes in ARDs not only by suppressing systemic inflammation but also by lowering CVD burden. Regarding atherosclerotic disease prevention, EULAR has recommended tight disease control accompanied by regular assessment of traditional CVD risk factors and lifestyle changes. However, this approach, although rational and evidence-based, does not account for important issues such as myocardial inflammation and the long asymptomatic period that usually proceeds clinical manifestations of CVD disease in ARDs before or after the diagnosis of systemic disease. Cardiovascular magnetic resonance (CMR) can offer reliable, reproducible and operator independent information regarding myocardial inflammation, ischemia and fibrosis. Some studies suggest a role for CMR in the risk stratification of ARDs and demonstrate that oedema/fibrosis visualisation with CMR may have the potential to inform cardiac and rheumatic treatment modification in ARDs with or without abnormal routine cardiac evaluation. In this review, we discuss how CMR findings could influence anti-rheumatic treatment decisions targeting optimal control of both systemic and myocardial inflammation irrespective of clinical manifestations of cardiac disease. CMR can provide a different approach that is very promising for risk stratification and treatment modification; however, further studies are needed before the inclusion of CMR in the routine evaluation and treatment of patients with ARDs.


Characterization of excipients to improve pharmaceutical properties of sirolimus in the supercritical anti-solvent fluidized process.
Enhanced drug release and bioavailability of poorly soluble active pharmaceutical ingredient (API) can be achieved via a fluidized bed coating integrated with supercritical anti-solvent (SAS-FB) - a process of precipitating drug particles onto carrier granules. However, in the absence of excipients, SAS-FB often results in crystalline of the API on the surface of carriers, limiting the improvement of pharmaceutical properties. Co-processing with excipients is considered an effective approach to improve drug release in the SAS-FB process. Our study used sirolimus, an immune suppressive agent, as the model API to characterize excipients for their effect on pharmaceutical properties in the SAS-FB process. We show that co-precipitation of excipients and sirolumus impacts on carrier specific surface area and drug yield. Among the tested excipients, formulation containing polyvinylpyrrolidone K30 achieved the highest drug yield. Importantly, compared with Rapamune® tablet, our optimized formulation displayed a superior in vivo oral bioavailability by 3.05-fold in Sprague-Dawley rats and 3.99-fold in beagle dogs. A series of characterization of the processed API was performed to understand the mechanism by which excipients contributed to drug dissolution properties. Our study provides a useful guidance for the use of excipients in the SAS-FB technology to improve pharmaceutical properties of sirolimus and other poorly soluble drugs.


Bevacizumab for Ovarian Cancer at High Risk of Progression: Reproducibility of Trial Results in 'Real-world' Patients.
Bevacizumab has become a 'community standard' at many UK centres as part of first-line treatment of patients with ovarian cancer at high risk of progression [International Federation of Gynecology and Obstetrics (FIGO) stage IV, or suboptimally debulked stage III] based on the results of phase III trials such as ICON-7. Its impact in patients treated outside clinical trials is, however, still unknown. In this study, we investigated patient characteristics, treatment patterns, adverse events and progression-free survival in 'real-world' patients in South West Wales. A total of 60 patients, treated between 2012 and 2015, were included in the study. Patient characteristics were less favourable compared to the bevacizumab-treated high-risk group in the ICON-7 trial (median age: 66 vs. 60 years; stage IV: 58% vs. 42%; performance status 0: 18% vs. 41%); 75% had received neoadjuvant chemotherapy before starting bevacizumab. After a median treatment duration of 8 months (range=0-34 months), 45 patients (75%) had experienced disease progression and 34 (56.7%) had died. Median progression-free survival was 16 months (95% confidence interval=14.4-17.6 months). The most common toxicities consisted of proteinuria (66.7%, all grade 1) and grade 1-2 hypertension (15%). Cardiovascular incidents, two of which were fatal, occurred in 6.7% of patients. In conclusion, our study provides encouraging evidence that the routine use of bevacizumab as part of first-line treatment of patients with ovarian cancer at high risk of progression may be associated with outcomes comparable with those obtained in clinical trials.


Bleeding to death in a big city: An analysis of all trauma deaths from hemorrhage in a metropolitan area during 1 year.
Hemorrhage is the most common cause of potentially preventable trauma deaths, but no studies have focused on all civilian traumatic deaths from hemorrhage, so we describe a year of these deaths from a large county to identify opportunities for preventing hemorrhagic deaths. All trauma-related deaths in Harris County, Texas, in 2014 underwent examination by the medical examiner; patients were excluded if hemorrhage was not their primary reason for death. Deaths were then categorized as preventable/potentially preventable hemorrhage (PPH) or nonpreventable hemorrhage. These categories were compared across mechanism of injury, death location, and anatomic locations of hemorrhage to determine significant differences. A total of 1,848 deaths were reviewed, and 305 were from uncontrolled hemorrhage. One hundred thirty-seven (44.9%) of these deaths were PPH. Of these PPH, 49 (35.8%) occurred prehospital and an additional 28 (20.4%) died within 1 hour of arriving at an acute care setting. Of the 83 PPH who arrived at a hospital, 21 (25.3%) died at a center not designated as level 1. Isolated truncal bleeding was the source of hemorrhage in 102 (74.5%) of the PPH. Of those who died with truncal PPH, the distribution was 22 chest (21.6%), 39 chest and abdomen (38.2%), 16 abdomen (15.7%), and 25 all other combinations (24.5%). When patients who died within 1 hour of arrival to a hospital were combined with the 168 deaths that occurred prehospital, 223 (74.3%) of 300 deaths occurred before spending 1 hour in a hospital and 77 (34.5%) of 223 of these deaths were PPH. In a well-developed, urban trauma system, 34.5% of patients died from PPH in the prehospital setting or within an hour of hospitalization. Earlier, more effective prehospital resuscitation and truncal hemorrhage control strategies are needed to decrease deaths from PPH. Therapeutic/Care management, level IV.


Cost-effectiveness of 6 and 12 months of interferon-alpha therapy for chronic hepatitis C.
Interferon-alpha is effective in only a small number of patients with chronic hepatitis C, although prolonged treatment may increase the response rate. There is concern that the expense of interferon-alpha therapy may not be justified by the low response rates and uncertain long-term benefit. To compare clinical and economic outcomes after 6 months and 12 months of interferon-alpha therapy for chronic hepatitis C. A Markov model depicting the natural progression of chronic hepatitis C. On the basis of this model, a simulated trial compared no therapy with 6 and 12 months of interferon-alpha therapy at standard doses (3 million U three times weekly). Four age-specific cohorts (30, 40, 50, and 60 years of age) with chronic hepatitis C. Number of deaths from liver disease, total costs, and cumulative quality-adjusted life-years (QALYs). Six and 12 months of interferon-alpha treatment gained 0.25 QALYs at an incremental cost of $1000 and 0.37 QALYs at an incremental cost of $1900, respectively. Thus, although 6 months of interferon-alpha therapy was less efficacious than 12 months of therapy, it was more cost-effective ($4000 per QALY gained compared with $5000 per QALY gained). Nonetheless, in patients younger than 60 years of age, both 6 and 12 months of therapy compared favorably with other established medical interventions, such as screening mammography and cholesterol reduction programs. Important variables affecting the cost-effectiveness of interferon-alpha treatment included the cost and efficacy of interferon-alpha, the cost of treatment for decompensated cirrhosis, and quality of life in patients with chronic hepatitis C. From the standpoint of cost-effectiveness, interferon-alpha therapy for 6 or 12 months may be justified in patients with chronic hepatitis C. The possible exception is patients older than 60 years of age.


Remarkable homology among the internal repeats of erythroid and nonerythroid spectrin.
A cDNA clone for nonerythroid alpha-spectrin was identified by direct immunological screening of a chicken smooth muscle cDNA library. A library prepared in the expression plasmids pUC8 and pUC9 was screened with an antiserum specific for chicken alpha-spectrin. Blots of poly(A)+ RNA from various tissues of chicken and mouse show that the cDNA hybridizes to an 8-kilobase mRNA. The cDNA hybridizes to a single-copy sequence on Southern blots of chicken genomic DNA. The complete nucleic acid sequence of the clone has a single 1419-base open reading frame. The derived amino acid sequence is organized into two partial and three complete 106-amino-acid repeats that show homology to the repeats described for human erythroid alpha- and beta-spectrin. Immunological and biochemical data indicate that chicken nonerythroid and human erythroid alpha-spectrin are two of the more widely diverged members of the spectrin family of proteins. In this respect, the degree of homology found between them was unexpected. Our data suggest a common evolutionary origin for these two alpha-spectrins and allow some predictions concerning spectrin gene structure.