Axon-induced mitogenesis of human Schwann cells involves heregulin and p185erbB2.
The ability of sensory axons to stimulate Schwann cell proliferation by contact was established in the 1970s. Although the mitogen responsible for this proliferation has been localized to the axon surface and biochemically characterized, it has yet to be identified. Recently a family of proteins known as heregulins (HRGs) has been isolated, characterized, and shown to interact with a number of class 1 receptor tyrosine kinases, including the erbB2, erbB3, and erbB4 gene products. These factors include glial growth factor, a Schwann cell mitogen. We have tested the effects of antibodies against components of this system (HRG beta 1 and p185erbB2) in cocultures of rat sensory neurons and human (or rat) Schwann cells to elucidate the role of these proteins in axon-induced Schwann cell proliferation. 2C4, a monoclonal antibody specific for the human p185erbB2 receptor tyrosine kinase, bound to the surface of human Schwann cells and reduced human Schwann cell incorporation of [3H]thymidine by > 90% compared with untreated controls in this coculture system. This antibody had no effect on rat Schwann cell incorporation of [3H]thymidine under similar conditions. A polyclonal antibody raised against HRG beta 1 reduced human and rat Schwann cell incorporation of [3H]thymidine by nearly 80% and up to 49%, respectively, relative to controls. These results imply that a HRG, or a HRG-like molecule, is a component of the axonal mitogen. This mitogen is presented to Schwann cells by axons and induces proliferation through an interaction that involves p185erbB2 on Schwann cells.


External validation of the national healthcare safety network risk models for surgical site infections in total hip and knee replacements.
The National Healthcare Safety Network surgical site infections risk models for hip (HPRO) and knee (KPRO) replacement are intended for case-mix adjustment when reporting surgical site infection rates across institutions, but they are not validated in external data sets. To evaluate the validity of HPRO and KPRO risk models and improvement in risk prediction with inclusion of information on morbid obesity and diabetes mellitus. Retrospective cohort study. A single-center cohort of 21,941 hip and knee replacement procedures performed between 2002 and 2009. Discriminative ability was assessed using the concordance statistic (C statistic). Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit tests. The discrimination of HPRO was good, with a C statistic of 0.695 for surgical site infections and 0.749 for prosthetic joint infections. The discrimination of KPRO was worse than that of HPRO, with a C statistic of 0.592 for surgical site infections and 0.675 for prosthetic joint infections. Adding morbid obesity and diabetes mellitus to the HPRO and KPRO risk models modestly improved discrimination. There was no significant evidence of miscalibration based on the Hosmer-Lemeshow tests, but calibration of HPRO models appeared to be better than that of the KPRO models. HPRO performed better than the KPRO in predicting surgical site infections after hip and knee replacements. Both fared well in predicting prosthetic joint infections.


Modeling of molecular and cellular mechanisms involved in Ca2+ signal encoding in airway myocytes.
In airway myocytes signal transduction via cytosolic calcium plays an important role. In relation with experimental results we review models of basic molecular and cellular mechanisms involved in the signal transduction from the myocyte stimulation to the activation of the contractile apparatus. We concentrate on mechanisms for encoding of input signals into Ca2+ signals and the mechanisms for their decoding. The mechanisms are arranged into a general scheme of cellular signaling, the so-called bow-tie architecture of signaling, in which calcium plays the role of a common media for cellular signals and links the encoding and decoding part. The encoding of calcium signals in airway myocytes is better known and is presented in more detail. In particular, we focus on three recent models taking into account the intracellular calcium handling and ion fluxes through the plasma membrane. The model of membrane conductances was originally proposed for predicting membrane depolarization and voltage-dependent Ca2+ influx triggered by initial cytosolic Ca2+ increase as observed on cholinergic stimulation. Cellular models of intracellular Ca2+ handling were developed to investigate the role of a mixed population of InsP3 receptor isoforms and the cellular environment in the occurrence of Ca2+ oscillations, and the respective role of the sarcoplasmic reticulum, mitochondria, and cytosolic Ca2+-binding proteins in cytosolic Ca2+ clearance. Modeling the mechanisms responsible for the decoding of calcium signals is developed in a lesser extent; however, the most recent theoretical studies are briefly presented in relation with the known experimental results.


Dissociating the time courses of the cross-modal semantic priming effects elicited by naturalistic sounds and spoken words.
The present study compared the time courses of the cross-modal semantic priming effects elicited by naturalistic sounds and spoken words on visual picture processing. Following an auditory prime, a picture (or blank frame) was briefly presented and then immediately masked. The participants had to judge whether or not a picture had been presented. Naturalistic sounds consistently elicited a cross-modal semantic priming effect on visual sensitivity (d') for pictures (higher d' in the congruent than in the incongruent condition) at the 350-ms rather than at the 1,000-ms stimulus onset asynchrony (SOA). Spoken words mainly elicited a cross-modal semantic priming effect at the 1,000-ms rather than at the 350-ms SOA, but this effect was modulated by the order of testing these two SOAs. It would therefore appear that visual picture processing can be rapidly primed by naturalistic sounds via cross-modal associations, and this effect is short lived. In contrast, spoken words prime visual picture processing over a wider range of prime-target intervals, though this effect was conditioned by the prior context.


Lactococcal 949 group phages recognize a carbohydrate receptor on the host cell surface.
Lactococcal bacteriophages represent one of the leading causes of dairy fermentation failure and product inconsistencies. A new member of the lactococcal 949 phage group, named WRP3, was isolated from cheese whey from a Sicilian factory in 2011. The genome sequence of this phage was determined, and it constitutes the largest lactococcal phage genome currently known, at 130,008 bp. Detailed bioinformatic analysis of the genomic region encoding the presumed initiator complex and baseplate of WRP3 has aided in the functional assignment of several open reading frames (ORFs), particularly that for the receptor binding protein required for host recognition. Furthermore, we demonstrate that the 949 phages target cell wall phospho-polysaccharides as their receptors, accounting for the specificity of the interactions of these phages with their lactococcal hosts. Such information may ultimately aid in the identification of strains/strain blends that do not present the necessary saccharidic target for infection by these problematic phages.


Highly emissive platinum(II) metallacages.
Light-emitting materials, especially those with tunable wavelengths, attract considerable attention for applications in optoelectronic devices, fluorescent probes, sensors and so on. Many species evaluated for these purposes either emit as a dilute solution or on aggregation, with the former often self-quenching at high concentrations, and the latter falling dark when aggregation is disrupted. Here we preserve emissive behaviour at both low- and high-concentration regimes for two discrete supramolecular coordination complexes (SCCs). These tetragonal prismatic SCCs are self-assembled on mixing a metal acceptor, Pt(PEt3)2(OSO2CF3)2, with two organic donors, a pyridyl-decorated tetraphenylethylene and one of two benzene dicarboxylate species. The rigid organization of these fluorescence-active ligands imparts an emissive behaviour to dilute solutions of the resulting assemblies. Furthermore, on aggregation the prisms exhibit variable-wavelength visible-light emission, including rare white-light emission in tetrahydrofuran. The favourable photophysical properties and solvent-dependent aggregation behaviour provide a means to tune emission wavelengths.


A pH-responsive bioassay for paper-based diagnosis of exosomes via mussel-inspired surface chemistry.
The analysis of exosomes, which shows an increasing potential as prognostic biomarkers for non-invasive cancer diagnosis, can reveal their biological functions and disease associations. Nevertheless, the development of a convenient and quantitative method for determination of exosomes is still challenging. Herein, a novel approach for exosome quantification using pH test paper is developed via HRP-mediated promotion of mussel-inspired surface engineering and reagent-free functionalization of urease molecules. Uerase can hydrolyse urea into ammonia and carbon dioxide, and simultaneously raise the pH value of the solution. By establishing the relationship between exosome recognition and the change of pH value of the sensing solution, we can directly employ the low-cost, widely used and commercially available pH test paper to quantitatively analyse exosomes. The pH-responsive bioassay enables sensitive detection of exosomes with a detection of limit down to 4.46 × 103 particles/µL and can be successfully applied for determination of exosomes in clinical specimens. The versatility and reliability of our sensing platform may open up opportunities towards paper-based diagnosis of cancer.


Haematological validation of a computer-based bone marrow reporting system.
To prove the safety and effectiveness of "Professor Belmonte", a knowledge-based system for bone marrow reporting, a formal evaluation of the reports generated by the system was performed. Three haematologists (a consultant, a senior registrar, and a junior registrar), none of whom were involved in the development of the software, compared the unedited reports generated by Professor Belmonte with the original bone marrow reports in 785 unselected cases. Each haematologist independently graded the quality of Belmonte's reports using one of four categories: (a) better than the original report (more informative, containing useful information missing in the original report); (b) equivalent to the original report; (c) satisfactory, but missing information that should have been included; and (d) unsatisfactory. The consultant graded 64 reports as more informative than the original, 687 as equivalent to the original, 32 as satisfactory, and two as unsatisfactory. The senior registrar considered 29 reports to be better than the original, 739 to be equivalent to the original, 15 to be satisfactory, and two to be unsatisfactory. The junior registrar found that 88 reports were better than the original, 681 were equivalent to the original, 14 were satisfactory, and two were unsatisfactory. Each judge found two different reports to be unsatisfactory according to their criteria. All 785 reports generated by the computer system received at least two scores of satisfactory or better. In this representative study, Professor Belmonte generated bone marrow reports that proved to be as accurate as the original reports in a large university hospital. The haematology knowledge contained within the system, the reasoning process, and the function of the software are safe and effective for assisting haematologists in generating high quality bone marrow reports.


Efficacy and safety of hepatectomy performed with intermittent portal triad clamping with low central venous pressure.
This retrospective study was designed to investigate the efficacy and safety of intermittent portal triad clamping (PTC) with low central venous pressure (CVP) in liver resections. Between January 2007 and August 2013, 115 patients underwent liver resection with intermittent PTC. The patients' data were retrospectively analyzed. There were 58 males and 57 females with a mean age of 55 years (± 13.7). Cirrhosis was found in 23 patients. Resections were performed for malignant disease in 62.6% (n = 72) and for benign disease in 37.4% (n = 43). Major hepatectomy was performed in 26 patients (22.4%). Mean liver ischemia period was 27.1 min (± 13.9). The mortality rate was 1.7% and the morbidity rate was 22.6%. Cumulative clamping time (t = 3.61, P < 0.001) and operation time (t = 2.38, P < 0.019) were significantly correlated with AST alterations (D-AST). Cumulative clamping time (t = 5.16, P < 0.001) was significantly correlated with D-ALT. Operation time (t = 5.81, P < 0.001) was significantly correlated with D-LDH. Intermittent PTC under low CVP was performed with low morbidity and mortality. Intermittent PTC can be safely applied up to 60 minutes in both normal and impaired livers.


Case Report: Application of hepatitis B virus (HBV) deep sequencing to distinguish between acute and chronic infection.
Deep sequencing of the full-length hepatitis B virus (HBV) genome provides the opportunity to determine the extent to which viral diversity, genotype, polymorphisms, insertions and deletions may influence presentation and outcomes of disease. Increasing experience with analysis of HBV genomic data opens up the potential for using these data to inform insights into pathophysiology of infection and to underpin decision making in clinical practice. We here set out to undertake whole genome HBV sequencing from an adult who presented acutely unwell with a new diagnosis of HBV infection, and tested positive for both HBV anti-core IgM and IgG, possibly representing either acute hepatitis B infection (AHB) or chronic hepatitis B with an acute reactivation (CHB-AR). The distinction between these two scenarios may be important in predicting prognosis and underpinning treatment decisions, but can be challenging based on routine laboratory tests. Through application of deep whole-genome sequencing we typed the isolate as genotype-D1, and identified several minority variants including G1764A and G1986A substitutions in the pre-core promoter and pre-core regions, which support CHB-AR rather than AHB. In the longer term, enhanced deep sequencing data for HBV may provide improved evidence to distinguish between acute and chronic infection, to predict outcomes and to stratify treatment.


Agro-ecological suitability assessment of Chinese Medicinal Yam under future climate change.
Chinese Medicinal Yam (CMY) has been prescribed as medicinal food for thousand years in China by Traditional Chinese Medicine (TCM) practitioners. Its medical benefits include nourishing the stomach and spleen to improve digestion, replenishing lung and kidney, etc., according to the TCM literature. As living standard rises and public health awareness improves in recent years, the potential medicinal benefits of CMY have attracted increasing attention in China. It has been found that the observed climate change in last several decades, together with the change in economic structure, has driven significant shift in the pattern of the traditional CMY planting areas. To identify suitable planting area for CMY in the near future is critical for ensuring the quality and supply quantity of CMY, guiding the layout of CMY industry, and safeguarding the sustainable development of CMY resources for public health. In this study, we first collect 30-year records of CMY varieties and their corresponding phenology and agro-meteorological observations. We then consolidate these data and use them to enrich and update the eco-physiological parameters of CMY in the agro-ecological zone (AEZ) model. The updated CMY varieties and AEZ model are validated using the historical planting area and production under observed climate conditions. After the successful validation, we use the updated AEZ model to simulate the potential yield of CMY and identify the suitable planting regions under future climate projections in China. This study shows that regions with high ecological similarity to the genuine and core producing areas of CMY mainly distribute in eastern Henan, southeastern Hebei, and western Shandong. The climate suitability of these areas will be improved due to global warming in the next 50 years, and therefore, they will continue to be the most suitable CMY planting regions.


Secretion of Yop proteins by Yersiniae.
Upon incubation at 37 degrees C in the absence of Ca2+ ions, pathogenic strains of the genus Yersinia cease growing and produce large amounts of a series of plasmid-encoded proteins involved in pathogenicity. These proteins, called Yops (for Yersinia outer membrane proteins), are detected in both the outer membrane fraction and the culture supernatant. We present here the nucleotide sequence of genes yop20 and yop25 from Yersinia enterocolitica O:9. Protein Yop25 is very similar to YopE, the corresponding protein from Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica O:8 (A. Forsberg and H. Wolf-Watz, J. Bacteriol. 172:1547-1555, 1990). This is the first report of a yop20 sequence of yersiniae. We present evidences that Yops are not membrane proteins. Their detection in the membrane fraction results either from copurification of large aggregates of extracellular Yops with the membrane fraction or from the adsorption of released proteins to the cell surface. In contrast with Yops, protein P1 has characteristics of a true membrane protein. The release of Yops by Y. enterocolitica occurs by a novel secretion mechanism that does not involve the cleavage of a typical signal sequence or the recognition of a carboxy-terminal domain.


Evaluating the importance of policy amenable factors in explaining influenza vaccination: a cross-sectional multinational study.
Despite continuous efforts to improve influenza vaccination coverage, uptake among high-risk groups remains suboptimal. We aimed to identify policy amenable factors associated with vaccination and to measure their importance in order to assist in the monitoring of vaccination sentiment and the design of communication strategies and interventions to improve vaccination rates. The USA, the UK and France. A total of 2412 participants were surveyed across the three countries. Self-reported influenza vaccination. Between March and April 2014, a stratified random sampling strategy was employed with the aim of obtaining nationally representative samples in the USA, the UK and France through online databases and random-digit dialling. Participants were asked about vaccination practices, perceptions and feelings. Multivariable logistic regression was used to identify factors associated with past influenza vaccination. The models were able to explain 64%-80% of the variance in vaccination behaviour. Overall, sociopsychological variables, which are inherently amenable to policy, were better at explaining past vaccination behaviour than demographic, socioeconomic and health variables. Explanatory variables included social influence (physician), influenza and vaccine risk perceptions and traumatic childhood experiences. Our results indicate that evidence-based sociopsychological items should be considered for inclusion into national immunisation surveys to gauge the public's views, identify emerging concerns and thus proactively and opportunely address potential barriers and harness vaccination drivers.


Detection of T cells secreting type 1 and type 2 cytokines in the peripheral blood of patients with oral lichen planus.
The purpose of this study was to detect and enumerate T cells secreting type 1 and 2 cytokines in the peripheral blood of patients with oral lichen planus (OLP) and in healthy controls. The study group consisted of 80 OLP patients and 80 healthy individuals. Cytokine secreting T cells were detected using ELISPOT assay. There was a statistically significant decrease (p<0.05) in the number of IFN- and IL-12 secreting cells in the peripheral blood of patients with OLP compared to the controls. No statistical difference was observed in the number of IL-2 and TNF-a secreting cells between OLP patients and controls (p>0.05). Also there was no significant difference in the numbers of IFN-gamma, IL-12, IL-2 and TNF-a secreting cells between reticular and erosive forms of OLP (p>0.05). As regards type 2 cytokines, the number of IL-5 and IL-10 secreting cells was significantly decreased in OLP patients compared to the healthy control group (p<0.05). No statistical difference was observed in the number of IL-6 secreting cells between OLP patients and control group (p>0.05). Similarly, no statistical difference was observed in the number of IL-4 secreting cells between OLP patients and controls (p>0.05). No significant difference was also found in the numbers of IL-4, IL-5, IL-10 and IL-6 secreting cells between reticular and erosive OLP group. These data suggest decreased type 1 and type 2 cytokine production (except IL-4) in OLP patients.


New approaches to the study of cellulose biosynthesis.
Examples of a variety of approaches for studying the mechanism and regulation of cellulose biosynthesis are presented. Attempts to demonstrate conclusively a cellulose synthase activity using membrane preparations derived from higher plants have not been successful; the predominant UDP-glucose: beta-glucan-beta-glucosyltransferase detected in these preparations is a beta-(1----3)-glucan synthase that is dependent upon Ca2+ and a beta-glucobiose, such as laminaribiose or cellobiose, for activity. Xyloglucan glucosyltransferase activity is detected in all plant preparations examined and, in cotton fibres, the activity of this enzyme correlates well with the level of xyloglucan found in the fibre. Low activity for a Mg2+-dependent beta-(1----4)-glucan synthase is found in extracts from soybeans and mung beans, but not cotton fibres; this enzyme could represent either a dissociated form of xyloglucan glucosyltransferase or a partially latent form of cellulose synthase. In vitro translation of RNA from developing cotton fibres shows notable increases in the level of several relatively abundant translatable mRNAs associated with the time of onset of secondary-wall cellulose synthesis. In order to determine whether these apparent changes in gene expression represent enhanced expression of specific genes required for cellulose synthesis, several strategies are being developed for identification of specific polypeptides required for this process. One strategy involves the successful development of a technique for detection of glucan synthase activity in acrylamide gels, a technique that should prove useful for characterization of the polypeptide composition of such enzymes. We have also synthesized a photoaffinity analogue of 2,6-dichlorobenzonitrile (DCB), a potent and specific inhibitor of cellulose synthesis. The analogue is also an effective inhibitor in vivo, and upon ultraviolet irradiation of extracts in the presence of the radioactive analogue, we observe a relatively specific labelling of a polypeptide of 18 X 10(3)Mr. Finally, we have studied the spatial regulation and structural requirements for cellulose synthesis in internode cells of the alga Chara corallina. Cellulose deposition in vivo shows spatial localization, which correlates with acid and base bands along the cell. Using internodes perfused with solutions containing UDP-[14C]glucose and subsequently ligated, we were able to demonstrate synthesis of a highly insoluble cell-wall-localized glucan, thus offering hope that Chara can be developed as another useful system for studying the mechanism and regulation of cellulose synthesis.


Population dynamics and genetic changes of Picea abies in the South Carpathians revealed by pollen and ancient DNA analyses.
Studies on allele length polymorphism designate several glacial refugia for Norway spruce (Picea abies) in the South Carpathian Mountains, but infer only limited expansion from these refugia after the last glaciation. To better understand the genetic dynamics of a South Carpathian spruce lineage, we compared ancient DNA from 10,700 and 11,000-year-old spruce pollen and macrofossils retrieved from Holocene lake sediment in the Retezat Mountains with DNA extracted from extant material from the same site. We used eight primer pairs that amplified short and variable regions of the spruce cpDNA. In addition, from the same lake sediment we obtained a 15,000-years-long pollen accumulation rate (PAR) record for spruce that helped us to infer changes in population size at this site. We obtained successful amplifications for Norway spruce from 17 out of 462 pollen grains tested, while the macrofossil material provided 22 DNA sequences. Two fossil sequences were found to be unique to the ancient material. Population genetic statistics showed higher genetic diversity in the ancient individuals compared to the extant ones. Similarly, statistically significant Ks and Kst values showed a considerable level of differentiation between extant and ancient populations at the same loci.Lateglacial and Holocene PAR values suggested that population size of the ancient population was small, in the range of 1/10 or 1/5 of the extant population. PAR analysis also detected two periods of rapid population growths (from ca. 11,100 and 3900 calibrated years before present (cal yr BP)) and three bottlenecks (around 9180, 7200 and 2200 cal yr BP), likely triggered by climatic change and human impact. Our results suggest that the paternal lineages observed today in the Retezat Mountains persisted at this site at least since the early Holocene. Combination of the results from the genetic and the PAR analyses furthermore suggests that the higher level of genetic variation found in the ancient populations and the loss of ancient allele types detected in the extant individuals were likely due to the repeated bottlenecks during the Holocene; however our limited sample size did not allow us to exclude sampling effect.This study demonstrates how past population size changes inferred from PAR records can be efficiently used in combination with ancient DNA studies. The joint application of palaeoecological and population genetics analyses proved to be a powerful tool to understand the influence of past population demographic changes on the haplotype diversity and genetic composition of forest tree species.


Safeguarding the ADA's Antidiscrimination Mandate: Subjecting Arrests to Title II Coverage.
The news has been peppered with tragic stories of individuals with disabilities who have been killed or injured following police encounters. In the aftermath of these incidents, as injured parties seek accountability, a question looms: Can arrest proceedings violate the Americans with Disabilities Act? The ADA was enacted to prohibit disability discrimination. The law had an ambitious agenda, supported by broad statutory authority, to ensure equality in all areas of public life for individuals with disabilities. But while the ADA has fostered integration into many aspects of modern life, one area remains deeply contested: arrests. If Congress envisioned that Americans with disabilities would enjoy lives free from discrimination, excluding arrests from ADA coverage undermines the law's broad promise of protection. In 2015, a Supreme Court opinion raised but failed to resolve this very issue, leaving an important question unanswered. This Note examines whether arrest proceedings must comply with the ADA and argues that they should. It then proposes comprehensive disability training as a tool to aid ADA compliance and avoid discriminatory arrest proceedings.


First Report of Lavender Wilt Caused by Fusarium sporotrichioides in Croatia.
In May 2011, samples of lavender plants (Lavandula × intermedia) showing wilt symptoms were collected from two commercial plantings in Slavonia County. Disease was observed on 20 to 30% of the plants. Symptoms of the disease consisted of chlorosis, stunting, wilting, and death. Vascular tissue of stems and roots exhibited brown discoloration. Isolations of the pathogen were made from the discolored tissues on potato dextrose agar (PDA). Colonies were initially white, but with age became red, and red pigments were produced in agar. Microconidia were pear shaped, oval, and fusoid, and ranged from 4.5 to 14.0 × 2.8 to 4.7 μm. Macroconidia were curved, mostly three septate, and ranged from 21.8 to 24.3 × 2.9 to 3.9 μm. Morphology of colonies and conidia matched the description of Fusarium sporotrichioides Sherb. (1). Identity of the fungus was confirmed by examining a portion of the EF1-α gene using the degenerated primers EF1 and EF2 (2). BLAST searches of the obtained sequences showed a 100% homology with several isolates of F. sporotrichioides from GenBank. Pathogenicity tests were conducted on 20 4-month-old rooted cuttings under greenhouse conditions. Each plant was planted in a separate pot containing 0.7 liter of sterile soil. Inoculum for artificial infection was prepared with sterilized mixtures of wheat and barley seeds (10 g of each). Seeds were inoculated with a F. sporotrichioides spore suspension (106 conidia/ml) and incubated at 22°C for 10 days. Noninoculated seeds served as controls. Ten seeds were placed under the soil surface around the root of each plant. Plants were irrigated and placed in a greenhouse (22°C and a 12-h day/night photoperiod). Sixteen days after inoculation, 80% of inoculated plants were wilted. Symptoms on infected plants were similar to those observed in the field. The pathogen was reisolated and confirmed from the infected vascular tissue, thus fulfilling Koch's postulates. A previous paper reported lavender as host of F. solani in China (4) and F. oxysporum in Saudi Arabia (3). To our knowledge, this is the first report of Fusarium wilt of lavender caused by F. sporotrichioides. References: (1) J. F. Leslie and B. A. Summerell. Page 256 in: The Fusarium Laboratory Manual. Blackwell Publishing Professional, Hoboken, NJ, 2006. (2) K. O'Donnell et al. Appl Biol. Sci. 95:2044, 1998. (3) K. Perveen and N. Bokhari. Plant Dis. 94:1163, 2010. (4) Y. Z. Ren et al. New Dis. Rep. 15:55, 2007.


Occlus-o-Guide® versus Andresen activator appliance: neuromuscular evaluation.
The aim of the present study was to assess the muscular variations at the electromyography (EMG) level for the anterior temporalis muscles and masseter muscles during treatment with Occlus-o-Guide® and Andresen activator appliances. Eighty-two patients (35 males and 47 females) aged between 8 and 12 years (mean age, 10.5±0.8 years) participated in the study. Fifty patients underwent treatment with an Occlus-o-Guide® and 32 patients with an Andresen activator. All patients underwent EMG examination using a Freely EMG (De Gotzen, Legnano, Italy) and surface bipolar electrodes when the appliances were worn for the first time (T0), and after 6 months (T1) and after 12 months (T2) of appliance use. Statistical analysis showed that both at T0 and T2, the percent overlapping coefficient (POC) of the anterior temporalis muscles was not statistically different between the appliance groups. At T0, the POC of the masseter muscles was significantly lower for the Andresen appliance as compared to the Occlus-o-Guide® (p=0.02), while at T2 this significance was lost. At insertion of an appliance, all patients show neuromuscular balance that does not correspond to orthognathic occlusion. Both appliances work by creating muscular imbalance. With the appliances in situ, EMG responses were generally analogous for the Occlus-o-Guide® and the Andresen activator; however, the imbalance was greater and the recovery of the orthological muscular balance was slower in patients under treatment with the Andresen activator as compared to those with the Occlus-o-Guide®.


Sleep problems, tiredness, and psychological symptoms among healthy adolescents.
To examine the contribution of adolescents' sleep problems and tiredness to psychological symptoms after accounting for shared risk and psychological co-morbidity. Secondary analyses of cross-sectional data on 12-16-year-old (N = 980) adolescents without chronic illness, functional limitation, or developmental delay. Adolescents rated sleep problems, tiredness, and psychological symptoms. Parents provided information about risk factors, adolescent tiredness, and psychological symptoms. Prior to accounting for psychological co-morbidity, most sleep variables were significant correlates of adolescent-, but not parent-rated, psychological symptoms. After accounting for psychological co-morbidity: nightmares were associated with adolescent-rated anxiety/depression; sleeping more than others was associated with adolescent-rated aggression; trouble sleeping was associated with adolescent-rated attention problems, anxiety/depression, and withdrawal; and adolescent-rated tiredness was associated with adolescent-rated aggression and withdrawal. Studies examining sleep and psychopathology should control for psychological co-morbidity.


The CD14(bright) CD16+ monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population.
Circulating monocytes contain a subpopulation of CD14+CD16+ cells; this subpopulation of cells has been described to be proinflammatory and to have an increased frequency in rheumatoid arthritis (RA). New evidence suggests that this subpopulation can be further subdivided into CD14(dim) CD16+ and CD14(bright) CD16+ cells. The aim of this study was to determine which of the two CD16+ monocyte subpopulations is expanded in patients with RA and to investigate their possible role in disease pathogenesis. The frequencies of monocyte subpopulations in the peripheral blood of healthy donors and patients with RA were determined by flow cytometry. Monocyte subpopulations were sorted and cocultured with CD4+ T cells. Cytokines were determined in the supernatant, and Th17 cell frequencies were measured by flow cytometry. In comparison with the other monocyte subpopulations, CD14(bright) CD16+ cells showed higher HLA-DR and CCR5 expression and responded with higher tumor necrosis factor production to direct cell contact with preactivated T cells. They were observed at increased frequencies in the peripheral blood of patients with RA, while CD14(dim) CD16+ monocyte frequencies were not increased. CD14(bright) CD16+ cells were extremely potent inducers of Th17 cell expansion in vitro. Their frequency in the peripheral blood of patients with RA correlated closely with Th17 cell frequencies determined ex vivo. This study is the first to provide a link between the increased frequency of the CD14(bright) CD16+ monocyte subpopulation in RA and the expansion of Th17 cells, which are likely to have a role in the pathogenesis of autoimmunity.


Predicting the combined effect of multiple genetic variants.
Many genetic variants have been identified in the human genome. The functional effects of a single variant have been intensively studied. However, the joint effects of multiple variants in the same genes have been largely ignored due to their complexity or lack of data. This paper uses HMMvar, a hidden Markov model based approach, to investigate the combined effect of multiple variants from the 1000 Genomes Project. Two tumor suppressor genes, TP53 and phosphatase and tensin homolog (PTEN), are also studied for the joint effect of compensatory indel variants. Results show that there are cases where the joint effect of having multiple variants in the same genes is significantly different from that of a single variant. The deleterious effect of a single indel variant can be alleviated by their compensatory indels in TP53 and PTEN. Compound mutations in two genes, β-MHC and MyBP-C, leading to severer cardiovascular disease compared to single mutations, are also validated. This paper extends the functionality of HMMvar, a tool for assigning a quantitative score to a variant, to measure not only the deleterious effect of a single variant but also the joint effect of multiple variants. HMMvar is the first tool that can predict the functional effects of both single and general multiple variations on proteins. The precomputed scores for multiple variants from the 1000 Genomes Project and the HMMvar package are available at https://bioinformatics.cs.vt.edu/zhanglab/HMMvar/.


Melanoides tuberculata (Mollusca: Thiaridae) harboring renicolid cercariae (Trematoda: Renicolidae) in Brazil.
Melanoides tuberculata , naturally infected by gymnocephalous cercariae, were found in aquatic collections from Belo Horizonte, Minas Gerais, Brazil. After morphological characterization, larvae were used for experimental infection of Poecilia reticulata. Metacercariae were obtained from the liver of these fish, which were also found to be naturally infected in the same locality. The morphology and biology of the developmental stages of trematodes we obtained were characteristic of Renicola sp. This is the first record of renicolid cercariae and metacercariae in Brazil.


Myonucleus-related properties in soleus muscle fibers of mdx mice.
Distribution and total number of myonuclei in single soleus muscle fibers, sampled from tendon to tendon, were analyzed in mdx and wild-type (WT) mice. Apoptotic myonuclei and the microscopic structure around the myonuclei were also analyzed. Three types of muscle fibers of mdx mice with myonuclear distribution at either central, peripheral, or both central and peripheral regions were observed in the longitudinal analyses. All of the myonuclei were located at the peripheral region in WT mice. The total number of myonuclei counted in the whole length of fibers with peripheral myonuclei only was 17% less in mdx than in WT mice (p < 0.05). But the total myonuclear numbers in mdx mouse fibers with different distribution (peripheral vs. central) of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Myonuclei located between the center and peripheral regions were also seen in the cross-sectional analyses of muscle fibers. The cross-sectional area and length of fibers, sarcomere number, myonuclear size, myosin heavy chain expression, satellite cell number and neuromuscular junction were identical between each type of fiber. Apoptosis was not detected in any myonuclei located either in central or peripheral regions of muscle fibers. Thus, it was suggested that apoptosis-related loss of central myonuclei and regeneration-related new accretion at the peripheral region is not the cause of different distribution of myonuclei seen in muscle fibers in mdx mice. However, it was speculated that cross-sectional migration of myonuclei from central to peripheral regions may be induced in response to regeneration, because the total myonuclear numbers in fibers with different distribution of myonuclei were identical, and the peripheral nucleus was noted where the central nucleus was missing. Further, myonuclei located between the center and peripheral regions were also seen. However, the question remains as to how or why nuclei might migrate to the periphery in a regenerating muscle fiber, since there was no microscopic evidence of any structural changes around the myonuclei that may be responsible for the movement of the nucleus.


Insulin and glucocorticoid-dependent suppression of the IGF-I system in diabetic wounds.
Growth-promoting polypeptides, including insulin-like growth factor-I (IGF-I), orchestrate different biochemical events that culminate in the restoration of functional integrity of wounded skin. The nonhealing cutaneous wound is a well-documented phenomenon in experimental and clinical diabetes. Accordingly, we undertook this study to ascertain whether diabetes impairs the healing process by suppressing the wound microenvironmental IGF-I system (eg, IGF-I; IGF-I receptor [IGF-I R]; and IGF-I binding protein [IGF-BP(3)]). The induction of diabetes was achieved by the intravenous injection of streptozotocin at a dose of 55 mg/kg. Subcutaneously implanted polyvinyl alcohol sponge and stainless steel mesh chamber models were used to study wound healing. Nondiabetic and diabetic animals received, respectively, subcutaneous 30-day time-release pellets of glucocorticoid (200 mg) and mifepristone (RU-486, 25 mg). Corresponding control animals received placebo pellets. Polyvinyl alcohol sponge and wound fluid expression of the IGF-I system were evaluated by using ligand blotting, radioimmunoassay, and reverse transcriptase polymerase chain reaction-based techniques. Polyvinyl alcohol sponge contents of messenger RNA (mRNA) transcripts encoding for IGF-I, IGF-I R, and IGF-BP(3) were reduced in diabetic and glucocorticoid-treated control animals. A similar pattern of changes in protein levels of IGF-I and IGF-BP(3) occurred in wound fluid collected from these animals. Partial normalization of the associated hyperglycemic and hypercortisolemic states of diabetes with insulin (hyperglycemia) and the glucocorticoid receptor blocker RU-486 (hypercortisolemia) ameliorated the diabetes-related decrease in the IGF-I system during wound healing. The current data, together with data garnered from the literature, support the concept that the state of hypercortisolemia in diabetes mellitus impairs the healing process, at least in part, by suppressing the wound microenvironmental IGF-I system. Confirmation regarding this premise awaits further investigation.


Single-cell RNA sequencing of the mammalian pineal gland identifies two pinealocyte subtypes and cell type-specific daily patterns of gene expression.
The vertebrate pineal gland is dedicated to the production of the hormone melatonin, which increases at night to influence circadian and seasonal rhythms. This increase is associated with dramatic changes in the pineal transcriptome. Here, single-cell analysis of the rat pineal transcriptome was approached by sequencing mRNA from ~17,000 individual pineal cells, with the goals of profiling the cells that comprise the pineal gland and examining the proposal that there are two distinct populations of pinealocytes differentiated by the expression of Asmt, which encodes the enzyme that converts N-acetylserotonin to melatonin. In addition, this analysis provides evidence of cell-specific time-of-day dependent changes in gene expression. Nine transcriptomically distinct cell types were identified: ~90% were classified as melatonin-producing α- and β-pinealocytes (1:19 ratio). Non-pinealocytes included three astrocyte subtypes, two microglia subtypes, vascular and leptomeningeal cells, and endothelial cells. α-Pinealocytes were distinguished from β-pinealocytes by ~3-fold higher levels of Asmt transcripts. In addition, α-pinealocytes have transcriptomic differences that likely enhance melatonin formation by increasing the availability of the Asmt cofactor S-adenosylmethionine, resulting from increased production of a precursor of S-adenosylmethionine, ATP. These transcriptomic differences include ~2-fold higher levels of the ATP-generating oxidative phosphorylation transcriptome and ~8-fold lower levels of the ribosome transcriptome, which is expected to reduce the consumption of ATP by protein synthesis. These findings suggest that α-pinealocytes have a specialized role in the pineal gland: efficiently O-methylating the N-acetylserotonin produced and released by β-pinealocytes, thereby improving the overall efficiency of melatonin synthesis. We have also identified transcriptomic changes that occur between night and day in seven cell types, the majority of which occur in β-pinealocytes and to a lesser degree in α-pinealocytes; many of these changes were mimicked by adrenergic stimulation with isoproterenol. The cellular heterogeneity of the pineal gland as revealed by this study provides a new framework for understanding pineal cell biology at single-cell resolution.


Percutaneous clot removal devices in acute ischemic stroke: a systematic review and meta-analysis.
We conducted a systematic review and meta-analysis of mechanical thrombectomy in the treatment of ischemic stroke and assessed factors for technical and clinical success and survival. We searched the literature using MEDLINE and EMBASE for January 1, 2000, through March 1, 2006. Studies were limited to those in human beings; there were no language or study design restrictions. Validity assessment was performed using the Newcastle-Ottawa Scale. The pooled cohort was compared with a historical cohort matched for sex, age, and National Institutes of Health Stroke Survey score. The search yielded 114 publications. Two authors determined inclusibility (interrater agreement, kappa = 0.94). Mean preprocedure National Institutes of Health Stroke Survey score was 20.4. The middle cerebral artery (36%) and the posterior circulation (38%) were the most frequently occluded areas. The clot was accessible in 85% of the patients. Hemorrhage occurred in 22% of the patients. Of 81 patients with concurrent thrombolysis, 18.5% had hemorrhage compared with 27.3% of 66 patients without thrombolysis (P = .21). Of the 126 patients with accessible clots, 36% had a good modified Rankin score (<or=2) and 29% died; in patients with inaccessible clots, 24% had a good modified Rankin score and 38% died. Factors associated with clinical success were younger age (P = .001) and lower National Institutes of Health Stroke Survey score at admission to the hospital (P = .001). Compared with a matched cohort, patients who received mechanical intervention were 14.8 times more likely to have a good modified Rankin score (95% confidence interval, 4.4-50.0; P < .001). Percutaneous mechanical embolectomy in the treatment of acute ischemic stroke is feasible and seems to provide an option for some patients seen after the interval for administration of intravenous tissue plasminogen activator therapy has elapsed.


Muscle protein synthesis in response to nutrition and exercise.
Muscle protein synthesis (MPS) is the driving force behind adaptive responses to exercise and represents a widely adopted proxy for gauging chronic efficacy of acute interventions, (i.e. exercise/nutrition). Recent findings in this arena have been progressive. Nutrient-driven increases in MPS are of finite duration (∼1.5 h), switching off thereafter despite sustained amino acid availability and intramuscular anabolic signalling. Intriguingly, this 'muscle-full set-point' is delayed by resistance exercise (RE) (i.e. the feeding × exercise combination is 'more anabolic' than nutrition alone) even 24 h beyond a single exercise bout, casting doubt on the importance of nutrient timing vs. sufficiency per se. Studies manipulating exercise intensity/workload have shown that increases in MPS are negligible with RE at 20-40% but maximal at 70-90% of one-repetition maximum when workload is matched (according to load × repetition number). However, low-intensity exercise performed to failure equalises this response. Analysing distinct subcellular fractions (e.g. myofibrillar, sarcoplasmic, mitochondrial) may provide a readout of chronic exercise efficacy in addition to effect size in MPS per se, i.e. while 'mixed' MPS increases similarly with endurance and RE, increases in myofibrillar MPS are specific to RE, prophetic of adaptation (i.e. hypertrophy). Finally, the molecular regulation of MPS by exercise and its regulation via 'anabolic' hormones (e.g. IGF-1) has been questioned, leading to discovery of alternative mechanosensing-signalling to MPS.


Survived infancy but still vulnerable: spatial-temporal trends and risk factors for child mortality in the Agincourt rural sub-district, South Africa, 1992-2007.
Targeting of health interventions to poor children at highest risk of mortality are promising approaches for enhancing equity. Methods have emerged to accurately quantify excess risk and identify space-time disparities. This provides useful and detailed information for guiding policy. A spatio-temporal analysis was performed to identify risk factors associated with child (1-4 years) mortality in the Agincourt sub-district, South Africa, to assess temporal changes in child mortality patterns within the study site between 1992 and 2007, and to produce all-cause and cause-specific mortality maps to identify high risk areas. Demographic, maternal, paternal and fertility-related factors, household mortality experience, distance to health care facility and socio-economic status were among the examined risk factors. The analysis was carried out by fitting a Bayesian discrete time Bernoulli survival geostatistical model using Markov chain Monte Carlo simulation. Bayesian kriging was used to produce mortality risk maps. Significant temporal increase in child mortality was observed due to the HIV epidemic. A distinct spatial risk pattern was observed with higher risk areas being concentrated in poorer settlements on the eastern part of the study area, largely inhabited by former Mozambican refugees. The major risk factors for childhood mortality, following multivariate adjustment, were mother's death (especially when due to HIV and tuberculosis), greater number of children under 5 years living in the same household and winter season. This study demonstrates the use of Bayesian geostatistical models for accurately quantifying risk factors and producing maps of child mortality risk in a health and demographic surveillance system. According to the space-time analysis, the southeast and upper central regions of the site appear to have the highest mortality risk. The results inform policies to address health inequalities in the Agincourt sub-district and to improve access to health services. Targeted efforts to prevent vertical transmission of HIV in specific settings need to be undertaken as well as ensuring the survival of the mother and father in childhood.


Adversarial search by evolutionary computation.
In this paper, we consider the problem of finding good next moves in two-player games. Traditional search algorithms, such as minimax and alpha-beta pruning, suffer great temporal and spatial expansion when exploring deeply into search trees to find better next moves. The evolution of genetic algorithms with the ability to find global or near global optima in limited time seems promising, but they are inept at finding compound optima, such as the minimax in a game-search tree. We thus propose a new genetic algorithm-based approach that can find a good next move by reserving the board evaluation values of new offspring in a partial game-search tree. Experiments show that solution accuracy and search speed are greatly improved by our algorithm.


Continuous feelings of love? The parental bond from pregnancy to toddlerhood.
Both prenatal and postnatal parental bonding (i.e., the affective tie from parent to child) have important effects on parental and child functioning. However, research on the continuity and correlates of parental bonding is lacking. Therefore, the goal of the present study was to examine the stability of bonding levels and to explore distinct bonding patterns with a latent class analysis. Moreover, the correlates of these bonding patterns in the parental-, child-, and contextual domain were studied. Levels of maternal (N = 370) and paternal (N = 292) bonding and potential correlates were assessed at 26 weeks of pregnancy, 6 months, and 24 months postpartum. Results showed moderate stability of bonding from pregnancy to toddlerhood. For both mothers and fathers, 4 distinct bonding patterns were found. Parents with low bonding patterns were characterized by increased anxiety and parenting stress, less partner support, less adaptive personality profiles, and children with difficult temperament. These findings indicate the importance of monitoring young children's parents with poor levels of bonding as their bonding patterns remain stable from pregnancy until toddlerhood and because those parents experience problems in multiple domains.


Hydrogen resuscitation, a new cytoprotective approach.
1. Hydrogen is a colourless, odourless, tasteless and flammable gas. Hydrogen is considered a physiologically inert gas and is often used in deep sea diving medicine. In mammals, endogenous hydrogen is produced as a result of the fermentation of non-digestible carbohydrates by intestinal bacteria and it is absorbed into the systemic circulation. 2. Recent evidence indicates that hydrogen is a potent anti-oxidative, anti-apoptotic and anti-inflammatory agent and so may have potential medical application. The present review evaluates the concept of 'hydrogen resuscitation', based on knowledge that hydrogen treatment effectively protects cells, tissues and organs against oxidative injury and helps them recover from dysfunction. 3. Hydrogen therapy can be delivered by inhalation, the administration of hydrogen-enriched fluid or by approaches that affect endogenous hydrogen production. 4. Studies have shown that hydrogen resuscitation has cytoprotective effects in different cell types and disease models, including ischaemia-reperfusion injury, inflammation, toxicity, trauma and metabolic disease. The underlying mechanism may be the selective elimination of hydroxyl radicals, although other mechanisms may also be involved (e.g. hydrogen functioning as a gaseous signalling molecule). 5. Hydrogen resuscitation may have several potential advantages over current pharmacological therapies for oxidative injuries. However, more work is needed to identify the precise mechanism underlying the actions of hydrogen and to validate its therapeutic potential in the clinical setting.


Pluronic copolymer encapsulated SCR7 as a potential anticancer agent.
Nonhomologous end joining (NHEJ) of DNA double strand breaks (DSBs) inside cells can be selectively inhibited by 5,6-bis-(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) which possesses anticancer properties. The hydrophobicity of SCR7 decreases its bioavailability which is a major setback in the utilization of this compound as a therapeutic agent. In order to circumvent the drawback of SCR7, we prepared a polymer encapsulated form of SCR7. The physical interaction of SCR7 and Pluronic® copolymer is evident from different analytical techniques. The in vitro cytotoxicity of the drug formulations is established using the MTT assay.


The toxic effects of a chronic administration of the gut-stimulating principle in Croton penduliflorus hutch. seeds in mice.
Albino mice (8-10 wks) weighing between 14 and 25 g were divided into 2 groups and dosed orally once per week with 2 doses (7 mg/kg and 21 mg/kg) of the gut-stimulating principle in Croton penduliflorus seeds (CP crystals) for 12 weeks. Some mice (3-4) from each group were killed at 10 days intervals for the first 6 wks of the experiment and at 20 days intervals for the last 6 weeks. Gross and histopathological changes in the brain, heart, liver, kidney, adrenal, spleen, testis, lung and various segments of the gastrointestinal tract including the stomach, duodenum, ileum and colon were observed. The relative weights of the visceral organs were also recorded. Significant weight change in the spleen was evident. The congestion of the lung was the most common gross pathological observation made. Other observations were splenomegaly, enlarged heart, swollen uterine horns, etc. Histopathological changes observed included haemorrhages in the lungs, myocardium, liver, kidney, testis, brain etc. Goblet cell hyperplasia with mucin present in the lumen were observed in the jejunum, ileum and colon. In conclusion, CP crystals produced severe lesions in the visceral organs and the brain after chronic oral administration at low and high dosage levels which should indicate caution in administering the extract to humans.


Clinicopathologic study of early stage esophageal carcinoma.
As part of a consecutive series of 370 patients who underwent subtotal esophagectomy because of carcinoma of the thoracic area of the esophagus, between January 1965 and July 1988, in the Second Department of Surgery, Kyushu University Hospital, 42 patients (11.4%) with early stage esophageal carcinomas confined to the intraepithelium, mucosa, or submucosa were studied clinicopathologically. Of these 42, 26 (61.9%) had symptoms; slight dysphagia or chest discomfort was the most common symptom. The remaining 16 (38.1%) had no subjective symptoms. Endoscopic examination proved to be more useful than barium studies. Lugol-combined endoscopy was most effective in detecting the presence and spread of small malignant lesions of the esophagus. At the time of surgery, six patients with submucosal carcinoma of the esophagus had lymph node metastasis, and five died of recurrence. Described herein are the diagnostic features, clinicopathologic characteristics, and long-term results of these 42 patients with early stage, and 328 patients with advanced, carcinomas of the esophagus, detected and surgically treated in our clinics.


The role of extracellular DNA in uranium precipitation and biomineralisation.
Bacterial extra polymeric substances (EPS) have been associated with the extracellular precipitation of uranium. Here we report findings on the biomineralisation of uranium, with extracellular DNA (eDNA) used as a model biomolecule representative of EPS. The complexation and precipitation of eDNA with uranium were investigated as a function of pH, ionic strength and varying concentrations of reactants. The role of phosphate moieties in the biomineralisation mechanism was studied by enzymatically releasing phosphate (ePO4) from eDNA compared to abiotic phosphate (aPO4). The eDNA-uranium precipitates and uranium minerals obtained were characterised by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FT-IR) spectroscopy, Scanning Electron Microscopy-Energy Dispersive X-Ray analysis (SEM-EDX), X-Ray Powder Diffraction (XRD) and X-Ray Photoelectron Spectroscopy (XPS). ATR-FT-IR showed that at pH 5, the eDNA-uranium precipitation mechanism was predominantly mediated by interactions with phosphate moieties from eDNA. At pH 2, the uranium interactions with eDNA occur mainly through phosphate. The solubility equilibrium was dependent on pH with the formation of precipitate reduced as the pH increased. The XRD data confirmed the formation of a uranium phosphate precipitate when synthesised using ePO4. XPS and SEM-EDX studies showed the incorporation of carbon and nitrogen groups from the enzymatic orthophosphate hydrolysis on the obtained precipitated. These results suggested that the removal of uranium from solution occurs via two mechanisms: complexation by eDNA molecules and precipitation of a uranium phosphate mineral of the type (UO2HPO4)·xH2O by enzymatic orthophosphate hydrolysis. This demonstrated that eDNA from bacterial EPS is a key contributor to uranium biomineralisation.


Identifying and Exploring Sustainability Determinants of Mental Health Recovery-Oriented Interventions: A Mixed Methods Study Protocol.
Mental health recovery is the new paradigm in the mental health service delivery system worldwide. Recovery-oriented services go beyond traditional clinical care that is centered on symptom remission, aiming to help people: restore social connections with other individuals and the community; develop hope and optimism for the future; reconstruct an identity beyond that of a "mental patient"; discover meaning in life; and feel empowered to gain control over treatment (CHIME framework). Over the last ten years, several efforts at implementation of recovery-oriented interventions have been documented in the scientific literature. However, little attention has been given to their sustainability, even though it is reported that not all health interventions can fully sustain their activities beyond the initial implementation phase. The aim of this mixed methods case study is to better understand the factors that determine the sustainability of two recovery-oriented interventions (peer support and recovery training) after their roll-out in four organizations in Canada that provide community housing for adults with mental health challenges. Qualitative and quantitative data will be collected from managers, service providers, and implementation team members that oversaw the implementation process along with organizational documents. Data collection and analysis will be guided by the Consolidated Framework for Sustainability Constructs in Healthcare, the Framework for Reporting Adaptations and Modifications, and the Program Sustainability Assessment Tool. Findings will expand our current evidence base on the intersection of sustainability and mental health recovery interventions that remains under-explored.


Image-guided drainage of pericardial effusions in oncology patients.
The purpose of this study was to report our clinical experience with image-guided drainage of pericardial effusions in oncology patients. IRB approval was obtained for this retrospective, HIPAA-compliant study. From November 2002 to January 2008, 40 patients underwent 43 image-guided drainages of pericardial effusions. The medical records were reviewed to analyze the technical aspects of the procedures, complications, and clinical outcomes. Thirty-three pericardial drains were placed and 10 pericardiocenteses were performed. The technical success rate was 100%. Thirty-three procedures were performed under computed tomographic (CT) guidance, five under ultrasound (US) guidance, and five using both CT and US guidance. There were no technical, procedure-related complications. Delayed postprocedure complications and arrhythmias occurred in 11 cases, for an overall complication rate of 25.6%. All complications occurred in patients who had undergone drain placement. Nine patients developed new or worsening arrhythmias and six of these patients required transfer to a higher level of care or the initiation of pharmacological management. In 58.6% of drain placements, including 4 of 11 patients who developed complications, the catheter could have been removed earlier. The median overall survival was 6.47 months (95% CI: 2.37, 12.7). In conclusion, image-guided pericardial drain placement is safe and feasible. Due to the frequency of delayed postprocedure arrhythmias, follow-up monitoring in a telemetry unit is recommended. Prompt catheter removal after drainage may reduce the incidence of delayed post-catheter-insertion arrhythmias.


Apocynin attenuates angiotensin II-induced vascular smooth muscle cells osteogenic switching via suppressing extracellular signal-regulated kinase 1/2.
Vascular calcification (VC) is a significant risk factor for cardiovascular morbidity and mortality. We recently reported that apocynin had benefits for preventing cardiovascular diseases. However, whether apocynin could attenuate VC is unknown. Here, we investigated the role of apocynin in VC and its underlying mechanisms. 163 participants with high or normal ankle-brachial index (ABI) were enrolled in this study for analyzing the demographic and biochemical data. In vitro, vascular smooth muscle cells (VSMCs) were exposed to calcification medium containing b-glycerophosphate and angiotensin II (Ang II) for 24 hours. The results showed that serum level of Ang II was significantly increased in patients with high ABI (P<0.05). In cultured VSMCs, Ang II significantly exacerbated osteogenic switching. The expression of osteogenic phenotype markers, including bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2) and osteopontin (OPN), were significantly upregulated, whereas contractile markers expression, including alpha smooth muscle actin (a-SMA) and smooth muscle 22 alpha (SM22a) were simultaneously downregulated. However, these effects were greatly attenuated by apocynin. Apocynin enhanced expression of a-SMA by 5.3%, and reduced expression of BMP2, Runx2, OPN by 3.37%, 0.61% and 3.07%, respectively. Furthermore, extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation was upregulated by Ang II, and this effect was also reversed by apocynin. Intriguingly, pretreatment with U0126, an inhibitor of ERK1/2, had similar effects with apocynin. Apocynin may act as a novel molecular candidate to protect against VSMCs osteogenic switching through suppressing ERK1/2 pathway.


Autism voices: Perspectives of the needs, challenges, and hopes for the future of autistic youth.
Currently, our understanding of the adolescent period for autistic youth has relied on the expertise of researchers, clinicians, parents, and teachers, yet rarely involves their unique first-person experiences. Our study attempted to understand the experiences and perspectives of autistic adolescents in their home, school, and community environments using the Autism Voices protocol, a semi-structured interview specifically designed and tailored to engage with autistic youth with various language and intellectual levels. The analysis of the 31 interviews conducted with autistic adolescents aged 11-18 years highlighted six themes: (1) autistic identities, (2) thinking about the future, (3) seeking social connection on their own terms, (4) seeking autonomy, (5) school as both a stressor and social facilitator, and (6) experiences of stress and anxiety. These results highlight similarities and differences in the adolescent experiences of autistic youth compared to their typically developing peers. Our findings suggest that by removing assumptions about the experiences of autistic individuals and investing in inclusive interview methods, we can faithfully capture the experiences of autistic youth regardless of their communication and cognitive abilities. Being able to capture and amplify these diverse voices will facilitate the active involvement of autistic communities in research and clinical and policy decisions that impact them.


Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host.
Peripheral blood CD4+ T cell counts are a key measure for assessing disease progression and need for antiretroviral therapy in HIV-infected patients. More recently, studies have demonstrated a dramatic depletion of mucosal CD4+ T cells during acute infection that is maintained during chronic pathogenic HIV as well as SIV infection. A different clinical disease course is observed during the infection of natural hosts of SIV infection, such as sooty mangabeys (Cercocebus atys), which typically do not progress to AIDS. Previous studies have determined that SIV+ mangabeys generally maintain healthy levels of CD4+ T cells despite having viral replication comparable to HIV-infected patients. In this study, we identify the emergence of a multitropic (R5/X4/R8-using) SIV infection after 43 or 71 wk postinfection in two mangabeys that is associated with an extreme, persistent (>5.5 years), and generalized loss of CD4+ T cells (5-80 cells/microl of blood) in the absence of clinical signs of AIDS. This study demonstrates that generalized CD4+ T cell depletion from the blood and mucosal tissues is not sufficient to induce AIDS in this natural host species. Rather, AIDS pathogenesis appears to be the cumulative result of multiple aberrant immunologic parameters that include CD4+ T cell depletion, generalized immune activation, and depletion/dysfunction of non-CD4+ T cells. Therefore, these data provide a rationale for investigating multifaceted therapeutic strategies to prevent progression to AIDS, even following dramatic CD4 depletion, such that HIV+ humans can survive normal life spans analogous to what occurs naturally in SIV+ mangabeys.


Impact of extreme prematurity on families of adolescent children.
To compare the impact of burden of illness on families of teenaged children who were extremely low birth weight (ELBW) with that of members of a term control group (C) and to determine whether the attitudes toward active treatment of very immature infants differ between the 2 cohorts. In a cross-sectional survey, parents of 145 (86%) of 169 members of an ELBW cohort and 123 (85%) of 145 members of a control cohort completed a 23-item self-completed questionnaire encompassing occupational, marital, and family-related issues and attitudes toward treatment of infants of borderline viability. Both positive (P =.0003) and negative (P <.005) effects on marriage were higher in parents of the ELBW group; although more parents in the ELBW group felt that their child had brought their families closer together (P =.0001), their child's health had adversely affected their emotional health (P =.02) and that of other children in the family (P =.003). Despite this result, a significant proportion of parents from both cohorts supported saving all infants (ELBW 68%; C 58%) and favored the role of parents in decision making (ELBW 98%; C 97%). In the long term, it appears that parents of ELBW children have adjusted fairly well to their work and family life. Although some negative effects were identified, there was still considerable support for active treatment of infants of borderline viability.


Carriage of Neisseria meningitidis in the Hajj and Umrah mass gatherings.
Meningococcal disease is a serious public health threat, especially during mass gatherings such as Hajj and Umrah which provide optimal conditions for disease transmission. The disease is caused by Neisseria meningitidis and transmitted mainly via asymptomatic carriers. A review of the literature on asymptomatic N. meningitidis carriage among Hajj and Umrah pilgrims and their household contacts was performed. Carriage studies reported carriage rates to be higher in Hajj pilgrims compared to Umrah pilgrims and that these events promote acquisition of carriage among pilgrims. With some outliers, most studies found carriage rates among pilgrims to be comparable to those in populations under non-epidemic settings. However, these results should be interpreted with caution, taking into account the limitations within the studies identified. A wide variety of N. meningitidis serogroups appear to be circulating among Hajj and Umrah pilgrims, with serogroups W135 and B being most prominent. Current Hajj and Umrah meningococcal disease preventative measures do not necessarily prevent carriage and transmission, which may result in local and international outbreaks among susceptible populations. Monitoring carriage states of visitors and local inhabitants in the Kingdom of Saudi Arabia, as well as the implementation of preventive measures that impact carriage, are warranted to reduce the risk of Hajj and Umrah-related meningococcal disease outbreaks.


Static droplet array for culturing single live adherent cells in an isolated chemical microenvironment.
We present here a new method to easily and reliably generate an array of hundreds of dispersed nanoliter-volume semi-droplets for single-cells culture and analysis. The liquid segmentation step occurs directly in indexed traps by a tweezer-like mechanism and is stabilized by spatial confinement. Unlike common droplet-based techniques, the semi-droplet wets its surrounding trap walls thus supporting the culturing of both adherent and non-adherent cells. To eliminate cross-droplet cell migration and chemical cross-talk each semi-droplet is separated from a nearby trap by an ∼80 pL air plug. The overall setup and injection procedure takes less than 10 minutes, is insensitive to fabrication defects and supports cell recovery for downstream analysis. The method offers a new approach to easily capture, image and culture single cells in a chemically isolated microenvironment as a preliminary step towards high-throughput single-cell assays.


Colloidal probe dynamics in gelatin solution during the sol-gel transition.
The dynamics of the colloidal probes in a gelatin solution during the time-dependent sol-gel transition was investigated by multi-particle tracking. The relationship between the relaxation of the medium at the critical gel point and the mean square displacement of the probes was elucidated. Based on this understanding, the critical gel point of gelatin and the corresponding critical exponent n were unambiguously determined by the loss angle criterion and the time-cure superposition. The shift factors of the latter are further used to estimate the time/length-scale evolution of the gelatin during the sol-gel transition. The growth of the medium length scale crossed with the two measuring length scales successively at the pre-gel regime. Coinciding with the length-scale crossovers, the probability density function (PDF) of the probe displacements displayed two transient peaks of non-Gaussianity. In the post-gel regime, the third peak of Gaussianity suggested inhomogeneity in the gel network. The non-Gaussianity results from the bifurcation of diffusivity. The present work showed that the non-Gaussian dynamics of the probes are not the direct equivalence of that of the medium, but an effect of length-scale coupling.


Radiological assessment of bioengineered bone in a muscle flap for the reconstruction of critical-size mandibular defect.
This study presents a comprehensive radiographic evaluation of bone regeneration within a pedicled muscle flap for the reconstruction of critical size mandibular defect. The surgical defect (20 mm × 15 mm) was created in the mandible of ten experimental rabbits. The masseter muscle was adapted to fill the surgical defect, a combination of calcium sulphate/hydroxyapatite cement (CERAMENT™ |SPINE SUPPORT), BMP-7 and rabbit mesenchymal stromal cells (rMSCs) was injected inside the muscle tissue. Radiographic assessment was carried out on the day of surgery and at 4, 8, and 12 weeks postoperatively. At 12 weeks, the animals were sacrificed and cone beam computerized tomography (CBCT) scanning and micro-computed tomography (µ-CT) were carried out. Clinically, a clear layer of bone tissue was identified closely adherent to the border of the surgical defect. Sporadic radio-opaque areas within the surgical defect were detected radiographically. In comparison with the opposite non operated control side, the estimated quantitative scoring of the radio-opacity was 46.6% ± 15, the mean volume of the radio-opaque areas was 63.4% ± 20. Areas of a bone density higher than that of the mandibular bone (+35% ± 25%) were detected at the borders of the surgical defect. The micro-CT analysis revealed thinner trabeculae of the regenerated bone with a more condensed trabecular pattern than the surrounding native bone. These findings suggest a rapid deposition rate of the mineralised tissue and an active remodelling process of the newly regenerated bone within the muscle flap. The novel surgical model of this study has potential clinical application; the assessment of bone regeneration using the presented radiolographic protocol is descriptive and comprehensive. The findings of this research confirm the remarkable potential of local muscle flaps as local bioreactors to induce bone formation for reconstruction of maxillofacial bony defects.


Comparison of cross-sectional hardness and transverse microradiography of artificial carious enamel lesions induced by different demineralising solutions and gels.
The aims of this study were: (1) to correlate surface (SH) and cross-sectional hardness (CSH) with microradiographic parameters of artificial enamel lesions; (2) to compare lesions prepared by different protocols. Fifty bovine enamel specimens were allocated by stratified randomisation according to their initial SH values to five groups and lesions produced by different methods: MC gel (methylcellulose gel/lactic acid, pH 4.6, 14 days); PA gel (polyacrylic acid/lactic acid/hydroxyapatite, pH 4.8, 16 h); MHDP (undersaturated lactate buffer/methyl diphosphonate, pH 5.0, 6 days); buffer (undersaturated acetate buffer/fluoride, pH 5.0, 16 h), and pH cycling (7 days). SH of the lesions (SH(1)) was measured. The specimens were longitudinally sectioned and transverse microradiography (TMR) and CSH measured at 10- to 220-microm depth from the surface. Overall, there was a medium correlation but non-linear and variable relationship between mineral content and radicalCSH. radicalSH(1) was weakly to moderately correlated with surface layer properties, weakly correlated with lesion depth but uncorrelated with integrated mineral loss. MHDP lesions showed the highest subsurface mineral loss, followed by pH cycling, buffer, PA gel and MC gel lesions. The conclusions were: (1) CSH, as an alternative to TMR, does not estimate mineral content very accurately, but gives information about mechanical properties of lesions; (2) SH should not be used to analyse lesions; (3) artificial caries lesions produced by the protocols differ, especially considering the method of analysis.


Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma.
Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms. How transforming delta-retroviruses induce malignancy, however, remains poorly understood, especially as viral mRNA/protein are tightly silenced in tumors. Here, using deep sequencing of broad windows of small RNA sizes in the bovine leukemia virus ovine model of leukemia/lymphoma, we provide in vivo evidence of the production of noncanonical RNA polymerase III (Pol III)-transcribed viral microRNAs in leukemic B cells in the complete absence of Pol II 5'-LTR-driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, bovine leukemia virus microRNAs represent ∼40% of all microRNAs in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and/or viral targets. Bovine leukemia virus microRNAs are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent microRNAs subvert cellular and viral pathways will contribute to deciphering the intricate perturbations that underlie malignant transformation.


[Treatment of non-alcoholic fatty liver disease].
Non-alcoholic fatty liver disease (NAFLD) comprises benign steatosis and steatohepatitis (NASH) and may lead to liver fibrosis, cirrhosis and hepatocellular carcinoma. Its prevalence is estimated to be 20% in the general population and 50-100% in patients with overweight and obesity. In about 15-30% of patients steatosis evolves to NASH which can only be diagnosed by means of a liver biopsy. NAFLD may be described as the hepatic component of the metabolic syndrome and is a consequence of the Western lifestyle. The pathogenesis is multifactorial; oxidative stress plays a crucial role in maintaining inflammation and progressive fibrosis. Lifestyle modification with weight loss and increased physical activity is the cornerstone of the treatment, which should take place in a multidisciplinary setting. To date, no specific registered drug for NAFLD treatment is available. Supportive drug therapy is mainly focused on aspects of the metabolic syndrome and chronic inflammation.


Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting.
Radial arteries are increasingly used as conduits for coronary artery bypass grafts, but perioperative graft vasospasm continues to be a concern. Phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine have been advocated as topical antispasmodic agents. We compared the relative efficacies and durations of action of these agents. Isometric tension developed in response to clinically important vasoconstrictors was measured in 100 radial artery rings (from patients undergoing coronary artery bypass grafting, n = 25) after 15 minutes of ex vivo incubation with phenoxybenzamine, verapamil/nitroglycerin solution, papaverine, or vehicle (control). Duration of action was assessed by measuring responses to vasoconstrictors in antispasmodic pretreated and control rings at intervals through 5 hours. Verapamil/nitroglycerin solution reduced vasoconstriction in response to epinephrine, angiotensin II, prostaglandin F(2alpha), and phenylephrine but its effect had almost completely waned after 5 hours. Phenoxybenzamine prevented vasoconstriction in response to epinephrine, dopamine, and phenylephrine, with its effect lasting at least 5 hours. Papaverine had limited antispasmodic efficacy and prevented vasoconstriction in response to potassium (60 mmol/L) and phenylephrine for only 1 hour at the longest. Verapamil/nitroglycerin solution has a broad efficacy against a range of vasoconstrictors but a limited duration of action. Papaverine has the shortest duration of action. Phenoxybenzamine is an effective agent with a prolonged duration of action, specifically preventing catecholamine mediated vasospasm of radial artery conduits.


Intestinal intussusception due to a pyogenic granuloma.
Pyogenic granuloma (PG), also known as lobular capillary hemangioma, is a benign vascular tumor, most commonly arising on the skin and the oral mucosa. Gastrointestinal localization of PG, except for the oral cavity, is exceptionally rare. We describe a case of ileal PG occurring in a 13-year-old girl, presenting with intestinal obstruction. Histological examination revealed proliferation of capillary-sized vessels, with prominent intravascular component, involving the entire thickness of the intestinal wall. Immunohistochemistry showed positivity for CD31, CD34 and von Willebrand factor, whereas immunostaining for glucose transporter-1 protein (GLUT1) and for human herpes virus 8 (HHV-8) was negative. We suggest that PG should be considered in the differential diagnosis of childhood gastrointestinal polypoid lesions.


Ion channels in rabbit cultured fibroblasts.
Large outward currents are recorded with the whole-cell patch-clamp technique on depolarization of rabbit cultured fibroblasts. Our findings suggest that these outward currents consist of two voltage-dependent components, one of which also depends on cytoplasmic calcium concentration. Total replacement of external Cl- by the large anion ascorbate does not affect the amplitude of the currents, indicating that both components must be carried by K+. Consistent with these findings with whole-cell currents, in single channel recordings from fibroblasts we found that most patches contain high-conductance potassium-selective channels whose activation depends on both membrane potential and the calcium concentration at the cytoplasmic surface of the membrane. In a smaller number of patches, a second population of high-conductance calcium-independent potassium channels is observed having different voltage-dependence. The calcium- and voltage-dependence suggest that these two channels correspond with the two components of outward current seen in the whole-cell recordings. The single channel conductance of both channels in symmetrical KCl (150 mM) is 260-270 pS. Both channels are highly selective for K+ over both Na+ and Cl-. The conductance of the channels when outward current is carried by Rb+ is considerably smaller than when it is carried by K+. Some evidence is adduced to support the hypothesis that these potassium channel populations may be involved in the control of cell proliferation.


Sodium channels SCN1A, SCN2A and SCN3A in familial autism.
Autism is a psychiatric disorder with estimated heritability of 90%. One-third of autistic individuals experience seizures. A susceptibility locus for autism was mapped near a cluster of voltage-gated sodium channel genes on chromosome 2. Mutations in two of these genes, SCN1A and SCN2A, result in the seizure disorder GEFS+. To evaluate these sodium channel genes as candidates for the autism susceptibility locus, we screened for variation in coding exons and splice sites in 117 multiplex autism families. A total of 27 kb of coding sequence and 3 kb of intron sequence were screened. Only six families carried variants with potential effects on sodium channel function. Five coding variants and one lariat branchpoint mutation were each observed in a single family, but were not present in controls. The variant R1902C in SCN2A is located in the calmodulin binding site and was found to reduce binding affinity for calcium-bound calmodulin. R542Q in SCN1A was observed in one autism family and had previously been identified in a patient with juvenile myoclonic epilepsy. The effect of the lariat branchpoint mutation was tested in cultured lymphoblasts. Additional population studies and functional tests will be required to evaluate pathogenicity of the coding and lariat site variants. SNP density was 1/kb in the genomic sequence screened. We report 38 sodium channel SNPs that will be useful in future association and linkage studies.


Biodegradation during contaminant transport in porous media: 3. Apparent condition-dependency of growth-related coefficients.
The biodegradation of organic contaminants in the subsurface has become a major focus of attention, in part, due to the tremendous interest in applying in situ biodegradation and natural attenuation approaches for site remediation. The biodegradation and transport of contaminants is influenced by a combination of microbial and physicochemical properties and processes. The purpose of this paper is to investigate the impact of hydrodynamic residence time, substrate concentration, and growth-related factors on the simulation of contaminant biodegradation and transport, with a specific focus on potentially condition-dependent growth coefficients. Two sets of data from miscible-displacement experiments, performed with different residence times and initial solute concentrations, were simulated using a transport model that includes biodegradation described by the Monod nonlinear equations and which incorporates microbial growth and oxygen limitation. Two variations of the model were used, one wherein metabolic lag and cell transport are explicitly accounted for, and one wherein they are not. The magnitude of the maximum specific growth rates obtained from calibration of the column-experiment results using the simpler model exhibits dependency on pore-water velocity and initial substrate concentration (C0) for most cases. Specifically, the magnitude of micron generally increases with increasing pore-water velocity for a specific C0, and increases with decreasing C0 for a specific pore-water velocity. Conversely, use of the model wherein observed lag and cell elution are explicitly accounted for produces growth coefficients that are similar, both to each other and to the batch-measured value. These results illustrate the potential condition-dependency of calibrated coefficients obtained from the use of models that do not account explicitly for all pertinent processes influencing transport of reactive solutes.


The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study.
The aim of this study was to determine the independent risk factors, morbidity, and mortality of central nervous system (CNS) infections caused by Listeria monocytogenes. We retrospectively evaluated 100 episodes of neuroinvasive listeriosis in a multinational study in 21 tertiary care hospitals of Turkey, France, and Italy from 1990 to 2014. The mean age of the patients was 57 years (range, 19-92 years), and 64% were males. The all-cause immunosuppression rate was 54 % (54/100). Forty-nine (49 %) patients were referred to a hospital because of the classical triad of symptoms (fever, nuchal rigidity, and altered level of consciousness). Rhombencephalitis was detected radiologically in 9 (9 %) cases. Twenty-seven (64 %) of the patients who had cranial magnetic resonance imaging (MRI) performed had findings of meningeal and parenchymal involvement. The mean delay in the initiation of specific treatment was 6.8 ± 7 days. Empiric treatment was appropriate in 52 (52 %) patients. The mortality rate was 25 %, while neurologic sequelae occurred in 13 % of the patients. In the multivariate analysis, delay in treatment [odds ratio (OR), 1.07 [95 % confidence interval (CI), 1.01-1.16]] and seizures (OR, 3.41 [95 % CI, 1.05-11.09]) were significantly associated with mortality. Independent risk factors for neurologic sequelae were delay in treatment (OR, 1.07 [95 % CI, 1.006-1.367]) and presence of bacteremia (OR, 45.2 [95 % CI, 2.73-748.1]). Delay in the initiation of treatment of neuroinvasive listeriosis was a poor risk factor for unfavorable outcomes. Bacteremia was one of the independent risk factors for morbidity, while the presence of seizures predicted worse prognosis. Moreover, the addition of aminoglycosides to ampicillin monotherapy did not improve patients' prognosis.


Cognition About the Creative Process - Interview With Dr Andrew P. Allen.
What is the relationship between the creative process and cognition and perception? Lynda Loughnane, a master's student in Art and Process in Crawford College of Art and Design, Cork, Ireland interviewed Dr Andrew P. Allen about the subject. Areas covered include mindfulness, Type 1 and Type 2 thinking, stage theories of creativity, engagement with the art process and the artwork, phenomenology and consciousness with and without self report. The interview was constructed to cover a wide range of subject matter, so as to gather as much information as possible in layman's language about the cognitive process in relation to creativity and interaction with art.


Pelvic floor muscle functions are improved after successful transobturator vaginal mesh procedures.
To explore functional changes of pelvic floor muscle (PFM) after successful Perigee procedures. We retrospectively analyzed information from 145 women having achieved anatomic success, defined as <stage II cystocele according to the pelvic organ prolapse quantification (POP-Q) system. The investigated data included results from the POP-Q system and four-dimensional ultrasound at the preoperative and 12-month postoperative evaluations. The involuntary and voluntary PFM functions were, respectively, investigated during coughing and squeezing using the ultrasound parameters of the bladder neck distance (BND), bladder neck angle (BNA), genitohiatal distance (GHD), and genitohiatal angle. Postoperatively more women displayed normal involuntary PFM function in maintaining a stable bladder neck (preoperative vs. postoperative: 4.8% vs. 22.8%, P < 0.001) and genitohiatal (preoperative vs. postoperative: 16.6% vs. 30.3%, P = 0.008) locations upon coughing and could perform voluntary PFM contractions (preoperative vs. postoperative: 49.7% vs. 64.1%, P = 0.018). Compared with preoperative manifestations, less caudal displacement of the bladder neck indicated by smaller ranges of dynamic changes in BNA following coughing (preoperative vs. postoperative: 28° vs. 12°, P < 0.001), more cranial movement of the bladder neck indicated by larger values of changes in BND following squeezing (-0.26 vs. 0.06 cm, P < 0.001), and less reduction of genitohiatal size indicated by larger values of changes in GHD following squeezing (preoperative vs. postoperative: -0.95 vs. -0.63 cm, P = 0.027) were demonstrated postoperatively. Involuntary and voluntary PFM functions are improved after successful Perigee procedures. Neurourol. Urodynam. 36:380-384, 2017. © 2015 Wiley Periodicals, Inc.


'We are ordinary men': MSM identity categories in Tbilisi, Georgia.
Men who have sex with men remain largely absent from the health statistics of many Eastern European countries. This relative dearth compared to other parts of the world may be attributed to the generally hidden nature of this population. The tendency to employ Western sexual identity labels, rather than locally meaningful categories of identity, may also make it difficult to identify men who have sex with other men. In a pilot study of HIV risk in Tbilisi (Georgia), we used a suite of qualitative techniques - focus groups, individual semi-structured interviews and pile-sort exercises - to probe the opinions, knowledge and experiences of 65 Georgian men. We identified locally meaningful men-who-have-sex-with-men types, demonstrating a complex intersectionality of sexual preference, socio-economic status, behaviour and geography. Positioning within these types appeared to impact a man's exposure to the social stigma of homosexuality; the sexual, physical and mental health risks that he faced; and his access to treatment and counselling. Our results suggest the use of imported identity categories limits researchers' ability to identify men who have sex with other men in Georgia and that further research aimed at elucidating locally meaningful categories is needed - research likely to lead to more-effective group interventions and facilitate a better understanding of holistic individual health needs.


Piperine Plays an Anti-Inflammatory Role in Staphylococcus aureus Endometritis by Inhibiting Activation of NF-κB and MAPK Pathways in Mice.
Endometritis is commonly caused by pathogenic microorganisms, including Staphylococcus aureus (S. aureus). Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine on S. aureus endometritis, a mouse model of S. aureus endometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury in S. aureus endometritis. The qPCR and ELISA results showed that piperine effectively reduced the S. aureus-induced overexpression of TNF-α, IL-1β, and IL-6 but increased the expression of IL-10. The S. aureus-induced inflammation was related to TLR-2 and TLR-4 because the results showed that their expression was increased in S. aureus infection but then decreased with piperine treatment. To further confirm that piperine caused an anti-inflammatory response by targeting NF-κB and MAPKs, the expression of I-κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I-κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose-dependent manner. All of the results indicated that piperine may be a potential anti-inflammatory drug both in endometritis and in other S. aureus-induced diseases.


Female mate preferences for male body size and shape promote sexual isolation in threespine sticklebacks.
Female mate preferences for ecologically relevant traits may enhance natural selection, leading to rapid divergence. They may also forge a link between mate choice within species and sexual isolation between species. Here, we examine female mate preference for two ecologically important traits: body size and body shape. We measured female preferences within and between species of benthic, limnetic, and anadromous threespine sticklebacks (Gasterosteus aculeatus species complex). We found that mate preferences differed between species and between contexts (i.e., within vs. between species). Within species, anadromous females preferred males that were deep bodied for their size, benthic females preferred larger males (as measured by centroid size), and limnetic females preferred males that were more limnetic shaped. In heterospecific mating trials between benthics and limnetics, limnetic females continued to prefer males that were more limnetic like in shape when presented with benthic males. Benthic females showed no preferences for size when presented with limnetic males. These results show that females use ecologically relevant traits to select mates in all three species and that female preference has diverged between species. These results suggest that sexual selection may act in concert with natural selection on stickleback size and shape. Further, our results suggest that female preferences may track adaptation to local environments and contribute to sexual isolation between benthic and limnetic sticklebacks.


Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling mechanism during skeletal muscle wasting.
Ubiquitination-mediated proteolysis is a hallmark of skeletal muscle wasting manifested in response to negative growth factors, including myostatin. Thus, the characterization of signaling mechanisms that induce the ubiquitination of intracellular and sarcomeric proteins during skeletal muscle wasting is of great importance. We have recently characterized myostatin as a potent negative regulator of myogenesis and further demonstrated that elevated levels of myostatin in circulation results in the up-regulation of the muscle-specific E3 ligases, Atrogin-1 and muscle ring finger protein 1 (MuRF1). However, the exact signaling mechanisms by which myostatin regulates the expression of Atrogin-1 and MuRF1, as well as the proteins targeted for degradation in response to excess myostatin, remain to be elucidated. In this report, we have demonstrated that myostatin signals through Smad3 (mothers against decapentaplegic homolog 3) to activate forkhead box O1 and Atrogin-1 expression, which further promotes the ubiquitination and subsequent proteasome-mediated degradation of critical sarcomeric proteins. Smad3 signaling was dispensable for myostatin-dependent overexpression of MuRF1. Although down-regulation of Atrogin-1 expression rescued approximately 80% of sarcomeric protein loss induced by myostatin, only about 20% rescue was seen when MuRF1 was silenced, implicating that Atrogin-1 is the predominant E3 ligase through which myostatin manifests skeletal muscle wasting. Furthermore, we have highlighted that Atrogin-1 not only associates with myosin heavy and light chain, but it also ubiquitinates these sarcomeric proteins. Based on presented data we propose a model whereby myostatin induces skeletal muscle wasting through targeting sarcomeric proteins via Smad3-mediated up-regulation of Atrogin-1 and forkhead box O1.