Understanding factors that contribute to variations in bronchiolitis management in acute care settings: a qualitative study in Australia and New Zealand using the Theoretical Domains Framework.
Bronchiolitis is the most common reason for infants under one year of age to be hospitalised. Despite management being well defined with high quality evidence of no efficacy for salbutamol, adrenaline, glucocorticoids, antibiotics or chest x-rays, substantial variation in practice occurs. Understanding factors that influence practice variation is vital in order to tailor knowledge translation interventions to improve practice. This study explores factors influencing the uptake of five evidence-based guideline recommendations using the Theoretical Domains Framework. Semi-structured interviews were undertaken with clinicians in emergency departments and paediatric inpatient areas across Australia and New Zealand exploring current practice, and factors that influence this, based on the Theoretical Domains Framework. Interview transcripts were coded using thematic content analysis. Between July and October 2016, 20 clinicians (12 doctors, 8 nurses) were interviewed. Most clinicians believed chest x-rays were not indicated and caused radiation exposure (beliefs about consequences). However, in practice their decisions were influenced by concerns about misdiagnosis, severity of illness, lack of experience (knowledge) and confidence in managing infants with bronchiolitis (skills), and parental pressure influencing practice (social influences). Some senior clinicians believed trialling salbutamol might be of benefit for some infants (beliefs about consequences) but others strongly discounted this, believing salbutamol to be ineffective, with high quality evidence supporting this (knowledge). Most were concerned about antibiotic resistance and did not believe in antibiotic use in infants with bronchiolitis (beliefs about consequences) but experienced pressure from parents to prescribe (social influences). Glucocorticoid use was generally believed to be of no benefit (knowledge) with concerns surrounding frequency of use in primary care, and parental pressure (social influences). Nurse's reinforced evidence-based management of bronchiolitis with junior clinicians (social/professional role and identity). Regular turnover of medical staff, a lack of 'paediatric confident' nurses and doctors, reduced senior medical coverage after hours, and time pressure in emergency departments were factors influencing practice (environmental context and resources). Factors influencing the management of infants with bronchiolitis in the acute care period were identified using the Theoretical Domains Framework. These factors will inform the development of tailored knowledge translation interventions.


Complete Genome Sequence of Lelliottia Podophage phD2B.
The genus Lelliottia was recently created from the group of environmental gammaproteobacteria previously included in the genus Enterobacter. Here, we report the complete genome sequence of phD2B, the first (according to our current knowledge) known phage that infects bacterium from the taxon.


Parenting stress in infancy and psychosocial adjustment in toddlerhood: a longitudinal study of children with craniofacial anomalies.
To evaluate the association between parenting stress during infancy and child psychosocial adjustment during toddlerhood, within a sample of children with craniofacial anomalies (CFAs). Retrospective chart review. Urban medical center department of reconstructive plastic surgery. Parents of 47 children aged birth to 24 months at time 1 and 24 to 46 months at time 2. Parenting Stress Index/Short Form completed at times 1 and 2; Child Behavior Checklist completed at time 2. Relative to norms, more parents of children with CFAs experienced serious levels of parenting stress at times 1 and 2; however, fewer children with CFAs experienced serious levels of adjustment problems. Parenting stress during infancy predicted psychosocial adjustment in toddlerhood but was mediated by parenting stress in toddlerhood. Parents high on stress at both assessments showed clinical levels of total parenting stress and parent-child dysfunctional interaction when their children were infants; their toddlers showed higher levels of maladjustment than those with parents elevated on parenting stress during only infancy. Elevated levels of parenting stress during infancy may be stable through toddlerhood for families having a child with a CFA. The relation between parenting stress and child adjustment is likely to be reciprocal. These findings should be replicated with a larger sample and multiple informants.


[Evaluation of fetal oxygen saturation (FSpO2) during the course of underwater labor].
During controlled, randomized prospective trials, fetal arterial hemoglobin saturation (FSpO2) was estimated during 25 underwater labors and compared to results obtained from 34 classical deliveries. Mean fetal hemoglobin saturation during the first stage of labor was similar in both groups while a gradual decreasing trend in fetal FSpO2 was noticed throughout the progress of labor. In the second stage of labor higher mean FSpO2 values were observed in the group of fetuses born underwater. The author emphasized in discussion that underwater labor constitutes delicate and mild procedure particularly for the fetus.


Joint-level determinants of the dynamic strength index: implications for testing and monitoring.
The aims of this study were to determine the associations and differences between the traditional dynamic strength index (DSIGRF, calculated from ground reaction force [GRF] data) and joint-level dynamic strength indices (DSINJM, calculated from net joint moment [NJM] data). Eight female NCAA Division I lacrosse players performed three maximal effort isometric mid-thigh pulls (IMTP) and countermovement jumps (CMJ). GRF and motion capture data were recorded and used to calculate hip, knee, and ankle NJM. The ratio between peak forces during the IMTP and CMJ tests was used to calculate the DSIGRF and the ratio of peak NJM was used to calculate ankle, knee, and hip DSINJM. Associations and differences between DSIGRF and DSINJM were examined with Pearson's correlation coefficients, paired t-tests and Hedge's g effect sizes. The results showed that only the hip DSINJM was correlated with DSIGRF (hip: p = 0.037; r = 0.738). In addition, athletes exhibited significantly greater DSINJM than DSIGRF. Although these results suggest DSIGRF are associated with hip DSINJM, the fact that joint-level DSINJM were generally greater than DSIGRF suggests the ratio between peak NJM during the CMJ and IMTP may not provide intuitive or useful data for strength and conditioning coaches or sport scientists.


Psychological Impact of Facial Trauma.
Examination of the mental state of patients suffering from facial trauma is rarely ever recorded, let alone screening them for posttraumatic stress disorders (PTSDs) or generalized anxiety disorder. Providing early support to the patient in light of such psychological conditions can improve the overall quality of life. The aim of this study was to perform a literature review to assess the relation of mental state disorders to facial trauma in terms of their prevalence, assess screening methodology, and also to evaluate the prognosis of individuals subjected to psychological intervention/screening at an early stage of clinical examination. Research databases such as ScienceDirect, Google Scholar, PubMed, and Medline were searched using the keywords "psychological trauma," "facial trauma," and "PTSD." Only meta-analyses, systematic reviews, and original research articles in the English language were included in the study. Correspondence to journal editors and clinician opinions were excluded from the study. Out of a total of 459 results, only 8 articles satisfied the inclusion criteria of the study. The literature review showed that patients suffering from orofacial trauma had significantly increased levels of mental state disorders such as PTSD and generalized anxiety disorder, more so in victims of assault. The results of this literature review clearly point toward an increased prevalence of mental state disorders in patients suffering from facial trauma, which warrants for early intervention in this regard to improve the quality of life of these patients.


[Prevalence and public-health-aspects of toxoplasmosis].
Toxoplasmosis is one of the most common infectious diseases of man, which usually is not dangerous. Infection results from ingestion of cyst-containing meat products or by contact with oocyst-contaminated soil. Clinically relevant are (1) reactivation of latent infection in immunocompromised individuals or (2) primary infection during pregnancy with subsequent prenatal toxoplasmosis of the fetus. In Germany, law requires the prenatal infection to be reported to the Robert Koch-Institute. Since most Toxoplasma-infected children are asymptomatic at birth and later develop sequelae (retinochoroiditis) up to the age of 20 years, no valid epidemiological data are currently available for Germany. However, some studies indicate that seroprevalence correlates with age and that 26-54% of women of childbearing age have antibodies against Toxoplasma gondii; incidence rates during pregnancy have been calculated to be between 0.5 and 0.6%. Knowing the life cycle of Toxoplasma gondii will help to maintain preventive measures for seronegative pregnant women, children, and immunocompromised individuals.


Selection of words for implementation of the Picture Exchange Communication System - PECS in non-verbal autistic children.
It is known that some autistic individuals are considered non-verbal, since they are unable to use verbal language and barely use gestures to compensate for the absence of speech. Therefore, these individuals' ability to communicate may benefit from the use of the Picture Exchange Communication System - PECS. The objective of this study was to verify the most frequently used words in the implementation of PECS in autistic children, and on a complementary basis, to analyze the correlation between the frequency of these words and the rate of maladaptive behaviors. This is a cross-sectional study. The sample was composed of 31 autistic children, twenty-five boys and six girls, aged between 5 and 10 years old. To identify the most frequently used words in the initial period of implementation of PECS, the Vocabulary Selection Worksheet was used. And to measure the rate of maladaptive behaviors, we applied the Autism Behavior Checklist (ABC). There was a significant prevalence of items in the category "food", followed by "activities" and "beverages". There was no correlation between the total amount of items identified by the families and the rate of maladaptive behaviors. The categories of words most mentioned by the families could be identified, and it was confirmed that the level of maladaptive behaviors did not interfere directly in the preparation of the vocabulary selection worksheet for the children studied.


Chemical characterization, pharmacological effects, and toxicity of an ethanol extract of Celtis pallida Torr. (Cannabaceae) aerial parts.
Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases. The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE). The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000 µg/ml) for 5 h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000 mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200 mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200 mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200 mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively. The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100 µg/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000 mg/kg p.o.). Additionally, CPE lacked (MIC > 400 µg/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5 ± 1.5 mg/kg) and antidiarrheal effects (ED50 = 2.8 mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway. C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.


Acute behavioural disturbance: recognition, assessment and management.
Acute behavioural disturbance (ABD) is a clinical emergency which typically affects overweight men in their mid-thirties who chronically misuse illicit stimulants. People with ABD are most likely to be seen in police custody or emergency departments, therefore nurses working in these areas must be able to recognise the signs and symptoms and know how to respond appropriately. Presentation varies, but the signs and symptoms commonly include extreme agitation, hyperthermia, hostility and exceptional strength without fatigue. Further, it is important to recognise that people with ABD are at risk of developing metabolic acidosis, hyperkalaemia, rhabdomyolysis or disseminated intravascular coagulation. This article gives an overview of ABD and describes the main elements of management and treatment.


Multiple aromatic side chains within a disordered structure are critical for transcription and transforming activity of EWS family oncoproteins.
Chromosomal translocations involving the N-terminal approximately 250 residues of the Ewings sarcoma (EWS) oncogene produce a group of EWS fusion proteins (EFPs) that cause several distinct human cancers. EFPs are potent transcriptional activators and interact with other proteins required for mRNA biogenesis, indicating that EFPs induce tumorigenesis by perturbing gene expression. Although EFPs were discovered more than a decade ago, molecular analysis has been greatly hindered by the repetitive EWS activation domain (EAD) structure, containing multiple degenerate hexapeptide repeats (consensus SYGQQS) with a conserved tyrosine residue. By exploiting total gene synthesis, we have been able to systematically mutagenize the EAD and determine the effect on transcriptional activation by EWS/ATF1 and cellular transformation by EWS/Fli1. In both assays, we find the following requirements for EAD function. First, multiple tyrosine residues are essential. Second, phenylalanine can effectively substitute for tyrosine, showing that an aromatic ring can confer EAD function in the absence of tyrosine phosphorylation. Third, there is little requirement for specific peptide sequences and, thus, overall sequence composition (and not the degenerate hexapeptide repeat) confers EAD activity. Consistent with the above findings, we also report that the EAD is intrinsically disordered. However, a sensitive computational predictor of natural protein disorder (PONDR VL3) identifies potential molecular recognition features that are tyrosine-dependent and that correlate well with EAD function. In summary we have uncovered several molecular features of the EAD that will impact future studies of the broader EFP family and molecular recognition by complex intrinsically disordered proteins.


Laparoscopic versus open right hemicolectomy in colon carcinoma: A propensity score analysis of the DGAV StuDoQ|ColonCancer registry.
To assess whether laparoscopy has any advantages over open resection for right-sided colon cancer. Right hemicolectomy can be performed using either a conventional open or a minimally invasive laparoscopic technique. It is not clear whether these different access routes differ with regard to short-term postoperative outcomes. Patients documented in the German Society for General and Visceral Surgery StuDoQ|ColonCancer registry who underwent right hemicolectomy were analyzed regarding early postoperative complications according to Clavien-Dindo (primary endpoint), operation (OP) time, length of postoperative hospital stay (LOS), MTL30 and number of lymph nodes retrieved (secondary endpoints). A total of 4.997 patients were identified as undergoing oncological right hemicolectomy without additional interventions. Of these, 4.062 (81.3%) underwent open, 935 (18.7%) laparoscopic surgery. Propensity score analysis showed a significantly shorter LOS (OR: 0.55 CI 95%0.47-.64) and a significantly longer OP time (OR2.32 CI 1.98-2.71) for the laparoscopic route. Risk factors for postoperative complications, anastomotic insufficiency, ileus, reoperation and positive MTL30 were higher ASA status, higher age and increasing BMI. The surgical access route (open / lap) had no influence on these factors, but the laparoscopic group did have markedly fewer lymph nodes retrieved. The present registry-based analysis could detect no relevant advantages for the minimally invasive laparoscopic access route. Further oncological analyses are needed to clarify the extent to which the smaller lymph node harvest in the laparoscopic group is accompanied by a poorer oncological outcome.


Cerebral Epidural Abscess Secondary to Blastomyces Masquerading as an Epidermoid Tumor.
There have been infrequent reports of isolated central nervous system blastomycosis. We report a case of intracranial epidural abscess secondary to Blastomyces dermatitidis in a patient residing in Rhode Island with a history of remote travel to an endemic area. The clinical, radiographic, and pathologic features of this unique case are reviewed.


Head acceleration measurements in middle school football.
Although youth football players account for approximately 70% of all football players, the majority of research investigating concussion in football has focused on adults. The objective of this study was to investigate the head impact exposure experienced by middle school football players between the ages of 12 and 14 years. Recruited players were equipped with helmets instrumented with accelerometer arrays for 5 games and 27 practices. Linear accelerations ranged from 10 g to 150 g and rotational accelerations ranged from 4 rad/s2 to 9019 rad/s2. The average player experienced 210 ± 162 impacts while instrumented. The average player sustained a median impact of 21 ± 1 g and 885 ± 104 rad/s2, and a 95th percentile impact of 57 ± 12 g and 2570 ± 544 rad/s2. Data were then used to estimate a full middle school football season's head impacexposure for comparisons. Both impact magnitude and impact location distributions were similar to past studies investigating head impacts in high school and collegiate football players. Middle school players experience a greater number of impacts during games than during practices, and the majority of impacts occurred to the front or rear of the helmet. With an increased understanding of the head impact exposure experienced by youth football players, measures can be implemented to better protect players.


The Biosynthetic Gene Cluster for Andrastin A in Penicillium roqueforti.
Penicillium roqueforti is a filamentous fungus involved in the ripening of several kinds of blue cheeses. In addition, this fungus produces several secondary metabolites, including the meroterpenoid compound andrastin A, a promising antitumoral compound. However, to date the genomic cluster responsible for the biosynthesis of this compound in P. roqueforti has not been described. In this work, we have sequenced and annotated a genomic region of approximately 29.4 kbp (named the adr gene cluster) that is involved in the biosynthesis of andrastin A in P. roqueforti. This region contains ten genes, named adrA, adrC, adrD, adrE, adrF, adrG, adrH, adrI, adrJ and adrK. Interestingly, the adrB gene previously found in the adr cluster from P. chrysogenum, was found as a residual pseudogene in the adr cluster from P. roqueforti. RNA-mediated gene silencing of each of the ten genes resulted in significant reductions in andrastin A production, confirming that all of them are involved in the biosynthesis of this compound. Of particular interest was the adrC gene, encoding for a major facilitator superfamily transporter. According to our results, this gene is required for the production of andrastin A but does not have any role in its secretion to the extracellular medium. The identification of the adr cluster in P. roqueforti will be important to understand the molecular basis of the production of andrastin A, and for the obtainment of strains of P. roqueforti overproducing andrastin A that might be of interest for the cheese industry.


Sonographic Findings of Accessory Breast Tissue in Axilla and Related Diseases.
Accessory breast tissue results from failed regression of primitive mammary tissue and is most often located in the axilla. Accessory breast tissue itself is normal and should not be misdiagnosed as an abnormality. Both benign and malignant diseases that occur in the normal breast can also develop in accessory breast tissue in the axilla. In this pictorial essay, we show sonographic findings of normal accessory breast tissue in the axilla and various lesions that occur in accessory axillary breast tissue, along with other imaging findings and pathologic features.


Myeloperoxidase isoform activities released by human neutrophils in response to dental and periodontal bacteria.
Myeloperoxidase is an enzyme released by polymorphonuclear leukocytes which has been used, experimentally, as an indicator of periodontal disease activity when measured in gingival crevicular fluid. There are three myeloperoxidase isoforms: MPO I, MPO II and MPO III. We examined the activities of myeloperoxidase isoforms released by neutrophils in response to serum-opsonized Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Eikenella corrodens, Capnocytophaga sputigena and Streptococcus sanguis. Isoform activities were determined using intermediate-pressure liquid chromatography and microenzyme assay. A. actinomycetemcomitans stimulated higher levels of myeloperoxidase release than any other oral bacteria unless pre-opsonized with serum (or protein-A-purified immunoglobulin) from an individual with localized juvenile periodontitis. Most oral bacteria stimulated the release of all myeloperoxidase isoforms with a profile enriched in MPO I and diminished in MPO III. Exceptionally, serum-opsonized A. actinomycetemcomitans stimulated myeloperoxidase isoform release in proportion to the neutrophil granule constituency with or without localized juvenile periodontitis serum pre-opsonization. Because myeloperoxidase isoform profiles reflect how neutrophils were stimulated, isoform analysis may refine future diagnostic tests based upon myeloperoxidase.


Segmental distribution and morphometric features of primary sensory neurons projecting to the tibial periosteum in the rat.
Previous reports have demonstrated very rich innervation pattern in the periosteum. Most of the periosteal fibers were found to be sensory in nature. The aim of this study was to identify the primary sensory neurons that innervate the tibial periosteum in the adult rat and to describe the morphometric features of their perikarya. To this end, an axonal fluorescent carbocyanine tracer, DiI, was injected into the periosteum on the medial surface of the tibia. The perikarya of the sensory fibers were traced back in the dorsal root ganglia (DRG) L1-L6 by means of fluorescent microscopy on cryosections. DiI-containing neurons were counted in each section and their segmental distribution was determined. Using PC-assisted image analysis system, the size and shape of the traced perikarya were analyzed. DiI-labeled sensory neurons innervating the periosteum of the tibia were located in the DRG ipsilateral to the injection site, with the highest distribution in L3 and L4 (57% and 23%, respectively). The majority of the traced neurons were of small size (area < 850 microm2), which is consistent with the size distribution of CGRP- and SP-containing cells, regarded as primary sensory neurons responsible for perception of pain and temperature. A small proportion of labeled cells had large perikarya and probably supplied corpuscular sense receptors observed in the periosteum. No differences were found in the shape distribution of neurons belonging to different size classes.


The long road. Interview by Lynne Pearce.
In the fifth aticle on the management of change, Joy Jones describes how she improved services for people with eating disorders, while Stephen Wright explores the skills she brought to the work.


"Metabolic reprogramming" in ovarian cancer cells resistant to cisplatin.
The way cancer cells escape cisplatin-induced apoptosis has not been completely elucidated yet. We questioned the relevance of "metabolic reprogramming" in cisplatin-resistance by studying mitochondrial function and metabolism in human ovarian carcinoma cell lines, both cisplatin-sensitive (2008) and resistant (C13). C13 cells, in comparison to 2008 cells, showed lower apoptotic response to cisplatin exposure, lower basal oxygen consumption (4.2±0.2 vs 6.5±0.7 fmol/cell/min, p<0.005) and a lower basal transmembrane mitochondrial potential (Δψm) (18.7±1.5 vs 32.2±1 MFI p<0.001). Moreover, C13 cells showed a lower sensitivity to rotenone and oligomycin, two mitochondrial respiratory chain inhibitors. To further investigate the impact of mitochondria on cisplatin-resistance, 2008 and C13 cells were depleted of their mitochondrial DNA (rho(0)-clones). The cytotoxicity of cisplatin was lower in 2008-rho(0)clones than in 2008 cells (IC(50) of 3.56 µM and 0.72 µM, respectively) but similar between C13-rho(0) and C13 cells (IC(50) of 5.49 µM and 6.49 µM, respectively). The time-course of cell viability in glucose-free galactose medium indicated that C13 cells are more strictly dependent on glucose than 2008 cells. (1)H-NMR spectroscopy showed a higher basal content of intracellular glutathione (GSH) and mobile lipids (MLs) in C13 cells as compared to 2008 cells, with higher lipid accumulation mainly within cytoplasmic droplets of the C13 cells. These findings allow us to propose a "metabolic remodelling" of ovarian carcinoma cells to a lipogenic phenotype, which includes alteration of mitochondrial function, as an advantageous mechanism to escape cisplatin-induced apoptosis. This hypothesis is of interest to exploit new pharmacological targets to improve the clinical impact of platinum drugs.


Negative Linear Compressibility in Organic-Inorganic Hybrid Perovskite [NH2NH3]X(HCOO)3 (X = Mn, Fe, Co).
Hybrid organic-inorganic perovskites [NH2NH3][X(HCOO)3] (X = Mn, Fe, Co) have a so-called "wine-rack" type of geometry that could give origin to the rare property of negative linear compressibility, which is an exotic and highly desirable material response. We use first-principles density functional theory computations to probe the response of these materials to hydrostatic pressure and predict that, indeed, all three of them exhibit negative linear compressibility above a critical pressure of 1 GPa. Calculations reveal that, under pressure, XO6 octahedra and -HCOO ligands remain relatively rigid while XO6 octahedra tilt significantly, which leads to highly anisotropic mechanical properties and expansion along certain directions. These trends are common for the three materials considered.


Design study of a micro illumination platform based on GaN microLED arrays.
The design study of a micro illumination tool based on GaN microLED arrays is presented. The high spatio-temporal resolution and the capability of generating fully customized optical patterns that characterize the proposed platform would enable the manipulation of biological systems, e.g., for optogenetics applications. Based on ray tracing simulations, the design aspects that mainly affect the device performance have been identified, and the related structural parameters have been optimized to improve the extraction efficiency and the spatial resolution of the resulting light patterns. Assuming that the device is a bottom emitter, and the light is extracted from the n-side, the presence of mesa-structures on the p-side of the GaN layer can affect both the efficiency and the resolution, being optimized for different values of the mesa-side inclination angle. The full width at half maximum (FWHM) of the extracted spots is mainly determined by the substrate thickness, and the relation between the FWHM and the array pitch represents a criterion to define the resolution. Namely, when F W H M<p i t c h, the spots are assumed to be resolved, while, when F W H M=p i t c h, a homogeneous distribution of light intensity is observed. The best performance is obtained when an in-GaN micro-lens array is included in the simulated structure, assuming that the substrate has been removed. The spatial resolution of the generated light pattern results as fully preserved, while the extraction efficiency in the best case is up to three times larger than that of a planar GaN/air interface.


Genetic Screening of a Hungarian Cohort with Focal Dystonia Identified Several Novel Putative Pathogenic Gene Variants.
Dystonia is a rare movement disorder which is characterized by sustained or intermittent muscle contractions causing abnormal and often repetitive movements, postures, or both. The two most common forms of adult-onset focal dystonia are cervical dystonia (CD) and benign essential blepharospasm (BSP). A total of 121 patients (CD, 74; BSP, 47) were included in the study. The average age of the patients was 64 years. For the next-generation sequencing (NGS) approach, 30 genes were selected on the basis of a thorough search of the scientific literature. Assessment of 30 CD- and BSP-associated genes from 121 patients revealed a total of 209 different heterozygous variants in 24 genes. Established clinical and genetic validity was determined for nine heterozygous variations (three likely pathogenic and six variants of uncertain significance). Detailed genetic examination is an important part of the work-up for focal dystonia forms. To our knowledge, our investigation is the first such study to be carried out in the Middle-European region.


Long-term neurodevelopmental outcome in children born after vacuum-assisted delivery compared with second-stage caesarean delivery and spontaneous vaginal delivery: a cohort study.
To evaluate long-term neurodevelopment in children born after low-or mid-station vacuum-assisted delivery (VAD) compared with children delivered by second-stage caesarean delivery (SSCD) or spontaneous vaginal delivery (SVD). Cross-sectional cohort study. Two delivery wards, Karolinska University Hospital, Sweden. 253 children born by low-station or mid-station VAD, 247 children born after an SVD, and 86 children born via an SSCD accepted to participate. The Five-to-Fifteen questionnaire was used as a validated screening method for neurodevelopmental difficulties, assessed by parents. Results in the Five-to-Fifteen questionnaire. In addition, registered neurodevelopmental ICD-10 diagnoses were collected. Regression analyses estimated associations between delivery modes. Children born after VAD exhibited an increased rate of long-term neurodevelopmental difficulties in motor skills (OR 2.2, 95% CI 1.3 to 3.8) and perception (OR 1.7, 95% CI 1.002 to 2.9) compared with SVD. Similar findings were seen in the group delivered with an SSCD compared with SVD (motor skills: OR 3.3, 95% CI 1.8 to 6.4 and perception: OR 2.3, 95% CI 1.2 to 4.4). The increased odds for motor skills difficulties after VAD and SSCD remained after adjusting for proposed confounding variables. There were significantly more children in the VAD group with registered neurodevelopmental ICD-10 diagnoses such as attention deficit/hyperactivity disorders. The differences in long-term neurodevelopmental difficulties in children delivered with a VAD or SSCD compared with SVD in this study indicate the need for increased knowledge in the field to optimise the management of second stage of labour.


Endometrial resection and ablation techniques for heavy menstrual bleeding.
Heavy menstrual bleeding (HMB) is a significant health problem in premenopausal women; it can reduce their quality of life and can cause social disruption and physical problems such as iron deficiency anaemia. First-line treatment has traditionally consisted of medical therapy (hormonal and non-hormonal), but this is not always successful in reducing menstrual bleeding to acceptable levels. Hysterectomy is a definitive treatment, but it is more costly and carries some risk. Endometrial ablation may be an alternative to hysterectomy that preserves the uterus. Many techniques have been developed to 'ablate' (remove) the lining of the endometrium. First-generation techniques require visualisation of the uterus with a hysteroscope during the procedure; although it is safe, this procedure requires specific technical skills. Newer techniques for endometrial ablation (second- and third-generation techniques) have been developed that are quicker than previous approaches because they do not require hysteroscopic visualisation during the procedure. To compare the efficacy, safety, and acceptability of endometrial destruction techniques to reduce heavy menstrual bleeding (HMB) in premenopausal women. We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, CINAHL, and PsycInfo (from inception to May 2018). We also searched trials registers, other sources of unpublished or grey literature, and reference lists of retrieved studies, and we made contact with experts in the field and with pharmaceutical companies that manufacture ablation devices. Randomised controlled trials (RCTs) comparing different endometrial ablation or resection techniques for women reporting HMB without known uterine pathology, other than fibroids outside the uterine cavity and smaller than 3 centimetres, were eligible. Outcomes included improvement in HMB and in quality of life, patient satisfaction, operative outcomes, complications, and the need for further surgery, including hysterectomy. Two review authors independently selected trials for inclusion, assessed trials for risk of bias, and extracted data. We contacted study authors for clarification of methods or for additional data. We assessed adverse events only if they were separately measured in the included trials. We undertook comparisons with individual techniques as well as an overall comparison of first- and second-generation ablation methods. We included in this update 28 studies (4287 women) with sample sizes ranging from 20 to 372. Most studies had low risk of bias for randomisation, attrition, and selective reporting. Less than half of these studies had adequate allocation concealment, and most were unblinded. Using GRADE, we determined that the quality of evidence ranged from moderate to very low. We downgraded evidence for risk of bias, imprecision, and inconsistency.Overall comparison of second-generation versus first-generation (i.e. gold standard hysteroscopic ablative) techniques revealed no evidence of differences in amenorrhoea at 1 year and 2 to 5 years' follow-up (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.78 to 1.27; 12 studies; 2145 women; I² = 77%; and RR 1.16, 95% CI 0.78 to 1.72; 672 women; 4 studies; I² = 80%; very low-quality evidence) and showed subjective improvement at 1 year follow-up based on a Pictorial Blood Assessment Chart (PBAC) (< 75 or acceptable improvement) (RR 1.03, 95% CI 0.98 to 1.09; 5 studies; 1282 women; I² = 0%; and RR 1.12, 95% CI 0.97 to 1.28; 236 women; 1 study; low-quality evidence). Study results showed no difference in patient satisfaction between second- and first-generation techniques at 1 year follow-up (RR 1.01, 95% CI 0.98 to 1.04; 11 studies; 1750 women; I² = 36%; low-quality evidence) nor at 2 to 5 years' follow-up (RR 1.02, 95% CI 0.93 to 1.13; 672 women; 4 studies; I² = 81%).Compared with first-generation techniques, second-generation endometrial ablation techniques were associated with shorter operating times (mean difference (MD) -13.52 minutes, 95% CI -16.90 to -10.13; 9 studies; 1822 women; low-quality evidence) and more often were performed under local rather than general anaesthesia (RR 2.8, 95% CI 1.8 to 4.4; 6 studies; 1434 women; low-quality evidence).We are uncertain whether perforation rates differed between second- and first-generation techniques (RR 0.32, 95% CI 0.10 to 1.01; 1885 women; 8 studies; I² = 0%).Trials reported little or no difference between second- and first-generation techniques in requirement for additional surgery (ablation or hysterectomy) at 1 year follow-up (RR 0.72, 95% CI 0.41 to 1.26; 6 studies: 935 women; low-quality evidence). At 5 years, results showed probably little or no difference between groups in the requirement for hysterectomy (RR 0.85, 95% CI 0.59 to 1.22; 4 studies; 758 women; moderate-quality evidence). Approaches to endometrial ablation have evolved from first-generation techniques to newer second- and third-generation approaches. Current evidence suggests that compared to first-generation techniques (endometrial laser ablation, transcervical resection of the endometrium, rollerball endometrial ablation), second-generation approaches (thermal balloon endometrial ablation, microwave endometrial ablation, hydrothermal ablation, bipolar radiofrequency endometrial ablation, endometrial cryotherapy) are of equivalent efficacy for heavy menstrual bleeding, with comparable rates of amenorrhoea and improvement on the PBAC. Second-generation techniques are associated with shorter operating times and are performed more often under local rather than general anaesthesia. It is uncertain whether perforation rates differed between second- and first-generation techniques. Evidence was insufficient to show which second-generation approaches were superior to others and to reveal the efficacy and safety of third-generation approaches versus first- and second-generation techniques.


Topographical relationship between beta-amyloid and tau protein epitopes in tangle-bearing cells in Alzheimer disease.
Double-labeling immunohistochemistry was used to investigate the topographical relationship between beta-amyloid and tau protein epitopes present in cells bearing neurofibrillary tangles found in the hippocampal formation of patients with Alzheimer disease. An antiserum raised against the amino terminus of beta-amyloid stained numerous tangle-bearing cells and other bodies ("extracellular tangles"), but double labeling showed that the beta-amyloid staining is invariably peripheral to that of the tau-positive tangle proper. This and other results suggest that the extracellular amyloid plaques and the intracellular neurofibrillary tangles are biochemically distinct but may result from related pathological events that originate at the level of the nerve cell and lead to its degeneration.


What Patients Think: A Study Examining Perceptions of Teamwork, Self-Management, and Quality of Life of Patients Diagnosed With Diabetic Foot Ulceration.
Identifying strategies to support patients diagnosed with diabetic foot ulceration (DFU) is essential to affect not only wound outcomes but also mortality and quality of life. This article reports on a cross-sectional, descriptive, correlational study of patients receiving treatment for DFU at a specialty clinic. Most participants were <60 years of age and had been diagnosed with diabetes for >5 years. Results indicated that patients with higher self-management scores reported improved general health, physical functioning, and quality of life. These findings, in a younger patient population with normal work and family obligations, suggest that interventions supporting self-management behaviors can improve physical, emotional, and general health and, ultimately, quality of life. The involvement of an interprofessional care team enhances these self-management behaviors.


Dietary calcium intake and hypertension risk: a dose-response meta-analysis of prospective cohort studies.
The association of calcium intake with risk of developing hypertension in the general population has not been established yet. We systematically searched PubMed and Scopus databases up to February 2018 to find prospective observational studies investigating the association of calcium intake with risk of developing hypertension. The reported risk estimates were pooled using a random-effects model. Eight prospective cohort studies (248,398 participants and 30,838 cases) were included. Seven studies measured dietary calcium intake, but one study measured total calcium intake (calcium from food and supplements). A significant inverse association was found for the highest versus lowest category of calcium intake (relative risk: 0.89, 95%CI: 0.86, 0.93; I2 = 0%, n = 8), and for each 500 mg/d increment (relative risk: 0.93, 95%CI: 0.90, 0.97; I2 = 64%, n = 7). Summary results were the same with the main analyses when the analyses were restricted only to dietary calcium intake. A nonlinear dose-response meta-analysis exhibited a linear inverse association, with a somewhat steeper trend within the low and moderate intakes. In conclusion, higher dietary calcium intake, independent of adiposity and intake of other blood pressure-related minerals, is slightly associated with a lower risk of developing hypertension.


Corrosion Resistance Enhancement of CoCrFeMnNi High-Entropy Alloy with WC Particle Reinforcements via Laser Melting Deposition.
In the present work, a WC particle-reinforced CoCrFeMnNi high-entropy alloy (HEA) was fabricated by laser melting deposition (LMDed). The LMDed CoCrFeMnNi high-entropy alloy (CoCrFeMnNi) composite is primarily comprised of a face-centered cubic (FCC) crystal structure. However, in the case of CoCrFeMnNi with 2.5 wt.% WC, it exhibits a combination of an FCC matrix and a ceramic phase known as M23C6. The corrosion behavior of CoCrFeMnNi and CoCrFeMnNi with 2.5 wt.% WC particle in 0.5 M H2SO4 was comparatively investigated. Compared with CoCrFeMnNi, the passive film formed on the CoCrFeMnNi with 2.5 wt.% WC had a more stable and stronger protective property. The corrosion current density of the CoCrFeMnNi with 2.5 wt.% WC dropped by 149.1% compared to that of the CoCrFeMnNi, indicating that the CoCrFeMnNi with 2.5 wt.% WC had better corrosion resistance than that of the CoCrFeMnNi.


An irritable infant and the runaway redback: an instructive case.
The envenomation syndrome of Redback spider bites, lactrodectism, is distinctive. However diagnosis can be difficult due to an atypical presentation. We describe the case of a 1 year old boy with irritability, diaphoresis and reduced oral intake, in whom a diagnosis was made of redback spider bite. Successful resolution of symptoms was achieved following treatment with antivenom. The symptoms and management of redback spider bites is discussed.


The Chlamydomonas reinhardtii gtr gene encoding the tetrapyrrole biosynthetic enzyme glutamyl-trna reductase: structure of the gene and properties of the expressed enzyme.
Plants, algae, cyanobacteria and many other bacteria synthesize the tetrapyrrole precursor, delta-aminolevulinic acid (ALA), from glutamate by means of a tRNAGlu-mediated pathway. The enzyme glutamyl-tRNA reductase (GTR) catalyzes the first committed step in this pathway, which is the reduction of tRNA-bound glutamate to produce glutamate 1-semialdehyde. Chlamydomonas reinhardtii mRNA encoding gtr was sequenced from a cDNA and genomic libraries. The 3179-bp gtr cDNA contains a 1566-bp open reading frame that encodes a 522-amino acid polypeptide. After removal of the predicted transit peptide, the mature 480-residue GTR has a calculated molecular weight of 52,502. The deduced C. reinhardtii mature GTR amino acid sequence has more than 55% identity to a GTR sequence of Arabidopsis thaliana, and significant similarity to GTR proteins of other plants and prokaryotes. Southern blot analysis of C. reinhardtii genomic DNA indicates that C. reinhardtii has only one gtr gene. Genomic DNA sequencing revealed the presence of a small intron near the putative transit peptide cleavage site. Expression constructs for the full-length initial gtr translation product, the mature protein after transit peptide removal, and the coding sequence of the second exon were cloned into expression vector that also introduced a C-terminal His6 tag. All of these constructs were expressed in E. coli, and both the mature protein and the exon 2 translation product complemented a hemA mutation. The expressed proteins were purified by Ni-affinity column chromatography to yield active GTR. Purified mature GTR was not inhibited by heme, but heme inhibition was restored upon addition of C. reinhardtii soluble proteins.


Minireview: recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners.
Glucose transporter (GLUT) 4 is the major glucose transporter of muscle and adipose cells, exquisitely regulated by insulin through posttranslational events. Twenty years after the seminal observations that GLUT4 levels rapidly rise at the plasma membrane (PM) and drop in endomembranes in response to an acute insulin challenge, we are still mapping the intracellular traffic of the transporter and the regulatory events that insulin unleashes. Newly synthesized GLUT4 enters an insulin-responsive compartment aided by GGA2 (an Arf-binding protein). In cultured adipocytes and myocytes, GLUT4 concentrates in a perinuclear pole through participation of microtubules and the EHD1 Eps15 homology domain-containing protein 1. In the absence of stimuli, GLUT4 distributes between recycling endosomes and the insulin-responsive compartment. A handful of proteins that bind to GLUT4 appear to regulate its half-life (e.g. Ubc9) and tethering within endomembranes (e.g. TUG). Insulin-derived signals promote not only GLUT4 mobilization toward the PM but also its traffic between endosomal compartments and internalization from the PM. Class IA phosphatidylinositol (PI) 3-kinase plays a pivotal role at several steps of GLUT4 mobilization. The PI 3-kinase --> atypical PKC and --> Akt/PKB --> AS160 signaling cascades are major regulators of GLUT4 exocytosis aided by small GTPases. At the cell periphery, GLUT4-containing vesicles tether, dock, and fuse with the PM assisted by the exocyst complex followed by engagement of a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex [with vesicle-associated membrane protein (VAMP)2 as the vesicular (v)-SNARE and soluble NSF-attachment protein (SNAP)23 and syntaxin4 as target (t)-SNAREs] regulated by the accessory proteins Munc18c, Synip and Tomosyn. Vesicle tethering and fusion are regulated by insulin through input from class IA PI 3-kinase.


Molecular alterations of the RB1, TP53, and MDM2 genes in primary and xenografted human osteosarcomas.
We report the status of the RB1, TP53, and MDM2 genes in human osteosarcomas and cell lines established from surgical specimens and transplanted into athymic naked mice. By using reverse transcriptase-polymerase chain reaction (RT-PCR) as a prescreening technique and posterior sequencing, we observe new mutations in the RB1 gene, notably a duplication in tandem of exons 3 through 6. TP53 mutations appear in codons most frequently mutated in osteosarcomas. We have not seen MDM2 gene amplification in any reported case. These molecular alterations appear in different osteosarcomas not simultaneously present in the same tumor sample. A link has been described between these three genes in the pathways that control the cell cycle and the tumoral progression, but their functions are probably independent in the development of osteosarcomas. TP53 mutations appear in adult patients, whereas RB1 alterations occur mostly in younger patients.


[Endoscopic treatment of gastroduodenal perforations].
A 93-year-old patient underwent endoscopic treatment of perforated duodenal ulcer after previous laparoscopic suturing complicated by failure of sutured defect. A self-expanding nitinol stent with partial polyurethane coating was used. Positive effect of the treatment was noted. Further study of this method and its clinical introduction in case of favorable results can significantly reduce the incidence of complications and mortality in patients with perforated gastroduodenal ulcers.


Stimulation of atrial natriuretic peptide receptor/guanylyl cyclase- A signaling pathway antagonizes the activation of protein kinase C-alpha in murine Leydig cells.
Atrial natriuretic peptide (ANP) regulates diverse physiological responses by binding to its specific guanylyl cyclase-A receptor (Npra) which synthesizes the intracellular second messenger cGMP. To understand the molecular mechanisms of cellular signaling of ANP, we have studied its effect on the enzymatic activity of overexpressed protein kinase C (PKC) in murine Leydig tumor (MA-10) cells which were transfected with PKC-alpha cDNA. Treatments with 12-O-tetradecanoylphorbol-13-acetate (TPA), angiotensin II (ANG II) and endothelin-1 (ET-1) stimulated the PKC activity by 4-5-fold in PKC-alpha cDNA transfected MA-10 cells. The pretreatment of PKC-alpha transfected cells with ANP significantly inhibited the TPA-, ANG II- and ET-1-stimulated PKC activity. The agonist-stimulated PKC activity was also inhibited in the presence of 8-bromo-cGMP, however, cAMP had no effect on stimulatory PKC activity. The exposure of cells to Npra- antagonist A71915, which blocks the production of cGMP, significantly reduced the inhibitory effect of ANP on agonist-stimulated PKC activity and accumulation of intracellular cGMP in MA-10 cells. Similarly, inhibition of cGMP-dependent protein kinase by KT5823, restored the stimulatory levels of PKC activity in the presence of ANP. These results provide direct evidence that ANP antagonizes the agonist-stimulated PKC activity in MA-10 cells, involving the specific receptor Npra, its second messenger cGMP and cGMP-dependent protein kinase. Together, these findings implicate that ANP may act as a negative mediator of 'cross-talk' between PKC-alpha and Npra signaling pathway in MA-10 cells.


"A different atmosphere of love": a qualitative study of the experiences of participants in Evangelical substance user rehabilitation programs in the Russian Federation.
This article explores the lived experiences of individuals who have participated in faith-based substance user rehabilitation programs in the Russian Federation. The Russian Federation has high rates of alcohol and opioid dependence and a dearth of professional treatment options. In the post-Soviet period, Evangelical Christian groups have developed substance user rehabilitation programs to attempt to address substance use and its related problems. Data were collected during 2010 via focus group interviews with participants in three Evangelical rehabilitation programs in the Volga region of the Russian Federation. Themes emerging from the qualitative data analysis process were classified into three broad categories: Typical Day, Personal Background/Decision to Enter Rehabilitation, and Helpful Aspects of Rehabilitation Process.


[Prevention of atherosclerosis in children--the role of statins and aspirin].
Cardiovascular diseases remain the leading cause of death in Poland and in Europe. Children rarely suffer from them, although most of the risk factors which accelerate progression of atherosclerosis commence in childhood, including: dyslipidemias, hypertension, diabetes, and obesity. Moreover during last few years the incidence of some of risk factors in children, such as obesity, diabetes and dyslipidemia has increased significantly. It is known from the autopsy studies that atherosclerosis can be identified at very young age in healthy children. In adult population medications such as HMG-CoA reductase inhibitors (statins) and acetylsalicylic acid (ASA, aspirin) have strong position confirmed by many multicenter clinical trials. They significantly reduce cardiovascular risk and increase life expectancy. Latest recommendations on management of hyperlipidemias in children expand indications for screening of lipid level imbalances and indicate statins as main pharmacotherapy after failure of life style changes. On the other hand acetylsalicylic acid is not used so broadly. Only children at high risk of thrombosis may benefit from its antiplatelet property. This review presents the latest recommendations and the therapeutic role of these medications in pediatric population.


Beneficial reuse of Brest-Harbor (France)-dredged sediment as alternative material in road building: laboratory investigations.
The scarcity of natural aggregates promotes waste reuse as secondary raw material in the field of civil engineering. This article focuses on the beneficial reuse of marine-dredged sediments in road building. Thus, mixtures of raw sediments and dredged sand collected from Brest Harbur (Bretagne, France) were treated with road hydraulic binders. Formulation were prepared and characterized as recommended by the French Technical Guidelines for soil treatment with lime and/or hydraulic binders. Mechanical resistance results are quite similar for both the hydraulic binders, suggesting a similar reactivity with the studied sediment sample. However, some discrepancies can be noted on sustainability parameters. Indeed, water resistance after immersion at 40°C is significantly better for the mixtures treated with cement containing more glass-forming oxides (SiO2 + Al2O3) and fluxing (Fe2O3+CaO + MgO + K2O + Na2O). Moreover, the both hydraulic binders can lead to swelling in the road materials as observed in scanning electron microscopy analyses. Indeed, microscopic observations indicated volumetric swelling of treated samples, which is greatly influenced on the one side by ettringite quantity and on the other hand by the presence of water in pores material.


Molecular epidemiology of Staphylococcus epidermidis clinical isolates from U.S. hospitals.
The epidemiology of Staphylococcus epidermidis in U.S. hospitals remains limited. This study aimed to address the genetic backgrounds of linezolid-susceptible and -resistant S. epidermidis strains (isolated in 2010), including cfr-carrying strains. In addition, the antimicrobial susceptibility profiles and linezolid resistance mechanisms among clonal lineages were assessed. A total of 71 S. epidermidis isolates were selected, and linezolid-resistant strains were screened for cfr and mutations in 23S rRNA, L3, and L4. All isolates were subjected to multilocus sequence typing (MLST), and the results were analyzed by eBURST. Overall, 27 sequence types (STs) were detected, and ST5 (21.1%) and ST2 (16.9%) predominated. The majority (62/71; 87.3%) of STs belonged to clonal complex 2 (CC2), which was mostly comprised of subclusters CC2-II (41/62; 66.1%) and CC2-I (21/62; 33.9%). Other STs were grouped within CC23 or CC32 or were singletons. CC2-I strains were more likely to display a methicillin (95.2% versus 33.3 to 70.7%), a linezolid (47.6% versus 0.0 to 7.3%), or a multidrug (81.0% versus 33.3 to 36.6%) resistance phenotype. Among linezolid-resistant isolates, cfr was noted only within CC2 strains, and it was detected equally in the CC2-I (3/10; 30.0%) and CC2-II (1/3; 33.3%) subclusters. 23S rRNA mutations (G2576 [seven strains] and C2534 [one strain]) were observed only among CC2-I (8/10; 80.0%) isolates. Strains showing a G2576 alteration also had M156 (7/7; 100.0%) and/or H146 (6/7; 85.7%) L3 modifications. This study provides an overview of the S. epidermidis clonal distribution and reports higher resistance rates among CC2-I strains. The results show that cfr may be acquired and expressed by both CC2 main subclusters, while 23S rRNA mutations appeared more often within CC2-I strains. Interestingly, these 23S rRNA mutants also had L3 alterations, which may act synergistically or in a compensatory manner to minimize the fitness cost while providing survival advantages under selective pressure.


Cytotoxic effect of cytokines on murine colon carcinoma cells involves TNF-mediated apoptosis.
We have studied the cytotoxic effect of TNF-alpha on C-26 murine colon carcinoma cells in vitro. Treatment with TNF-alpha alone did not result in any demonstrable cytotoxicity. However, when combined with IFN-gamma, the cytotoxic effect of TNF-alpha was enhanced in a dose-dependent manner. An agonistic TNF-R1 specific antibody and recombinant human TNF-alpha both exerted a cytotoxic effect when combined with IFN-gamma, suggesting that the cytotoxicity was mediated through the TNF-R1. The cytotoxicity was associated with production of nitric oxide without any direct involvement in the cytotoxic effect. At the ultrastructural level, treated cells displayed a typical apoptotic morphology which was not accompanied by internucleosomal cleavage of DNA as shown by conventional electrophoresis.


Virus-like particles in Australia antigen-associated hepatitis. An immunoelectron microscopic study of human liver.
IN A PREVIOUS REPORT (HUANG SN: Hepatitis-associated antigen hepatitis: an electron microscopic study. Am J Pathol 64:483-500, 1971) liver biopsies of renal transplant patients who developed chronic progressive viral hepatitis associated with persistence of Australia antigenemia [Au(1)] while under immunosuppressive therapy were studied. Predominantly intranuclear 210-250 A spherical, virus-like particles were revealed in 12 of 13 biopsies examined by electron microscope. No such particles were found in biopsies from Australia antigen negative patients. To investigate the relationship of these virus-like particles to Australia antigen, 2 of the Au(1) hepatitis renal transplant patients were restudied 6 to 8 months later. Liver biopsy material was prepared for light microscopy, immunofluorescent microscopy, electron microscopy and immunoelectron microscopy. The specificity of the anti-Au(1) serum used in this study was ascertained by immunodiffusion and immunoelectrophoresis, and by immunoelectron microscopic studies of the antigen-antibody complex prepared in vitro by mixing the ferritin-conjugated anti-Au(1) reagent with the purified Au(1) particles. Electron microscopy of biopsies from liver not treated with antibody showed that virus-like particles persisted in liver cells. Immunofluorescent microscopy of teased liver biopsy suspensions showed nuclear and some cytoplasmic fluorescence, indicating the cellular localization of Au(1). The immunoelectron microscopic preparations showed agglutination of the virus-like particles and the presence of antibody coupled ferritin in the intranuclear and cytoplasmic particle agglutinates. No virus-like particles were seen in the biopsy from a control patient without Au(1) antigenemia, and results of the immunoelectron microscopic procedure were negative. Our observations that massive amounts of Au(1)-associated particles are located in liver cell nuclei of individuals with chronic active hepatitis strengthen the hypothesis of Blumberg et al that Au(1) is an infectious agent and/or the antigenic determinant of a hepatitis virus.


Hypertension and plasma renin activity in experimentally induced chronic pyelonephritis.
The present authors conducted a series of experiments with mongrel dogs, in which unilateral chronic pyelonephritis was induced and postoperative changes in blood pressure and plasma renin activity were observed over a period of 3 months. The pyelonephritis infection was brought about by a method involving vesicoureteral reflux and ureteral dysfunction, as described in a previous paper. Pre- and postoperative levels of systolic pressure were compared, but no definite trends were found for the first 3 weeks after operation. At 30, 60 and 90 days the pressures were found to have risen by 21.2 +/- 14.6 and 17.1 +/- 16.7 mm Hg, respectively. No appreciable change in the plasma renin activity was found, however, at any stage. From these results it was concluded that experimentally induced chronic pyelonephritis in dogs caused a rise in blood pressure. No connection between the pyelonephritis and the renin angiotensin system was found.


Marine fouling release silicone/carbon nanotube nanocomposite coatings: on the importance of the nanotube dispersion state.
The present work reports on the influence of the dispersion quality of multiwall carbon nanotubes (MWCNTs) in a silicone matrix on the marine fouling-release performance of the resulting nanocomposite coatings. A first set of coatings filled with different nanofiller contents was prepared by the dilution of a silicone/MWCNTs masterbatch within a hydrosilylation-curing polydimethylsiloxane resin. The fouling-release properties of the nanocomposite coatings were studied through laboratory assays with the marine alga (seaweed) Ulva, a common fouling species. As reported previously (see Ref. [19]), the addition of a small (0.05%) amount of carbon nanotubes substantially improves the fouling-release properties of the silicone matrix. This paper shows that this improvement is dependent on the amount of filler, with a maximum obtained with 0.1 wt% of multiwall carbon nanotubes (MWCNTs). The method of dispersion of carbon nanotubes in the silicone matrix is also shown to significantly (p = 0.05) influence the fouling-release properties of the coatings. Dispersing 0.1% MWCNTs using the masterbatch approach yielded coatings with circa 40% improved fouling-release properties over those where MWCNTs were dispersed directly in the polymeric matrix. This improvement is directly related to the state of nanofiller dispersion within the cross-linked silicone coating.


Direct medical expenditure associated with rheumatoid arthritis in a nationally representative sample from the medical expenditure panel survey.
To quantify the incremental direct medical expenditure associated with rheumatoid arthritis (RA) in the US population from a payer's perspective. A probability-weighted sample of adult respondents from the Medical Expenditure Panel Survey (2008) was used to identify a cohort of patients with RA and compared to a control cohort without RA. Annual expenditure outcomes, including total expenditure and subgroups related to pharmacy, office-based visits, emergency department visits, hospital inpatient stays, and residual expenditures were estimated. Differences between the RA and control cohort were adjusted for sociodemographic factors, employment status, insurance coverage, health behavior, and health status using a generalized linear model with log link and gamma distribution. Statistical inferences on difference in expenditures between RA and non-RA controls were based on nonparametric cluster bootstrapping using percentiles. The adjusted average annual total expenditure of the RA cohort in 2008 US dollars (USD) was $13,012 (95% confidence interval [95% CI] $1,737-$47,081), while that of the control cohort was $4,950 (95% CI $567-$17,425). The incremental total expenditure of the RA patients as compared to non-RA controls was $2,085 (95% CI $250-$7,822). RA patients also had a significantly higher pharmacy expenditure of $5,825 (95% CI $446-$30,998) that was on average $1,380 (95% CI $94-$7,492) higher as compared to the controls. The summated total incremental expenditure of all RA patients in the US was $22.3 billion (2008 USD). RA exerts considerable incremental economic burden on US health care, which is primarily driven by the incremental pharmacy expenditure.


Palliation of dysphagia from inoperable oesophageal carcinoma using Atkinson tubes or self-expanding metal stents.
Until recently, intubation for the palliation of malignant dysphagia has relied upon the insertion of a variety of plastic tubes. Self-expanding metal stents are reported to have a lower complication rate. We have compared the results of Atkinson tube insertion with self-expanding metal stents in patients with inoperable oesophageal carcinoma. From 1990 to 1994 Atkinson tubes were inserted for the palliation of dysphagia from oesophageal cancer, from 1994 onwards self-expanding metal stents were used. Complications, mortality and hospital stay were compared in both groups of patients. In all, 87 patients with inoperable oesophageal carcinoma were treated, 46 with an Atkinson tube and 41 with metal stents. Complications occurred at similar rates in both groups (56% Atkinson tubes, 44% metal stents). There was a significantly higher perforation rate associated with Atkinson tube insertion (8 patients, 17%) compared with metal stents (1 patient, 2.4%, P = 0.02, chi 2). The length of stay was also significantly higher in the Atkinson tube group (median 10 days) compared with the metal stent group (3 days, P < 0.01, Mann-Whitney U test). Mortality rates were similar in both groups. The use of metal stents for the palliation of dysphagia in inoperable oesophageal carcinoma results in a lower perforation rate and a reduced length of stay and they represent a significant advantage over Atkinson tubes.


Optimizing Ambulance Transport of Hemodialysis Patients to the Emergency Department: A Cohort Study.
Dialysis patients who require ambulance transport to the emergency department ("ambulance-ED") may subsequently require timely dialysis in a monitored setting ("urgent dialysis"). The purpose of this study was to develop and internally validate a risk prediction model for urgent dialysis based on patient characteristics at the time of paramedic assessment before ambulance-ED. Cohort Study. Region of Nova Scotia, Canada, covered by a single emergency medical services provider. Thrice-weekly hemodialysis patients who initiated dialysis between 2009 and 2013 (follow-up to 2015) and experienced one or more ambulance-ED events. The primary outcome ("urgent dialysis") was defined as dialysis within 24 hours of an ambulance-ED in a monitored setting or dialysis within 24 hours of an ambulance-ED with an initial ED potassium of >6.5 mmol/L. Predictors of urgent dialysis based on paramedic assessment before ambulance-ED included presenting complaint, vital signs and time from last dialysis to ambulance dispatch. Associations with urgent dialysis were analyzed using logistic regression from which a risk prediction model was created. The model was internally validated using bootstrapping and model performance was assessed by discrimination and calibration. Among 197 patients, there were 624 ambulance-ED events and 87 episodes of urgent dialysis. Weakness as a presenting complaint (odds ratio [OR]: 4.62, 95% confidence interval [CI]: 1.23-17.29), >24 hours since last dialysis (OR: 2.09, 95% CI: 1.15-3.81), and vital signs, including heart rate <60 beats/minute (OR: 3.06, 95% CI: 1.09-8.61), oxygen saturation <90% (OR: 3.04, 95% CI: 1.55-5.94), elevated respiratory rate (≥20 breaths/min), and systolic blood pressure>160 mmHg, were associated with urgent dialysis after ambulance-ED. A risk prediction model incorporating these variables had very good discrimination (C-statistic: 0.81, 95% CI: 0.76-0.86). The negative predictive value was 93.6% using the optimal cut point. Of patients who were predicted to need urgent dialysis but were transported to a facility incapable of providing it, 31% were re-transported for urgent dialysis. Findings of our study may not be generalizable to other centers where the practice of ambulance transfer and availability of monitored dialysis may differ, and data were lacking for potential missed dialysis sessions or changes in routine dialysis scheduling. Patient characteristics at the time of paramedic assessment are associated with urgent dialysis after ambulance-ED. This risk prediction model has the potential to guide dialysis patient transport to dialysis-capable facilities when needed.


Human Ovarian Cortex biobanking: A Fascinating Resource for Fertility Preservation in Cancer.
Novel anti-cancer treatments have improved the survival rates of female young patients, reopening pregnancy issues for female cancer survivors affected by the tumor treatment-related infertility. This condition occurs in approximately one third of women of fertile age and is mainly dependent on gonadotoxic protocols, including radiation treatments. Besides routine procedures such as the hormonal induction of follicular growth and subsequent cryopreservation of oocytes or embryos, the ovarian protection by gonadotropin-releasing hormone (GnRH) agonists during chemotherapy as well as even gonadal shielding during radiotherapy, other innovative techniques are available today and need to be optimized to support their introduction into the clinical practice. These novel methods are hormone stimulation-free and include the ovarian cortex cryopreservation before anti-cancer treatments and its subsequent autologous reimplantation and a regenerative medicine approach using oocytes derived in vitro from ovarian stem cells (OSCs). For both procedures, the major benefit is related to the prompt recruitment and processing of the ovarian cortex fragments before gonadotoxic treatments. However, while the functional competence of oocytes within the cryopreserved cortex is not assessable, the in vitro maturation of OSCs to oocytes, allows to select the most competent eggs to be cryopreserved for fertility restoration.


Antioxidant Activity Derived from Marine Green-Lipped Mussel Perna canaliculus Extracts in Mice.
This study investigates the antioxidant activities of lipid, protein, and carbohydrate extracts from the marine mollusk Perna canaliculus. Lipids were extracted using acetone, which was followed by protein extraction using the broad-spectrum enzyme Alcalase and then carbohydrate extraction using cetylpyridinium chloride. Eighty white BALB/c mice were divided into eight groups according to the administered extracts. Groups 1 and 5 were the control and toxin control groups, respectively. Groups 2, 3, and 4 were administered lipid, protein, and carbohydrate extracts, respectively. The other groups were administered P. canaliculus extracts as well as gentamicin and acetaminophen, known as ethanolic extracts, derived from Nerium oleander to induce oxidation stress. All groups showed significant improvements in body weight (p < 0.05). The lipid extract group showed a significant decrease in low-density lipoprotein cholesterol (p < 0.05) and a significant increase in high-density lipoprotein cholesterol (p < 0.05). After the toxin injection, all groups treated with P. canaliculus extracts showed increased antioxidant effects on hepatocytes (p < 0.05). The lipid extracts induced antioxidant effects to protect the kidney by increasing lipid peroxidation (p < 0.05) and catalase activities (p < 0.05). Also, protein extracts showed antioxidant effects by increasing glutathione and catalase levels significantly (p < 0.005). In conclusion, P. canaliculus extracts, especially lipids and proteins, have potent antioxidant activities that protect vital organs from oxidation stress.


[Dynamic path analysis on life course epidemiology].
In the studies of modern epidemiology, exposure in a short term cannot fully elaborate the mechanism of the development of diseases or health-related events. Thus, lights have been shed on to life course epidemiology, which studies the exposures in early life time and their effects related to the development of chronic diseases. When exploring the mechanism leading from one exposure to an outcome and its effects through other factors, due to the existence of time-variant effects, conventional statistic methods could not meet the needs of etiological analysis in life course epidemiology. This paper summarizes the dynamic path analysis model, including the model structure and significance, and its application in life course epidemiology. Meanwhile, the procedure of data processing and etiology analyzing were introduced. In conclusion, dynamic path analysis is a useful tool which can be used to better elucidate the mechanisms that underlie the etiology of chronic diseases.


Electrochemical Oxidation as a Tool for Generating Vitamin D Metabolites.
The electrochemical behavior of the vitamers cholecalciferol and ergocalciferol was investigated in order to determine whether it is possible to evaluate phase-I and phase-II metabolism of these steroids and yield metabolites that can serve as reference material. The vitamers were electrochemically-oxidized using an electrochemical system (ROXY™ EC system). The influence of pH value, solvent, and potential was evaluated. When using methanol or ethanol, the formation of artificial methoxy or ethoxy groups, respectively, was observed, while the use of acetonitrile did not show any formation of further functional groups. A neutral pH value and use of a constant potential led to the highest number of oxidation products with intensive signals. Additionally, a binding study between vitamin D and glucuronic acid as an example for phase-II conjugation was carried out. It was possible to detect adduct formation. Coupling mass spectrometry directly to electrochemistry (EC-MS) is a promising approach for generating vitamin D metabolites and/or yielding a number of metabolites without in vivo or in vitro test systems. It can support or even replace animal studies in the long-term and might be promising for yielding reference compounds.


Recent advances and clinical insights into the use of proteomics in the study of atherosclerosis.
The application of new proteomics methods may help to identify new diagnostic/predictive molecular markers in an attempt to improve the clinical management of atherosclerosis. Areas covered: Technological advances in proteomics have enhanced its sensitivity and multiplexing capacity, as well as the possibility of studying protein interactions and tissue structure. These advances will help us better understand the molecular mechanisms at play in atherosclerosis as a biological system. Moreover, this should help identify new predictive/diagnostic biomarkers and therapeutic targets that may facilitate effective risk stratification and early diagnosis, with the ensuing rapid implementation of treatment. This review provides a comprehensive overview of the novel methods in proteomics, including state-of-the-art techniques, novel biological samples and applications for the study of atherosclerosis. Expert commentary: Collaboration between clinicians and researchers is crucial to further validate and introduce new molecular markers to manage atherosclerosis that are identified using the most up to date proteomic approaches.


Biogeography, succession, and origin of the chicken intestinal mycobiome.
Extensive work has been accomplished to characterize the intestinal bacterial community, known as the microbiota, and its association with host health and disease. However, very little is known about the spatiotemporal development and the origin of a minor intestinal fungal community, known as the mycobiota, in humans and animals, particularly in avian species. In this study, we comprehensively characterized the biogeography and succession of the gastrointestinal (GI) mycobiota of broiler chickens and further revealed the fungal sources that are responsible for initial and long-term establishment of the mycobiota in the GI tract. Using Illumina sequencing of the internal transcribed spacer 2 (ITS2) region of fungal rRNA genes, we detected significant spatial and temporal differences in the mycobiota along the GI tract. In contrary to the microbiota, the mycobiota was more diverse in the upper than the lower GI tract with no apparent trend of succession up to 42 days of age. The intestinal mycobiota was dominated by the phyla Ascomycota and Basidiomycota with Gibberella, Aspergillus, and Candida being the most abundant genera. Although the chicken mycobiota was highly dynamic, Fusarium pseudonygamai was dominant throughout the GI tract regardless of age in this study. The core chicken mycobiome consisted of 26 fungal taxa accounting for greater than 85% of the fungal population in each GI location. However, we observed high variations of the intestinal mycobiota among different studies. We also showed that the total fungal population varied greatly from 1.0 × 104 to 1.1 × 106 /g digesta along the GI tract and only accounted for less than 0.06% of the bacteria in day-42 broilers. Finally, we revealed that the mycobiota from the hatchery environment was responsible for initial colonization in the GI tract of newly hatched chickens, but was quickly replaced by the fungi in the diet within 3 days. Relative to the intestinal microbiota that consists of trillions of bacteria in hundreds of different species and becomes relatively stabilized as animals age, the chicken intestinal mycobiota is a minor microbial community that is temporally dynamic with limited diversity and no obvious pattern of successive changes. However, similar to the microbiota, the chicken mycobiota is spatially different along the GI tract, although it is more diverse in the upper than the lower GI tract. Dietary fungi are the major source of the intestinal mycobiota in growing chickens. Video abstract.


Outcome of cataract operations performed to permit diagnosis, to determine eligibility for laser therapy, or to perform laser therapy of retinal disorders.
Cataract operations may be recommended when retinal disease is suspected but cannot be adequately diagnosed or treated because of lens opacity. We evaluated the outcome of cataract operations performed under those circumstances. We reviewed the records of 119 patients who were examined at the Wilmer Retinal Vascular Center and within three months underwent a cataract operation. We identified 17 patients (20 eyes) who underwent a cataract operation at the recommendation of a retinal specialist, to permit diagnosis, to determine eligibility for laser therapy, or to perform laser therapy. After the cataract operation, eight (40%) of the 20 eyes were found to have a retinal disease for which laser therapy was recommended, and six (30%) of the 20 eyes underwent laser therapy that, before the cataract operation, had been impossible. These results indicate that a cataract operation may be useful when lenticular opacity prevents diagnosis or treatment in a patient with a suspected retinal disorder.


[Intraocular injections of bevacizumab in rare indications--two cases].
Intravitreal anti-VEGF injections are currently the most effective treatment option for neovascular age-related macular degeneration. The anti-VEGF treatment of other, more common ocular diseases, such as diabetic retinopathy and vascular occlusions with neovascularization and retinal edema, is currently described in numerous studies and cases. Rare neovascular ocular diseases, such as Eales disease, presumed ocular histoplasmosis syndrome (POHS), retinopathy of prematurity, and idiopathic telangiectasia, may be future areas for anti-VEGF therapy. In our case report we describe intravitreal bevacizumab (Avastin) therapy for central serous chorioretinopathy and for pseudoxanthoma elasticum with angioid streaks and choroidal neovascularization. In both cases the intravitreal injection resulted in morphological and functional rehabilitation.


Infection control measures on ships and in ports during the early stage of pandemic influenza A (H1N1) 2009.
Shipping companies were surveyed to evaluate the effect of public health measures during the influenza A (H1N1) pandemic of 2009 on ship and port operations. Of 31 companies that operated 960 cruise, cargo, and other ships, 32% experienced health-screening measures by port health authorities. Approximately a quarter of ports (26%) performed screening at embarkation and 77% of shipping companies changed procedures during the early stage of the pandemic. Four companies reported outbreaks of pandemic influenza A (H1N1) 2009 on ships, which were ultimately stopped through infection control practices. Public health measures did not interfere substantially with port and ship operations with the exception of some port authorities that delayed embarking and disembarking procedures in a few ships. However, in the shipping companies' experience, measures were inconsistent between port health authorities. Access to antiviral drugs and pandemic vaccine was not provided in all ports. Current guidelines on medical care, hygiene, and emergency procedures on ships need to address pandemic influenza preparedness in future revisions.


Unique pattern of enzootic primate viruses in Gibraltar macaques.
Because Gibraltar's macaques (Macaca sylvanus) have frequent contact with humans, we assayed 79 macaques for antibodies to enzootic primate viruses. All macaques were seronegative for herpesvirus B, simian T-cell lymphotropic virus, simian retrovirus, simian immunodeficiency virus, and rhesus cytomegalovirus. Seroprevalence of simian foamy virus reached 88% among adult animals.


Complete remission of two canine cases with precursor-targeted immune-mediated anemia after combination therapy with prednisolone, cyclosporine, and oclacitinib.
Precursor-targeted immune-mediated anemia (PIMA) has been described in dogs presenting with nonregenerative anemia and evidence of ineffective erythropoiesis. Although it has been suggested that its occurrence may be related to the immune targeting of erythroid precursors, this pathogenesis has not been established. PIMA is mainly treated with glucocorticoids, and in cases where glucocorticoids alone are not effective, immunosuppressants are also used as combination therapy. However, not all cases of PIMA go into remission after these treatments. Two dogs with severe nonregenerative anemia diagnosed as PIMA based on the results of clinical pathological examinations, including bone marrow examination, were treated with whole-blood transfusion and immunosuppressive doses of prednisolone, mycophenolate mofetil, and cyclosporine. However, these treatments failed to achieve remission of PIMA. Therefore, concomitant administration of oclacitinib, which is a Janus kinase-1 inhibitor that has been applied recently to the treatment of immune-mediated diseases, was performed; this combined regimen improved the anemia and achieved complete remission of PIMA. Oclacitinib may be an option for the treatment of PIMA in dogs failing to achieve remission with conventional immunosuppressive therapy.


Negative and positive interpretations of emotionally neutral situations modulate the desire to eat personally craved foods.
Emotions play an important role in modulating food craving. Previous studies demonstrated that exposure to negative or positive stimuli can subsequently influence the desire to eat. However, in many daily situations, individuals self-generate their emotions, for example, by interpreting emotionally-neutral situations as positive or negative. So far, no studies have examined if and how positive and negative interpretations of emotionally-neutral situations modulate food craving. In this study, 65 healthy participants were asked to interpret emotionally-neutral images negatively or positively or observe the images naturally. Subsequently, participants rated their state negative/positive affect and their desire to eat their personally craved foods. The results demonstrate a lower desire to eat craved foods after negative interpretations and a higher desire to eat after positive interpretations, compared to an observe-naturally condition. Additionally, the impact of emotional interpretations on the desire to eat was mediated by participants' state negative/positive affect. These findings suggest that self-generated emotion as a result of negative/positive interpretations plays a significant role in modulating food craving. The results highlight the potential of modifying affective interpretations for the treatment of disorders that are characterized by both dysregulated food craving and emotion.


Maximum-likelihood scintillation detection for EM-CCD based gamma cameras.
Gamma cameras based on charge-coupled devices (CCDs) coupled to continuous scintillation crystals can combine a good detection efficiency with high spatial resolutions with the aid of advanced scintillation detection algorithms. A previously developed analytical multi-scale algorithm (MSA) models the depth-dependent light distribution but does not take statistics into account. Here we present and validate a novel statistical maximum-likelihood algorithm (MLA) that combines a realistic light distribution model with an experimentally validated statistical model. The MLA was tested for an electron multiplying CCD optically coupled to CsI(Tl) scintillators of different thicknesses. For (99m)Tc imaging, the spatial resolution (for perpendicular and oblique incidence), energy resolution and signal-to-background counts ratio (SBR) obtained with the MLA were compared with those of the MSA. Compared to the MSA, the MLA improves the energy resolution by more than a factor of 1.6 and the SBR is enhanced by more than a factor of 1.3. For oblique incidence (approximately 45°), the depth-of-interaction corrected spatial resolution is improved by a factor of at least 1.1, while for perpendicular incidence the MLA resolution does not consistently differ significantly from the MSA result for all tested scintillator thicknesses. For the thickest scintillator (3 mm, interaction probability 66% at 141 keV) a spatial resolution (perpendicular incidence) of 147 µm full width at half maximum (FWHM) was obtained with an energy resolution of 35.2% FWHM. These results of the MLA were achieved without prior calibration of scintillations as is needed for many statistical scintillation detection algorithms. We conclude that the MLA significantly improves the gamma camera performance compared to the MSA.


Probing the interactions of phosphosulfomannans with angiogenic growth factors by surface plasmon resonance.
The binding interactions of the phosphosulfomannan anticancer agent PI-88 (1) with the angiogenic growth factors FGF-1, FGF-2, and VEGF were studied by surface plasmon resonance (SPR) on a BIAcore 3000 biosensor. Compared with heparin, PI-88 has at least 11-fold higher affinity for FGF-1 and at least 3-fold higher affinity for VEGF, but at least 13-fold lower affinity for FGF-2. To define the structural features of PI-88 that are important for growth factor binding, several analogues, such as dephosphorylated PI-88 and a sulfated pentasaccharide, were prepared. The binding interactions of these analogues with FGF-1, FGF-2, and VEGF were similarly studied by SPR, and structure-activity relationships were determined.


Probing Gelation and Rheological Behavior of a Self-Assembled Molecular Gel.
Molecular gels have been investigated over the last few decades; however, mechanical behavior of these self-assembled gels is not well understood, particularly how these materials fail at large strain. Here, we report the gelation and rheological behavior of a molecular gel formed by self-assembly of a low molecular weight gelator (LMWG), di-Fmoc-l-lysine, in 1-propanol/water mixture. Gels were prepared by solvent-triggered technique, and gelation was tracked using Fourier transform infrared (FTIR) spectroscopy and shear rheology. FTIR spectroscopy captures the formation of hydrogen bonding between the gelator molecules, and the change in IR spectra during the gelation process correlates with the gelation kinetics results captured by rheology. Self-assembly of gelator molecules leads to a fiber-like structure, and these long fibers topologically interact to form a gel-like material. Stretched-exponential function can capture the stress-relaxation data. Stress-relaxation time for these gels have been found to be long owing to long fiber dimensions, and the stretching exponent value of 1/3 indicates polydispersity in fiber dimensions. Cavitation rheology captures fracture-like behavior of these gels, and critical energy release rate has been estimated to be of the order 0.1 J/m2. Our results provide new understanding of the rheological behavior of molecular gels and their structural origin.


Radio frequency scanning tunneling spectroscopy for single-molecule spin resonance.
We probe nuclear and electron spins in a single molecule even beyond the electromagnetic dipole selection rules, at readily accessible magnetic fields (few mT) and temperatures (5 K) by resonant radio-frequency current from a scanning tunneling microscope. We achieve subnanometer spatial resolution combined with single-spin sensitivity, representing a 10 orders of magnitude improvement compared to existing magnetic resonance techniques. We demonstrate the successful resonant spectroscopy of the complete manifold of nuclear and electronic magnetic transitions of up to ΔI(z)=±3 and ΔJ(z)=±12 of single quantum spins in a single molecule. Our method of resonant radio-frequency scanning tunneling spectroscopy offers, atom-by-atom, unprecedented analytical power and spin control with an impact on diverse fields of nanoscience and nanotechnology.


Physical-chemical properties of precipitated and fractionated allergens from Mycobacterium bovis.
Seven allergens were prepared from cultures of Mycobacterium bovis. The culture filtrates were divided in half and each aliquot precipitated with either ammonium sulfate or trichloroacetic acid to prepare purified protein derivatives (PPD). These samples of PPD-bovis were analyzed for nitrogen, carbohydrate, RNA and DNA. Physical tests, such as: cellulose acetate electrophoresis, disc gel electrophoresis, ultracentrifugation, isoelectricfocusing and gel filtration were also performed. Precipitation with ammonium sulfate provided PPD's with less impurities than those precipitated with trichloroacetic acid although there was little difference in the allergenic activity of the products precipitated by either method. Several lots of PPD-bovis were fractionated by means of ultrafiltration and the fractions analyzed by many of the above chemical and physical tests as well as tests for amino acid composition and allergenic activity. The greatest amount of protein was found in the fractions with an apparent molecular weight in excess of 300,000. The carbohydrate was usually distributed in proportion to the amount of protein in each fraction while the nucleic acids were predominately found in the higher molecular weight fractions. The amino acid analysis and allergenic activity of the various molecular weight fractions provided data that would support the theory that the various fractions are polymers of a small molecular weight sub-unit. The number of amino acid residues were calculated and the minimum molecular weight of the tubercular protein estimated to be 8700. The estimated molecular weights of the fractions and the amino acid data concur with those previously reported for proteins from other mycobacteria.


Electronic structure, optical properties and the mechanism of the B3-B8 phase transition of BeSe: insights from hybrid functionals, lattice dynamics and NPH molecular dynamics.
We have investigated the electronic structure and the mechanism of the pressure induced phase transition of beryllium selenide (BeSe) by employing a first-principles pseudopotential method within the framework of density functional theory. Our study demonstrates that use of the hybrid PBE0 functional (PBE stands for Perdew, Burke and Ernzerhof) leads to significant improvement in the band gap calculations, compared to those using either of the common density functionals (local density approximation (LDA) and generalized gradient approximation (GGA)), which severely underestimate the band gap of BeSe. The band gap obtained from the hybrid PBE0 functional shows excellent agreement with available experimental data. A constant-pressure (NPH) first-principles molecular dynamics (FPMD) approach has been adopted to characterize the first-order pressure induced phase transition from the zinc blende (ZB) to the nickel arsenide (NiAs) structure. We have shown that the FPMD simulation overestimates the transition pressure P(T) (compared to static enthalpy and experimental data) due to overpressure in the simulation box. The MD simulation reveals the structural pathway (cubic → orthorhombic → monoclinic → hexagonal), leading from the ZB phase to the NiAs phase. To find an explanation for the phase transition we calculated the vibrational and elastic properties under pressure. Negative Grüneisen parameters were obtained for the transverse acoustic phonon modes at the X and L high symmetry points. However, no mechanical instability or imaginary frequencies were found at pressures near P(T). Thus the transition results from a thermodynamic instability rather than an elastic/dynamical one. We have also calculated the optical properties of both the B3 and B8 phases, such as the real and imaginary parts of the dielectric constant, reflectivity, loss function and refractive index, and compared them with the existing experimental and theoretical data. An abrupt decrease is obtained from the reflectivity spectrum of the NiAs phase at P(T), which is supported from the peaks in the loss function.


Overexpression of IκBα in cardiomyocytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation.
Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway. The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins. IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation. IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.


Early expression of IL-10, IL-12, ARG1, and NOS2 genes in peripheral blood mononuclear cells synergistically correlate with patient outcome after burn injury.
No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. This prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells. We then performed confirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid quantitative polymerase chain reaction. Findings were validated and modeled associations with clinical outcomes using a regression model. A total of 149 genes with a significant difference in expression from burn patients compared with controls were identified. Pathway analysis identified pathways related to interleukin (IL)-10 and inducible nitric oxide synthase signaling to have significant z scores. quantitative polymerase chain reaction analysis of IL-10, IL-12, arginase 1 (ARG1), and inducible nitric oxide synthase demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of nitric oxide synthase 2 (NOS2) and IL-12. Burn severity, acute lung injury, development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2, and (ARG1-IL-10)/(NOS2-IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1-IL-10)/(NOS2-IL-12) significantly correlated with burn severity and development of acute lung injury. We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction. Prognostic/Epidemiological; Level II.


A self-contained photoacid generator for super acid based on photochromic terarylene.
A self-contained photoacid generator for super acid along with the photoinduced 6π-electrocyclization reaction of the terarylene backbone is demonstrated. The photoinitiated cationic polymerization of epoxy-monomers is achieved with an efficient photochemical quantum yield, Φacid = 0.47.