Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

Muscle atrophy and metal-on-metal hip implants

Background and purpose — Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. Patients and methods — We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23–83) years. The median time post-implantation was 83 (35–142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. Results — The median blood cobalt was 6.84 (0.24–90) ppb and median chromium level was 4.42 (0.20–45) ppb. The median Oxford hip score was 34 (5–48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). Interpretation — Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs

MEASUREMENTS OF THE CONFINEMENT LEAKTIGHTNESS AT THE KOLA NUCLEAR POWER STATION (UNIT 2) IN RUSSIA

This is the final report on the INSP project entitled, ``Kola Confinement Leaktightness'' conducted by BNL under the authorization of Project Work Plan WBS 1.2.2.1. This project was initiated in February 1993 to assist the Russians to reduce risks associated with the continued operation of older Soviet-designed nuclear power plants, specifically the Kola VVER-440/230 Units 1 and 2, through upgrades in the confinement performance to reduce the uncontrolled leakage rate. The major technical objective of this-project was to improve the leaktightness of the Kola NPP VVER confinement boundaries, through the application of a variety of sealants to penetrations, doors and hatches, seams and surfaces, to the extent that current technology permitted. A related objective was the transfer, through training of Russian staff, of the materials application procedures to the staff of the Kola NPP. This project was part of an overall approach to minimizing uncontrolled releases from the Kola NPP VVER440/230s in the event of a serious accident, and to thereby significantly mitigate the consequences of such an accident. The US provided materials, application technology, and applications equipment for application of sealant materials, surface coatings, potting materials and gaskets, to improve the confinement leaktightness of the Kola VVER-440/23Os. The US provided for training of Russian personnel in the applications technology

Audition in vampire bats, Desmodus rotundus

1. Within the tonotopic organization of the inferior colliculus two frequency ranges are well represented: a frequency range within that of the echolocation signals from 50 to 100 kHz, and a frequency band below that of the echolocation sounds, from 10 to 35 kHz. The frequency range between these two bands, from about 40 to 50 kHz is distinctly underrepresented (Fig. 3B). 2. Units with BFs in the lower frequency range (10–25 kHz) were most sensitive with thresholds of -5 to -11 dB SPL, and units with BFs within the frequency range of the echolocation signals had minimal thresholds around 0 dB SPL (Fig. 1). 3. In the medial part of the rostral inferior colliculus units were encountered which preferentially or exclusively responded to noise stimuli. — Seven neurons were found which were only excited by human breathing noises and not by pure tones, frequency modulated signals or various noise bands. These neurons were considered as a subspeciality of the larger sample of noise-sensitive neurons. — The maximal auditory sensitivity in the frequency range below that of echolocation, and the conspicuous existence of noise and breathing-noise sensitive units in the inferior colliculus are discussed in context with the foraging behavior of vampire bats

The Impact of Cyberstalking

To access the diversity of the population who define themselves as having been cyberstalked and to assess the levels of anxiety and trauma that victims reported. Participants who were self-defined cyberstalking victims (N = 353) were asked to complete an online survey, which consisted of items relating to the experience of offline harassment and cyberstalking, general anxiety and post-traumatic stress symptoms. Participants were also asked to report on the type of relationship they had with the harasser, changes in working life, relationships, finance and third parties subsequent to the experience of being stalked. Overall, the findings revealed that victims of harassment may suffer high levels of psychological distress as a consequence of the experience, with victims of cyberstalking experiencing psychological effects which are broadly comparable to the symptoms seen in PTSD, leaving the victim experiencing feelings of isolation, irritability and guilt. In addition, as with other research on the effects of adverse experiences on mental health outcomes, the respondents of the survey reported much higher levels of psychological distress than levels that have been reported in the general population. It is suggested that both offline and cyberstalking victims suffer comparable high levels of psychological distress as a consequence of the experience and, despite the wide variation in individual experience and reactions to being cyberstalked, this study was able to determine patterns of psychological distress which were comparable to the symptoms associated with PTSD. Individuals displaying symptoms of PTSD find themselves experiencing adverse effects in major domains of life activity, such as social relations and occupational activities

The Impact of Diet-Induced Weight Loss on Biomarkers for Colorectal Cancer: An Exploratory Study (INTERCEPT)

Objective: The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue. Methods: This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m2 completing an 8-week, complete, low-energy liquid diet. Pre- and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF-1), C-reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki-67), and insulin signaling (phospho-mTOR) were assessed using immunohistochemical staining. Results: Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P < 0.05), but IGF-1 and CRP were not. Colorectal tissue expression of Ki-67 was significantly reduced (preintervention mean score = 7, postintervention mean score = 3.9, mean % change −43.8; P = 0.027). There were no significant changes in M30 or phospho-mTOR. Conclusions: Weight loss in individuals with obesity was associated with improvements in insulin sensitivity and blood lipid profiles and a significant reduction in tissue Ki-67 expression. This is one of the first studies to demonstrate potential cancer-relevant changes in colorectal tissue following weight loss achieved through diet

Who uses NHS health checks? Investigating the impact of ethnicity and gender and method of invitation on uptake of NHS health checks

Background NHS Health Checks is a national risk assessment prevention programme for all individuals aged 40-74 that reside in England. Through the systematic assessment of an individual’s ten year disease risk, this programme aims to provide early identification and subsequent management of this risk. However, there is limited evidence on how socio-demographic factors impact on uptake and what influence the invitation method has on uptake to this programme. Methods NHS Health Check data from April 2013 to March 2014 was analysed (N = 50,485) for all 30 GP Practices in Luton, a culturally diverse town in England, UK. Data was collected for age, ethnicity, uptake (attendance and non attendance) and invitation method (letter written, verbal face-to-face, telephone). Actual usage of NHS Health Checks was determined for each ethnic group of the population and compared using Chi-square analysis. Results The overall uptake rate for Luton was 44 %, markedly lower that the set target of 50–75 %. The findings revealed a variation of uptake in relation to age, gender, level of deprivation. Ethnicity and gender variations were also found, with ‘White British’ ‘Black Caribbean’ and ‘Indian’ patients most likely to take up a NHS Health Check. However, patients from ‘Any Other White Background’ and ‘Black African’ were significantly less likely to uptake an NHS Health Check compared to all other ethnic groups. Ethnicity and gender differences were also noted in relation to invitation method. Conclusions The findings revealed that different invitation methods were effective for different ethnic and gender groups. Therefore, it is suggested that established protocols of invitation are specifically designed for maximizing the response rate for each population group. Future research should now focus on uncovering the barriers to uptake in particular culturally diverse population groups to determine how public health teams can better engage with these communities

Development and validation of a RAD-Seq target-capture based genotyping assay for routine application in advanced black tiger shrimp (Penaeus monodon) breeding programs

Background: The development of genome-wide genotyping resources has provided terrestrial livestock and crop industries with the unique ability to accurately assess genomic relationships between individuals, uncover the genetic architecture of commercial traits, as well as identify superior individuals for selection based on their specific genetic profile. Utilising recent advancements in de-novo genome-wide genotyping technologies, it is now possible to provide aquaculture industries with these same important genotyping resources, even in the absence of existing genome assemblies. Here, we present the development of a genome-wide SNP assay for the Black Tiger shrimp (Penaeus monodon) through utilisation of a reduced-representation whole-genome genotyping approach (DArTseq). Results: Based on a single reduced-representation library, 31,262 polymorphic SNPs were identified across 650 individuals obtained from Australian wild stocks and commercial aquaculture populations. After filtering to remove SNPs with low read depth, low MAF, low call rate, deviation from HWE, and non-Mendelian inheritance, 7542 high-quality SNPs were retained. From these, 4236 high-quality genome-wide loci were selected for baits-probe development and 4194 SNPs were included within a finalized target-capture genotype-by-sequence assay (DArTcap). This assay was designed for routine and cost effective commercial application in large scale breeding programs, and demonstrates higher confidence in genotype calls through increased call rate (from 80.2 ± 14.7 to 93.0% ± 3.5%), increased read depth (from 20.4 ± 15.6 to 80.0 ± 88.7), as well as a 3-fold reduction in cost over traditional genotype-by-sequencing approaches. Conclusion: Importantly, this assay equips the P. monodon industry with the ability to simultaneously assign parentage of communally reared animals, undertake genomic relationship analysis, manage mate pairings between cryptic family lines, as well as undertake advance studies of genome and trait architecture. Critically this assay can be cost effectively applied as P. monodon breeding programs transition to undertaking genomic selection