Binding and Retrograde Transport of Leukemia Inhibitory Factor by the Sensory Nervous-System

Leukemia inhibitory factor (LIF), a peptide growth factor with multiple activities, has recently been shown to support the generation and survival of sensory neurons in cultures of mouse neural crest and dorsal root ganglia (DRG). We have conducted binding experiments with I-125-LIF on cultures of DRG to determine the receptor distribution for LIF on these cells and found that at least 60% of the sensory neurons in the cultures bound I-125-LIF, all of which could be eliminated by the addition of unlabeled LIF. The other cells in the culture, which morphologically appeared to be Schwann cells, did not bind appreciable quantities of I-125-LIF. In order to investigate whether LIF is retrogradely transported to sensory neurons in vivo, I-125-LIF was injected into the footpads and gastrocnemius muscles of newborn and adult mice, following sciatic nerve ligation. Radioactivity accumulated in the distal portion of the sciatic nerve, indicating retrograde transport of LIF. Subsequent experiments on mice with unligated sciatic nerves showed that I-125-LIF is specifically transported into the sensory neurons of the DRG. There was no apparent transport of I-125-LIF into motor neurons in the spinal cord. These experiments demonstrate that LIF can specifically bind to and be transported by sensory neurons and further support the idea that LIF acts as a target-derived neurotrophic factor, analogous to NGF

Pattern scaling using ClimGen: monthly-resolution future climate scenarios including changes in the variability of precipitation

Development, testing and example applications of the pattern-scaling approach for generating future climate change projections are reported here, with a focus on a particular software application called “ClimGen”. A number of innovations have been implemented, including using exponential and logistic functions of global-mean temperature to represent changes in local precipitation and cloud cover, and interpolation from climate model grids to a finer grid while taking into account land-sea contrasts in the climate change patterns. Of particular significance is a new approach for incorporating changes in the inter-annual variability of monthly precipitation simulated by climate models. This is achieved by diagnosing simulated changes in the shape of the gamma distribution of monthly precipitation totals, applying the pattern-scaling approach to estimate changes in the shape parameter under a future scenario, and then perturbing sequences of observed precipitation anomalies so that their distribution changes according to the projected change in the shape parameter. The approach cannot represent changes to the structure of climate timeseries (e.g. changed autocorrelation or teleconnection patterns) were they to occur, but is shown here to be more successful at representing changes in low precipitation extremes than previous pattern-scaling methods

Perceived Sufficiency of Full-Field Digital Mammograms With and Without Irreversible Image Data Compression for Comparison with Next-Year Mammograms

Problems associated with the large file sizes of digital mammograms have impeded the integration of digital mammography with picture archiving and communications systems. Digital mammograms irreversibly compressed by the novel wavelet Access Over Network (AON) compression algorithm were compared with lossless-compressed digital mammograms in a blinded reader study to evaluate the perceived sufficiency of irreversibly compressed images for comparison with next-year mammograms. Fifteen radiologists compared the same 100 digital mammograms in three different comparison modes: lossless-compressed vs 20:1 irreversibly compressed images (mode 1), lossless-compressed vs 40:1 irreversibly compressed images (mode 2), and 20:1 irreversibly compressed images vs 40:1 irreversibly compressed images (mode 3). Compression levels were randomly assigned between monitors. For each mode, the less compressed of the two images was correctly identified no more frequently than would occur by chance if all images were identical in compression. Perceived sufficiency for comparison with next-year mammograms was achieved by 97.37% of the lossless-compressed images and 97.37% of the 20:1 irreversibly compressed images in mode 1, 97.67% of the lossless-compressed images and 97.67% of the 40:1 irreversibly compressed images in mode 2, and 99.33% of the 20:1 irreversibly compressed images and 99.19% of the 40:1 irreversibly compressed images in mode 3. In a random-effect analysis, the irreversibly compressed images were found to be noninferior to the lossless-compressed images. Digital mammograms irreversibly compressed by the wavelet AON compression algorithm were as frequently judged sufficient for comparison with next-year mammograms as lossless-compressed digital mammograms

The Cytotoxic T Lymphocyte Antigen-4+49A/G Single Nucleotide Polymorphism Association With Visceral Leishmaniasis

Background: Several lines of evidence approve that innate and adaptive immunity play key roles in the defense against visceral leishmaniasis (VL). The polymorphism within the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene alters its expression. Objectives: The main aim of this study was to evaluate the polymorphism within the +49 position of the CTLA-4 gene of Iranian patients with VL in comparison with healthy controls. Materials and Methods: In this cross-sectional study, 88 patients with clinical presentations of VL, who were seropositive for Leishmania (group 1), 86 patients without clinical presentations but seropositive (group 2), and 115 healthy controls (group 3) were assessed with respect to the CTLA-4 +49A/G polymorphism, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The anti-Leishmania antibody titration was evaluated using an immunofluorescence method. Results: Our results indicated that both CTLA-4 +49A/G polymorphisms were significantly associated with VL. Conclusions: According to the results, the polymorphisms within the +49 position of CTLA-4 can be associated with VL and may be considered as risk factors for the disease

Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States.

BACKGROUND: Methylation levels may be associated with and serve as markers to predict risk of progression of precancerous cervical lesions. We conducted an epigenome-wide association study (EWAS) of CpG methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2 +) following an abnormal screening test. METHODS: A prospective US cohort of 289 colposcopy patients with normal or CIN1 enrollment histology was assessed. Baseline cervical sample DNA was analyzed using Illumina HumanMethylation 450K (n = 76) or EPIC 850K (n = 213) arrays. Participants returned at provider-recommended intervals and were followed up to 5 years via medical records. We assessed continuous CpG M values for 9 cervical cancer-associated genes and time-to-progression to CIN2+. We estimated CpG-specific time-to-event ratios (TTER) and hazard ratios using adjusted, interval-censored Weibull accelerated failure time models. We also conducted an exploratory EWAS to identify novel CpGs with false discovery rate (FDR) < 0.05. RESULTS: At enrollment, median age was 29.2 years; 64.0% were high-risk HPV-positive, and 54.3% were non-white. During follow-up (median 24.4 months), 15 participants progressed to CIN2+. Greater methylation levels were associated with a shorter time-to-CIN2+ for CADM1 cg03505501 (TTER = 0.28; 95%CI 0.12, 0.63; FDR = 0.03) and RARB Cluster 1 (TTER = 0.46; 95% CI 0.29, 0.71; FDR = 0.01). There was evidence of similar trends for DAPK1 cg14286732, PAX1 cg07213060, and PAX1 Cluster 1. The EWAS detected 336 novel progression-associated CpGs, including those located in CpG islands associated with genes FGF22, TOX, COL18A1, GPM6A, XAB2, TIMP2, GSPT1, NR4A2, and APBB1IP. CONCLUSIONS: Using prospective time-to-event data, we detected associations between CADM1-, DAPK1-, PAX1-, and RARB-related CpGs and cervical disease progression, and we identified novel progression-associated CpGs. IMPACT: Methylation levels at novel CpG sites may help identify individuals with ≤CIN1 histology at higher risk of progression to CIN2+ and inform risk-based cervical cancer screening guidelines

Pneumonia caused by Moraxella catarrhalis in haematopoietic stem cell transplant patients. Report of two cases and review of the literature

Moraxella catarrhalis is a gram negative diplococcus that causes a variety of upper and lower respiratory tract infections. Patients with malignant, hematological disorders treated with intensive cytotoxic chemotherapy, and recipients of various forms of haematopoietic stem cell transplant receiving immunosuppressive agents are at high risk of developing severe infections and septic complications. Early detection of the organism and prompt treatment with appropriate antibiotics provide both resolution of the infection and prevention of further consequences. Two patients with haematopoietic stem cell transplant who developed pneumonia caused by M. catarrhalis at King Faisal Specialist Hospital and Research Centre in Riyadh are reported and the literature is reviewed. To our knowledge, these are the first case reports of M. catarrhalis pneumonia in haematopoietic stem cell transplant patients

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

A pairwise likelihood augmented Cox estimator for left‐truncated data

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142901/1/biom12746.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142901/2/biom12746-sup-0001-SuppData-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142901/3/biom12746_am.pd