Investigation of the Effect of MDM2 SNP309 and TP53 Arg72Pro Polymorphisms on the Age of Onset of Cutaneous Melanoma

Melanoma accounts for the majority of deaths from skin cancer. Women tend to be diagnosed at a younger age and have better survival than men. A tumor–host interaction might be responsible for these gender-specific differences. Recently, a functional single-nucleotide polymorphism in the promoter of the human homolog of mouse double minute 2 (MDM2) gene was characterized: single-nucleotide polymorphism (SNP)309 increases the MDM2 transcription. In melanoma, the effects for SNP309 and the related tumor protein p53 (TP53) Arg72Pro are inconsistent among published reports. This study investigated the association between SNP309 (RefSNP accession ID (rs)2279744) and TP53 codon 72 (rs1042522) polymorphisms, with outcome in a hospital-based cohort of 990 patients with melanoma. We assessed whether these polymorphisms were associated with clinicopathological and phenotypic characteristics and whether these SNPs affect the age of onset of the disease, recurrence, and survival. No significant associations were found between the SNPs and survival. However, women carrying the SNP309 GG genotype were less likely to be diagnosed at a younger age: odds ratioadjusted<50 0.52 (0.29–0.92). Our results suggest that women carrying the SNP309 GG genotype might be at lower risk of developing melanoma at a younger age compared with those carrying TG or TT. Further studies are needed to determine whether a nearby functional polymorphism is responsible for this effect in premenopausal women

Safety and Immunogenicity of the Live Attenuated Varicella Vaccine Following T Replete or T Cell-Depleted Related and Unrelated Allogeneic Hematopoietic Cell Transplantation (alloHCT)

There are limited studies assessing the live attenuated varicella vaccine following allogeneic hematopoietic cell transplantation (alloHCT). Because of the morbidity of varicella acquired after childhood, we immunized and retrospectively analyzed the safety and immunogenicity of this vaccine in 46 varicella zoster virus (VZV) seronegative patients <20 years old at HCT who achieved a CD4 cell count ≥200/μL, were off immunosuppression, and responded to ≥1 post-HCT vaccines. Two vaccinated patients lacking follow-up titers were excluded from analysis. Stem cells were derived from an HLA-matched sibling (n = 18) or an alternative (HLA mismatched related or unrelated) donor (n = 26). Median time to vaccination was 4 years. Sixty-four percent of patients seroconverted following 1 immunization. There was no significant difference in response between recipients of a matched related or alternative donor graft (P = .2) or between those given a T cell-depleted or T-replete alternative donor graft (P = .27). Three of 44 patients developed a self-limited varicella-like rash within 2.5 weeks of immunization. With a median follow-up of 29.1 (range: 6.9-167.1) months, there were no subsequent cases of varicella-like rashes. No patient developed shingles. This study suggests that this vaccine is safe and immunogenic when given according to preset clinical and immunologic milestones, warranting larger prospective studies in patients ≥24 months following HCT as outlined in current post-HCT vaccine guidelines

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Seroepidemiology of coxsackievirus A6, coxsackievirus A16, and Enterovirus 71 infections among children and adolescents in Singapore, 2008-2010

10.1371/journal.pone.0127999PLoS ONE105e012799

Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of ch

Multi-institutional development and external validation of a nomogram to predict recurrence after curative resection of pancreatic neuroendocrine tumors

Objective: To develop a nomogram estimating the probability of recurrence free at 5 years after resection for localized grade 1 (G1)/ grade 2 (G2) pancreatic neuroendocrine tumors (PanNETs). Background: Among patients undergoing resection of PanNETs, approximately 17% experience recurrence. It is not established which patients are at risk, with no consensus on optimal follow-up. Method: A multi-institutional database of patients with G1/G2 PanNETs treated at 2 institutions was used to develop a nomogram estimating the rate of freedom from recurrence at 5 years after curative resection. A second cohort of patients from 3 additional institutions was used to validate the nomogram. Prognostic factors were assessed by univariate analysis using Cox regression model. The nomogram was internally validated using bootstrap resampling method and on the external cohort. Performance was assessed by concordance index (c-index) and a calibration curve. Results: The nomogram was constructed using a cohort of 632 patients. Overall, 68% of PanNETs were G1, the median follow-up was 51 months, and we observed 74 recurrences. Variables included in the nomogram were the number of positive nodes, tumor diameter, Ki-67, and vascular/perineural invasion. The model bias-corrected c-index from the internal validation was 0.85, which was higher than European Neuroendocrine Tumors Society/American Joint Committee on Cancer 8th staging scheme (c-index 0.76, P = &lt;0.001). On the external cohort of 328 patients, the nomogram c-index was 0.84 (95% confidence interval 0.79–0.88). Conclusion: Our externally validated nomogram predicts the probability of recurrence-free survival at 5 years after PanNETs curative resection, with improved accuracy over current staging systems. Estimating individual recurrence risk will guide the development of personalized surveillance programs after surgery

Individuals with chronic low back pain have greater difficulty in engaging in positive lifestyle behaviours than those without back pain: An assessment of health literacy

Background: Despite the large volume of research dedicated to understanding chronic low back pain (CLBP), patient outcomes remain modest while healthcare costs continue to rise, creating a major public health burden. Health literacy - the ability to seek, understand and utilise health information - has been identified as an important factor in the course of other chronic conditions and may be important in the aetiology of CLBP. Many of the currently available health literacy measurement tools are limited since they measure narrow aspects of health literacy. The Health Literacy Measurement Scale (HeLMS) was developed recently to measure broader elements of health literacy. The aim of this study was to measure broad elements of health literacy among individuals with CLBP and without LBP using the HeLMS.Methods: Thirty-six community-dwelling adults with CLBP and 44 with no history of LBP responded to the HeLMS. Individuals were recruited as part of a larger community-based spinal health study in Western Australia. Scores for the eight domains of the HeLMS as well as individual item responses were compared between the groups.Results: HeLMS scores were similar between individuals with and without CLBP for seven of the eight health literacy domains (p &gt; 0.05). However, compared to individuals with no history of LBP, those with CLBP had a significantly lower score in the domain &lsquo;Patient attitudes towards their health&rsquo; (mean difference [95% CI]: 0.46 [0.11- 0.82]) and significantly lower scores for each of the individual items within this domain (p &lt; 0.05). Moderate effect sizes ranged from d = 0.47-0.65.Conclusions: Although no differences were identified in HeLMS scores between the groups for seven of the health literacy domains, adults with CLBP reported greater difficulty in engaging in general positive health behaviours. This aspect of health literacy suggests that self-management support initiatives may benefit individuals with CLBP.<br /

Consumers’ experiences of back pain in rural Western Australia: Access to information and services, and self-management behaviours.

Background: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. Methods: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals’ access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. Results: Five key themes were identified that affected individuals’ experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP.Conclusions: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care

GWAS analysis of handgrip and lower body strength in older adults in the CHARGE consortium

Decline in muscle strength with aging is an important predictor of health trajectory in the elderly. Several factors, including genetics, are proposed contributors to variability in muscle strength. To identify genetic contributors to muscle strength, a meta-analysis of genomewide association studies of handgrip was conducted. Grip strength was measured using a handheld dynamometer in 27 581 individuals of European descent over 65 years of age from 14 cohort studies. Genomewide association analysis was conducted on ~2.7 million imputed and genotyped variants (SNPs). Replication of the most significant findings was conducted using data from 6393 individuals from three cohorts. GWAS of lower body strength was also characterized in a subset of cohorts. Two genomewide significant (P-value< 5 × 10−8) and 39 suggestive (P-value< 5 × 10−5) associations were observed from meta-analysis of the discovery cohorts. After meta-analysis with replication cohorts, genomewide significant association was observed for rs752045 on chromosome 8 (β = 0.47, SE = 0.08, P-value = 5.20 × 10−10). This SNP is mapped to an intergenic region and is located within an accessible chromatin region (DNase hypersensitivity site) in skeletal muscle myotubes differentiated from the human skeletal muscle myoblasts cell line. This locus alters a binding motif of the CCAAT/enhancer-binding protein-β (CEBPB) that is implicated in muscle repair mechanisms. GWAS of lower body strength did not yield significant results. A common genetic variant in a chromosomal region that regulates myotube differentiation and muscle repair may contribute to variability in grip strength in the elderly. Further studies are needed to uncover the mechanisms that link this genetic variant with muscle strength