High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation

<p>Abstract</p> <p>Background</p> <p>This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery.</p> <p>Methods</p> <p>Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests.</p> <p>Results</p> <p>Seventy-seven percent (482) had a smoking history while 11.3% (71) were current smokers. The length of smoking cessation to cancer diagnosis was <1 year for 56 (13.6%), 1-10 years for 110 (26.8%), 11-20 years for 87 (21.2%), 21-30 years for 66 (16.1%), 31-40 years for 44 (10.7%), 41-50 years for 40 (9.7%) and 51-60 years for 8 (1.9%). The mean cessation was 18.1 ± 15.7 years (n = 411 former smokers). Fifty-nine percent had stage 1 disease and 68.0% had adenocarcinoma. Squamous cell carcinoma was more prevalent in smokers (15.6% vs. 8.3%, p = 0.028); adenocarcinoma was more prevalent in never-smokers (79.9% versus 64.3%, p = 0.0004). The prevalence of adenocarcinoma varied inversely with pack year (p < 0.0001) and directly with years of smoking cessation (p = 0.0005).</p> <p>Conclusions</p> <p>In a surgical lung cancer cohort, the majority of patients were smoking abstinent greater than one decade before the diagnosis of lung cancer.</p

Evaluation of a student-run smoking cessation clinic for a medically underserved population

<p>Abstract</p> <p>Background</p> <p>Smoking is common among medically underserved populations. Accessible resources to encourage and support smoking cessation among these patients are limited. Volunteer medical student-run free smoking cessation clinics may provide an effective option to help these individuals achieve smoking abstinence. In order to demonstrate the feasibility and cost-effectiveness of a student-run clinic, we analyzed a case series of patients receiving care in a medical student-run Smoking Cessation Clinic (SCC) at the Rochester, Minnesota Salvation Army Good Samaritan Health Clinic (GSHC).</p> <p>Findings</p> <p>Between January 2005 and March 2009, 282 cigarette smokers seeking care at the SCC were analyzed. Student providers at the SCC conducted 1652 weekly individual counseling sessions averaging 18 minutes per encounter. Patients were offered a choice of pharmacotherapies including nicotine replacement therapy (NRT), bupropion, and varenicline for up to 12 weeks. Smoking abstinence was confirmed with exhaled carbon monoxide (CO). Thirty-two patients completed the entire 12-week program (11.3%). At last contact, 94 patients (33.3%) abstained from smoking for ≥ 7 days and 39 patients (13.8%) were continuously abstinent for ≥ 4 weeks. The 7-day point prevalence abstinence rates at last contact were 58.6% for varenicline, 41.2% for bupropion, 33.9% for NRT, and 23.5% for bupropion and NRT. Analyzing missing patients as smoking, the 7-day point prevalence abstinence rates were 7.1%, 8.9%, and 8.2%, at 1 month, 2 months, and 3 months after program enrollment, respectively. No serious adverse drug reactions were recorded.</p> <p>Conclusions</p> <p>Our medical student-run smoking cessation clinic provided an effective and safe experience for medically underserved patients who might not otherwise have access to conventional smoking cessation programs because of high cost, lack of insurance, or other disparities. Similar medical student initiatives focusing on healthy lifestyles may be feasible and beneficial for individuals with limited access to healthcare resources.</p

Alternative patterns of sex chromosome differentiation in Aedes aegypti (L).

BACKGROUND: Some populations of West African Aedes aegypti, the dengue and zika vector, are reproductively incompatible; our earlier study showed that divergence and rearrangements of genes on chromosome 1, which bears the sex locus (M), may be involved. We also previously described a proposed cryptic subspecies SenAae (PK10, Senegal) that had many more high inter-sex FST genes on chromosome 1 than did Ae.aegypti aegypti (Aaa, Pai Lom, Thailand). The current work more thoroughly explores the significance of those findings. RESULTS: Intersex standardized variance (FST) of single nucleotide polymorphisms (SNPs) was characterized from genomic exome capture libraries of both sexes in representative natural populations of Aaa and SenAae. Our goal was to identify SNPs that varied in frequency between males and females, and most were expected to occur on chromosome 1. Use of the assembled AaegL4 reference alleviated the previous problem of unmapped genes. Because the M locus gene nix was not captured and not present in AaegL4, the male-determining locus, per se, was not explored. Sex-associated genes were those with FST values ≥ 0.100 and/or with increased expected heterozygosity (H exp , one-sided T-test, p < 0.05) in males. There were 85 genes common to both collections with high inter-sex FST values; all genes but one were located on chromosome 1. Aaa showed the expected cluster of high inter-sex FST genes proximal to the M locus, whereas SenAae had inter-sex FST genes along the length of chromosome 1. In addition, the Aaa M-locus proximal region showed increased H exp levels in males, whereas SenAae did not. In SenAae, chromosomal rearrangements and subsequent suppressed recombination may have accelerated X-Y differentiation. CONCLUSIONS: The evidence presented here is consistent with differential evolution of proto-Y chromosomes in Aaa and SenAae

Environmental risk factors for dementia: a systematic review

Background - Dementia risk reduction is a major and growing public health priority. While certain modifiable risk factors for dementia have been identified, there remains a substantial proportion of unexplained risk. There is evidence that environmental risk factors may explain some of this risk. Thus, we present the first comprehensive systematic review of environmental risk factors for dementia. Methods - We searched the PubMed and Web of Science databases from their inception to January 2016, bibliographies of review articles, and articles related to publically available environmental data. Articles were included if they examined the association between an environmental risk factor and dementia. Studies with another outcome (for example, cognition), a physiological measure of the exposure, case studies, animal studies, and studies of nutrition were excluded. Data were extracted from individual studies which were, in turn, appraised for methodological quality. The strength and consistency of the overall evidence for each risk factor identified was assessed. Results - We screened 4784 studies and included 60 in the review. Risk factors were considered in six categories: air quality, toxic heavy metals, other metals, other trace elements, occupational-related exposures, and miscellaneous environmental factors. Few studies took a life course approach. There is at least moderate evidence implicating the following risk factors: air pollution; aluminium; silicon; selenium; pesticides; vitamin D deficiency; and electric and magnetic fields. Conclusions - Studies varied widely in size and quality and therefore we must be circumspect in our conclusions. Nevertheless, this extensive review suggests that future research could focus on a short list of environmental risk factors for dementia. Furthermore, further robust, longitudinal studies with repeated measures of environmental exposures are required to confirm these associations

Long-read sequencing reveals the complex splicing profile of the psychiatric risk gene CACNA1C in human brain

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline. We identify the full-length coding transcripts of CACNA1C in human brain. CACNA1C is a psychiatric risk gene that encodes the voltage-gated calcium channel CaV1.2. We show that CACNA1C’s transcript profile is substantially more complex than appreciated, identifying 38 novel exons and 241 novel transcripts. Importantly, many of the novel variants are abundant, and predicted to encode channels with altered function. The splicing profile varies between brain regions, especially in cerebellum. We demonstrate that human transcript diversity (and thereby protein isoform diversity) remains under-characterised, and provide a feasible and cost-effective methodology to address this. A detailed understanding of isoform diversity will be essential for the translation of psychiatric genomic findings into pathophysiological insights and novel psychopharmacological targets

Plos Med

Background The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level