Ejaculate sperm number compensation in stalk-eyed flies carrying a selfish meiotic drive element

Meiotic drive genes cause the degeneration of non-carrier sperm to bias transmission in their favour. Males carrying meiotic drive are expected to suffer reduced fertility due to the loss of sperm and associated harmful side-effects of the mechanisms causing segregation distortion. However, sexual selection should promote adaptive compensation to overcome these deleterious effects. We investigate this using SR, an X-linked meiotic drive system in the stalk-eyed fly, Teleopsis dalmanni. Despite sperm destruction caused by drive, we find no evidence that SR males transfer fewer sperm to the female's spermathecae (long-term storage organs). Likewise, migration from the spermathecae to the ventral receptacle for fertilisation is similar for SR and wildtype male sperm, both over short and long time-frames. In addition, sperm number in storage is similar even after males have mated multiple times. Our study challenges conventional assumptions about the deleterious effects of drive on male fertility. This suggests that SR male ejaculate investment per ejaculate has been adjusted to match sperm delivery by wildtype males. We interpret these results in the light of recent theoretical models that predict how ejaculate strategies evolve when males vary in the resources allocated to reproduction or in sperm fertility. Adaptive compensation is likely in species where meiotic drive has persisted over many generations and predicts a higher stable frequency of drive maintained in wild populations. Future research must determine exactly how drive males compensate for failed spermatogenesis, and how such compensation may trade-off with investment in other fitness traits

Development and initial testing of a computer-based patient decision aid to promote colorectal cancer screening for primary care practice

BACKGROUND: Although colorectal cancer screening is recommended by major policy-making organizations, rates of screening remain low. Our aim was to develop a patient-directed, computer-based decision aid about colorectal cancer screening and investigate whether it could increase patient interest in screening. METHODS: We used content from evidence-based literature reviews and our previous decision aid research to develop a prototype. We performed two rounds of usability testing with representative patients to revise the content and format. The final decision aid consisted of an introductory segment, four test-specific segments, and information to allow comparison of the tests across several key parameters. We then conducted a before-after uncontrolled trial of 80 patients 50–75 years old recruited from an academic internal medicine practice. RESULTS: Mean viewing time was 19 minutes. The decision aid improved patients' intent to ask providers for screening from a mean score of 2.8 (1 = not at all likely to ask, 4 = very likely to ask) before viewing the decision aid to 3.2 afterwards (difference, 0.4; p < 0.0001, paired t-test). Most found the aid useful and reported that it improved their knowledge about screening. Sixty percent said they were ready to be tested, 18% needed more information, and 22% were not ready to be screened. Within 6 months of viewing, 43% of patients had completed screening tests. CONCLUSION: We conclude that a computer-based decision aid can increase patient intent to be screened and increase interest in screening. Practice Implications: This decision aid can be viewed by patients prior to provider appointments to increase motivation to be screened and to help them decide about which modality to use for screening. Further work is required to integrate the decision aid with other practice change strategies to raise screening rates to target levels

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Determining Supersymmetric Parameters With Dark Matter Experiments

In this article, we explore the ability of direct and indirect dark matter experiments to not only detect neutralino dark matter, but to constrain and measure the parameters of supersymmetry. In particular, we explore the relationship between the phenomenological quantities relevant to dark matter experiments, such as the neutralino annihilation and elastic scattering cross sections, and the underlying characteristics of the supersymmetric model, such as the values of mu (and the composition of the lightest neutralino), m_A and tan beta. We explore a broad range of supersymmetric models and then focus on a smaller set of benchmark models. We find that by combining astrophysical observations with collider measurements, mu can often be constrained far more tightly than it can be from LHC data alone. In models in the A-funnel region of parameter space, we find that dark matter experiments can potentially determine m_A to roughly +/-100 GeV, even when heavy neutral MSSM Higgs bosons (A, H_1) cannot be observed at the LHC. The information provided by astrophysical experiments is often highly complementary to the information most easily ascertained at colliders.Comment: 46 pages, 76 figure

A systematic review of interventions to improve knowledge and self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis

This systematic review aimed to determine the effectiveness of interventions for improving knowledge and/or self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis (RA). We searched four databases (MEDLINE, CINAHL, Cochrane Trials, PsycINFO) using a comprehensive search strategy. Studies were eligible if they were prospective, published in English from 2004 to 2015, included participants with RA and tested an intervention designed to improve knowledge and/or self-management skills relating to family planning, pregnancy or breastfeeding. As no studies met the latter criterion, the search strategy was expanded to include all prospective studies evaluating RA educational and/or self-management interventions. Data on study characteristics, participant characteristics and programme content were extracted to summarise the evidence base for interventions to support people with RA during their reproductive years. Expanded literature searches identified 2290 papers, of which 68 were eligible. Of these, nine papers (13 %) specifically excluded pregnant women/breastfeeding mothers or recruited only older people.Only one study (1 %) explicitly evaluated pregnancy-focused education via a motherhood decision aid, while eight studies (12 %) incorporated relevant (albeit minor) components within broader RA educational or self-management interventions. Of these, three studies provided methotrexate education in relation to conception/pregnancy/breastfeeding; three incorporated discussions on RA and relationships, impact of RA on the family or sexual advice; one provided information regarding contraception and fertility; and one issued a warning regarding use of biologic therapy in pregnancy/breastfeeding. In conclusion, information regarding family planning, pregnancy or breastfeeding represents a negligible part of published RA educational interventions, with scope to develop targeted resources

Aerobic Exercise Training Reduces Cannabis Craving and Use in Non-Treatment Seeking Cannabis-Dependent Adults

Cannabis dependence is a significant public health problem. Because there are no approved medications for this condition, treatment must rely on behavioral approaches empirically complemented by such lifestyle change as exercise.To examine the effects of moderate aerobic exercise on cannabis craving and use in cannabis dependent adults under normal living conditions.Participants attended 10 supervised 30-min treadmill exercise sessions standardized using heart rate (HR) monitoring (60-70% HR reserve) over 2 weeks. Exercise sessions were conducted by exercise physiologists under medical oversight.Sedentary or minimally active non-treatment seeking cannabis-dependent adults (n = 12, age 25±3 years, 8 females) met criteria for primary cannabis dependence using the Substance Abuse module of the Structured Clinical Interview for DSM-IV (SCID).Self-reported drug use was assessed for 1-week before, during, and 2-weeks after the study. Participants viewed visual cannabis cues before and after exercise in conjunction with assessment of subjective cannabis craving using the Marijuana Craving Questionnaire (MCQ-SF).Daily cannabis use within the run-in period was 5.9 joints per day (SD = 3.1, range 1.8-10.9). Average cannabis use levels within the exercise (2.8 joints, SD = 1.6, range 0.9-5.4) and follow-up (4.1 joints, SD = 2.5, range 1.1-9.5) periods were lower than during the run-in period (both P<.005). Average MCQ factor scores for the pre- and post-exercise craving assessments were reduced for compulsivity (P  = .006), emotionality (P  = .002), expectancy (P  = .002), and purposefulness (P  = .002).The findings of this pilot study warrant larger, adequately powered controlled trials to test the efficacy of prescribed moderate aerobic exercise as a component of cannabis dependence treatment. The neurobiological mechanisms that account for these beneficial effects on cannabis use may lead to understanding of the physical and emotional underpinnings of cannabis dependence and recovery from this disorder.ClinicalTrials.gov NCT00838448]

Primary Coenzyme Q Deficiency in Pdss2 Mutant Mice Causes Isolated Renal Disease

Coenzyme Q (CoQ) is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment

Measuring Dysfunctional Attitudes in the General Population: The Dysfunctional Attitude Scale (form A) Revised

The Dysfunctional Attitude Scale (DAS) was designed to measure the intensity of dysfunctional attitudes, a hallmark feature of depression. Various exploratory factor analytic studies of the DAS form A (DAS-A) yielded mixed results. The current study was set up to compare the fit of various factor models. We used a large community sample (N = 8,960) to test the previously proposed factor models of the DAS-A using confirmatory factor analysis. The retained model of the DAS-A was subjected to reliability and validity analyses. All models showed good fit to the data. Finally, a two-factor solution of the DAS-A was retained, consisting of 17 items. The factors demonstrated good reliability and convergent construct validity. Significant associations were found with depression. Norm-scores were presented. We advocate the use of a 17-item DAS-A, which proved to be useful in measuring dysfunctional beliefs. On the basis of previous psychometric studies, our study provides solid evidence for a two-factor model of the DAS-A, consisting of ‘dependency’ and ‘perfectionism/performance evaluation’

Colorectal cancer screening among African American church members: A qualitative and quantitative study of patient-provider communication

BACKGROUND: A healthcare provider's recommendation to undergo screening has been shown to be one of the strongest predictors of completing a colorectal cancer (CRC) screening test. We sought to determine the relationship between the general quality of self-rated patient-provider communication and the completion of CRC screening. METHODS: A formative study using qualitative data from focus groups and quantitative data from a cross-sectional survey of church members about the quality of their communication with their healthcare provider, their CRC risk knowledge, and whether they had completed CRC screening tests. Focus group participants were a convenience sample of African American church members. Participants for the survey were recruited by telephone from membership lists of 12 African American churches located in rural counties of North Carolina to participate in the WATCH (Wellness for African Americans Through Churches) Project. RESULTS: Focus Groups. Six focus groups (n = 45) were conducted prior to the baseline survey. Discussions focused on CRC knowledge, and perceived barriers/motivators to CRC screening. A theme that emerged during each groups' discussion about CRC screening was the quality of the participants' communication with their health care provider. Survey. Among the 397 participants over age 50, 31% reported CRC screening within the recommended guidelines. Participants who self-rated their communication as good were more likely to have been screened (36%) within the recommended guidelines than were participants with poor communication (17%) (OR = 2.8, 95% CI 1.2, 6.4; p = 0.013). Participants who had adequate CRC knowledge completed CRC screening at a higher rate than those with inadequate knowledge (p = 0.011). The percentage of participants with CRC screening in the recommended guidelines, stratified by communication and knowledge group were: 42% for good communication/adequate knowledge; 27% for good communication/inadequate knowledge; 29% for poor communication/adequate knowledge; and 5% for poor communication/inadequate knowledge. CONCLUSIONS: Participants who rated their patient-provider communication as good were more likely to have completed CRC screening tests than those reporting poor communication. Among participants reporting good communication, knowledge about colorectal cancer was also associated with test completion. Interventions to improve patient-provider communication may be important to increase low rates of CRC screening test completion among African Americans