Diabetes mellitus and risk of pancreatic cancer: A meta-analysis of cohort studies

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X–Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner’s syndrome and in phenotypic differences between the sexes in health and disease.

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

Medications, psychotherapy, and other treatments are effective for many patients with psychiatric disorders. However, with currently available interventions, a substantial number of patients experience incomplete resolution of symptoms, and relapse rates are high. In the search for better treatments, increasing interest has focused on focal neuromodulation. This focus has been driven by improved neuroanatomical models of mood, thought, and behavior regulation, as well as by more advanced strategies for directly and focally altering neural activity. Deep brain stimulation (DBS) is one of the most invasive focal neuromodulation techniques available; data have supported its safety and efficacy in a number of movement disorders. Investigators have produced preliminary data on the safety and efficacy of DBS for several psychiatric disorders, as well. In this review, we describe the development and justification for testing DBS for various psychiatric disorders, carefully consider the available clinical data, a...

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Deep brain stimulation for psychiatric disorders.

Breaking the loop: oxytocin as a potential treatment for drug addiction.

Increasing evidence suggests that a history of diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC). To provide a quantitative assessment of the association between DM and risk of CRC, We evaluated the relation between DM and incidence and mortality of CRC in a systematic review of cohort studies. Full publications of cohort studies were identified in MEDLINE, EMBASE and Science Citation Index Expanded, through February 28, 2011. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were summarized using a random-effects model. Between-study heterogeneity was assessed using the Cochran’s Q and I2 statistics. A total of 41 cohort studies (35 articles) were included in this systematic review. Combining 30 cohort studies which presented results on diabetes and CRC incidence, diabetes was associated with an increased incidence of CRC (SRRs 1.27, 95% CI: 1.21–1.34), with evident heterogeneity among studies (P = 0.002, I2 = 48.4%). Subgroup analysis and meta-regression analysis by controlling the confounders showed that the increased incidence of CRC was independent of geographic locations, sex, family history of colorectal cancer, smoking, physical activity and body mass index. Diabetes was also positively associated with CRC mortality (SRR 1.20, 95% CI: 1.03–1.40), with evidence of heterogeneity between studies (P < 0.001, I2 = 81.4%). Results from this systematic review support that compared to non-diabetic individuals, diabetic individuals have an increased risk of CRC.

Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies

Type 2 diabetes mellitus has been associated with an increased risk of a variety of cancers in observational studies, but few have reported the relationship between diabetes and cancer risk in men and women separately. The main goal of this retrospective cohort study was to evaluate the sex-specific risk of incident overall and site-specific cancer among people with DM compared with those without, who had no reported history of cancer at the start of the follow-up in January 2000. During an average of 8 years of follow-up (SD = 2.5), we documented 1,639 and 7,945 incident cases of cancer among 16,721 people with DM and 83,874 free of DM, respectively. In women, DM was associated with an adjusted hazard ratio of 1.96 (95% CI: 1.53-2.50) and 1.41 (95% CI: 1.20-1.66) for cancers of genital organs and digestive organs, respectively. A significantly reduced HR was observed for skin cancer (0.38; 95% CI: 0.22-0.66). In men with DM, there was no significant increase in overall risk of cancer. DM was related with a 47% reduction in the risk of prostate cancer. These findings suggest that the nature of the association between DM and cancer depends on sex and specific cancer site.

Diabetes and risk of incident cancer: a large population-based cohort study in Israel

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

Birth weight is the single most significant determinant of infant mortality and the chances of a newborn to experience healthy development. Low birth weight also appears to be related to higher risks of several important chronic conditions, such as ischemic heart disease, non-insulin-dependent diabetes, and cancer in adults. Thus factors that influence in utero growth and birth weight may have a serious effect on health outcomes many years later in life. Analysis of seasonal variations in birth weights may enable us to suggest specific factors that influence this measure. In this review we summarize the literature on seasonal variations in birth weight. Although causes of seasonal variation in developing regions are more clearly understood, it is not yet clear which factors affect apparent seasonal variation in birth weight in developed countries. In our analysis we observed a pattern of seasonal variations in developed countries that differed between low-, middle-, and high-latitude countries, and we suggest several mechanisms that may be responsible for this diversity. Namely, we suggest that in middle-latitude climates, the large annual temperature range may cause low birth weights during summer, whereas in high- and low-latitude regions variations in sunlight exposure between seasons may contribute to low birth weights apparent during winter. Identification of the suggested causal environmental factors may have public health implications in the development of primary prevention programs for low birth weight and macrosomia in developed countries.

Seasonality in Birth Weight: Review of Global Patterns and Potential Causes

http://people.socsci.tau.ac.il/mu/daphnajoel/files/2014/11/Klavir2009.pdf

High frequency stimulation and pharmacological inactivation of the subthalamic nucleus reduces 'compulsive' lever-pressing in rats.

Different lines of evidence point to dysfunction of basal ganglia-thalamocortical circuits in obsessive-compulsive disorder (OCD). It has been hypothesized that the circuits' dysfunction in OCD may be characterized by a relative under-activity of the indirect compared with the direct pathway within these circuits. The present study tested whether lesions of the subthalamic nucleus (STN), a major node of the indirect pathway, would affect compulsive behavior, using the signal attenuation rat model of OCD. In this model, compulsive lever-pressing is induced by the attenuation of an external signal of reward delivery; an attenuation that is hypothesized to simulate the deficient response feedback suggested to underlie obsessions and compulsions in patients with OCD. Rats sustaining lesions to the STN showed a selective increase in compulsive lever-pressing compared with sham-operated rats. A post mortem biochemical analysis revealed a decrease in serotonin content in the prelimbic and infralimbic cortices, caudate-putamen (but not nucleus accumbens), globus pallidus and substantia nigra-ventral tegmental area, as well as a decrease in dopamine content in the caudate-putamen in STN-lesioned compared with sham rats. A comparison to recent findings that lesions to the orbitofrontal cortex, which also result in a selective increase in compulsive lever-pressing, lead to a decrease in serotonin and dopamine content in the caudate-putamen suggests that there may be a final common pathway by which different brain pathologies may lead to a pro-compulsive state.

http://people.socsci.tau.ac.il/mu/daphnajoel/files/2014/11/Winter2008.pdf

Shira Flash

Papers

Diabetes and risk of incident cancer: a large population-based cohort study in Israel

Sex differences in psychiatric disorders: what we can learn from sex chromosome aneuploidies

Seasonality in Birth Weight: Review of Global Patterns and Potential Causes

High frequency stimulation and pharmacological inactivation of the subthalamic nucleus reduces 'compulsive' lever-pressing in rats.

The role of the subthalamic nucleus in 'compulsive' behavior in rats.