Self-reported sleep duration and quality and cardiovascular disease and mortality: A dose-response meta-analysis

Background-There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results-We conducted a systematic review, meta-analysis, and spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies. We utilized linear and nonlinear dose-response meta-analysis models and used DerSimonian-Laird random-effects meta-analysis models of risk ratios, with inverse variance weighting, and the I2statistic to quantify heterogeneity. Seventy-four studies including 3 340 684 participants with 242 240 deaths among 2 564 029 participants who reported death events were reviewed. Findings were broadly similar across both linear and nonlinear dose-response models in 30 studies with >1 000 000 participants, and we report results from the linear model. Self-reported duration of sleep >8 hours was associated with a moderate increased risk of all-cause mortality, with risk ratio, 1.14 (1.05-1.25) for 9 hours, risk ratio, 1.30 (1.19-1.42) for 10 hours, and risk ratio, 1.47 (1.33-1.64) for 11 hours. No significant difference was identified for periods of selfreported sleep <7 hours, whereas similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio, 1.44; 95% confidence interval, 1.09-1.90), but no difference in mortality and other outcomes. Conclusions-Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep may be more associated with adverse outcomes compared with shorter sleep durations

Eye bank issues: II. Preservation techniques: warm versus cold storage

Most of the tissue used for penetrating keratoplasty is issued through eye banks that store the corneoscleral button either in hypothermic storage at 2–6°C or in organ culture at 31–37°C

A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease

<p>Abstract</p> <p>Background</p> <p>Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems.</p> <p>Methods</p> <p>To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis.</p> <p>Results</p> <p>We isolated tumor-initiating cells (TICs) by sorting for CD24⁺/CD44^high/ALDH1⁺cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24⁺/CD44^high/ALDH1⁺cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24^-/CD44^-/ALDH1^-cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A).</p> <p>Conclusions</p> <p>Taken together, we have developed a TNBC-TICs model system based on the 4T1 cells which is a very useful metastasis model with the advantage of being able to be transplanted into immune competent recipients. Our data demonstrates that the TNBC-TICs model system could be a useful tool for studies on the pathogenesis and therapeutic treatment for TNBC.</p

Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders

Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms

The Two-Tier Fecal Occult Blood Test: Cost-Effective Screening

The two-tier test represents a strategy combining HO Sensa and Hemeselect fecal occult blood tests (FOBTs) with the aim of greater specificity and consequent economic advantages. If patients register a positive result on any HO Sensa guaiac test, they are once again tested by a hemoglobin-specific Hemeselect test. This concept was applied to a multicentre study involving persons 40 years or older. One component of the study enrolled 573 high risk patients while the second arm recruited an additional 1301 patients (52% asymptomatic/48% symptomatic) stratified according to personal history and symptoms. The two-tier test produced fewer false positives than traditional tests in both groups evaluated in the study. In the high risk group, specificity (88.7% for two-tier versus 80.6% for Hemoccult and 69.5% for HO Sensa) was higher and false positive rates were lower (11.3% for two-tier versus 19.5% for Hemoccultand 30.5% for HO Sensa) for the two-tier test versus Hemoccult and HO Sensa FOBTs (95% CI for all colorectal cancers [CRCs] and polyps greater than 1 cm, α=0.05 ). No significant differences in sensitivity were observed between tests in the same group. Also, in the high risk group, benefits of the two-tier test outweighed the costs. Due to the small number of cancers and polyps in the second arm of the study, presentation of data is meant to be descriptive and representative of trends in a ‘normal’ population. Nevertheless, specificity of the two-tier test was higher (96.8% for two-tier versus 87.2% for Hemoccult and 69.5% for HO Sensa) and false positive rate lower (3.2% for two-tier versus 12.8% for Hemoccult and 22.3% for HO Sensa) than either the Hemoccult or HO Sensa FOBT (95% CI for all CRCs and polyps greater than 1 cm). This initial study, focusing on the cost-benefit relationship of increased specificity, represents a new way of economically evaluating existing FOBTs

Omeprazole Inhibits Acetylsalicylic Acid-Modified Histamine Stimulation of Acid Secretion in Rabbit Gastric Glands

The effects of misoprostol and omeprazole on basal-, histamine- and acetylsalicylic acid (ASA)-induced gastric acid secretion by isolated rabbit gastric glands were studied. The authors found that ASA at a concentration of 2.4×10-3 M significantly inhibited acid secretion in the isolated gastric glands to 65% of basal levels, and that ASA at a concentration of 2.4×l0-2 M significantly inhibited the histamine stimulation of acid secretion to 78% of maximal. Misoprostol inhibited acid secretion to 76% of basal acid secretion, while omeprazole inhibited secretion to 58% of basal values. Misoprostol inhibited the ASA-modified histamine stimulation to 82% of maximal stimulation. In contrast, omeprazole was able to inhibit the ASA-modified histamine stimulation to 48% of maximal. This omeprazole inhibition of secretagogue-induced acid production reduced acid secretion to levels below basal secretion, indicating that neither histamine nor ASA (at the concentrations used), alone or in combination, had any stimulatory effect in the presence of omeprazole. Misoprostol is the recommended drug of choice for prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury. In vitro results suggest that omeprazole appears to treat this condition more effectively if gastric acid secretion is a necessary prerequisite for NSAID-induced mucosal injury