The Influences of Montesquieu on American Ideals

The ideologies of French philosopher, Charles de Secondat Baron de Montesquieu, played a prominent role in the founding of the American governmental system in the realm of Separation of Powers. Within his work, Spirit of Laws, he emphasizes the need for a government to separate executive, legislative, and judicial powers by the means of checks and balances. The Federalists support and uphold the idea of a “balanced democracy” within Federalist No. 47. In opposition, the Anti-Federalists describe in Anti-Federalist No. 46-47 their concerns regarding the responsibilities ensured by the separation of powers; they believe that the legislative branch should assume the most power of the three branches in which the most responsibility would be applied. Thus, with responsibility in the American government, liberty could only then be prosperous. The exchanges of political thought between the Federalists and the Anti-Federalists promote the need for continued discussions in modern-day America, as well as the importance of defending one’s ideologies with substantial evidence to effectively support or refute a concept

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring : Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

Aim. - To assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery. Methods. - For the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) >= 30 kg/m(2) and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Ageand gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance. Results. - Offspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P= 0.010). Offspring body composition was similar in both groups (P> 0.05). Conclusion. - The lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age. (C) 2019 Elsevier Masson SAS. All rights reserved.Peer reviewe

Work careers in adults separated temporarily from their parents in childhood during World War II

Introduction: Traumatic experiences, such as separation from parents in childhood causing early life stress (ELS) may increase the risk of adverse long-term health outcomes and biological age-related changes. This may have an impact on work career. Our aim was to examine long term consequences of ELS due to temporary separation from parents during World War II (WWII) in relation to work career. Material and methods: The Helsinki Birth Cohort Study comprises 13,345 individuals born in Helsinki, Finland, between the years 1934-1944. From the original cohort, 1781 individuals were identified as being separated temporarily from their parents due to World War II. Information on date and type of pension was provided by the Finnish Centre for Pensions and the Social Insurance Institution of Finland. The cohort members either transitioned into old age pension at the statutory retirement age or retired earlier and transitioned into disability, unemployment, part-time pension or died before retirement. Results: Those who were separated were more likely to have transitioned into disability pension (RRR: 1.26: 95% CI: 1.06-1.48), especially due to diseases of the musculoskeletal system (OR: 1.57; 95% CI: 1.20-2.07), or into unemployment pension (RRR: 1.25; 95% CI: 1.02-1.53) compared with those not separated from their parents. Longer duration of separation was associated with early exit from the workforce compared with non-separation. Conclusions: Exposure to ELS may have an impact upon lifetime work career. Early interventions preventing exposure to ELS or mitigating its negative effects may prolong future work careers along with healthier aging across the life-span.Peer reviewe

Depressive symptoms and mortality-findings from Helsinki birth cohort study

Background: Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon.Methods: One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated.Results: Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02-2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85-1.44)] and melancholic depressive [1.26 (95% CI: 0.87-1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73-0.93)].Conclusions: Melancholic depressive symptoms are most strongly related to a higher mortality risk.</p

Overexpression of cathepsin f, matrix metalloproteinases 11 and 12 in cervical cancer

BACKGROUND: Cervical carcinoma (CC) is one of the most common cancers among women worldwide and the first cause of death among the Mexican female population. CC progression shows a continuum of neoplastic transitions until invasion. Matrix metalloproteinases (MMPs) and cathepsins play a central role on the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. MMPs -2 and -9 expression has been widely studied in cervical cancer. Nevertheless, no other metalloproteinases or cathepsins have been yet related with the progression and/or invasion of this type of cancer. METHODS: Three HPV18 CC cell lines, two HPV16 CC cell lines and three HPV16 tumor CC tissues were compared with three morphologically normal, HPV negative, cervical specimens by cDNA arrays. Overexpression of selected genes was confirmed by end point semiquantitative reverse transcription-PCR with densitometry. In situ hybridization and protein expression of selected genes was further studied by means of two tissue microarrays, one consisting of 10 HSIL and 15 CC and the other one of 15 normal cervical and 10 LSIL tissues. RESULTS: TIMP1, Integrins alpha 1 and 4, cadherin 2 and 11, Cathepsins F, B L2, MMP 9, 10 11 and 12 were upregulated and Cathepsin S, L, H and C, Cadherins 3 and 4, TIMP3, MMP 13, Elastase 2 and Integrin beta 8 were found to be downregulated by cDNA arrays. Endpoint RT-PCR with densitometry gave consistent results with the cDNA array findings for all three genes selected for study (CTSF, MMP11 and MMP12). In situ hybridization of all three genes confirmed overexpression in all the HSIL and CC. Two of the selected proteins were detected in LSIL, HSIL and CC by immunohistochemistry. CONCLUSION: Novel undetected CC promoting genes have been identified. Increased transcription of these genes may result in overexpression of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the pathogenesis of CC

Activating mutation in MET oncogene in familial colorectal cancer

<p>Abstract</p> <p>Background</p> <p>In developed countries, the lifetime risk of developing colorectal cancer (CRC) is 5%, and it is the second leading cause of death from cancer. The presence of family history is a well established risk factor with 25-35% of CRCs attributable to inherited and/or familial factors. The highly penetrant inherited colon cancer syndromes account for approximately 5%, leaving greater than 20% without clear genetic definition. Familial colorectal cancer has been linked to chromosome 7q31 by multiple affected relative pair studies. The <it>MET </it>proto-oncogene which resides in this chromosomal region is considered a candidate for genetic susceptibility.</p> <p>Methods</p> <p><it>MET </it>exons were amplified by PCR from germline DNA of 148 affected sibling pairs with colorectal cancer. Amplicons with altered sequence were detected with high-resolution melt-curve analysis using a LightScanner (Idaho Technologies). Samples demonstrating alternative melt curves were sequenced. A TaqMan assay for the specific c.2975C <b>></b>T change was used to confirm this mutation in a cohort of 299 colorectal cancer cases and to look for allelic amplification in tumors.</p> <p>Results</p> <p>Here we report a germline non-synonymous change in the <it>MET </it>proto-oncogene at amino acid position T992I (also reported as <it>MET </it>p.T1010I) in 5.2% of a cohort of sibling pairs affected with CRC. This genetic variant was then confirmed in a second cohort of individuals diagnosed with CRC and having a first degree relative with CRC at prevalence of 4.1%. This mutation has been reported in cancer cells of multiple origins, including 2.5% of colon cancers, and in <1% in the general population. The threonine at amino acid position 992 lies in the tyrosine kinase domain of MET and a change to isoleucine at this position has been shown to promote metastatic behavior in cell-based models. The average age of CRC diagnosis in patients in this study is 63 years in mutation carriers, which is 8 years earlier than the general population average for CRC.</p> <p>Conclusions</p> <p>Although the <it>MET </it>p.T992I genetic mutation is commonly found in somatic colorectal cancer tissues, this is the first report also implicating this <it>MET </it>genetic mutation as a germline inherited risk factor for familial colorectal cancer. Future studies on the cancer risks associated with this mutation and the prevalence in different at-risk populations will be an important extension of this work to define the clinical significance.</p