The incompatibility of the United Nations' goals and conventionalist ethical relativism

The Universal Draft Declaration on Bioethics and Human Rights seeks to provide moral direction to nations and their citizens on a series of bioethical concerns. In articulating principles, it ranks respect for human rights, human dignity and fundamental freedoms ahead of respect for cultural diversity and pluralism. This ranking is controversial because it entails the rejection of the popular theory, conventionalist ethical relativism. If consistently defended, this theory also undercuts other United Nations activities that assume member states and people around the world can reach trans-cultural judgments having moral authority about health, pollution, aggression, rights, slavery, and so on. To illustrate problems with conventionalist ethical relativism and the importance of rejecting it for reasons of health, human rights, human dignity and fundamental freedoms, the widespread practice of female genital circumcision or cutting is discussed. These surgeries are virtually a test case for conventionalist ethical relativism since they are widely supported within these cultures as religious and health practices and widely condemned outside them, including by the United Nations.     

Adult obesity does not predict 6-year weight gain in men: the Aerobics Center Longitudinal Study

Objective: To determine the longitudinal relation between history of adult obesity and the 6‐year trajectory of weight change in men. Research Methods and Procedures: Subjects were healthy, affluent men (n = 761) between the ages of 20 and 78 years who completed at least four comprehensive medical exams at the Cooper Clinic between 1987 and 2003. Maximum adult weight was reported, and current height was measured at baseline. Body weight and cardiorespiratory fitness were measured at all examinations. Adult obesity status was determined from self‐reported maximum weight and measured height at baseline as BMI ≥ 30 kg/m². Weight at all examinations was regressed on a history of adult obesity using linear mixed effects modeling. Results: At baseline, men reporting a history of adult obesity were significantly heavier than men reporting no such history (BMI 29.8 vs. 25.0 kg/m²; p < 0.05). However, the rate of weight gain among men with a history of obesity was slower than among men without a history of adult obesity (0.04 vs. 0.18 kg/yr; p = 0.09), although this difference was only marginally significant. Fitness modulated the relationship between history of obesity and weight change over time, and both higher levels of fitness and greater frequency of dieting were associated with attenuated weight gain. In contrast, chronic disease and depression were associated with accelerated weight gain. Discussion: Although a history of obesity was associated with higher weight, it did not seem to result in accelerated weight gain over time. Additionally, dieting and fitness were important for minimizing weight gain.     

A Further Investigation of Combined Mismatch Repair and BRAFV600E Mutation Specific Immunohistochemistry as a Predictor of Overall Survival in Colorectal Carcinoma

Mutation specific immunohistochemistry (IHC) is a promising new technique to detect the presence of the BRAFV600E mutation in colorectal carcinoma (CRC). When performed in conjunction with mismatch repair (MMR) IHC, BRAFV600E IHC can help to further triage genetic testing for Lynch Syndrome. In a cohort of 1426 patients undergoing surgery from 2004 to 2009 we recently demonstrated that the combination of MMR and BRAFV600E IHC holds promise as a prognostic marker in CRC, particularly because of its ability to identify the poor prognosis MMR proficient (MMRp) BRAFV600E mutant subgroup. We attempted to validate combined MMR and BRAFV600E IHC as a prognostic indicator in a separate cohort comprising consecutive CRC patients undergoing surgery from 1998 to 2003. IHC was performed on a tissue microarray containing tissue from 1109 patients with CRC. The 5 year survivals stratified by staining patterns were: MMRd/BRAFwt 64%, MMRd/BRAFV600E 64%, MMRp/BRAFwt 60% and MMRp/BRAFV600E 53%. Using the poor prognosis MMRp/BRAFV600E phenotype as baseline, univariate Cox regression modelling demonstrated the following hazard ratios for death: MMRd/BRAFwt HR = 0.71 (95%CI = 0.40–1.27), p = 0.31; MMRd/BRAFV600E HR = 0.74 (95%CI = 0.51–1.07), p = 0.11 and MMRp/BRAFwt HR = 0.79 (95%CI = 0.60–1.04), p = 0.09. Although the findings did not reach statistical significance, this study supports the potential role of combined MMR and BRAF IHC as prognostic markers in CRC.     

Influence of upper-body external loading on anaerobic exercise performance

The purpose of this study was to assess the threshold where simulated adipose tissue weight gain significantly affects performance in common anaerobic tasks and determine whether differences exist between men and women. Forty-six subjects (men = 21; women = 25) were tested for vertical jump, 20- and 40-yd dash, and 20-yd shuttle tests under 6 different loading conditions (0, 2, 4, 6, 8, and 10% of added body weight). Results were compared to each subject's baseline values (0% loading condition). Results demonstrate significant decrements in performance, starting at the 2% loading condition, for both genders, in every performance test (p < 0.05). On average, subjects jumped 4.91 ± 0.29 to 9.83 ± 0.30 cm less, increased agility test times from 5.49 ± 0.56 to 5.86 ± 0.61 seconds, and increased sprint times from 7.80 ± 0.96 to 8.39 ± 1.07 seconds (2-10%, respectively; p < 0.05). When lower-body power was corrected for total body mass, men exerted significantly more power than women did in every loading condition. Conversely, when lower-body power was corrected for lean body mass, men exerted significantly more power than did women only at the 2% loading condition. This study demonstrates that for the specific anaerobic performance tests performed, increases in external loading as low as 2% of body weight results in significant decreases in performance. Moreover, for these specific tests, men and women tend to express the same threshold in performance decrements.     

New insights into placozoan sexual reproduction and development

Unraveling animal life cycles and embryonic development is basic to understanding animal biology and often sheds light on phylogenetic relationships. A key group for understanding the evolution of the Metazoa is the early branching phylum Placozoa, which has attracted rapidly increasing attention. Despite over a hundred years of placozoan research the life cycle of this enigmatic phylum remains unknown. Placozoa are a unique model system for which the nuclear genome was published before the basic biology (i.e. life cycle and development) has been unraveled. Four organismal studies have reported the development of oocytes and one genetic study has nourished the hypothesis of sexual reproduction in natural populations at least in the past. Here we report new observations on sexual reproduction and embryonic development in the Placozoa and support the hypothesis of current sexual reproduction. The regular observation of oocytes and expressed sperm markers provide support that placozoans reproduce sexually in the field. Using whole genome and EST sequences and additional cDNA cloning we identified five conserved sperm markers, characteristic for different stages in spermatogenesis. We also report details on the embryonic development up to a 128-cell stage and new ultrastructural features occurring during early development. These results suggest that sperm and oocyte generation and maturation occur in different placozoans and that clonal lineages reproduce bisexually in addition to the standard mode of vegetative reproduction. The sum of observations is best congruent with the hypothesis of a simple life cycle with an alternation of reproductive modes between bisexual and vegetative reproduction.     

Distinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cells

Tubulointerstitial injury is a common pathway in progressive renal impairment and human proximal tubular epithelial cells (PTEC) play a crucial role in this process. Kidney injury molecule-1 (KIM-1) has received increasing attention due to its potential utility as the therapeutic target and biomarker for kidney injury. This study aims to explore the underlying mechanism regulating the release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from the apical surface through an ectodomain shedding process mediated by matrix metalloproteinase (MMP), independent of gene expression and protein synthesis. The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time-dependent manner by human serum albumin (HSA) or tumor necrosis factor-α (TNF-α), two important physiological stimuli found during kidney injury. Data from PCR array screening of MMPs gene expression in PTEC following activation by HSA or TNF-α, and from blocking experiments using either synthetic MMP inhibitors or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up-regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of reactive oxygen species. In a mouse model of acute kidney injury induced by ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as their co-localization were observed in kidney from ischemic but not in sham-operated mice. Taken together, these in vitro and in vivo evidences suggest that MMP-3 plays an inductive role in KIM-1 shedding by PTEC.     

Living without mitochondria: spermatozoa and spermatogenesis in two species of Urodasys (Gastrotricha, Macrodasyida) from dysoxic sediments

Abstract. The spermatozoa of two species of Macrodasyida (Gastrotricha), Urodasys anorektoxys and U. acanthostylis , show an ultrastructural organization diverging from one another and from other gastrotrichs: their main peculiarity is in the absence of mitochondria. In U. anorektoxys , the acrosome is a long, twisted column inserted into the nucleus, which is basally cylindrical, and the flagellum shows rows of peculiar, large globules parallel to the axonemal doublets. In U. acanthostylis , the acrosome is completely cork-screwed and surrounds the nucleus, and the tail shows columnar accessory fibers. At present, the absence of mitochondria in the mature sperm, and the peculiar fingerprint aspect of condensed chromatin are the only traits shared by the two species. The features of the spermatozoa of these two species of Urodasys widen the range of different models of gastrotrich spermatozoa, and place the genus in a peculiar position, from the spermatological point of view, within the Macrodasyida. The loss of mitochondria in mature spermatozoa is possibly related to either the dysoxic habitat of the two species or a peculiar fertilization mechanism.