Relationship between risk information on total colonoscopy and patient preferences for colorectal cancer screening options: Analysis using the Analytic Hierarchy Process

<p>Abstract</p> <p>Background</p> <p>Although the fecal occult blood test (FOBT) is the preferred program for colorectal cancer screening in Japan, many medical institutions have recently begun to provide total colonoscopy (TCS) as an initial screening program. However, there are a number of severe risks associated with TCS, such as colorectal bleeding and perforation. The justification for performing such a procedure on healthy patients remains unclear. We used the analytic hierarchy process (AHP) to investigate whether risk information on TCS affects patient preferences for colorectal cancer screening.</p> <p>Methods</p> <p>We performed a questionnaire survey using an AHP decision-making model, targeting 285 people aged 40–59 years. We randomly assigned the subjects into Groups A (n = 146) and B (n = 139). Both groups were provided with information on the effectiveness, cost and disadvantages of the two screening programs. Group A was provided with additional information regarding the risks of TCS. Individual priorities were calculated with pair-wise comparisons between the two alternatives in each selection criteria. The influence of the risk information was analyzed using a logistic regression analysis.</p> <p>Results</p> <p>The aggregated priorities in Group A for 'effectiveness', 'costs', and 'risks' were 0.603, 0.147, and 0.250, respectively, while those in Group B were 0.652, 0.149, and 0.199, respectively. A logistic regression analysis showed that the provision of risk information significantly reduced the subjects' priorities for TCS (p = 0.036).</p> <p>Conclusion</p> <p>The lack of risk information was related to the differences in priorities assigned to effectiveness and risks of the two procedures. Patients must be well informed before making decisions concerning their preferred colorectal cancer screening procedure.</p

mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1

The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission and fusion, ATP production, metabolite biogenesis and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) protein to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase, dynamin-related protein 1 (DRP1). Potent active-site mTOR inhibitors engender mitochondrial hyperfusion due to the diminished translation of MTFP1 mediated by the translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs). Uncoupling MTFP1 levels from the mTORC1/4EBP pathway upon mTOR inhibition blocks the hyperfusion response and leads to apoptosis by converting mTOR inhibitor action from cytostatic to cytotoxic. These data provide direct evidence for the survival function of mitochondrial hyperfusion upon mTOR inhibition by employing MTFP1 as a critical effector of mTORC1 to govern cell fate decisions

Differential effects on gene transcription and hematopoietic differentiation correlate with GATA2 mutant disease phenotypes

Heterozygous GATA2 mutations underlie an array of complex hematopoietic and lymphatic diseases. Analysis of the literature reporting three recurrent GATA2 germline (g) mutations (gT354M, gR396Q and gR398W) revealed different phenotype tendencies. Although all three mutants differentially predispose to myeloid malignancies, there was no difference in leukemia-free survival for GATA2 patients. Despite intense interest, the molecular pathogenesis of GATA2 mutation is poorly understood. We functionally characterized a GATA2 mutant allelic series representing major disease phenotypes caused by germline and somatic (s) mutations in zinc finger 2 (ZF2). All GATA2 mutants, except for sL359V, displayed reduced DNA-binding affinity and transactivation compared with wild type (WT), which could be attributed to mutations of arginines critical for DNA binding or amino acids required for ZF2 domain structural integrity. Two GATA2 mutants (gT354M and gC373R) bound the key hematopoietic differentiation factor PU.1 more strongly than WT potentially perturbing differentiation via sequestration of PU.1. Unlike WT, all mutants failed to suppress colony formation and some mutants skewed cell fate to granulocytes, consistent with the monocytopenia phenotype seen in GATA2-related immunodeficiency disorders. These findings implicate perturbations of GATA2 function shaping the course of development of myeloid malignancy subtypes and strengthen complete or nearly complete haploinsufficiency for predisposition to lymphedema.C-E Chong, P Venugopal, PH Stokes, YK Lee, PJ Brautigan, DTO Yeung, M Babic, GA Engler, SW Lane, M Klingler-Hoffmann, JM Matthews, RJ D'Andrea, AL Brown, CN Hahn, and HS Scot

Formation of Tc(IV) Oxide Colloids by Bremsstrahlung Irradiation of Aqueous Solutions of Pertechnetate(II. Radiochemistry)

Technetium(IV) oxide colloids (TcO_2・nH_2O) were formed by bremsstrahlung irradiation of aqueous solutions of pertechnetate (TcO_4^-). A transmission electron microscopy (TEM) analysis showed that the size of colloids distributed around 30 to 130 nm in diameter. The characteristic X-rays from technetium and oxygen were detected from colloid particles at the TEM measurements. Round-shaped colloids were produced by the irradiation at 40℃, whereas irregular-shaped colloid particles composed of tiny particles (2 nm in diameter) were produced at 17℃. The concentration of TcO_4^- in the target solution decreased with an increase of the absorbed dose, corresponding to an increase of the colloids yield. The yield of colloids sharply increased in the solution deaerated by Ar bubbling before irradiation, but strongly suppressed in the solution saturated with oxygen (O_2) or nitrous oxide (N_2O) gas. The fact suggests that hydrated electrons play an important role in the course of the reduction of TcO_4^- and that Tc(IV) oxide colloid is formed via successive disproportionation reactions of Tc(VI) and Tc(V)