Introduction
The direct relationship between surgical radicality to compensate biologic behavior and improvement of patient outcome at the time of primary or interval cytoreduction remains unclear.
...Objective
The aim of this study was to evaluate the impact of disease extension and surgical complexity on survival after complete macroscopic resection for stage IIIC–IV ovarian cancer.
Materials and Methods
Medical records from seven referral centers in France were reviewed to identify all patients who had complete cytoreductive surgery for stage IIIC–IV epithelial ovarian, fallopian, or primary peritoneal cancer. All patients had at least six cycles of carboplatin and paclitaxel combination therapy.
Results
From the 374 consecutive patients with complete cytoreduction who were included in this study, stage, grade, upper abdominal disease, surgical complexity, and carcinomatosis extent were significantly associated with disease-free survival (DFS) at univariate analysis. Stage IV and the need for ultra-radical procedures were significantly associated with lower overall survival (OS). On multivariate analysis, radical surgery, including more than two visceral resections, was significantly associated with decreased DFS and OS.
Conclusions
Patients who need complex surgical procedures involving two or more visceral resections in order to achieve successful complete cytoreduction have worse outcome than patients with less extensive procedures. The negative impact of surgical complexity was not significant in patients who underwent upfront procedures. Tumor volume and extension were associated with decreased DFS in patients undergoing a primary surgical approach. This adds to the evidence that, even though complete cytoreduction is currently the objective of surgery, tumor load remains an independent poor prognostic factor and probably reflects a more aggressive behavior.
Aims
To examine (1) the prevalence of depressive symptoms in women with Type 2 diabetes, (2) the associations between depressive symptoms and the following dependent variables: sleep disturbance; ...physical activity; physical health‐related; and global quality of life, and (3) the potential moderating effects of antidepressants and optimism on the relationship between depressive symptoms and dependent variables.
Methods
Participants in the Women's Health Initiative who had Type 2 diabetes and data on depressive symptoms (N=8895) were included in the analyses. In multivariable linear regression models controlling for sociodemographic, medical and psychosocial covariates, we examined the main effect of depressive symptoms, as well as the interactions between depressive symptoms and antidepressant use, and between depressive symptoms and optimism, on sleep disturbance, physical activity, physical health‐related quality of life; and global quality of life.
Results
In all, 16% of women with Type 2 diabetes reported elevated depressive symptoms. In multivariable analyses, women with depressive symptoms had greater sleep disturbance (P<0.0001) and lower global quality of life (P<.0001). We found evidence of significant statistical interaction in the models for quality‐of‐life outcomes: the increased risk of poor physical health‐related quality of life associated with antidepressant use was stronger in women without vs with depressive symptoms, and the association between greater optimism and higher global quality of life was stronger in women with vs without depressive symptoms.
Conclusions
To improve health behaviours and quality of life in women with Type 2 diabetes, sociodemographic and medical characteristics may identify at‐risk populations, while psychosocial factors including depression and optimism may be important targets for non‐pharmacological intervention.
What's new?
Depression in women with diabetes is common and has a negative impact on health. Research in large samples is needed to better estimate its prevalence, outcomes and clinical implications.
Among the 8895 participants with Type 2 diabetes in the Women's Health Initiative, 16% reported elevated depressive symptoms, which were associated with greater sleep disturbance and lower quality of life.
Increased risk of poor physical health‐related quality of life associated with antidepressant use was stronger in women without depressive symptoms.
The positive association between optimism and global quality of life was stronger in women with depressive symptoms.
Depression and optimism may be important targets for non‐pharmacological intervention.
The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and ...guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com).
The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs).
This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines.
Median age at diagnosis was 49 years old (range 10–89). The median size of tumor was 94 mm (range 5–400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%).
Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery.
Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.
•Surgical management of GCT is better since the creation of the national network dedicated to rare gynecological tumors.•Surgery is the gold standard treatment for GCT and includes complete surgery.•Better surgical management seems to improve the survival of patients with GCT.
During myelination of the peripheral nervous system, the myelin protein zero (Mpz) gene is induced to produce the most abundant protein component (P0) of mature myelin. Although the basal embryonic ...expression of Mpz in Schwann cells has been attributed to regulation by Sox10, the molecular mechanism for the profound up-regulation of this gene during myelination has not been established. In this study, we have identified a highly conserved element within the first intron of the Mpz gene, which contains binding sites for the early growth response 2 (Egr2/Krox20) transcription factor, a critical regulator of peripheral nerve myelination. Egr2 can transactivate the intron element, and the induction is blocked by two known repressors of Egr2 activity. Using chromatin immunoprecipitation assays, we find that Egr2 binds in vivo to the intron element, but not to the Mpz promoter. Known inducers of Mpz expression such as forskolin and insulin-like growth factor-1 also activate the element in an Egr2-dependent manner. In addition, we found that Egr2 can act synergistically with Sox10 to activate this intron element, suggesting a model in which cooperative interactions between Egr2 and Sox10 mediate a large increase in Mpz expression to the high levels found in myelinating Schwann cells.
Differentiation signaling results in reprogramming of cellular gene expression that leads to morphological changes and functional specialization of a precursor cell. This global change in gene ...expression involves temporal regulation of differentiation-specific genes that are located throughout the genome, raising the idea that genome structure may also be re-organized during cell differentiation to facilitate regulated gene expression. Using in vitro adipocyte differentiation as a model, we explored whether gene organization within the nucleus is altered upon exposure of precursor cells to signaling molecules that induce adipogenesis. The peroxisome proliferator-activated receptor gamma (PPARγ) nuclear hormone receptor is a master determinant of adipogenesis and is required for adipose differentiation. We utilized the chromosome conformation capture (3C) assay to determine whether the position of the PPARγ locus relative to other adipogenic genes is changed during differentiation. We report that the PPARγ2 promoter is transiently positioned in proximity to the promoters of genes encoding adipokines and lipid droplet associated proteins at 6 hours post-differentiation, a time that precedes expression of any of these genes. In contrast, the PPARγ2 promoter was not in proximity to the EF1α promoter, which drives expression of a constitutively active, housekeeping gene that encodes a translation elongation factor, nor was the PPARγ2 promoter in proximity to the promoter driving the expression of the C/EBPα regulatory protein. The formation of the long-range, intergenic interactions involving the PPARγ2 promoter required the regulatory factor C/EBPβ, elevated cyclic AMP (cAMP) levels, and protein kinase A (PKA) signaling. We conclude that genome organization is dynamically remodeled in response to adipogenic signaling, and we speculate that these transient inter-genic interactions may be formed for the purposes of selecting some of the transcriptionally silent tissue-specific loci for subsequent transcriptional activation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Extra TFIIIC (ETC) sites are chromosomal locations bound in vivo by the RNA polymerase III (Pol III) transcription factor III C (TFIIIC) complex, but are not necessarily associated with Pol III ...transcription. Although the location of ETC sequences are conserved in budding yeast, and similar sites are found in other organisms, their functions are largely unstudied. One such site, ETC6 in Saccharomyces cerevisiae, lies upstream of TFC6, a gene encoding a subunit of the TFIIIC complex itself. Promoter analysis shows that the ETC6 B-box sequence is involved in autoregulation of the TFC6 promoter. Mutation of ETC6 increases TFC6 mRNA levels, whereas mutation immediately upstream severely weakens promoter activity. A temperature-sensitive mutation in TFC3 that weakens DNA binding of TFIIIC also results in increased TFC6 mRNA levels; however, no increase is observed in mutants of TFIIIB or Pol III subunits, demonstrating a specific role for the TFIIIC complex in TFC6 promoter regulation. Chromatin immunoprecipitation shows an inverse relationship of TFIIIC occupancy at ETC6 versus TFC6 mRNA levels. Overexpression of TFC6 increases association of TFIIIC at ETC6 (and other loci) and results in reduced expression of a TFC6 promoter-URA3 reporter gene. Both of these effects are dependent on the ETC6 B-box. These results demonstrate that the TFC6 promoter is directly regulated by the TFIIIC complex, a demonstration of an RNA polymerase II promoter being directly responsive to a core Pol III transcription factor complex. This regulation could have implications in controlling global tRNA expression levels.
Germline HAVCR2 mutations, recently identified in a large subset of patients with subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic ...lymphohistiocytosis (HLH). Discovery of this heritable HLH/SPTCL diathesis has expanded our understanding of a rare and molecularly heterogeneous lymphoma. Furthermore, patients with SPTCL have excellent survival unless they develop HLH. Therefore, through compiling data on SPTCL‐related conditions that predispose patients to HLH, we are better able to predict which patients with SPTCL have the greatest risk of mortality. We present the first case of SPTCL with concomitant HLH and autoimmune lymphoproliferative syndrome (ALPS) in a patient who was subsequently diagnosed with familial HLH (F‐HLH) attributable to a germline STXBP2 splice‐site mutation. She had wild‐type HAVCR2. Reports including ours show how SPTCL can evolve in the setting of an exaggerated host inflammatory response attributable to a variety of unusual underlying etiologies.
A new retrieval scheme for cloud optical thickness, effective radius, and thermodynamic phase was developed for ground-based measurements of cloud shortwave solar spectral transmittance. Fifteen ...parameters were derived to quantify spectral variations in shortwave transmittance due to absorption and scattering of liquid water and ice clouds, manifested by shifts in spectral slopes, curvatures, maxima, and minima. To retrieve cloud optical thickness and effective particle radius, a weighted least square fit that matched the modeled parameters was applied. The measurements for this analysis were made with the ground-based Solar Spectral Flux Radiometer in Boulder, Colorado, between May 2012 and January 2013. We compared the cloud optical thickness and effective radius from the new retrieval to two other retrieval methods. By using multiple spectral features, we find a closer fit (with a root mean square difference over the entire spectra of 3.1% for a liquid water cloud and 5.9% for an ice cloud) between measured and modeled spectra compared to two other retrieval methods which diverge by a root mean square of up to 6.4% for a liquid water cloud and 22.5% for an ice cloud. The new retrieval introduced here has an average uncertainty in effective radius (± 1.2 μm) smaller by factor of at least 2.5 than two other methods when applied to an ice cloud.
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