Surgery in recurrent ovarian cancer

Ovarian cancer is one of the most challenging diseases in gynecologic oncology. The presentation of frequent recurrences requires the establishment and further development of therapy standards for this patient group. Surgery is crucial in the therapy of patients with primary ovarian cancer, and the postoperative residual tumor mass is the most relevant clinical prognostic factor. The surgical management of recurrent disease is still subject to an emotional international discussion. Only a few prospective clinical trials focused on the effects of surgery in relapsed ovarian cancer have been published. The available data show improvements in the prognosis due to complete cytoreduction in the setting of recurrence. However, the selection of eligible patients is the essential issue. Therefore, the establishment of reliable predictive factors for complete tumor resection as well as a definition of the group of patients who might profit from this approach remains a field for research. Further randomized trials designed to develop and incorporate operative standards for recurrent ovarian cancer should follow

Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically.</p> <p>Case presentation</p> <p>We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation.</p> <p>Conclusion</p> <p>The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma). In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.</p

Zebrafish Krüppel-Like Factor 4a Represses Intestinal Cell Proliferation and Promotes Differentiation of Intestinal Cell Lineages

BACKGROUND:Mouse krüppel-like factor 4 (Klf4) is a zinc finger-containing transcription factor required for terminal differentiation of goblet cells in the colon. However, studies using either Klf4(-/-) mice or mice with conditionally deleted Klf4 in their gastric epithelia showed different results in the role of Klf4 in epithelial cell proliferation. We used zebrafish as a model organism to gain further understanding of the role of Klf4 in the intestinal cell proliferation and differentiation. METHODOLOGY/PRINCIPAL FINDINGS:We characterized the function of klf4a, a mammalian klf4 homologue by antisense morpholino oligomer knockdown. Zebrafish Klf4a shared high amino acid similarities with human and mouse Klf4. Phylogenetic analysis grouped zebrafish Klf4a together with both human and mouse Klf4 in a branch with high bootstrap value. In zebrafish, we demonstrate that Klf4a represses intestinal cell proliferation based on results of BrdU incorporation, p-Histone 3 immunostaining, and transmission electron microscopy analyses. Decreased PepT1 expression was detected in intestinal bulbs of 80- and 102-hours post fertilization (hpf) klf4a morphants. Significant reduction of alcian blue-stained goblet cell number was identified in intestines of 102- and 120-hpf klf4a morphants. Embryos treated with γ-secretase inhibitor showed increased klf4a expression in the intestine, while decreased klf4a expression and reduction in goblet cell number were observed in embryos injected with Notch intracellular domain (NICD) mRNA. We were able to detect recovery of goblet cell number in 102-hpf embryos that had been co-injected with both klf4a and Notch 1a NICD mRNA. CONCLUSIONS/SIGNIFICANCE:This study provides in vivo evidence showing that zebrafih Klf4a is essential for the repression of intestinal cell proliferation. Zebrafish Klf4a is required for the differentiation of goblet cells and the terminal differentiation of enterocytes. Moreover, the regulation of differentiation of goblet cells in zebrafish intestine by Notch signaling at least partially mediated through Klf4a

Prevalence and age-of-onset distributions of DSM IV mental disorders and their severity among school going Omani adolescents and youths: WMH-CIDI findings

<p>Abstract</p> <p>Background</p> <p>There is a dearth of studies exploring the magnitude of mental disorders amongst adolescents and youths in the Arab world. To our knowledge, this phase 2 survey in Oman is the first nationally representative school-based study to determine the prevalence of DSM-IV mental disorders (lifetime and over the preceding 12 months), their age-of-onset distributions and determine their severity over the past 12 months using the World Mental Health-Composite International Diagnostic Interview, the WMH-CIDI, used for international comparison.</p> <p>Methods</p> <p>A total of 1,682 (91.61%) students out of 1836 students who formed the phase 2 random sub-sample of a multi-stage, stratified, random sampling design (phase 1), participated in the face-to-face structured interview using the Arabic-version of WMH-CIDI 3.0.</p> <p>Results</p> <p>The phase 1 results using the General Health Questionnaire (GHQ-12) and Child Depression Inventory (CDI) showed depressive symptoms to be 17% prevalent in the larger sample of 5409 adolescents and youths. Amongst the phase 2 respondents from this sample, 13.9% had at least one DSM IV diagnostic label. The lifetime prevalence of Major Depressive Disorder (MDD) was 3.0%; Bipolar Mood Disorder (BMD) was 1%, Specific phobia 5.8% and Social phobia 1.6%. The female gender was a strong predictor of a lifetime risk of MDD (OR 3.3, 95% CI 1.7-6.3, <it>p </it>= 0.000); Any Mood Disorders (OR 2.5, 95% CI 1.4-4.3, p = 0.002) and Specific Phobia (OR 1.5, 95% CI 1.0-2.4, p = 0.047). The severity of illness for cases diagnosed with 12 month DSM IV disorders was found to be 80% lower in females (OR 0.2, 95%CI 0.0-0.8). The estimates over the previous 12 month period when compared with the lifetime prevalence showed a 25% to 40% lower prevalence for MDD, Specific phobia, Social phobia, Any Anxiety Disorders (AAD) and Any Mood disorders (AMD) while the rate was 80% lower for Separation Anxiety Disorder/Adult Separation Anxiety (SAD/ASA). Mood disorders were significantly lower in the 14-16 age groups (70% lower) in comparison to the older age groups and AMD showed a linear increase in prevalence across increasing age groups (<it>p </it>= 0.035).</p> <p>Conclusion</p> <p>The implications of the present findings are not clear cut, however this study endorses the adult CIDI studies findings that mental disorders do begin earlier in life. The relatively lower prevalence of DSM IV depressive disorders cautions against any conclusive interpretation of the inflated results based on the exclusive study of the depressive symptoms alone in the same sample in the same time period. The female gender proved to be a strong predictor of lifetime risk of MDD, any mood disorder and specific phobia. Under-reporting by males or some other gender-specific factors may have contributed to such a discrepancy. The odds of the severity of illness for cases with 12 month DSM IV disorders were significantly lower in females.</p

Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury

BACKGROUND: In the present study, by comparing the responses in wild-type mice (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation, (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii) lung Transforming Growth Factor beta1 (TGF-β1) expression. METHODS: Mice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice. RESULTS: The intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly attenuated all of the above indicators of lung damage and inflammation. CONCLUSION: Taken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice

A web-based Alcohol Clinical Training (ACT) curriculum: Is in-person faculty development necessary to affect teaching?

<p>Abstract</p> <p>Background</p> <p>Physicians receive little education about unhealthy alcohol use and as a result patients often do not receive efficacious interventions. The objective of this study is to evaluate whether a free web-based alcohol curriculum would be used by physician educators and whether in-person faculty development would increase its use, confidence in teaching and teaching itself.</p> <p>Methods</p> <p>Subjects were physician educators who applied to attend a workshop on the use of a web-based curriculum about alcohol screening and brief intervention and cross-cultural efficacy. All physicians were provided the curriculum web address. Intervention subjects attended a 3-hour workshop including demonstration of the website, modeling of teaching, and development of a plan for using the curriculum. All subjects completed a survey prior to and 3 months after the workshop.</p> <p>Results</p> <p>Of 20 intervention and 13 control subjects, 19 (95%) and 10 (77%), respectively, completed follow-up. Compared to controls, intervention subjects had greater increases in confidence in teaching alcohol screening, and in the frequency of two teaching practices – teaching about screening and eliciting patient health beliefs. Teaching confidence and teaching practices improved significantly in 9 of 10 comparisons for intervention, and in 0 comparisons for control subjects. At follow-up 79% of intervention but only 50% of control subjects reported using any part of the curriculum (p = 0.20).</p> <p>Conclusion</p> <p>In-person training for physician educators on the use of a web-based alcohol curriculum can increase teaching confidence and practices. Although the web is frequently used for disemination, in-person training may be preferable to effect widespread teaching of clinical skills like alcohol screening and brief intervention.</p

Genome sequencing and comparative genomics of the broad host-range pathogen Rhizoctonia solani AG8

Rhizoctonia solani is a soil-borne basidiomycete fungus with a necrotrophic lifestyle which is classified into fourteen reproductively incompatible anastomosis groups (AGs). One of these, AG8, is a devastating pathogen causing bare patch of cereals, brassicas and legumes. R. solani is a multinucleate heterokaryon containing significant heterozygosity within a single cell. This complexity posed significant challenges for the assembly of its genome. We present a high quality genome assembly of R. solani AG8 and a manually curated set of 13,964 genes supported by RNA-seq. The AG8 genome assembly used novel methods to produce a haploid representation of its heterokaryotic state. The whole-genomes of AG8, the rice pathogen AG1-IA and the potato pathogen AG3 were observed to be syntenic and co-linear. Genes and functions putatively relevant to pathogenicity were highlighted by comparing AG8 to known pathogenicity genes, orthology databases spanning 197 phytopathogenic taxa and AG1-IA.We also observed SNP-level “hypermutation” of CpG dinucleotides to TpG between AG8 nuclei, with similarities to repeat-induced point mutation (RIP). Interestingly, gene-coding regions were widely affected along with repetitive DNA, which has not been previously observed for RIP in mononuclear fungi of the Pezizomycotina. The rate of heterozygous SNP mutations within this single isolate of AG8 was observed to be higher than SNP mutation rates observed across populations of most fungal species compared. Comparative analyses were combined to predict biological processes relevant to AG8 and 308 proteins with effector-like characteristics, forming a valuable resource for further study of this pathosystem. Predicted effector-like proteins had elevated levels of non-synonymous point mutations relative to synonymous mutations (dN/dS), suggesting that they may be under diversifying selection pressures. In addition, the distant relationship to sequenced necrotrophs of the Ascomycota suggests the R. solani genome sequence may prove to be a useful resource in future comparative analysis of plant pathogens

Prospective Monitoring Reveals Dynamic Levels of T Cell Immunity to Mycobacterium Tuberculosis in HIV Infected Individuals

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3–21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from −150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r = 0.6527, p = 0.0114; IP-10: r = 0.6967, p = 0.0056; IP-10+MIG: r = 0.7055, p = 0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting

Gender Equality and Corporate Social Responsibility in the Middle East

This chapter focuses on corporate social responsibility (CSR) in relation to gender equality in the Arab Middle East. It examines the relationship between CSR and gender in the workplace whilst exploring the link between CSR and human resource management (HRM) policies and practices. The chapter first presents some seminal work on gender equality and diversity management, looking at the business case for gender equality within the CSR and HRM contexts, before engaging with relevant work on gender equality in the Arab Middle East. It concludes by offering recommendations on advancing the equality agenda at the macro- and meso-levels, within a framework which recognises the centrality of agency of women, as well as the potential of positive changes through corporations being seen as ‘agents of change’. The chapter advocates for organisational and governmental policies to promote gender equality in the Arab Middle East