Bony spinal canal changes that differentiate conjoined nerve roots from herniated nucleus pulposus

CT examinations of the lumbar spine in 12 consecutive patients with conjoined nerve roots were reviewed. Asymmetry of the bony spinal canal, seen as slight dilatation of the ipsilateral lateral recess, was present in all cases. This finding, which is not typically associated with extruded free intervertebral disk fragments, should serve to distinguish these two entities.     

Computed tomography manifestations of peritoneal diseases

The peritoneal cavity is a potential space that is divided by the peritoneal reflections into various complex subspaces. It can be involved in many disease processes including developmental, inflammatory, neoplastic and traumatic conditions. Computed tomography is highly sensitive and consistent in detecting peritoneal pathology. This pictorial essay aims to emphasize and illustrate the CT features of the spectrum of peritoneal diseases.     

The effects of Rhizoma Curculiginis and Rhizoma Drynariae extracts on bones

Background  

The etiology and treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) remain poorly understood. Pain, lower urinary tract voiding symptoms and negative impact on quality of life (QOL) are the most common complaints. Acupuncture, which has been widely used to treat painful and chronic conditions, may be a potential treatment to alleviate the constellation of symptoms experienced by men with CP/CPPS. The purpose of our study was to assess the impact of standardized full body and auricular acupuncture in men refractory to conventional therapies and collect pilot data to warrant further randomized trials.     

Suicide of older people in Asian societies: an international comparison

Objective : To verify in a systematic study if the Chinese tradition of venerating older people results in lower suicide rates compared to other countries. Method : The ratio between suicide rates in the older population and total population were calculated and used to compare 40 countries. Results : The highest male suicide ratios in the world were found in Urban China, Singapore, Rural China and Hong Kong. Singapore, Urban China and Hong Kong had the worst female suicide ratios. The highest rate of suicide among females was in Rural China, which also had the highest suicide rate among older people. Conclusion : These findings raise questions about the adequacy of support to older Asian people. It is surprising that high suicide rates are found in Hong Kong, Korea, Japan and Singapore, which are affluent societies. The possibility of this being the result of ageism is discussed. Country‐specific research is needed to improve suicide prevention measures, especially for older people.     

新型STAT3信号转导通路抑制剂WP1193在体外对脑肿瘤干细胞生物学特性影响的研究

背景与目的：恶性脑胶质母细胞瘤（glioblastoma Multiforme,GBM）是最常见的成人原发性脑肿瘤,预后仍不理想。近年来,肿瘤干细胞理论认为脑肿瘤干细胞是GBM进展及治疗耐受的主要原因,只有针对脑肿瘤干细胞的靶向治疗才能更加有效的治疗GBM。本研究旨在探讨新型STAT3信号转导通路抑制剂WP1193在体外对脑肿瘤干细胞生物学特性的影响。方法：从新鲜手术切除的GBM标本中,分离、培养及鉴定脑肿瘤干细胞。采用Western blot及RT-PCR法检测WP1193给药后,STAT3信号转导通路的变化。使用神经球形成实验评估WP1193对GBM干细胞形成神经球能力的影响。利用RT-PCR及流式细胞技术检测WP1193对CD133阳性细胞的影响。采用MTS及PI染色结合流式细胞技术检测WP1193对GBM干细胞增殖及细胞周期的影响。采用AnnexinV流式细胞术分析WP1193对GBM干细胞的凋亡诱导效应。结果：WP1193抑制GBM干细胞STAT3磷酸化及下游基因的表达。WP1193有效抑制GBM干细胞形成神经球的能力及增殖,并可将细胞阻滞于G1期。WP1193在体外通过改变Bax/Bcl-2比例诱导GBM干细胞凋亡。结论：WP1193通过抑制STAT3信号转导通路,有效的抑制GBM干细胞的增殖及形成神经球的能力,并能诱导凋亡。STAT3信号转导通路可作为GBM干细胞的治疗靶点。     

Vascular endothelial growth factor regulates myeloid cell leukemia-1 expression through neuropilin-1-dependent activation of c-MET signaling in human prostate cancer cells

Background

Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines.

Results

Three pharmacologic inhibitors of NF-κB differentially inhibited growth in a panel of advanced thyroid cancer cell lines, suggesting that these NF-κB inhibitors may have off-target effects. We therefore used a selective genetic approach to inhibit NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα). These studies revealed decreased cell growth in only one of five thyroid cancer cell lines (8505C), which occurred through a block in the S-G2/M transition. Resistance to TNFα-induced apoptosis was observed in all cell lines, likely through an NF-κB-dependent mechanism. Inhibition of NF-κB by mIκBα sensitized a subset of cell lines to TNFα-induced apoptosis. Sensitive cell lines displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway, defining a potential mechanism of response. Finally, NF-κB inhibition by mIκBα expression differentially reduced thyroid cancer cell invasion in these thyroid cancer cell lines. Sensitive cell lines demonstrated approximately a two-fold decrease in invasion, which was associated with differential expression of MMP-13. MMP-9 was reduced by mIκBα expression in all cell lines tested.

Conclusions

These data indicate that selective inhibition of NF-κB represents an attractive therapeutic target for the treatment of advanced thyroid. However, it is apparent that global regulation of thyroid cancer cell growth and invasion is not achieved by NF-κB signaling alone. Instead, our findings suggest that other important molecular processes play a critical role in defining the extent of NF-κB function within cancer cells.     

Smoking and mortality among women with type 2 diabetes: The Nurses' Health Study cohort.

OBJECTIVE: To assess the relationship between cigarette smoking and mortality among women with type 2 diabetes in the Nurses' Health Study cohort. RESEARCH DESIGN AND METHODS: The Nurses' Health Study, a prospective cohort of U.S. female registered nurses, included 7,401 women with type 2 diabetes diagnosed at baseline or during follow-up from 1976 to 1996. Total and cause-specific mortality of these diabetic women were the outcomes of interest. RESULTS: We documented 724 deaths during 20 years of follow-up (67,420 person-years) among women with type 2 diabetes. In multivariate analyses, adjusting for age, history of high blood pressure and high cholesterol, and other cardiovascular risk factors, compared with never smokers, the RRs of mortality were 1.31 (95% CI 1.11-1.55) for past smokers, 1.43 (0.96-2.14) for current smokers of 1-14 cigarettes/day, 1.64 (1.24-2.17) for current smokers of 15-34 cigarettes/day, and 2.19 (1.32-3.65) for current smokers of > or =35 cigarettes/day (P for trend = 0.0002). Women with type 2 diabetes who had stopped smoking for > or =10 years had a mortality RR of 1.11 (0.92-1.35) compared with diabetic women who were never smokers. CONCLUSIONS: Cigarette smoking is associated in a dose-response manner with an increased mortality among women with type 2 diabetes. Furthermore, quitting smoking appears to decrease this excess risk substantially. Diabetes patients should be strongly advised against smoking.     

Multifaceted Therapeutic Targeting of Ovarian Peritoneal Carcinomatosis Through Virus-induced Immunomodulation

Immunosuppression associated with ovarian cancer (OC) and resultant peritoneal carcinomatosis (PC) hampers the efficacy of many promising treatment options, including immunotherapies. It is hypothesized that oncolytic virus-based therapies can simultaneously kill OC and mitigate immunosuppression. Currently, reovirus-based anticancer therapy is undergoing phase I/II clinical trials for the treatment of OC. Hence, this study was focused on characterizing the effects of reovirus therapy on OC and associated immune microenvironment. Our data shows that reovirus efficiently killed OC cells and induced higher expression of the molecules involved in antigen presentation including major histocompatibility complex (MHC) class I, β2-microglobulin (β2M), TAP-1, and TAP-2. In addition, in the presence of reovirus, dendritic cells (DCs) overcame the OC-mediated phenotypic suppression and successfully stimulated tumor-specific CD8+ T cells. In animal studies, reovirus targeted local and distal OC, alleviated the severity of PC and significantly prolonged survival. These therapeutic effects were accompanied by decreased frequency of suppressive cells, e.g., Gr1.1+, CD11b+ myeloid derived suppressor cells (MDSCs), and CD4+, CD25+, FOXP3+ Tregs, tumor-infiltration of CD3+ cells and higher expression of Th1 cytokines. Finally, reovirus therapy during early stages of OC also resulted in the postponement of PC development. This report elucidates timely information on a therapeutic approach that can target OC through clinically desired multifaceted mechanisms to better the outcomes.     

COL4A1 mutations should not be a contraindication for epilepsy surgery

Purpose

We describe the first case in the literature of complication-free epilepsy surgery in a paediatric patient with collagen type IV alpha 1 (COL4A1) mutation.

Methods

This is a case report.

Results

COL4A1 mutations disrupt the integrity of vascular basement membranes, so predisposing to a broad spectrum of disorders including periventricular leucomalacia, haemorrhagic stroke, aneurysm formation, epilepsy and developmental delay. Intracranial haemorrhage is reported and may be recurrent or associated with trauma and anticoagulant therapy. Children have an increased risk of stroke with general anaesthesia. A 6-year-old girl, COL4A1 mutation positive, had drug-resistant epilepsy, cerebral palsy and developmental delay. Following presurgical evaluation, she was a candidate for corpus callosotomy. Previous general anaesthesia had been uncomplicated. Preoperative full blood count and coagulation studies were normal. Perioperatively, normotension was maintained, and anticoagulation was avoided. A complete corpus callosotomy was performed with no intracranial haemorrhage or other perioperative complications.

Conclusion

Although there is an increased risk of intracranial haemorrhages in COL4A1 patients, this is not clearly quantifiable. There are minimal data in the literature on the subject. COL4A1 mutations should not be a contraindication for presurgical evaluation. Each patient should be individually evaluated and assessed, risks and benefits were carefully weighed, and informed decisions were reached after thorough discussions with patients and families.