Intermediate-term outcomes of combined phacoemulsification and Aurolab aqueous drainage implant in eyes with refractory glaucoma and coexistent cataract

International Ophthalmology - To investigate the efficacy and safety of non-valved Aurolab aqueous drainage implant (AADI) surgery combined with phacoemulsification in eyes with refractory glaucoma...     

Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.     

Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.

To determine whether the mouse loses bone with aging and whether the changes mimic those observed in human aging, we examined the changes in the tibial metaphysis and diaphysis in the male C57BL/6J mouse over its life span using microcomputed tomography (microCT). Cancellous bone volume fraction (BV/TV) decreased 60% between 6 weeks and 24 months of age. Loss was characterized by decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and decreased connectivity. Anisotropy decreased while the structure model index increased with age. Cortical bone thickness increased between 6 weeks and 6 months of age and then decreased continuously to 24 months (-12%). Cortical bone area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a peak at 12 months and gradually declined to 24 months. Total mass lost between 12 and 24 months reached 10%. Overall, the age-related changes in skeletal mass and architecture in the mouse were remarkably similar to those seen in human aging. Furthermore, the rapid early loss of cancellous bone suggests that bone loss is not just associated with old age in the mouse but rather occurs as a continuum from early growth. We conclude that the C57BL/6J male mouse maybe a useful model to study at least some aspects of age-related bone loss in humans.     

腹腔镜高选择性迷走神经切断术联合Nissen胃底折叠术:效果如何?——腹腔镜Nissen迷走神经切断术治疗胃食管返流

背景：Nissen胃底折叠术（Nissen fundoplication，NF）已不是治疗胃食管返流性疾病（gastroesophageal reflux disease，GERD）的唯一、有效的方法。对于能降低胃酸的手术方式来讲，如高选择性迷走神经切断术（highly selective vagotomy，HSV），也不仅仅是一种辅助治疗方法。对高选择性迷走神经切断术联合Nissen胃底折叠术（Nissen fundoplication with highly selective vagotomy，NFHSV）治疗GERD的作用目前尚无完整的评价。方法：2003年6月～2005年6月8例女性病人接受NFHSV，8例均有6个月GERD病史，经药物治疗症状无缓解，有餐前痛、消化性溃疡或严重的胃炎。平均随访时间12个月，术前、术后进行烧心严重程度评分测定（heart burn severity score，HSS）。结果：平均手术时间110min，无手术并发症。1例术后须用质子泵抑制剂，术后经戒烟5个月后停药。8例术后症状和烧心严重程度评分测定有明显改善。结论：NFHSV是有效的联合手术方式，尚需要进一步的研究证实这一联合术式的完全有效性和安全性。     

Isolated pure lipoma of the uterus--a case report

Lipoma primary to uterus is a rare entity among uterine fatty tumors. These create preoperative diagnostic confusion and their histogenesis is still unclear. Only a few cases of pure lipoma of uterus have been reported in the last few decades. A case of isolated pure lipoma primary to uterus diagnosed postoperatively by pathological examination is presented.     

Plasma protein haptoglobin modulates renal iron loading

Haptoglobin is the plasma protein with the highest binding affinity for hemoglobin. The strength of hemoglobin binding and the existence of a specific receptor for the haptoglobin-hemoglobin complex in the monocyte/macrophage system clearly suggest that haptoglobin may have a crucial role in heme-iron recovery. We used haptoglobin-null mice to evaluate the impact of haptoglobin gene inactivation on iron metabolism. Haptoglobin deficiency led to increased deposition of hemoglobin in proximal tubules of the kidney instead of the liver and the spleen as occurred in wild-type mice. This difference in organ distribution of hemoglobin in haptoglobin-deficient mice resulted in abnormal iron deposits in proximal tubules during aging. Moreover, iron also accumulated in proximal tubules after renal ischemia-reperfusion injury or after an acute plasma heme-protein overload caused by muscle injury, without affecting morphological and functional parameters of renal damage. These data demonstrate that haptoglobin crucially prevents glomerular filtration of hemoglobin and, consequently, renal iron loading during aging and following acute plasma heme-protein overload.     

Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.

     

Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications.

Activation of cell surface death receptors by their cognate ligands triggers apoptosis. Several human death receptors (Fas, TNF-R1, TRAMP, DR4, DR5, DR6, EDA-R and NGF-R) have been identified. The most promising cytokine for anticancer therapy is TRAIL/APO-2L, which induces apoptosis in cancer cells by binding to death receptors TRAIL-R1/DR4 and TRAIL-R2/DR5. The cytotoxic activity of TRAIL is relatively selective to cancer cells compared to normal cells. Signaling by TRAIL and its receptors is tightly regulated process essential for key physiological functions in a variety of organs, as well as the maintenance of immune homeostasis. Despite early promising results, recent studies have identified several TRAIL-resistant cancer cells of various origins. Based on molecular analysis of death-receptor signaling pathways several new approaches have been developed to increase the efficacy of TRAIL. Resistance of cancer cells to TRAIL appears to occur through the modulation of various molecular targets. They may include differential expression of death receptors, constitutively active Akt and NFkappaB, overexpression of cFLIP and IAPs, mutations in Bax and Bak genes, and defects in the release of mitochondrial proteins in resistant cells. Conventional chemotherapeutic and chemopreventive drugs, and irradiation can sensitize TRAIL-resistant cells to undergo apoptosis. Thus, these agents enhance the therapeutic potential of TRAIL in TRAIL-sensitive cells and sensitize TRAIL-resistant cells. TRAIL and TRAIL-receptor antibodies may prove to be useful for cancer therapy, either alone or in association with conventional approaches such as chemotherapy or radiation therapy. This review discusses intracellular mechanisms of TRAIL resistance and various approaches that can be taken to sensitize TRAIL-resistant cancer cells.