Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia

Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-β superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.     

Prognostic value of bax, cytochrome C, and caspase-8 protein expression in primary osteosarcoma

The prognostic significance of bax, cytochrome c, and caspase-8 in patients with primary osteosarcoma is unknown. We examined the immunohistochemical expression of these genes in 35 surgically treated patients with primary osteosarcoma. Clinicopathological and survival data were correlated with the staining result. Eighteen tissue specimens from non-malignant osseous lesions were used as controls. Bax, cytochrome c, and caspase-8 positive staining was observed in 29 (82.9%), 16 (45.7%), and 0 (0%) patients, respectively, but did not stain any of the 18 benign osseous lesions used as controls. None of the genes studied predicted overall or disease-free survival. Patients, however, bearing bax(+)/cytochrome c(+) or bax(+)/cytochrome c(+ +) tumors had a decreased 4-year disease-free survival rate compared to the rest of the group (p = 0.0489 and p = 0.0208, respectively), identifying two groups of patients where more intensive adjuvant treatment could possibly be applied to prevent high postoperative recurrence rates.     

Does percutaneous nephrolithotomy in children cause significant renal scarring?

ObjectiveTo determine the frequency of renal parenchymal damage following percutaneous nephrolithotomy (PCNL) in children.Patients and methodsFifty-six children undergoing PCNL in 60 renal units between January 2000 and December 2004 were included in this prospective study, and were subjected to postoperative technetium-99m dimercaptosuccinic acid (^99mTc-DMSA). Using a standard questionnaire, demographics, number, size and location of stones, procedure details, outcome as indicated by clearance with PCNL alone or additional procedures, and follow up were documented. Presence of focal renal damage and its association with the PCNL tract were examined.ResultsOut of 60 renal units, cortical defects on ^99mTc-DMSA scan were seen in 10 renal units (17%). In three of these kidneys, the site of focal defect corresponded to the access site for tract formation during PCNL. Two additional kidneys had scarring at multiple sites, one of which corresponded to the access site during PCNL. In the remaining five kidneys no association between focal renal damage and nephrostomy tract site could be ascertained. No association was seen between renal damage and the size of nephroscope used during PCNL.ConclusionThere exists a risk of focal damage to renal parenchyma from the formation of the nephrostomy tract. In our series, focal damage was seen in 5% of patients; this may be an overestimate since preoperative ^99mTc-DMSA scans were not available for our patients. Meticulous technique is important combined with a smaller nephroscope to minimize renal damage. Long-term follow up of such children is required to assess how many are left with permanent renal scars.     

Effect of weight loss by bariatric surgery on the risk of miscarriage

The aim of this paper is to appraise the literature with a view to establish whether weight loss by bariatric surgery has a beneficial effect on lowering the risk of miscarriage in morbidly obese women. Literature review revealed that weight loss by bariatric surgery on miscarriage rate has not been studied enough.     

Preparation,characterization, and biological activity study of thymoquinone-cucurbit[7]uril inclusion complex

In this study, the formation of a host–guest inclusion complex between cucurbit[7]uril (CB[7]) and thymoquinone (TQ) was investigated in aqueous solution. The formation of a stable inclusion complex, CB[7]–TQ, was confirmed by using different techniques, such as ¹H NMR and UV-visible spectroscopy. The aqueous solubility of TQ was clearly enhanced upon the addition of CB[7], which provided an initial indication for supramolecular complexation. The complexation stoichiometry and the binding constant of the inclusion complex were determined through a combination of two sets of titration methods, including UV-visible and fluorescence displacement titrations. Both methods suggested the formation of a 1 : 1 stoichiometry between CB[7] and TQ with moderate binding affinity of 3 × 10³ M⁻¹. Density functional theory (DFT) calculations were also performed to verify the structure of the resulted host–guest complex and to support the complexation stoichiometry. The theoretical calculations were in agreement with experimental results obtained by ¹H NMR spectroscopy. Most importantly, the cytotoxic effect of the CB[7]–TQ complex was investigated against cancer and normal cell lines. The results showed that the anticancer activity of TQ against MDA-MB-231 cells was enhanced by the complexation with CB[7], while no significant effect was observed in MCF-7 cells. The results also confirmed the low toxicity of the CB[7] host molecule that supports the use of CB[7] as a drug carrier.

The host–guest inclusion complexation of thymoquinone by cucurbit[7]uril in aqueous solution is established, which results in an enhanced biological activity.     

Streptobacillus notomytis Bacteremia after Exposure to Rat Feces

To determine the source of Streptobacillus notomytis bacteremia in a woman in Japan with signs of rat-bite fever, we examined rat feces from her home. After culture and PCR failed to identify the causative organism in the feces, next-generation sequencing detected Streptobacillus spp., illustrating this procedure’s value for identifying causative environmental organisms.     

Impact of epilepsy surgery on quality of life: Systematic review and meta-analysis

Improved quality of life (QoL) is an important outcome goal following epilepsy surgery. This study aims to quantify change in QoL for adults with drug-resistant epilepsy (DRE) who undergo epilepsy surgery, and to explore clinicodemographic factors associated with these changes. We conducted a systematic review and meta-analysis using Medline, Embase, and Cochrane Central Register of Controlled Trials. All studies reporting pre- and post-epilepsy surgery QoL scores in adults with DRE via validated instruments were included. Meta-analysis assessed the postsurgery change in QoL. Meta-regression assessed the effect of postoperative seizure outcomes on postoperative QoL as well as change in pre- and postoperative QoL scores. A total of 3774 titles and abstracts were reviewed, and ultimately 16 studies, comprising 1182 unique patients, were included. Quality of Life in Epilepsy Inventory–31 item (QOLIE-31) meta-analysis included six studies, and QOLIE-89 meta-analysis included four studies. Postoperative change in raw score was 20.5 for QOLIE-31 (95% confidence interval [CI] = 10.9–30.1, I² = 95.5) and 12.1 for QOLIE-89 (95% CI = 8.0–16.1, I² = 55.0%). This corresponds to clinically meaningful QOL improvements. Meta-regression demonstrated a higher postoperative QOLIE-31 score as well as change in pre- and postoperative QOLIE-31 score among studies of cohorts with higher proportions of patients with favorable seizure outcomes. At an individual study level, preoperative absence of mood disorders, better preoperative cognition, fewer trials of antiseizure medications before surgery, high levels of conscientiousness and openness to experience at the baseline, engagement in paid employment before and after surgery, and not being on antidepressants following surgery were associated with improved postoperative QoL. This study demonstrates the potential for epilepsy surgery to provide clinically meaningful improvements in QoL, as well as identifies clinicodemographic factors associated with this outcome. Limitations include substantial heterogeneity between individual studies and high risk of bias.