Emergence of influenza A H1N2 reassortant viruses in the human population during 2001

A recombinant vaccinia virus encoding rotavirus protein NSP3 driven by an internal ribosome entry site (IRES) from the encephalomyocarditis (EMC) virus was able to abate protein synthesis in BSC1 cells by 25-fold, with as much as 30% of the remaining protein synthesis being NSP3. Hence NSP3 shuts off host cell protein synthesis down to the level seen during rotavirus infection but is unable to prevent translation from EMC IRES-driven genes. This effect was abolished by deletions in the eIF4G-binding (aa 274-313) and the dimerization (aa 150-206) but not the viral mRNA-binding (aa 83-149) domains, supporting that NSP3 functions in vivo as a dimer. Binding of eIF4G by NSP3 has been implicated in interfering with mRNA 5'-3' circularization, hence such circularization is essential for translation in mammalian cells.     

Hyperhomocysteinemia and vitamin score: correlations with silent brain ischemic lesions and brain atrophy

Elevated fasting plasma total homocysteine concentration (tHcy) and lower vitamin status are associated with atherosclerotic states. Silent brain ischemic lesions and brain atrophy, prevailing in the elderly, are affected by tHcy and vitamin status. The study was performed on 56 outpatients who had undergone brain computed tomography (CT) before the onset of the study. According to brain CT evaluation, three groups were set: minor brain ischemia, brain atrophy and control. Brain CT, tHcy, plasma pyridoxal phosphate (PLP), vitamin B(12), folic acid and cognitive and functional capacities were measured or evaluated in all of the subjects. Plasma vitamin score for three vitamins was calculated. In subjects with minor brain ischemic lesions (n = 21), tHcy was higher by 5.6 microM, whereas vitamin score and cognitive function were lower than in controls (n = 24). In subjects with brain atrophy (n = 11), plasma PLP and cognitive function were lower. Particular attention should be paid to tHcy monitoring, vitamin status assessment and brain impairment evaluation.     

Subfascial drainage and clipping technique for treatment of cerebrospinal fluid leak following spinal surgery

Objectives:To investigate the treatment of iatrogenic cerebrospinal fluid (CSF) leak that develops after degenerative lumbar spinal surgery with a subfascial drainage and clipping (SDC) technique.Methods:This study retrospectively reviewed the medical records of 46 patients who developed iatrogenic CSF leak after surgery for lumbar degenerative spine disease from 2007 to 2019. Twenty-five patients were treated with the SDC procedure (SDC group), whereas 21 were not (control group). Outcomes were compared between the two groups.Results:CSF leakage ceased within 6–9 days (average 7.4±1) after the procedure in the SDC group. In the control group, CSF leakage was controlled with conservative measures in 14 patients, and in 7 patients, lumbar external drainage was performed. Among these 7, the CSF leak was controlled by lumbar external drainage in 3, and 4 required reoperation to repair the dural defect. No infection occurred in either group. Length of hospital stay was also shorter in SDC group (8.4±1 vs 10.0±1.3 days, p < 0.001).Conclusion:The SDC technique is effective for the treatment of iatrogenic CSF leak that develops after degenerative lumbar spinal surgery.

Iatrogenic cerebrospinal fluid (CSF) leaks are one of the most common surgical complications of spinal surgery. Incidental dural injury is common during spinal surgery, epidural injection, and myelography. Previous studies have reported incidence rates ranging between 1% and 17% for incidental durotomy during surgery,¹ and Gerardi et al² reported a 6.8% incidence of intraoperatively undiagnosed CSF leak. As many patients with this condition are asymptomatic, it is difficult to predict CSF leaks that are not diagnosed at the time of surgery. Patients with symptomatic CSF leaks may suffer intracranial hypotension-related vertigo, posture-related headache, photophobia, double vision, neck stiffness and dizziness.Patients who are not diagnosed at the time of surgery or undergo inadequate dural repair may develop a postoperative dural leakage or pseudomeningocele.³In 1983, Teplick and Haskin⁴ reported a pseudomeningocele incidence of 1.6% detected by computerised tomography imaging among 750 patients who underwent lumbar spinal surgery and remained free of dural leak. When they occur, cutaneous leakage usually develop between the first and seventh days after surgery.In spinal CSF leaks, oversuturing the incision and application of a pressure dressing may suffice in most cases. When these measures fail, bed rest in the semi-Fowler’s position is recommended. The main target of bed rest is to reduce the CSF hydrostatic pressure in the lumbar region. In 2 previous studies, Wang et al² systematically prescribed short-term (2.9 days) bed rest, and Camisa et al² prescribed bed rest for 3–5 days. In addition, acetazolamide,⁵ repair with blood patch, and closed lumbar subarachnoid CSF drainage can be used. Kitchel et al reported that closed subarachnoid CSF drainage is an effective technique for treatment of postoperative CSF leaks and can prevent a repeat surgical intervention.⁶ Despite this, the outcomes are not always favourable. When these measures fail, a second surgery for primary dural repair can be performed.Cain et al⁷ examined the biology of a dural CSF leak repair in a canine model. They reported that fibroblastic bridging started on the 6th day and dural defects were healed on the 10th day.We did not encounter any other study in the literature that described the subfascial drainage and clipping (SDC) technique that we perform to treat CSF leaks after degenerative lumbar spinal surgery and report our experience herein.     

Spousal versus living unrelated renal transplantation: a retrospective analysis of allograft outcomes

Objective

To compare the outcomes of spousal and living unrelated donor (LUD) allografts.

Patients and methods

The 378 ABO-compatible living and cadaveric kidney transplantations between February 2005 and August 2010 included 25 wife-to-husband (group 1), 15 husband-to-wife (group 2), and 20 LUD cases (group 3). Donor nephrectomy was performed by open surgery. Induction therapy with antithymocyte globulin or anti-interleukin-2 receptor antibody was followed by maintenance regimens using cyclosporine (CsA) or tacrolimus (Tac) plus mycophenolate mofetil (MMF) and corticosteroids. We compared spousal donor and LUDs in terms of clinical characteristics as well as graft and patient survival rates.

Results

Fifty-six (93.3%) patients underwent induction therapy with either antithymocyte globulin (n = 30) or anti-interleukin-2 receptor antibody (n = 26). Maintenance immunosuppression was administered with Tac + MMF (n = 37; 61.6%) or CsA + MMF (n = 23; 38.4) with corticosteroids. Mean follow-up was 34 ± 16 months. There were four graft losses and five patient deaths. There were no significant differences between spousal and living unrelated transplants in terms of clinical characteristics or biopsy-proven acute rejection episodes. The Kaplan-Meier analysis showed 3-year patient survival rates of 94%, 100%, and 88% in group 1, group 2, and group 3, respectively (P > .05). Overall graft survival rates were 94%, 100%, and 77% in group 1, group 2, and group 3, respectively (P > .05). Graft and patient survival rates were similar at 3 years for wife-to-husband, husband-to-wife, or LUDs.

Conclusion

In conclusion, family members should be encouraged as LUD or spousal donors, based on similar patient and graft survival rates.     

Adsorption of nitrogen-containing compounds on hydroxylated α-quartz surfaces

Adsorption energies of various nitrogen-containing compounds (specifically, 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4-dinitroanisole (DNAn), and 3-nitro-1,2,4-triazole-5-one (NTO)) on the hydroxylated (001) and (100) α-quartz surfaces are computed. Different density functionals are utilized and both periodic as well as cluster approaches are applied. From the adsorption energies, partition coefficients on the considered α-quartz surfaces are derived. While TNT and DNT are preferably adsorbed on the (001) surface of α-quartz, NTO is rather located on both α-quartz surfaces.

Adsorption energies of different nitrogen-containing compounds on two hydroxylated (001) and (100) quartz surfaces are computed.     

Paradoxical Brain Embolism From Thrombus Associated With Vena Caval Filter in a Patient With Cancer

A 71-year-old man experienced sudden onset of hemiparesis and aphasia. He had a 4-month history of gallbladder cholangiocarcinoma, complicated with a postoperative deep-vein thrombosis (DVT) that necessitated a vena caval filter placement. Diffusion-weighted magnetic resonance imaging of the brain showed multiple hyperintense foci. Magnetic resonance spectroscopy was compatible with cerebral infarction. Abdominal computed tomography showed a thrombus in the inferior vena cava extending through the filters. A transcranial Doppler bubble study revealed the presence of a right-to-left shunt. Paradoxical cerebral embolism must be considered in patients with DVT who have new onset neurologic deficits even in the presence of a caval filter.     

Sulforaphane counteracts aggressiveness of pancreatic cancer driven by dysregulated Cx43-mediated gap junctional intercellular communication

The extreme aggressiveness of pancreatic ductal adenocarcinoma (PDA) has been associated with blocked gap junctional intercellular communication (GJIC) and the presence of cancer stem cells (CSCs). We examined whether disturbed GJIC is responsible for a CSC phenotype in established and primary cancer cells and patient tissue of PDA using interdisciplinary methods based in physiology, cell and molecular biology, histology and epigenetics. Flux of fluorescent dyes and gemcitabine through gap junctions (GJs) was intact in less aggressive cells but not in highly malignant cells with morphological dysfunctional GJs. Among several connexins, only Cx43 was expressed on the cell surface of less aggressive and GJIC-competent cells, whereas Cx43 surface expression was absent in highly malignant, E-cadherin-negative and GJIC-incompetent cells. The levels of total Cx43 protein and Cx43 phosphorylated at Ser368 and Ser279/282 were high in normal tissue but low to absent in malignant tissue. si-RNA-mediated inhibition of Cx43 expression in GJIC-competent cells prevented GJIC and induced colony formation and the expression of stem cell-related factors. The bioactive substance sulforaphane enhanced Cx43 and E-cadherin levels, inhibited the CSC markers c-Met and CD133, improved the functional morphology of GJs and enhanced GJIC. Sulforaphane altered the phosphorylation of several kinases and their substrates and inhibition of GSK3, JNK and PKC prevented sulforaphane-induced CX43 expression. The sulforaphane-mediated expression of Cx43 was not correlated with enhanced Cx43 RNA expression, acetylated histone binding and Cx43 promoter de-methylation, suggesting that posttranslational phosphorylation is the dominant regulatory mechanism. Together, the absence of Cx43 prevents GJIC and enhances aggressiveness, whereas sulforaphane counteracts this process, and our findings highlight dietary co-treatment as a viable treatment option for PDA.     

Inhibition of glucose turnover by 3-bromopyruvate counteracts pancreatic cancer stem cell features and sensitizes cells to gemcitabine

According to the cancer stem cell (CSC) hypothesis, the aggressive growth and early metastasis of pancreatic ductal adenocarcinoma (PDA) is due to the activity of CSCs, which are not targeted by current therapies. Otto Warburg suggested that the growth of cancer cells is driven by a high glucose metabolism. Here, we investigated whether glycolysis inhibition targets CSCs and thus may enhance therapeutic efficacy. Four established and 3 primary PDA cell lines, non-malignant cells, and 3 patient-tumor-derived CSC-enriched spheroidal cultures were analyzed by glucose turnover measurements, MTT and ATP assays, flow cytometry of ALDH1 activity and annexin positivity, colony and spheroid formation, western blotting, electrophoretic mobility shift assay, xenotransplantation, and immunohistochemistry. The effect of siRNA-mediated inhibition of LDH-A and LDH-B was also investigated. The PDA cells exhibited a high glucose metabolism, and glucose withdrawal or LDH inhibition by siRNA prevented growth and colony formation. Treatment with the anti-glycolytic agent 3-bromopyruvate almost completely blocked cell viability, self-renewal potential, NF-κB binding activity, and stem cell-related signaling and reverted gemcitabine resistance. 3-bromopyruvate was less effective in weakly malignant PDA cells and did not affect non-malignant cells, predicting minimal side effects. 3-bromopyruvate inhibited in vivo tumor engraftment and growth on chicken eggs and mice and enhanced the efficacy of gemcitabine by influencing the expression of markers of proliferation, apoptosis, self-renewal, and metastasis. Most importantly, primary CSC-enriched spheroidal cultures were eliminated by 3-bromopyruvate. These findings propose that CSCs may be specifically dependent on a high glucose turnover and suggest 3-bromopyruvate for therapeutic intervention.