Branching patterns of the foetal popliteal artery

Background: The objective of the study is to evaluate the popliteal artery topography and the origin variability of its branches in human foetuses at the gestational age of from 4 to 9 months. The basis for the analysis are direct observations of classic anatomic dissections of the popliteal fossa. Possible dimorphic and bilateral differen- ces, as well as the gestational age variability at the foetal period, were considered. A typology of popliteal artery branches will be made on the basis of the studies.  Materials and methods: The research material of this study comprises 231 foetuses (including 116 males and 115 females). The foetuses were divided into five 28-day age classes. The vessels of the lower extremity were injected with LBSK 5545 latex through the femoral artery. The bilateral dissection of the po- pliteal artery along with its branches was performed. No visible malformations were found in the research material, and the foetuses came from spontaneous abortions and premature births.  Results and Conclusions: Ten per cent of the cases featured the variations of popliteal artery terminal branches. Three most commonly seen variations are the trifurcation, anterior tibial-peroneal trunk, and high terminal division of the po- pliteal artery. The most common course of the superior muscular branches is that there are two large branches which are distributed from the popliteal artery at the height of the knee joint cavity and they do not distribute cutaneous branches. Sural branches are also present as two large vessels without cutaneous branches. The genicular anastomosis branches that run on their own are a typical topographic system of these branches.

Morphometric and morphological evaluation of mastoid emissary canal using cone-beam computed tomography

Objectives: This study aimed to determine mastoid emissary canal’s (MEC) and mastoid foramen (MF) prevalence and morphometric characteristics on cone-beam computed tomography (CBCT) images to underline its clinical significance and discuss its surgical consequences. Methods: In the retrospective analysis, two oral and maxillofacial radiologists analyzed the CBCT images of 135 patients (270 sides). The biggest MF and MEC were measured in the images evaluated in MultiPlanar Reconstruction (MPR) views. The MF and MEC mean diameters were calculated. The mastoid foramina number was recorded. The prevalence of MF was studied according to gender and side of the patient. Results: The overall prevalence of MEC and MF was 119 (88.1%). The prevalence of MEC and MF is 55.5% in females and 44.5% in males. MEC and MF were identified as bilateral in 80 patients (67.20%) and unilateral in 39 patients (32.80%). The mean diameter of MF was 2.4 ± 0.9 mm. The mean height of MF was 2.3 ± 0.9. The mean diameter of the MEC was 2.1 ± 0.8, and the mean height of the MEC was 2.1 ± 0.8. There is a statistical difference between the genders (p = 0.043) in foramen diameter. Males had a significantly larger mean diameter of MF in comparison to females. Conclusion: MEC and MF must be evaluated thoroughly if the surgery is contemplated. Radiologists and surgeons should be aware of mastoid emissary canal morphology, variations, clinical relevance, and surgical consequences while operating in the suboccipital and mastoid areas to avoid unexpected and catastrophic complications. CBCT may be a reliable imaging diagnostic technique

Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX's suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER

Simulation and Measurements of HOM Filter of the LARP Prototype RF-Dipole Crabbing Cavity Using an RF Test Box

The RF-Dipole Crabbing Cavity designed for the LHC High Luminosity Upgrade includes two higher order mode (HOM) couplers. One of the HOM couplers is an rf filter, which is a high pass filter designed to couple to the horizontal dipole modes and accelerating modes up to 2 GHz, while rejecting the fundamental operating mode at 400 MHz. The coupler consists of a high pass filter circuit where the rejection of the operating mode and transmission of HOMs are sensitive to dimensional deviations. An rf test box has been designed to measure the transmission of the rf filter in order to qualify the fabricated HOM coupler and to tune the coupler. This paper presents the measurements of the HOM coupler with the rf test box

Kinking of Frozen Elephant Trunk Hybrid Prostheses: Incidence, Mechanism, and Management

Introduction: Kinking of the Frozen Elephant Trunk (FET) stent graft is one of the most devastating complications of the FET procedure. It can present post-operatively with reduced arterial pressures in the lower limbs and intermittent claudication. However, it can also be visualized intra-operatively by the surgeons. Unresolved kinking of the stent graft can result in intraluminal thrombus formation and subsequent multi-organ septic emboli. Aims: The main scope of this review is to collate, summarize and present all the evidence in the literature on kinking of FET stent grafts. Methods: We carried out a comprehensive literature search on multiple electronic databases including PubMed, EMBASE, Ovid, and Scopus to collate all research evidence on the incidence, mechanism, and management of FET graft kinking. Results: Incidence of kinking is variable, ranging from 0% to 8% in the literature, with varying rates associated with each stent graft type. The Thoraflex HybridTM prosthesis seemed to be the most commonly used and superior graft, and out of all the 15 cases of kinking reported in the literature, 5 (33.3%) were associated with just the Frozenix graft which had the highest incidence. There are multiple theories regarding the mechanism of kinking, including the direction of blood flow, the length of the stent grafts used, and the position of the prosthesis in relation to the flexure of the aorta. Multiple reparative management techniques have been suggested in the literature and include total endovascular repair, open repair, balloon dilatation, and deploying a second stent graft. Conclusion: Graft kinking is one of the most critical complications of the FET technique. Its life-threatening sequelae warrant appropriate follow-up of these patients post-operatively, in addition to time management if kinking is suspected. Given the limited evidence in the literature, future studies should incorporate graft kinking into their outcomes reporting

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis

BACKGROUND: Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the TYMS 5'-untranslated enhanced region (TSER) and a 6-bp deletion/insertion in the TYMS 3'-untranslated region (TS 3'-UTR)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk. METHODS: To test the hypothesis that polymorphisms of the TYMS gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population. RESULTS: We found that the distribution of TS3'-UTR (1494del6) genotype frequencies were significantly different between the cases and controls (P = 0.026). Compared with the TS3'-UTR del6/del6 wild-type genotype, a significantly reduced risk was associated with the ins6/ins6 homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35–0.97) but not the del6/ins6 genotype (OR = 1.09, 95% CI = 0.82–1.46). Furthermore, breast cancer risks associated with the TS3'-UTR del6/del6 genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the TSER polymorphism and breast cancer risks. CONCLUSION: These findings suggest that the TS3'-UTR del6 polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings