Patient-specific hemodynamic analysis of small internal carotid artery-ophthalmic artery aneurysms

BackgroundProphylactic treatment of unruptured small brain aneurysms is still controversial due to the low risk of rupture. Distinguishing which small aneurysms are at risk for rupture has become important for treatment. Previous studies have indicated a variety of hemodynamic properties that may influence aneurysm rupture. This study uses hemodynamic principles to evaluate these in the context of ruptured and unruptured small aneurysms in a single location.MethodsEight small internal carotid artery-ophthalmic artery (ICA-Oph) aneurysms (<10 mm) were selected from the University of California, Los Angeles, database. We analyzed rupture-related hemodynamic characteristics including flow patterns, wall shear stress (WSS), and flow impingement using previously developed patient-specific computational fluid dynamics software.ResultsMost ruptured aneurysms had complicated flow patterns in the aneurysm domes, but all of the unruptured cases showed a simple vortex. A reduction in flow velocity between the parent artery and the aneurysm sac was found in all the cases. Inside the aneurysms, the highest flow velocities were found either at the apex or neck. We also observed a trend of higher and more inhomogeneous WSS distribution within ruptured aneurysms (10.66 ± 5.99 Pa) in comparison with the unruptured ones (6.31 ± 6.47 Pa) (P < .01).ConclusionA comparison of hemodynamic properties between ruptured and unruptured small ICA-Oph aneurysms found that some hemodynamic properties vary between small aneurysms although they are similar in size and share the same anatomical location. In particular, WSS may be a useful hemodynamic factor for studying small aneurysm rupture.     

LED‐based red light photostimulation improves short‐term response of cooled boar semen exposed to thermal stress at 37°C

Pre‐treatment of boar semen with a red light photostimulation procedure increases its “in vivo” fertilising ability. However, “in vitro” conducted studies shown contradictory results regarding the ability of photostimulated spermatozoa to react against strong stress and to achieve the capacitation status. The aim here was to determine the effect of photostimulation on the response to short‐term moderate thermal stress of boar semen. Boar semen was exposed to red LED light regime emitting a 620–630 nm during 10 min of light, 10 min of rest and 10 min of light after 3 hr since semen was collected. An aliquot without photostimulation was included as a control. After the photostimulation, the sperm cells were incubated for 15 min at 37°C. Afterwards, motility, viability, intracellular Ca²⁺ level and production of reactive oxygen species (ROS) and peroxynitrite were analysed. The results showed that the photostimulated group maintained total motility throughout the time, whereas a significant decrease in total motility was observed in the nonphotostimulated control group. Furthermore, for kinetic parameters of motility, a significant increase was observed in LIN, STR and WOB in photostimulated spermatozoa. Peroxynitrite production was significantly increased in the photostimulated spermatozoa, whereas viability, ROS production and intracellular Ca²⁺ levels were not affected by photostimulation. In conclusion, photostimulation of commercial boar semen has a positive effect on motility of spermatozoa subjected to a short‐term moderate thermal stress, which was concomitant with an increase in peroxynitrite production.     

Differential 3,5,3'-triiodothyronine-mediated regulation of uncoupling protein 3 transcription: role of Fatty acids

T(3) regulates energy metabolism by stimulating metabolic rate and decreasing metabolic efficiency. The discovery of mitochondrial uncoupling protein 3 (UCP3), its homology to UCP1, and regulation by T(3) rendered it a possible molecular determinant of the action of T(3) on energy metabolism, but data are controversial. This controversy may in part be attributable to discrepancies observed between the regulation by T(3) of UCP3 expression in rats, humans, and mice. To clarify this issue, we studied 1) the induction kinetics of the UCP3 gene by T(3) in rat skeletal muscle, 2) the influence of fatty acids, and 3) the structure and regulation of the various UCP3 promoters by T(3). Within 8 h of single-dose T(3) administration, hypothyroid rats showed a rise in serum fatty acid levels concomitant with a rapid increase in UCP3 expression in gastrocnemius muscle, followed by inductions of peroxisome proliferator activated receptor delta (PPARdelta) (within 24 h) and PPAR target gene expression (after 24 h). This T(3)-induced early UCP3 expression depended on fatty acid-PPAR signaling because depleting serum fatty acid levels abolished its expression, restorable by administration of the PPARdelta agonist L165,041 (4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]phenoxy]acetic acid). In transfected rat L6 myoblasts, only the rat UCP3 promoter positively responded to T(3) and L165,041 together in the presence of MyoD, thyroid hormone receptor beta1 (TRbeta1), PPARdelta, or PPARdelta plus the TR dimerization partner retinoid X receptor alpha. All promoters share a response element common to TR and PPAR (TRE 1), but the observed species differences may be attributable to different localizations of the MyoD response element, which in the rat maps to exon 1.     

Gender Differences in Office and Ambulatory Control of Hypertension

Background

Gender differences in hypertension control have not been explored fully.

Methods

We studied 15,212 white men and 13,936 white women with treated hypertension who were drawn from the Spanish Ambulatory Blood Pressure Registry. For each participant, we obtained office blood pressure (BP) (average of 2 readings) and 24-hour ambulatory BP (average of measurements performed every 20 minutes during day and night).

Results

Only 16.4% of women and 14.7% of men had both office (<140/90 mm Hg) and ambulatory (<130/80 mm Hg) BP controlled (P < .001). Women had a lower frequency of masked hypertension (office BP < 140/90 mm Hg and ambulatory BP ≥ 130/80 mm Hg) than men (5.9% vs 7.9%, P < .001). Women had a higher frequency of isolated office hypertension (office BP ≥ 140/90 mm Hg and ambulatory BP < 130/80 mm Hg) (32.5% vs 24.2%, P < .001). Although office BP control (office BP < 140/90 mm Hg, regardless of ambulatory values) was similar in women and men (22.3% vs 22.6%, P = .542), ambulatory BP control (ambulatory BP < 130/80 mm Hg, regardless of office values) was higher in women than in men (48.9% vs 38.9%, P < .001). After adjustment for age, number of antihypertensive drugs, hypertension duration, and risk factors, gender differences in BP control remained practically unchanged.

Conclusion

Ambulatory BP control was higher in women than in men. This may be due to the higher frequency of isolated office hypertension in women, and it is not explained by gender differences in other important clinical characteristics.     

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

The pathogenesis of autoimmune hepatitis （AIH） is complex. However, it is believed that a susceptible individual, owing to his genetic background, sex and age, can develop the disease following exposure to an environmental trigger. Autoimmune hepatitis does not follow a Mendelian pattern of inheritance; hence no single causative genetic locus has been identified. However, several genes, inside and outside the HLA locus, have been linked to an increased susceptibility to AIH. Epidemiological evidence also suggests that the sex and age of the patient plays a role in AIH pathogenesis as the disease onset occurs mainly in the two first decades of life and a higher disease incidence is observed in females. No environmental trigger has been identified, but several have been proposed, mainly viruses and xenobiotics. This article aims at reviewing the current knowledge on susceptibility factors leading to AIH and putative triggers, emphasizing fundamental mechanisms responsible for the break of liver immunological tolerance.     

Improved Quality of Anorectal Endoluminal Ultrasonography Using Emulsion of Dimethicone

PURPOSE: This study was designed to show the benefits of filling echography probes with water mixed with dimethicone to preclude artifacts caused by bubbles. METHODS: One hundred consecutive healthy volunteers (42 males; mean age, 46 years; range, 17–72 years) were blindly randomized to undergo rectal ultrasonography using conventional degassed water or degassed aqueous solution made of 40 ml of water and 10 ml of dimethicone emulsion (1 ml/100 mg). All examinations performed by the same surgeon—unaware of nature of filler liquid—for ten minutes, and number of rectal ultrasonographies with artifacts attributable to air bubbles was recorded. RESULTS: Endoluminal ultrasonography performed with conventional degassed water presented artifacts attributed to presence of air bubbles in 30 of 50 examinations (60 percent). When degassed aqueous solution was used, only 5 of 50 examinations showed artifacts caused by presence of air bubbles (10 percent). This difference was statistically significant (P < 0.0005). The use of conventional fluid was associated with artifacts secondary to the presence of air bubbles, adjusted odds ratio 13.5 (95 percent confidence interval, 4.56–39.88). During this experience, the solution did not damage ultrasound scanner. CONCLUSIONS: We found that use of a dimethicone-degassed water mixture is simple, not expensive, safe, effective, and may reduce frequency of sonographic distortion in presence of air bubbles.     

Deoxynivalenol: Toxicology,Degradation by Bacteria,and Phylogenetic Analysis

Deoxynivalenol (DON) is a toxic secondary metabolite produced by fungi that contaminates many crops, mainly wheat, maize, and barley. It affects animal health, causing intestinal barrier impairment and immunostimulatory effect in low doses and emesis, reduction in feed conversion rate, and immunosuppression in high doses. As it is very hard to completely avoid DON’s production in the field, mitigatory methods have been developed. Biodegradation has become a promising method as new microorganisms are studied and new enzymatic routes are described. Understanding the common root of bacteria with DON degradation capability and the relationship with their place of isolation may bring insights for more effective ways to find DON-degrading microorganisms. The purpose of this review is to bring an overview of the occurrence, regulation, metabolism, and toxicology of DON as addressed in recent publications focusing on animal production, as well as to explore the enzymatic routes described for DON’s degradation by microorganisms and the phylogenetic relationship among them.     

Natural Compound Shikonin Induces Apoptosis and Attenuates Epithelial to Mesenchymal Transition in Radiation-Resistant Human Colon Cancer Cells

Radiation resistance represents an imperative obstacle in the treatment of patients with colorectal cancer, which remains difficult to overcome. Here, we explored the anti-proliferative and migration-inhibiting properties of the natural product shikonin on a radiation-resistant human colon carcinoma cell line (SNU-C5RR). Shikonin reduced the viability of these cells in a dose-dependent manner; 38 μM of shikonin was determined as the half-maximal inhibitory concentration. Shikonin induced apoptotic cell death, as demonstrated by increased apoptotic body formation and the number of TUNEL-positive cells. Moreover, shikonin enhanced mitochondrial membrane depolarization and Bax expression and also decreased Bcl-2 expression with translocation of cytochrome c from mitochondria into the cytosol. In addition, shikonin activated mitogen-activated protein kinases, and their specific inhibitors reduced the cytotoxic effects of shikonin. Additionally, shikonin decreased the migration of SNU-C5RR cells via the upregulation of E-cadherin and downregulation of N-cadherin. Taken together, these results suggest that shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in SNU-C5RR cells.