Maximal Dilation Research Articles

Evaluation of local changes in radio-frequency signal waveform and brightness caused by vessel dilatation for ascertaining reliability of elasticity estimation inside heterogeneous plaque: a preliminary study.

To diagnose plaque characteristics, we previously developed an ultrasonic method to estimate the local elastic modulus from the ratio of the pulse pressure to the strain of the arterial wall due to dilatation in systole by transcutaneously measuring the minute thinning in thickness during one cardiac cycle. For plaques, however, some target regions became thicker as the vessel dilates, resulting in false elasticity. Therefore, a method to identify a reliable target for the elastic modulus estimation is indispensable. As a candidate for an identification index of plaques that become thicker during one cardiac cycle, the correlation of the radio-frequency (RF) signals remains high and it is not sufficient to obtain the elasticity. In this study, we thoroughly observed the target with a high correlation but positive strain in the plaque and characterized it by the property of the surrounding area. For the plaque formed in the right carotid sinus of a patient with hyperlipidemia and the wall of the right common carotid artery of a young healthy male, (1) the correlation value as the similarity between the RF signals, (2) change in brightness obtained from the log-compressed envelope signals, and (3) strain obtained between the time of the R-wave and that of the maximum vessel dilatation were observed to characterize the region in the plaque. In the plaque, it was found that the region with high correlation and positive strain and its surrounding area could be classified into one of the three typical patterns. As a preliminary study, this study provides a clue to assert the reliability of elasticity estimates for a region with high correlation and positive strain in the plaque based on measurable properties.

442-P: Sorbs2 Deficiency–Mediated Vascular BK Channel Dysfunction in Type 2 Diabetes

Vascular BK channels, composed of the pore-forming α-subunits (BK-α) and the regulatory β1 subunits (BK-β1) , is a key determinant of vasoreactivity, and its function is impaired in diabetes. However, our understanding of the mechanisms causing BK channel dysfunction in diabetic vessels is incomplete. The Sorbin and SH3 domain-containing protein 2 (Sorbs2) is abundantly expressed in vascular smooth muscle cells (SMCs) . We hypothesize that Sorbs2 is critical for vascular BK channel physiology. In this study, we compared vascular BK channel function between Sorbs2 KO and WT mice at 4 months of age. There was no difference in body weight and blood glucose between WT and Sorbs2 KO mice (body weight: 25.9±1.3 g of WT vs. 23.3±1.5 g of KO, n=14, p=N.S.; blood glucose: 166.4±7.7 mg/dL of WT vs. 152.2±12.2 mg/dL of KO, n=14, p=N.S.) . However, Sorbs2 KO mice have markedly reduced cell surface and cytoplasmic expression of BK-α and BK-β1, as well as BK channel-mediated vasodilation in carotid arteries with a maximal dilatation of 64.70±1.92% for WT mice (n=4) and 20.74±4.66% for KO mice (n=5, p<0.05) . Patch clamp experiments revealed that BK channel sensitivity to Ca2+ activation was impaired in the coronary SMCs of Sorbs2 KO mice (EC50: 2.87±0.68 µM, n=13, p<0.05) with decreased Hill coefficient (nH: 1.26) , compared to those of WT mice (EC50: 0.48±0.µM, nH: 2.70, n=13) . In vivo studies showed that Sorbs2 interacted with BK-α and BK-β1 protein in vascular SMCs. Silencing of Sorbs2 by shRNA decreased BK-α and BK-β1 expression, while adenoviral expression of Sorbs2 increased BK-α and BK-β1 expression in vascular SMCs. Most importantly, Sorbs2 expression was significantly reduced in the arteries of db/db type 2 diabetic mice and high fat diet-induced diabetic mice. Our results indicate that Sorbs2 plays an important role in regulating BK channel function and expression in vascular SMCs. Sorbs2 deficiency is a risk factor of BK channelopathy and vasculopathy in diabetes, independent of obesity and glucotoxicity. Disclosure T.Lu: None.

The Impact of One Week of Pre-Stenting on Porcine Ureteral Luminal Circumference.

Objectives: Larger ureteral access sheaths (UASs) have the potential to improve ureteroscopic stone removal outcomes but are often avoided by surgeons because of concerns of ureteral injury. Using our novel UAS force sensor and previously defined force thresholds for ureteral injury, we sought to evaluate the impact of 1 week of stenting on the maximum safe dilation of ureteral luminal circumference. Methods: Twelve juvenile female Yorkshire pigs (24 ureters) were evaluated. The inner (i.e., luminal) circumference of each ureter was determined using Cook urethral dilators ranging from 8F to 24F in 2F increments, 37 cm in length. Each dilator was sequentially passed while applying the UAS force sensor to measure insertion force before and after 1 week of stent placement. Each ureter was randomized to receive either a 4.7F or 7.0F stent (20 cm). Maximum ureteral luminal circumference was defined as effective passage of the dilator to the ureteropelvic junction with ≤6 newtons (N) of force (the force threshold previously defined by porcine and clinical studies to avoid ureteral damage). After passage of the largest dilator at 6 N, flexible ureteroscopy was performed and a post-ureteroscopic lesion scale (PULS) was recorded. Results: After 1 week of stent placement, the median ureteral luminal circumference increased to 15F representing a mean increase of 3.8F ± 2.8F (p < 0.001). Twenty-one (88%) of the pre-stented ureters had an increase in luminal circumference, with 12 ureters (50%) dilated to ≥16F (p = 0.032), 6 ureters (25%) dilated to ≥18F, and in 2 cases a maximum size of 24F was recorded. The PULS grade was ≤2 in all cases, indicating no high-grade ureteral injuries. Laterality and stent size did not impact ureteral luminal circumference after pre-stenting (p = 0.232 and p = 0.337, respectively). Conclusions: One week of ureteral stenting resulted in nearly a 4F increase in the luminal circumference of porcine ureters.

Hypertensive Female Mice Are Protected from Impaired Parenchymal Arteriolar TRPV4‐Mediated Dilation and Reactive Astrogliosis

Hypertension is a leading risk factor for cerebral small vessel disease. Our lab has previously demonstrated that cerebral parenchymal arterioles (PAs) are dependent on transient receptor potential vanilloid 4 (TRPV4) function for endothelium‐dependent dilation, and that this dilation is impaired in angiotensin II (AngII)‐hypertensive male mice. This PA dilation impairment is associated with cognitive deficits and increased inflammation. However, sex differences in hypertension‐associated dementia development are not well understood. To better understand the effect of female sex hormones during hypertension, we tested the hypothesis that young, cycling hypertensive female mice will be protected from impaired TRPV4‐mediated PA dilation and reactive astrogliosis observed in male mice. AngII‐filled osmotic minipumps (800ng/kg/min, 4 weeks) were implanted in 16‐18‐week‐old male C56BL/6 mice. Age‐matched female mice received either an AngII dose that matches the dose used in male mice (800ng/kg/min) or a higher dose (1200ng/kg/day) that produces an elevation in blood pressure similar to male mice. Sham mice served as control. Blood pressure was measured by tail‐cuff plethysmography. Pressure myography was used to assess TRPV4‐mediated dilation in PAs. An anti‐glial fibrillary acidic protein (GFAP) antibody was used in paraformaldehyde‐fixed 40μm coronal brain sections to assess the quantity and morphology of astrocytes. Data are presented as means ± SEM (n=5‐10). Male data were compared by Student’s t‐test and female data were compared by one‐way ANOVA unless otherwise stated. Systolic blood pressure was elevated in AngII‐treated male mice (sham: 133 ± 10, AngII: 181 ± 11mmHg; p=0.005) and in 1200ng AngII‐treated female mice (sham: 146 ± 8, 800ng AngII: 161 ± 13, 1200ng AngII: 179 ± 7mmHg; p=0.0482) vs sham. PA dilation in response to the TRPV4 agonist GSK1016790A (10‐9‐10‐5M) was not impaired in AngII‐treated female mice (sham: 85 ± 5, 800ng AngII: 73 ± 7, 1200ng AngII: 77 ± 8% maximum dilation; p=0.4381), contrasting with what we have previously reported in male mice. There was an increase in astrocytes in the corpus callosum of hypertensive male mice (sham: 65 ± 2; AngII: 77 ± 5; p=0.039). Interestingly, sham female mice had more astrocytes than sham male mice, and AngII infusion reduced the quantity (sham: 81 ± 3, 800ng AngII: 71 ± 3, 1200ng AngII: 69 ± 3; p=0.011). Sholl analysis was used to assess astrocyte morphology. Astrocytes from hypertensive male mice had more arborization further from the soma compared to sham (p=0.0348 at 14‐15μm from the soma, by two‐way ANOVA and Bonferroni correction). Female mice receiving the 1200ng dose AngII, however, had fewer arborizations away from the soma compared to sham (p=0.0263 at 13‐15μm from the soma, by two‐way ANOVA and Bonferroni correction). Female mice are resistant to AngII‐induced hypertension and protected from the associated deleterious cerebrovascular effects, supporting our hypothesis.

Role of NOX2 in Ceramide‐Induced Human Microvascular Endothelial Dysfunction

Endothelial dysfunction, or the loss of nitric oxide (NO)‐mediated dilation to shear stress (flow‐induced dilation; FID), is observed in human adipose arterioles from patients with coronary artery disease (CAD). FID is maintained during CAD by release of the mitochondrial‐derived, pro‐inflammatory dilator, H2O2. Ceramide, a sphingolipid that when elevated in plasma is an independent risk factor for future cardiac events, also induces this transition in human arterioles (10µM, 16‐20hrs). The initial events leading to ceramide‐induced endothelial dysfunction are unknown. Here we hypothesize that activation of NADPH oxidase 2 (NOX2), an endothelial membrane enzyme activated by acute stress, occurs prior to the formation of mitochondrial H2O2 in arterioles exposed to chronic ceramide. Human arterioles (100‐250µm in diameter) were dissected from discarded surgical adipose tissues and prepared for videomicroscopy. Following preconstriction with endothelin‐1, internal diameters were measured in response to increased flow. To determine the minimum exposure time necessary to convert to H2O2‐dependent FID in arterioles exposed to ceramide, microvessels from healthy nonCAD adults were incubated with C2 ceramide for 30 min, 2 hrs, and 4 hrs. FID remained mediated by NO at 30min and 2hrs, however, following a 4hr incubation, FID was significantly impaired in the presence of PEG‐catalase (44.6% of maximal dilator capacity ±13.8 (SEM), n=8, p&lt;0.05, one‐way ANOVA*) compared to vehicle control (83.5%±5.0, n=8). The source of H2O2 generated during FID in arterioles treated for 4hr with ceramide was not mitochondrial as increases in fluorescent intensity of mito peroxy yellow 1 (mitoPY1) were not observed during maximal flow. To test whether NOX2 is the initial source of H2O2 during FID in arterioles exposed to 4hr ceramide, nonCAD arterioles were first treated with the NOX2 inhibitor GSK2795039 (NOX2i, 10‐6 M) or underwent intraluminal administration of siRNA to decrease NOX2 expression prior to treatment with ceramide. FID was reduced in vessels treated with both ceramide and the NOX2 inhibitor in the presence of cPTIO (NO scavenger) (50.2%±30.1, n=4* vs. NOX2 inhibitor and ceramide alone 80.8%±6.4, n=7). L‐NAME also impaired FID in vessels with reduced expression of NOX2 and subsequently treated with ceramide (10.8%±38.9, n=3* compared to siNOX2 and ceramide alone 85.5%±5.8, n=3). This suggests that activation of NOX2 may be the initial event in the conversion of NO‐ to H2O2‐dependent FID due to ceramide and may serve as a potential therapeutic target in those at risk for developing cardiovascular disease due to increased plasma ceramide.

Is Estrogen a Friend or Foe of the Human Microcirculation Throughout the Lifespan?

Cardiovascular disease (CVD) risk increases with estrogen (E2) deficiency as well as during the transition to menopause, suggesting that estrogen is protective against CVD. On the contrary, increases in plasma E2 from contraception in cis‐females or hormone therapy (HT) in trans‐females (male‐to‐female transition) is also associated with increased CVD. Microvascular endothelial dysfunction, or the loss of nitric oxide (NO)‐mediated dilation in response to flow (flow‐induced dilation; FID), precedes large artery disease and is predictive of future cardiac events. We hypothesize that the effect of E2 on human microvascular endothelial function is hormetic with low or elevated E2 promoting dysfunction. We further posit that the effect of estrogen on the microvascular endothelium is influenced by both age and sex. Small adipose arterioles (100‐350µm) from healthy adults (0‐1 risk factors for coronary artery disease) were prepared for videomicroscopy and constricted with endothelin‐1 prior to measuring changes in internal diameters in response to flow. Historical data was analyzed to examine changes in FID over time in healthy women, and it showed that FID is maintained over time (75.4%±4.2 of maximal dilator capacity±SEM, n=26 age&lt;40yrs; 75.39%±3.0 age&gt;40yrs). L‐NAME significantly inhibited FID in healthy women &lt;40yrs of age (30.6%±9.9 n=17; p&lt;0.0005, two‐way ANOVA*) compared to control (75.4%±4.2, n=26), however this effect was abolished when incubated with E2 (100nM, 16‐20hrs) (71.2%±10.3, n=5 vs. control 84.7%±3.8, n=5). L‐NAME also decreased FID in arterioles from women 40‐60yrs of age (46.9%±9.8, n=19) compared to control (81.3%±2.6, n=37, p&lt;0.005), however there was a greater amount of residual dilation compared to women &lt;40yrs. E2 also resulted in a loss of NO‐mediated FID in women &gt;40yrs as L‐NAME had no effect (82.9%±4.3, n=4 vs. control 72.6%±8.8, n=5). In biological males, FID appears to be reduced in microvessels after E2 treatment regardless of age (52.1%±5.1 n=2, age&lt;40yrs; ‐2.7%±9.5, n=3, age&gt;40yrs). Together these data suggest that exposure to elevated levels of E2 may induce microvascular endothelial dysfunction in adult women regardless of age and appears to be more damaging in biological males. We conclude that elevated levels of E2 are detrimental to the microvasculature and may increase CVD risk in young women taking oral contraceptives as well as older women and trans‐females undergoing HT.

Abstract 470: Sphingosine-1-Phosphate Signaling In The Human Microvascular Endothelium During Health And Disease

The loss of nitric oxide (NO)-mediated flow-induced dilation (FID) in the microvasculature, or microvascular endothelial dysfunction, is strongly linked to future cardiovascular events. Our lab has previously shown that chronic inhibition of sphingosine-1-phosphate (S1P) formation induces the change in FID mediator from the vasoprotective NO to the pro-inflammatory, pro-atherosclerotic hydrogen peroxide. The same transition is observed in arterioles from patients with coronary artery disease (CAD). Since S1P promotes NO-mediated FID, we hypothesized that formation of S1P and activation of S1P receptor 1 (S1PR1) is critical for FID in microvessels from healthy adults as opposed to arterioles from patients with CAD. Videomicroscopy was used to perform vascular function studies on human resistance arterioles (100-250μm) dissected from discarded surgical adipose tissue. The vessels were pre-constricted with endothelin-1 and changes in internal diameter in response to flow was measured. In arterioles from healthy adults, treatment with a sphingosine kinase (SpK) inhibitor for 30 minutes abolished FID (7.7±8.0% of maximal dilator capacity, n=3; mean±SEM) compared to control (73.1±8.2% n=9, p&lt;0.05; *two-way ANOVA), whereas inhibition of S1PR1 appeared to delay the response to dilation (19.1±10.5% vs. 52.8±9.0% at 20mmHg pressure gradient, p&lt;0.05*). In microvessels from patients with disease, both inhibition of SpK (91.8±2.8%, n=5) and S1PR1 (72.5±6.4%, n=6) did not affect FID compared to control (90.9±2.4%, n=4). Interestingly, S1PR1 expression was similar in CAD and nonCAD arterioles. Together these data suggest that formation of S1P and potentially the activation of S1PR1 is critical for FID during health, however this pathway does not contribute to FID during disease. We conclude that while arterioles can compensate for loss of this pathway in disease to maintain tissue perfusion, formation of S1P and activation of its receptors may be necessary to promote NO formation during shear and may serve as potential targets to prevent future cardiovascular disease.

Uterine Microvascular Dysfunction After Plastic Particle Inhalation

Adverse cardiovascular and inflammatory outcomes after airborne particulate matter (PM) inhalation have long been a topic of epidemiological studies. Previous studies have identified, the microcirculation as particularly vulnerable to this insult. However, the mechanisms of microvascular dysfunction are complex and vary with each specific aerosol. Variations in neurohormonal and inflammatory status contribute to the complexity of defining mechanisms of microvascular dysfunction caused by aerosols. Given the recent identification and toxicological concerns surrounding micro‐ and nanoplastic exposures, we aimed to evaluate microvascular reactivity after acute plastic particle inhalation in this study. Virgin female Sprague Dawley rats in estrus were exposed to filtered air or aerosolized polyamide (i.e., nylon) particles in a whole‐body inhalation chamber. We hypothesized the uterine microvascular reactivity would achieve a vasoconstrictive state due to plastic particle inhalation. Exposure only during estrus served to control for neurohormonal differences within groups. 24h later, the radial arteriole of the uterus was selected as a representative vessel for the microcirculation. Ex vivouterine radial arteriole reactivity was assessed using pressure myography Living Systems Instrumentation, St. Albans, VT). Vascular reactivity was assessed based on responses to endothelium‐dependent (methacholine, MCh, 10‐9‐10‐4 M), –independent (sodium nitroprusside, SNP, 10‐9‐10‐4 M), and smooth muscle contractility (phenylephrine, PE, 10‐9‐10‐4 M). Inflammatory cytokines (IL‐4, IL‐6, MCP‐1, CXCL1; Sigma, St. Louis, MO and IL 5; Abcam, Cambridge, UK) were quantified in plasma with ELISA. Acute inhalation exposure to polyamide MNPs led to significantly impaired vascular reactivity through endothelium‐dependent and vascular smooth muscle mechanisms. Percent maximum dilation in response to 10‐9 M MCh was significantly reduced in exposed animals when compared to controls (‐9.44% ± 3.65 vs. 7.26% ± 4.61). Smooth muscle contraction was also impaired with percent maximum dilation in response to 10‐8 M PE being significantly increased in exposed animals compared to controls (‐9.56%±7.28 vs. ‐59.7±17.4). The levels of IL‐6 were not significant between groups which suggests systemic inflammation may not be a key component of plastic aerosol induced vascular dysfunction. In summary, exposure to polyamide MNPs resulted in less vascular reactivity to pharmacologic stimuli during estrus. However, the mechanisms attributing to disrupted microvascular function remain elusive. An important consideration for future studies will be the proper time point in which various cytokines can be assessed and the reproductive ramifications of these findings. Future studies should examine the impact of plastic particulate inhalation on endothelial inflammatory activation, metabolism, or apoptotic mechanisms. Altogether this information may give insight into how plastic particle inhalation could impair distal tissue health, including endometrial perfusion and ability to sustain pregnancy.

Treatment of preeclamptic vessels with pravastatin enhances vessel function and alters caveolae form and distribution through removal of cellular cholesterol

IntroductionPreeclampsia (PE) causes significant maternal and foetal morbidity and mortality. Maternal vascular endothelial dysfunction contributes to PE resulting in systemic organ dysfunction. Symptoms of PE are most effectively alleviated/managed through pre‐term delivery and/or expectant care, highlighting the need for effective therapies to be identified. The potential clinical applications of pravastatin in the treatment of PE has been reported across multiple studies, however the mechanism(s) behind this is have yet to be elucidated [1, 2].AimsThis study aims to investigate the effect of in vitro pravastatin on uterine microvascular endothelial function in PE, specifically its role in modulating caveolae form and distribution and hence vascular function in PEMethodsMyometrial radial arterioles from caesarean‐section normotensive (NT) and PE patients were incubated with pravastatin (2mM/6h) in vitro. Electron microscopy, immunohistochemistry and pressure myography were used to characterize caveolae and vessel structure and function. Parallel studies conducted with methyl‐β‐cyclodextrin (MβCD) (10mM/1h) examined the effects of removing cholesterol on function.ResultsOverall caveolae density/µm is reduced 24% from 5.5 ± 0.1/µm in NT (n=4, P&lt;0.05) to 4.2 ± 0.01/µm (n=4, P&lt;0.05) in PE vessels, a further 31% to 1.9 ± 0.8/µm (n=4, P&lt;0.05) in PE vessels following treatment with pravastatin. Myoendothelial gap junction density/5mm of vessel length is reduced ~215% from 5.7 ± 1.3/5mm in NT (n=3, P&lt;0.05) to 1.8 ± 0.9/5mm (n=3, P&lt;0.05) in PE vessels. Confocal immunohistochemistry showed decreased caveolin‐1 expression in PE arterioles relative to NT with expression redistributed to endothelial cell borders, following treatment with pravastatin expression was reduced a further ~50% in PE vessels (n=6‐8, P&lt;0.05). Functionally, endothelium‐dependent relaxation was inhibited in arteries from PE compared to NT. Inhibition of NOS/COX reduced bradykinin‐induced dilation in arteries from NT but not PE, suggesting NO/PG‐mediated dilation is lost in PE.. Pravastatin incubation restored endothelium‐dependent relaxation in PE samples to NT levels enhancing the NO and IKCa‐mediated components of relaxation. Incubation with MβCD increased sensitivity (LogEC50 from ‐7.37 to ‐8.24, P&lt;0.05) and maximum dilation to bradykinin in arteries from NT (81.7 ± 4.9.% (n=13) to 94.8 ± 5.2 % (n=8), P&lt;0.05), but had no significant effect in arteries from PE (max 65.6 ± 6.4% (n=17) to 86.5 ± 13.5% (n=3), P&gt;0.05).DiscussionThis data suggests treatment of preeclamptic vessels with pravastatin can be associated with improved vessel function as well as modulation of caveolae form and distribution, specifically though the removal of cellular cholesterol.1. Costantine, M. M. &amp; Cleary, M. K. Obstetrics &amp; Gynecology 121, 349‐353, (2013).2. Esteve‐Valverde, E. et al. Obstetrical &amp; Gynecological Survey 73, 40‐55, (2018).

Small Diameter Penile Implants: A Survey on Current Utilization and Review of Literature

ABSTRACT Introduction The small diameter penile implant (SDPI) is a modified IPP with a smaller diameter cylinder utilized in cases of anatomically small corpora or severe corporal fibrosis. SDPIs allow for patients to obtain useable erections, sometimes with the intent to upsize in the future. There is a dearth of literature on the optimal clinical scenarios for utilization of SDPIs, volume of SDPIs placed nationwide, and patient satisfaction results. Objective Our aim is to identify current usage patterns and perceived patient satisfaction of SDPIs among urologic prosthetic surgeons. Methods A 23-question online survey was distributed via email to physician members of the Sexual Medicine Society of North America (SMSNA) and Society of Urologic Prosthesis Surgeons (SUPS). The survey included questions regarding surgeon experience and volume, frequency of SDPI utilization, indications for SDPI, surgical strategy in the setting of SDPI (approach, use of concordant modeling/grafting), reservoir and pump management, and perceived infection risk and patient satisfaction. Results 50 individuals responded to the survey, 48 of whom routinely utilized SDPIs. The most common indication for SDPI placement was corporal fibrosis from prior infection, followed by anatomically small corpora and priapism. The most common maximal dilation diameter was 10 mm (47%), with an additional 23% of respondents utilizing SDPI with 11 mm dilation. 75.4% of respondents sometimes or always intended to upsize to standard diameter cylinders in the future. 68.8% of surgeons routinely counseled patients on the possibility of reduced girth and rigidity with SDPI. Patient satisfaction was perceived to be comparable to standard diameter cylinders in 56.3% of respondents, while the remaining 43.6% believed it to be lower than traditional cylinders. Conclusions SDPI are utilized by prosthetic surgeons in a variety of clinical situations and are frequently effective. Future research is needed to better characterize patient satisfaction and define which patients are best suited for SDPI. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast and Boston Scientific

Cognitive impairment and microvascular function in end-stage renal disease.

ObjectiveHemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age‐matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels.Methods152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions.ResultsIn unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained.ConclusionThis is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.

Prediction of persistent ventricular dilation by initial ventriculomegaly and clot volume in a porcine model.

While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood. Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time. The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014). Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Carbon dioxide detection using polymer-coated fiber Bragg grating based on volume dilation mechanism and molecular dynamics simulation

Here, we report the polyimide-coated fiber Bragg gratings (FBGs) for CO2 detection based on the mechanism of CO2-induced volume dilation in the polyimide matrix, which resulted in a shift of the Bragg wavelength. The detection results indicate that the polyimide-coated FBGs were of good reversibility and repeatability within CO2-N2 cycles. The molecular mechanism was investigated through the analysis of radial distribution function (RDF) and free accessible volume distributions. The RDF analyses of N2, CH4 and CO2 gases reveal that CO2 has stronger intermolecular interactions with polyimide chains. In the adsorption process, the total fractional free volume inside the polyimide matrix increases as the CO2 concentration increases, simultaneously, the small voids in the polyimide matrix gradually turn into the large voids and the opposite trend is found in the desorption process. The maximum volume dilation values of two polyimide systems are 1.04% (Matrimid® 5218) and 1.13% (P84), thus the corresponding coefficients of gas-sensitive expansion are 3.47 × 10-5/vol% CO2 and 3.77 × 10-5/vol% CO2, respectively. Moreover, theoretical formulas of the relationship between the response strain of the sensor and the gas concentration were obtained, which is invaluable and generic and can be applied to detect various gases.

The Role of Brain-Derived Neurotrophic Factor in Obstructive Sleep Apnea and Endothelial Function in a Pediatric Population With Obesity.

BackgroundChildhood obesity has increased worldwide, becoming a significant public health concern. Brain-derived neurotrophic factor (BDNF) plays an important role in the central regulation of food intake and body weight, but little is known regarding its role in childhood obesity. Next to obesity, BDNF has been linked to obstructive sleep apnea (OSA) and endothelial dysfunction, two obesity-related comorbidities. The aim of this study is to investigate how BDNF, OSA and endothelial dysfunction interact in children with obesity and to determine the effect of weight loss on serum BDNF levels.MethodsChildren and adolescents with obesity aged 8–18 years who were enrolled in a multidisciplinary obesity treatment (MOT) in a tertiary hospital, were prospectively included. Several examinations were conducted during this MOT; at baseline, after 6 months and after 12 months, including the assessment of endothelial function, body composition measurements and a polysomnography. BDNF levels were measured on a serum sample by means of ELISA.ResultsA total of 103 patients with obesity was included, of which 20 had OSA (19.4%). BDNF levels were comparable in children with obesity and OSA and children with obesity but without OSA (26.75 vs. 27.87 ng/ml, p = 0.6). No correlations were found between BDNF and sleep-related variables or between BDNF and endothelial function parameters nor between BDNF and adiposity measures. To investigate if the interaction between OSA and endothelial dysfunction had an influence on BDNF levels, a general linear model was used. This model revealed that a diagnosis of OSA, as well as the interaction between OSA and maximal endothelial dilatation, contributed significantly (p = 0.03, p = 0.04, respectively) to BDNF levels. After 1 year of weight loss therapy, BDNF levels did not change (26.18 vs. 25.46 ng/ml, p = 0.7) in our population.ConclusionBDNF concentrations were comparable in children with obesity, both with and without OSA, indicating that BDNF levels are not affected by OSA. However, we did find an interaction effect of OSA and endothelial function on BDNF levels.

Sutureless Manual Extracapsular Cataract Extraction with Club

Purpose: To evaluate the efficacy and safety of cataract extraction through small pupil with the help of a specially designed instrument called club. Study Design: Interventional case series. Place and Duration of Study: Euro eye clinic from January 2019 to December 2019. Methods: Seventeen consecutive patients with pupil diameter of &lt;4mm after maximal pharmacological dilatation were recruited for study. Inclusion criteria was patients with less than 4mm pupil size after maximum pharmacological dilation. Patient with previous anterior segment surgery and small pupil with posterior synechea were excluded. The instrument (club) was originally designed for breaking posterior synechae. Sutureless Manual Extracapsular Cataract Extraction (SMECE), more commonly known as MSICS, was performed in all cases. After tunnel formation and capsulotomy, club was used to bring lens edge out in pupillary margin. Lens was then maneuvered into anterior chamber and expressed out. Results: All 17 patients had successful SMECE. In one patient pupil was stretched before applying instrument. None of the patients had posterior capsular rupture or hyphaema. Conclusion: This instrument designed in Center of Ophthalmic Instrument and Equipment Designing (COIED) is very useful, safe and cost effective. In Extra Capsular Cataract Extraction (ECCE) or SMECE, surgeons usually do keyhole iridotomy, mechanical stretching or multiple sphincterotomies for managing small pupil. With this new instrument, cataract extraction can be done without surgical trauma to the pupil, thus preserving pupil shape. Key Words: Sutureless Manual Extra capsular Cataract Extraction (SMECE), Manual Small Incision Cataract Surgery (MSICS), Miosis.

Impact of Exercise Modalities on Peripheral and Central Components of Cardiorespiratory Capacity in Heart Transplantation Patients: A Systematic Review and Meta-Analysis.

Background and Objectives: To analyze the effects of aerobic, resistance, and combined training on peripheral and central components related to cardiorespiratory capacity after HTx. Materials and Methods: No time restriction was applied for study inclusion. MEDLINE/PubMed; EMBASE, CENTRAL, and PEDro databases were investigated. Studies reporting heart transplanted patients older than 19 years following aerobic, resistance, and combined training according. The outcomes included: V′O2 peak, VE/V’CO2 slope, heart rate (HR peak), systolic and diastolic blood pressure (SBP and DBP peak), maximum repetition test(1RM), sit-to-stand test, and flow-mediated dilation (FMD). The studies were selected by consensus. Four hundred ninety-two studies initially met the selection criteria. Cochrane handbook was used for abstracting data and assessing data quality and validity. Independent extraction by two observers was applied. Results: Isolated aerobic training leads to a greater increase in V′O2 peak than combined training compared to the control group (p < 0.001, I2 = 0%). However, no significant differences were found in the subgroup comparison (p = 0.19, I2 = 42.1%). HR peak increased similarly after aerobic and combined training. High-intensity interval training (HIIT) was better than moderate continuous intensity to increase the V′O2 after long term in HTx. Still, there is scarce evidence of HIIT on muscle strength and FMD. No change on VE/V’CO2 slope, FMD, and SBP, DBP peak. 1RM and the sit-to-stand test increased after resistance training (p < 0.001, I2 = 70%) and CT (p < 0.001, I2 = 0%) when compared to control. Conclusions: Aerobic and combined training effectively improve VO2 peak and muscle strength, respectively. HIIT seems the better choice for cardiorespiratory capacity improvements. More studies are needed to examine the impact of training modalities on VE/V’CO2 slope and FMD.

Longitudinal ultrasound evaluation of Dilapan-S diameter during cervical ripening

Dilapan-S is commonly inserted in the cervix for a 12-24 hour duration. In vitro evaluation has shown that Dilapan-S rods reach near maximum dilation within 6 to 8 hours. Using transvaginal ultrasound, we sought to evaluate the diameter rate-change of each Dilapan-S rod during cervical ripening. We also evaluated whether soaked gauze placement affects the rate of Dilapan-S diameter change over time.

Small Diameter Penile Implants: A Survey on Current Utilization and Review of Literature.

BackgroundInflatable penile prostheses (IPPs) with smaller diameter cylinders have been in use for over 30 years, yet the literature is sparse on their utilization patterns amongst prosthetic surgeons.AimTo understand current usage of small diameter penile implants (SDPI) among prosthetic surgeons.MethodsIRB approval was obtained to conduct a survey of prosthetic surgeons. A 23-question online survey was distributed via email to physician members of the Sexual Medicine Society of North America (SMSNA) and Society of Urologic Prosthesis Surgeons (SUPS). The survey included questions regarding surgeon experience and volume, frequency of SDPI utilization, indications for SDPI, surgical strategy in the setting of SDPI (approach, use of concordant modeling/grafting), reservoir and pump management, and perceived infection risk and patient satisfaction.Main Outcome MeasureSDPI were utilized by the vast majority of respondents in certain clinical situations such as corporal fibrosis or anatomically small corpora, and surgeons have had a favorable experience with these as a final destination implant or as a place-holder until reimplantation with a normal diameter device.ResultsFifty individuals responded to the survey, 48 of whom routinely utilized SDPI. The most common indication for SDPI placement was corporal fibrosis from prior infection, followed by anatomically small corpora and priapism. The most common maximal dilation diameter was 10 mm (47%), an additional 23% of respondents utilized SDPI with 11 mm dilation. 75.4% of respondents sometimes or always intended to upsize to standard diameter cylinders in the future. 68.8% of surgeons routinely counseled patients on the possibility of reduced grith and rigidity with SDPI. Patient satisfaction was perceived to be comparable to standard diameter cylinders in 56.3% of respondents, while the remaining 43.6% believed it to be lower than traditional cylinders. Utilization of SDPI can be an important tool for prosthetic surgeons faced with difficult cases due to corporal fibrosis or small corpora. This survey provides new insight into patterns of SDPI utilization by surgeons. A limitation of the study is that patient satisfaction is indirectly addressed through surgeons’ perception and experience, further research will be necessary to include patient questionnaires regarding device satisfaction.ConclusionSDPI are necessary in certain scenarios that preclude the use of normal diameter cylinders. These implants may offer satisfactory erections, but can also be upsized to standard diameter cylinders in the future.Campbell SP, Kim CJ, Allkanjari A et al. Small Diameter Penile Implants: A Survey on Current Utilization and Review of Literature. Sex Med 2022;10:100458.

Chronic social defeat stress causes retinal vascular dysfunction

PurposeThe roles of vascular dysfunction and chronic stress have been extensively discussed in the pathophysiology of glaucoma. Our aim was to test whether chronic stress causes retinal vascular dysfunction and therewith induces retinal ganglion cells (RGCs) loss. MethodsTwelve mice underwent chronic social defeat (CSD) stress, while 12 mice received control treatment only. Intraocular pressure (IOP) was measured with a rebound tonometer. Blood plasma corticosterone concentration and adrenal gland weight were used to assess stress levels. Brn-3a staining in retinas and PPD staining in optic nerve cross sections were conducted to assess the survival of RGCs and axons respectively. The ET-1 and α-SMA levels were determined in retina. Retinal vascular autoregulation, functional response to various vasoactive agents and vascular mechanics were measured using video microscopy. ResultsNo significant difference in IOP levels was observed during and after CSD between CSD mice and controls. CSD stress caused hypercortisolemia 2 days post-CSD. However, increased corticosterone levels went back to normal 8 months after CSD. CSD-exposed mice developed adrenal hyperplasia 3 days post-CSD, which was normalized by 8 months. RGC and axon survival were similar between CSD mice and controls. However, CSD stress caused irreversible, impaired autoregulation and vascular dysfunction of retinal arterioles in CSD mice. In addition, impaired maximal dilator capacity of retinal arterioles was observed 8 months post-CSD rather than 3 days post-CSD. Remarkably, ET-1 levels were increased 3 days post-CSD while α-SMA levels were decreased 8 months post-CSD. ConclusionsWe found that CSD stress does not cause IOP elevation, nor loss of RGCs and their axons. However, it strikingly causes irreversible impaired autoregulation and endothelial function in murine retinal arterioles. In addition, CSD changed vascular mechanics on a long-term basis. Increased ET-1 levels and loss of pericytes in retina vessels may involve in this process.

Oxysterols and Retinal Microvascular Dysfunction as Early Risk Markers for Cardiovascular Disease in Normal, Ageing Individuals.

The aim of the present paper is to assess the relationship between oxysterol levels and retinal microvascular function in individuals of various age groups, free of clinically evident diseases. Forty-two apparently healthy individuals were included in the present study (group 1: 19–30 years, group 2: 31–50 years, and group 3: 51–70 years). Retinal microvascular function was assessed using the dynamic retinal vessel analyzer (DVA, IMEDOS GmbH, Jena, Germany). Fasting plasma was obtained from all subjects and quantification of monohydroxy and dihydroxy oxysterols assessment was performed using LC-MS/MS following reverse phase chromatography. A Griess assay was used to evaluate the Nitric Oxide (NO) concentration in all individuals. The glutathione redox ratio was also analyzed by means of whole blood glutathione recycling assay. In all participants, the levels of 7-Ketocholesterol, 25-hydroxycholesterol and 7β-hydroxycholesterol correlated significantly and positively with the time to maximum arteriolar dilation. In addition, 25-hydroxycholesterol and 7β-hydroxycholesterol negatively correlated to the percentage of maximum arteriolar dilation. A negative correlation was observed for 27-hydroxycholesterol and 7β-hydroxycholesterol with microvascular arteriolar constriction. These results suggest that, with age, abnormal oxysterol levels correlate with early changes in microvascular bed function. This relationship could signal early risk for cardiovascular diseases (CVDs) in an ageing population.