Epidemiological studies have shown that cardiovascular disease (CVD) is less common in pre-menopausal women (Pre-MW) compared to men of the same age or post-menopausal women (Post-MW), suggesting ...cardiovascular benefits of estrogen. Estrogen receptors (ERs) have been identified in the vasculature, and experimental studies have demonstrated vasodilator effects of estrogen/ER on the endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several natural and synthetic estrogenic preparations have been developed for relief of menopausal vasomotor symptoms. However, whether menopausal hormone therapy (MHT) is beneficial in postmenopausal CVD remains controversial. Despite reports of vascular benefits of MHT from observational and experimental studies, randomized clinical trials (RCTs), such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women's Health Initiative (WHI), have suggested that, contrary to expectations, MHT may increase the risk of CVD. These discrepancies could be due to agerelated changes in sex hormone synthesis and metabolism, which would influence the effective dose of MHT and the sex hormone environment in Post-MW. Age-related changes in the vascular ER subtype, structure, expression, distribution, and post-ER signaling pathways in the endothelium and VSM, along with factors related to the design of RCTs, preexisting CVD condition, and structural changes in the blood vessels architecture have also been suggested as possible causes of MHT failure in CVD. Careful examination of these factors should help in identifying the causes of the changes in the vascular effects of estrogen with age. The sex hormone metabolic pathways, the active versus inactive estrogen metabolites, and their effects on vascular function, the mitochondria, the inflammatory process and angiogenesis should be further examined. Also, the genomic and non-genomic effects of estrogenic compounds should be viewed as integrated rather than discrete responses. The complex interactions between these factors highlight the importance of careful design of MHT RCTs, and the need of a more customized approach for each individual patient in order to enhance the vascular benefits of MHT in postmenopausal CVD.
An algorithm for estimating signals from short-time magnitude spectra is introduced offering a significant improvement in quality and efficiency over current methods. The key issue is how to invert a ...sequence of overlapping magnitude spectra (a ldquospectrogramrdquo) containing no phase information to generate a real-valued signal free of audible artifacts. Also important is that the algorithm performs in real-time, both structurally and computationally. In the context of spectrogram inversion, structurally real-time means that the audio signal at any given point in time only depends on transform frames at local or prior points in time. Computationally, real-time means that the algorithm is efficient enough to run in less time than the reconstructed audio takes to play on the available hardware. The spectrogram inversion algorithm is parameterized to allow tradeoffs between computational demands and the quality of the signal reconstruction. The algorithm is applied to audio time-scale and pitch modification and compared to classical algorithms for these tasks on a variety of signal types including both monophonic and polyphonic audio signals such as speech and music.
Background A greater incidence of varicose veins has been reported in premenopausal women than in men. We hypothesized that the sex differences in venous function reflect reduced constriction and ...enhanced venous dilation in women due to direct venous relaxation effects of estrogen on specific estrogen receptors (ER). Methods Circular segments of inferior vena cava (IVC) from male and female Sprague-Dawley rats were suspended between two wires, and isometric contraction (in mg/mg tissue) to phenylephrine, angiotensin II (AngII), and 96 mM KCl was measured. To investigate sex differences in venous smooth muscle, Ca2+ release from the intracellular stores, and Ca2+ entry from the extracellular space, the transient phenylephrine contraction in 0 Ca2+ Krebs was measured. Extracellular CaCl2 (0.1, 0.3, 0.6, 1, 2.5 mM) was added, and the Ca2+ e -dependent contraction was measured. To investigate sex differences in venous endothelial function, acetylcholine-induced relaxation was measured. To test the role of specific ERs, the amount of venous tissue ERs was measured using Western blots, and the venous relaxation in response to 17β-estradiol (E2, activator of most ERs), 4,4,′4′′-(4-propyl-1H-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ERα agonist), 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; ERβ agonist), and ICI 182,780 (ERα/ERβ antagonist, and G protein-coupled receptor 30 GPR30 agonist) was measured in IVC segments nontreated or treated with the nitric oxide synthase (NOS) inhibitor Nω -nitro-L-arginine methyl ester (L-NAME). Results Phenylephrine caused concentration-dependent contraction that was less in female (max 104.2 ± 16.2) than male IVC (172.4 ± 20.4). AngII (10−6 )-induced contraction was also less in female (81.0 ± 11.1) than male IVC (122.5 ± 15.0). Phenylephrine contraction in 0 Ca2+ Krebs was insignificantly less in female (4.8 ± 1.8) than male IVC (7.2 ± 1.7), suggesting little difference in the intracellular Ca2+ release mechanism. In contrast, the Ca2+ e -dependent contraction was significantly reduced in female than male IVC. Also, contraction to membrane depolarization by 96 mM KCl, which stimulates Ca2+ influx, was less in female (129.7 ± 16.7) than male IVC (319.7 ± 30.4), supporting sex differences in Ca2+ entry. Acetylcholine relaxation was greater in female (max 80.6% ± 4.1%) than male IVC (max 48.0% ± 6.1%), suggesting sex differences in the endothelium-dependent relaxation pathway. Western blots revealed greater amounts of ERα, ERβ, and GPR30 in female than male IVC. ER agonists caused concentration-dependent relaxation of phenylephrine contraction in female IVC. E2-induced relaxation (max 76.5% ± 3.4%) was more than DPN (74.8% ± 9.1%), PPT (71.4% ± 12.5%), and ICI 182,780 (67.4% ± 7.8%), and was similar in L-NAME-treated and nontreated IVC. Conclusion The reduced α-adrenergic, AngII, depolarization-induced, and Ca2+ e -dependent venous contraction in female rats is consistent with sex differences in the Ca2+ entry mechanisms, possibly due to enhanced endothelium-dependent vasodilation and increased ER expression/activity in female rats. E2/ER-mediated venous relaxation in female rats is not prevented by NOS blockade, suggesting activation of an NO-independent relaxation pathway. The decreased venous contraction and enhanced E2/ER-mediated venous relaxation would lead to more distensible veins in female rats.
Summary
Reasons for performing study: Previous studies have shown that in man ultrasonography is more accurate than radiography for detecting rib fractures.
Objectives: To describe clinical, ...radiographic and ultrasonographic findings related with rib fractures in newborn foals in an equine critical care unit; and to compare diagnostic accuracy of ultrasonography to radiography.
Methods: A prospective ultrasonographic study was performed on 29 foals presented to the emergency unit. This study was performed at the Centre Hospitalier Universitaire Vétérinaire (CHUV), University of Montreal. Physical examination as well as radiographic and ultrasonographic examinations were performed.
Results: Thoracic radiographs revealed 10 rib fractures in 5 of 26 (19%) foals. Ultrasonography revealed 49 fractures in 19 of 29 (65%) foals of which fillies (n = 13; 68%) were significantly over represented as were fractures to the left thorax (n = 15; 78%). Seventeen of 19 foals (90%) had rib fractures located 3 cm or less from the costochondral junction, the distal part of the rib being displaced laterally in all cases. In 2 foals, where both thoracic radiographs and ultrasonography detected rib fractures, the site of fractures was located on the mid portion of the rib. Rib fractures were detected only by thoracic radiographs in one foal. Sixty‐five percent (32/49) of fractured ribs had a moderate displacement (1–4 mm).
Conclusions: Rib fractures are seen frequently in newborn foals in equine critical care units. Ultrasonography is more accurate than radiography and reveals fractures in most patients presented in emergency. The position (costochondral junction) of rib fractures and of the fragments suggest that most thoracic trauma probably occurs during parturition.
Potential relevance: Ultrasound imaging increases awareness and improves the diagnosis of rib fractures in newborn foals.
To evaluate the sonographic findings of plantar fasciitis.
Both feet of 15 patients who had a clinical diagnosis of plantar fasciitis were evaluated with ultrasound (US) by using a 7.0-MHz ...linear-array transducer. Heel pain was unilateral in 11 patients and bilateral in four. Sagittal sonograms were obtained, and the thickness of the plantar fascia was measured at its proximal end near its insertion into the calcaneus. Other observations included hypoechoic fascia, fiber rupture, perifascial fluid collections, and calcifications. Both feet of 15 healthy volunteers were also evaluated as a control group.
Plantar fascia thickness was significantly increased in the heels in patients with plantar fasciitis (3.2-6.8 mm; mean, 5.2 mm +/- 1.13) compared with their asymptomatic heels (2.0-4.0 mm; mean, 2.9 mm +/- 0.70) (P < .0001) and compared with the heels of the patients in the control group (1.6-3.8 mm; mean, 2.6 mm +/- 0.48) (P < .0001). The proximal plantar fascia of 16 (84%) symptomatic heels were diffusely hypoechoic compared with none of the patients' asymptomatic heels and only one heel of a patient in the volunteer group. No fascia rupture, perifascial fluid collection, or calcifications were identified.
Increased thickness of the fascia and hypoechoic fascia are sonographic findings of plantar fasciitis. US may be a valuable noninvasive technique for the diagnosis of plantar fasciitis.
Background Varicose veins (VarVs) are a common disorder of venous dilation and tortuosity with unclear mechanism. The functional integrity and the ability of various regions of the VarVs to constrict ...is unclear. This study tested the hypothesis that the different degrees of venodilation in different VarV regions reflect segmental differences in the responsiveness to receptor-dependent vasoconstrictive stimuli and/or in the postreceptor signaling mechanisms of vasoconstriction. Methods Varix segments and adjacent proximal and distal segments were obtained from patients undergoing VarV stripping. Control great saphenous vein specimens were obtained from patients undergoing lower extremity arterial bypass and coronary artery bypass grafting. Circular vein segments were equilibrated under 2 g of tension in a tissue bath, and changes in isometric constriction in response to angiotensin II (AngII, 10–11 -10–7 M), phenylephrine (PHE, 10–9 -10–4 M), and KCl (96 mM) were recorded. The amount of angiotensin type 1 receptor (AT1 R) was measured in vein tissue homogenate. Results AngII caused concentration-dependent constriction in control vein (max 35.3 ± 9.6 mg/mg tissue, pED50 8.48 ± 0.34). AngII caused less contraction and was less potent in proximal (max 7.9 ± 2.5, pED50 6.85 ± 0.61), distal (max 5.7 ± 1.2, pED50 6.74 ± 0.68), and varix segments of VarV (max 7.2 ± 2.0, pED50 7.11 ± 0.50), suggesting reduced AT1 R-mediated contractile mechanisms. VarVs and control veins had similar amounts of AT1 R. α-adrenergic receptor stimulation with PHE caused concentration-dependent constriction in control veins (max 73.0 ± 13.9 mg/mg tissue, pED50 5.48 ± 0.12) exceeding that of AngII. PHE produced similar constriction and was equally potent in varix and distal segments but produced less constriction and was less potent in proximal segments of VarVs (max 32.1 ± 6.4 mg/mg tissue, pED50 4.89 ± 0.13) vs control veins. Membrane depolarization by 96 mM KCl, a receptor-independent Ca2+ -dependent response, produced significant constriction in control veins and similar contractile response in proximal, distal, and varix VarV segments, indicating tissue viability and intact Ca2+ -dependent contraction mechanisms. Conclusions Compared with control veins, different regions of VarV display reduced AngII-mediated venoconstriction, which may be involved in the progressive dilation in VarVs. Postreceptor Ca2+ -dependent contraction mechanisms remain functional in VarVs. The maintained α-adrenergic responses in distal and varix segments, and the reduced constriction in the upstream proximal segments, may represent a compensatory adaptation of human venous smooth muscle to facilitate venous return from the dilated varix segments of VarV.
We report on a search for elementary particles with charges much smaller than the electron charge using a data sample of proton-proton collisions provided by the CERN Large Hadron Collider in 2018, ...corresponding to an integrated luminosity of 37.5 fb−1 at a center-of-mass energy of 13 TeV. A prototype scintillator-based detector is deployed to conduct the first search at a hadron collider sensitive to particles with charges ≤ 0.1 e . The existence of new particles with masses between 20 and 4700 MeV is excluded at 95% confidence level for charges between 0.006 e and 0.3 e , depending on their mass. New sensitivity is achieved for masses larger than 700 MeV.
Abstract Aim Both type 1 and 2 diabetes are associated with differential regulation of leptin, adiponectin and ASP. Our aim was to examine whether or not acute hyperinsulinaemia and/or hyperglycaemia ...per se have differential regulation of these hormones in healthy subjects. Methods We examined changes in leptin, adiponectin and ASP concentrations and subcutaneous white adipose tissue mRNA expression with 3-hour hyperinsulinaemic (HI, n = 10), hyperglycaemic (HG, n = 7) and hyperinsulinaemic-hyperglycaemic (HGHI, n = 8) clamps in healthy lean young men. As somatostatin was used for the HG and HGHI clamps, a control somatostatin clamp was carried out ( n = 4). Changes in the expression of HKII and p85α Pi3K were examined as positive controls for the induction of gene expression by the insulin pathway. Results HI, HG and HGHI clamps increased expression of HKII and p85α Pi3K while somatostatin did not. The HI clamp decreased serum adiponectin (−15%, P < 0.001) and increased serum leptin (+11%, P = 0.031), while the HG clamp reduced serum leptin (−20%, P = 0.003). The HGHI clamp increased serum ASP (+21%, P = 0.047) and expression of C3 (+26%, P = 0.018) and leptin (+50%, P = 0.024). Interestingly, the control somatostatin clamp suppressed both serum leptin (−17%, P = 0.043) and adiponectin (−7%, P = 0.020). Conclusion HG and/or HI per se regulated the concentrations and expression of leptin, adiponectin and ASP in healthy lean young men, suggesting a contribution to dysregulation of these hormones in diabetes.
Ultrasound is a low-cost, nonionizing, readily available diagnostic technique for the evaluation of tendons, muscles, soft tissue masses, cysts, and other fluid collections. Ultrasound is also a ...valuable tool for guiding a variety of musculoskeletal interventions. Procedures that can be performed under ultrasound guidance include aspiration of fluid for analysis, injection for medication, decompression of cysts, drainage of abscess and hematoma, biopsy, treatment of calcified tendinitis, and foreign body retrieval.
Objective— To describe a surgical technique involving distraction and stabilization of the lumbosacral vertebral segment using an external skeletal fixator in dogs with lumbosacral instability caused ...by discospondylitis.
Study Design— Retrospective clinical study.
Animals— Four client‐owned dogs.
Methods— Medical records of all dogs diagnosed with discospondylitis from 1994 to 1997 were identified and reviewed. Four dogs with lumbosacral discospondylitis requiring surgical treatment were then specifically studied. Surgical technique, clinical signs, preoperative diagnostic investigation, radiographic findings, and the results of short‐term and long‐term reevaluations were recorded.
Results— Twelve dogs with discospondylitis were identified, 4 of which had lumbosacral discospondylitis. These 4 dogs underwent surgical distraction and stabilization because they failed to respond to medical treatment. Three dogs received a cancellous bone graft between L7 and S1 and had rapid interbody fusion of this vertebral segment. The dog that did not receive a graft did not have interbody fusion at the time of fixator removal. This did not affect the final clinical outcome. Lumbosacral pain and neurological deficits present before surgery rapidly subsided after the procedure. All dogs received concurrent antibiotic treatment for a minimum of 4 weeks. All dogs were clinically normal at the time of fixator removal and all continued to do well during the follow‐up period (8–48 months; mean, 27.5 months).
Conclusion and Clinical Relevance— Lumbosacral discospondylitis may not respond well to conservative treatment because of the mobility of the affected space. Surgical treatment involving distraction and stabilization to obtain intervertebral fusion is very effective in treating lumbosacral instability caused by discospondylitis.
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