Chronic Mesenteric Ischemia (CMI) presenting as acute abdomen can be treated percutaneously. An endovascular intervention has surpassed surgical revascularization over the past decade due to its lesser perioperative complication rate. Trans-femoral approach of revascularising is limited by its difficulty in coaxial alignment of the guiding catheter and hence, brachial artery and recently the radial approach have been utilized for mesenteric artery revascularisation for over a decade. Here by we report a case of chronic mesenteric ischemia having total occlusion of two and 70% occlusion of one of the three mesenteric vessels. The patient had presented with acute abdomen which in turn was percutaneously revascularised via the left brachial artery for the two major abdominal visceral vessels being superior mesenteric artery and inferior mesenteric artery.
Brachial artery; Chronic mesenteric ischemia; Inferior mesenteric artery; Superior mesenteric artery
We hypothesized that transfer of the olecranon tip for simulated type III coronoid fracture would restore posterior ulnohumeral translation to a level not different from that in the intact state.
The collateral ligaments were left intact in 12 fresh-frozen cadaveric elbows, and all other soft tissues were removed. The entire coronoid process was osteotomized flush with the ventral aspect of the ulna and was reconstructed using the tip of the olecranon process. Specimens were tested with an axial load of 100 N at 0.25 mm/s in 15° increments from 15 to 120° of flexion. Intact, osteotomized, and reconstructed posterior ulnohumeral displacement was measured.
The bony reconstruction did not obstruct range of motion of the elbow. Intact translation (mean ± SD) ranged from 0.3 ± 0.1 to 1.1 ± 0.6 mm, and translation in the osteotomized state ranged from 1.3 ± 1.0 to 2.0 ± 1.0 mm. Resection of the coronoid resulted in a significant increase in posterior ulnar translation compared with intact at all flexion angles (p < 0.05) except at 75°. Reconstruction decreased translation versus the osteotomized state at all flexion angles, significantly at 60 and 120°. No significant difference in translation was found between reconstructed and intact states at five of eight positions tested.
In this biomechanical study of irreparable coronoid fracture, autograft olecranon tip transfer restored posterior elbow stability to a level not significantly different from the intact elbow in five of eight elbow positions tested.
Olecranon; Coronoid; Osteochondral; Allograft; Biomechanical
An increasing number of hospitals and health systems utilize social media to allow users to provide feedback and ratings. The correlation between ratings on social media and more conventional hospital quality metrics remains largely unclear, raising concern that healthcare consumers may make decisions on inaccurate or inappropriate information regarding quality.
The purpose of this study was to examine the extent to which hospitals utilize social media and whether user-generated metrics on Facebook® correlate with a Hospital Compare® metric, specifically 30-day all cause unplanned hospital readmission rates.
DESIGN AND PARTICIPANTS
This was a retrospective cross-sectional study conducted among all U.S. hospitals performing outside the confidence interval for the national average on 30-day hospital readmission rates as reported on Hospital Compare. Participants were 315 hospitals performing better than U.S. national rate on 30-day readmissions and 364 hospitals performing worse than the U.S. national rate.
The study analyzed ratings of hospitals on Facebook’s five-star rating scale, 30-day readmission rates, and hospital characteristics including beds, teaching status, urban vs. rural location, and ownership type.
Hospitals performing better than the national average on 30-day readmissions were more likely to use Facebook than lower-performing hospitals (93.3 % vs. 83.5 %; p < 0.01). The average rating for hospitals with low readmission rates (4.15 ± 0.31) was higher than that for hospitals with higher readmission rates (4.05 ± 0.41, p < 0.01). Major teaching hospitals were 14.3 times more likely to be in the high readmission rate group. A one-star increase in Facebook rating was associated with increased odds of the hospital belonging to the low readmission rate group by a factor of 5.0 (CI: 2.6–10.3, p < 0.01), when controlling for hospital characteristics and Facebook-related variables.
Hospitals with lower rates of 30-day hospital-wide unplanned readmissions have higher ratings on Facebook than hospitals with higher readmission rates. These findings add strength to the concept that aggregate measures of patient satisfaction on social media correlate with more traditionally accepted measures of hospital quality.
Performance measurement; Patient satisfaction; Consumer health informatics
Molecular imprinting is earning worldwide attention from researchers in the field of sensing and diagnostic applications, due to its properties of inevitable specific affinity for the template molecule. The fabrication of complementary template imprints allows this technique to achieve high selectivity for the analyte to be sensed. Sensors incorporating this technique along with surface plasmon or localized surface plasmon resonance (SPR/LSPR) provide highly sensitive real time detection with quick response times. Unfolding these techniques with optical fiber provide the additional advantages of miniaturized probes with ease of handling, online monitoring and remote sensing. In this review a summary of optical fiber sensors using the combined approaches of molecularly imprinted polymer (MIP) and the SPR/LSPR technique is discussed. An overview of the fundamentals of SPR/LSPR implementation on optical fiber is provided. The review also covers the molecular imprinting technology (MIT) with its elementary study, synthesis procedures and its applications for chemical and biological anlayte detection with different sensing methods. In conclusion, we explore the advantages, challenges and the future perspectives of developing highly sensitive and selective methods for the detection of analytes utilizing MIT with the SPR/LSPR phenomenon on optical fiber platforms.
optical fiber; sensor; surface plasmon resonance; molecular imprinting
Tuberous Sclerosis Complex (TSC) is a genetic hamartoma syndrome frequently associated with severe intractable epilepsy. In some TSC patients epilepsy surgery is a promising treatment option provided that the epileptogenic zone can be precisely delineated. TSC brain lesions (cortical tubers) contain dysmorphic neurons, brightly eosinophilic giant cells and white matter alterations in various proportions. However, a histological classification system has not been established for tubers. Therefore, the aim of this study was to define distinct histological patterns within tubers based on semi-automated histological quantification and to find clinically significant correlations. In total, we studied 28 cortical tubers and seven samples of perituberal cortex from 28 TSC patients who had undergone epilepsy surgery. We assessed mammalian target of rapamycin complex 1 (mTORC1) activation, the numbers of giant cells, dysmorphic neurons, neurons, and oligodendrocytes, and calcification, gliosis, angiogenesis, inflammation, and myelin content. Three distinct histological profiles emerged based on the proportion of calcifications, dysmorphic neurons and giant cells designated types A, B, and C. In the latter two types we were able to subsequently associate them with specific features on presurgical MRI. Therefore, these histopathological patterns provide consistent criteria for improved definition of the clinico-pathological features of cortical tubers identified by MRI and provide a basis for further exploration of the functional and molecular features of cortical tubers in TSC.
Defaunation is causing declines of large-seeded animal-dispersed trees in tropical forests worldwide, but whether and how these declines will affect carbon storage across this biome is unclear. Here we show, using a pan-tropical data set, that simulated declines of large-seeded animal-dispersed trees have contrasting effects on aboveground carbon stocks across Earth's tropical forests. In our simulations, African, American and South Asian forests, which have high proportions of animal-dispersed species, consistently show carbon losses (2–12%), but Southeast Asian and Australian forests, where there are more abiotically dispersed species, show little to no carbon losses or marginal gains (±1%). These patterns result primarily from changes in wood volume, and are underlain by consistent relationships in our empirical data (∼2,100 species), wherein, large-seeded animal-dispersed species are larger as adults than small-seeded animal-dispersed species, but are smaller than abiotically dispersed species. Thus, floristic differences and distinct dispersal mode–seed size–adult size combinations can drive contrasting regional responses to defaunation.
Defaunation is linked to the decline of tree species that depend on large animals for seed dispersal, but it is unclear if this affects carbon storage. Here the authors show that defaunation effects on carbon storage vary across continents, driven by relationships between seed dispersal strategies and adult tree size.
Tuberous sclerosis complex (TSC) is a multisystem disorder that results from mutations in the TSC1 or TSC2 genes, leading to constitutive activation of the mammalian target of rapamycin (mTOR) signaling pathway. Cortical tubers represent typical lesions of the central nervous system (CNS) in TSC. The pattern of cortical layering disruption observed in brain tissue of TSC patients is not yet fully understood, and little is known about the origin and phenotype of individual abnormal cell types recognized in tubers.
In the present study, we aimed to characterize dysmorphic neurons (DNs) and giant cells (GCs) of cortical tubers using neocortical layer-specific markers (NeuN, SMI32, Tbr1, Satb2, Cux2, ER81, and RORβ) and to compare the features with the histo-morphologically similar focal cortical dysplasia (FCD) type IIb. We studied a cohort of nine surgically resected cortical tubers, five FCD type IIb, and four control samples using immunohistochemistry and in situ hybridization.
Cortical tuber displayed a prominent cell loss in all cortical layers. Moreover, we observed altered proportions of layer-specific markers within the dysplastic region. DNs, in both tubers and FCD type IIb, were found positive for different cortical layer markers, regardless of their laminar location, and their immunophenotype resembles that of cortical projection neurons.
These findings demonstrate that, similar to FCD type IIb, cortical layering is markedly disturbed in cortical tubers of TSC patients. Distribution of these disturbances is comparable in all tubers and suggests a dysmaturation affecting early and late migratory patterns, with a more severe impairment of the late stage of maturation.
Electronic supplementary material
The online version of this article (doi:10.1186/s11689-016-9142-0) contains supplementary material, which is available to authorized users.
Tuberous sclerosis complex; Cortical layer markers; Epilepsy; Neurosurgery; Neuropathology
We evaluated effects of botulinum toxin A (Botox) and cast immobilization on tendon healing in a rat model. Injection of Botox into rat supraspinatus was hypothesized to reduce muscle active force and improved healing.
Eighty-four supraspinatus tendons were surgically transected and repaired in 42 Sprague-Dawley rats (transosseous technique). After repair, supraspinatus muscle was injected with saline or Botox (3 or 6 U/kg). Half the shoulders were cast-immobilized for the entire postoperative period; half were allowed free cage activity. Histology was examined at 2, 4, 8, and 12 weeks. A healing zone cross-sectional area was measured, and biomechanical testing of repair strength and tendon viscoelastic properties was conducted at 4 and 12 weeks.
Botox alone and cast immobilization alone exhibited increased ultimate load compared with controls (saline injection, no immobilization) at 4 weeks. No difference in ultimate load occurred between Botox-only and cast-only groups. At 12 weeks, the Botox (6 U/kg) plus cast immobilization group was significantly weakest (p < 0.05). A trend was shown toward decreased healing zone cross-sectional areas in casted groups.
Supraspinatus Botox injection after rotator cuff repair might help protect the repair. However, cast immobilization plus Botox administration is harmful to rotator cuff healing in a rat tendon model.
Rotator cuff repair; Botulinum toxin A (Botox); Cast immobilization; Tendon healing; Rat model
The biological factors associated with shoulder osteoarthritis (OA) have not been elucidated. The purpose of this study was to investigate putative osteoarthritic biomarkers of the shoulder. To our knowledge, this is the first study to analyze shoulder cartilage for OA-associated genes and examine human shoulder cartilage for a novel biomarker, connexin 43 (Cx43).
Materials and methods
Cartilage from 16 osteoarthritic and 10 non-osteoarthritic humeral heads was assessed for expression of the following genes via real-time polymerase chain reaction: types I, II, and X collagen, metalloproteinases (MMP), tissue inhibitors of MMP (TIMP), interleukins, versican, cyclooxygenase-2 (Cox-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNFα), aggrecanase-2 (ADAMTS5), and Cx43.
In osteoarthritic shoulders, gene expression of Cx43, ADAMTS5, collagen type I, Cox-2, versican, and TIMP-3 showed predominance (85-, 33-, 13-, 12-, 11.5-, and 3-fold increases, respectively) relative to non-osteoarthritic controls. Spearman correlation analysis showed significant correlations between Cx43 and collagen types I, II, and X, MMP-9, TIMP-2 and -3, versican, Cox-2, iNOS, and ADAMTS5. In osteoarthritic shoulders, Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP3, and TNFα expressions were significantly increased compared with controls. TIMP-3 and iNOS trended toward significance, with robust expression in osteoarthritic shoulders and low expression in non-osteoarthritic shoulders.
Certain genes are markedly up-regulated in osteoarthritic shoulders compared with non-osteoarthritic shoulders, with Cx43, Cox-2, versican, collagen type I, ADAMTS5, MMP3, and TNFα expression being significantly increased. These genes might be useful biomarkers for examining shoulder OA.
Shoulder; osteoarthritis; biomarkers; connexin 43
Total shoulder arthroplasty (TSA) provides an effective solution for the treatment of glenohumeral arthritis. However, long-term outcomes have been limited by glenoid component aseptic loosening and polyethylene (PE) wear. Previous attempts to improve glenoid fixation with metal-backed glenoids resulted in inferior results. Newer component designs that contain porous metal allow for biological ingrowth of the prosthesis, potentially improving longevity and overall outcomes. Porous metal can also improve humeral component fixation, obviating the need for cement and simplifying revision surgery. Advances such as highly cross-linked polyethylene (HXLPE), vitamin E-doped HXLPE, and alternate bearing surfaces like ceramics and pyrolytic carbon have proven to provide superior wear characteristics in other joint replacements and may prove beneficial in the shoulder as well.
Total shoulder arthroplasty; Glenoid component failure; Porous metal; Trabecular metal; Stemless arthroplasty; Pyrolytic carbon
Asthma is a disease of acute and chronic inflammation in which cytokines play a critical role in orchestrating the allergic inflammatory response. IL-13 and transforming growth factor (TGF)-β promote fibrotic airway remodeling, a major contributor to disease severity. Improved understanding is needed, because current therapies are inadequate for suppressing development of airway fibrosis. IL-13 is known to stimulate respiratory epithelial cells to produce TGF-β, but the mechanism through which this occurs is unknown. Here, we tested the hypothesis that reactive oxygen species (ROS) are a critical signaling intermediary between IL-13 or allergen stimulation and TGF-β–dependent airway remodeling. We used cultured human bronchial epithelial cells and an in vivo mouse model of allergic asthma to map a pathway where allergens enhanced mitochondrial ROS, which is an essential upstream signal for TGF-β activation and enhanced collagen production and deposition in airway fibroblasts. We show that mitochondria in airway epithelium are an essential source of ROS that activate TGF-β expression and activity. TGF-β from airway epithelium stimulates collagen expression in fibroblasts, contributing to an early fibrotic response to allergen exposure in cultured human airway cells and in ovalbumin-challenged mice. Treatment with the mitochondrial-targeted antioxidant, (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mitoTEMPO), significantly attenuated mitochondrial ROS, TGF-β, and collagen deposition in OVA-challenged mice and in cultured human epithelial cells. Our findings suggest that mitochondria are a critical source of ROS for promoting TGF-β activity that contributes to airway remodeling in allergic asthma. Mitochondrial-targeted antioxidants may be a novel approach for future asthma therapies.
airway remodeling; asthma; reactive oxygen species; mitochondria
Introduction. Digoxin is used to control ventricular rate in atrial fibrillation (AF). There is conflicting evidence regarding safety of digoxin. We aimed to evaluate the risk of mortality with digoxin use in patients with AF using meta-analyses. Methods. PubMed was searched for studies comparing outcomes of patients with AF taking digoxin versus no digoxin, with or without heart failure (HF). Studies were excluded if they reported only a point estimate of mortality, duplicated patient populations, and/or did not report adjusted hazard ratios (HR). The primary endpoint was all-cause mortality. Adjusted HRs were combined using generic inverse variance and log hazard ratios. A multivariate metaregression model was used to explore heterogeneity in studies. Results. Twelve studies with 321,944 patients were included in the meta-analysis. In all AF patients, irrespective of heart failure status, digoxin is associated with increased all-cause mortality (HR [1.23], 95% confidence interval [CI] 1.16–1.31). However, digoxin is not associated with increased mortality in patients with AF and HF (HR [1.08], 95% CI 0.99–1.18). In AF patients without HF digoxin is associated with increased all-cause mortality (HR [1.38], 95% CI 1.12–1.71). Conclusion. In patients with AF and HF, digoxin use is not associated with an increased risk of all-cause mortality when used for rate control.
Implants have been gaining popularity amongst the patients and frequently are being considered as a first treatment option. Modern dentistry is beginning to understand, realize, and utilize the benefits of biotechnology in health care. Study of material sciences along with the biomechanical sciences provides optimization of design and material concepts for surgical implants. Biocompatibility is property of implant material to show favorable response in given biological environment. In attempt to replace a missing tooth many biomaterials have been evolved as implants for many years in an effort to create an optimal interaction between the body and the implanted material. With all the advancements and developments in the science and technology, the materials available for dental implants also improved. The choice of material for a particular implant application will generally be a compromise to meet many different required properties. There is, however, one aspect that is always of prime importance that how the tissue at the implant site responds to the biochemical disturbance that a foreign material presents.
Titanium; Osteointegration; Zirconia; Sandblasting; Bioglass; Hydroxyapetite
Gagging is of great concern to the dentist as it is a serious impediment during the execution of various dental procedures. The etiology of gagging is multifactorial, and several suggestions have been offered to arrest this reflex, some of which are nonsustainable and does not show the immediate result. Acupuncture has been successfully employed as an adjunct to local anesthesia in dental extractions, pain management and also in the symptomatic management of temporomandibular joint disorders. The author highlights the application of acupuncture in the management of patients with gag reflex during dental procedures and its benefits are reported.
Acupuncture; alternative medicine; gagging; gag reflex
The use of questionable abutments has been made possible by modifying the design of the prosthesis. Telescopic retainers help to retain a prosthesis on a tilted and malaligned abutments.
Copings; removable prosthesis; telescopic bridge; telescopic retainer
Tuberous sclerosis complex (TSC) is a genetic disease resulting from mutation in TSC1 or TSC2 and subsequent hyperactivation of mammalian Target of Rapamycin (mTOR). Common TSC features include brain lesions, such as cortical tubers and subependymal giant cell astrocytomas (SEGAs). However, the current treatment with mTOR inhibitors has critical limitations. We aimed to identify new targets for TSC pharmacotherapy.
The results of our shRNA screen point to glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme in glutathione synthesis, as a contributor to TSC-related phenotype. GCLC inhibition increased cellular stress and reduced mTOR hyperactivity in TSC2-depleted neurons and SEGA-derived cells. Moreover, patients’ brain tubers showed elevated GCLC and stress markers expression. Finally, GCLC inhibition led to growth arrest and death of SEGA-derived cells.
We describe GCLC as a part of redox adaptation in TSC, needed for overgrowth and survival of mutant cells, and provide a potential novel target for SEGA treatment.
Electronic supplementary material
The online version of this article (doi:10.1186/s40478-015-0225-z) contains supplementary material, which is available to authorized users.
Tuberous Sclerosis Complex; Glutamate-cysteine ligase; Cellular stress; Brain tumors; Cell death
The microseminoprotein gene encoding prostate secretory protein of 94 amino acids (PSP94) harbours a potential risk allele (rs10993994) for prostate cancer (PCa) in its promoter region. However, studies on rs10993994 have been sparse in Asian Indians.
The present study recruited a sample population of 44 benign prostatic hyperplasia patients, 33 PCa patients and 60 healthy participants, of which, participants without other confounding risk factors for PCa were retained. The serum PSP94 (sPSP94) levels were measured by a serum-based ELISA in an earlier study. A novel RFLP technique was developed to screen for rs10993994 which was validated with direct sequencing.
Sequencing showed additional 4 SNPs (rs41274660, rs141211965, rs12770171, rs10669586) and 2 novel variants (GenBank accession nos. KM265191 and KM265192). In silico DNA topographical studies predicted that KM265192 would have higher cleavage intensity and more accessibility for binding of transcription factors. Even though, similar frequencies were observed for all the variants in all the three study groups, the risk allele ‘T’ (rs10993994) was seen to be associated with reduced PSP94 expression both at mRNA and protein level. Further, mRNA expression as studied by real-time PCR correlated positively with sPSP94 levels. Interestingly, CC genotype of rs10993994 showed highest sPSP94 levels in all the three study groups and was associated with Gleason score ≤7 in PCa patients. In contrast, TT genotype of rs10993994 was associated with lesser sPSP94 levels and with aggressiveness of PCa.
rs10993994 was found to be a functional SNP in the studied Asian Indian population.
PCa; BPH; RFLP; Novel variants
An outbreak investigation identified a plausible transmission route that may contribute to the large and poorly characterized human disease burden of Campylobacter jejuni from cattle and demonstrated an approach to testing this hypothesis through integration of genomic analysis in surveillance.
Background. Cattle are the second most common source of human campylobacteriosis. However, routes to account for this scale of transmission have not been identified. In contrast to chicken, red meat is not heavily contaminated at point of sale. Although effective pasteurization prevents milk-borne infection, apparently sporadic infections may include undetected outbreaks from raw or perhaps incompletely pasteurized milk.
Methods. A rise in Campylobacter gastroenteritis in an isolated population was investigated using whole-genome sequencing (WGS), an epidemiological study, and environmental investigations.
Results. A single strain was identified in 20 cases, clearly distinguishable from other local strains and a reference population by WGS. A case-case analysis showed association of infection with the outbreak strain and milk from a single dairy (odds ratio, 8; Fisher exact test P value = .023). Despite temperature records indicating effective pasteurization, mechanical faults likely to lead to incomplete pasteurization of part of the milk were identified by further testing and examination of internal components of dairy equipment.
Conclusions. Here, milk distribution concentrated on a small area, including school-aged children with low background incidence of campylobacteriosis, facilitated outbreak identification. Low-level contamination of widely distributed milk would not produce as detectable an outbreak signal. Such hidden outbreaks may contribute to the substantial burden of apparently sporadic Campylobacter from cattle where transmission routes are not certain. The effective discrimination of outbreak isolates from a reference population using WGS shows that integrating these data and approaches into surveillance could support the detection as well as investigation of such outbreaks.
Campylobacter; cattle; milk; whole-genome sequencing; pasteurization
Multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by angiotensin II (Ang II) in cultured vascular smooth muscle cells (VSMCs), but its function in experimental hypertension has not been explored. The aim of this study was to determine the impact of CaMKII inhibition selectively in VSMCs on Ang II hypertension.
Methods and Results
Transgenic expression of a CaMKII peptide inhibitor in VSMCs (TG SM-CaMKIIN model) reduced the blood pressure response to chronic Ang II infusion. The aortic depressor nerve activity was reset in hypertensive versus normotensive wild-type animals but not in TG SM-CaMKIIN mice, suggesting that changes in baroreceptor activity account for the blood pressure difference between genotypes. Accordingly, aortic pulse wave velocity, a measure of arterial wall stiffness and a determinant of baroreceptor activity, increased in hypertensive versus normotensive wild-type animals but did not change in TG SM-CaMKIIN mice. Moreover, examination of blood pressure and heart rate under ganglionic blockade revealed that VSMC CaMKII inhibition abolished the augmented efferent sympathetic outflow and renal and splanchnic nerve activity in Ang II hypertension. Consequently, we hypothesized that VSMC CaMKII controls baroreceptor activity by modifying arterial wall remodeling in Ang II hypertension. Gene expression analysis in aortas from normotensive and Ang II–infused mice revealed that TG SM-CaMKIIN aortas were protected from Ang II–induced upregulation of genes that control extracellular matrix production, including collagen. VSMC CaMKII inhibition also strongly altered the expression of muscle contractile genes under Ang II.
CaMKII in VSMCs regulates blood pressure under Ang II hypertension by controlling structural gene expression, wall stiffness, and baroreceptor activity.
angiotensin II; calcium/calmodulin-dependent kinase II; hypertension; sympathetic nerve activity; vascular remodeling
Previously, a static and adjustable image overlay systems were proposed for aiding needle interventions. The system was either fixed to a scanner or mounted over a large articulated counterbalanced arm. Certain drawbacks associated with these systems limited the clinical translation. In order to minimize these limitations, we present the mobile image overlay system with the objective of reduced system weight, smaller dimension, and increased tracking accuracy. The design study includes optimal workspace definition, selection of display device, mirror, and laser source. The laser plane alignment, phantom design, image overlay plane calibration, and system accuracy validation methods are discussed. The virtual image is generated by a tablet device and projected into the patient by using a beamsplitter mirror. The viewbox weight (1.0kg) was reduced by 8.2 times and image overlay plane tracking precision (0.21mm, STD=0.05) was improved by 5 times compared to previous system. The automatic self-calibration of the image overlay plane was achieved in two simple steps and can be done away from patient table. The fiducial registration error of the physical phantom to scanned image volume registration was 1.35mm (STD=0.11). The reduced system weight and increased accuracy of optical tracking should enable the system to be hand held by the physician and explore the image volume over the patient for needle interventions.
Oxidized low-density lipoprotein (OxLDL) induces endothelial cell death through the activation of NF-κB and AP-1 pathways. TRAF3IP2 is a redox-sensitive cytoplasmic adapter protein and an upstream regulator of IKK/NF-κB and JNK/AP-1. Here we show that OxLDL-induced death in human primary coronary artery endothelial cells (EC) was markedly attenuated by the knockdown of TRAF3IP2 or the lectin-like OxLDL receptor 1 (LOX-1). Further, OxLDL induced Nox2/superoxide-dependent TRAF3IP2 expression, IKK/p65 and JNK/c-Jun activation and LOX-1 upregulation, suggesting a reinforcing mechanism. Similarly, the lysolipids present in oxLDL (16:0-LPC and 18:0-LPC) and minimally modified LDL also upregulated TRAF3IP2 expression. Notably, while native HDL3 reversed OxLDL-induced TRAF3IP2 expression and cell death, 15-lipoxygenase-modified HDL3 potentiated its pro-apoptotic effects. The activators of the AMPK/Akt pathway, adiponectin, AICAR and metformin attenuated superoxide generation, TRAF3IP2 expression, and OxLDL/TRAF3IP2-mediated EC death. Further, both HDL3 and adiponectin reversed OxLDL/TRAF3IP2-dependent monocyte adhesion to endothelial cells in vitro. Importantly, TRAF3IP2 gene deletion and the AMPK activators reversed OxLDL-induced impaired vasorelaxation ex-vivo. These results indicate that OxLDL-induced endothelial cell death and dysfunction are mediated via TRAF3IP2, and that native HDL3 and the AMPK activators inhibit this response. Targeting TRAF3IP2 could potentially inhibit progression of atherosclerotic vascular diseases.
Atherosclerosis; Oxidative stress; NADPH oxidases; Endothelial dysfunction
Increased reactive oxygen species (ROS) contribute to asthma, but little is known about the molecular mechanisms connecting increased ROS with characteristic features of asthma. We show that enhanced oxidative activation of the Ca2+/calmodulin-dependent protein kinase (ox-CaMKII) in bronchial epithelium positively correlates with asthma severity and that epithelial ox-CaMKII increases in response to inhaled allergens in patients. We used mouse models of allergic airway disease induced by ovalbumin (OVA) or Aspergillus fumigatus (Asp) and found that bronchial epithelial ox-CaMKII was required to increase a ROS- and picrotoxin-sensitive Cl− current (ICl) and MUC5AC expression, upstream events in asthma progression. Allergen challenge increased epithelial ROS by activating NADPH oxidases. Mice lacking functional NADPH oxidases due to knockout of p47 and mice with epithelial-targeted transgenic expression of a CaMKII inhibitory peptide or wild-type mice treated with inhaled KN-93, an experimental small molecule CaMKII antagonist, were protected against increases in ICl, MUC5AC expression, and airway hyper-reactivity to inhaled methacholine. Our findings support the view that CaMKII is a ROS-responsive, pluripotent pro-asthmatic signal and provide proof-of-concept evidence that CaMKII is a therapeutic target in asthma.
To minimize the weight of the prosthesis various techniques that create a hollow prosthesis have been known. There are a lot of drawbacks of these techniques as they are complex, time consuming, and of high cost. Here is a technique that utilizes putty material for fabricating hollow denture prosthesis.
Edentulous; hollow; prosthesis; weight
The multifunctional calcium/calmodulin-dependent kinase II (CaMKII) is activated by vasoconstrictors in vascular smooth muscle cells (VSMC), but its impact on vasoconstriction remains unknown. We hypothesized that CaMKII inhibition in VSMC decreases vasoconstriction. Using novel transgenic mice that express the inhibitor peptide CaMKIIN in smooth muscle (TG SM-CaMKIIN), we investigated the effect of CaMKII inhibition on L-type Ca2+ channel (LTCC) current (ICa), cytoplasmic and sarcoplasmic reticulum (SR) Ca2+ and vasoconstriction in mesenteric arteries. In mesenteric VSMC, CaMKII inhibition significantly reduced action potential duration and the residual ICa 50 ms after peak amplitude, indicative of loss of LTCC-dependent ICa facilitation. Treatment with angiotensin-II or phenylephrine increased the intracellular Ca2+ concentration ([Ca2+]i) in WT but not TG SM-CaMKIIN VSMC. The difference in [Ca2+]i was abolished by pretreatment with nifedipine, an LTCC antagonist. In TG SM-CaMKIIN VSMC, the total SR Ca2+ content was reduced as a result of diminished SR Ca2+ ATPase (SERCA) activity via impaired derepression of the SERCA inhibitor phospholamban. Despite the differences in [Ca2+]i, CaMKII inhibition did not alter myogenic tone or vasoconstriction of mesenteric arteries in response to KCl, angiotensin-II and phenylephrine. However, it increased myosin light chain kinase activity. These data suggest that CaMKII activity maintains intracellular calcium homeostasis but is not required for vasoconstriction of mesenteric arteries.
CaMKII; Ca2+ signaling; contraction; L-type Ca2+ channel