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Science (New York, N.Y.) May 2015Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for...
Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues.
Topics: Alleles; Blood Pressure; Disease; GTPase-Activating Proteins; Gene Expression Regulation; Gene Regulatory Networks; Genetic Variation; Genome, Human; Genome-Wide Association Study; Genotype; Humans; Multigene Family; Organ Specificity; Pilot Projects; Quantitative Trait Loci; RNA Splicing; RNA, Untranslated; Sequence Analysis, RNA; Tibial Arteries; Transcriptome
PubMed: 25954001
DOI: 10.1126/science.1262110 -
The Medical Journal of Malaysia May 2021A pseudoaneurysm, or false aneurysm, is a haematoma that is formed secondary to a leaking hole in an artery. This haematoma is contained by surrounding fascia. In...
A pseudoaneurysm, or false aneurysm, is a haematoma that is formed secondary to a leaking hole in an artery. This haematoma is contained by surrounding fascia. In contrast, a true aneurysm contains all three layers of vessel wall, namely intima. Pseudoaneurysms are scarce and can arise consequential of numerous iatrogenic influences, including but not limited to, blunt or penetrating trauma, orthopedic procedures like tibial nailing or ankle arthroscopy, and sports injury. A thorough history taking focusing on the recent history of trauma or instrumentation and clinical examination should raise the suspicion of a pseudoaneurysm. In doubtful cases, imaging modalities such as an ultrasound and doppler examination of the lower limb can be utilized to confirm the diagnosis. Our case was a 37-year-old gentleman presented with progressive swelling in the anterior aspect of his left leg for the past two weeks. The patient had a atypical presentation, with absence of classic signs of a pseudoaneurysm such as a pulsatile mass, absence distal pulses or a thrill or bruit. However, these injuries albeit rare can be sinister and prompt diagnosis is critical, so that pertinent treatment can be delivered. Our case highlights the importance of sonographic approaches for suspected vascular injuries.
Topics: Adult; Aneurysm, False; Hematoma; Humans; Leg; Male; Tibial Arteries; Wounds, Penetrating
PubMed: 34031347
DOI: No ID Found -
Arteriosclerosis, Thrombosis, and... Mar 2020Vascular calcification is highly prevalent in patients with chronic kidney disease. Increased plasma trimethylamine N-oxide (TMAO), a gut microbiota-dependent product,...
Trimethylamine-N-Oxide Promotes Vascular Calcification Through Activation of NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome and NF-κB (Nuclear Factor κB) Signals.
OBJECTIVES
Vascular calcification is highly prevalent in patients with chronic kidney disease. Increased plasma trimethylamine N-oxide (TMAO), a gut microbiota-dependent product, concentrations are found in patients undergoing hemodialysis. However, a clear mechanistic link between TMAO and vascular calcification is not yet established. In this study, we investigate whether TMAO participates in the progression of vascular calcification using in vitro, ex vivo, and in vivo models. Approach and Results: Alizarin red staining revealed that TMAO promoted calcium/phosphate-induced calcification of rat and human vascular smooth muscle cells in a dose-dependent manner, and this was confirmed by calcium content assay. Similarly, TMAO upregulated the expression of bone-related molecules including Runx2 (Runt-related transcription factor 2) and BMP2 (bone morphogenetic protein-2), suggesting that TMAO promoted osteogenic differentiation of vascular smooth muscle cells. In addition, ex vivo study also showed the positive regulatory effect of TMAO on vascular calcification. Furthermore, we found that TMAO accelerated vascular calcification in rats with chronic kidney disease, as indicated by Mico-computed tomography analysis, alizarin red staining and calcium content assay. By contrast, reducing TMAO levels by antibiotics attenuated vascular calcification in chronic kidney disease rats. Interestingly, TMAO activated NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3) inflammasome and NF-κB (nuclear factor κB) signals during vascular calcification. Inhibition of NLRP3 inflammasome and NF-κB signals attenuated TMAO-induced vascular smooth muscle cell calcification.
CONCLUSIONS
This study for the first time demonstrates that TMAO promotes vascular calcification through activation of NLRP3 inflammasome and NF-κB signals, suggesting the potential link between gut microbial metabolism and vascular calcification. Reducing the levels of TMAO could become a potential treatment strategy for vascular calcification in chronic kidney disease.
Topics: Adult; Aged; Animals; Anti-Bacterial Agents; Aorta, Thoracic; Cells, Cultured; Disease Models, Animal; Female; Humans; Inflammasomes; Male; Methylamines; Middle Aged; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Osteogenesis; Renal Insufficiency, Chronic; Signal Transduction; Tibial Arteries; Tissue Culture Techniques; Vascular Calcification
PubMed: 31941382
DOI: 10.1161/ATVBAHA.119.313414 -
Surgical and Radiologic Anatomy : SRA May 2023The tarsal tunnel (TT) is a fibro-osseous anatomical space coursing from the medial ankle to the medial midfoot. This tunnel acts as a passage for both tendinous and...
PURPOSE
The tarsal tunnel (TT) is a fibro-osseous anatomical space coursing from the medial ankle to the medial midfoot. This tunnel acts as a passage for both tendinous and neurovascular structures, including the neurovascular bundle containing the posterior tibial artery (PTA), posterior tibial veins (PTVs) and tibial nerve (TN). Tarsal tunnel syndrome (TTS) is the entrapment neuropathy that describes the compression and irritation of the TN within this space. Iatrogenic injury to the PTA plays a significant role in both the onset and exacerbation of TTS symptoms. The current study aims to produce a method to allow clinicians and surgeons to easily and accurately predict the bifurcation of the PTA, to avoid iatrogenic injury during treatment of TTS.
METHODS
Fifteen embalmed cadaveric lower limbs were dissected at the medial ankle region to expose the TT. Various measurements regarding the location of the PTA within the TT were recorded and multiple linear regression analysis performed using RStudio.
RESULTS
Analysis provided a clear correlation (p < 0.05) between the length of the foot (MH), length of hind-foot (MC) and location of bifurcation of the PTA (MB). Using these measurements, this study developed an equation (MB = 0.3*MH + 0.37*MC - 28.24 mm) to predict the location of bifurcation of the PTA within a 23° arc inferior to the medial malleolus.
CONCLUSIONS
This study successfully developed a method whereby clinicians and surgeons can easily and accurately predict the bifurcation of the PTA, to avoid iatrogenic injury that would previously lead to an exacerbation of TTS symptoms.
Topics: Humans; Tibial Arteries; Tarsal Tunnel Syndrome; Tibial Nerve; Ankle; Iatrogenic Disease
PubMed: 36912942
DOI: 10.1007/s00276-023-03115-w -
Jornal Vascular Brasileiro Nov 2020Vascular Doppler ultrasound is a noninvasive method that can help in diagnostic and therapeutic planning in case of pedal arterial obstructive disease. The dorsalis... (Review)
Review
Vascular Doppler ultrasound is a noninvasive method that can help in diagnostic and therapeutic planning in case of pedal arterial obstructive disease. The dorsalis pedis artery is the direct continuation of the anterior tibial artery and follows a straight course along the dorsum of the foot, leading medially to the first intermetatarsal space, where it gives off its terminal branches. The posterior tibial artery forks distal to the medial malleolus and gives rise to the lateral plantar and medial plantar arteries. The medial plantar artery has a smaller caliber and runs medially in the sole of the foot, while the lateral plantar artery is of larger caliber, following a lateral course in the plantar region and forming the deep plantar arch, which anastomoses with the dorsalis pedis artery via the deep plantar artery. The arteries of the foot can be assessed noninvasively with Doppler, providing an adequate level of anatomical detail.
PubMed: 34211519
DOI: 10.1590/1677-5449.200068 -
Journal of Vascular Surgery Feb 2023
Topics: Humans; Endovascular Procedures; Tibial Arteries; Treatment Outcome; Ischemia; Retrospective Studies; Vascular Patency
PubMed: 36681483
DOI: 10.1016/j.jvs.2022.09.004 -
BMC Musculoskeletal Disorders Nov 2021Planning surgical procedures of the lower leg benefits from considering the possibility of an aberrant anterior tibial artery (AATA), but previously published data on... (Review)
Review
BACKGROUND
Planning surgical procedures of the lower leg benefits from considering the possibility of an aberrant anterior tibial artery (AATA), but previously published data on the frequency of this anatomic variant shows heterogeneity. We assessed the prevalence of AATA in a Latin American cohort using magnetic resonance imaging (MRI) and compared these with other studies reported in the literature.
METHODS
We retrospectively included consecutive patients who had undergone multiplanar knee MRI at a radiology department in Lima, Peru. The MRI protocol included coronal T1 weighted, axial, sagittal and coronal proton density fat-saturated (PDFS) and sagittal T2 weighted images. Two experienced radiologists assessed all images and were blinded to each other's findings. The frequency of the AATA was compared to previous cohorts. A scoping review was undertaken to provide an overview of previously published data on the prevalence of ATAA.
RESULTS
We analyzed 280 knee MRI examinations of 253 patients (median age 41 years (IQR 31-52), 53.8% male). The aberrant anterior tibial artery variant was present in 8 of 280 (2.9%) evaluated knees, resulting in a prevalence of 3.2% in our study population. The PDFS sequence in the axial or sagittal orientation was most effective to identify AATA. The frequency of AATA in the reviewed literature using different radiological modalities ranged from 0.4 to 6% (median 1%, IQR (0.5-2.3%).
CONCLUSIONS
The AATA is a frequent vascular variant that can be detected by MRI in the preparation of invasive interventions of the lower leg.
Topics: Adult; Female; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Prevalence; Retrospective Studies; Tibial Arteries
PubMed: 34727902
DOI: 10.1186/s12891-021-04801-9 -
The Pan African Medical Journal 2022Aneurysms of the tibial arteries are rare, and they most commonly occur due to trauma of the lower extremities. Acquired arteriovenous fistulas of the tibial arteries...
Aneurysms of the tibial arteries are rare, and they most commonly occur due to trauma of the lower extremities. Acquired arteriovenous fistulas of the tibial arteries are a recognized complication of trauma of the lower extremity and they are related to the mechanism of the injury. Although the natural history of stable arteriovenous fistula is relatively benign, the aneurysms of the tibial arteries should be repaired with autologous vein bypass grafts, if there is distal ischemia. Endovascular repair has been reported as an effective alternative treatment for traumatic tibial artery aneurysms. The case of a 60-year-old male with the rare combination of a tibial artery aneurysm and traumatic arteriovenous fistula of the left lower extremity is reported in view of its rarity and the modern holistic endovascular approach used for treatment. A covered stent graft in the anterior tibial artery was used for the treatment of both the aneurysm and the arteriovenous fistula. The patient was discharged under dual antiplatelet treatment for three months, continued by clopidogrel as monotherapy. At the six-month follow-up, the patient has restored palpable peripheral pulses and no sign of recurrence or complication was recognized. A total endovascular approach can be an effective treatment for these complicated traumatic aneurysms.
Topics: Aneurysm; Arteriovenous Fistula; Humans; Male; Middle Aged; Stents; Tibial Arteries; Vascular System Injuries
PubMed: 36060853
DOI: 10.11604/pamj.2022.42.122.29735