The von Hippel-Lindau tumor suppressor protein controls ciliogenesis by orienting microtubule growth

Cilia are specialized organelles that play an important role in several biological processes, including mechanosensation, photoperception, and osmosignaling. Mutations in proteins localized to cilia have been implicated in a growing number of human diseases. In this study, we demonstrate that the von Hippel-Lindau (VHL) protein (pVHL) is a ciliary protein that controls ciliogenesis in kidney cells. Knockdown of pVHL impeded the formation of cilia in mouse inner medullary collecting duct 3 kidney cells, whereas the expression of pVHL in VHL-negative renal cancer cells rescued the ciliogenesis defect. Using green fluorescent protein–tagged end-binding protein 1 to label microtubule plus ends, we found that pVHL does not affect the microtubule growth rate but is needed to orient the growth of microtubules toward the cell periphery, a prerequisite for the formation of cilia. Furthermore, pVHL interacts with the Par3–Par6–atypical PKC complex, suggesting a mechanism for linking polarity pathways to microtubule capture and ciliogenesis

Advances in the healing of flexor tendon injuries

The intrasynovial flexor tendons of the hand are critical for normal hand function. Injury to these tendons can result in absent finger flexion, and a subsequent loss of overall hand function. The surgical techniques used to repair these tendons have improved in the past few decades, as have the postoperative rehabilitation protocols. In spite of these advances, intrasynovial flexor tendon repairs continue to be plagued by postoperative scar formation, which limits tendon gliding and prevents a full functional recovery. This paper describes the current challenges of flexor tendon repair, and evaluates the most recent advances and strategies for achieving an excellent functional outcome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106844/1/wrr12161.pd

A European research agenda for somatic symptom disorders, bodily distress disorders, and functional disorders: Results of an estimate-talk-estimate delphi expert study

Background: Somatic Symptom Disorders (SSD), Bodily Distress Disorders (BDD) and functional disorders (FD) are associated with high medical and societal costs and pose a substantial challenge to the population and health policy of Europe. To meet this challenge, a specific research agenda is needed as one of the cornerstones of sustainable mental health research and health policy for SSD, BDD, and FD in Europe. Aim: To identify the main challenges and research priorities concerning SSD, BDD, and FD from a European perspective. Methods: Delphi study conducted from July 2016 until October 2017 in 3 rounds with 3 workshop meetings and 3 online surveys, involving 75 experts and 21 European countries. EURONET-SOMA and the European Association of Psychosomatic Medicine (EAPM) hosted the meetings. Results: Eight research priorities were identified: (1) Assessment of diagnostic profiles relevant to course and treatment outcome. (2) Development and evaluation of new, effective interventions. (3) Validation studies on questionnaires or semi-structured interviews that assess chronic medical conditions in this context. (4) Research into patients preferences for diagnosis and treatment. (5) Development of new methodologic designs to identify and explore mediators and moderators of clinical course and treatment outcomes (6). Translational research exploring how psychological and somatic symptoms develop from somatic conditions and biological and behavioral pathogenic factors. (7) Development of new, effective interventions to personalize treatment. (8) Implementation studies of treatment interventions in different settings, such as primary care, occupational care, general hospital and specialty mental health settings. The general public and policymakers will benefit from the development of new, effective, personalized interventions for SSD, BDD, and FD, that will be enhanced by translational research, as well as from the outcomes of research into patient involvement, GP-patient communication, consultation-liaison models and implementation. Conclusion: Funding for this research agenda, targeting these challenges in coordinated research networks such as EURONET-SOMA and EAPM, and systematically allocating resources by policymakers to this critical area in mental and physical well-being is urgently needed to improve efficacy and impact for diagnosis and treatment of SSD, BDD, and FD across Europe

Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification

Background The purpose of this study was to determine the cerebrovascular risk stratification potential of baseline degree of stenosis, clinical features, and ultrasonic plaque characteristics in patients with asymptomatic internal carotid artery (ICA) stenosis. Methods This was a prospective, multicenter, cohort study of patients undergoing medical intervention for vascular disease. Hazard ratios for ICA stenosis, clinical features, and plaque texture features associated with ipsilateral cerebrovascular or retinal ischemic (CORI) events were calculated using proportional hazards models. Results A total of 1121 patients with 50% to 99% asymptomatic ICA stenosis in relation to the bulb (European Carotid Surgery Trial [ECST] method) were followed-up for 6 to 96 months (mean, 48). A total of 130 ipsilateral CORI events occurred. Severity of stenosis, age, systolic blood pressure, increased serum creatinine, smoking history of more than 10 pack-years, history of contralateral transient ischemic attacks (TIAs) or stroke, low grayscale median (GSM), increased plaque area, plaque types 1, 2, and 3, and the presence of discrete white areas (DWAs) without acoustic shadowing were associated with increased risk. Receiver operating characteristic (ROC) curves were constructed for predicted risk versus observed CORI events as a measure of model validity. The areas under the ROC curves for a model of stenosis alone, a model of stenosis combined with clinical features and a model of stenosis combined with clinical, and plaque features were 0.59 (95% confidence interval [CI] 0.54-0.64), 0.66 (0.62-0.72), and 0.82 (0.78-0.86), respectively. In the last model, stenosis, history of contralateral TIAs or stroke, GSM, plaque area, and DWAs were independent predictors of ipsilateral CORI events. Combinations of these could stratify patients into different levels of risk for ipsilateral CORI and stroke, with predicted risk close to observed risk. Of the 923 patients with <70% stenosis, the predicted cumulative 5-year stroke rate was <5% in 495, 5% to 9.9% in 202, 10% to 19.9% in 142, and <20% in 84 patients. Conclusion Cerebrovascular risk stratification is possible using a combination of clinical and ultrasonic plaque features. These findings need to be validated in additional prospective studies of patients receiving optimal medical intervention alone. Copyright © 2010 by the Society for Vascular Surgery

The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke

Objective: To test the hypothesis that the size of a juxtaluminal black (hypoechoic) area (JBA) in ultrasound images of asymptomatic carotid artery plaques predicts future ipsilateral ischemic stroke. Methods: A JBA was defined as an area of pixels with a grayscale value &lt;25 adjacent to the lumen without a visible echogenic cap after image normalization. The size of a JBA was measured in the carotid plaque images of 1121 patients with asymptomatic carotid stenosis 50% to 99% in relation to the bulb (Asymptomatic Carotid Stenosis and Risk of Stroke study); the patients were followed for up to 8 years. Results: The JBA had a linear association with future stroke rate. The area under the receiver-operating characteristic curve was 0.816. Using Kaplan-Meier curves, the mean annual stroke rate was 0.4% in 706 patients with a JBA &lt;4 mm 2, 1.4% in 171 patients with a JBA 4 to 8 mm2, 3.2% in 46 patients with a JBA 8 to 10 mm2, and 5% in 198 patients with a JBA &gt;10 mm2 (P &lt;.001). In a Cox model with ipsilateral ischemic events (amaurosis fugax, transient ischemic attack [TIA], or stroke) as the dependent variable, the JBA (&lt;4 mm2, 4-8 mm2, &gt;8 mm2) was still significant after adjusting for other plaque features known to be associated with increased risk, including stenosis, grayscale median, presence of discrete white areas without acoustic shadowing indicating neovascularization, plaque area, and history of contralateral TIA or stroke. Plaque area and grayscale median were not significant. Using the significant variables (stenosis, discrete white areas without acoustic shadowing, JBA, and history of contralateral TIA or stroke), this model predicted the annual risk of stroke for each patient (range, 0.1%-10.0%). The average annual stroke risk was &lt;1% in 734 patients, 1% to 1.9% in 94 patients, 2% to 3.9% in 134 patients, 4% to 5.9% in 125 patients, and 6% to 10% in 34 patients. Conclusions: The size of a JBA is linearly related to the risk of stroke and can be used in risk stratification models. These findings need to be confirmed in future prospective studies or in the medical arm of randomized controlled studies in the presence of optimal medical therapy. In the meantime, the JBA may be used to select asymptomatic patients at high stroke risk for carotid endarterectomy and spare patients at low risk from an unnecessary operation

Differential prognostic utility of adiposity measures in chronic kidney disease

Objective Adipose tissue contributes to adverse outcomes in chronic kidney disease (CKD), but there is uncertainty regarding the prognostic relevance of different adiposity measures. We analyzed the associations of neck circumference (NC), waist circumference (WC), and body mass index (BMI) with clinical outcomes in patients with mild to severe CKD. Methods The German Chronic Kidney Disease (GCKD) study is a prospective cohort study, which enrolled Caucasian adults with mild to severe CKD, defined as estimated glomerular filtration rate (eGFR): 30–60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 in the presence of overt proteinuria. Associations of NC, WC and BMI with all-cause death, major cardiovascular events (MACE: a composite of non-fatal stroke, non-fatal myocardial infarction, peripheral artery disease intervention, and cardiovascular death), kidney failure (a composite of dialysis or transplantation) were analyzed using multivariable Cox proportional hazards regression models adjusted for confounders and the Akaike information criteria (AIC) were calculated. Models included sex interactions with adiposity measures. Results A total of 4537 participants (59% male) were included in the analysis. During a 6.5-year follow-up, 339 participants died, 510 experienced MACE, and 341 developed kidney failure. In fully adjusted models, NC was associated with all-cause death in women (HR 1.080 per cm; 95% CI 1.009–1.155), but not in men. Irrespective of sex, WC was associated with all-cause death (HR 1.014 per cm; 95% CI 1.005–1.038). NC and WC showed no association with MACE or kidney failure. BMI was not associated with any of the analyzed outcomes. Models of all-cause death including WC offered the best (lowest) AIC. Conclusion In Caucasian patients with mild to severe CKD, higher NC (in women) and WC were significantly associated with increased risk of death from any cause, but BMI was not

The Greek-Orthodox version of the Brief Religious Coping (B-RCOPE) instrument: psychometric properties in three samples and associations with mental disorders, suicidality, illness perceptions, and quality of life

Background: The B-RCOPE is a brief measure assessing religious coping. We aimed to assess the psychometric properties of its Greek version in people with and without long-term conditions (LTCs). Associations between religious coping and mental illness, suicidality, illness perceptions, and quality of life were also investigated. Methods: The B-RCOPE was administered to 351 patients with diabetes, chronic pulmonary obstructive disease (COPD), and rheumatic diseases attending either the emergency department (N = 74) or specialty clinics (N = 302) and 127 people without LTCs. Diagnosis of mental disorders was established by the MINI. Associations with depressive symptom severity (PHQ-9), suicidal risk (RASS), illness perceptions (B-IPQ), and health-related quality of life (WHOQOL-BREF) were also investigated. Results: The Greek version of B-RCOPE showed a coherent two-dimensional factor structure with remarkable stability across the three samples corresponding to the positive (PRC) and negative (NRC) religious coping dimensions. Cronbach’s alphas were 0.91–0.96 and 0.77–0.92 for the PRC and NRC dimensions, respectively. Furthermore, NRC was associated with poorer mental health, greater depressive symptom severity and suicidality, and impaired HRQoL. In patients with LTCs, PRC correlated with lower perceived illness timeline, while NRC was associated with greater perceived illness consequences, lower perceived treatment control, greater illness concern, and lower illness comprehensibility. Conclusions: These findings indicate that the Greek-Orthodox B-RCOPE version may reliably assess religious coping. In addition, negative religious coping (i.e., religious struggle) is associated with adverse illness perceptions, and thus may detrimentally impact adaptation to medical illness. These findings deserve replication in prospective studies

A Pearl-Like 30-Year-Old Moving Phlebolith in the Left Cephalic Vein

Background: Phleboliths are a common finding, especially in the pelvic veins. There are generally multiple thrombi associated with vascular malformations, trauma, or iatrogenic or noniatrogenic intravenous foreign bodies. Methods: Herein, we report a unique case of a single moving phlebolith in the cephalic vein of a 65-year-old man, not associated with any vascular lesion, trauma, or foreign body. Results: Too many cases of phleboliths have been reported in the literature since 1948, referred to vascular disorders, injuries, or foreign bodies. Only this work we are presenting refers to a phlebolith not associated with other vascular, pathological, or traumatic lesion. Conclusion: Phleboliths not associated with other vascular lesions are not common and less rare when not associated with injuries or iatrogenic interventions. Clinicians should be aware of the existence of this pathology and include it as the differential diagnosis of various pathological conditions

Retroperitoneal semi-closed eversion ring endarterectomy of the left common iliac artery as a bridge for EVAR in a patient with a bilateral obstructive iliac disease

Concomitant abdominal aortic aneurysm (AAA) and bilateral iliac occlusive disease constitute a challenge for the application of endovascular repair of the aorta. We present the case of an 84-year-old man with an AAA, coronary disease, intermittent claudication of both legs, comorbidities including a hostile abdomen, and a stent protruding in the aneurysm sac following previous stenting of the right common iliac artery, and with a previous thrombosed axillobifemoral graft. We treated him with a hybrid retroperitoneal technique by placing an aortouniiliac (AUI) stent-graft via an intervening graft-conduit sutured to the bifurcation of the left common iliac artery following a semi-closed eversion ring endarterectomy of the left occluded common iliac artery. The intervening graft was then anastomosed to a new femoral-femoral bypass. The patient is in good condition with all vessels patent for twenty-one months following the operation

Surgical Considerations for the Management of an Ectopic Main Renal Artery Originating from an Abdominal Aortic Aneurysm

Ectopic major renal arteries are rare but anatomically important because they can complicate aortic surgery and make the operation challenging for vascular surgeons. A 68-year-old male was presented with a 5.5-cm aneurysm of the infrarenal abdominal aorta combined with an ectopic main right renal artery arising from the middle of the aneurysm sac, perfusing a normotopic right kidney. The patient also had small right common iliac artery aneurysm. Open repair was performed with reimplantation of the right renal artery on the aortic tube graft, the right kidney was perfused with cold heparinized lactated Ringer solution during operation. The right common iliac artery aneurysm was wrapped with a polyester band. The patient’s postoperative courses were uneventful, with normal renal function during 5 years of follow-up. Preoperative planning is important for achieving optimal results in treating complex aneurysms with ectopic main renal artery