ImAge quantitates aging and rejuvenation.

For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling.

Imaging-based chromatin and epigenetic age, ImAge, quantitates aging and rejuvenation.

Biomarkers of biological age that predict the risk of disease and expected lifespan better than chronological age are key to efficient and cost-effective healthcare. To advance a personalized approach to healthcare, such biomarkers must reliably and accurately capture individual biology, predict biological age, and provide scalable and cost-effective measurements. We developed a novel approach - image-based chromatin and epigenetic age (ImAge) that captures intrinsic progressions of biological age, which readily emerge as principal changes in the spatial organization of chromatin and epigenetic marks in single nuclei without regression on chronological age.

Impairment of Nucleolin Activity and Phosphorylation by a Trachylobane Diterpene from in Cancer Cells.

Human nucleolin (hNcl) is a multifunctional protein involved in the progression of various cancers and plays a key role in other pathologies. Therefore, there is still unsatisfied demand for hNcl modulators. Recently, we demonstrated that the plant ent-kaurane diterpene oridonin inhibits hNcl but, unfortunately, this compound is quite toxic for healthy cells.

High-content analysis and Kinetic Image Cytometry identify toxicity and epigenetic effects of HIV antiretrovirals on human iPSC-neurons and primary neural precursor cells.

Introduction: Despite viral suppression due to combination antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) continue to affect half of people with HIV, suggesting that certain antiretrovirals (ARVs) may contribute to HAND.

Methods: We examined the effects of nucleoside/nucleotide reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) and the integrase inhibitors dolutegravir (DTG) and elvitegravir (EVG) on viability, structure, and function of glutamatergic neurons (a subtype of CNS neuron involved in cognition) derived from human induced pluripotent stem cells (hiPSC-neurons), and primary human neural precursor cells (hNPCs), which are responsible for neurogenesis.

Results: Using automated digital microscopy and image analysis (high content analysis, HCA), we found that DTG, EVG, and TDF decreased hiPSC-neuron viability, neurites, and synapses after 7 days of treatment.

The plant diterpene epoxysiderol targets Hsp70 in cancer cells, affecting its ATPase activity and reducing its translocation to plasma membrane.

The ATP-dependent molecular chaperone Hsp70 is over-expressed in cancer cells where it plays pivotal roles in stabilization of onco-proteins, promoting cell proliferation and protecting cells from apoptosis and necrosis. Moreover, a relationship between the ability of cancer cells to migrate and the abundance of membrane-associated Hsp70 was shown. However, although Hsp70 is a promising target for cancer therapy, there is a still unsatisfied requirement of inhibitors possibly blocking its cancer-associated activities.

Diterpenoids from Zhumeria majdae roots as potential heat shock protein 90 (HSP90) modulators.

Four undescribed and 17 known diterpenoids were isolated from the roots of Zhumeria majdae Rech.f. & Wendelbo.

VenaSeal closure despite allergic reaction to -butyl cyanoacrylate.

The VenaSeal closure system (Medtronic, Minneapolis, Minn) is a nonthermal, minimally invasive method for the treatment of superficial venous insufficiency using a proprietary -butyl cyanoacrylate. We report the case of a 45-year-old woman who underwent right great saphenous vein closure with VenaSeal and subsequently had a biphasic reaction to -butyl cyanoacrylate, confirmed on patch testing that had negative results for other cyanoacrylates. Despite the initial allergic response, which settled with antihistamines, follow-up duplex ultrasound imaging confirmed successful great saphenous vein closure, and the affected vein remained in situ without further complication.

Midterm outcomes in postpartum women following endovenous treatment for acute iliofemoral deep vein thrombosis.

Background: The development of post-thrombotic syndrome (PTS) after iliofemoral deep vein thrombosis (DVT) continues to be a considerable issue for both pregnant and postpartum women with rates as high as 70% among those managed with anticoagulation alone. This study aims to characterize the outcomes of interventional treatment for acute iliofemoral DVT in this at-risk population.

Methods: A retrospective analysis of all postpartum patients treated for acute iliofemoral DVT with lysis and stenting between January 2012 and December 2017 at a referral center.

Fusicoccane Diterpenes from Hypoestes forsskaolii as Heat Shock Protein 90 (Hsp90) Modulators.

Ten new (1-10) and six known (11-16) fusicoccane diterpenes were isolated from the roots of Hypoestes forsskaolii. The structural characterization of 1-10 was performed by spectroscopic analysis, including 1D and 2D NMR, ECD, and HRESIMS experiments. From a perspective of obtaining potential Hsp90α inhibitors, the isolates were screened by surface plasmon resonance measurements and their cytotoxic activity was assayed using Jurkat and HeLa cancer cells.

The anti-tumor diterpene oridonin is a direct inhibitor of Nucleolin in cancer cells.

The bioactive plant diterpene oridonin displays important pharmacological activities and is widely used in traditional Chinese medicine; however, its molecular mechanism of action is still incompletely described. In vitro and in vivo data have demonstrated anti-tumor activity of oridonin and its ability to interfere with several cell pathways; however, presently only the molecular chaperone HSP70 has been identified as a direct potential target of this compound. Here, using a combination of different proteomic approaches, innovative Cellular Thermal Shift Assay (CETSA) experiments, and classical biochemical methods, we demonstrate that oridonin interacts with Nucleolin, effectively modulating the activity of this multifunctional protein.

Expedient Access to 2-Benzazepines by Palladium-Catalyzed C-H Activation: Identification of a Unique Hsp90 Inhibitor Scaffold.

Bioactive 2-benzazepines were accessed in an atom- and step-economical manner through a versatile palladium-catalyzed C-H activation strategy. The C-H arylation required low catalyst loading and a mild base, which was reflected by a broad scope and high functional-group tolerance. The benzotriazolodiazepinones were identified as new heat shock protein 90 (Hsp90) inhibiting lead compounds, with considerable potential for anti-cancer applications.

Commentary: Giuseppe Campani (1635-1715, Rome, Italy): the First Use of a Microscope in Medicine and Surgery.

Giuseppe Campani (1635-1715) was a polymath in Rome, Italy, during the Scientific Revolution in the XVIIth century. In particular, he forged the screw barrel microscope and was manufacturing his own lenses for microscopes and telescopes. He mastered the art of lens grinding.

A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability.

Proteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments.

Mini Transsternal Approach to the Anterior High Thoracic Spine (T1-T4 Vertebrae).

Purpose. The anterior high thoracic spine is one of the most complex segments to be accessed surgically due to anatomical constraints and transitional characteristics. We describe in detail the mini transsternal approach to metastatic, infective, traumatic, and degenerative pathologies of T1 to T4 vertebral bodies.

Original approach for thrombolytic therapy in patients with Ilio-femoral deep vein thrombosis : 2 years follow-up.

Objective: The aim of the study was to discuss the results of catheter-directed thrombolysis and complementary procedures to treat acute iliofemoral deep vein thrombosis (DVT) evaluating the safety and effectivness of an easy access such as the Great Saphenous Vein.

Methods And Materials: A total of 22 consecutive patients with iliofemoral thrombosis and two patients with femoro-popliteal thrombosis on recent onset diagnosed with Ultrasound Doppler and contrast venography underwent intrathrombus drip infusion of urokinase while intravenous heparin was continued using saphenical access. Residual venous stenosis were treated in six patients by percutaneous balloon Angioplasty and stenting.

Giant cardiac hydatid cyst in children: case report and review of the literature.

Cardiac echinococcus is a rare affliction of the heart caused by the tapeworm Echinococcus granulosus. Primary echinococcosis of the heart represents 0.5-2% of all hydatid disease cases in endemic regions.

Critical limb ischemia in a young man: saddle embolism or unusual presentation of thromboangiitis obliterans?

Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a rare cause of peripheral arterial disease in western countries. Tobacco smoking is strongly correlated to the pathogenesis of this inflammatory vascular disease. We report the case of a 32-year-old tobacco and cannabis consumer presenting with right critical limb ischemia.

Play to become a surgeon: impact of Nintendo Wii training on laparoscopic skills.

Background: Video-games have become an integral part of the new multimedia culture. Several studies assessed video-gaming enhancement of spatial attention and eye-hand coordination. Considering the technical difficulty of laparoscopic procedures, legal issues and time limitations, the validation of appropriate training even outside of the operating rooms is ongoing.

Postpartum deep vein thrombosis and pulmonary embolism in twin pregnancy: undertaking of clinical symptoms leading to massive complications.

Background: Deep Vein Thrombosis (DVT) is an important cause of morbidity and is the first cause of maternal death after delivery in Western Nations. The risk of venous thromboembolism is present throughout the pregnancy and is maximal during postpartum, especially after twin delivery. Many of the signs and symptoms of DVT overlap those of a normal pregnancy causing difficulty for diagnosis.

Management of AAA and late Type II EL in a patient with concomitant renal cell carcinoma. Report of a case and review of the literature.

Purpose: Detection of cancer in patients with AAA complicates the treatment of both diseases. AAA associated with RN are rare, with an incidence of 0.1-3% representing a challenge in defining the surgical timing and approach.

[Stenting versus carotid endarterectomy for carotid stenosis. A single center experience].

Aim: The objective was to compare Carotid Endarterectomy (CEA) with Carotid Artery Stenting (CAS) in terms of efficacy and safety in patients with symptomatic and asymptomatic extracranial carotid stenosis.

Materials: This study enrolled 285 patients with symptomatic and asymptomatic carotid stenosis that underwent either to CAS or CEA. The primary end-points were death, stroke and myocardial infarction.

Radiotherapy-related axillary arteriopathy.

Treatment of breast cancer involves surgery, then perhaps radiation, hormonal or chemotherapy. Radiation-induced arterial injury is a well-known entity that represents a rare cause of arterial occlusion. We present the case of a 76-year old woman who complained of a severe intermittent claudication of the right upper limb.

Peripheral arterial disease in diabetic patients with renal insufficiency: a review.

Peripheral arterial disease is common among diabetic patients with renal insufficiency, and most of the diabetic patients with end-stage renal disease (ESRD) have peripheral arterial disease. Ischaemia is probably overrepresented as an etiological factor for a diabetic foot ulcer in this group of patients compared with other diabetic patients. ESRD is a strong risk factor for both ulceration and amputation in diabetic patients.

Abdominal aortic occlusion of young adults.

The occlusion of the infrarenal aorta is a rare event, which is potentially life threatening. We present the case of a heavy smoking, 35-year-old woman who was referred to the emergency department of our hospital because of sudden abdominal pain and urinary incontinence. She also complained of a two-year history of bilateral intermittent claudication.

Achille Louis Foville's atlas of brain anatomy and the Defoville syndrome.

Achille Louis Foville's atlas of brain anatomy (1844) is one of the most artistic and detailed works on neuroanatomy in the medical literature. The outstanding drawings by the 2 artists, Emile Beau and Frédéric-Michel Bion, highlight all the philosophy, ability, and sensibility of A.L.