Precision medicine in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that has diverse clinical manifestations, ranging from restricted cutaneous involvement to life-threatening systemic organ involvement. The heterogeneity of pathomechanisms that lead to SLE contributes to between-patient variation in clinical phenotype and treatment response. Ongoing efforts to dissect cellular and molecular heterogeneity in SLE could facilitate the future development of stratified treatment recommendations and precision medicine, which is a considerable challenge for SLE. In particular, some genes involved in the clinical heterogeneity of SLE and some phenotype-related loci (STAT4, IRF5, PDGF genes, HAS2, ITGAM and SLC5A11) have an association with clinical features of the disease. An important part is also played by epigenetic varation (in DNA methylation, histone modifications and microRNAs) that influences gene expression and affects cell function without modifying the genome sequence. Immune profiling can help to identify an individual’s specific response to a therapy and can potentially predict outcomes, using techniques such as flow cytometry, mass cytometry, transcriptomics, microarray analysis and single-cell RNA sequencing. Furthermore, the identification of novel serum and urinary biomarkers would enable the stratification of patients according to predictions of long-term outcomes and assessments of potential response to therapy

Clinical epigenetics and restoring of metabolic health in severely obese patients undergoing batriatric and metabolic surgery

Epigenetic-sensitive mechanisms, mainly DNA methylation, mirror the relationship between environmental and genetic risk factors able to affect the sensitiveness to development of obesity and its comorbidities. Bariatric and metabolic surgery may reduce obesity-related cardiovascular risk through tissue-specific DNA methylation changes. Among the most robust results, differential promoter methylation of ACACA, CETP, CTGF, S100A8, and S100A9 genes correlated significantly with the levels of mRNA before and after gastric bypass surgery (RYGB) in obese women. Additionally, promoter hypermethylation of NFKB1 gene was significantly associated with reduced blood pressure in obese patients after RYGB suggesting useful non-invasive biomarkers. Of note, sperm-related DNA methylation signatures of genes regulating the central control of appetite, such as MC4R, BDNF, NPY, and CR1, and other genes including FTO, CHST8, and SH2B1 were different in obese patients as compared to non-obese subjects and patients who lost weight after RYGB surgery. Importantly, transgenerational studies provided relevant evidence of the potential effect of bariatric and metabolic surgery on DNA methylation. For example, peripheral blood biospecimens isolated from siblings born from obese mothers before bariatric surgery showed different methylation signatures in the insulin receptor and leptin signaling axis as compared to siblings born from post-obese mothers who underwent surgery. This evidence suggests that bariatric and metabolic surgery of mothers may affect the epigenetic profiles of the offspring with potential implication for primary prevention of severe obesity. We update on tissue-specific epigenetic signatures as potential mechanisms underlying the restoration of metabolic health after surgery suggesting useful predictive biomarkers

The Impact of Direct Oral Anticoagulant Prophylaxis for Thromboembolism in Thrombophilic Patients Undergoing Abdominoplastic Surgery

Congenital or acquired thrombophilia is observed in 10-15% of the general population; therefore, careful screening is carried out in patients at higher risk of venous thrombo-embolism (VTE). High risk of VTE is a contraindication in patients undergoing abdominoplasty. We evaluated rivaroxaban, an oral Xa inhibitor, with enoxaparin, a subcutaneously low molecular weight heparin (LMWH), in 48 female patients with documented thrombophilia, undergoing thrombo-prophylaxis after abdominoplasty. Patients were stratified into two groups according to thrombo-prophylaxis procedure: enoxaparin Group (n = 28) and rivaroxaban Group (n = 20). Hematologic outcomes were evaluated including VTE and hematoma. No episodes of VTE occurred in both groups; two patients during their course of enoxaparin presented severe hematoma for drainage and hemostasis revision. This study suggests that abdominoplasty, in patients with thrombophilia, in combination with thrombo-prophylaxis can be performed safely. Rivaroxaban was as effective as LMWH for preventing VTE, with only a moderate risk of clinically relevant bleeding. More research is needed to determine the optimal timing and duration of prophylaxis in patients undergoing plastic surgery

At-home Cosmeceutical Application and Outpatient Treatments: A 3D Stepwise Facial Rejuvenation Approach

BACKGROUND: Aging affects the 3-dimensional structure of all the facial tissues: Bones, muscles, ligaments, adipose tissue, and skin. AIM: To customize minimally invasive treatments for facial rejuvenation, we present a standardized holistic approach characterized by at-home treatments in associations with outpatient procedures. METHODS: Forty-four patients underwent 3-dimensional stepwise facial rejuvenation and were evaluated prospectively. Each patient received a customized treatment plan based on a clinical examination and consultation. Treatment outcomes were evaluated from patient photographs with and skin analysis was performed with an A-One Smart automated skin analysis system. RESULTS: The mean age of the patients was 41.7 years and the approximate mean duration of treatment was 160 days. Patients applied cosmeceuticals such as retinoic acid. Outpatient procedures included the delivery of botulinum toxin or dermal fillers, thread lifting, chemical peels, etc. Upon treatment completion, significant improvements were noted in multiple domains: Skin elasticity and hydration increased, areas of hyper-pigmentation were less extensive, and there were fewer visible wrinkles and pores. CONCLUSION: Outcomes of the present article suggest how important is to customize facial anti-aging treatments. Nonsurgical treatments carried out progressively, involving the patient to perform at-home treatments in associations with outpatient procedures, let to achieve facial improvements in terms of increased skin elasticity and hydration, reduction of hyperpigmentation, wrinkles, and pores

The oval technique for nipple-areolar complex reconstruction

Background Nipple-areolar complex (NAC) reconstruction is the final stage of breast reconstruction. Ideal reconstruction of the NAC requires symmetry in position, size, shape, texture, pigmentation, and permanent projection, and although many technical descriptions of NAC reconstruction exist in the medical literature, there is no gold standard technique. The technique devised by the authors is very versatile, with excellent results, and it enables 1-step reconstruction with optimal results in terms of shape and nipple projection

Soft drinks and sweeteners intake: Possible contribution to the development of metabolic syndrome and cardiovascular diseases. Beneficial or detrimental action of alternative sweeteners?

Abstract The rapid increase in obesity, metabolic syndrome, and cardiovascular diseases (CVDs) has been related to the rise in sugar-added foods and sweetened beverages consumption. An interesting approach has been to replace sugar with alternative sweeteners (AS), due to their impact on public health. Preclinical and clinical studies, which analyze the safety of AS intake, are still limited. Major pathogenic mechanisms of these substances include ROS and AGEs formation. Indeed, endothelial dysfunction involving in the pathogenesis of micro- and macro-vascular diseases is mitochondrial dysfunction dependent. Hyperglycemia and endoplasmic reticulum stress together produce ROS, contributing to the development and progression of cardiovascular complications during type 2 diabetes (T2D), thus causing oxidative changes and direct damage of lipids, proteins, and DNA. Epidemiological studies in healthy subjects have suggested that the consumption of artificial AS can promote CV complications, such as glucose intolerance and predisposition to the onset of T2D, whereas natural AS could reduce hyperglycemia, improve lipid metabolism and have antioxidant effects. Long-term prospective clinical randomized studies are needed to evaluate precisely whether exposure to alternative sugars can have clinical implications on natural history and clinical outcomes, especially in children or during the gestational period through breast milk

Avulsion thighplasty:what about the consent for loss of reconstructive options for microsurgical breast reconstruction?

Avulsion Thighplasty: What about the Consent for Loss of Reconstructive Options for Microsurgical Breast Reconstruction?

Sulfolobus acidocaldarius terminal oxidase. A kinetic investigation and its structural interpretation.

Abstract The thermoacidophilic archaebacterium Sulfolobus acidocaldarius possesses a very unusual terminal oxidase. We report original kinetic experiments on membranes of this microorganism carried out by stopped flow, using time-resolved optical spectroscopy combined with singular value decomposition analysis. The reduced-oxidized kinetic difference spectrum of the Sulfolobus membranes is characterized by three significant peaks in the visible region at 605, 586, and 560 nm. The 605-nm peak and part of the 586-nm peak (cytochrome aa3-type quinol oxidase) are reduced synchronously by both ascorbate plus N,N,N',N'-tetramethyl-p-phenylendiamine (TMPD) and dithionite, and they are very rapidly oxidized by molecular oxygen. A second pool of cytochromes seems to contribute to the 586-nm peak which is not reduced by ascorbate plus TMPD and reacts very slowly with dithionite. The b-type cytochromes (560 nm peak) are reduced by both reductants and are essentially "non-autoxidizable" at room temperature. Only one CO binding site with spectral features, kinetic properties, and ligand affinity not very dissimilar from those of mammalian cytochrome oxidase can be detected in the ascorbate-reduced membranes. On the contrary, a second CO binding site having unusual properties for aa3 terminal oxidases can be detected in the dithionite-reduced membranes

Wearable and interactive mixed reality solutions for fault diagnosis and assistance in manufacturing systems: Implementation and testing in an aseptic bottling line

Abstract Thanks to the spread of technologies stemming from the fourth industrial revolution, also the topic of fault diagnosis and assistance in industrial contexts has benefited. Indeed, several smart tools were developed for assisting with maintenance and troubleshooting, without interfering with operations and facilitating tasks. In line with that, the present manuscript aims at presenting a web smart solution with two possible applications installed on an Android smartphone and Microsoft HoloLens. The solution aims at alerting the operators when an alarm occurs on a machine through notifications, and then at providing the instructions needed for solving the alarm detected. The two devices were tested by the operators of an industrial aseptic bottling line consisting of five machines in real working conditions. The usability of both devices was positively rated by these users based on the System Usability Scale (SUS) and additional appropriate statements. Moreover, the in situ application brought out the main difficulties and interesting issues for the practical implementation of the solutions tested

Disasters and emergency management in chemical and industrial plants: Drones simulation for education and training

The use of simulation for training is proven to be extremely effective both in term of costs and in term of its flexibility for different uses and applications, such as building situation awareness and creating scenarios for training scopes. The aim of the project proposed is to demonstrate the powerful rule of simulation in UAV pilots\u2019 cooperative training; the project presented makes use of a 3D simulation environment in order to build a realistic condition of an emergency situation in a chemical plant for the first responders. The model proposed makes use of HLA (High Level Architecture) standards in order to be potentially federated with other existing simulators. In the solution proposed, the pilot of the drone must accomplish the mission in a given time piloting a UAV; the scenario is based inside a chemical plant where a disaster is newly occurred. Then ability of the pilot is measured by the system and several constraints are reproduced to provide a realistic training scenario (such as small spaces and barriers to overcome, battery durations, risks of damages due to high temperatures zones, etc.); the system records and tracks all the actions of the pilot and gives a feedback to the user at the end of the simulation time