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SummaryNon-alcoholic fatty liver disease (NAFLD) is a rapidly growing cause of morbidity with few treatment options available. Thus, accuratein vitrosystems to test new therapies are indispensable. Recently, human liver organoid (HLO) NAFLD models have emerged. However, a systematic evaluation of their translational potential is currently missing. Here, we develop a structured approach to evaluate NAFLD-HLO models, testing oleic acid (OA) and palmitic acid (PA) in comparison to TGF-β1 for disease induction. Through analysis of ∼100K single-cell transcriptomes of the HLO injury landscape, we find all three models induce inflammatory signatures. However, only TGF-β1 promotes collagen production, fibrosis, and hepatic stellate cell (HSC) expansion. In striking contrast, OA ameliorates fibrotic signatures and reduces the HSC population. Integrating data from each model with that of NAFLD patients across disease progression further demonstrates PA and TGF-β1 more robustly model inflammation and fibrosis. Our findings highlight the importance to stratify NAFLD-HLO models by clinical disease progression, provide a single-cell reference to benchmark future organoid injury models, and allow us to study evolving steatohepatitis, fibrosis, and HSC susceptibility to injury in a dynamic, multi-lineage humanin vitrosystem.

Introduction Mid Ventricular (MVO) and Left Ventricular Outflow Tract Obstruction (LVOTO) after Trans–catheter Aortic Valve Implantation (TAVI) have been previously described and are associated with adverse outcome. Pre–procedural identification of patient at risk of MVO and LVOTO after TAVI may help pre–operative risk stratification and patient selection and facilitate intra–operative management, finally improving clinical outcomes. This study aims to identify CT–scan and Echocardiographic predictors of Left Ventricular Obstruction (LVO), defined as the composite of MVO and LVOTO. Methods We retrospectively reviewed pre–operative CT scans and Trans–Thoracic Echocardiography of 349 patients treated with TAVI at our Centre between January 2019 and December 2021. Correlations between post–operative development of MVO and LVOTO and pre–operative Echocardiographic and CT scan measurements were tested. Results LVO occurred in 16.3% of patients after TAVI. At univariate analysis clinical factors associated to LVO were female gender (OR=2.2, p=0.006) and body surface area (OR=0.19, p=0.006); pre–procedural echocardiographic parameters identified were end–diastolic–diameter (OR=0.89, p Conclusions Left ventricle obstruction (LVOTO + MVO) after TAVI can be predicted by CT scan derived parameters. Pre–procedural identification of patients at risk may help intraprocedural and postprocedural management, thus improving clinical outcomes.

Introduction Recent guidelines suggest a limited duration of triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) at elevated bleeding risk. Indeed, in patients who are also at elevated thrombotic risk and with indication to prolonged dual antiplatelet therapy, percutaneous left atrial appendage closure (LAAC) could be a possible safe and effective option to prevent both bleeding and thrombotic events. Methods retrospective single–center study enrolling all consecutive patients between September 2012 and February 2020, comparing patients deemed at increased thrombotic and bleeding risk who received LAA percutaneous closure to avoid TAT before or after PCI with patients who received TAT after PCI. The aim of the study was to establish the safety and efficacy of LAAC in comparison to TAT. Results A total of 168 patients were included in the study: 56 underwent percutaneous LAAC while 112 were discharged in TAT. Median age was 75 (69–79). TAT patients had a CHA2DS2–VASc score of 4 (3–5) and a mean HAS–BLED score of 3 (2–3), whereas in LAAC patients the mean CHA2DS2–VASc was 4.9 (±1.5) and the mean HAS–BLED was 3.9 (±0.9); the difference in Score Points was statistically significant (p=0.001). The population who underwent LAAC was characterized by a remarkable procedural PCI complexity with a mean DAPT score of 1.4 (±1.3), with respect to the population discharged in TAT which was 0 (0–2). At follow–up (mean follow–up period in days: 727 [489–1000]), four bleeding episodes were recorded in LAAC population in comparison to 16 bleeding episodes observed in TAT population (12.6% vs. 15.4%; p–value=0.142): two bleeding episodes were major in LAAC group and five in TAT group (3.6% vs. 4.8%; p–value=1). One case of stroke (1.8%) occurred in LAAC population and two cases (1.8%) in TAT population (p=1.000). Conclusions In a single–centre retrospective study no significant difference was observed in terms of bleeding between TAT and LAAC, in patients at high ischemic and thrombotic risk with indication to prolonged dual antiplatelet therapy after PCI and anticoagulation for AF. Nevertheless, the non statistical trend to reduction of bleeding events in LAAC group might be explored in a larger study population.

The use of energy-based devices as surgical tools during rhytidectomy was introduced in early 2007 to 2008 and occurred when the first fiber laser was approved for laser lipolysis. It became evident that the fiber laser-assisted rhytidectomy could offer several advantages compared with conventional rhytidectomy. The use of energy devices now includes temperature-controlled radiofrequency and helium plasma devices. Energy devices continue to offer advantages compared with knife and scissor approaches: improved hemostasis; an ability to dissect into areas without full flap elevation; and the shrink-wrap late effects of collagen remodeling after energy-based treatment, which improves the results of rhytidectomy.

Picosecond laser technology was cleared by Food and Drug Administration in 2012 and enhanced our ability to clear both benign pigmentation and dermal ink through a photomechanical impact created in the tissue. This impact created is greater than comparative nanotechnology and can be accomplished with lower fluences and smaller pulse durations. The addition of a diffractive lens array (FOCUS lens) has created a new category in skin rejuvenation by stimulating elastin and collagen through photomechanical and photoacoustic effects and not only through traditional photothermal tissue effects.

Energy-based skin rejuvenation has, like other forms of aesthetic treatments, the capability of achieving desirable end results. These end results must be balanced with the degree and duration of morbidity, which affect recovery from treatment. Renuvion skin resurfacing protocols include a free hand approach and we describe our preferred approach of pulsing and fractionating the helium plasma resurfacing energy.

The process of obtaining blood biologics, including platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), can be complicated and expensive and is influenced by many vendors and proprietary techniques. The indications for PRP/PRF use remain controversial, and complicated or expensive modes of generating this biologic may lead to many facial plastic surgeons to pass on the use of these potentially useful agents. The lack of standardization of PRP procurement also has led to difficulties in assessing clinical efficacy and comparing study protocols.

In this article the authors discuss and analyze technological devices also known as energy-based devices and their use in skin rejuvenation, facial contouring, skin tightening, and other applications in facial plastic surgery. Energy has been applied in some form to tissue since the beginning of recorded history. The practice of applying heat to tissue with the use of cauters was used for thousands of years as an invaluable method of controlling hemorrhage. Continuous improvement of methods for using the beneficial effects of heat on tissue eventually led to the development of the basic concepts of electrosurgery we know today.

Energy-based facelifting techniques are a relatively new genre of surgery. In this approach, the energy-based device—whether laser, radiofrequency plasma, or ultrasound—can be used in the superficial plane to elevate skin flaps before performing more traditional facelift techniques involving the superficial musculoaponeurotic system (SMAS) or platysma. The initial reports of utilizing fiber lasers as surgical tools date back to approximately 2007 and initial lipolasers were used to elevate facial skin flaps. The other energy-based devices were also tested. The author has probably the largest series of energy-based facial rejuvenation procedures, having performed over 3,000 of these procedures. The advantages of laser-assisted rhytidectomy include hemostasis, facilitated dissection in areas hard to elevate conventionally such as nasolabial folds or distal neck and the remodeling and tightening of tissue that results from the activation of the wound healing cascade of neocollagenesis and wound contraction. The author currently has a preference for energy device used during rhytidectomy and it is a high frequency ultrasound energy delivered by a five-ring 2.9- and 3.7-mm probe. The use of the ultrasound dissector in both superficial and deep procedures is highlighted in this article with emphasis on its use for deep cervicoplasty and subplatysmal procedures as well as sub-SMAS elevations of the facial deep plane.

The study of the liver progenitor cell microenvironment has demonstrated the important roles of both biochemical and biomechanical signals in regulating the progenitor cell functions that underlie liver morphogenesis and regeneration. While controllable two-dimensional in vitro culture systems have provided key insights into the effects of growth factors and extracellular matrix composition and mechanics on liver differentiation, it remains unclear how microenvironmental signals may differentially affect liver progenitor cell responses in a three-dimensional (3D) culture context. In addition, there have only been limited efforts to engineer 3D culture models of liver progenitor cells through the tunable presentation of microenvironmental stimuli. We present an in vitro model of 3D liver progenitor spheroidal cultures with integrated polyethylene glycol hydrogel microparticles for the internal presentation of modular microenvironmental cues and the examination of the combinatorial effects with an exogenous soluble factor. In particular, treatment with the growth factor TGFβ1 directs differentiation of the spheroidal liver progenitor cells toward a biliary phenotype, a behavior which is further enhanced in the presence of hydrogel microparticles. We further demonstrate that surface modification of the hydrogel microparticles with heparin influences the behavior of liver progenitor cells toward biliary differentiation. Taken together, this liver progenitor cell culture system represents an approach for controlling the presentation of microenvironmental cues internalized within 3D spheroidal aggregate cultures. Overall, this strategy could be applied toward the engineering of instructive microenvironments that control stem and progenitor cell differentiation within a 3D context for studies in tissue engineering, drug testing, and cellular metabolism.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT. © European Stroke Organisation 2020.

Three doctors discuss the current issues and controversies involving the use of radiofrequency and energy-based devices for skin tightening, facial contouring, and other indications. The use of transcutaneous monopolar-, bipolar-, multipolar-, subcutaneous-, and microneedle-based delivery methods are discussed. The controversies involved in the various devices are discussed.

A new temperature-controlled device has been used as a percutaneous radio frequency probe to treat lax submental and other facial areas. It has significant advantages over other esthetic devices as it provides the dual benefit of fat lipolysis and skin tightening. Our goal here is to present consensus recommendations for treating the aging neck.A panel of 11 expert physicians convened in Dallas, Texas, on October 15, 2016 to arrive at a consensus on the best current practice for submental skin tightening and contour improvement. Prior to the meeting, a comprehensive review of the literature was performed and a survey was sent to esthetic dermatologists and plastic surgeons who were queried about various aspects of neck rejuvenation.The literature search revealed 10 different technologies for neck rejuvenation evaluated in double-blind (n = 2) and single-blind (n = 1) clinical trials and other clinical evaluations (n = 21). The survey was sent via an email to 1248 individuals and was completed by 92 respondents. Review of the data and discussion by meeting attendees generated eight consensus recommendations.Subdermal monopolar radio frequency represents an effective means for disrupting fat volume and skin tightening of the face, neck, and jawline. For suitable patients, this treatment can be used to achieve significant esthetic improvements.

Picosecond laser technology was cleared by Food and Drug Administration in 2012 and enhanced our ability to clear both benign pigmentation and dermal ink through a photomechanical impact created in the tissue. This impact created is greater than comparative nanotechnology and can be accomplished with lower fluences and smaller pulse durations. The addition of a diffractive lens array (FOCUS lens) has created a new category in skin rejuvenation by stimulating elastin and collagen through photomechanical and photoacoustic effects and not only through traditional photothermal tissue effects.

Technology impacts the lives of everyone nowadays and has had perhaps a greater impact on the lives of facial plastic surgeons and the patients they seek to help with both surgery and procedures. This article will discuss modern technology's impact on intervening in the aging process including technology used for facial and skin rejuvenation and reconstruction concentrating on the techniques and care to minimize complications as well as dealing with complication from the treatments.

The modern environment is characterized by convenient access to a variety of high-fat (HF) foods and encourages excess energy intake, which leads to weight gain. While healthier diets and exercise are common interventions that facilitate energy balance, meal patterns also influence body weight and energy metabolism. The current study characterized the association among exercise, diet choice, and meal patterns in rats. Unlike sedentary rats, which prefer a HF to a chow diet, wheel-running rats initially avoid the HF diet. Subsequently, the running-induced HF diet avoidance persists longer in males than in females. We hypothesized that differences in meal patterns contribute to sex differences in the prevalence and persistency of HF diet avoidance. During two-diet choice, rats did not mix chow and HF diet within a meal and consumed discrete meals of each diet. Exercise decreased chow meal size in both sexes (4.5 vs. 5.7 kcal) but decreased total meal frequency only in male rats. Analyses of individual differences revealed WR rats that maintained HF diet avoidance (HF avoiders) had larger chow than HF meals (5.2 vs. 1.3 kcal) upon initial 3 days of diet choice. When compared with rats that reversed HF avoidance (HF eaters), HF avoiders had shorter latency to consume their first meal of HF diet (2.6 vs. 98.9 min) upon initial running and diet choice. Taken together, these results suggest that both sex and individual differences in meal patterns contribute to differences in the persistency of exercise-associated HF diet avoidance.

Cell labeling and tracking methodologies can play an important role in experiments aimed at understanding biological systems. However, many current cell labeling and tracking techniques have limitations that preclude their use in a variety of multiplexed and high-throughput applications that could best represent the heterogeneity and combinatorial complexity present in physiologic contexts. Here, we demonstrate an approach for labeling, tracking, and quantifying cells using double-stranded DNA barcodes. These barcodes are introduced to the outside of the cell membrane, giving the labeled cells a unique identifier. This approach is compatible with flow cytometric and PCR-based identification and relative quantification of the presence of barcode-labeled cells. Further, utilizing this strategy, we demonstrate the capacity for sorting and enrichment of barcoded cells from a bulk population. In addition, we illustrate the design and utility of a range of orthogonal barcode sequences, which can enable the use of multiple independent barcodes to track, sort, and enrich multiple cell types and/or cells receiving distinct treatments from a pooled sample. Overall, this method of labeling cells has the potential to track multiple populations of cells in both high-throughput in vitro and physiologic in vivo settings.

Treating patients with heavy or thick features comes with challenges not present in those patients lacking these physical characteristics. The authors report our experience with cool atmospheric plasma for facial contouring and skin rejuvenation of the heavy face and neck including rhinophyma. Cool atmospheric plasma is generated by running helium gas over radiofrequency energy. The resulting plasma is a fourth state of matter and has enhanced clinical effects for ablation and thinning of skin and soft tissues as well of contouring and tightening of deeper soft tissues and fascia. Cool helium plasma has been a very effective tool for skin rejuvenation and skin tightening as well as using it as a tool for nonexcisional microinvasive face and neck rejuvenation. Future research may indicate that it can help treat primary or recurrent superficial cutaneous malignancies.

Scarring of the neck affects millions of people every year. The appearance of neck scarring can be disturbing both physically and psychologically. Scarring of the neck can be accompanied by morbidities because of the limitation of functional motion of the neck. Treatment options and modalities for reduction and prevention of scar formation include topical steroids, intralesional steroids, interferon, 5-fluorouracil, silicone gel, radiation, laser therapy, and surgeries. There is no general consensus in the literature as to the optimal treatment of neck scarring. Patients should understand that the scar is likely to be improved but not eliminated by treatment.

Carcinoma progression is influenced by interactions between epithelial tumor cells and components of their microenvironment. In particular, cell–extracellular matrix (ECM) interactions are known to drive tumor growth, metastatic potential, and sensitivity or resistance to therapy. Yet the intrinsic complexity of ECM composition within the tumor microenvironment remains a barrier to comprehensive investigation of these interactions. We present here a high-throughput cell microarray-based approach to study the impact of defined combinations of ECM proteins on tumor cell drug responses. Using this approach, we quantitatively evaluated the effects of 55 different ECM environments representing all single and two-factor combinations of 10 ECM proteins on the responses of lung adenocarcinoma cells to a selection of cancer-relevant small molecule drugs. This drug panel consisted of an alkylating agent and five receptor tyrosine kinase inhibitors. We further determined that expression of the neuroendocrine transcription factor ASCL1, which has been previously associated with poor patient outcome when co-expressed with the RET oncogene, altered cell responses to drugs and modulated cleavage of the pro-apoptotic protein caspase-3 depending on ECM context. Our results suggest that co-expression of specific ECM proteins with known genetic drivers in lung adenocarcinoma may impact therapeutic efficacy. Furthermore, this approach could be utilized to define the molecular mechanisms by which cell–matrix interactions drive drug resistance through integration with clinical cell samples and genomics data.

Introduzione. Nella moderna fitoterapia si registra un aumento dello studio e dell'uso dei fitocomplessi con l'intento di sfruttare l'effetto sinergico di entità chimiche differenti. Gli oli essenziali (OE) sono fitocomplessi di molecole volatili in grado di esplicare molteplici attività biologiche tra cui quella antimicrobica e quella antiproliferativa. Oltre al frutto edibile, la pianta di Pistacchio (Pistacia vera L.), come altre Anacardiacee, produce una oleoresina facilmente recuperabile da incisioni superficiali del tronco. Da questa oleoresina, per idrodistillazione, è possibile recuperare un OE. Da informazioni etnofarmacologiche raccolte in territorio siciliano e da dati riportati in letteratura per specie analoghe alla Pistacia vera L., è risultato che le oleoresine di queste piante vengono utilizzate come fitoterapici in particolare come antisettici del cavo orale, come rimedio ai sintomi di disturbi gastrointestinali e come promotori di cicatrizzazione per ferite superficiali. Scopo. Lo scopo di questo studio è stato quello di caratterizzare chimicamente e di valutare in vitro l'attività antimicrobica ed antiproliferativa ed in vivo l'attività di promozione della cicatrizzazione dell'OE di oleoresina di Pistacia vera L. Materiali e metodi. La composizione chimica è stata determinata tramite GC-FID e GC-MS. La Concentrazione Minima Inibitoria (MIC) e la Concentrazione Minima Battericida (MBC) sono state determinate in accordo con le linee guida del Clinical and Laboratory Standards Institute (CLSI), valutando l'attività antimicrobica su 18 ceppi batterici (sia gram positivi che negativi). La vitalità cellulare è stata misurata con il test MTT, determinando l'effetto antiproliferativo dell'olio essenziale su tre linee cellulari di cancro al colon, Caco-2, HT-29, e HCT-116. I test in vivo di irritazione e cicatrizzazione sono stati effettuati su conigli New Zealand White. Risultati. L'analisi chimica ha mostrato un'elevata percentuale di monoterpeni idrocarburici con l'?-pinene come componente principale dell'OE. Oltre all'attività antimicrobica sui ceppi di streptococchi orali, l'OE ha mostrato una buona attività antiproliferativa contro tutte e tre le linee testate. Particolarmente interessanti sono risultati i dati di promozione della cicatrizzazione anche alla luce degli studi istologici effettuati. Conclusioni. I dati presentati rappresentano una preliminare valutazione delle potenziali attività biologiche dell'OE di oleoresina di Pistacia vera L. e possono essere considerati come il primo contributo all'utilizzo fitoterapico di questo promettente prodotto secondario della produzione di Pistacchio.

Less invasive procedures for facial rejuvenation are becoming more and more popular as prospective patients seek out treatment options that offer the best possible results with the least amount of downtime. As the demand for "quick recovery" procedures increases and patients spend more time researching options, more informed choices are being made, and many times patients opt for technologically advanced procedures. Less invasive procedures can be so described because they utilize small incisions, less anesthesia, or advanced technology to reduce morbidity. We describe a minimally invasive "laser neck-lift" that utilizes minimal access incisions, no general anesthesia, and an internal aesthetic laser to dissect in the plane between skin and subcutaneous fat and the platysma. The procedure relies on laser lipolysis and skin tightening via dermal heating as well as two Quill™ sutures that serve to define the neck. The procedure is well tolerated and not complicated and gives long-lasting results.

The goal of this article is to explain both the options and the techniques that are available when considering the rejuvenation of the eyelid and brow complex. We first explain the relevant anatomy. We then list and explain the different techniques with both the brow lift and the blepharoplasty. During this discussion we also explain a newer technique that we have been using. This combines the endoscopic technique with a trichophytic incision. The selection of patients is discussed in reference to which technique is appropriate given each patient's particular anatomy and desired effects. We also highlight the unique differences that the male patient presents.

The demand for laser facial plastic surgery for men has been increasing. Because men tend not to wear make-up and do not wish to take the time off from work associated with surgical procedures, they prefer laser type procedures that usually have minimal associated recovery. These procedures can be used to treat multiple conditions including: photoaging, acne, acne scars, superficial cutaneous problems, and rhinophyma.

Experimental and modeling results for resistance degradation in thin Ba0.5Sr0.5TiO3 (BST) film capacitors with platinum (Pt) electrodes are reported. The main experimental results are as follows. Under a constant applied voltage, the current density is observed to increase with time until it reaches a maximum value. Once the maximum value is reached, the current density becomes constant with time. The barrier height at the BST/Pt (cathode) interface is observed to decrease after prolonged electrical stressing. The resistance degradation effect is observed to be reversible, particularly at elevated temperatures. Based on the experimental results, a quantitative model for resistance degradation is proposed. In this model, the increase in the current density is attributed to a decrease in the barrier height at the cathode and this decrease is assumed to have a stretched exponential dependence on time. Using experimentally determined parameters, the model calculates the current density as a function of time at various temperatures. The calculated results are verified and the model is shown to be self-consistent. Hence the model provides an accelerated method for determining the lifetime of thin BST films at the operating conditions for advanced memory applications.