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    3714 research outputs found

    Lip rejuvenation and filler complications in the perioral region

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    Lip and perioral augmentation procedures have become increasingly popular over the last two decades due to cultural trends, emphasizing youth and beauty. An understanding of lip anatomy and aesthetics has traditionally formed the basis for successful results. However, as new technology becomes available, patient standards have increased, requiring an intricate understanding of filler properties and the advantages of different technical approaches. This chapter touches on pertinent anatomy and aesthetics of perioral evaluation. It also provides an overview of the properties of the fillers currently available in the United States marketplace for perioral rejuvenation. The technique and materials currently favored by the senior author are described in greater detail. Finally, the chapter will overview potential complications and recommended management

    Current concepts in microsurgical soft tissue reconstruction of lower extremity trauma in a single-vessel extremity

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    Advancements in microsurgical techniques have allowed for the salvage of extremities that would otherwise be amputated. Despite these improvements, mangling injuries of the lower extremity with concomitant open fracture continue to present a challenge for reconstructive surgeons. These injuries are further complicated by circumstances in which a single vessel is perfusing the foot after trauma (Gustilo 3C injuries). Although the foot may remain perfused in this instance, free flap coverage of open fractures with concomitant vascular injury requires careful planning to maintain a viable foot. The surgeon must adapt surgical plans based on both preoperative and intraoperative findings. In this review, we discuss current concepts and reconstructive techniques for performing free flap reconstruction in single-vessel lower extremities

    Surgical circumferential contouring: lower body, upper body, and in-between

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    Deformities in the body contouring population are rarely isolated to one area, and procedures can be combined to achieve more substantial results. While there is no formula for optimal surgical sequencing and timing, there are certain principles which - when applied appropriately - can yield results that are reliable, aesthetically pleasing, and aligned with the patient’s desires and preferences. In this article, we outline our latest thinking in circumferential body contouring and how to integrate the lower body lift with procedures of the abdomen, upper body, breasts, back, and arms to achieve the complete 360° look

    Management of urethral strictures after masculinizing genital surgery in transgender men

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    Transgender men undergoing phalloplasty and metoidioplasty have a high rate of urethral stricture. Evaluation of stricture includes evaluation of symptoms and uroflow, cystoscopy, and retrograde urethrogram. Important anatomic differences between the phallus of cis-gender and transgender men increase the likelihood and complexity of treating urethral strictures in transgender men after surgery. Urethral strictures after masculinizing procedures are more likely to require open surgical treatment and recur after treatment. There is a paucity of data, but less invasive options such as dilation and urethrotomy have had minimal success. Open surgical options with a variety of techniques, including one-stage and two-stage techniques, have higher success rates in treating strictures, but there is minimal comparative data on outcomes. We present a review on management options for urethral reconstruction in transgender men and our data on urethroplasty for these patients

    The role of VISTA in the tumor microenvironment

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    V-domain Ig Suppressor of T cell Activation (VISTA) is a negative immune checkpoint that is expressed on multiple immune cell subsets and has been characterized in T cells, macrophages, and myeloid-derived suppressor cells. As the only immune checkpoint expressed on naïve T cells, VISTA contributes to the maintenance of T cell quiescence and tolerance. VISTA also regulates multiple myeloid cell activities such as chemotaxis, differentiation, and migration. In the context of cancer, antagonistic monoclonal antibody targeting of VISTA has been shown to aid anti-tumor immunity. Furthermore, combination therapies that include other immune checkpoints such as PD-1 or CTLA-4 with VISTA blockade may enhance therapeutic efficacy in a variety of cancers. Combination therapy may help overcome adaptive resistance to individual checkpoint therapies, thereby improving patient outcomes and survival. Here, we summarize the role of VISTA in myeloid cells and T cells within the tumor microenvironment. We discuss the proposed counter-receptors for VISTA, VISTA antibodies currently in development, and the potential for combination therapies with checkpoint inhibitors such as PD-1 and CTLA-4

    Vascular and metabolic risk factors of late-life depression

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    Late-life depression (LLD) is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, cognitive decline, and increased mortality. The mechanisms underlying LLD are incompletely understood. The heterogeneity of depression complicates research into the underlying mechanisms, and factors involved in LLD may differ from those involved in early-life depression. This narrative review provides an overview of (micro-)vascular and metabolic factors involved in the development of LLD. Evidence suggests that cerebral small vessel disease, generalized microvascular dysfunction, and metabolic risk factors, including diabetes and inflammation, may contribute to the development of LLD, while the role of neurodegeneration needs further in-depth investigation. Accordingly, vascular and metabolic factors may provide promising targets for the prevention and improvement of treatment of LLD. Guidelines to screen for LLD in cardiovascular care need further implementation, as do integrated care approaches that treat LLD and diabetes jointly. However, intervention studies are needed to assess which interventions are appropriate and most effective in clinical practice

    Nutritional deficiencies following metabolic surgery

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    Nutritional deficiencies can develop into challenging problems in patients undergoing metabolic surgery for weight loss. In order to prevent the development of serious complications, effective screening algorithms and routine supplementation should be employed in the postoperative period. This paper outlines the nutritional function of different positions of the gastrointestinal tract, and common nutritional deficiencies associated with sleeve gastrectomy, Roux-en-Y gastric bypass, and duodenal switch. We present appropriate screening/supplementation protocols for each metabolic surgery, supplementation regimens when nutritional deficiencies develop, and surgical approaches to overcome nutritional deficiencies refractory to medical management

    GD2+ cancer stem cells in triple-negative breast cancer: mechanisms of resistance to breast cancer therapies

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    Research has led to the development of tailored treatment options for different cancers in different patients. Despite some treatments being able to provide remarkable responses, nearly all current treatments encounter the same issue: resistance. Here, we discuss our experiences with how breast cancers resist therapies. The focus of our discussion revolves around the cancer stem cell subpopulation and their mechanisms for resistance

    Role of extracellular vesicles secretion in paclitaxel resistance of prostate cancer cells

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    Aim: The development of chemotherapy resistance is the major obstacle in the treatment of advanced prostate cancer (PCa). Extracellular vesicles (EVs) secretion plays a significant role among different mechanisms contributing to chemoresistance. Hence, inhibition of EVs release may increase the efficacy of chemotherapeutic drugs against PCa.Methods: Paclitaxel (PTX) resistant PCa cells (PC3-R and DU145-R) were treated with GW4869, a known exosome biogenesis inhibitor. EVs were isolated from the conditioned media by ExoQuick-based precipitation method and characterized for concentration and size distribution by nanoparticle tracking analysis. The effect of GW4869 treatment on the survival and growth of PCa cells was assessed by MTT, and colony formation assays in vitro, and ectopic PC3-R xenografts in male athymic nude mice in vivo. The effect of other EV biogenesis inhibitors, imipramine and dimethyl amiloride (DMA), treatment was also analyzed on the survival of PC3-R cells.Results: GW4869 (10-20 µM) treatment of PTX resistant PCa cells significantly reduced the release of small EVs (50-100 nm size range) while increasing the release of larger EVs (> 150 nm in size), and inhibited their clonogenicity. Moreover, GW4869 (5-20 µM) treatment (24-72h) significantly inhibited the survival of PC3-R cells in a dose-dependent manner. We observed a similar growth inhibition with both imipramine (5-20 µg/mL) and DMA (5-20 µg/mL) treatment in PC3-R cells. Furthermore, GW4869 treatment (IP) in mice bearing PC3-R xenografts significantly reduced the tumor weight (65% reduction, P = 0.017) compared to the vehicle-treated control mice without causing any noticeable toxicity.Conclusion: Inhibiting the release of EVs could sensitize the resistant PCa cells to chemotherapy

    Epilepsy and electroencephalography in Pitt-Hopkins syndrome

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    Aim: Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mono-allelic loss of function variants of transcription factor 4 (TCF4), which plays a key role in early brain developmental and neuronal differentiation. Up to one-half of patients with PTHS will have epilepsy; however, little is known about the characteristic electroencephalogram (EEG) findings in this population. Because there is significant phenotypic overlap between PTHS and other neurodevelopmental disorders such as Angelman syndrome and Rett syndrome, which have characteristic EEG patterns, exploration of a potential EEG signature in patients with PTHS was warranted.Methods: We conducted a retrospective review of clinical EEGs in patients with PTHS.Results: In this cohort of patients with PTHS (n = 16), over half had abnormal EEGs; however, no characteristic EEG signature was identified. Further, all patients with epilepsy (5/16) had focal onset seizures with or without secondary generalization, and all five had focal abnormalities on EEG. There was no specific correlation between EEG results and developmental trajectories or age in our patient group, and there was no clear genotype-phenotype correlation.Conclusion: Although a distinctive EEG signature was not identified, all individuals with epilepsy in our cohort had focal onset seizures with corresponding focal epileptiform discharges or focal slowing on EEG. Future studies are needed to fully elucidate the spectrum of EEG findings in PTHS and explore the pathogenesis of focal seizures in a disorder of neuronal differentiation and development

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